Intermediate Care: Role for Hospitalists

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Results of a retrospective observational study of intermediate care staffed by hospitalists: Impact on mortality, co‐management, and teaching

Hospitalized patients are becoming increasingly complex. The care of such patients may be impacted by the limited resources of the general ward and might benefit from more intensive monitoring in an intensive care unit (ICU)‐like setting. In light of this problem, the intermediate care units (ImCU) may provide a cost‐effective alternative by providing higher levels of staffing tailored to patient needs, without incurring the cost of an ICU admission. The ImCU can reduce costs and improves ICU utilization for sicker patients, decrease ICU readmissions, promote greater flexibility in patient triage, and decrease mortality rates in hospital wards.18

The characteristics of ImCUs depend on resource availability, institutional infrastructure, and the organization and funding of the parent healthcare system. The ImCU may function as a step‐up or step‐down unit, or may provide specialty care for cardiac, neurologic, respiratory, or surgical conditions.811 These units can expand opportunities for co‐management and, at the same time, offer the occasion for training residents to follow up patients through different levels of care (from the general ward to ImCU). In the same way, the multidisciplinary approach of the ImCU can improve the center's teaching potential.

Characterizing the ImCU population requires the assessment of their severity of illness, which is crucial for the evaluation of risk‐adjusted outcomes. The present study evaluated the impact of a hospitalist‐led ImCU on observed‐to‐expected mortality ratios, as well as its role in co‐management and teaching.

PATIENTS AND METHODS

We performed a retrospective observational study, with data collected from April 2006 to April 2010 in a single academic medical center in Pamplona, Spain. The ImCU is a 9‐bed unit adjacent to, but independent from, the mixed ICU. Each bed is equipped with continuous telemetry, pulse oximetry, noninvasive arterial blood pressure, central venous pressure monitoring, and noninvasive pressure support ventilation. The signals are relayed to a central monitoring station and the nurse‐to‐patient ratio is 1:3.

The ImCU rounding team is multidisciplinary, and involves the hospital pharmacist, a nurse, the ImCU resident, the specialist or surgeon, and the attending hospitalist. After the triage process, ImCU patients were admitted to the attending hospitalist, who was responsible for admission and discharge of all ImCU patients. The hospitalist ordered diagnostic or therapeutic interventions as needed, with the exception of orders for procedures or consultations related with specialist/surgeon's specific needs.

Admission and discharge criteria for the ImCU were set according to guidelines defined by The American College of Critical Care Medicine,10 and also served as inclusion criteria for the present study. Exclusion criteria included: age less than 18 years old, severe respiratory failure, status epilepticus, and catastrophic brain illness. Patients admitted for drug administration and desensitization, and also ImCU readmissions, were excluded from data analysis. Patients came from medical and surgical wards, ICU, the operating room, and the emergency room.

A total of 756 patients were admitted to our ImCU during the study period. Patient demographics, past medical history, physiologic parameters at the time of admission, and survival to hospital discharge were recorded for all patients. Patient demographics include: age, gender, location before ImCU admission, length of stay before ImCU admission, reason for ImCU admission, anatomic site of surgery (if applicable), planned or unplanned admission, and infection status (nosocomial). Past medical history includes: the presence of arterial hypertension, diabetes, cirrhosis, chronic renal failure, chronic heart failure, cancer, hematological malignancy, chronic obstructive pulmonary disease (COPD), human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), immunosuppression, radiotherapy, chemotherapy, steroid treatment, and alcoholism. Physiologic parameters abstracted are described in Table 1. We used the Simplified Acute Physiology Score II (SAPS II),12 as a prognostic and severity score. SAPS II is the only previously validated score in intermediate care.13 In‐hospital mortality was the clinical outcome measured.

Physiologic Parameters Evaluated at ImCU Admission
  • Abbreviations: ImCU, intermediate care unit.

Vital signs
Glasgow Coma Scale
Serum bilirubin
Serum creatinine
Urea nitrogen
Leucocyte count
Serum sodium
Serum potassium
Bicarbonate levels
Urinary output in the first 24 hr
Oxygenation and ventilatory support

Data were entered into a computer database by the authors. Statistical analysis was not blinded, and was performed using SPSS for Windows, version 15.0 (SPSS Inc, Chicago, IL). Continuous variables were reported as mean standard deviation or median (25%‐75% interquartile range). For nonparametric measure of statistical dependence of quantitative variables, we used Spearman's correlation coefficient. Discrimination was evaluated by calculating the area under receiver operating characteristic curve (AUROC).

The study protocol was approved by the institutional review board at the Clnica Universidad de Navarra in Pamplona, Spain.

RESULTS

Four hundred fifty‐six patients were included in data analysis. Three hundred patients were excluded: 61 low‐risk patients (drug administration and desensitization), 147 readmissions, and 92 patients for missing variables. Patient characteristics, including probability of death following ImCU admission and discharge location, are summarized in Table 2. The mean age was 65.6 years, and about 35% of patients had a SAPS II‐based risk of death higher than 25% at the time of ImCU admission. The median length of stay was 4 (3‐7) days.

Patient Characteristics and Mortality (n = 456)
  • Abbreviations: ICU, intensive care unit; ImCU, intermediate care unit; O/E, observed‐to‐expected mortality ratio; SAPS II, Simplified Acute Physiology Score II.

  • Denominator data represents the total population of transferred patients.

Age (yr)65.6 14.3
Gender 
Male283 (62.1%)
Female173 (37.9%)
Location prior to admission 
General ward252 (55.3%)
Emergency room96 (21.1%)
ICU63 (13.8%)
Operating room28 (6.1%)
Other hospital17 (3.7%)
Probability of in‐hospital mortality based on SAPS II 
<10%128 (28.1%)
11%‐25%176 (38.6%)
26%‐50%107 (23.4%)
>50%45 (9.9%)
Global expected mortality (in‐hospital)23.2%
Global observed mortality (in‐hospital)20.6% (94/456)
O/E mortality ratio0.89
Discharge location 
General ward352/456 (77.2%)
ICU65/456 (14.3%)
Home1/456 (0.2%)
Other hospital11/456 (2.4%)
Death location 
ImCU27/456 (5.9%)
ICU (transferred patients)32/65* (49.2%)
General ward35/352* (9.9%)

Outcomes

The mean SAPS II of the cohort was 37 12 points, and the expected mortality derived from this score was 23.2%. The observed in‐hospital mortality was 20.6% (94/456) resulting in an observed‐to‐expected mortality ratio of 0.89 (Table 2). Reasons for ImCU admission, as well as mortality ratios, are described in Table 3. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (Rho = 1.0, P < 0.001) (Figure 1). The AUROC for SAPS II predicting in‐hospital mortality was 0.75 (P < 0.001).

Figure 1
Correlation between observed and expected mortality based on SAPS II. (A) Rho = 1.0, P < 0.001. (B) Simplified Acute Physiology Score II (SAPS II).
Reasons for ImCU Admission and Severity Score Index
ConditionPatientsSAPS IIExpected MortalityObserved MortalityO/E Ratio
  • Abbreviations: GI, gastrointestinal complications; ImCU, intermediate care unit; O/E ratio, observed‐to‐expected mortality ratios; SAPS II, Simplified Acute Physiology Score II.

Respiratory failure153 (33.6%)36.1 9.721.5 15.3%25.5% (39)1.19
Sepsis88 (19.3%)45.7 15.137.5 25.1%22.7% (20)0.61
Cardiovascular72 (15.8%)35.7 11.021.3 16.6%23.6% (17)1.11
Perioperative59 (12.9%)28.9 9.912.9 11.7%5.1% (3)0.40
Complex monitoring34 (7.5%)33.2 12.119.1 16.3%14.7% (5)0.77
GI complications33 (7.2%)32.1 8.315.6 10.7%12.1% (4)0.78
Neurologic10 (2.2%)40.9 10.629.7 20.0%30.0% (3)1.01
Liver failure7 (1.5%)42.1 17.230.9 29.4%42.9% (3)1.39

Co‐Management and Teaching

During the study period, 382/456 (83.8%) patients were co‐managed with 9 medical and 7 surgical teams (Table 4). From the period of 2006‐2008, a total of 37/106 (34.9%) patients were co‐managed with surgeons, and just 5/37 (13.5%) were co‐managed preoperatively before ImCU admission. In the next 2 years, the patient total increased to 69/106 (65.1%), and preoperative surgical co‐management significantly increased to 25/69 (36.2%) (P = 0.014).

Co‐Management Areas and Patient Distribution
Medical   
Surgical 
  • NOTE: Data are number of patients and percentage of total co‐managed patients (n = 382). Seventy‐four patients from the Department of Internal Medicine/Hospitalists Unit were excluded from this analysis.

Oncology100 (21.9%)Neurology17 (3.7%)
Hepatology43 (9.4%)Cardiology14 (3.1%)
Pulmonology36 (7.9%)Nephrology14 (3.1%)
Hematology20 (4.4%)Others13 (2.9%)
Gastroenterology19 (4.2%)  
Total276 
General44 (9.6%)Orthopedics6 (1.3%)
Vascular23 (5.0%)Urology5 (1.1%)
Thoracic11 (2.4%)Others10 (2.2%)
Neurosurgery7 (1.5%)  
Total106 

Our academic medical center enrolls 46 new residents every year. Since the creation of the ImCU in 2006, residents from different medical subspecialties and from general surgery received training in intermediate care and hospital medicine. All residents rotated into the ImCU for 1‐3 months working 8 hours a day. In 2006, when the unit was opened, 2 residents from internal medicine (4.3%) rotated in the ImCU. Thereafter, a significant increase in the number of training residents was observed, reaching 30.4% of the total resident pool (14/46) in 2010 (P = 0.002).

DISCUSSION

To the best of our knowledge, this is the first description of hospitalists in intermediate care. In Spain, where hospital medicine is early in development but expanding, critical and intermediate care units are usually staffed by intensivists or anesthesiologists. Staffing an ImCU with hospitalists, using a multidisciplinary co‐management model, is a novel staffing solution for acutely ill patients.

Approximately 35% of ICU patients are low risk, admitted mainly for monitoring purposes.9, 14 In contrast, some patients are treated on general wards when they should receive more intensive care and monitoring.15 Intermediate care units could improve cost containment and triage flexibility, while tailoring treatments according to patient needs. In general, ImCUs require lower nurse‐to‐patient ratios, and less expensive equipment and supplies than ICUs, while retaining the capability of responding appropriately to acute events.16 Moreover, patient and family satisfaction may be increased as a result of more liberal visitation policies and a less noisy environment.17

This study was not designed to measure the cost‐effectiveness of the ImCU. Surprisingly, there are few reports in the last 2 decades demonstrating the efficacy and cost containment of intermediate care. The majority of the studies were retrospective or uncontrolled observations.27 To our knowledge, only 1 randomized controlled trial1 and 1 multicenter prospective cost study exist.8 Further research is needed in this area, with larger, prospective randomized controlled trials, before the benefits and limitations of intermediate care can be fully determined.

Description of the ImCU patients depends on accurate severity scoring. The efficacy and reliability of these scores has been described only for ICU patients and their role for predicting mortality in the ImCU is uncertain. There is only 1 report using SAPS II in intermediate care, showing good discriminant power and calibration in a cohort of 433 patients.13 Auriant et al described, in that cohort, an observed mortality rate of 8.1% with an expected mortality rate of 8.7%.13 In contrast, our expected mortality rate was considerably higher (23.2%). Although ImCUs are generally created for low‐risk patients and monitoring purposes, our population was more similar to an ICU population, with very high risk for major complications and mortality.1823 The contribution of oncologic patients (22% of the total series; most of them with advanced disease, elevated SAPS II [42.2 13.6] and do‐not‐resuscitate orders), probably contributed to the higher acuity of our ImCU population. The correlation of our present data supports the value of SAPS II as a prognostic score in intermediate care, even for patients sicker than those reported by Auriant et al.13 Intermediate care is also a valuable setting to expand a co‐management model with different medical and surgical specialties.

Similarly, since the creation of the ImCU at our institution in 2006, there is a substantial increase in the number of residents rotating through our ImCU. Previous studies showed positive results of hospitalists as clinical educators in various settings.24, 25

In conclusion, intermediate care serves as an expansion of role for hospitalists at our institution; and clinicians, trainees, and patients may benefit from co‐management and teaching opportunities at this unique level of care. An ImCU led by hospitalists showed encouraging results in terms of observed‐to‐expected mortality ratios for acutely ill patients. SAPS II is a useful tool for prognostic evaluation of ImCU patients. However, results of this study should be confirmed with larger, prospective trials at multiple centers.

Acknowledgements

The authors thank Dr Efren Manjarrez for the final manuscript revision, and the ImCU Nursing Staff for their unconditional support in patient care.

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References
  1. Douglas S,Daly B,Rudy E,Song R,Dyer MA,Montenegro H.The cost‐effectiveness of a special care unit to care for the chronically critically ill.J Nurs Adm.1995;25:4753.
  2. Bone RC,Balk RA.Noninvasive respiratory care unit. A cost‐effective solution for the future.Chest.1988;93:390394.
  3. Elpern EH,Silver MR,Rosen RL,Bone RC.The noninvasive respiratory care unit. Patterns of use and financial implications.Chest.1991;99:205208.
  4. Franklin CM,Rackow EC,Mamdani B,Nightingale S,Burke G,Weil MH.Decreases in mortality on a large urban medical service by facilitating access to critical care. An alternative to rationing.Arch Intern Med.1988;148:14031405.
  5. Byrick RJ,Power JD,Ycas JO,Brown KA.Impact of an intermediate care area on ICU utilization after cardiac surgery.Crit Care Med.1986;14:869872.
  6. Byrick RJ,Mazer CD,Caskennette GM.Closure of an intermediate care unit. Impact on critical care utilization.Chest.1993;104:876881.
  7. Durbin CG,Kopel RF.A case‐control study of patients readmitted to the intensive care unit.Crit Care Med.1993;21:15471553.
  8. Bertolini G,Confalonieri M,Rossi C, et al.Costs of the COPD. Differences between intensive care unit and respiratory intermediate care unit.Respir Med.2005;99:894900.
  9. Junker C,Zimmerman JE,Alzola C,Draper EA,Wagner DP.A multicenter description of intermediate‐care patients. Comparison with ICU low‐risk monitor patients.Chest.2002;121:12531261.
  10. Nasraway SA,Cohen IL,Dennis RC, et al.Guidelines on admission and discharge for adult intermediate care units. American College of Critical Care Medicine of the Society of Critical Care Medicine.Crit Care Med.1998;26:607610.
  11. Vincent JL,Burchardi H.Do we need intermediate care units?Intensive Care Med.1999;25:13451349.
  12. Le Gall JR,Lemeshow S,Saulnier F.A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study.JAMA.1993;270:29572963.
  13. Auriant I,Vinatier I,Thaler F,Tourneur M,Loirat P.Simplified acute physiology score II for measuring severity of illness in intermediate care units.Crit Care Med.1998;26:13681371.
  14. Zimmerman JE,Wagner DP,Knaus WA,Williams JF,Kolakowski D,Draper EA.The use of risk predictions to identify candidates for intermediate care units. Implications for intensive care utilization and cost.Chest.1995;108:490499.
  15. Teres D,Rapoport J.Identifying patients with high risk of high cost.Chest1991;99:530531.
  16. Cheng DC,Byrick RJ,Knobel E.Structural models for intermediate care areas.Crit Care Med.1999;27:22662271.
  17. Lawless S,Zaritsky A,Phipps J,Riley‐Lawless K.Characteristics of pediatric intermediate care units in pediatric training programs.Crit Care Med.1991;19:10041007.
  18. Metnitz PG,Valentin A,Vesely H, et al.Prognostic performance and customization of the SAPS II: results of a multicenter Austrian study.Int Care Med.1999;25:192197.
  19. Katsaragakis S,Papadimitropoulos K,Antonakis P,Strergiopoulos S,Konstadoulakis MM,Androulakis G.Comparison of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems in a single Greek intensive care unit.Crit Care Med.2000;28:426432.
  20. Beck DH,Smith GB,Pappachan JV,Millar B.External validation of the SAPS II, APACHE II and APACHE III prognostic models in South England: a multicentre study.Intensive Care Med.2003;29:249256.
  21. Aegerter P,Boumendil A,Retbi A,Minvielle E,Dervaux B,Guidet B.SAPS II revisited.Intensive Care Med.2005;31:416423.
  22. Le Gall JR,Neuman A,Hemery F, et al.Mortality prediction using SAPS II: an update for French intensive care units.Crit Care.2005;9:R645R652.
  23. Campbell AJ,Cook JA,Adey G,Cuthbertson BH.Predicting death and readmission after intensive care discharge.Br J Anaesth.2008;100:656662.
  24. Kripalani S,Pope AC,Rask K, et al.Hospitalists as teachers.J Gen Intern Med.2004;19:815.
  25. Kulaga ME,Charney P,O'Mahony SP, et al.The positive impact of initiation of hospitalist clinician educators.J Gen Intern Med.2004;19:293301.
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Hospitalized patients are becoming increasingly complex. The care of such patients may be impacted by the limited resources of the general ward and might benefit from more intensive monitoring in an intensive care unit (ICU)‐like setting. In light of this problem, the intermediate care units (ImCU) may provide a cost‐effective alternative by providing higher levels of staffing tailored to patient needs, without incurring the cost of an ICU admission. The ImCU can reduce costs and improves ICU utilization for sicker patients, decrease ICU readmissions, promote greater flexibility in patient triage, and decrease mortality rates in hospital wards.18

The characteristics of ImCUs depend on resource availability, institutional infrastructure, and the organization and funding of the parent healthcare system. The ImCU may function as a step‐up or step‐down unit, or may provide specialty care for cardiac, neurologic, respiratory, or surgical conditions.811 These units can expand opportunities for co‐management and, at the same time, offer the occasion for training residents to follow up patients through different levels of care (from the general ward to ImCU). In the same way, the multidisciplinary approach of the ImCU can improve the center's teaching potential.

Characterizing the ImCU population requires the assessment of their severity of illness, which is crucial for the evaluation of risk‐adjusted outcomes. The present study evaluated the impact of a hospitalist‐led ImCU on observed‐to‐expected mortality ratios, as well as its role in co‐management and teaching.

PATIENTS AND METHODS

We performed a retrospective observational study, with data collected from April 2006 to April 2010 in a single academic medical center in Pamplona, Spain. The ImCU is a 9‐bed unit adjacent to, but independent from, the mixed ICU. Each bed is equipped with continuous telemetry, pulse oximetry, noninvasive arterial blood pressure, central venous pressure monitoring, and noninvasive pressure support ventilation. The signals are relayed to a central monitoring station and the nurse‐to‐patient ratio is 1:3.

The ImCU rounding team is multidisciplinary, and involves the hospital pharmacist, a nurse, the ImCU resident, the specialist or surgeon, and the attending hospitalist. After the triage process, ImCU patients were admitted to the attending hospitalist, who was responsible for admission and discharge of all ImCU patients. The hospitalist ordered diagnostic or therapeutic interventions as needed, with the exception of orders for procedures or consultations related with specialist/surgeon's specific needs.

Admission and discharge criteria for the ImCU were set according to guidelines defined by The American College of Critical Care Medicine,10 and also served as inclusion criteria for the present study. Exclusion criteria included: age less than 18 years old, severe respiratory failure, status epilepticus, and catastrophic brain illness. Patients admitted for drug administration and desensitization, and also ImCU readmissions, were excluded from data analysis. Patients came from medical and surgical wards, ICU, the operating room, and the emergency room.

A total of 756 patients were admitted to our ImCU during the study period. Patient demographics, past medical history, physiologic parameters at the time of admission, and survival to hospital discharge were recorded for all patients. Patient demographics include: age, gender, location before ImCU admission, length of stay before ImCU admission, reason for ImCU admission, anatomic site of surgery (if applicable), planned or unplanned admission, and infection status (nosocomial). Past medical history includes: the presence of arterial hypertension, diabetes, cirrhosis, chronic renal failure, chronic heart failure, cancer, hematological malignancy, chronic obstructive pulmonary disease (COPD), human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), immunosuppression, radiotherapy, chemotherapy, steroid treatment, and alcoholism. Physiologic parameters abstracted are described in Table 1. We used the Simplified Acute Physiology Score II (SAPS II),12 as a prognostic and severity score. SAPS II is the only previously validated score in intermediate care.13 In‐hospital mortality was the clinical outcome measured.

Physiologic Parameters Evaluated at ImCU Admission
  • Abbreviations: ImCU, intermediate care unit.

Vital signs
Glasgow Coma Scale
Serum bilirubin
Serum creatinine
Urea nitrogen
Leucocyte count
Serum sodium
Serum potassium
Bicarbonate levels
Urinary output in the first 24 hr
Oxygenation and ventilatory support

Data were entered into a computer database by the authors. Statistical analysis was not blinded, and was performed using SPSS for Windows, version 15.0 (SPSS Inc, Chicago, IL). Continuous variables were reported as mean standard deviation or median (25%‐75% interquartile range). For nonparametric measure of statistical dependence of quantitative variables, we used Spearman's correlation coefficient. Discrimination was evaluated by calculating the area under receiver operating characteristic curve (AUROC).

The study protocol was approved by the institutional review board at the Clnica Universidad de Navarra in Pamplona, Spain.

RESULTS

Four hundred fifty‐six patients were included in data analysis. Three hundred patients were excluded: 61 low‐risk patients (drug administration and desensitization), 147 readmissions, and 92 patients for missing variables. Patient characteristics, including probability of death following ImCU admission and discharge location, are summarized in Table 2. The mean age was 65.6 years, and about 35% of patients had a SAPS II‐based risk of death higher than 25% at the time of ImCU admission. The median length of stay was 4 (3‐7) days.

Patient Characteristics and Mortality (n = 456)
  • Abbreviations: ICU, intensive care unit; ImCU, intermediate care unit; O/E, observed‐to‐expected mortality ratio; SAPS II, Simplified Acute Physiology Score II.

  • Denominator data represents the total population of transferred patients.

Age (yr)65.6 14.3
Gender 
Male283 (62.1%)
Female173 (37.9%)
Location prior to admission 
General ward252 (55.3%)
Emergency room96 (21.1%)
ICU63 (13.8%)
Operating room28 (6.1%)
Other hospital17 (3.7%)
Probability of in‐hospital mortality based on SAPS II 
<10%128 (28.1%)
11%‐25%176 (38.6%)
26%‐50%107 (23.4%)
>50%45 (9.9%)
Global expected mortality (in‐hospital)23.2%
Global observed mortality (in‐hospital)20.6% (94/456)
O/E mortality ratio0.89
Discharge location 
General ward352/456 (77.2%)
ICU65/456 (14.3%)
Home1/456 (0.2%)
Other hospital11/456 (2.4%)
Death location 
ImCU27/456 (5.9%)
ICU (transferred patients)32/65* (49.2%)
General ward35/352* (9.9%)

Outcomes

The mean SAPS II of the cohort was 37 12 points, and the expected mortality derived from this score was 23.2%. The observed in‐hospital mortality was 20.6% (94/456) resulting in an observed‐to‐expected mortality ratio of 0.89 (Table 2). Reasons for ImCU admission, as well as mortality ratios, are described in Table 3. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (Rho = 1.0, P < 0.001) (Figure 1). The AUROC for SAPS II predicting in‐hospital mortality was 0.75 (P < 0.001).

Figure 1
Correlation between observed and expected mortality based on SAPS II. (A) Rho = 1.0, P < 0.001. (B) Simplified Acute Physiology Score II (SAPS II).
Reasons for ImCU Admission and Severity Score Index
ConditionPatientsSAPS IIExpected MortalityObserved MortalityO/E Ratio
  • Abbreviations: GI, gastrointestinal complications; ImCU, intermediate care unit; O/E ratio, observed‐to‐expected mortality ratios; SAPS II, Simplified Acute Physiology Score II.

Respiratory failure153 (33.6%)36.1 9.721.5 15.3%25.5% (39)1.19
Sepsis88 (19.3%)45.7 15.137.5 25.1%22.7% (20)0.61
Cardiovascular72 (15.8%)35.7 11.021.3 16.6%23.6% (17)1.11
Perioperative59 (12.9%)28.9 9.912.9 11.7%5.1% (3)0.40
Complex monitoring34 (7.5%)33.2 12.119.1 16.3%14.7% (5)0.77
GI complications33 (7.2%)32.1 8.315.6 10.7%12.1% (4)0.78
Neurologic10 (2.2%)40.9 10.629.7 20.0%30.0% (3)1.01
Liver failure7 (1.5%)42.1 17.230.9 29.4%42.9% (3)1.39

Co‐Management and Teaching

During the study period, 382/456 (83.8%) patients were co‐managed with 9 medical and 7 surgical teams (Table 4). From the period of 2006‐2008, a total of 37/106 (34.9%) patients were co‐managed with surgeons, and just 5/37 (13.5%) were co‐managed preoperatively before ImCU admission. In the next 2 years, the patient total increased to 69/106 (65.1%), and preoperative surgical co‐management significantly increased to 25/69 (36.2%) (P = 0.014).

Co‐Management Areas and Patient Distribution
Medical   
Surgical 
  • NOTE: Data are number of patients and percentage of total co‐managed patients (n = 382). Seventy‐four patients from the Department of Internal Medicine/Hospitalists Unit were excluded from this analysis.

Oncology100 (21.9%)Neurology17 (3.7%)
Hepatology43 (9.4%)Cardiology14 (3.1%)
Pulmonology36 (7.9%)Nephrology14 (3.1%)
Hematology20 (4.4%)Others13 (2.9%)
Gastroenterology19 (4.2%)  
Total276 
General44 (9.6%)Orthopedics6 (1.3%)
Vascular23 (5.0%)Urology5 (1.1%)
Thoracic11 (2.4%)Others10 (2.2%)
Neurosurgery7 (1.5%)  
Total106 

Our academic medical center enrolls 46 new residents every year. Since the creation of the ImCU in 2006, residents from different medical subspecialties and from general surgery received training in intermediate care and hospital medicine. All residents rotated into the ImCU for 1‐3 months working 8 hours a day. In 2006, when the unit was opened, 2 residents from internal medicine (4.3%) rotated in the ImCU. Thereafter, a significant increase in the number of training residents was observed, reaching 30.4% of the total resident pool (14/46) in 2010 (P = 0.002).

DISCUSSION

To the best of our knowledge, this is the first description of hospitalists in intermediate care. In Spain, where hospital medicine is early in development but expanding, critical and intermediate care units are usually staffed by intensivists or anesthesiologists. Staffing an ImCU with hospitalists, using a multidisciplinary co‐management model, is a novel staffing solution for acutely ill patients.

Approximately 35% of ICU patients are low risk, admitted mainly for monitoring purposes.9, 14 In contrast, some patients are treated on general wards when they should receive more intensive care and monitoring.15 Intermediate care units could improve cost containment and triage flexibility, while tailoring treatments according to patient needs. In general, ImCUs require lower nurse‐to‐patient ratios, and less expensive equipment and supplies than ICUs, while retaining the capability of responding appropriately to acute events.16 Moreover, patient and family satisfaction may be increased as a result of more liberal visitation policies and a less noisy environment.17

This study was not designed to measure the cost‐effectiveness of the ImCU. Surprisingly, there are few reports in the last 2 decades demonstrating the efficacy and cost containment of intermediate care. The majority of the studies were retrospective or uncontrolled observations.27 To our knowledge, only 1 randomized controlled trial1 and 1 multicenter prospective cost study exist.8 Further research is needed in this area, with larger, prospective randomized controlled trials, before the benefits and limitations of intermediate care can be fully determined.

Description of the ImCU patients depends on accurate severity scoring. The efficacy and reliability of these scores has been described only for ICU patients and their role for predicting mortality in the ImCU is uncertain. There is only 1 report using SAPS II in intermediate care, showing good discriminant power and calibration in a cohort of 433 patients.13 Auriant et al described, in that cohort, an observed mortality rate of 8.1% with an expected mortality rate of 8.7%.13 In contrast, our expected mortality rate was considerably higher (23.2%). Although ImCUs are generally created for low‐risk patients and monitoring purposes, our population was more similar to an ICU population, with very high risk for major complications and mortality.1823 The contribution of oncologic patients (22% of the total series; most of them with advanced disease, elevated SAPS II [42.2 13.6] and do‐not‐resuscitate orders), probably contributed to the higher acuity of our ImCU population. The correlation of our present data supports the value of SAPS II as a prognostic score in intermediate care, even for patients sicker than those reported by Auriant et al.13 Intermediate care is also a valuable setting to expand a co‐management model with different medical and surgical specialties.

Similarly, since the creation of the ImCU at our institution in 2006, there is a substantial increase in the number of residents rotating through our ImCU. Previous studies showed positive results of hospitalists as clinical educators in various settings.24, 25

In conclusion, intermediate care serves as an expansion of role for hospitalists at our institution; and clinicians, trainees, and patients may benefit from co‐management and teaching opportunities at this unique level of care. An ImCU led by hospitalists showed encouraging results in terms of observed‐to‐expected mortality ratios for acutely ill patients. SAPS II is a useful tool for prognostic evaluation of ImCU patients. However, results of this study should be confirmed with larger, prospective trials at multiple centers.

Acknowledgements

The authors thank Dr Efren Manjarrez for the final manuscript revision, and the ImCU Nursing Staff for their unconditional support in patient care.

Hospitalized patients are becoming increasingly complex. The care of such patients may be impacted by the limited resources of the general ward and might benefit from more intensive monitoring in an intensive care unit (ICU)‐like setting. In light of this problem, the intermediate care units (ImCU) may provide a cost‐effective alternative by providing higher levels of staffing tailored to patient needs, without incurring the cost of an ICU admission. The ImCU can reduce costs and improves ICU utilization for sicker patients, decrease ICU readmissions, promote greater flexibility in patient triage, and decrease mortality rates in hospital wards.18

The characteristics of ImCUs depend on resource availability, institutional infrastructure, and the organization and funding of the parent healthcare system. The ImCU may function as a step‐up or step‐down unit, or may provide specialty care for cardiac, neurologic, respiratory, or surgical conditions.811 These units can expand opportunities for co‐management and, at the same time, offer the occasion for training residents to follow up patients through different levels of care (from the general ward to ImCU). In the same way, the multidisciplinary approach of the ImCU can improve the center's teaching potential.

Characterizing the ImCU population requires the assessment of their severity of illness, which is crucial for the evaluation of risk‐adjusted outcomes. The present study evaluated the impact of a hospitalist‐led ImCU on observed‐to‐expected mortality ratios, as well as its role in co‐management and teaching.

PATIENTS AND METHODS

We performed a retrospective observational study, with data collected from April 2006 to April 2010 in a single academic medical center in Pamplona, Spain. The ImCU is a 9‐bed unit adjacent to, but independent from, the mixed ICU. Each bed is equipped with continuous telemetry, pulse oximetry, noninvasive arterial blood pressure, central venous pressure monitoring, and noninvasive pressure support ventilation. The signals are relayed to a central monitoring station and the nurse‐to‐patient ratio is 1:3.

The ImCU rounding team is multidisciplinary, and involves the hospital pharmacist, a nurse, the ImCU resident, the specialist or surgeon, and the attending hospitalist. After the triage process, ImCU patients were admitted to the attending hospitalist, who was responsible for admission and discharge of all ImCU patients. The hospitalist ordered diagnostic or therapeutic interventions as needed, with the exception of orders for procedures or consultations related with specialist/surgeon's specific needs.

Admission and discharge criteria for the ImCU were set according to guidelines defined by The American College of Critical Care Medicine,10 and also served as inclusion criteria for the present study. Exclusion criteria included: age less than 18 years old, severe respiratory failure, status epilepticus, and catastrophic brain illness. Patients admitted for drug administration and desensitization, and also ImCU readmissions, were excluded from data analysis. Patients came from medical and surgical wards, ICU, the operating room, and the emergency room.

A total of 756 patients were admitted to our ImCU during the study period. Patient demographics, past medical history, physiologic parameters at the time of admission, and survival to hospital discharge were recorded for all patients. Patient demographics include: age, gender, location before ImCU admission, length of stay before ImCU admission, reason for ImCU admission, anatomic site of surgery (if applicable), planned or unplanned admission, and infection status (nosocomial). Past medical history includes: the presence of arterial hypertension, diabetes, cirrhosis, chronic renal failure, chronic heart failure, cancer, hematological malignancy, chronic obstructive pulmonary disease (COPD), human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), immunosuppression, radiotherapy, chemotherapy, steroid treatment, and alcoholism. Physiologic parameters abstracted are described in Table 1. We used the Simplified Acute Physiology Score II (SAPS II),12 as a prognostic and severity score. SAPS II is the only previously validated score in intermediate care.13 In‐hospital mortality was the clinical outcome measured.

Physiologic Parameters Evaluated at ImCU Admission
  • Abbreviations: ImCU, intermediate care unit.

Vital signs
Glasgow Coma Scale
Serum bilirubin
Serum creatinine
Urea nitrogen
Leucocyte count
Serum sodium
Serum potassium
Bicarbonate levels
Urinary output in the first 24 hr
Oxygenation and ventilatory support

Data were entered into a computer database by the authors. Statistical analysis was not blinded, and was performed using SPSS for Windows, version 15.0 (SPSS Inc, Chicago, IL). Continuous variables were reported as mean standard deviation or median (25%‐75% interquartile range). For nonparametric measure of statistical dependence of quantitative variables, we used Spearman's correlation coefficient. Discrimination was evaluated by calculating the area under receiver operating characteristic curve (AUROC).

The study protocol was approved by the institutional review board at the Clnica Universidad de Navarra in Pamplona, Spain.

RESULTS

Four hundred fifty‐six patients were included in data analysis. Three hundred patients were excluded: 61 low‐risk patients (drug administration and desensitization), 147 readmissions, and 92 patients for missing variables. Patient characteristics, including probability of death following ImCU admission and discharge location, are summarized in Table 2. The mean age was 65.6 years, and about 35% of patients had a SAPS II‐based risk of death higher than 25% at the time of ImCU admission. The median length of stay was 4 (3‐7) days.

Patient Characteristics and Mortality (n = 456)
  • Abbreviations: ICU, intensive care unit; ImCU, intermediate care unit; O/E, observed‐to‐expected mortality ratio; SAPS II, Simplified Acute Physiology Score II.

  • Denominator data represents the total population of transferred patients.

Age (yr)65.6 14.3
Gender 
Male283 (62.1%)
Female173 (37.9%)
Location prior to admission 
General ward252 (55.3%)
Emergency room96 (21.1%)
ICU63 (13.8%)
Operating room28 (6.1%)
Other hospital17 (3.7%)
Probability of in‐hospital mortality based on SAPS II 
<10%128 (28.1%)
11%‐25%176 (38.6%)
26%‐50%107 (23.4%)
>50%45 (9.9%)
Global expected mortality (in‐hospital)23.2%
Global observed mortality (in‐hospital)20.6% (94/456)
O/E mortality ratio0.89
Discharge location 
General ward352/456 (77.2%)
ICU65/456 (14.3%)
Home1/456 (0.2%)
Other hospital11/456 (2.4%)
Death location 
ImCU27/456 (5.9%)
ICU (transferred patients)32/65* (49.2%)
General ward35/352* (9.9%)

Outcomes

The mean SAPS II of the cohort was 37 12 points, and the expected mortality derived from this score was 23.2%. The observed in‐hospital mortality was 20.6% (94/456) resulting in an observed‐to‐expected mortality ratio of 0.89 (Table 2). Reasons for ImCU admission, as well as mortality ratios, are described in Table 3. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (Rho = 1.0, P < 0.001) (Figure 1). The AUROC for SAPS II predicting in‐hospital mortality was 0.75 (P < 0.001).

Figure 1
Correlation between observed and expected mortality based on SAPS II. (A) Rho = 1.0, P < 0.001. (B) Simplified Acute Physiology Score II (SAPS II).
Reasons for ImCU Admission and Severity Score Index
ConditionPatientsSAPS IIExpected MortalityObserved MortalityO/E Ratio
  • Abbreviations: GI, gastrointestinal complications; ImCU, intermediate care unit; O/E ratio, observed‐to‐expected mortality ratios; SAPS II, Simplified Acute Physiology Score II.

Respiratory failure153 (33.6%)36.1 9.721.5 15.3%25.5% (39)1.19
Sepsis88 (19.3%)45.7 15.137.5 25.1%22.7% (20)0.61
Cardiovascular72 (15.8%)35.7 11.021.3 16.6%23.6% (17)1.11
Perioperative59 (12.9%)28.9 9.912.9 11.7%5.1% (3)0.40
Complex monitoring34 (7.5%)33.2 12.119.1 16.3%14.7% (5)0.77
GI complications33 (7.2%)32.1 8.315.6 10.7%12.1% (4)0.78
Neurologic10 (2.2%)40.9 10.629.7 20.0%30.0% (3)1.01
Liver failure7 (1.5%)42.1 17.230.9 29.4%42.9% (3)1.39

Co‐Management and Teaching

During the study period, 382/456 (83.8%) patients were co‐managed with 9 medical and 7 surgical teams (Table 4). From the period of 2006‐2008, a total of 37/106 (34.9%) patients were co‐managed with surgeons, and just 5/37 (13.5%) were co‐managed preoperatively before ImCU admission. In the next 2 years, the patient total increased to 69/106 (65.1%), and preoperative surgical co‐management significantly increased to 25/69 (36.2%) (P = 0.014).

Co‐Management Areas and Patient Distribution
Medical   
Surgical 
  • NOTE: Data are number of patients and percentage of total co‐managed patients (n = 382). Seventy‐four patients from the Department of Internal Medicine/Hospitalists Unit were excluded from this analysis.

Oncology100 (21.9%)Neurology17 (3.7%)
Hepatology43 (9.4%)Cardiology14 (3.1%)
Pulmonology36 (7.9%)Nephrology14 (3.1%)
Hematology20 (4.4%)Others13 (2.9%)
Gastroenterology19 (4.2%)  
Total276 
General44 (9.6%)Orthopedics6 (1.3%)
Vascular23 (5.0%)Urology5 (1.1%)
Thoracic11 (2.4%)Others10 (2.2%)
Neurosurgery7 (1.5%)  
Total106 

Our academic medical center enrolls 46 new residents every year. Since the creation of the ImCU in 2006, residents from different medical subspecialties and from general surgery received training in intermediate care and hospital medicine. All residents rotated into the ImCU for 1‐3 months working 8 hours a day. In 2006, when the unit was opened, 2 residents from internal medicine (4.3%) rotated in the ImCU. Thereafter, a significant increase in the number of training residents was observed, reaching 30.4% of the total resident pool (14/46) in 2010 (P = 0.002).

DISCUSSION

To the best of our knowledge, this is the first description of hospitalists in intermediate care. In Spain, where hospital medicine is early in development but expanding, critical and intermediate care units are usually staffed by intensivists or anesthesiologists. Staffing an ImCU with hospitalists, using a multidisciplinary co‐management model, is a novel staffing solution for acutely ill patients.

Approximately 35% of ICU patients are low risk, admitted mainly for monitoring purposes.9, 14 In contrast, some patients are treated on general wards when they should receive more intensive care and monitoring.15 Intermediate care units could improve cost containment and triage flexibility, while tailoring treatments according to patient needs. In general, ImCUs require lower nurse‐to‐patient ratios, and less expensive equipment and supplies than ICUs, while retaining the capability of responding appropriately to acute events.16 Moreover, patient and family satisfaction may be increased as a result of more liberal visitation policies and a less noisy environment.17

This study was not designed to measure the cost‐effectiveness of the ImCU. Surprisingly, there are few reports in the last 2 decades demonstrating the efficacy and cost containment of intermediate care. The majority of the studies were retrospective or uncontrolled observations.27 To our knowledge, only 1 randomized controlled trial1 and 1 multicenter prospective cost study exist.8 Further research is needed in this area, with larger, prospective randomized controlled trials, before the benefits and limitations of intermediate care can be fully determined.

Description of the ImCU patients depends on accurate severity scoring. The efficacy and reliability of these scores has been described only for ICU patients and their role for predicting mortality in the ImCU is uncertain. There is only 1 report using SAPS II in intermediate care, showing good discriminant power and calibration in a cohort of 433 patients.13 Auriant et al described, in that cohort, an observed mortality rate of 8.1% with an expected mortality rate of 8.7%.13 In contrast, our expected mortality rate was considerably higher (23.2%). Although ImCUs are generally created for low‐risk patients and monitoring purposes, our population was more similar to an ICU population, with very high risk for major complications and mortality.1823 The contribution of oncologic patients (22% of the total series; most of them with advanced disease, elevated SAPS II [42.2 13.6] and do‐not‐resuscitate orders), probably contributed to the higher acuity of our ImCU population. The correlation of our present data supports the value of SAPS II as a prognostic score in intermediate care, even for patients sicker than those reported by Auriant et al.13 Intermediate care is also a valuable setting to expand a co‐management model with different medical and surgical specialties.

Similarly, since the creation of the ImCU at our institution in 2006, there is a substantial increase in the number of residents rotating through our ImCU. Previous studies showed positive results of hospitalists as clinical educators in various settings.24, 25

In conclusion, intermediate care serves as an expansion of role for hospitalists at our institution; and clinicians, trainees, and patients may benefit from co‐management and teaching opportunities at this unique level of care. An ImCU led by hospitalists showed encouraging results in terms of observed‐to‐expected mortality ratios for acutely ill patients. SAPS II is a useful tool for prognostic evaluation of ImCU patients. However, results of this study should be confirmed with larger, prospective trials at multiple centers.

Acknowledgements

The authors thank Dr Efren Manjarrez for the final manuscript revision, and the ImCU Nursing Staff for their unconditional support in patient care.

References
  1. Douglas S,Daly B,Rudy E,Song R,Dyer MA,Montenegro H.The cost‐effectiveness of a special care unit to care for the chronically critically ill.J Nurs Adm.1995;25:4753.
  2. Bone RC,Balk RA.Noninvasive respiratory care unit. A cost‐effective solution for the future.Chest.1988;93:390394.
  3. Elpern EH,Silver MR,Rosen RL,Bone RC.The noninvasive respiratory care unit. Patterns of use and financial implications.Chest.1991;99:205208.
  4. Franklin CM,Rackow EC,Mamdani B,Nightingale S,Burke G,Weil MH.Decreases in mortality on a large urban medical service by facilitating access to critical care. An alternative to rationing.Arch Intern Med.1988;148:14031405.
  5. Byrick RJ,Power JD,Ycas JO,Brown KA.Impact of an intermediate care area on ICU utilization after cardiac surgery.Crit Care Med.1986;14:869872.
  6. Byrick RJ,Mazer CD,Caskennette GM.Closure of an intermediate care unit. Impact on critical care utilization.Chest.1993;104:876881.
  7. Durbin CG,Kopel RF.A case‐control study of patients readmitted to the intensive care unit.Crit Care Med.1993;21:15471553.
  8. Bertolini G,Confalonieri M,Rossi C, et al.Costs of the COPD. Differences between intensive care unit and respiratory intermediate care unit.Respir Med.2005;99:894900.
  9. Junker C,Zimmerman JE,Alzola C,Draper EA,Wagner DP.A multicenter description of intermediate‐care patients. Comparison with ICU low‐risk monitor patients.Chest.2002;121:12531261.
  10. Nasraway SA,Cohen IL,Dennis RC, et al.Guidelines on admission and discharge for adult intermediate care units. American College of Critical Care Medicine of the Society of Critical Care Medicine.Crit Care Med.1998;26:607610.
  11. Vincent JL,Burchardi H.Do we need intermediate care units?Intensive Care Med.1999;25:13451349.
  12. Le Gall JR,Lemeshow S,Saulnier F.A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study.JAMA.1993;270:29572963.
  13. Auriant I,Vinatier I,Thaler F,Tourneur M,Loirat P.Simplified acute physiology score II for measuring severity of illness in intermediate care units.Crit Care Med.1998;26:13681371.
  14. Zimmerman JE,Wagner DP,Knaus WA,Williams JF,Kolakowski D,Draper EA.The use of risk predictions to identify candidates for intermediate care units. Implications for intensive care utilization and cost.Chest.1995;108:490499.
  15. Teres D,Rapoport J.Identifying patients with high risk of high cost.Chest1991;99:530531.
  16. Cheng DC,Byrick RJ,Knobel E.Structural models for intermediate care areas.Crit Care Med.1999;27:22662271.
  17. Lawless S,Zaritsky A,Phipps J,Riley‐Lawless K.Characteristics of pediatric intermediate care units in pediatric training programs.Crit Care Med.1991;19:10041007.
  18. Metnitz PG,Valentin A,Vesely H, et al.Prognostic performance and customization of the SAPS II: results of a multicenter Austrian study.Int Care Med.1999;25:192197.
  19. Katsaragakis S,Papadimitropoulos K,Antonakis P,Strergiopoulos S,Konstadoulakis MM,Androulakis G.Comparison of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems in a single Greek intensive care unit.Crit Care Med.2000;28:426432.
  20. Beck DH,Smith GB,Pappachan JV,Millar B.External validation of the SAPS II, APACHE II and APACHE III prognostic models in South England: a multicentre study.Intensive Care Med.2003;29:249256.
  21. Aegerter P,Boumendil A,Retbi A,Minvielle E,Dervaux B,Guidet B.SAPS II revisited.Intensive Care Med.2005;31:416423.
  22. Le Gall JR,Neuman A,Hemery F, et al.Mortality prediction using SAPS II: an update for French intensive care units.Crit Care.2005;9:R645R652.
  23. Campbell AJ,Cook JA,Adey G,Cuthbertson BH.Predicting death and readmission after intensive care discharge.Br J Anaesth.2008;100:656662.
  24. Kripalani S,Pope AC,Rask K, et al.Hospitalists as teachers.J Gen Intern Med.2004;19:815.
  25. Kulaga ME,Charney P,O'Mahony SP, et al.The positive impact of initiation of hospitalist clinician educators.J Gen Intern Med.2004;19:293301.
References
  1. Douglas S,Daly B,Rudy E,Song R,Dyer MA,Montenegro H.The cost‐effectiveness of a special care unit to care for the chronically critically ill.J Nurs Adm.1995;25:4753.
  2. Bone RC,Balk RA.Noninvasive respiratory care unit. A cost‐effective solution for the future.Chest.1988;93:390394.
  3. Elpern EH,Silver MR,Rosen RL,Bone RC.The noninvasive respiratory care unit. Patterns of use and financial implications.Chest.1991;99:205208.
  4. Franklin CM,Rackow EC,Mamdani B,Nightingale S,Burke G,Weil MH.Decreases in mortality on a large urban medical service by facilitating access to critical care. An alternative to rationing.Arch Intern Med.1988;148:14031405.
  5. Byrick RJ,Power JD,Ycas JO,Brown KA.Impact of an intermediate care area on ICU utilization after cardiac surgery.Crit Care Med.1986;14:869872.
  6. Byrick RJ,Mazer CD,Caskennette GM.Closure of an intermediate care unit. Impact on critical care utilization.Chest.1993;104:876881.
  7. Durbin CG,Kopel RF.A case‐control study of patients readmitted to the intensive care unit.Crit Care Med.1993;21:15471553.
  8. Bertolini G,Confalonieri M,Rossi C, et al.Costs of the COPD. Differences between intensive care unit and respiratory intermediate care unit.Respir Med.2005;99:894900.
  9. Junker C,Zimmerman JE,Alzola C,Draper EA,Wagner DP.A multicenter description of intermediate‐care patients. Comparison with ICU low‐risk monitor patients.Chest.2002;121:12531261.
  10. Nasraway SA,Cohen IL,Dennis RC, et al.Guidelines on admission and discharge for adult intermediate care units. American College of Critical Care Medicine of the Society of Critical Care Medicine.Crit Care Med.1998;26:607610.
  11. Vincent JL,Burchardi H.Do we need intermediate care units?Intensive Care Med.1999;25:13451349.
  12. Le Gall JR,Lemeshow S,Saulnier F.A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study.JAMA.1993;270:29572963.
  13. Auriant I,Vinatier I,Thaler F,Tourneur M,Loirat P.Simplified acute physiology score II for measuring severity of illness in intermediate care units.Crit Care Med.1998;26:13681371.
  14. Zimmerman JE,Wagner DP,Knaus WA,Williams JF,Kolakowski D,Draper EA.The use of risk predictions to identify candidates for intermediate care units. Implications for intensive care utilization and cost.Chest.1995;108:490499.
  15. Teres D,Rapoport J.Identifying patients with high risk of high cost.Chest1991;99:530531.
  16. Cheng DC,Byrick RJ,Knobel E.Structural models for intermediate care areas.Crit Care Med.1999;27:22662271.
  17. Lawless S,Zaritsky A,Phipps J,Riley‐Lawless K.Characteristics of pediatric intermediate care units in pediatric training programs.Crit Care Med.1991;19:10041007.
  18. Metnitz PG,Valentin A,Vesely H, et al.Prognostic performance and customization of the SAPS II: results of a multicenter Austrian study.Int Care Med.1999;25:192197.
  19. Katsaragakis S,Papadimitropoulos K,Antonakis P,Strergiopoulos S,Konstadoulakis MM,Androulakis G.Comparison of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems in a single Greek intensive care unit.Crit Care Med.2000;28:426432.
  20. Beck DH,Smith GB,Pappachan JV,Millar B.External validation of the SAPS II, APACHE II and APACHE III prognostic models in South England: a multicentre study.Intensive Care Med.2003;29:249256.
  21. Aegerter P,Boumendil A,Retbi A,Minvielle E,Dervaux B,Guidet B.SAPS II revisited.Intensive Care Med.2005;31:416423.
  22. Le Gall JR,Neuman A,Hemery F, et al.Mortality prediction using SAPS II: an update for French intensive care units.Crit Care.2005;9:R645R652.
  23. Campbell AJ,Cook JA,Adey G,Cuthbertson BH.Predicting death and readmission after intensive care discharge.Br J Anaesth.2008;100:656662.
  24. Kripalani S,Pope AC,Rask K, et al.Hospitalists as teachers.J Gen Intern Med.2004;19:815.
  25. Kulaga ME,Charney P,O'Mahony SP, et al.The positive impact of initiation of hospitalist clinician educators.J Gen Intern Med.2004;19:293301.
Issue
Journal of Hospital Medicine - 7(5)
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Journal of Hospital Medicine - 7(5)
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Results of a retrospective observational study of intermediate care staffed by hospitalists: Impact on mortality, co‐management, and teaching
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Results of a retrospective observational study of intermediate care staffed by hospitalists: Impact on mortality, co‐management, and teaching
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Department of Internal Medicine, Division of Intermediate Care and Hospitalists Unit, Clínica Universidad de Navarra, Avda Pío XII 36, Pamplona, Navarra CP 31008, Spain===
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Hospitalist Practice Models

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Job characteristics, satisfaction, and burnout across hospitalist practice models

Over the past 15 years, there has been dramatic growth in the number of hospitalist physicians in the United States and in the number of hospitals served by them.13 Hospitals are motivated to hire experienced hospitalists to staff their inpatient services,4 with goals that include obtaining cost‐savings and higher quality.59 The rapid growth of Hospital Medicine saw multiple types of hospital practice models emerge with differing job characteristics, clinical duties, workload, and compensation schemes.10 The extent of the variability of hospitalist jobs across practice models is not known.

Intensifying recruitment efforts and the concomitant increase in compensation for hospitalists over the last decade suggest that demand for hospitalists is strong and sustained.11 As a result, today's cohort of hospitalists has a wide range of choices of types of jobs, practice models, and locations. The diversity of available hospitalist jobs is characterized, for example, by setting (community hospital vs academic hospital), employer (hospital vs private practice), job duties (the amount and type of clinical work, and other administrative, teaching, or research duties), and intensity (work hours and duties to maximize income or lifestyle). How these choices relate to job satisfaction and burnout are also unknown.

The Society of Hospital Medicine (SHM) has administered surveys to hospitalist group leaders biennially since 2003.1215 These surveys, however, do not address issues related to individual hospitalist worklife, recruitment, and retention. In 2005, SHM convened a Career Satisfaction Task Force that designed and executed a national survey of hospitalists in 2009‐2010. The objective of this study is to evaluate how job characteristics vary by practice model, and the association of these characteristics and practice models with job satisfaction and burnout.

METHODS

Survey Instrument

A detailed description of the survey design, sampling strategy, data collection, and response rate calculations is described elsewhere.16 Portions of the 118‐item survey instrument assessed characteristics of the respondents' hospitalist group (12 items), details about their individual work patterns (12 items), and demographics (9 items). Work patterns were evaluated by the average number of clinical work days, consecutive days, hours per month, percentage of work assigned to night duty, and number of patient encounters. Average hours spent on nonclinical work, and the percentage of time allocated for clinical, administrative, teaching, and research activities were solicited. Additional items assessed specific clinical responsibilities, pretax earnings in FY2010, the availability of information technology capabilities, and the adequacy of available resources. Job and specialty satisfaction and 11 satisfaction domain measures were measured using validated scales.1726 Burnout symptoms were measured using a validated single‐item measure.26, 27

Sampling Strategy

We surveyed a national stratified sample of hospitalists in the US and Puerto Rico. We used the largest database of hospitalists (>24,000 names) currently available and maintained by the SHM as our sampling frame. We linked hospitalist employer information to hospital statistics from the American Hospital Association database28 to stratify the sample by number of hospital beds, geographic region, employment model, and specialty training, oversampling pediatric hospitalists due to small numbers. A respondent sample of about 700 hospitalists was calculated to be adequate to detect a 0.5 point difference in job satisfaction scores between subgroups assuming 90% power and alpha of 0.05. However, we sampled a total of 5389 addresses from the database to overcome the traditionally low physician response rates, duplicate sampling, bad addresses, and non‐hospitalists being included in the sampling frame. In addition, 2 multistate hospitalist companies (EmCare, In Compass Health) and 1 for‐profit hospital chain (HCA, Inc) financially sponsored this project with the stipulation that all of their hospitalist employees (n = 884) would be surveyed.

Data Collection

The healthcare consulting firm, Press Ganey, provided support with survey layout and administration following the modified Dillman method.29 Three rounds of coded surveys and solicitation letters from the investigators were mailed 2 weeks apart in November and December 2009. Because of low response rates to the mailed survey, an online survey was created using Survey Monkey and sent to 650 surveyees for whom e‐mail addresses were available, and administered at a kiosk for sample physicians during the SHM 2010 annual meeting.

Data Analysis

Nonresponse bias was measured by comparing characteristics between respondents of separate survey waves.30 We determined the validity of mailing addresses immediately following the survey period by mapping each address using Google, and if the address was a hospital, researching online whether or not the intended recipient was currently employed there. Practice characteristics were compared across 5 model categories distilled from the SHM & Medical Group Management Association survey: local hospitalist‐only group, multistate hospitalist group, multispecialty physician group, employer hospital, and university or medical school. Weighted proportions, means, and medians were calculated to account for oversampling of pediatric hospitalists. Differences in categorical measures were assessed using the chi‐square test and the design‐based F test for comparing weighted data. Weighted means (99% confidence intervals) and medians (interquartile ranges) were calculated. Because each parameter yielded a single outlier value across the 5 practice models, differences across weighted means were assessed using generalized linear models with the single outlier value chosen as the reference mean. Pair‐wise Wilcoxon rank sum test was used to compare median values. In these 4‐way comparisons of means and medians, significance was defined as P value of 0.0125 per Bonferroni correction. A single survey item solicited respondents to choose exactly 4 of 13 considerations most pertinent to job satisfaction. The proportion of respondents who scored 4 on a 5‐point Likert scale of the 11 satisfaction domains and 2 global measures of satisfaction, and burnout symptoms defined as 3 on a 5‐point single item measure were bar‐graphed. Chi‐square statistics were used to evaluate for differences across practice models. Statistical significance was defined by alpha less than 0.05, unless otherwise specified. All analyses were performed using STATA version 11.0 (College Station, TX). This study was approved by the Loyola University Institutional Review Board.

Survey data required cleaning prior to analysis. Missing gender information was imputed using the respondents' name. Responses to the item that asked to indicate the proportion of work dedicated to administrative responsibilities, clinical care, teaching, and research that did not add up to 100% were dropped. Two responses that indicated full‐time equivalent (FTE) of 0%, but whose respondents otherwise completed the survey implying they worked as clinical hospitalists, were replaced with values calculated from the given number of work hours relative to the median work hours in our sample. Out of range or implausible responses to the following items were dropped from analyses: the average number of billable encounters during a typical day or shift, number of shifts performing clinical activities during a typical month, pretax earnings, the year the respondent completed residency training, and the number of whole years practiced as a hospitalist. The proportion of selective item nonresponse was small and we did not, otherwise, impute missing data.

RESULTS

Response Rate

Of the 5389 originally sampled addresses, 1868 were undeliverable. Addresses were further excluded if they appeared in duplicate or were outdated. This yielded a total of 3105 eligible surveyees in the sample. As illustrated in Figure 1, 841 responded to the mailed survey and 5 responded to the Web‐based survey. After rejecting 67 non‐hospitalist respondents and 3 duplicate surveys, a total of 776 surveys were included in the final analysis. The adjusted response rate was 25.6% (776/3035). Members of SHM were more likely to return the survey than nonmembers. The adjusted response rate from hospitalists affiliated with the 3 sponsoring institutions was 6% (40/662). Because these respondents were more likely to be non‐members of SHM, we opted to analyze the responses from the sponsor hospitalists together with the sampled hospitalists. The demographics of the resulting pool of 816 respondents affiliated with over 650 unique hospitalist groups were representative of the original survey frame. We analyzed data from 794 of these who responded to the item indicating their hospitalist practice model. Demographic characteristics of responders and nonresponders to the practice model survey item were similar.

Figure 1
Sampling flow chart. Sponsors are: EmCare; In Compass Health; and HCA, Inc. Abbreviations: PG, Press Ganey Associates; SHM, Society of Hospital Medicine.

Characteristics of Hospitalists and Their Groups

Table 1 summarizes the characteristics of hospitalist respondents and their organizations by practice model. More (44%) respondents identified their practice model as directly employed by the hospital than other models, including multispecialty physician group (15%), multistate hospitalist group (14%), university or medical school (14%), local hospitalist group (12%), and other (2%). The median age of hospitalist respondents was 42 years, with 6.8 years of mean experience as a hospitalist. One third were women, 84% were married, and 46% had dependent children 6 years old or younger at home. Notably, hospitalists in multistate groups had fewer years of experience, and fewer hospitalists in local and multistate groups were married compared to hospitalists in other practice models.

Characteristics of Hospitalist Respondents and Their Hospitalist Groups by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: AHA, American Hospital Association; CI, confidence interval; EHR, electronic health record; IQR, interquartile range.

  • indicate the pairs of values for which a significant difference exists.

Hospitalist characteristics      
Age, weighted mean (99% CI)45 (42, 48)44 (42, 47)45 (43, 47)45 (43, 46)43 (40, 46) 
Years hospitalist experience, weighted mean (99% CI)8 (6, 9)*5 (4, 6)*8 (7, 9)7 (6, 7)8 (6, 9)<0.010*
Women, weighted %29303931430.118
Married, weighted %76778289810.009
At least 1 dependent child younger than age 6 living in home, weighted %47484347450.905
Pediatric specialty, n (%)<10<1011 (10%)57 (16%)36 (34%)<0.001
Hospitalist group characteristics      
Region, weighted %     <0.001
Northeast (AHA 1 & 2)1310162713 
South (AHA 3 & 4)1937132421 
Midwest (AHA 5 & 6)2324252226 
Mountain (AHA 7 & 8)2220161324 
West (AHA 9)2410311416 
No. beds of primary hospital, weighted %     <0.001
Up to 1491726122414 
1502993036363321 
3004492624292019 
450599138171121 
600 or more12671324 
No. of hospital facilities served by current practice, weighted %     <0.001
15370677766 
22022201624 
3 or more27913710 
No. of physicians in current practice, median (IQR)10 (5, 18)8 (6, 12)*14 (8, 25)*12 (6, 18)12 (7, 20)<0.001*, 0.001
No. of non‐physician providers in current practice, median (IQR)0 (0, 2)0 (0, 2)0 (0, 3)1 (0, 2)0 (0, 2) 
Available information technology capabilities, weighted %      
EHR to access physician notes5757755879<0.001
EHR to access nursing documentations68677475760.357
EHR to access laboratory or test results97899596960.054
Electronic order entry3019533856<0.001
Electronic billing38313636380.818
Access to EHR at home or off site78737882840.235
Access to Up‐to‐Date or other clinical guideline resources8077919296<0.001
Access to schedules, calendars, or other organizational resources56576667750.024
E‐mail, Web‐based paging, or other communication resources7463888990<0.001

Several differences in respondent group characteristics by practice model were found. Respondents in multistate hospitalist groups were more likely from the South and Midwest, while respondents from multispecialty groups were likely from the West. More multistate group practices were based in smaller hospitals, while academic hospitalists tended to practice in hospitals with 600 or more beds. Respondents employed by hospitals were more likely to practice at 1 hospital facility only, while local group practices were more likely to practice at 3 or more facilities. The median number of physicians in a hospitalist group was 11 (interquartile range [IQR] 6, 19). Local and multistate groups had fewer hospitalists compared to other models. Nonphysician providers were employed by nearly half of all hospitalist practices. Although almost all groups had access to some information technology, more academic hospitalists had access to electronic order entry, electronic physician notes, electronic clinical guidelines resources and communication technology, while local and multistate groups were least likely to have access to these resources.

Work Pattern Variations

Table 2 further details hospitalist work hours by practice model. The majority of hospitalists (78%) reported their position was full‐time (FTE 1.0), while 13% reported working less than full‐time (FTE <1.0). Only 5% of local group hospitalists worked part‐time, while 20% of multispecialty group hospitalists did. An additional 9% reported FTE >1.0, indicating their work hours exceeded the definition of a full‐time physician in their practice. Among full‐time hospitalists, local group members worked a greater number of shifts per month than employees of multispecialty groups, hospitals, and academic medical centers. Academic hospitalists reported higher numbers of consecutive clinical days worked on average, but fewer night shifts compared to hospitalists employed by multistate groups, multispecialty groups, and hospitals; fewer billable encounters than hospitalists in local and multistate groups; and more nonclinical work hours than hospitalists of any other practice model. Academic hospitalists also spent more time on teaching and research than other practice models. Hospitalists spent 11%‐18% of their time on administrative and committee responsibilities, with the least amount spent by hospitalists in multistate groups and the most in academic practice.

Hospitalist Work Hours by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: CI, confidence interval; FTE, full‐time equivalent.

  • indicate the pairs of values for which a significant difference exists. P value calculated using chi‐square test for comparing FTE categories with alpha defined as <0.05. Pairwise P values calculated using generalized linear models with a single outlier value as the reference value for all other comparisons and alpha defined as <0.0125 per Bonferroni correction.

FTE, weighted %0.058
FTE < 1.0613201214 
FTE = 1.08575748082 
FTE > 1.01013685 
Workload parameters, weighted mean (99% CI) 
Clinical shifts per month for FTE 1.019 (17, 20)*17 (16, 19)15 (14, 17)*16 (15, 16)15 (13, 17)<0.001*
Hours per clinical shift10 (9, 11)11 (10, 11)*10 (10, 11.0)11 (10, 11.0)10 (9, 10)*0.006*, 0.002
Consecutive days on clinical shift8 (6, 9)7 (6, 7)*6 (6, 7)7 (6, 7)9 (7, 10)*0.002*, <0.001
% Clinical shifts on nights20 (15, 25)23 (18, 28)*23 (17, 29)21 (17, 24)14 (9, 18)*0.001*, 0.002
% Night shifts spent in hospital61 (49, 74)*63 (52, 75)72 (62, 83)73 (67, 80)43 (29, 57)*0.010*, 0.003, <0.001
Billable encounters per clinical shift17 (14, 19)*17 (16, 18)14 (13, 15)15 (14, 16)13 (11, 14)*<0.001*, 0.002
Hours nonclinical work per month23 (12, 34)*19 (11, 27)31 (20, 42)30 (24, 36)71 (55, 86)*<0.001*
Hours clinical and nonclinical work per month for FTE 1.0202 (186, 219)211 (196, 226)184 (170, 198)*193 (186, 201)221 (203, 238)*<0.001*
Professional activity, weighted mean % (99% CI) 
Clinical84 (78, 89)*86 (81, 90)78 (72, 84)79 (76, 82)58 (51, 64)*<0.001*
Teaching2.3 (1, 5)*3 (1, 4)6 (4, 9)6 (5, 8)17 (14, 20)*<0.001*
Administration and Committee work13 (8, 19)11 (8, 15)*16 (10, 21)14 (12, 17)19 (14, 24)*0.001*
Research0 (0, 0)*1 (0, 2)0 (0, 1)1 (0, 1)7 (3, 11)*<0.001*

Table 3 tabulates other work pattern characteristics. Most hospitalists indicated that their current clinical work as hospitalists involved the general medical wards (100%), medical consultations (98%), and comanagement with specialists (92%). There were wide differences in participation in comanagement (100%, local groups vs 71%, academic), intensive care unit (ICU) responsibilities (94%, multistate groups vs 27%, academic), and nursing home care (30%, local groups vs 8%, academic). Among activities that are potentially not reimbursable, academic hospitalists were less likely to participate in coordination of patient transfers and code or rapid response teams, while multistate groups were least likely to participate in quality improvement activities. In total, 99% of hospitalists reported participating in at least 1 potentially nonreimbursable clinical activity.

Hospitalist Work Patterns and Compensation by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: CI, confidence interval.

  • indicate the pairs of values for which a significant difference exists. Pairwise P value calculated using generalized linear models with a single outlier value as the reference value for comparing earnings and alpha defined as <0.0125 per Bonferroni correction. P values calculated using chi‐square test for all other comparisons with alpha defined as <0.05.

Reimbursable activities, overlapping weighted % 
General medical ward1009910099990.809
Medical consultations999910098950.043
Comanagement with specialists10096969371<0.001
Preoperative evaluations92929088770.002
Intensive care unit8694677527<0.001
Skilled nursing facility or long‐term acute care facility301912168<0.001
Outpatient general medical practice4455100.241
Potentially nonreimbursable activities, overlapping weighted % 
Coordination of patient transfers92949593820.005
Quality improvement or patient safety initiatives81788389890.029
Code team or rapid response team5657536237<0.001
Information technology design or implementation42394751510.154
Admission triage for emergency department49464340310.132
Compensation scheme, weighted %<0.001
Salary only1821302947 
Salary plus performance incentive5472596753 
Fee‐for‐service201720 
Capitation00000 
Other97430 
Compensation links to incentives, overlapping weighted % 
No incentives40282929480.003
Patient satisfaction2339383814<0.001
Length of stay18172013100.208
Overall cost8119560.270
Test utilization22710<0.001
Clinical processes and outcomes2634444324<0.001
Other17292631250.087
Earnings, weighted mean dollars (99% CI)226,065 (202,891, 249,240)*225,613 (210,772, 240,454)202,617 (186,036, 219,198)206,087 (198,413, 213,460)166,478 (151,135, 181,821)*<0.001*

Hospitalist compensation schemes were significantly different across the practice models. Salary‐only schemes were most common among academic hospitalists (47%), while 72% of multistate groups used performance incentives in addition to salary. More local groups used fee‐for‐service compensation than other models. Incentives differed by practice model, with more multistate groups having incentives based on patient satisfaction, while more multispecialty physician groups had incentives based on clinical processes and outcomes than other models. Finally, mean earnings for academic hospitalists were significantly lower than for hospitalists of other practice models. Local and multistate group hospitalists earned more than any other practice model (all P <0.001), and $60,000 more than the lowest compensated academic hospitalists.

Components of Job Satisfaction

Hospitalists' rankings of the most important factors for job satisfaction revealed differences across models (Figure 2). Overall, hospitalists were most likely to consider optimal workload and compensation as important factors for job satisfaction from a list of 13 considerations. Local groups and academics were least likely to rank optimal workload as a top factor, and local group hospitalists were more likely to rank optimal autonomy than those of other models. Academic hospitalists had less concern for substantial pay, and more concern for the variety of tasks they perform and recognition by leaders, than other hospitalists.

Figure 2
Weighted proportion of respondents indicating the consideration as among the top 4 most important factors for job satisfaction by practice model. P values calculated using chi‐square tests across practice models with alpha defined as <0.05.

Job Satisfaction and Burnout Risk

Differences in the ratings of 4 of the 11 satisfaction and job characteristic domains were found across the practice models (Figure 3). Multispecialty group hospitalists were less satisfied with autonomy and their relationship with patients than other practice models, and along with multistate groups, reported the highest perceived workload. Organizational fairness was rated much higher by local group hospitalists than other practice models. Despite these differences in work patterns and satisfaction, there were no differences found in level of global job satisfaction, specialty satisfaction, or burnout across the practice models. Overall, 62% of respondents reported high job satisfaction (4 on a 1 to 5 scale), and 30% indicated burnout symptoms.

Figure 3
Weighted proportion of respondents with satisfaction domain score ≥4 (out of 5) and burnout scale score ≥3 (out of 5) by practice model. P values calculated using chi‐square tests across practice models with alpha defined as <0.05.

DISCUSSION

In our sample of US hospitalists, we found major differences in work patterns and compensation across hospitalist practice models, but no differences in job satisfaction, specialty satisfaction, and burnout. In particular, differences across these models included variations in hospitalist workload, hours, pay, and distribution of work activities. We found that hospitalists perform a variety of clinical and nonclinical tasks, for many of which there are not standard reimbursement mechanisms. We also found that features of a job that individual hospitalists considered most important vary by practice model.

Previous analysis of this data explored the overall state of hospitalist satisfaction.16 The present analysis offers a glimpse into hospitalists' systems‐orientation through a deeper look at their work patterns. The growth in the number of hospitalists who participate in intensive care medicine, specialty comanagement, and other work that involves close working relationships with specialist physicians confirms collaborative care as one of the dominant drivers of the hospitalist movement. At the level of indirect patient care, nearly all hospitalists contributed to work that facilitates coordination, quality, patient safety, or information technology. Understanding the integrative value of hospitalists outside of their clinical productivity may be of interest to hospital administrators.

Global satisfaction measures were similar across practice models. This finding is particularly interesting given the major differences in job characteristics seen among the practice models. This similarity in global satisfaction despite real differences in the nature of the job suggests that individuals find settings that allow them to address their individual professional goals. Our study demonstrates that, in 2010, Hospital Medicine has evolved enough to accommodate a wide variety of goals and needs.

While global satisfaction did not differ among practice types, hospitalists from various models did report differences in factors considered important to global satisfaction. While workload and pay were rated as influential across most models, the degree of importance was significantly different. In academic settings, substantial pay was not a top consideration for overall job satisfaction, whereas in local and multistate hospitalist groups, pay was a very close second in importance to optimal workload. These results may prove helpful for individual hospitalists trying to find their optimal job. For example, someone who is less concerned about workload, but wants to be paid well and have a high degree of autonomy, may find satisfaction in local hospitalist groups. However, for someone who is willing to sacrifice a higher salary for variety of activities, academic Hospital Medicine may be a better fit.

There is a concerning aspect of hospitalist job satisfaction that different practice models do not seem to solve. Control over personal time is a top consideration for many hospitalists across practice models, yet their satisfaction with personal time is low. As control over personal time is seen as a draw to the Hospital Medicine specialty, group leaders may need to evaluate their programs to ensure that schedules and workload support efforts for hospitalists to balance work and homelife commitments.

There are additional findings that are important for Hospital Medicine group leaders. Regardless of practice model, compensation and workload are often used as tools to recruit and retain hospitalists. While these tools may be effective, leaders may find more nuanced approaches to improving their hospitalists' overall satisfaction. Leaders of local hospitalist groups may find their hospitalists tolerant of heavier workloads as long as they are adequately rewarded and are given real autonomy over their work. However, leaders of academic programs may be missing the primary factor that can improve their hospitalists' satisfaction. Rather than asking for higher salaries to remain competitive, it may be more effective to advocate for time and training for their hospitalists to pursue important other activities beyond direct clinical care. Given that resources will always be limited, group leaders need to understand all of the elements that can contribute to hospitalist job satisfaction.

We point out several limitations to this study. First, our adjusted response rate of 25.6% is low for survey research, in general. As mentioned above, hospitalists are not easily identified in any available national physician database. Therefore, we deliberately designed our sampling strategy to error on the side of including ineligible surveyees to reduce systematic exclusion of practicing hospitalists. Using simple post hoc methods, we identified many nonhospitalists and bad addresses from our sample, but because these methods were exclusionary as opposed to confirmatory, we believe that a significant proportion of remaining nonrespondents may also have been ineligible for the survey. Although this does not fully address concerns about potential response bias, we believe that our sample representing a large number of hospitalist groups is adequate to make estimations about a nationally representative sample of practicing hospitalists. Second, in spite of our inclusive approach, we may still have excluded categories of practicing hospitalists. We were careful not to allow SHM members to represent all US hospitalists and included non‐members in the sampling frame, but the possibility of systematic exclusion that may alter our results remains a concern. Additionally, one of our goals was to characterize pediatric hospitalists independently from their adult‐patient counterparts. Despite oversampling of pediatricians, their sample was too small for a more detailed comparison across practice models. Also, self‐reported data about workload and compensation are subject to inaccuracies related to recall and cognitive biases. Last, this is a cross‐sectional study of hospitalist satisfaction at one point in time. Consequently, our sample may not be representative of very dissatisfied hospitalists who have already left their jobs.

The diversity found across existing practice models and the characteristics of the practices provide physicians with the opportunity to bring their unique skills and motivations to the hospitalist movement. As hospitals and other organizations seek to create, maintain, or grow hospitalist programs, the data provided here may prove useful to understand the relationship between practice characteristics and individual job satisfaction. Additionally, hospitalists looking for a job can consider these results as additional information to guide their choice of practice model and work patterns.

Acknowledgements

The authors thank Kenneth A. Rasinski for assistance with survey items refinement, and members of the SHM Career Satisfaction Task Force for their assistance in survey development.

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References
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Over the past 15 years, there has been dramatic growth in the number of hospitalist physicians in the United States and in the number of hospitals served by them.13 Hospitals are motivated to hire experienced hospitalists to staff their inpatient services,4 with goals that include obtaining cost‐savings and higher quality.59 The rapid growth of Hospital Medicine saw multiple types of hospital practice models emerge with differing job characteristics, clinical duties, workload, and compensation schemes.10 The extent of the variability of hospitalist jobs across practice models is not known.

Intensifying recruitment efforts and the concomitant increase in compensation for hospitalists over the last decade suggest that demand for hospitalists is strong and sustained.11 As a result, today's cohort of hospitalists has a wide range of choices of types of jobs, practice models, and locations. The diversity of available hospitalist jobs is characterized, for example, by setting (community hospital vs academic hospital), employer (hospital vs private practice), job duties (the amount and type of clinical work, and other administrative, teaching, or research duties), and intensity (work hours and duties to maximize income or lifestyle). How these choices relate to job satisfaction and burnout are also unknown.

The Society of Hospital Medicine (SHM) has administered surveys to hospitalist group leaders biennially since 2003.1215 These surveys, however, do not address issues related to individual hospitalist worklife, recruitment, and retention. In 2005, SHM convened a Career Satisfaction Task Force that designed and executed a national survey of hospitalists in 2009‐2010. The objective of this study is to evaluate how job characteristics vary by practice model, and the association of these characteristics and practice models with job satisfaction and burnout.

METHODS

Survey Instrument

A detailed description of the survey design, sampling strategy, data collection, and response rate calculations is described elsewhere.16 Portions of the 118‐item survey instrument assessed characteristics of the respondents' hospitalist group (12 items), details about their individual work patterns (12 items), and demographics (9 items). Work patterns were evaluated by the average number of clinical work days, consecutive days, hours per month, percentage of work assigned to night duty, and number of patient encounters. Average hours spent on nonclinical work, and the percentage of time allocated for clinical, administrative, teaching, and research activities were solicited. Additional items assessed specific clinical responsibilities, pretax earnings in FY2010, the availability of information technology capabilities, and the adequacy of available resources. Job and specialty satisfaction and 11 satisfaction domain measures were measured using validated scales.1726 Burnout symptoms were measured using a validated single‐item measure.26, 27

Sampling Strategy

We surveyed a national stratified sample of hospitalists in the US and Puerto Rico. We used the largest database of hospitalists (>24,000 names) currently available and maintained by the SHM as our sampling frame. We linked hospitalist employer information to hospital statistics from the American Hospital Association database28 to stratify the sample by number of hospital beds, geographic region, employment model, and specialty training, oversampling pediatric hospitalists due to small numbers. A respondent sample of about 700 hospitalists was calculated to be adequate to detect a 0.5 point difference in job satisfaction scores between subgroups assuming 90% power and alpha of 0.05. However, we sampled a total of 5389 addresses from the database to overcome the traditionally low physician response rates, duplicate sampling, bad addresses, and non‐hospitalists being included in the sampling frame. In addition, 2 multistate hospitalist companies (EmCare, In Compass Health) and 1 for‐profit hospital chain (HCA, Inc) financially sponsored this project with the stipulation that all of their hospitalist employees (n = 884) would be surveyed.

Data Collection

The healthcare consulting firm, Press Ganey, provided support with survey layout and administration following the modified Dillman method.29 Three rounds of coded surveys and solicitation letters from the investigators were mailed 2 weeks apart in November and December 2009. Because of low response rates to the mailed survey, an online survey was created using Survey Monkey and sent to 650 surveyees for whom e‐mail addresses were available, and administered at a kiosk for sample physicians during the SHM 2010 annual meeting.

Data Analysis

Nonresponse bias was measured by comparing characteristics between respondents of separate survey waves.30 We determined the validity of mailing addresses immediately following the survey period by mapping each address using Google, and if the address was a hospital, researching online whether or not the intended recipient was currently employed there. Practice characteristics were compared across 5 model categories distilled from the SHM & Medical Group Management Association survey: local hospitalist‐only group, multistate hospitalist group, multispecialty physician group, employer hospital, and university or medical school. Weighted proportions, means, and medians were calculated to account for oversampling of pediatric hospitalists. Differences in categorical measures were assessed using the chi‐square test and the design‐based F test for comparing weighted data. Weighted means (99% confidence intervals) and medians (interquartile ranges) were calculated. Because each parameter yielded a single outlier value across the 5 practice models, differences across weighted means were assessed using generalized linear models with the single outlier value chosen as the reference mean. Pair‐wise Wilcoxon rank sum test was used to compare median values. In these 4‐way comparisons of means and medians, significance was defined as P value of 0.0125 per Bonferroni correction. A single survey item solicited respondents to choose exactly 4 of 13 considerations most pertinent to job satisfaction. The proportion of respondents who scored 4 on a 5‐point Likert scale of the 11 satisfaction domains and 2 global measures of satisfaction, and burnout symptoms defined as 3 on a 5‐point single item measure were bar‐graphed. Chi‐square statistics were used to evaluate for differences across practice models. Statistical significance was defined by alpha less than 0.05, unless otherwise specified. All analyses were performed using STATA version 11.0 (College Station, TX). This study was approved by the Loyola University Institutional Review Board.

Survey data required cleaning prior to analysis. Missing gender information was imputed using the respondents' name. Responses to the item that asked to indicate the proportion of work dedicated to administrative responsibilities, clinical care, teaching, and research that did not add up to 100% were dropped. Two responses that indicated full‐time equivalent (FTE) of 0%, but whose respondents otherwise completed the survey implying they worked as clinical hospitalists, were replaced with values calculated from the given number of work hours relative to the median work hours in our sample. Out of range or implausible responses to the following items were dropped from analyses: the average number of billable encounters during a typical day or shift, number of shifts performing clinical activities during a typical month, pretax earnings, the year the respondent completed residency training, and the number of whole years practiced as a hospitalist. The proportion of selective item nonresponse was small and we did not, otherwise, impute missing data.

RESULTS

Response Rate

Of the 5389 originally sampled addresses, 1868 were undeliverable. Addresses were further excluded if they appeared in duplicate or were outdated. This yielded a total of 3105 eligible surveyees in the sample. As illustrated in Figure 1, 841 responded to the mailed survey and 5 responded to the Web‐based survey. After rejecting 67 non‐hospitalist respondents and 3 duplicate surveys, a total of 776 surveys were included in the final analysis. The adjusted response rate was 25.6% (776/3035). Members of SHM were more likely to return the survey than nonmembers. The adjusted response rate from hospitalists affiliated with the 3 sponsoring institutions was 6% (40/662). Because these respondents were more likely to be non‐members of SHM, we opted to analyze the responses from the sponsor hospitalists together with the sampled hospitalists. The demographics of the resulting pool of 816 respondents affiliated with over 650 unique hospitalist groups were representative of the original survey frame. We analyzed data from 794 of these who responded to the item indicating their hospitalist practice model. Demographic characteristics of responders and nonresponders to the practice model survey item were similar.

Figure 1
Sampling flow chart. Sponsors are: EmCare; In Compass Health; and HCA, Inc. Abbreviations: PG, Press Ganey Associates; SHM, Society of Hospital Medicine.

Characteristics of Hospitalists and Their Groups

Table 1 summarizes the characteristics of hospitalist respondents and their organizations by practice model. More (44%) respondents identified their practice model as directly employed by the hospital than other models, including multispecialty physician group (15%), multistate hospitalist group (14%), university or medical school (14%), local hospitalist group (12%), and other (2%). The median age of hospitalist respondents was 42 years, with 6.8 years of mean experience as a hospitalist. One third were women, 84% were married, and 46% had dependent children 6 years old or younger at home. Notably, hospitalists in multistate groups had fewer years of experience, and fewer hospitalists in local and multistate groups were married compared to hospitalists in other practice models.

Characteristics of Hospitalist Respondents and Their Hospitalist Groups by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: AHA, American Hospital Association; CI, confidence interval; EHR, electronic health record; IQR, interquartile range.

  • indicate the pairs of values for which a significant difference exists.

Hospitalist characteristics      
Age, weighted mean (99% CI)45 (42, 48)44 (42, 47)45 (43, 47)45 (43, 46)43 (40, 46) 
Years hospitalist experience, weighted mean (99% CI)8 (6, 9)*5 (4, 6)*8 (7, 9)7 (6, 7)8 (6, 9)<0.010*
Women, weighted %29303931430.118
Married, weighted %76778289810.009
At least 1 dependent child younger than age 6 living in home, weighted %47484347450.905
Pediatric specialty, n (%)<10<1011 (10%)57 (16%)36 (34%)<0.001
Hospitalist group characteristics      
Region, weighted %     <0.001
Northeast (AHA 1 & 2)1310162713 
South (AHA 3 & 4)1937132421 
Midwest (AHA 5 & 6)2324252226 
Mountain (AHA 7 & 8)2220161324 
West (AHA 9)2410311416 
No. beds of primary hospital, weighted %     <0.001
Up to 1491726122414 
1502993036363321 
3004492624292019 
450599138171121 
600 or more12671324 
No. of hospital facilities served by current practice, weighted %     <0.001
15370677766 
22022201624 
3 or more27913710 
No. of physicians in current practice, median (IQR)10 (5, 18)8 (6, 12)*14 (8, 25)*12 (6, 18)12 (7, 20)<0.001*, 0.001
No. of non‐physician providers in current practice, median (IQR)0 (0, 2)0 (0, 2)0 (0, 3)1 (0, 2)0 (0, 2) 
Available information technology capabilities, weighted %      
EHR to access physician notes5757755879<0.001
EHR to access nursing documentations68677475760.357
EHR to access laboratory or test results97899596960.054
Electronic order entry3019533856<0.001
Electronic billing38313636380.818
Access to EHR at home or off site78737882840.235
Access to Up‐to‐Date or other clinical guideline resources8077919296<0.001
Access to schedules, calendars, or other organizational resources56576667750.024
E‐mail, Web‐based paging, or other communication resources7463888990<0.001

Several differences in respondent group characteristics by practice model were found. Respondents in multistate hospitalist groups were more likely from the South and Midwest, while respondents from multispecialty groups were likely from the West. More multistate group practices were based in smaller hospitals, while academic hospitalists tended to practice in hospitals with 600 or more beds. Respondents employed by hospitals were more likely to practice at 1 hospital facility only, while local group practices were more likely to practice at 3 or more facilities. The median number of physicians in a hospitalist group was 11 (interquartile range [IQR] 6, 19). Local and multistate groups had fewer hospitalists compared to other models. Nonphysician providers were employed by nearly half of all hospitalist practices. Although almost all groups had access to some information technology, more academic hospitalists had access to electronic order entry, electronic physician notes, electronic clinical guidelines resources and communication technology, while local and multistate groups were least likely to have access to these resources.

Work Pattern Variations

Table 2 further details hospitalist work hours by practice model. The majority of hospitalists (78%) reported their position was full‐time (FTE 1.0), while 13% reported working less than full‐time (FTE <1.0). Only 5% of local group hospitalists worked part‐time, while 20% of multispecialty group hospitalists did. An additional 9% reported FTE >1.0, indicating their work hours exceeded the definition of a full‐time physician in their practice. Among full‐time hospitalists, local group members worked a greater number of shifts per month than employees of multispecialty groups, hospitals, and academic medical centers. Academic hospitalists reported higher numbers of consecutive clinical days worked on average, but fewer night shifts compared to hospitalists employed by multistate groups, multispecialty groups, and hospitals; fewer billable encounters than hospitalists in local and multistate groups; and more nonclinical work hours than hospitalists of any other practice model. Academic hospitalists also spent more time on teaching and research than other practice models. Hospitalists spent 11%‐18% of their time on administrative and committee responsibilities, with the least amount spent by hospitalists in multistate groups and the most in academic practice.

Hospitalist Work Hours by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: CI, confidence interval; FTE, full‐time equivalent.

  • indicate the pairs of values for which a significant difference exists. P value calculated using chi‐square test for comparing FTE categories with alpha defined as <0.05. Pairwise P values calculated using generalized linear models with a single outlier value as the reference value for all other comparisons and alpha defined as <0.0125 per Bonferroni correction.

FTE, weighted %0.058
FTE < 1.0613201214 
FTE = 1.08575748082 
FTE > 1.01013685 
Workload parameters, weighted mean (99% CI) 
Clinical shifts per month for FTE 1.019 (17, 20)*17 (16, 19)15 (14, 17)*16 (15, 16)15 (13, 17)<0.001*
Hours per clinical shift10 (9, 11)11 (10, 11)*10 (10, 11.0)11 (10, 11.0)10 (9, 10)*0.006*, 0.002
Consecutive days on clinical shift8 (6, 9)7 (6, 7)*6 (6, 7)7 (6, 7)9 (7, 10)*0.002*, <0.001
% Clinical shifts on nights20 (15, 25)23 (18, 28)*23 (17, 29)21 (17, 24)14 (9, 18)*0.001*, 0.002
% Night shifts spent in hospital61 (49, 74)*63 (52, 75)72 (62, 83)73 (67, 80)43 (29, 57)*0.010*, 0.003, <0.001
Billable encounters per clinical shift17 (14, 19)*17 (16, 18)14 (13, 15)15 (14, 16)13 (11, 14)*<0.001*, 0.002
Hours nonclinical work per month23 (12, 34)*19 (11, 27)31 (20, 42)30 (24, 36)71 (55, 86)*<0.001*
Hours clinical and nonclinical work per month for FTE 1.0202 (186, 219)211 (196, 226)184 (170, 198)*193 (186, 201)221 (203, 238)*<0.001*
Professional activity, weighted mean % (99% CI) 
Clinical84 (78, 89)*86 (81, 90)78 (72, 84)79 (76, 82)58 (51, 64)*<0.001*
Teaching2.3 (1, 5)*3 (1, 4)6 (4, 9)6 (5, 8)17 (14, 20)*<0.001*
Administration and Committee work13 (8, 19)11 (8, 15)*16 (10, 21)14 (12, 17)19 (14, 24)*0.001*
Research0 (0, 0)*1 (0, 2)0 (0, 1)1 (0, 1)7 (3, 11)*<0.001*

Table 3 tabulates other work pattern characteristics. Most hospitalists indicated that their current clinical work as hospitalists involved the general medical wards (100%), medical consultations (98%), and comanagement with specialists (92%). There were wide differences in participation in comanagement (100%, local groups vs 71%, academic), intensive care unit (ICU) responsibilities (94%, multistate groups vs 27%, academic), and nursing home care (30%, local groups vs 8%, academic). Among activities that are potentially not reimbursable, academic hospitalists were less likely to participate in coordination of patient transfers and code or rapid response teams, while multistate groups were least likely to participate in quality improvement activities. In total, 99% of hospitalists reported participating in at least 1 potentially nonreimbursable clinical activity.

Hospitalist Work Patterns and Compensation by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: CI, confidence interval.

  • indicate the pairs of values for which a significant difference exists. Pairwise P value calculated using generalized linear models with a single outlier value as the reference value for comparing earnings and alpha defined as <0.0125 per Bonferroni correction. P values calculated using chi‐square test for all other comparisons with alpha defined as <0.05.

Reimbursable activities, overlapping weighted % 
General medical ward1009910099990.809
Medical consultations999910098950.043
Comanagement with specialists10096969371<0.001
Preoperative evaluations92929088770.002
Intensive care unit8694677527<0.001
Skilled nursing facility or long‐term acute care facility301912168<0.001
Outpatient general medical practice4455100.241
Potentially nonreimbursable activities, overlapping weighted % 
Coordination of patient transfers92949593820.005
Quality improvement or patient safety initiatives81788389890.029
Code team or rapid response team5657536237<0.001
Information technology design or implementation42394751510.154
Admission triage for emergency department49464340310.132
Compensation scheme, weighted %<0.001
Salary only1821302947 
Salary plus performance incentive5472596753 
Fee‐for‐service201720 
Capitation00000 
Other97430 
Compensation links to incentives, overlapping weighted % 
No incentives40282929480.003
Patient satisfaction2339383814<0.001
Length of stay18172013100.208
Overall cost8119560.270
Test utilization22710<0.001
Clinical processes and outcomes2634444324<0.001
Other17292631250.087
Earnings, weighted mean dollars (99% CI)226,065 (202,891, 249,240)*225,613 (210,772, 240,454)202,617 (186,036, 219,198)206,087 (198,413, 213,460)166,478 (151,135, 181,821)*<0.001*

Hospitalist compensation schemes were significantly different across the practice models. Salary‐only schemes were most common among academic hospitalists (47%), while 72% of multistate groups used performance incentives in addition to salary. More local groups used fee‐for‐service compensation than other models. Incentives differed by practice model, with more multistate groups having incentives based on patient satisfaction, while more multispecialty physician groups had incentives based on clinical processes and outcomes than other models. Finally, mean earnings for academic hospitalists were significantly lower than for hospitalists of other practice models. Local and multistate group hospitalists earned more than any other practice model (all P <0.001), and $60,000 more than the lowest compensated academic hospitalists.

Components of Job Satisfaction

Hospitalists' rankings of the most important factors for job satisfaction revealed differences across models (Figure 2). Overall, hospitalists were most likely to consider optimal workload and compensation as important factors for job satisfaction from a list of 13 considerations. Local groups and academics were least likely to rank optimal workload as a top factor, and local group hospitalists were more likely to rank optimal autonomy than those of other models. Academic hospitalists had less concern for substantial pay, and more concern for the variety of tasks they perform and recognition by leaders, than other hospitalists.

Figure 2
Weighted proportion of respondents indicating the consideration as among the top 4 most important factors for job satisfaction by practice model. P values calculated using chi‐square tests across practice models with alpha defined as <0.05.

Job Satisfaction and Burnout Risk

Differences in the ratings of 4 of the 11 satisfaction and job characteristic domains were found across the practice models (Figure 3). Multispecialty group hospitalists were less satisfied with autonomy and their relationship with patients than other practice models, and along with multistate groups, reported the highest perceived workload. Organizational fairness was rated much higher by local group hospitalists than other practice models. Despite these differences in work patterns and satisfaction, there were no differences found in level of global job satisfaction, specialty satisfaction, or burnout across the practice models. Overall, 62% of respondents reported high job satisfaction (4 on a 1 to 5 scale), and 30% indicated burnout symptoms.

Figure 3
Weighted proportion of respondents with satisfaction domain score ≥4 (out of 5) and burnout scale score ≥3 (out of 5) by practice model. P values calculated using chi‐square tests across practice models with alpha defined as <0.05.

DISCUSSION

In our sample of US hospitalists, we found major differences in work patterns and compensation across hospitalist practice models, but no differences in job satisfaction, specialty satisfaction, and burnout. In particular, differences across these models included variations in hospitalist workload, hours, pay, and distribution of work activities. We found that hospitalists perform a variety of clinical and nonclinical tasks, for many of which there are not standard reimbursement mechanisms. We also found that features of a job that individual hospitalists considered most important vary by practice model.

Previous analysis of this data explored the overall state of hospitalist satisfaction.16 The present analysis offers a glimpse into hospitalists' systems‐orientation through a deeper look at their work patterns. The growth in the number of hospitalists who participate in intensive care medicine, specialty comanagement, and other work that involves close working relationships with specialist physicians confirms collaborative care as one of the dominant drivers of the hospitalist movement. At the level of indirect patient care, nearly all hospitalists contributed to work that facilitates coordination, quality, patient safety, or information technology. Understanding the integrative value of hospitalists outside of their clinical productivity may be of interest to hospital administrators.

Global satisfaction measures were similar across practice models. This finding is particularly interesting given the major differences in job characteristics seen among the practice models. This similarity in global satisfaction despite real differences in the nature of the job suggests that individuals find settings that allow them to address their individual professional goals. Our study demonstrates that, in 2010, Hospital Medicine has evolved enough to accommodate a wide variety of goals and needs.

While global satisfaction did not differ among practice types, hospitalists from various models did report differences in factors considered important to global satisfaction. While workload and pay were rated as influential across most models, the degree of importance was significantly different. In academic settings, substantial pay was not a top consideration for overall job satisfaction, whereas in local and multistate hospitalist groups, pay was a very close second in importance to optimal workload. These results may prove helpful for individual hospitalists trying to find their optimal job. For example, someone who is less concerned about workload, but wants to be paid well and have a high degree of autonomy, may find satisfaction in local hospitalist groups. However, for someone who is willing to sacrifice a higher salary for variety of activities, academic Hospital Medicine may be a better fit.

There is a concerning aspect of hospitalist job satisfaction that different practice models do not seem to solve. Control over personal time is a top consideration for many hospitalists across practice models, yet their satisfaction with personal time is low. As control over personal time is seen as a draw to the Hospital Medicine specialty, group leaders may need to evaluate their programs to ensure that schedules and workload support efforts for hospitalists to balance work and homelife commitments.

There are additional findings that are important for Hospital Medicine group leaders. Regardless of practice model, compensation and workload are often used as tools to recruit and retain hospitalists. While these tools may be effective, leaders may find more nuanced approaches to improving their hospitalists' overall satisfaction. Leaders of local hospitalist groups may find their hospitalists tolerant of heavier workloads as long as they are adequately rewarded and are given real autonomy over their work. However, leaders of academic programs may be missing the primary factor that can improve their hospitalists' satisfaction. Rather than asking for higher salaries to remain competitive, it may be more effective to advocate for time and training for their hospitalists to pursue important other activities beyond direct clinical care. Given that resources will always be limited, group leaders need to understand all of the elements that can contribute to hospitalist job satisfaction.

We point out several limitations to this study. First, our adjusted response rate of 25.6% is low for survey research, in general. As mentioned above, hospitalists are not easily identified in any available national physician database. Therefore, we deliberately designed our sampling strategy to error on the side of including ineligible surveyees to reduce systematic exclusion of practicing hospitalists. Using simple post hoc methods, we identified many nonhospitalists and bad addresses from our sample, but because these methods were exclusionary as opposed to confirmatory, we believe that a significant proportion of remaining nonrespondents may also have been ineligible for the survey. Although this does not fully address concerns about potential response bias, we believe that our sample representing a large number of hospitalist groups is adequate to make estimations about a nationally representative sample of practicing hospitalists. Second, in spite of our inclusive approach, we may still have excluded categories of practicing hospitalists. We were careful not to allow SHM members to represent all US hospitalists and included non‐members in the sampling frame, but the possibility of systematic exclusion that may alter our results remains a concern. Additionally, one of our goals was to characterize pediatric hospitalists independently from their adult‐patient counterparts. Despite oversampling of pediatricians, their sample was too small for a more detailed comparison across practice models. Also, self‐reported data about workload and compensation are subject to inaccuracies related to recall and cognitive biases. Last, this is a cross‐sectional study of hospitalist satisfaction at one point in time. Consequently, our sample may not be representative of very dissatisfied hospitalists who have already left their jobs.

The diversity found across existing practice models and the characteristics of the practices provide physicians with the opportunity to bring their unique skills and motivations to the hospitalist movement. As hospitals and other organizations seek to create, maintain, or grow hospitalist programs, the data provided here may prove useful to understand the relationship between practice characteristics and individual job satisfaction. Additionally, hospitalists looking for a job can consider these results as additional information to guide their choice of practice model and work patterns.

Acknowledgements

The authors thank Kenneth A. Rasinski for assistance with survey items refinement, and members of the SHM Career Satisfaction Task Force for their assistance in survey development.

Over the past 15 years, there has been dramatic growth in the number of hospitalist physicians in the United States and in the number of hospitals served by them.13 Hospitals are motivated to hire experienced hospitalists to staff their inpatient services,4 with goals that include obtaining cost‐savings and higher quality.59 The rapid growth of Hospital Medicine saw multiple types of hospital practice models emerge with differing job characteristics, clinical duties, workload, and compensation schemes.10 The extent of the variability of hospitalist jobs across practice models is not known.

Intensifying recruitment efforts and the concomitant increase in compensation for hospitalists over the last decade suggest that demand for hospitalists is strong and sustained.11 As a result, today's cohort of hospitalists has a wide range of choices of types of jobs, practice models, and locations. The diversity of available hospitalist jobs is characterized, for example, by setting (community hospital vs academic hospital), employer (hospital vs private practice), job duties (the amount and type of clinical work, and other administrative, teaching, or research duties), and intensity (work hours and duties to maximize income or lifestyle). How these choices relate to job satisfaction and burnout are also unknown.

The Society of Hospital Medicine (SHM) has administered surveys to hospitalist group leaders biennially since 2003.1215 These surveys, however, do not address issues related to individual hospitalist worklife, recruitment, and retention. In 2005, SHM convened a Career Satisfaction Task Force that designed and executed a national survey of hospitalists in 2009‐2010. The objective of this study is to evaluate how job characteristics vary by practice model, and the association of these characteristics and practice models with job satisfaction and burnout.

METHODS

Survey Instrument

A detailed description of the survey design, sampling strategy, data collection, and response rate calculations is described elsewhere.16 Portions of the 118‐item survey instrument assessed characteristics of the respondents' hospitalist group (12 items), details about their individual work patterns (12 items), and demographics (9 items). Work patterns were evaluated by the average number of clinical work days, consecutive days, hours per month, percentage of work assigned to night duty, and number of patient encounters. Average hours spent on nonclinical work, and the percentage of time allocated for clinical, administrative, teaching, and research activities were solicited. Additional items assessed specific clinical responsibilities, pretax earnings in FY2010, the availability of information technology capabilities, and the adequacy of available resources. Job and specialty satisfaction and 11 satisfaction domain measures were measured using validated scales.1726 Burnout symptoms were measured using a validated single‐item measure.26, 27

Sampling Strategy

We surveyed a national stratified sample of hospitalists in the US and Puerto Rico. We used the largest database of hospitalists (>24,000 names) currently available and maintained by the SHM as our sampling frame. We linked hospitalist employer information to hospital statistics from the American Hospital Association database28 to stratify the sample by number of hospital beds, geographic region, employment model, and specialty training, oversampling pediatric hospitalists due to small numbers. A respondent sample of about 700 hospitalists was calculated to be adequate to detect a 0.5 point difference in job satisfaction scores between subgroups assuming 90% power and alpha of 0.05. However, we sampled a total of 5389 addresses from the database to overcome the traditionally low physician response rates, duplicate sampling, bad addresses, and non‐hospitalists being included in the sampling frame. In addition, 2 multistate hospitalist companies (EmCare, In Compass Health) and 1 for‐profit hospital chain (HCA, Inc) financially sponsored this project with the stipulation that all of their hospitalist employees (n = 884) would be surveyed.

Data Collection

The healthcare consulting firm, Press Ganey, provided support with survey layout and administration following the modified Dillman method.29 Three rounds of coded surveys and solicitation letters from the investigators were mailed 2 weeks apart in November and December 2009. Because of low response rates to the mailed survey, an online survey was created using Survey Monkey and sent to 650 surveyees for whom e‐mail addresses were available, and administered at a kiosk for sample physicians during the SHM 2010 annual meeting.

Data Analysis

Nonresponse bias was measured by comparing characteristics between respondents of separate survey waves.30 We determined the validity of mailing addresses immediately following the survey period by mapping each address using Google, and if the address was a hospital, researching online whether or not the intended recipient was currently employed there. Practice characteristics were compared across 5 model categories distilled from the SHM & Medical Group Management Association survey: local hospitalist‐only group, multistate hospitalist group, multispecialty physician group, employer hospital, and university or medical school. Weighted proportions, means, and medians were calculated to account for oversampling of pediatric hospitalists. Differences in categorical measures were assessed using the chi‐square test and the design‐based F test for comparing weighted data. Weighted means (99% confidence intervals) and medians (interquartile ranges) were calculated. Because each parameter yielded a single outlier value across the 5 practice models, differences across weighted means were assessed using generalized linear models with the single outlier value chosen as the reference mean. Pair‐wise Wilcoxon rank sum test was used to compare median values. In these 4‐way comparisons of means and medians, significance was defined as P value of 0.0125 per Bonferroni correction. A single survey item solicited respondents to choose exactly 4 of 13 considerations most pertinent to job satisfaction. The proportion of respondents who scored 4 on a 5‐point Likert scale of the 11 satisfaction domains and 2 global measures of satisfaction, and burnout symptoms defined as 3 on a 5‐point single item measure were bar‐graphed. Chi‐square statistics were used to evaluate for differences across practice models. Statistical significance was defined by alpha less than 0.05, unless otherwise specified. All analyses were performed using STATA version 11.0 (College Station, TX). This study was approved by the Loyola University Institutional Review Board.

Survey data required cleaning prior to analysis. Missing gender information was imputed using the respondents' name. Responses to the item that asked to indicate the proportion of work dedicated to administrative responsibilities, clinical care, teaching, and research that did not add up to 100% were dropped. Two responses that indicated full‐time equivalent (FTE) of 0%, but whose respondents otherwise completed the survey implying they worked as clinical hospitalists, were replaced with values calculated from the given number of work hours relative to the median work hours in our sample. Out of range or implausible responses to the following items were dropped from analyses: the average number of billable encounters during a typical day or shift, number of shifts performing clinical activities during a typical month, pretax earnings, the year the respondent completed residency training, and the number of whole years practiced as a hospitalist. The proportion of selective item nonresponse was small and we did not, otherwise, impute missing data.

RESULTS

Response Rate

Of the 5389 originally sampled addresses, 1868 were undeliverable. Addresses were further excluded if they appeared in duplicate or were outdated. This yielded a total of 3105 eligible surveyees in the sample. As illustrated in Figure 1, 841 responded to the mailed survey and 5 responded to the Web‐based survey. After rejecting 67 non‐hospitalist respondents and 3 duplicate surveys, a total of 776 surveys were included in the final analysis. The adjusted response rate was 25.6% (776/3035). Members of SHM were more likely to return the survey than nonmembers. The adjusted response rate from hospitalists affiliated with the 3 sponsoring institutions was 6% (40/662). Because these respondents were more likely to be non‐members of SHM, we opted to analyze the responses from the sponsor hospitalists together with the sampled hospitalists. The demographics of the resulting pool of 816 respondents affiliated with over 650 unique hospitalist groups were representative of the original survey frame. We analyzed data from 794 of these who responded to the item indicating their hospitalist practice model. Demographic characteristics of responders and nonresponders to the practice model survey item were similar.

Figure 1
Sampling flow chart. Sponsors are: EmCare; In Compass Health; and HCA, Inc. Abbreviations: PG, Press Ganey Associates; SHM, Society of Hospital Medicine.

Characteristics of Hospitalists and Their Groups

Table 1 summarizes the characteristics of hospitalist respondents and their organizations by practice model. More (44%) respondents identified their practice model as directly employed by the hospital than other models, including multispecialty physician group (15%), multistate hospitalist group (14%), university or medical school (14%), local hospitalist group (12%), and other (2%). The median age of hospitalist respondents was 42 years, with 6.8 years of mean experience as a hospitalist. One third were women, 84% were married, and 46% had dependent children 6 years old or younger at home. Notably, hospitalists in multistate groups had fewer years of experience, and fewer hospitalists in local and multistate groups were married compared to hospitalists in other practice models.

Characteristics of Hospitalist Respondents and Their Hospitalist Groups by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: AHA, American Hospital Association; CI, confidence interval; EHR, electronic health record; IQR, interquartile range.

  • indicate the pairs of values for which a significant difference exists.

Hospitalist characteristics      
Age, weighted mean (99% CI)45 (42, 48)44 (42, 47)45 (43, 47)45 (43, 46)43 (40, 46) 
Years hospitalist experience, weighted mean (99% CI)8 (6, 9)*5 (4, 6)*8 (7, 9)7 (6, 7)8 (6, 9)<0.010*
Women, weighted %29303931430.118
Married, weighted %76778289810.009
At least 1 dependent child younger than age 6 living in home, weighted %47484347450.905
Pediatric specialty, n (%)<10<1011 (10%)57 (16%)36 (34%)<0.001
Hospitalist group characteristics      
Region, weighted %     <0.001
Northeast (AHA 1 & 2)1310162713 
South (AHA 3 & 4)1937132421 
Midwest (AHA 5 & 6)2324252226 
Mountain (AHA 7 & 8)2220161324 
West (AHA 9)2410311416 
No. beds of primary hospital, weighted %     <0.001
Up to 1491726122414 
1502993036363321 
3004492624292019 
450599138171121 
600 or more12671324 
No. of hospital facilities served by current practice, weighted %     <0.001
15370677766 
22022201624 
3 or more27913710 
No. of physicians in current practice, median (IQR)10 (5, 18)8 (6, 12)*14 (8, 25)*12 (6, 18)12 (7, 20)<0.001*, 0.001
No. of non‐physician providers in current practice, median (IQR)0 (0, 2)0 (0, 2)0 (0, 3)1 (0, 2)0 (0, 2) 
Available information technology capabilities, weighted %      
EHR to access physician notes5757755879<0.001
EHR to access nursing documentations68677475760.357
EHR to access laboratory or test results97899596960.054
Electronic order entry3019533856<0.001
Electronic billing38313636380.818
Access to EHR at home or off site78737882840.235
Access to Up‐to‐Date or other clinical guideline resources8077919296<0.001
Access to schedules, calendars, or other organizational resources56576667750.024
E‐mail, Web‐based paging, or other communication resources7463888990<0.001

Several differences in respondent group characteristics by practice model were found. Respondents in multistate hospitalist groups were more likely from the South and Midwest, while respondents from multispecialty groups were likely from the West. More multistate group practices were based in smaller hospitals, while academic hospitalists tended to practice in hospitals with 600 or more beds. Respondents employed by hospitals were more likely to practice at 1 hospital facility only, while local group practices were more likely to practice at 3 or more facilities. The median number of physicians in a hospitalist group was 11 (interquartile range [IQR] 6, 19). Local and multistate groups had fewer hospitalists compared to other models. Nonphysician providers were employed by nearly half of all hospitalist practices. Although almost all groups had access to some information technology, more academic hospitalists had access to electronic order entry, electronic physician notes, electronic clinical guidelines resources and communication technology, while local and multistate groups were least likely to have access to these resources.

Work Pattern Variations

Table 2 further details hospitalist work hours by practice model. The majority of hospitalists (78%) reported their position was full‐time (FTE 1.0), while 13% reported working less than full‐time (FTE <1.0). Only 5% of local group hospitalists worked part‐time, while 20% of multispecialty group hospitalists did. An additional 9% reported FTE >1.0, indicating their work hours exceeded the definition of a full‐time physician in their practice. Among full‐time hospitalists, local group members worked a greater number of shifts per month than employees of multispecialty groups, hospitals, and academic medical centers. Academic hospitalists reported higher numbers of consecutive clinical days worked on average, but fewer night shifts compared to hospitalists employed by multistate groups, multispecialty groups, and hospitals; fewer billable encounters than hospitalists in local and multistate groups; and more nonclinical work hours than hospitalists of any other practice model. Academic hospitalists also spent more time on teaching and research than other practice models. Hospitalists spent 11%‐18% of their time on administrative and committee responsibilities, with the least amount spent by hospitalists in multistate groups and the most in academic practice.

Hospitalist Work Hours by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: CI, confidence interval; FTE, full‐time equivalent.

  • indicate the pairs of values for which a significant difference exists. P value calculated using chi‐square test for comparing FTE categories with alpha defined as <0.05. Pairwise P values calculated using generalized linear models with a single outlier value as the reference value for all other comparisons and alpha defined as <0.0125 per Bonferroni correction.

FTE, weighted %0.058
FTE < 1.0613201214 
FTE = 1.08575748082 
FTE > 1.01013685 
Workload parameters, weighted mean (99% CI) 
Clinical shifts per month for FTE 1.019 (17, 20)*17 (16, 19)15 (14, 17)*16 (15, 16)15 (13, 17)<0.001*
Hours per clinical shift10 (9, 11)11 (10, 11)*10 (10, 11.0)11 (10, 11.0)10 (9, 10)*0.006*, 0.002
Consecutive days on clinical shift8 (6, 9)7 (6, 7)*6 (6, 7)7 (6, 7)9 (7, 10)*0.002*, <0.001
% Clinical shifts on nights20 (15, 25)23 (18, 28)*23 (17, 29)21 (17, 24)14 (9, 18)*0.001*, 0.002
% Night shifts spent in hospital61 (49, 74)*63 (52, 75)72 (62, 83)73 (67, 80)43 (29, 57)*0.010*, 0.003, <0.001
Billable encounters per clinical shift17 (14, 19)*17 (16, 18)14 (13, 15)15 (14, 16)13 (11, 14)*<0.001*, 0.002
Hours nonclinical work per month23 (12, 34)*19 (11, 27)31 (20, 42)30 (24, 36)71 (55, 86)*<0.001*
Hours clinical and nonclinical work per month for FTE 1.0202 (186, 219)211 (196, 226)184 (170, 198)*193 (186, 201)221 (203, 238)*<0.001*
Professional activity, weighted mean % (99% CI) 
Clinical84 (78, 89)*86 (81, 90)78 (72, 84)79 (76, 82)58 (51, 64)*<0.001*
Teaching2.3 (1, 5)*3 (1, 4)6 (4, 9)6 (5, 8)17 (14, 20)*<0.001*
Administration and Committee work13 (8, 19)11 (8, 15)*16 (10, 21)14 (12, 17)19 (14, 24)*0.001*
Research0 (0, 0)*1 (0, 2)0 (0, 1)1 (0, 1)7 (3, 11)*<0.001*

Table 3 tabulates other work pattern characteristics. Most hospitalists indicated that their current clinical work as hospitalists involved the general medical wards (100%), medical consultations (98%), and comanagement with specialists (92%). There were wide differences in participation in comanagement (100%, local groups vs 71%, academic), intensive care unit (ICU) responsibilities (94%, multistate groups vs 27%, academic), and nursing home care (30%, local groups vs 8%, academic). Among activities that are potentially not reimbursable, academic hospitalists were less likely to participate in coordination of patient transfers and code or rapid response teams, while multistate groups were least likely to participate in quality improvement activities. In total, 99% of hospitalists reported participating in at least 1 potentially nonreimbursable clinical activity.

Hospitalist Work Patterns and Compensation by Practice Model
 Local Hospitalist‐Only GroupMulti‐State Hospitalist GroupMultispecialty Physician GroupEmployer HospitalUniversity or Medical School 
 n = 95n = 111n = 115n = 348n = 107P Value
  • Abbreviations: CI, confidence interval.

  • indicate the pairs of values for which a significant difference exists. Pairwise P value calculated using generalized linear models with a single outlier value as the reference value for comparing earnings and alpha defined as <0.0125 per Bonferroni correction. P values calculated using chi‐square test for all other comparisons with alpha defined as <0.05.

Reimbursable activities, overlapping weighted % 
General medical ward1009910099990.809
Medical consultations999910098950.043
Comanagement with specialists10096969371<0.001
Preoperative evaluations92929088770.002
Intensive care unit8694677527<0.001
Skilled nursing facility or long‐term acute care facility301912168<0.001
Outpatient general medical practice4455100.241
Potentially nonreimbursable activities, overlapping weighted % 
Coordination of patient transfers92949593820.005
Quality improvement or patient safety initiatives81788389890.029
Code team or rapid response team5657536237<0.001
Information technology design or implementation42394751510.154
Admission triage for emergency department49464340310.132
Compensation scheme, weighted %<0.001
Salary only1821302947 
Salary plus performance incentive5472596753 
Fee‐for‐service201720 
Capitation00000 
Other97430 
Compensation links to incentives, overlapping weighted % 
No incentives40282929480.003
Patient satisfaction2339383814<0.001
Length of stay18172013100.208
Overall cost8119560.270
Test utilization22710<0.001
Clinical processes and outcomes2634444324<0.001
Other17292631250.087
Earnings, weighted mean dollars (99% CI)226,065 (202,891, 249,240)*225,613 (210,772, 240,454)202,617 (186,036, 219,198)206,087 (198,413, 213,460)166,478 (151,135, 181,821)*<0.001*

Hospitalist compensation schemes were significantly different across the practice models. Salary‐only schemes were most common among academic hospitalists (47%), while 72% of multistate groups used performance incentives in addition to salary. More local groups used fee‐for‐service compensation than other models. Incentives differed by practice model, with more multistate groups having incentives based on patient satisfaction, while more multispecialty physician groups had incentives based on clinical processes and outcomes than other models. Finally, mean earnings for academic hospitalists were significantly lower than for hospitalists of other practice models. Local and multistate group hospitalists earned more than any other practice model (all P <0.001), and $60,000 more than the lowest compensated academic hospitalists.

Components of Job Satisfaction

Hospitalists' rankings of the most important factors for job satisfaction revealed differences across models (Figure 2). Overall, hospitalists were most likely to consider optimal workload and compensation as important factors for job satisfaction from a list of 13 considerations. Local groups and academics were least likely to rank optimal workload as a top factor, and local group hospitalists were more likely to rank optimal autonomy than those of other models. Academic hospitalists had less concern for substantial pay, and more concern for the variety of tasks they perform and recognition by leaders, than other hospitalists.

Figure 2
Weighted proportion of respondents indicating the consideration as among the top 4 most important factors for job satisfaction by practice model. P values calculated using chi‐square tests across practice models with alpha defined as <0.05.

Job Satisfaction and Burnout Risk

Differences in the ratings of 4 of the 11 satisfaction and job characteristic domains were found across the practice models (Figure 3). Multispecialty group hospitalists were less satisfied with autonomy and their relationship with patients than other practice models, and along with multistate groups, reported the highest perceived workload. Organizational fairness was rated much higher by local group hospitalists than other practice models. Despite these differences in work patterns and satisfaction, there were no differences found in level of global job satisfaction, specialty satisfaction, or burnout across the practice models. Overall, 62% of respondents reported high job satisfaction (4 on a 1 to 5 scale), and 30% indicated burnout symptoms.

Figure 3
Weighted proportion of respondents with satisfaction domain score ≥4 (out of 5) and burnout scale score ≥3 (out of 5) by practice model. P values calculated using chi‐square tests across practice models with alpha defined as <0.05.

DISCUSSION

In our sample of US hospitalists, we found major differences in work patterns and compensation across hospitalist practice models, but no differences in job satisfaction, specialty satisfaction, and burnout. In particular, differences across these models included variations in hospitalist workload, hours, pay, and distribution of work activities. We found that hospitalists perform a variety of clinical and nonclinical tasks, for many of which there are not standard reimbursement mechanisms. We also found that features of a job that individual hospitalists considered most important vary by practice model.

Previous analysis of this data explored the overall state of hospitalist satisfaction.16 The present analysis offers a glimpse into hospitalists' systems‐orientation through a deeper look at their work patterns. The growth in the number of hospitalists who participate in intensive care medicine, specialty comanagement, and other work that involves close working relationships with specialist physicians confirms collaborative care as one of the dominant drivers of the hospitalist movement. At the level of indirect patient care, nearly all hospitalists contributed to work that facilitates coordination, quality, patient safety, or information technology. Understanding the integrative value of hospitalists outside of their clinical productivity may be of interest to hospital administrators.

Global satisfaction measures were similar across practice models. This finding is particularly interesting given the major differences in job characteristics seen among the practice models. This similarity in global satisfaction despite real differences in the nature of the job suggests that individuals find settings that allow them to address their individual professional goals. Our study demonstrates that, in 2010, Hospital Medicine has evolved enough to accommodate a wide variety of goals and needs.

While global satisfaction did not differ among practice types, hospitalists from various models did report differences in factors considered important to global satisfaction. While workload and pay were rated as influential across most models, the degree of importance was significantly different. In academic settings, substantial pay was not a top consideration for overall job satisfaction, whereas in local and multistate hospitalist groups, pay was a very close second in importance to optimal workload. These results may prove helpful for individual hospitalists trying to find their optimal job. For example, someone who is less concerned about workload, but wants to be paid well and have a high degree of autonomy, may find satisfaction in local hospitalist groups. However, for someone who is willing to sacrifice a higher salary for variety of activities, academic Hospital Medicine may be a better fit.

There is a concerning aspect of hospitalist job satisfaction that different practice models do not seem to solve. Control over personal time is a top consideration for many hospitalists across practice models, yet their satisfaction with personal time is low. As control over personal time is seen as a draw to the Hospital Medicine specialty, group leaders may need to evaluate their programs to ensure that schedules and workload support efforts for hospitalists to balance work and homelife commitments.

There are additional findings that are important for Hospital Medicine group leaders. Regardless of practice model, compensation and workload are often used as tools to recruit and retain hospitalists. While these tools may be effective, leaders may find more nuanced approaches to improving their hospitalists' overall satisfaction. Leaders of local hospitalist groups may find their hospitalists tolerant of heavier workloads as long as they are adequately rewarded and are given real autonomy over their work. However, leaders of academic programs may be missing the primary factor that can improve their hospitalists' satisfaction. Rather than asking for higher salaries to remain competitive, it may be more effective to advocate for time and training for their hospitalists to pursue important other activities beyond direct clinical care. Given that resources will always be limited, group leaders need to understand all of the elements that can contribute to hospitalist job satisfaction.

We point out several limitations to this study. First, our adjusted response rate of 25.6% is low for survey research, in general. As mentioned above, hospitalists are not easily identified in any available national physician database. Therefore, we deliberately designed our sampling strategy to error on the side of including ineligible surveyees to reduce systematic exclusion of practicing hospitalists. Using simple post hoc methods, we identified many nonhospitalists and bad addresses from our sample, but because these methods were exclusionary as opposed to confirmatory, we believe that a significant proportion of remaining nonrespondents may also have been ineligible for the survey. Although this does not fully address concerns about potential response bias, we believe that our sample representing a large number of hospitalist groups is adequate to make estimations about a nationally representative sample of practicing hospitalists. Second, in spite of our inclusive approach, we may still have excluded categories of practicing hospitalists. We were careful not to allow SHM members to represent all US hospitalists and included non‐members in the sampling frame, but the possibility of systematic exclusion that may alter our results remains a concern. Additionally, one of our goals was to characterize pediatric hospitalists independently from their adult‐patient counterparts. Despite oversampling of pediatricians, their sample was too small for a more detailed comparison across practice models. Also, self‐reported data about workload and compensation are subject to inaccuracies related to recall and cognitive biases. Last, this is a cross‐sectional study of hospitalist satisfaction at one point in time. Consequently, our sample may not be representative of very dissatisfied hospitalists who have already left their jobs.

The diversity found across existing practice models and the characteristics of the practices provide physicians with the opportunity to bring their unique skills and motivations to the hospitalist movement. As hospitals and other organizations seek to create, maintain, or grow hospitalist programs, the data provided here may prove useful to understand the relationship between practice characteristics and individual job satisfaction. Additionally, hospitalists looking for a job can consider these results as additional information to guide their choice of practice model and work patterns.

Acknowledgements

The authors thank Kenneth A. Rasinski for assistance with survey items refinement, and members of the SHM Career Satisfaction Task Force for their assistance in survey development.

References
  1. Kralovec PD,Miller JA,Wellikson L,Huddleston JM.The status of hospital medicine groups in the United States.J Hosp Med.2006;1(2):7580.
  2. Kuo Y‐F,Sharma G,Freeman JL,Goodwin JS.Growth in the care of older patients by hospitalists in the United States.N Engl J Med.2009;360(11):11021112.
  3. Wachter RM.The state of hospital medicine in 2008.Med Clin North Am.2008;92(2):265273,vii.
  4. Pham HH,Devers KJ,Kuo S,Berenson R.Health care market trends and the evolution of hospitalist use and roles.J Gen Intern Med.2005;20(2):101107.
  5. Meltzer D,Manning WG,Morrison J, et al.Effects of physician experience on costs and outcomes on an academic general medicine service: results of a trial of hospitalists.Ann Intern Med.2002;137(11):866874.
  6. Freese RB.The Park Nicollet experience in establishing a hospitalist system.Ann Intern Med.1999;130(4 pt 2):350354.
  7. Molinari C,Short R.Effects of an HMO hospitalist program on inpatient utilization.Am J Manag Care.2001;7(11):10511057.
  8. Coffman J,Rundall TG.The impact of hospitalists on the cost and quality of inpatient care in the United States: a research synthesis.Med Care Res Rev.2005;62(4):379406.
  9. Landrigan CP,Conway PH,Edwards S,Srivastava R.Pediatric hospitalists: a systematic review of the literature.Pediatrics.2006;117(5):17361744.
  10. Wachter RM,Goldman L.The hospitalist movement 5 years later.JAMA.2002;287(4):487494.
  11. Auerbach AD,Chlouber R,Singler J,Lurie JD,Bostrom A,Wachter RM.Trends in market demand for internal medicine 1999 to 2004: an analysis of physician job advertisements.J Gen Intern Med.2006;21(10):10791085.
  12. SHM. 2003–2004 Survey by the Society of Hospital Medicine on Productivity and Compensation: Analysis of Results. 2004 [updated 2004]. Available at: http://www.hospitalmedicine.org/AM/Template. cfm?Section=Practice_Resources Available at: http://cme.medscape.com/viewarticle/578134. Accessed October 21,2010.
  13. State of Hospital Medicine: 2010 Report Based on 2009 Data.Englewood, CO and Philadelphia, PA:Medical Group Management Association and Society of Hospital Medicine;2010.
  14. Hinami K,Whelan CT,Wolosin RJ,Miller JA,Wetterneck TB.Worklife and satisfaction of hospitalists: toward flourishing careers.J Gen Intern Med.2011, Jul 20. PMID: 21773849.
  15. Wetterneck TB,Linzer M,McMurray JE, et al.Worklife and satisfaction of general internists.Arch Intern Med.2002;162(6):649656.
  16. Linzer M,Manwell L,Mundt M, et al.Organizational climate, stress, and error in primary care: the MEMO study. In: Henriksen K, Battles JB, Marks ES, Lewin DI, eds.Advances in Patient Safety: From Research to Implementation. Vol 1: Research Findings.Rockville, MD:Agency for Healthcare Research and Quality;2005;1:6577.
  17. Lindenauer PK,Pantilat SZ,Katz PP,Wachter RM.Hospitalists and the practice of inpatient medicine: results of a survey of the National Association of Inpatient Physicians.Ann Intern Med.1999;130(4 pt 2):343349.
  18. Auerbach AD,Nelson EA,Lindenauer PK,Pantilat SZ,Katz PP,Wachter RM.Physician attitudes toward and prevalence of the hospitalist model of care: results of a national survey.Am J Med.2000;109(8):648653.
  19. Fields DL.Taking the Measure of Work: A Guide to Validated Scales for Organizational Research and Diagnosis.Thousand Oaks, CA:Sage Publications;2002.
  20. Caplan RD,Cobb S,French JRP,Van Harrison R,Penneau SR.Job Demands and Worker Health.Ann Arbor, MI:University of Michigan, Institute for Social Research;1980.
  21. Colquitt JA.On the dimensionality of organizational justice: a construct validation of a measure.J Appl Psychol.2001;86(3):386400.
  22. Yang CL,Carayon P.Effect of job demands and social support on worker stress—a study of VDT users.Behav Inform Technol.1995;14(1):3240.
  23. Konrad TR,Williams ES,Linzer M, et al.Measuring physician job satisfaction in a changing workplace and a challenging environment. SGIM Career Satisfaction Study Group. Society of General Internal Medicine.Med Care.1999;37(11):11741182.
  24. Linzer M,Manwell LB,Williams ES, et al.Working conditions in primary care: physician reactions and care quality.Ann Intern Med.2009;151(1):28U48.
  25. Rohland BM,Kruse GR,Rohrer JE.Validation of a single‐item measure of burnout against the Maslach Burnout Inventory among physicians.Stress Health.2004;20(2):7579.
  26. American Hospital Association. AHA Hospital Statistics. 2009 [updated 2009]. Available at: http://www.ahadata.com/ahadata/html/AHAStatistics.html. Accessed April 12,2011.
  27. Thorpe C,Ryan B,McLean SL, et al.How to obtain excellent response rates when surveying physicians.Fam Pract.2009;26(1):6568.
  28. Armstrong JS,Overton TS.Estimating nonresponse bias in mail surveys.J Marketing Res.1977;14(3):396402.
References
  1. Kralovec PD,Miller JA,Wellikson L,Huddleston JM.The status of hospital medicine groups in the United States.J Hosp Med.2006;1(2):7580.
  2. Kuo Y‐F,Sharma G,Freeman JL,Goodwin JS.Growth in the care of older patients by hospitalists in the United States.N Engl J Med.2009;360(11):11021112.
  3. Wachter RM.The state of hospital medicine in 2008.Med Clin North Am.2008;92(2):265273,vii.
  4. Pham HH,Devers KJ,Kuo S,Berenson R.Health care market trends and the evolution of hospitalist use and roles.J Gen Intern Med.2005;20(2):101107.
  5. Meltzer D,Manning WG,Morrison J, et al.Effects of physician experience on costs and outcomes on an academic general medicine service: results of a trial of hospitalists.Ann Intern Med.2002;137(11):866874.
  6. Freese RB.The Park Nicollet experience in establishing a hospitalist system.Ann Intern Med.1999;130(4 pt 2):350354.
  7. Molinari C,Short R.Effects of an HMO hospitalist program on inpatient utilization.Am J Manag Care.2001;7(11):10511057.
  8. Coffman J,Rundall TG.The impact of hospitalists on the cost and quality of inpatient care in the United States: a research synthesis.Med Care Res Rev.2005;62(4):379406.
  9. Landrigan CP,Conway PH,Edwards S,Srivastava R.Pediatric hospitalists: a systematic review of the literature.Pediatrics.2006;117(5):17361744.
  10. Wachter RM,Goldman L.The hospitalist movement 5 years later.JAMA.2002;287(4):487494.
  11. Auerbach AD,Chlouber R,Singler J,Lurie JD,Bostrom A,Wachter RM.Trends in market demand for internal medicine 1999 to 2004: an analysis of physician job advertisements.J Gen Intern Med.2006;21(10):10791085.
  12. SHM. 2003–2004 Survey by the Society of Hospital Medicine on Productivity and Compensation: Analysis of Results. 2004 [updated 2004]. Available at: http://www.hospitalmedicine.org/AM/Template. cfm?Section=Practice_Resources Available at: http://cme.medscape.com/viewarticle/578134. Accessed October 21,2010.
  13. State of Hospital Medicine: 2010 Report Based on 2009 Data.Englewood, CO and Philadelphia, PA:Medical Group Management Association and Society of Hospital Medicine;2010.
  14. Hinami K,Whelan CT,Wolosin RJ,Miller JA,Wetterneck TB.Worklife and satisfaction of hospitalists: toward flourishing careers.J Gen Intern Med.2011, Jul 20. PMID: 21773849.
  15. Wetterneck TB,Linzer M,McMurray JE, et al.Worklife and satisfaction of general internists.Arch Intern Med.2002;162(6):649656.
  16. Linzer M,Manwell L,Mundt M, et al.Organizational climate, stress, and error in primary care: the MEMO study. In: Henriksen K, Battles JB, Marks ES, Lewin DI, eds.Advances in Patient Safety: From Research to Implementation. Vol 1: Research Findings.Rockville, MD:Agency for Healthcare Research and Quality;2005;1:6577.
  17. Lindenauer PK,Pantilat SZ,Katz PP,Wachter RM.Hospitalists and the practice of inpatient medicine: results of a survey of the National Association of Inpatient Physicians.Ann Intern Med.1999;130(4 pt 2):343349.
  18. Auerbach AD,Nelson EA,Lindenauer PK,Pantilat SZ,Katz PP,Wachter RM.Physician attitudes toward and prevalence of the hospitalist model of care: results of a national survey.Am J Med.2000;109(8):648653.
  19. Fields DL.Taking the Measure of Work: A Guide to Validated Scales for Organizational Research and Diagnosis.Thousand Oaks, CA:Sage Publications;2002.
  20. Caplan RD,Cobb S,French JRP,Van Harrison R,Penneau SR.Job Demands and Worker Health.Ann Arbor, MI:University of Michigan, Institute for Social Research;1980.
  21. Colquitt JA.On the dimensionality of organizational justice: a construct validation of a measure.J Appl Psychol.2001;86(3):386400.
  22. Yang CL,Carayon P.Effect of job demands and social support on worker stress—a study of VDT users.Behav Inform Technol.1995;14(1):3240.
  23. Konrad TR,Williams ES,Linzer M, et al.Measuring physician job satisfaction in a changing workplace and a challenging environment. SGIM Career Satisfaction Study Group. Society of General Internal Medicine.Med Care.1999;37(11):11741182.
  24. Linzer M,Manwell LB,Williams ES, et al.Working conditions in primary care: physician reactions and care quality.Ann Intern Med.2009;151(1):28U48.
  25. Rohland BM,Kruse GR,Rohrer JE.Validation of a single‐item measure of burnout against the Maslach Burnout Inventory among physicians.Stress Health.2004;20(2):7579.
  26. American Hospital Association. AHA Hospital Statistics. 2009 [updated 2009]. Available at: http://www.ahadata.com/ahadata/html/AHAStatistics.html. Accessed April 12,2011.
  27. Thorpe C,Ryan B,McLean SL, et al.How to obtain excellent response rates when surveying physicians.Fam Pract.2009;26(1):6568.
  28. Armstrong JS,Overton TS.Estimating nonresponse bias in mail surveys.J Marketing Res.1977;14(3):396402.
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Job characteristics, satisfaction, and burnout across hospitalist practice models
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Job characteristics, satisfaction, and burnout across hospitalist practice models
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ACUTE Center for Eating Disorders

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ACUTE center for eating disorders

Anorexia nervosa occurs in 0.9% of women and 0.3% of men in the United States1 and is associated with a prolonged course,2 extensive medical complications that can affect almost every organ system,3, 4 and a 5% mean crude mortality rate9.6 times expected for age‐matched women in the United States.2, 5 Those with anorexia nervosa die as a complication of their illness more frequently than any other mental illness.3 Anorexia nervosa is commonly diagnosed during the adolescent years,2 with almost 25% going on to develop chronic anorexia nervosa.2, 6 Consequently, many patients with severe anorexia nervosa will receive treatment by adult medicine practitioners.

Patients with anorexia nervosa frequently require hospitalization. Published guidelines suggest that those who are 70% or less than ideal body weight, bradycardic, hypotensive, or those with severe electrolyte disturbances warrant admission for medical stabilization.79 Once admitted, however, there are no published guidelines for best practices to medically stabilize patients.7, 10 Although most experts advocate a multidisciplinary approach with weight restoration and medical stability as the goals of hospital admission,8, 9 controversy exists in the literature about how best to achieve these goals.7, 10

It is known, however, that for patients with complicated medical illnesses, such as human immunodeficiency virus (HIV) and sepsis, higher volumes of patient caseloads treated by physicians with disease‐specific expertise has been found to lead to improved outcomes in patients.11, 12 The adult patient with severe anorexia nervosa who requires inpatient medical stabilization may also benefit from a multidisciplinary trained staff familiar with the medical management of anorexia nervosa. Accordingly, we have developed the Acute Comprehensive Urgent Treatment for Eating Disorders (ACUTE) Center.

PROGRAM DESCRIPTION

The ACUTE Center at Denver Health is a 5‐bed unit dedicated to the medical stabilization of patients with severe malnutrition due to anorexia nervosa or severe electrolyte disorders due to bulimia nervosa. ACUTE accepts patients 17 years and older with medical complications related to chronic malnutrition and refeeding.

ACUTE uses a multidisciplinary approach to patient care. The physician team is composed of a hospital medicine attending physician, consultative expertise by an internal medicine specialist in the management of the medical complications of eating disorders, and a psychiatrist specializing in eating disorders. There is a dedicated team of nurses, two dieticians, physical therapists, certified nursing assistants, speech therapists, a psychotherapist, and a chaplain.

ACUTE patients are on continuous telemetry monitoring for the duration of their hospitalization to monitor for arrhythmias as well as signs of covert exercise. As part of the initial intake, a full set of vital signs is obtained, including height and weight. Patients are weighed daily with their back to the scale. There is no discussion of weight fluctuations. Patients may walk at a slow pace around the unit. No exercise is allowed.

Each patient at the ACUTE Center has an individualized meal plan and are started on an oral caloric intake 200 kcal below their basal energy expenditure (BEE). Indirect calorimetry is performed on the first hospital day. Each patient meets on a daily basis with the registered dietician to choose meals that meet their caloric goals.

All patients have a sitter continuously for their first week, and thereafter sitter time may be reduced to supervision surrounding each meal. Patients who fail to finish their prescribed meal are required to drink a liquid supplement to meet caloric goals. Calories are increased weekly until the patient's weight shows a clear pattern of weight increase. 0

Figure 1
The ACUTE Center at Denver Health initial intake form.

Patients are discharged from the ACUTE Center when they have achieved several basic goals: They are consuming greater than 2000 kcal per day, they are consistently gaining 23 pounds per week, their laboratory values have stabilized without electrolyte supplementation, and they are strong enough for an inpatient eating disorder program.

METHODS

Patients admitted to the ACUTE Center between October 2008 and December 2010 for medical stabilization and monitored refeeding were included. Patients with a diagnosis of bulimia nervosa were excluded. Demographic data and laboratory results were obtained electronically from our data repository, whereas weight, height, and other clinical characteristics were obtained by manual chart abstraction. The statistical analysis was conducted in SAS Enterprise Guide v4.1 (SAS Institute, Cary, NC).

RESULTS

In its first 27 months, the ACUTE Center had 76 total admissions, comprising 59 patients. Of the 76 admissions, the 62 admissions for medical stabilization and monitored refeeding of 54 patients with anorexia nervosa were included. Forty‐eight of the 54 (89%) included patients were female. Six patients were hospitalized twice, and 1 patient 3 times. There were 3 transfers to the intensive care unit, and no inpatient mortality. Of the 62 admissions, 11 (18%) discharges were to home, and 51 (82%) were to inpatient psychiatric eating disorder units.

The mean age at admission was 27 years (range 1765 years). The mean percent of ideal body weight (IBW) on admission was 62.2% 10.2%. The mean body mass index (BMI) was 12.9 2.0 kg/m2 on admission, and 13.1 1.9 kg/m2 upon discharge. The median length of stay was 16 days (interquartile range [IQR] 929 days). Median calculated BEE (1119 [10671184 IQR]) was higher than measured BEE by indirect calorimetry (792 [6341094]), (Table 1).

Patient Characteristics (N = 62 Admissions)
Median (Interquartile Range)* Range
  • Abbreviations: BEE, basal energy expenditure; BMI, body mass index; DEXA, dual energy x‐ray absorptiometry.

  • Mean standard deviation displayed if normally distributed.

  • Frequency and percentage shown for categorical variables.

  • Measured BEE available for 42 admission and DEXA scans for 38 patients.

Age, yr 27 (2135) 1765
Female 56 90%
Length of hospitalization, days 16 (929) 570
Calculated BEE 1119 (10671184) 9061491
Measured BEE 792 (6341094) 5001742
DEXA Z‐score 2.2 1.1 4.40.7
Height, in 65 (6167) 5774
Weight on admission, lb 76.1 14.4 50.8110.0
% Ideal body weight on admission 62.2 10.2 42.4101.0
% Ideal body weight on discharge 63.2 9.1 42.3 82.7
BMI on admission 12.9 2.0 8.719.7
BMI nadir 12.4 1.9 8.415.7
BMI on discharge 13.1 1.9 8.717.0

The majority of admission laboratory values, including serum albumin, blood urea nitrogen (BUN), creatinine, potassium, magnesium, and phosphate levels, were within normal limits. Fifty‐six percent were hyponatremic at admission, with a mean serum sodium level of 133 6 mmol/L (Table 2).

Admission Labs (N = 62)
Median (Interquartile Range)* Range
  • NOTE: Reference range shown in parentheses.

  • Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; INR, international normalized ratio; MCV, mean corpuscular volume; TSH, thyroid stimulating hormone; WBC, white blood cell.

  • Mean standard deviation displayed if normally distributed.

  • Pre‐albumin was available on 49 admissions. TSH was available on 50 admissions. INR was available on 59 admissions. 1,25 Hydroxy vitamin D was available on 53 admissions. Neutrophils and lymphocytes were available on 60 admissions.

Sodium (135143 mmol/L) 133 6 117145
Potassium (3.65.1 mmol/L) 3.8 (3.0 4.0) 1.85.5
Carbon dioxide (1827 mmol/L) 28 (2531) 1845
Glucose (60199 mg/dL) 85 (76105) 41166
BUN (622 mg/dL) 16 (923) 344
Creatinine (0.61.2 mg/dL) 0.7 (0.61.0) 0.31.6
Calcium (8.110.5 mg/dL) 8.9 0.6 7.610.1
Phosphorus (2.74.8 mg/dL) 3.2 (2.83.7) 2.15.7
Magnesium (1.32.1 mEq/L) 1.8 0.3 1.22.5
AST (1040 U/L) 38 (2391) 122402
ALT (745 U/L) 45 (2498) 152436
Total bilirubin (0.01.2 mg/dL) 0.5 (0.30.7) 0.12.2
Pre‐albumin (2052 mg/dL) 21 7 842
Albumin (3.05.3 g/dL) 3.7 0.7 1.64.8
WBC (4.510.0 k/L) 4.0 (3.25.7) 1.120.3
Neutrophils (%) (48.069.0%) 55.5 13.1 17.082.0
Lymphocytes (%) (21.043.0%) 34.9 13.0 10.864.0
Platelet count (150450 k/L) 266 (193371) 40819
Hematocrit (37.047.0%) 36.1 5.4 19.145.7
MCV (80100 fL) 91 7 73105
TSH (0.346.00 IU/mL) 1.52 (0.962.84) 0.1864.1
INR (0.821.17) 1.09 (1.001.22) 0.812.05
1,25 Hydroxy vitamin D (3080 ng/mL) 41 (3058) 8171

DISCUSSION

Hospital Medicine is currently the fastest growing area of specialization in medicine.13 Palliative care, inpatient geriatrics, short stay units, and bedside procedures have evolved into hospitalist‐led services.1418 The management of the medical complications of severe eating disorders is another potential niche for hospitalists.

The ACUTE Center at Denver Health represents a center in which highly specialized, multidisciplinary care is provided for a rare and extremely ill population of patients. Prior to entering the ACUTE Center, the patients described in our program had each experienced prolonged and unsuccessful stays for medical stabilization in acute care hospitals across the country, after being denied treatment in eating disorder programs due to medical instability.

Patients transferred to ACUTE often received medical care reflecting a lack of specific expertise, training, and exposure. The most common management discrepancy we noted was over‐aggressive provision of intravenous fluids. Consequently, we often diurese 1020 pounds of edema weight, gained during a prior medical hospitalization, before beginning the process of weight restoration. This edema weight artificially increases admission weight and results in less than expected weight gain from admission to discharge.

Even without substantial weight gain, medical stabilization is evidenced by consistent caloric oral intake, and fluid and electrolyte stabilization after initial refeeding. Accordingly, patients who have been treated at the ACUTE Center often become eligible for admission to eating disorder programs at body weights below the typical 70% of ideal body weight that most programs use as a threshold for admission.

From a clinical research perspective, centers such as ACUTE allow for opportunities to better understand and investigate the nuances of patient care in the setting of severe malnutrition. From our cohort of patients to date, we have noted unique issues in albumin levels,19 coagulopathy,20 and liver function,21 among others. As an example, the cohort of patients with anorexia nervosa described here had profoundly low body weight, but relatively normal admission labs. Even the serum albumin, a parameter often used to reflect nutrition in an adult internal medicine setting, is usually normal, reflecting, in an otherwise generally healthy young population, the absence of a malignant, inflammatory, or infectious etiology of weight loss.19

Hospitalists also advocate for their patients by helping to maximize the benefits of their health care coverage. Many health care plans place limits on inpatient psychiatric care benefits. Patients who are severely malnourished from their eating disorder may waste valuable psychiatric care benefits undergoing medical stabilization in psychiatric units while physically unable to undergo psychotherapy. This has become increasingly important as health insurance plans continue to decrease coverage for residential care of patients with anorexia.22

In contrast, the medical benefits of most health plans are more robust. Accordingly, from the patient perspective, medical stabilization in an acute medical unit before admission to a psychiatry unit maximizes their ability to participate in the intensive psychiatric therapy which is still needed after medical stabilization. A recent study from a residential eating disorder program confirmed that a higher discharge BMI was the single best predictor of full recovery from anorexia nervosa.23

In the future, we believe that a continuing concentration of care and experience may also lend itself to the development of protocols and management guidelines which may benefit patients beyond our own unit. Severely malnourished patients with anorexia nervosa, or bulimic patients with complicated electrolyte disorders, are likely to benefit both medically and financially from centers of excellence. Inpatient or residential psychiatric eating disorder programs may act in synergy with medical eating disorders units, like ACUTE, to most efficiently care for the severely malnourished patient. Hospitalists, with the proper training and experience, are uniquely positioned to develop such centers of excellence.

Files
References
  1. Hudson JI,Hiripi E,Harrison GP,Kessler RC.The prevalence and correlates of eating disorders in the national comorbidity survey replication.Biol Psychiatry.2007;61:348358.
  2. Steinhausen HC.The outcome of anorexia nervosa in the 20th century.Am J Psychiatry.2002;159:12841293.
  3. Mehler PS,Krantz M.Anorexia nervosa medical issues.J Womens Health.2003;12:331340.
  4. Mehler PS.Diagnosis and care of patients with anorexia nervosa in primary care settings.Ann Intern Med.2001;134:10481059.
  5. Herzog DB,Greenwood DN,Dorer DJ, et al.Mortality in eating disorders: a descriptive study.Int J Eat Disord.2000;28:2026.
  6. Zipfel S,Lowe B,Reas DL,Deter HC,Herzog W.Long‐term prognosis in anorexia nervosa: lessons from a 21‐year follow‐up study.Lancet.2000;355:721722.
  7. Schwartz BI,Mansbach JM,Marion JG,Katzman DK,Forman SF.Variations in admissions practices for adolescents with anorexia nervosa: a North American sample.J Adolesc Health.2008;43:425431.
  8. American Psychiatric Association.Treatment of patients with eating disorders, third edition.Am J Psychiatry.2006;163(suppl 7):454.
  9. American Dietetic Association.Position of the American Dietetic Association: nutrition intervention in the treatment of anorexia nervosa, bulimia nervosa, and other eating disorders (ADA reports).J Am Diet Assoc.2006;106:20732082.
  10. Sylvester CJ,Forman SF.Clinical practice guidelines for treating restrictive eating disorder patients during medical hospitalization.Curr Opin Pediatr.2008;20:390397.
  11. Hellinger F.Practice makes perfect: a volume‐outcome study of hospital patients with HIV disease.J Acquir Immune Defic Syndr.2008;47:226233.
  12. Chen CH,Chen YH,Lin HC,Lin HC.Association between physician caseload and patient outcome for sepsis treatment.Infect Control Hosp Epidemiol.2009;30:556562.
  13. Wachter RM.Reflections: the hospitalist movement ten years later.J Hosp Med.2006;1:248252.
  14. What will board certification be‐and mean‐for hospitalists?Meier DE.Palliative care in hospitals.J Hosp Med.2006;1:2128.
  15. Pantilat SZ.Palliative care and hospitalists: a partnership for hope.J Hosp Med.2006;1:56.
  16. Lucas BP,Asbury JK,Wang Y, et al.Impact of a bedside procedure service on general medicine inpatients: a firm‐based trial.J Hosp Med.2007;2:143149.
  17. Kuo YF,Sharma G,Freeman JL,Goodwin JS.Growth in the care of older patients by hospitalists in the United States.N Engl J Med.2009;360:11021112.
  18. Lucas BP,Kumapley R,Mba B, et al.A hospitalist run short stay unit: features that predict length of stay and eventual admission to traditional inpatient services.J Hosp Med.2009;4:276284.
  19. Narayanan V,Gaudiani JL,Mehler PS.Serum albumin levels may not correlate with weight status in severe anorexia nervosa.Eat Disord.2009;17:322326.
  20. Gaudiani JL,Kashuk JL,Chu ES,Narayanan V,Mehler PS.The use of thrombelastography to determine coagulation status in severe anorexia nervosa: a case series.Int J Eat Disord.2010;43(4):382385.
  21. Narayanan V,Gaudiani JL,Harris RH,Mehler PS.Liver function test abnormalities in anorexia nervosa—cause or effect.Int J Eat Disord.2010;43(4):378381.
  22. Pollack A.Eating disorders: a new front in insurance fight.New York Times. October 13, 2011. Available at: http://www.nytimes.com/2011/10/14/business/ruling‐offers‐hope‐to‐eating‐disorder‐sufferers. html?ref=business.
  23. Brewerton RD,Costin C.Long‐term outcome of residential treatment for anorexia nervosa and bulimia nervosa.Eat Disord.2011;19:132144.
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Journal of Hospital Medicine - 7(4)
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Anorexia nervosa occurs in 0.9% of women and 0.3% of men in the United States1 and is associated with a prolonged course,2 extensive medical complications that can affect almost every organ system,3, 4 and a 5% mean crude mortality rate9.6 times expected for age‐matched women in the United States.2, 5 Those with anorexia nervosa die as a complication of their illness more frequently than any other mental illness.3 Anorexia nervosa is commonly diagnosed during the adolescent years,2 with almost 25% going on to develop chronic anorexia nervosa.2, 6 Consequently, many patients with severe anorexia nervosa will receive treatment by adult medicine practitioners.

Patients with anorexia nervosa frequently require hospitalization. Published guidelines suggest that those who are 70% or less than ideal body weight, bradycardic, hypotensive, or those with severe electrolyte disturbances warrant admission for medical stabilization.79 Once admitted, however, there are no published guidelines for best practices to medically stabilize patients.7, 10 Although most experts advocate a multidisciplinary approach with weight restoration and medical stability as the goals of hospital admission,8, 9 controversy exists in the literature about how best to achieve these goals.7, 10

It is known, however, that for patients with complicated medical illnesses, such as human immunodeficiency virus (HIV) and sepsis, higher volumes of patient caseloads treated by physicians with disease‐specific expertise has been found to lead to improved outcomes in patients.11, 12 The adult patient with severe anorexia nervosa who requires inpatient medical stabilization may also benefit from a multidisciplinary trained staff familiar with the medical management of anorexia nervosa. Accordingly, we have developed the Acute Comprehensive Urgent Treatment for Eating Disorders (ACUTE) Center.

PROGRAM DESCRIPTION

The ACUTE Center at Denver Health is a 5‐bed unit dedicated to the medical stabilization of patients with severe malnutrition due to anorexia nervosa or severe electrolyte disorders due to bulimia nervosa. ACUTE accepts patients 17 years and older with medical complications related to chronic malnutrition and refeeding.

ACUTE uses a multidisciplinary approach to patient care. The physician team is composed of a hospital medicine attending physician, consultative expertise by an internal medicine specialist in the management of the medical complications of eating disorders, and a psychiatrist specializing in eating disorders. There is a dedicated team of nurses, two dieticians, physical therapists, certified nursing assistants, speech therapists, a psychotherapist, and a chaplain.

ACUTE patients are on continuous telemetry monitoring for the duration of their hospitalization to monitor for arrhythmias as well as signs of covert exercise. As part of the initial intake, a full set of vital signs is obtained, including height and weight. Patients are weighed daily with their back to the scale. There is no discussion of weight fluctuations. Patients may walk at a slow pace around the unit. No exercise is allowed.

Each patient at the ACUTE Center has an individualized meal plan and are started on an oral caloric intake 200 kcal below their basal energy expenditure (BEE). Indirect calorimetry is performed on the first hospital day. Each patient meets on a daily basis with the registered dietician to choose meals that meet their caloric goals.

All patients have a sitter continuously for their first week, and thereafter sitter time may be reduced to supervision surrounding each meal. Patients who fail to finish their prescribed meal are required to drink a liquid supplement to meet caloric goals. Calories are increased weekly until the patient's weight shows a clear pattern of weight increase. 0

Figure 1
The ACUTE Center at Denver Health initial intake form.

Patients are discharged from the ACUTE Center when they have achieved several basic goals: They are consuming greater than 2000 kcal per day, they are consistently gaining 23 pounds per week, their laboratory values have stabilized without electrolyte supplementation, and they are strong enough for an inpatient eating disorder program.

METHODS

Patients admitted to the ACUTE Center between October 2008 and December 2010 for medical stabilization and monitored refeeding were included. Patients with a diagnosis of bulimia nervosa were excluded. Demographic data and laboratory results were obtained electronically from our data repository, whereas weight, height, and other clinical characteristics were obtained by manual chart abstraction. The statistical analysis was conducted in SAS Enterprise Guide v4.1 (SAS Institute, Cary, NC).

RESULTS

In its first 27 months, the ACUTE Center had 76 total admissions, comprising 59 patients. Of the 76 admissions, the 62 admissions for medical stabilization and monitored refeeding of 54 patients with anorexia nervosa were included. Forty‐eight of the 54 (89%) included patients were female. Six patients were hospitalized twice, and 1 patient 3 times. There were 3 transfers to the intensive care unit, and no inpatient mortality. Of the 62 admissions, 11 (18%) discharges were to home, and 51 (82%) were to inpatient psychiatric eating disorder units.

The mean age at admission was 27 years (range 1765 years). The mean percent of ideal body weight (IBW) on admission was 62.2% 10.2%. The mean body mass index (BMI) was 12.9 2.0 kg/m2 on admission, and 13.1 1.9 kg/m2 upon discharge. The median length of stay was 16 days (interquartile range [IQR] 929 days). Median calculated BEE (1119 [10671184 IQR]) was higher than measured BEE by indirect calorimetry (792 [6341094]), (Table 1).

Patient Characteristics (N = 62 Admissions)
Median (Interquartile Range)* Range
  • Abbreviations: BEE, basal energy expenditure; BMI, body mass index; DEXA, dual energy x‐ray absorptiometry.

  • Mean standard deviation displayed if normally distributed.

  • Frequency and percentage shown for categorical variables.

  • Measured BEE available for 42 admission and DEXA scans for 38 patients.

Age, yr 27 (2135) 1765
Female 56 90%
Length of hospitalization, days 16 (929) 570
Calculated BEE 1119 (10671184) 9061491
Measured BEE 792 (6341094) 5001742
DEXA Z‐score 2.2 1.1 4.40.7
Height, in 65 (6167) 5774
Weight on admission, lb 76.1 14.4 50.8110.0
% Ideal body weight on admission 62.2 10.2 42.4101.0
% Ideal body weight on discharge 63.2 9.1 42.3 82.7
BMI on admission 12.9 2.0 8.719.7
BMI nadir 12.4 1.9 8.415.7
BMI on discharge 13.1 1.9 8.717.0

The majority of admission laboratory values, including serum albumin, blood urea nitrogen (BUN), creatinine, potassium, magnesium, and phosphate levels, were within normal limits. Fifty‐six percent were hyponatremic at admission, with a mean serum sodium level of 133 6 mmol/L (Table 2).

Admission Labs (N = 62)
Median (Interquartile Range)* Range
  • NOTE: Reference range shown in parentheses.

  • Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; INR, international normalized ratio; MCV, mean corpuscular volume; TSH, thyroid stimulating hormone; WBC, white blood cell.

  • Mean standard deviation displayed if normally distributed.

  • Pre‐albumin was available on 49 admissions. TSH was available on 50 admissions. INR was available on 59 admissions. 1,25 Hydroxy vitamin D was available on 53 admissions. Neutrophils and lymphocytes were available on 60 admissions.

Sodium (135143 mmol/L) 133 6 117145
Potassium (3.65.1 mmol/L) 3.8 (3.0 4.0) 1.85.5
Carbon dioxide (1827 mmol/L) 28 (2531) 1845
Glucose (60199 mg/dL) 85 (76105) 41166
BUN (622 mg/dL) 16 (923) 344
Creatinine (0.61.2 mg/dL) 0.7 (0.61.0) 0.31.6
Calcium (8.110.5 mg/dL) 8.9 0.6 7.610.1
Phosphorus (2.74.8 mg/dL) 3.2 (2.83.7) 2.15.7
Magnesium (1.32.1 mEq/L) 1.8 0.3 1.22.5
AST (1040 U/L) 38 (2391) 122402
ALT (745 U/L) 45 (2498) 152436
Total bilirubin (0.01.2 mg/dL) 0.5 (0.30.7) 0.12.2
Pre‐albumin (2052 mg/dL) 21 7 842
Albumin (3.05.3 g/dL) 3.7 0.7 1.64.8
WBC (4.510.0 k/L) 4.0 (3.25.7) 1.120.3
Neutrophils (%) (48.069.0%) 55.5 13.1 17.082.0
Lymphocytes (%) (21.043.0%) 34.9 13.0 10.864.0
Platelet count (150450 k/L) 266 (193371) 40819
Hematocrit (37.047.0%) 36.1 5.4 19.145.7
MCV (80100 fL) 91 7 73105
TSH (0.346.00 IU/mL) 1.52 (0.962.84) 0.1864.1
INR (0.821.17) 1.09 (1.001.22) 0.812.05
1,25 Hydroxy vitamin D (3080 ng/mL) 41 (3058) 8171

DISCUSSION

Hospital Medicine is currently the fastest growing area of specialization in medicine.13 Palliative care, inpatient geriatrics, short stay units, and bedside procedures have evolved into hospitalist‐led services.1418 The management of the medical complications of severe eating disorders is another potential niche for hospitalists.

The ACUTE Center at Denver Health represents a center in which highly specialized, multidisciplinary care is provided for a rare and extremely ill population of patients. Prior to entering the ACUTE Center, the patients described in our program had each experienced prolonged and unsuccessful stays for medical stabilization in acute care hospitals across the country, after being denied treatment in eating disorder programs due to medical instability.

Patients transferred to ACUTE often received medical care reflecting a lack of specific expertise, training, and exposure. The most common management discrepancy we noted was over‐aggressive provision of intravenous fluids. Consequently, we often diurese 1020 pounds of edema weight, gained during a prior medical hospitalization, before beginning the process of weight restoration. This edema weight artificially increases admission weight and results in less than expected weight gain from admission to discharge.

Even without substantial weight gain, medical stabilization is evidenced by consistent caloric oral intake, and fluid and electrolyte stabilization after initial refeeding. Accordingly, patients who have been treated at the ACUTE Center often become eligible for admission to eating disorder programs at body weights below the typical 70% of ideal body weight that most programs use as a threshold for admission.

From a clinical research perspective, centers such as ACUTE allow for opportunities to better understand and investigate the nuances of patient care in the setting of severe malnutrition. From our cohort of patients to date, we have noted unique issues in albumin levels,19 coagulopathy,20 and liver function,21 among others. As an example, the cohort of patients with anorexia nervosa described here had profoundly low body weight, but relatively normal admission labs. Even the serum albumin, a parameter often used to reflect nutrition in an adult internal medicine setting, is usually normal, reflecting, in an otherwise generally healthy young population, the absence of a malignant, inflammatory, or infectious etiology of weight loss.19

Hospitalists also advocate for their patients by helping to maximize the benefits of their health care coverage. Many health care plans place limits on inpatient psychiatric care benefits. Patients who are severely malnourished from their eating disorder may waste valuable psychiatric care benefits undergoing medical stabilization in psychiatric units while physically unable to undergo psychotherapy. This has become increasingly important as health insurance plans continue to decrease coverage for residential care of patients with anorexia.22

In contrast, the medical benefits of most health plans are more robust. Accordingly, from the patient perspective, medical stabilization in an acute medical unit before admission to a psychiatry unit maximizes their ability to participate in the intensive psychiatric therapy which is still needed after medical stabilization. A recent study from a residential eating disorder program confirmed that a higher discharge BMI was the single best predictor of full recovery from anorexia nervosa.23

In the future, we believe that a continuing concentration of care and experience may also lend itself to the development of protocols and management guidelines which may benefit patients beyond our own unit. Severely malnourished patients with anorexia nervosa, or bulimic patients with complicated electrolyte disorders, are likely to benefit both medically and financially from centers of excellence. Inpatient or residential psychiatric eating disorder programs may act in synergy with medical eating disorders units, like ACUTE, to most efficiently care for the severely malnourished patient. Hospitalists, with the proper training and experience, are uniquely positioned to develop such centers of excellence.

Anorexia nervosa occurs in 0.9% of women and 0.3% of men in the United States1 and is associated with a prolonged course,2 extensive medical complications that can affect almost every organ system,3, 4 and a 5% mean crude mortality rate9.6 times expected for age‐matched women in the United States.2, 5 Those with anorexia nervosa die as a complication of their illness more frequently than any other mental illness.3 Anorexia nervosa is commonly diagnosed during the adolescent years,2 with almost 25% going on to develop chronic anorexia nervosa.2, 6 Consequently, many patients with severe anorexia nervosa will receive treatment by adult medicine practitioners.

Patients with anorexia nervosa frequently require hospitalization. Published guidelines suggest that those who are 70% or less than ideal body weight, bradycardic, hypotensive, or those with severe electrolyte disturbances warrant admission for medical stabilization.79 Once admitted, however, there are no published guidelines for best practices to medically stabilize patients.7, 10 Although most experts advocate a multidisciplinary approach with weight restoration and medical stability as the goals of hospital admission,8, 9 controversy exists in the literature about how best to achieve these goals.7, 10

It is known, however, that for patients with complicated medical illnesses, such as human immunodeficiency virus (HIV) and sepsis, higher volumes of patient caseloads treated by physicians with disease‐specific expertise has been found to lead to improved outcomes in patients.11, 12 The adult patient with severe anorexia nervosa who requires inpatient medical stabilization may also benefit from a multidisciplinary trained staff familiar with the medical management of anorexia nervosa. Accordingly, we have developed the Acute Comprehensive Urgent Treatment for Eating Disorders (ACUTE) Center.

PROGRAM DESCRIPTION

The ACUTE Center at Denver Health is a 5‐bed unit dedicated to the medical stabilization of patients with severe malnutrition due to anorexia nervosa or severe electrolyte disorders due to bulimia nervosa. ACUTE accepts patients 17 years and older with medical complications related to chronic malnutrition and refeeding.

ACUTE uses a multidisciplinary approach to patient care. The physician team is composed of a hospital medicine attending physician, consultative expertise by an internal medicine specialist in the management of the medical complications of eating disorders, and a psychiatrist specializing in eating disorders. There is a dedicated team of nurses, two dieticians, physical therapists, certified nursing assistants, speech therapists, a psychotherapist, and a chaplain.

ACUTE patients are on continuous telemetry monitoring for the duration of their hospitalization to monitor for arrhythmias as well as signs of covert exercise. As part of the initial intake, a full set of vital signs is obtained, including height and weight. Patients are weighed daily with their back to the scale. There is no discussion of weight fluctuations. Patients may walk at a slow pace around the unit. No exercise is allowed.

Each patient at the ACUTE Center has an individualized meal plan and are started on an oral caloric intake 200 kcal below their basal energy expenditure (BEE). Indirect calorimetry is performed on the first hospital day. Each patient meets on a daily basis with the registered dietician to choose meals that meet their caloric goals.

All patients have a sitter continuously for their first week, and thereafter sitter time may be reduced to supervision surrounding each meal. Patients who fail to finish their prescribed meal are required to drink a liquid supplement to meet caloric goals. Calories are increased weekly until the patient's weight shows a clear pattern of weight increase. 0

Figure 1
The ACUTE Center at Denver Health initial intake form.

Patients are discharged from the ACUTE Center when they have achieved several basic goals: They are consuming greater than 2000 kcal per day, they are consistently gaining 23 pounds per week, their laboratory values have stabilized without electrolyte supplementation, and they are strong enough for an inpatient eating disorder program.

METHODS

Patients admitted to the ACUTE Center between October 2008 and December 2010 for medical stabilization and monitored refeeding were included. Patients with a diagnosis of bulimia nervosa were excluded. Demographic data and laboratory results were obtained electronically from our data repository, whereas weight, height, and other clinical characteristics were obtained by manual chart abstraction. The statistical analysis was conducted in SAS Enterprise Guide v4.1 (SAS Institute, Cary, NC).

RESULTS

In its first 27 months, the ACUTE Center had 76 total admissions, comprising 59 patients. Of the 76 admissions, the 62 admissions for medical stabilization and monitored refeeding of 54 patients with anorexia nervosa were included. Forty‐eight of the 54 (89%) included patients were female. Six patients were hospitalized twice, and 1 patient 3 times. There were 3 transfers to the intensive care unit, and no inpatient mortality. Of the 62 admissions, 11 (18%) discharges were to home, and 51 (82%) were to inpatient psychiatric eating disorder units.

The mean age at admission was 27 years (range 1765 years). The mean percent of ideal body weight (IBW) on admission was 62.2% 10.2%. The mean body mass index (BMI) was 12.9 2.0 kg/m2 on admission, and 13.1 1.9 kg/m2 upon discharge. The median length of stay was 16 days (interquartile range [IQR] 929 days). Median calculated BEE (1119 [10671184 IQR]) was higher than measured BEE by indirect calorimetry (792 [6341094]), (Table 1).

Patient Characteristics (N = 62 Admissions)
Median (Interquartile Range)* Range
  • Abbreviations: BEE, basal energy expenditure; BMI, body mass index; DEXA, dual energy x‐ray absorptiometry.

  • Mean standard deviation displayed if normally distributed.

  • Frequency and percentage shown for categorical variables.

  • Measured BEE available for 42 admission and DEXA scans for 38 patients.

Age, yr 27 (2135) 1765
Female 56 90%
Length of hospitalization, days 16 (929) 570
Calculated BEE 1119 (10671184) 9061491
Measured BEE 792 (6341094) 5001742
DEXA Z‐score 2.2 1.1 4.40.7
Height, in 65 (6167) 5774
Weight on admission, lb 76.1 14.4 50.8110.0
% Ideal body weight on admission 62.2 10.2 42.4101.0
% Ideal body weight on discharge 63.2 9.1 42.3 82.7
BMI on admission 12.9 2.0 8.719.7
BMI nadir 12.4 1.9 8.415.7
BMI on discharge 13.1 1.9 8.717.0

The majority of admission laboratory values, including serum albumin, blood urea nitrogen (BUN), creatinine, potassium, magnesium, and phosphate levels, were within normal limits. Fifty‐six percent were hyponatremic at admission, with a mean serum sodium level of 133 6 mmol/L (Table 2).

Admission Labs (N = 62)
Median (Interquartile Range)* Range
  • NOTE: Reference range shown in parentheses.

  • Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; INR, international normalized ratio; MCV, mean corpuscular volume; TSH, thyroid stimulating hormone; WBC, white blood cell.

  • Mean standard deviation displayed if normally distributed.

  • Pre‐albumin was available on 49 admissions. TSH was available on 50 admissions. INR was available on 59 admissions. 1,25 Hydroxy vitamin D was available on 53 admissions. Neutrophils and lymphocytes were available on 60 admissions.

Sodium (135143 mmol/L) 133 6 117145
Potassium (3.65.1 mmol/L) 3.8 (3.0 4.0) 1.85.5
Carbon dioxide (1827 mmol/L) 28 (2531) 1845
Glucose (60199 mg/dL) 85 (76105) 41166
BUN (622 mg/dL) 16 (923) 344
Creatinine (0.61.2 mg/dL) 0.7 (0.61.0) 0.31.6
Calcium (8.110.5 mg/dL) 8.9 0.6 7.610.1
Phosphorus (2.74.8 mg/dL) 3.2 (2.83.7) 2.15.7
Magnesium (1.32.1 mEq/L) 1.8 0.3 1.22.5
AST (1040 U/L) 38 (2391) 122402
ALT (745 U/L) 45 (2498) 152436
Total bilirubin (0.01.2 mg/dL) 0.5 (0.30.7) 0.12.2
Pre‐albumin (2052 mg/dL) 21 7 842
Albumin (3.05.3 g/dL) 3.7 0.7 1.64.8
WBC (4.510.0 k/L) 4.0 (3.25.7) 1.120.3
Neutrophils (%) (48.069.0%) 55.5 13.1 17.082.0
Lymphocytes (%) (21.043.0%) 34.9 13.0 10.864.0
Platelet count (150450 k/L) 266 (193371) 40819
Hematocrit (37.047.0%) 36.1 5.4 19.145.7
MCV (80100 fL) 91 7 73105
TSH (0.346.00 IU/mL) 1.52 (0.962.84) 0.1864.1
INR (0.821.17) 1.09 (1.001.22) 0.812.05
1,25 Hydroxy vitamin D (3080 ng/mL) 41 (3058) 8171

DISCUSSION

Hospital Medicine is currently the fastest growing area of specialization in medicine.13 Palliative care, inpatient geriatrics, short stay units, and bedside procedures have evolved into hospitalist‐led services.1418 The management of the medical complications of severe eating disorders is another potential niche for hospitalists.

The ACUTE Center at Denver Health represents a center in which highly specialized, multidisciplinary care is provided for a rare and extremely ill population of patients. Prior to entering the ACUTE Center, the patients described in our program had each experienced prolonged and unsuccessful stays for medical stabilization in acute care hospitals across the country, after being denied treatment in eating disorder programs due to medical instability.

Patients transferred to ACUTE often received medical care reflecting a lack of specific expertise, training, and exposure. The most common management discrepancy we noted was over‐aggressive provision of intravenous fluids. Consequently, we often diurese 1020 pounds of edema weight, gained during a prior medical hospitalization, before beginning the process of weight restoration. This edema weight artificially increases admission weight and results in less than expected weight gain from admission to discharge.

Even without substantial weight gain, medical stabilization is evidenced by consistent caloric oral intake, and fluid and electrolyte stabilization after initial refeeding. Accordingly, patients who have been treated at the ACUTE Center often become eligible for admission to eating disorder programs at body weights below the typical 70% of ideal body weight that most programs use as a threshold for admission.

From a clinical research perspective, centers such as ACUTE allow for opportunities to better understand and investigate the nuances of patient care in the setting of severe malnutrition. From our cohort of patients to date, we have noted unique issues in albumin levels,19 coagulopathy,20 and liver function,21 among others. As an example, the cohort of patients with anorexia nervosa described here had profoundly low body weight, but relatively normal admission labs. Even the serum albumin, a parameter often used to reflect nutrition in an adult internal medicine setting, is usually normal, reflecting, in an otherwise generally healthy young population, the absence of a malignant, inflammatory, or infectious etiology of weight loss.19

Hospitalists also advocate for their patients by helping to maximize the benefits of their health care coverage. Many health care plans place limits on inpatient psychiatric care benefits. Patients who are severely malnourished from their eating disorder may waste valuable psychiatric care benefits undergoing medical stabilization in psychiatric units while physically unable to undergo psychotherapy. This has become increasingly important as health insurance plans continue to decrease coverage for residential care of patients with anorexia.22

In contrast, the medical benefits of most health plans are more robust. Accordingly, from the patient perspective, medical stabilization in an acute medical unit before admission to a psychiatry unit maximizes their ability to participate in the intensive psychiatric therapy which is still needed after medical stabilization. A recent study from a residential eating disorder program confirmed that a higher discharge BMI was the single best predictor of full recovery from anorexia nervosa.23

In the future, we believe that a continuing concentration of care and experience may also lend itself to the development of protocols and management guidelines which may benefit patients beyond our own unit. Severely malnourished patients with anorexia nervosa, or bulimic patients with complicated electrolyte disorders, are likely to benefit both medically and financially from centers of excellence. Inpatient or residential psychiatric eating disorder programs may act in synergy with medical eating disorders units, like ACUTE, to most efficiently care for the severely malnourished patient. Hospitalists, with the proper training and experience, are uniquely positioned to develop such centers of excellence.

References
  1. Hudson JI,Hiripi E,Harrison GP,Kessler RC.The prevalence and correlates of eating disorders in the national comorbidity survey replication.Biol Psychiatry.2007;61:348358.
  2. Steinhausen HC.The outcome of anorexia nervosa in the 20th century.Am J Psychiatry.2002;159:12841293.
  3. Mehler PS,Krantz M.Anorexia nervosa medical issues.J Womens Health.2003;12:331340.
  4. Mehler PS.Diagnosis and care of patients with anorexia nervosa in primary care settings.Ann Intern Med.2001;134:10481059.
  5. Herzog DB,Greenwood DN,Dorer DJ, et al.Mortality in eating disorders: a descriptive study.Int J Eat Disord.2000;28:2026.
  6. Zipfel S,Lowe B,Reas DL,Deter HC,Herzog W.Long‐term prognosis in anorexia nervosa: lessons from a 21‐year follow‐up study.Lancet.2000;355:721722.
  7. Schwartz BI,Mansbach JM,Marion JG,Katzman DK,Forman SF.Variations in admissions practices for adolescents with anorexia nervosa: a North American sample.J Adolesc Health.2008;43:425431.
  8. American Psychiatric Association.Treatment of patients with eating disorders, third edition.Am J Psychiatry.2006;163(suppl 7):454.
  9. American Dietetic Association.Position of the American Dietetic Association: nutrition intervention in the treatment of anorexia nervosa, bulimia nervosa, and other eating disorders (ADA reports).J Am Diet Assoc.2006;106:20732082.
  10. Sylvester CJ,Forman SF.Clinical practice guidelines for treating restrictive eating disorder patients during medical hospitalization.Curr Opin Pediatr.2008;20:390397.
  11. Hellinger F.Practice makes perfect: a volume‐outcome study of hospital patients with HIV disease.J Acquir Immune Defic Syndr.2008;47:226233.
  12. Chen CH,Chen YH,Lin HC,Lin HC.Association between physician caseload and patient outcome for sepsis treatment.Infect Control Hosp Epidemiol.2009;30:556562.
  13. Wachter RM.Reflections: the hospitalist movement ten years later.J Hosp Med.2006;1:248252.
  14. What will board certification be‐and mean‐for hospitalists?Meier DE.Palliative care in hospitals.J Hosp Med.2006;1:2128.
  15. Pantilat SZ.Palliative care and hospitalists: a partnership for hope.J Hosp Med.2006;1:56.
  16. Lucas BP,Asbury JK,Wang Y, et al.Impact of a bedside procedure service on general medicine inpatients: a firm‐based trial.J Hosp Med.2007;2:143149.
  17. Kuo YF,Sharma G,Freeman JL,Goodwin JS.Growth in the care of older patients by hospitalists in the United States.N Engl J Med.2009;360:11021112.
  18. Lucas BP,Kumapley R,Mba B, et al.A hospitalist run short stay unit: features that predict length of stay and eventual admission to traditional inpatient services.J Hosp Med.2009;4:276284.
  19. Narayanan V,Gaudiani JL,Mehler PS.Serum albumin levels may not correlate with weight status in severe anorexia nervosa.Eat Disord.2009;17:322326.
  20. Gaudiani JL,Kashuk JL,Chu ES,Narayanan V,Mehler PS.The use of thrombelastography to determine coagulation status in severe anorexia nervosa: a case series.Int J Eat Disord.2010;43(4):382385.
  21. Narayanan V,Gaudiani JL,Harris RH,Mehler PS.Liver function test abnormalities in anorexia nervosa—cause or effect.Int J Eat Disord.2010;43(4):378381.
  22. Pollack A.Eating disorders: a new front in insurance fight.New York Times. October 13, 2011. Available at: http://www.nytimes.com/2011/10/14/business/ruling‐offers‐hope‐to‐eating‐disorder‐sufferers. html?ref=business.
  23. Brewerton RD,Costin C.Long‐term outcome of residential treatment for anorexia nervosa and bulimia nervosa.Eat Disord.2011;19:132144.
References
  1. Hudson JI,Hiripi E,Harrison GP,Kessler RC.The prevalence and correlates of eating disorders in the national comorbidity survey replication.Biol Psychiatry.2007;61:348358.
  2. Steinhausen HC.The outcome of anorexia nervosa in the 20th century.Am J Psychiatry.2002;159:12841293.
  3. Mehler PS,Krantz M.Anorexia nervosa medical issues.J Womens Health.2003;12:331340.
  4. Mehler PS.Diagnosis and care of patients with anorexia nervosa in primary care settings.Ann Intern Med.2001;134:10481059.
  5. Herzog DB,Greenwood DN,Dorer DJ, et al.Mortality in eating disorders: a descriptive study.Int J Eat Disord.2000;28:2026.
  6. Zipfel S,Lowe B,Reas DL,Deter HC,Herzog W.Long‐term prognosis in anorexia nervosa: lessons from a 21‐year follow‐up study.Lancet.2000;355:721722.
  7. Schwartz BI,Mansbach JM,Marion JG,Katzman DK,Forman SF.Variations in admissions practices for adolescents with anorexia nervosa: a North American sample.J Adolesc Health.2008;43:425431.
  8. American Psychiatric Association.Treatment of patients with eating disorders, third edition.Am J Psychiatry.2006;163(suppl 7):454.
  9. American Dietetic Association.Position of the American Dietetic Association: nutrition intervention in the treatment of anorexia nervosa, bulimia nervosa, and other eating disorders (ADA reports).J Am Diet Assoc.2006;106:20732082.
  10. Sylvester CJ,Forman SF.Clinical practice guidelines for treating restrictive eating disorder patients during medical hospitalization.Curr Opin Pediatr.2008;20:390397.
  11. Hellinger F.Practice makes perfect: a volume‐outcome study of hospital patients with HIV disease.J Acquir Immune Defic Syndr.2008;47:226233.
  12. Chen CH,Chen YH,Lin HC,Lin HC.Association between physician caseload and patient outcome for sepsis treatment.Infect Control Hosp Epidemiol.2009;30:556562.
  13. Wachter RM.Reflections: the hospitalist movement ten years later.J Hosp Med.2006;1:248252.
  14. What will board certification be‐and mean‐for hospitalists?Meier DE.Palliative care in hospitals.J Hosp Med.2006;1:2128.
  15. Pantilat SZ.Palliative care and hospitalists: a partnership for hope.J Hosp Med.2006;1:56.
  16. Lucas BP,Asbury JK,Wang Y, et al.Impact of a bedside procedure service on general medicine inpatients: a firm‐based trial.J Hosp Med.2007;2:143149.
  17. Kuo YF,Sharma G,Freeman JL,Goodwin JS.Growth in the care of older patients by hospitalists in the United States.N Engl J Med.2009;360:11021112.
  18. Lucas BP,Kumapley R,Mba B, et al.A hospitalist run short stay unit: features that predict length of stay and eventual admission to traditional inpatient services.J Hosp Med.2009;4:276284.
  19. Narayanan V,Gaudiani JL,Mehler PS.Serum albumin levels may not correlate with weight status in severe anorexia nervosa.Eat Disord.2009;17:322326.
  20. Gaudiani JL,Kashuk JL,Chu ES,Narayanan V,Mehler PS.The use of thrombelastography to determine coagulation status in severe anorexia nervosa: a case series.Int J Eat Disord.2010;43(4):382385.
  21. Narayanan V,Gaudiani JL,Harris RH,Mehler PS.Liver function test abnormalities in anorexia nervosa—cause or effect.Int J Eat Disord.2010;43(4):378381.
  22. Pollack A.Eating disorders: a new front in insurance fight.New York Times. October 13, 2011. Available at: http://www.nytimes.com/2011/10/14/business/ruling‐offers‐hope‐to‐eating‐disorder‐sufferers. html?ref=business.
  23. Brewerton RD,Costin C.Long‐term outcome of residential treatment for anorexia nervosa and bulimia nervosa.Eat Disord.2011;19:132144.
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Macrolides for Mycoplasmal Pneumonia

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Macrolide therapy and outcomes in a multicenter cohort of children hospitalized with Mycoplasma pneumoniae pneumonia

Mycoplasma pneumoniae is a common cause of community‐acquired pneumonia (CAP), among school‐age children and adolescents.14 Though pneumonia caused by M. pneumoniae is typically self‐limited, severe illness may occur.5 M. pneumoniae has also been implicated in airway inflammation, which may lead to the onset and development of chronic pulmonary disease.610 Few studies have directly addressed appropriate treatment strategies for M. pneumoniae pneumonia,11 and, despite its high prevalence and potential for causing severe complications, treatment recommendations remain inconsistent.

The efficacy of macrolide therapy in particular for M. pneumoniae remains unclear. In vitro susceptibility studies have shown bacteriostatic activity of erythromycin, clarithromycin, and azithromycin against M. pneumoniae.1218 Additionally, several small retrospective studies have shown that among children with atypical CAP (including M. pneumoniae pneumonia), those treated with macrolides were less likely to have persistence or progression of signs and symptoms after 3 days of therapy.19, 20 Lu et al21 found a shorter duration of fever among macrolide recipients compared with non‐recipients. In adults, Shames et al22 found a shorter duration of fever and hospitalization among erythromycin recipients compared with controls. Other randomized controlled trials have also addressed the use of macrolides in treatment of M. pneumoniae, but the ability to draw meaningful conclusions is limited by small samples sizes and by lack of details about the number of patients with M. pneumoniae.11

In addition to their antimicrobial effect, macrolides also have anti‐inflammatory properties.2327 The importance of these anti‐inflammatory properties is supported by studies showing clinical cure in patients treated with macrolides despite persistence of M. pneumoniae organisms,2831 clinical improvement despite the administration of doses that provide tissue levels below the minimum inhibitory concentration of the organism,3234 and clinical cure in patients with macrolide‐resistant M. pneumoniae.18, 35

The objectives of the current study were to examine the impact of macrolide therapy on the length of stay (LOS) and short‐ and longer‐term readmissions, including longer‐term asthma‐related readmissions, in children hospitalized with M. pneumoniae pneumonia.

METHODS

Data Source

Data for this retrospective cohort study were obtained from the Pediatric Health Information System (PHIS), which contains administrative data from 38 freestanding children's hospitals. Data quality and reliability are assured through a joint effort by the Child Health Corporation of America (Shawnee Mission, KS) and PHIS‐participating hospitals as described previously.36, 37 Encrypted medical record numbers allow for tracking of individual patients across hospitalizations. This study was reviewed and approved by the Committees for the Protection of Human Subjects at The Children's Hospital of Philadelphia (Philadelphia, PA).

Patients

Children 6‐18 years of age with CAP were eligible if they were discharged from a participating hospital between January 1, 2006 and December 31, 2008. Subjects were included if they received antibiotic therapy on the first day of hospitalization and if they satisfied one of the following International Classification of Diseases, 9th revision (ICD‐9) discharge diagnosis code criteria: 1) Principal diagnosis of M. pneumoniae pneumonia (483.0); 2) Principal diagnosis of a pneumonia‐related symptom (eg, fever, cough) (780.6 or 786.00‐786.52 [except 786.1]) and a secondary diagnosis of M. pneumoniae pneumonia; or 3) Principal diagnosis of pneumonia (481‐483.8 [except 483.0], 485‐486) and a secondary diagnosis of Mycoplasma (041.81).

Children younger than 6 years of age were excluded due to the low prevalence of M. pneumoniae infection.2, 38 Patients with comorbid conditions predisposing to severe or recurrent pneumonia (eg, cystic fibrosis, malignancy) were excluded using a previously reported classification scheme.39 In addition, we excluded patient data from 2 hospitals due to incomplete reporting of discharge information; thus data from 36 hospitals were included in this study.

Validation of Discharge Diagnosis Codes for Mycoplasma pneumoniae

To assess for misclassification of the diagnosis of M. pneumoniae, we reviewed records of a randomly selected subset of subjects from The Children's Hospital of Philadelphia; 14 of 15 patients had signs of lower respiratory tract infection in conjunction with a positive M. pneumoniae polymerase chain reaction test from nasopharyngeal washings to confirm the diagnosis of M. pneumoniae pneumonia. Hence, the positive predictive value of our algorithm for diagnosing M. pneumoniae pneumonia was 93.3%.

Study Definitions

We identified children with asthma in 2 ways. Asthma‐related hospitalizations were identified by an ICD‐9 code for asthma (493.0‐493.92) in any discharge diagnosis field during any hospitalization in the 24 months prior to the current hospitalization. Baseline controller medications were identified by receipt of inhaled corticosteroids (eg, fluticasone) or leukotriene receptor antagonists on the first day of hospitalization.

Systemic corticosteroids (either oral or intravenous) included dexamethasone, hydrocortisone, methylprednisolone, prednisolone, and prednisone. Measures of disease severity included admission to the intensive care unit within 48 hours of hospitalization, and administration of vancomycin or clindamycin, vasoactive infusions (epinephrine, norepinephrine, dopamine, and dobutamine), and invasive (endotracheal intubation) and noninvasive (continuous positive airway pressure) mechanical ventilation within 24 hours of hospitalization, as previously described.40, 41 Viral respiratory season was defined as October through March.

Measured Outcomes

The primary outcomes of interest were hospital LOS and all‐cause readmission within 28 days and 15 months after index discharge. We examined readmissions for asthma 15 months after index discharge as a secondary outcome measure because of the potential role for M. pneumoniae infection in long‐term lung dysfunction, including asthma.42 The 15‐month time frame was selected based on longitudinal data available in PHIS for the entire study cohort.

Measured Exposures

The main exposure was early initiation of macrolide therapy, defined as receipt of erythromycin, clarithromycin, or azithromycin on the first day of hospitalization.

Data Analysis

Continuous variables were described using median and interquartile range (IQR) or range values, and compared using the Wilcoxon rank‐sum test. Categorical variables were described using counts and frequencies, and compared using the chi‐square test. Multivariable linear (for LOS) and logistic (for readmission) regression analyses were performed to assess the independent association of macrolide therapy with the primary outcomes. Because the LOS data had a skewed distribution, our analyses were performed using logarithmically transformed LOS values as the dependent variable. The resulting beta‐coefficients were transformed to reflect the percent difference in LOS between subjects receiving and not receiving macrolide therapy.

Building of the multivariable models began with the inclusion of macrolide therapy. Variables associated with primary outcomes on univariate analysis (P < 0.20) were also considered for inclusion as potential confounders.43 These variables were included in the final multivariable model if they remained significant after adjusting for other factors, or if their inclusion in the model resulted in a 15% or greater change in the effect size of the primary association of interest (ie, macrolide therapy).44 Because corticosteroids also have anti‐inflammatory properties, we assessed for interactions with macrolide therapy. There was no interaction between macrolide and systemic corticosteroid therapy (P = 0.26, Likelihood ratio test), therefore our primary model adjusted for systemic corticosteroids.

Despite adjusting for systemic corticosteroid therapy in our primary analysis, residual confounding by indication for corticosteroid therapy might exist. We therefore repeated the analysis after stratifying by receipt or non‐receipt of systemic corticosteroid therapy. Because the benefit of macrolides in preventing long‐term dysfunction may be limited to those without a prior diagnosis of asthma, we repeated the analysis of readmissions within 15 months of index discharge (any readmission and asthma‐related readmissions) while limiting the cohort to those without evidence of asthma (ie, no prior asthma‐related hospitalizations and no chronic asthma medications). Because children with underlying conditions or circumstances that would predispose to prolonged hospitalizations may have been included, despite our restriction of the cohort to those without an identified chronic complex condition, we also repeated the analysis while limiting the cohort to those with a LOS 7 days. Finally, all analyses were clustered on hospital using the robust standard errors of Huber and White to account for the correlation of exposures and outcomes among children within centers.

Data were analyzed using Stata version 11 (Stata Corporation, College Station, TX). Statistical significance was determined a priori as a two‐tailed P value <0.05.

RESULTS

Patient Characteristics

During the study, 690 children ages 6 to 18 years met inclusion criteria. Characteristics of these patients are shown in Table 1. The median age was 10 years (IQR, 7‐13 years). Ten patients (1.4%) also had a concomitant discharge diagnosis of pneumococcal pneumonia, while 19 patients (2.7%) had a concomitant discharge diagnosis of viral pneumonia; 1 of these patients had discharge diagnoses of both viral and pneumococcal pneumonia.

Demographic Information and Processes of Care for Children With a Discharge Diagnosis of Mycoplasma pneumoniae Pneumonia
  Empiric Macrolide Therapy 
VariableAll SubjectsYesNoP
  • NOTE: Values listed as number (percent).

  • Includes chest computed tomography or ultrasound.

Demographics    
Male sex356 (51.6)200 (49.4)156 (54.7)0.166
Race    
Black135 (19.6)81 (20.0)54 (19.0)0.506
White484 (70.1)287 (70.9)197 (69.1) 
Other62 (9.0)31 (7.7)31 (10.9) 
Missing9 (1.3)6 (1.5)3 (1.1) 
Presentation during viral respiratory season420 (60.9)242 (59.8)178 (62.5) 
Prior asthma hospitalization41 (5.9)31 (7.7)10 (3.5)0.023
Intensive care unit admission127 (18.4)74 (18.3)53 (18.6)0.914
Laboratory tests and procedures    
Additional radiologic imaging*24 (3.5)13 (3.2)11 (3.9)0.646
Arterial blood gas116 (17.3)72 (18.5)44 (15.6)0.316
Complete blood count433 (64.4)249 (64.0)184 (65.0)0.788
Blood culture280 (41.7)167 (42.9)113 (39.9)0.436
Mechanical ventilation16 (2.3)5 (1.2)11 (3.86)0.024
Medications    
Chronic asthma medication116 (16.8)72 (17.8)44 (15.4)0.419
Beta‐agonist therapy328 (47.5)215 (53.1)113 (39.7)0.001
Vasoactive infusions22 (3.2)13 (3.2)9 (3.2)0.969
Systemic corticosteroids252 (36.5)191 (47.2)61 (21.4)<0.001
Clindamycin or vancomycin86 (12.5)24 (5.9)62 (21.8)<0.001

Macrolide therapy was administered to 405 (58.7%) patients. Systemic corticosteroid therapy was administered to 252 (36.5%) patients. Overall, 191 (27.7%) of the 690 patients received both macrolides and systemic corticosteroids empirically, while 224 (32.5%) received neither; 61 (8.8%) received corticosteroids but not macrolides, while 214 (31.0%) received macrolides but not corticosteroids. Asthma hospitalization within the 24 months prior to admission was more common among those receiving macrolides (N = 60/405, 14.8%) than among those not receiving macrolides (N = 30/285, 10.5%) (P = 0.023). Macrolide recipients also more commonly received concomitant systemic corticosteroids (N = 191/405, 47.2%) than macrolide non‐recipients (N = 61/285, 21.4%) (P < 0.001) and more commonly received beta‐agonist therapy (N = 215/405, 53.1%) than macrolide non‐recipients (N = 113/285, 39.7%) (P = 0.001).

Length of Stay

The overall median LOS was 3 days (IQR, 2‐6 days); the median LOS was 3 days (IQR, 2‐5 days) for empiric macrolide recipients and 4 days (IQR, 2‐9 days) for non‐recipients (P < 0.001). Overall, 22.9% (N = 158) of children had an LOS 7 days and 8.8% (N = 61) of children had an LOS 14 days. The LOS was 7 days for 15.3% (N = 62) of macrolide recipients and 33.7% (N = 96) of non‐recipients. LOS was 7 days for 17.5% (N = 44) of systemic steroid recipients and 26% (N = 114) of non‐recipients. In unadjusted analysis, macrolide therapy (beta‐coefficient, 0.49; 95% confidence interval [CI]: 0.72 to 0.25; P < 0.001) and systemic corticosteroid administration (beta‐coefficient, 0.26; CI: 0.37 to 0.14; P < 0.001) were associated with shorter hospital LOS (Appendix 1).

In multivariable analysis, macrolide therapy remained associated with a shorter LOS (Table 2; Appendix 2). Systemic corticosteroid administration was associated with a 23% shorter LOS (adjusted beta‐coefficient, 0.26; 95% CI: 0.39 to 0.14; P < 0.001). In contrast, previous hospitalization for asthma was associated with a 31% longer LOS (adjusted beta‐coefficient, 0.27; 95% CI: 0.09‐0.045; P = 0.004). Receipt of beta‐agonist therapy or chronic asthma medications were not associated with significant differences in LOS. In analysis stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy, empiric macrolide therapy remained associated with a significantly shorter LOS in both systemic corticosteroid recipients and non‐recipient (Table 4). When the cohort was restricted to subjects with a LOS 7 days, macrolide therapy remained significantly associated with a shorter LOS (adjusted percent change, 20%; 95% CI: 32% to 5%; P = 0.015).

Adjusted Association of Empiric Macrolide Therapy With Outcomes
 Association of Empiric Macrolide Therapy With Outcomes*
  • All models adjusted for age, prior asthma hospitalization, intensive care unit admission, chronic asthma medications, albuterol, systemic corticosteroid therapy, and vancomcyin or clindamycin.

  • Abbreviation: CI, confidence interval.

Length of stay (days) 
Adjusted beta‐coefficient (95 % CI)0.38 (0.59 to 0.17)
Adjusted percent change (95% CI)32% (45% to 15%)
P value0.001
Any readmission within 28 days 
Adjusted odds ratio (95% CI)1.12 (0.22 to 5.78)
P value0.890
Any readmission within 15 mo 
Adjusted odds ratio (95% CI)1.00 (0.59 to 1.70)
P value0.991
Asthma hospitalization within 15 mo 
Adjusted odds ratio (95% CI)1.09 (0.54 to 2.17)
P value0.820

Readmission

Overall, 8 children (1.2%) were readmitted for pneumonia‐associated conditions within 28 days of index discharge. Readmission occurred in 1.2% of macrolide recipients and 1.1% of non‐recipients (P = 0.83) (Table 4). In unadjusted analysis, neither macrolide therapy (odds ratio [OR], 1.18; 95% CI: 0.25‐5.45; P = 0.84) nor systemic corticosteroid administration (OR, 1.04; 95% CI: 0.27‐4.10; P = 0.95) was associated with 28‐day readmission (Appendix 3). In multivariable analysis, empiric macrolide therapy was not associated with 28‐day readmission in the overall cohort (Table 2; Appendix 4)), or when the analysis was stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy (Table 3).

Multivariable Analysis of the Association Between Empiric Macrolide Therapy and Outcomes, Stratified by Receipt or Non‐Receipt of Systemic Corticosteroid Therapy
 Concomitant Systemic Corticosteroid Therapy*
 YesNo
  • All models adjusted for age, prior asthma hospitalization, intensive care unit admission, chronic asthma medications, albuterol, and vancomcyin or clindamycin.

  • Abbreviation: CI, confidence interval.

Length of stay  
Adjusted beta‐coefficient (95% CI)0.40 (0.74 to 0.07)0.37 (0.58 to 0.16)
Adjusted percent change (95% CI)33% (52% to 7%)31% (44% to 15%)
P value0.0200.001
Readmission within 28 days  
Adjusted odds ratio (95% CI)1.09 (0.05 to 26.7)1.50 (0.21 to 10.8)
P value0.9600.687
Readmission within 15 mo  
Adjusted odds ratio (95% CI)1.57 (0.65 to 3.82)0.81 (0.45 to 1.46)
P value0.320.49
Asthma hospitalization within 15 mo  
Adjusted odds ratio (95% CI)1.51 (0.58 to 3.93)0.85 (0.36 to 1.97)
P value0.3950.700
Readmissions Following Index Hospital Discharge Stratified by Receipt of Empiric Macrolide Therapy
 Empiric Macrolide Therapy
 N/Total (%)
ReadmissionYesNo
Any readmission within 28 days  
Overall5/405 (1.2)3/285 (1.1)
Systemic corticosteroid therapy2/186 (1.1)1/66 (1.5)
No systemic corticosteroid therapy3/177 (1.7)2/261 (0.8)
Any readmission within 15 mo  
Overall96/405 (23.7)64/285 (22.5)
Systemic corticosteroid therapy52/186 (28.0)17/66 (25.8)
No systemic corticosteroid therapy32/177 (18.1)59/261 (22.6)
Asthma hospitalization within 15 mo  
Overall61/405 (15.1)34/285 (11.9)
Systemic corticosteroid therapy39/186 (21.0)13/66 (19.7)
No systemic corticosteroid therapy14/177 (7.9)29/261 (11.1)

Overall, 160 children (23.2%) were readmitted within 15 months of index discharge; 95 were readmitted for asthma during this time (Table 3). Overall readmission occurred in 23.7% of macrolide recipients and 22.5% of macrolide non‐recipients (P = 0.702). Asthma readmission occurred in 15.1% of macrolide recipients and 11.9% of macrolide non‐recipients (P = 0.240). In unadjusted analysis, empiric macrolide therapy was not significantly associated with any readmission within 15 months (OR, 1.07; 95% CI: 0.69‐1.68; P = 0.759) or with asthma‐related readmission within 15 months (OR, 1.31; 95% CI: 0.73‐ 2.36; P = 0.369). In multivariable analysis, neither any readmission nor asthma readmission within 15 months was associated with empiric macrolide therapy overall (Table 2) or when stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy (Table 3).

The analyses for readmissions within 15 months of index discharge were repeated while limiting the cohort to those without prior asthma hospitalizations or chronic asthma medications. In this subset of patients, readmissions for any reason occurred in 55 (18.6%) of 295 macrolide recipients and 50 (22.0%) of 227 non‐recipients. The difference was not statistically significant in multivariable analysis (adjusted odds ratio, 0.79; 95% CI: 0.41‐1.51; P = 0.47). Readmissions for asthma occurred in 30 (10.2%) of 295 macrolide recipients and 26 (11.5%) of 227 non‐recipients; this difference was also not significant in multivariable analysis (adjusted odds ratio, 0.83; 95% CI: 0.36‐1.93; P = 0.83). The magnitude of the estimate of effect for 28‐day and 15‐month readmissions, and 15‐month asthma hospitalizations, was similar to the primary analysis when the cohort was restricted to subjects with a LOS 7 days.

DISCUSSION

This multicenter study examined the role of macrolide therapy in children hospitalized with M. pneumoniae pneumonia. Empiric macrolide therapy was associated with an approximately 30% shorter hospital LOS and, in stratified analysis, remained associated with a significantly shorter hospital LOS in both systemic corticosteroid recipients and non‐recipients. Empiric macrolide therapy was not associated with short‐ or longer‐term hospital readmission.

Previous small randomized trials have been inconclusive regarding the potential benefit of macrolide therapy in M. pneumoniae pneumonia.11 Our study, which demonstrated a shorter LOS among macrolides recipients compared with non‐recipients, has several advantages over prior studies including a substantively larger sample size and multicenter design. Animal models support our observations regarding the potential beneficial antimicrobial role of macrolides. M. pneumoniae concentrations in bronchoalveolar lavage specimens were significantly lower among experimentally infected mice treated with clarithromycin, a macolide‐class antibiotic, compared with either placebo or dexamethasone.45 Combination therapy with clarithromycin and dexamethasone reduced histopathologic inflammation to a greater degree than dexamethasone alone.45

While the relative importance of the antimicrobial and anti‐inflammatory properties of macrolides is not known, observational studies of children infected with macrolide‐resistant M. pneumoniae suggest that the antimicrobial properties of macrolides may provide disproportionate clinical benefit. The duration of fever in macrolide recipients with macrolide‐resistant M. pneumoniae (median duration, 9 days) reported by Suzuki et al46 was significantly longer than those with macrolide‐susceptible infections (median duration, 5 days), and similar to the duration of fever in patients with M. pneumoniae infection treated with placebo (median duration, 8 days) reported by Kingston et al.47 Additionally, macrolide therapy was associated with significant improvements in lung function in patients with asthma and concomitant M. pneumoniae infection, but not in patients with asthma without documented M. pneumoniae infection.9 As corticosteroids also have anti‐inflammatory properties, we expect that any anti‐inflammatory benefit of macrolide therapy would be mitigated by the concomitant administration of corticosteroids. The shorter LOS associated with empiric macrolide therapy in our study was comparable among corticosteroid recipients and non‐recipients.

Atypical bacterial pathogens, including M. pneumoniae, are associated with diffuse lower airway inflammation6, 48 and airway hyperresponsiveness,6 and have been implicated as a cause of acute asthma exacerbations.7, 4954 Among patients with previously diagnosed asthma, acute M. pneumoniae infection was identified in up to 20% of those having acute exacerbations.7, 54 Macrolide therapy has a beneficial effect on lung function and airway hyperresponsiveness in adults with asthma.9, 55 Among mice infected with M. pneumoniae, 3 days of macrolide therapy resulted in a significant reduction in airway hyperresponsiveness compared with placebo or dexamethasone; however, after 6 days of therapy, there was no significant difference in airway hyperresponsiveness between those receiving macrolides, dexamethasone, or placebo, suggesting that the benefit of macrolides on airway hyperresponsiveness may be brief. Our findings of a shorter LOS but no difference in readmissions at 28 days or longer, for macrolide recipients compared with non‐recipients, support the limited benefit of macrolide therapy beyond the initial reduction in bacterial load seen in the first few days of therapy.

M. pneumoniae infection has also been implicated as a cause of chronic pulmonary disease, including asthma.610 In the mouse model, peribronchial and perivascular mononuclear infiltrates, increased airway methacholine reactivity, and increased airway obstruction were observed 530 days after M. pneumoniae inoculation.6 M. pneumoniae has been identified in 26 (50%) of 51 children experiencing their first asthma attack,7 and 23 (42%) of 55 adults with chronic, stable asthma.9 Nevertheless, results of other studies addressing the issue are inconsistent, and the role of M. pneumoniae in the development of asthma remains unclear.56 In order to investigate the impact of macrolide therapy on the development of chronic pulmonary disease requiring hospitalization, we examined the readmission rates in the 15 months following index discharge. The proportion of children hospitalized with asthma following the hospitalization for M. pneumoniae pneumonia was higher for both macrolide recipients and non‐recipients compared with the 24‐months prior to infection. These results support a possible role for M. pneumoniae in chronic pulmonary disease. However, macrolide therapy was not associated with long‐term overall hospital readmission or long‐term asthma readmission, either in the entire cohort or in the subset of patients without prior asthma hospitalizations or medications.

This study had several limitations. First, because the identification of children with M. pneumoniae pneumonia relied on ICD‐9 discharge diagnosis codes, it is possible that there was misclassification of disease. We minimized the inclusion of children without M. pneumoniae by including only children who received antibiotic therapy on the first day of hospitalization and by excluding patients younger than 6 years of age, a group at relatively low‐risk for M. pneumoniae infection. Further, our algorithm for identification of M. pneumoniae pneumonia was validated through review of the medical records at 1 institution and was found to have a high positive predictive value. However, the positive predictive value of these ICD‐9 codes may vary across institutions. Additionally, the sensitivity of ICD‐9 codes for identifying children with M. pneumoniae pneumonia is not known. Also, not all children with pneumonia undergo testing for M. pneumoniae, and different tests have varying sensitivity and specificity.57, 58 Thus, some children with M. pneumoniae pneumonia were not diagnosed and so were not included in our study. It is not known how inclusion of these children would affect our results.

Second, the antibiotic information used in this study was limited to empiric antibiotic therapy. It is possible that some patients received macrolide therapy before admission. It is also likely that identification of M. pneumoniae during the hospitalization prompted the addition or substitution of macrolide therapy for some patients. If this therapy was initiated beyond the first day of hospitalization, these children would be classified as macrolide non‐recipients. Since macrolide administration was associated with a shorter hospital LOS, such misclassification would bias our results towards finding no difference in LOS between macrolide recipients and non‐recipients. It is therefore possible that the benefit of macrolide therapy is even greater than found in our study.

Third, there may be unmeasured confounding or residual confounding by indication for adjunct corticosteroid therapy related to clinical presentation. We expect that corticosteroid recipients would be sicker than non‐recipients. We included variables associated with a greater severity of illness (such as intensive care unit admission) in the multivariable analysis. Additionally, the shorter LOS among macrolide recipients remained when the analysis was stratified by receipt or non‐receipt of systemic corticosteroid therapy.

Fourth, we were only able to record readmissions occurring at the same hospital as the index admission; any readmission presenting to a different hospital following their index admission did not appear in our records, and was therefore not counted. It is thus possible that the true number of readmissions is higher than that represented here. Finally, despite the large number of patients included in this study, the number of short‐term readmissions was relatively small. Thus, we may have been underpowered to detect small but significant differences in short‐term readmission rates.

In conclusion, macrolide therapy was associated with shorter hospital LOS, but not with short‐term or longer‐term readmission in children presenting with M. pneumoniae pneumonia.

Appendix

0, 0, 0, 0

UNIVARIATE ANALYSIS OF LENGTH OF STAY
VariableBeta CoefficientConfidence IntervalP Value
Demographics   
Sex0.12(0.22, 0.02)0.022
Race   
Blackreference category   
White0.01(0.21, 0.23)0.933
Other0.13(0.39, 0.13)0.323
Missing0.46(0.81, 0.11)0.012
Presentation during viral respiratory season0.05(0.19, 0.09)0.462
Prior asthma hospitalization0.36(0.64, 0.08)0.015
Intensive care unit admission1.05(0.87, 1.23)<0.001
Labs and procedures performed   
Additional radiologic imaging0.23(0.20, 0.67)0.287
Arterial blood gas0.69(0.50, 0.87)<0.001
Complete blood count0.34(0.24, 0.45)<0.001
Blood culture0.17(0.98, 0.44)0.204
Mechanical ventilation1.15(0.68, 1.63)<0.001
Therapies received   
Empiric macrolide therapy0.49(0.72, 0.25)<0.001
Systemic steroids0.26(0.38, 0.14)<0.001
Chronic asthma medications0.20(0.38, 0.013)0.037
Beta‐agonist therapy0.07(0.21, 0.08)0.357
Vasoactive infusion1.08(0.727, 1.45)<0.001
Clindamycin or vancomycin0.55(0.34, 0.75)<0.001
UNIVARIATE ANALYSIS OF 28‐DAY READMISSION
VariableOdds Ratio*Confidence IntervalP Value
  • Ellipses indicate that variables correlated perfectly with the outcome in univariate analysis.

Demographics   
Sex0.56(0.23, 1.33)0.190
Race   
Blackreference category   
White0.46(0.19, 1.14)0.093
Other   
Missing   
Presentation during viral respiratory season0.64(0.09, 4.75)0.662
Prior asthma hospitalization   
Intensive care unit admission4.54(1.21, 17.03)0.025
Laboratory tests and procedures   
Additional radiologic imaging10.00(2.25, 44.47)0.002
Arterial blood gas   
Complete blood count0.92(0.24, 3.48)0.901
Blood culture0.85(0.30, 2.36)0.738
Mechanical ventilation   
Medications   
Macrolide therapy1.18(0.25, 5.45)0.837
Systemic corticosteroids1.04(0.276, 4.09)0.951
Chronic asthma medication1.66(0.71, 3.88)0.242
Beta‐agonist therapy0.66(0.16, 2.65)0.557
Vasoactive infusions   
Clindamycin or vancomycin1.00(0.10, 9.90)0.998
MULTIVARIATE ANALYSIS OF LENGTH OF STAY
VariableCoefficientConfidence IntervalP Value% ChangeConfidence Interval for % Change
Demographics     
Age0.287(0.012, 0.045)0.0012.9(1.2, 4.6)
Prior asthma hospitalization0.272(0.094, 0.45)0.00431.3(9.9, 56.8)
Intensive care unit admission1.015(0.802, 1.23)<0.001175.9(123.0, 241.3)
Therapies received     
Macrolide therapy0.379(0.59, 0.166)0.00131.6(44.6, 15.3)
Systemic corticosteroids0.264(0.391, 0.138)<0.00123.2(32.3, 12.9)
Chronic asthma medications0.056(0.255, 0.142)0.5685.5(22.5, 15.2)
Albuterol0.07(0.059, 0.199)0.2817.2(5.8, 22.0)
Clindamycin or vancomycin0.311(0.063, 0.559)0.01536.5(6.5, 74.9)
MULTIVARIATE ANALYSIS OF 28‐DAY READMISSION
VariableAdjusted Odds RatioConfidence IntervalP Value
Demographics   
Age0.910.72, 1.150.423
Prior asthma hospitalization1.940.42, 8.900.394
Intensive care unit admission5.732.03, 16.200.001
Therapies received   
Macrolide therapy1.120.22, 5.780.890
Systemic corticosteroids0.6960.10, 4.700.710
Chronic asthma medications1.980.32, 12.200.460
Albuterol0.5190.081, 3.310.488
Clindamycin or vancomycin0.9040.07, 11.130.937
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Journal of Hospital Medicine - 7(4)
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Mycoplasma pneumoniae is a common cause of community‐acquired pneumonia (CAP), among school‐age children and adolescents.14 Though pneumonia caused by M. pneumoniae is typically self‐limited, severe illness may occur.5 M. pneumoniae has also been implicated in airway inflammation, which may lead to the onset and development of chronic pulmonary disease.610 Few studies have directly addressed appropriate treatment strategies for M. pneumoniae pneumonia,11 and, despite its high prevalence and potential for causing severe complications, treatment recommendations remain inconsistent.

The efficacy of macrolide therapy in particular for M. pneumoniae remains unclear. In vitro susceptibility studies have shown bacteriostatic activity of erythromycin, clarithromycin, and azithromycin against M. pneumoniae.1218 Additionally, several small retrospective studies have shown that among children with atypical CAP (including M. pneumoniae pneumonia), those treated with macrolides were less likely to have persistence or progression of signs and symptoms after 3 days of therapy.19, 20 Lu et al21 found a shorter duration of fever among macrolide recipients compared with non‐recipients. In adults, Shames et al22 found a shorter duration of fever and hospitalization among erythromycin recipients compared with controls. Other randomized controlled trials have also addressed the use of macrolides in treatment of M. pneumoniae, but the ability to draw meaningful conclusions is limited by small samples sizes and by lack of details about the number of patients with M. pneumoniae.11

In addition to their antimicrobial effect, macrolides also have anti‐inflammatory properties.2327 The importance of these anti‐inflammatory properties is supported by studies showing clinical cure in patients treated with macrolides despite persistence of M. pneumoniae organisms,2831 clinical improvement despite the administration of doses that provide tissue levels below the minimum inhibitory concentration of the organism,3234 and clinical cure in patients with macrolide‐resistant M. pneumoniae.18, 35

The objectives of the current study were to examine the impact of macrolide therapy on the length of stay (LOS) and short‐ and longer‐term readmissions, including longer‐term asthma‐related readmissions, in children hospitalized with M. pneumoniae pneumonia.

METHODS

Data Source

Data for this retrospective cohort study were obtained from the Pediatric Health Information System (PHIS), which contains administrative data from 38 freestanding children's hospitals. Data quality and reliability are assured through a joint effort by the Child Health Corporation of America (Shawnee Mission, KS) and PHIS‐participating hospitals as described previously.36, 37 Encrypted medical record numbers allow for tracking of individual patients across hospitalizations. This study was reviewed and approved by the Committees for the Protection of Human Subjects at The Children's Hospital of Philadelphia (Philadelphia, PA).

Patients

Children 6‐18 years of age with CAP were eligible if they were discharged from a participating hospital between January 1, 2006 and December 31, 2008. Subjects were included if they received antibiotic therapy on the first day of hospitalization and if they satisfied one of the following International Classification of Diseases, 9th revision (ICD‐9) discharge diagnosis code criteria: 1) Principal diagnosis of M. pneumoniae pneumonia (483.0); 2) Principal diagnosis of a pneumonia‐related symptom (eg, fever, cough) (780.6 or 786.00‐786.52 [except 786.1]) and a secondary diagnosis of M. pneumoniae pneumonia; or 3) Principal diagnosis of pneumonia (481‐483.8 [except 483.0], 485‐486) and a secondary diagnosis of Mycoplasma (041.81).

Children younger than 6 years of age were excluded due to the low prevalence of M. pneumoniae infection.2, 38 Patients with comorbid conditions predisposing to severe or recurrent pneumonia (eg, cystic fibrosis, malignancy) were excluded using a previously reported classification scheme.39 In addition, we excluded patient data from 2 hospitals due to incomplete reporting of discharge information; thus data from 36 hospitals were included in this study.

Validation of Discharge Diagnosis Codes for Mycoplasma pneumoniae

To assess for misclassification of the diagnosis of M. pneumoniae, we reviewed records of a randomly selected subset of subjects from The Children's Hospital of Philadelphia; 14 of 15 patients had signs of lower respiratory tract infection in conjunction with a positive M. pneumoniae polymerase chain reaction test from nasopharyngeal washings to confirm the diagnosis of M. pneumoniae pneumonia. Hence, the positive predictive value of our algorithm for diagnosing M. pneumoniae pneumonia was 93.3%.

Study Definitions

We identified children with asthma in 2 ways. Asthma‐related hospitalizations were identified by an ICD‐9 code for asthma (493.0‐493.92) in any discharge diagnosis field during any hospitalization in the 24 months prior to the current hospitalization. Baseline controller medications were identified by receipt of inhaled corticosteroids (eg, fluticasone) or leukotriene receptor antagonists on the first day of hospitalization.

Systemic corticosteroids (either oral or intravenous) included dexamethasone, hydrocortisone, methylprednisolone, prednisolone, and prednisone. Measures of disease severity included admission to the intensive care unit within 48 hours of hospitalization, and administration of vancomycin or clindamycin, vasoactive infusions (epinephrine, norepinephrine, dopamine, and dobutamine), and invasive (endotracheal intubation) and noninvasive (continuous positive airway pressure) mechanical ventilation within 24 hours of hospitalization, as previously described.40, 41 Viral respiratory season was defined as October through March.

Measured Outcomes

The primary outcomes of interest were hospital LOS and all‐cause readmission within 28 days and 15 months after index discharge. We examined readmissions for asthma 15 months after index discharge as a secondary outcome measure because of the potential role for M. pneumoniae infection in long‐term lung dysfunction, including asthma.42 The 15‐month time frame was selected based on longitudinal data available in PHIS for the entire study cohort.

Measured Exposures

The main exposure was early initiation of macrolide therapy, defined as receipt of erythromycin, clarithromycin, or azithromycin on the first day of hospitalization.

Data Analysis

Continuous variables were described using median and interquartile range (IQR) or range values, and compared using the Wilcoxon rank‐sum test. Categorical variables were described using counts and frequencies, and compared using the chi‐square test. Multivariable linear (for LOS) and logistic (for readmission) regression analyses were performed to assess the independent association of macrolide therapy with the primary outcomes. Because the LOS data had a skewed distribution, our analyses were performed using logarithmically transformed LOS values as the dependent variable. The resulting beta‐coefficients were transformed to reflect the percent difference in LOS between subjects receiving and not receiving macrolide therapy.

Building of the multivariable models began with the inclusion of macrolide therapy. Variables associated with primary outcomes on univariate analysis (P < 0.20) were also considered for inclusion as potential confounders.43 These variables were included in the final multivariable model if they remained significant after adjusting for other factors, or if their inclusion in the model resulted in a 15% or greater change in the effect size of the primary association of interest (ie, macrolide therapy).44 Because corticosteroids also have anti‐inflammatory properties, we assessed for interactions with macrolide therapy. There was no interaction between macrolide and systemic corticosteroid therapy (P = 0.26, Likelihood ratio test), therefore our primary model adjusted for systemic corticosteroids.

Despite adjusting for systemic corticosteroid therapy in our primary analysis, residual confounding by indication for corticosteroid therapy might exist. We therefore repeated the analysis after stratifying by receipt or non‐receipt of systemic corticosteroid therapy. Because the benefit of macrolides in preventing long‐term dysfunction may be limited to those without a prior diagnosis of asthma, we repeated the analysis of readmissions within 15 months of index discharge (any readmission and asthma‐related readmissions) while limiting the cohort to those without evidence of asthma (ie, no prior asthma‐related hospitalizations and no chronic asthma medications). Because children with underlying conditions or circumstances that would predispose to prolonged hospitalizations may have been included, despite our restriction of the cohort to those without an identified chronic complex condition, we also repeated the analysis while limiting the cohort to those with a LOS 7 days. Finally, all analyses were clustered on hospital using the robust standard errors of Huber and White to account for the correlation of exposures and outcomes among children within centers.

Data were analyzed using Stata version 11 (Stata Corporation, College Station, TX). Statistical significance was determined a priori as a two‐tailed P value <0.05.

RESULTS

Patient Characteristics

During the study, 690 children ages 6 to 18 years met inclusion criteria. Characteristics of these patients are shown in Table 1. The median age was 10 years (IQR, 7‐13 years). Ten patients (1.4%) also had a concomitant discharge diagnosis of pneumococcal pneumonia, while 19 patients (2.7%) had a concomitant discharge diagnosis of viral pneumonia; 1 of these patients had discharge diagnoses of both viral and pneumococcal pneumonia.

Demographic Information and Processes of Care for Children With a Discharge Diagnosis of Mycoplasma pneumoniae Pneumonia
  Empiric Macrolide Therapy 
VariableAll SubjectsYesNoP
  • NOTE: Values listed as number (percent).

  • Includes chest computed tomography or ultrasound.

Demographics    
Male sex356 (51.6)200 (49.4)156 (54.7)0.166
Race    
Black135 (19.6)81 (20.0)54 (19.0)0.506
White484 (70.1)287 (70.9)197 (69.1) 
Other62 (9.0)31 (7.7)31 (10.9) 
Missing9 (1.3)6 (1.5)3 (1.1) 
Presentation during viral respiratory season420 (60.9)242 (59.8)178 (62.5) 
Prior asthma hospitalization41 (5.9)31 (7.7)10 (3.5)0.023
Intensive care unit admission127 (18.4)74 (18.3)53 (18.6)0.914
Laboratory tests and procedures    
Additional radiologic imaging*24 (3.5)13 (3.2)11 (3.9)0.646
Arterial blood gas116 (17.3)72 (18.5)44 (15.6)0.316
Complete blood count433 (64.4)249 (64.0)184 (65.0)0.788
Blood culture280 (41.7)167 (42.9)113 (39.9)0.436
Mechanical ventilation16 (2.3)5 (1.2)11 (3.86)0.024
Medications    
Chronic asthma medication116 (16.8)72 (17.8)44 (15.4)0.419
Beta‐agonist therapy328 (47.5)215 (53.1)113 (39.7)0.001
Vasoactive infusions22 (3.2)13 (3.2)9 (3.2)0.969
Systemic corticosteroids252 (36.5)191 (47.2)61 (21.4)<0.001
Clindamycin or vancomycin86 (12.5)24 (5.9)62 (21.8)<0.001

Macrolide therapy was administered to 405 (58.7%) patients. Systemic corticosteroid therapy was administered to 252 (36.5%) patients. Overall, 191 (27.7%) of the 690 patients received both macrolides and systemic corticosteroids empirically, while 224 (32.5%) received neither; 61 (8.8%) received corticosteroids but not macrolides, while 214 (31.0%) received macrolides but not corticosteroids. Asthma hospitalization within the 24 months prior to admission was more common among those receiving macrolides (N = 60/405, 14.8%) than among those not receiving macrolides (N = 30/285, 10.5%) (P = 0.023). Macrolide recipients also more commonly received concomitant systemic corticosteroids (N = 191/405, 47.2%) than macrolide non‐recipients (N = 61/285, 21.4%) (P < 0.001) and more commonly received beta‐agonist therapy (N = 215/405, 53.1%) than macrolide non‐recipients (N = 113/285, 39.7%) (P = 0.001).

Length of Stay

The overall median LOS was 3 days (IQR, 2‐6 days); the median LOS was 3 days (IQR, 2‐5 days) for empiric macrolide recipients and 4 days (IQR, 2‐9 days) for non‐recipients (P < 0.001). Overall, 22.9% (N = 158) of children had an LOS 7 days and 8.8% (N = 61) of children had an LOS 14 days. The LOS was 7 days for 15.3% (N = 62) of macrolide recipients and 33.7% (N = 96) of non‐recipients. LOS was 7 days for 17.5% (N = 44) of systemic steroid recipients and 26% (N = 114) of non‐recipients. In unadjusted analysis, macrolide therapy (beta‐coefficient, 0.49; 95% confidence interval [CI]: 0.72 to 0.25; P < 0.001) and systemic corticosteroid administration (beta‐coefficient, 0.26; CI: 0.37 to 0.14; P < 0.001) were associated with shorter hospital LOS (Appendix 1).

In multivariable analysis, macrolide therapy remained associated with a shorter LOS (Table 2; Appendix 2). Systemic corticosteroid administration was associated with a 23% shorter LOS (adjusted beta‐coefficient, 0.26; 95% CI: 0.39 to 0.14; P < 0.001). In contrast, previous hospitalization for asthma was associated with a 31% longer LOS (adjusted beta‐coefficient, 0.27; 95% CI: 0.09‐0.045; P = 0.004). Receipt of beta‐agonist therapy or chronic asthma medications were not associated with significant differences in LOS. In analysis stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy, empiric macrolide therapy remained associated with a significantly shorter LOS in both systemic corticosteroid recipients and non‐recipient (Table 4). When the cohort was restricted to subjects with a LOS 7 days, macrolide therapy remained significantly associated with a shorter LOS (adjusted percent change, 20%; 95% CI: 32% to 5%; P = 0.015).

Adjusted Association of Empiric Macrolide Therapy With Outcomes
 Association of Empiric Macrolide Therapy With Outcomes*
  • All models adjusted for age, prior asthma hospitalization, intensive care unit admission, chronic asthma medications, albuterol, systemic corticosteroid therapy, and vancomcyin or clindamycin.

  • Abbreviation: CI, confidence interval.

Length of stay (days) 
Adjusted beta‐coefficient (95 % CI)0.38 (0.59 to 0.17)
Adjusted percent change (95% CI)32% (45% to 15%)
P value0.001
Any readmission within 28 days 
Adjusted odds ratio (95% CI)1.12 (0.22 to 5.78)
P value0.890
Any readmission within 15 mo 
Adjusted odds ratio (95% CI)1.00 (0.59 to 1.70)
P value0.991
Asthma hospitalization within 15 mo 
Adjusted odds ratio (95% CI)1.09 (0.54 to 2.17)
P value0.820

Readmission

Overall, 8 children (1.2%) were readmitted for pneumonia‐associated conditions within 28 days of index discharge. Readmission occurred in 1.2% of macrolide recipients and 1.1% of non‐recipients (P = 0.83) (Table 4). In unadjusted analysis, neither macrolide therapy (odds ratio [OR], 1.18; 95% CI: 0.25‐5.45; P = 0.84) nor systemic corticosteroid administration (OR, 1.04; 95% CI: 0.27‐4.10; P = 0.95) was associated with 28‐day readmission (Appendix 3). In multivariable analysis, empiric macrolide therapy was not associated with 28‐day readmission in the overall cohort (Table 2; Appendix 4)), or when the analysis was stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy (Table 3).

Multivariable Analysis of the Association Between Empiric Macrolide Therapy and Outcomes, Stratified by Receipt or Non‐Receipt of Systemic Corticosteroid Therapy
 Concomitant Systemic Corticosteroid Therapy*
 YesNo
  • All models adjusted for age, prior asthma hospitalization, intensive care unit admission, chronic asthma medications, albuterol, and vancomcyin or clindamycin.

  • Abbreviation: CI, confidence interval.

Length of stay  
Adjusted beta‐coefficient (95% CI)0.40 (0.74 to 0.07)0.37 (0.58 to 0.16)
Adjusted percent change (95% CI)33% (52% to 7%)31% (44% to 15%)
P value0.0200.001
Readmission within 28 days  
Adjusted odds ratio (95% CI)1.09 (0.05 to 26.7)1.50 (0.21 to 10.8)
P value0.9600.687
Readmission within 15 mo  
Adjusted odds ratio (95% CI)1.57 (0.65 to 3.82)0.81 (0.45 to 1.46)
P value0.320.49
Asthma hospitalization within 15 mo  
Adjusted odds ratio (95% CI)1.51 (0.58 to 3.93)0.85 (0.36 to 1.97)
P value0.3950.700
Readmissions Following Index Hospital Discharge Stratified by Receipt of Empiric Macrolide Therapy
 Empiric Macrolide Therapy
 N/Total (%)
ReadmissionYesNo
Any readmission within 28 days  
Overall5/405 (1.2)3/285 (1.1)
Systemic corticosteroid therapy2/186 (1.1)1/66 (1.5)
No systemic corticosteroid therapy3/177 (1.7)2/261 (0.8)
Any readmission within 15 mo  
Overall96/405 (23.7)64/285 (22.5)
Systemic corticosteroid therapy52/186 (28.0)17/66 (25.8)
No systemic corticosteroid therapy32/177 (18.1)59/261 (22.6)
Asthma hospitalization within 15 mo  
Overall61/405 (15.1)34/285 (11.9)
Systemic corticosteroid therapy39/186 (21.0)13/66 (19.7)
No systemic corticosteroid therapy14/177 (7.9)29/261 (11.1)

Overall, 160 children (23.2%) were readmitted within 15 months of index discharge; 95 were readmitted for asthma during this time (Table 3). Overall readmission occurred in 23.7% of macrolide recipients and 22.5% of macrolide non‐recipients (P = 0.702). Asthma readmission occurred in 15.1% of macrolide recipients and 11.9% of macrolide non‐recipients (P = 0.240). In unadjusted analysis, empiric macrolide therapy was not significantly associated with any readmission within 15 months (OR, 1.07; 95% CI: 0.69‐1.68; P = 0.759) or with asthma‐related readmission within 15 months (OR, 1.31; 95% CI: 0.73‐ 2.36; P = 0.369). In multivariable analysis, neither any readmission nor asthma readmission within 15 months was associated with empiric macrolide therapy overall (Table 2) or when stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy (Table 3).

The analyses for readmissions within 15 months of index discharge were repeated while limiting the cohort to those without prior asthma hospitalizations or chronic asthma medications. In this subset of patients, readmissions for any reason occurred in 55 (18.6%) of 295 macrolide recipients and 50 (22.0%) of 227 non‐recipients. The difference was not statistically significant in multivariable analysis (adjusted odds ratio, 0.79; 95% CI: 0.41‐1.51; P = 0.47). Readmissions for asthma occurred in 30 (10.2%) of 295 macrolide recipients and 26 (11.5%) of 227 non‐recipients; this difference was also not significant in multivariable analysis (adjusted odds ratio, 0.83; 95% CI: 0.36‐1.93; P = 0.83). The magnitude of the estimate of effect for 28‐day and 15‐month readmissions, and 15‐month asthma hospitalizations, was similar to the primary analysis when the cohort was restricted to subjects with a LOS 7 days.

DISCUSSION

This multicenter study examined the role of macrolide therapy in children hospitalized with M. pneumoniae pneumonia. Empiric macrolide therapy was associated with an approximately 30% shorter hospital LOS and, in stratified analysis, remained associated with a significantly shorter hospital LOS in both systemic corticosteroid recipients and non‐recipients. Empiric macrolide therapy was not associated with short‐ or longer‐term hospital readmission.

Previous small randomized trials have been inconclusive regarding the potential benefit of macrolide therapy in M. pneumoniae pneumonia.11 Our study, which demonstrated a shorter LOS among macrolides recipients compared with non‐recipients, has several advantages over prior studies including a substantively larger sample size and multicenter design. Animal models support our observations regarding the potential beneficial antimicrobial role of macrolides. M. pneumoniae concentrations in bronchoalveolar lavage specimens were significantly lower among experimentally infected mice treated with clarithromycin, a macolide‐class antibiotic, compared with either placebo or dexamethasone.45 Combination therapy with clarithromycin and dexamethasone reduced histopathologic inflammation to a greater degree than dexamethasone alone.45

While the relative importance of the antimicrobial and anti‐inflammatory properties of macrolides is not known, observational studies of children infected with macrolide‐resistant M. pneumoniae suggest that the antimicrobial properties of macrolides may provide disproportionate clinical benefit. The duration of fever in macrolide recipients with macrolide‐resistant M. pneumoniae (median duration, 9 days) reported by Suzuki et al46 was significantly longer than those with macrolide‐susceptible infections (median duration, 5 days), and similar to the duration of fever in patients with M. pneumoniae infection treated with placebo (median duration, 8 days) reported by Kingston et al.47 Additionally, macrolide therapy was associated with significant improvements in lung function in patients with asthma and concomitant M. pneumoniae infection, but not in patients with asthma without documented M. pneumoniae infection.9 As corticosteroids also have anti‐inflammatory properties, we expect that any anti‐inflammatory benefit of macrolide therapy would be mitigated by the concomitant administration of corticosteroids. The shorter LOS associated with empiric macrolide therapy in our study was comparable among corticosteroid recipients and non‐recipients.

Atypical bacterial pathogens, including M. pneumoniae, are associated with diffuse lower airway inflammation6, 48 and airway hyperresponsiveness,6 and have been implicated as a cause of acute asthma exacerbations.7, 4954 Among patients with previously diagnosed asthma, acute M. pneumoniae infection was identified in up to 20% of those having acute exacerbations.7, 54 Macrolide therapy has a beneficial effect on lung function and airway hyperresponsiveness in adults with asthma.9, 55 Among mice infected with M. pneumoniae, 3 days of macrolide therapy resulted in a significant reduction in airway hyperresponsiveness compared with placebo or dexamethasone; however, after 6 days of therapy, there was no significant difference in airway hyperresponsiveness between those receiving macrolides, dexamethasone, or placebo, suggesting that the benefit of macrolides on airway hyperresponsiveness may be brief. Our findings of a shorter LOS but no difference in readmissions at 28 days or longer, for macrolide recipients compared with non‐recipients, support the limited benefit of macrolide therapy beyond the initial reduction in bacterial load seen in the first few days of therapy.

M. pneumoniae infection has also been implicated as a cause of chronic pulmonary disease, including asthma.610 In the mouse model, peribronchial and perivascular mononuclear infiltrates, increased airway methacholine reactivity, and increased airway obstruction were observed 530 days after M. pneumoniae inoculation.6 M. pneumoniae has been identified in 26 (50%) of 51 children experiencing their first asthma attack,7 and 23 (42%) of 55 adults with chronic, stable asthma.9 Nevertheless, results of other studies addressing the issue are inconsistent, and the role of M. pneumoniae in the development of asthma remains unclear.56 In order to investigate the impact of macrolide therapy on the development of chronic pulmonary disease requiring hospitalization, we examined the readmission rates in the 15 months following index discharge. The proportion of children hospitalized with asthma following the hospitalization for M. pneumoniae pneumonia was higher for both macrolide recipients and non‐recipients compared with the 24‐months prior to infection. These results support a possible role for M. pneumoniae in chronic pulmonary disease. However, macrolide therapy was not associated with long‐term overall hospital readmission or long‐term asthma readmission, either in the entire cohort or in the subset of patients without prior asthma hospitalizations or medications.

This study had several limitations. First, because the identification of children with M. pneumoniae pneumonia relied on ICD‐9 discharge diagnosis codes, it is possible that there was misclassification of disease. We minimized the inclusion of children without M. pneumoniae by including only children who received antibiotic therapy on the first day of hospitalization and by excluding patients younger than 6 years of age, a group at relatively low‐risk for M. pneumoniae infection. Further, our algorithm for identification of M. pneumoniae pneumonia was validated through review of the medical records at 1 institution and was found to have a high positive predictive value. However, the positive predictive value of these ICD‐9 codes may vary across institutions. Additionally, the sensitivity of ICD‐9 codes for identifying children with M. pneumoniae pneumonia is not known. Also, not all children with pneumonia undergo testing for M. pneumoniae, and different tests have varying sensitivity and specificity.57, 58 Thus, some children with M. pneumoniae pneumonia were not diagnosed and so were not included in our study. It is not known how inclusion of these children would affect our results.

Second, the antibiotic information used in this study was limited to empiric antibiotic therapy. It is possible that some patients received macrolide therapy before admission. It is also likely that identification of M. pneumoniae during the hospitalization prompted the addition or substitution of macrolide therapy for some patients. If this therapy was initiated beyond the first day of hospitalization, these children would be classified as macrolide non‐recipients. Since macrolide administration was associated with a shorter hospital LOS, such misclassification would bias our results towards finding no difference in LOS between macrolide recipients and non‐recipients. It is therefore possible that the benefit of macrolide therapy is even greater than found in our study.

Third, there may be unmeasured confounding or residual confounding by indication for adjunct corticosteroid therapy related to clinical presentation. We expect that corticosteroid recipients would be sicker than non‐recipients. We included variables associated with a greater severity of illness (such as intensive care unit admission) in the multivariable analysis. Additionally, the shorter LOS among macrolide recipients remained when the analysis was stratified by receipt or non‐receipt of systemic corticosteroid therapy.

Fourth, we were only able to record readmissions occurring at the same hospital as the index admission; any readmission presenting to a different hospital following their index admission did not appear in our records, and was therefore not counted. It is thus possible that the true number of readmissions is higher than that represented here. Finally, despite the large number of patients included in this study, the number of short‐term readmissions was relatively small. Thus, we may have been underpowered to detect small but significant differences in short‐term readmission rates.

In conclusion, macrolide therapy was associated with shorter hospital LOS, but not with short‐term or longer‐term readmission in children presenting with M. pneumoniae pneumonia.

Appendix

0, 0, 0, 0

UNIVARIATE ANALYSIS OF LENGTH OF STAY
VariableBeta CoefficientConfidence IntervalP Value
Demographics   
Sex0.12(0.22, 0.02)0.022
Race   
Blackreference category   
White0.01(0.21, 0.23)0.933
Other0.13(0.39, 0.13)0.323
Missing0.46(0.81, 0.11)0.012
Presentation during viral respiratory season0.05(0.19, 0.09)0.462
Prior asthma hospitalization0.36(0.64, 0.08)0.015
Intensive care unit admission1.05(0.87, 1.23)<0.001
Labs and procedures performed   
Additional radiologic imaging0.23(0.20, 0.67)0.287
Arterial blood gas0.69(0.50, 0.87)<0.001
Complete blood count0.34(0.24, 0.45)<0.001
Blood culture0.17(0.98, 0.44)0.204
Mechanical ventilation1.15(0.68, 1.63)<0.001
Therapies received   
Empiric macrolide therapy0.49(0.72, 0.25)<0.001
Systemic steroids0.26(0.38, 0.14)<0.001
Chronic asthma medications0.20(0.38, 0.013)0.037
Beta‐agonist therapy0.07(0.21, 0.08)0.357
Vasoactive infusion1.08(0.727, 1.45)<0.001
Clindamycin or vancomycin0.55(0.34, 0.75)<0.001
UNIVARIATE ANALYSIS OF 28‐DAY READMISSION
VariableOdds Ratio*Confidence IntervalP Value
  • Ellipses indicate that variables correlated perfectly with the outcome in univariate analysis.

Demographics   
Sex0.56(0.23, 1.33)0.190
Race   
Blackreference category   
White0.46(0.19, 1.14)0.093
Other   
Missing   
Presentation during viral respiratory season0.64(0.09, 4.75)0.662
Prior asthma hospitalization   
Intensive care unit admission4.54(1.21, 17.03)0.025
Laboratory tests and procedures   
Additional radiologic imaging10.00(2.25, 44.47)0.002
Arterial blood gas   
Complete blood count0.92(0.24, 3.48)0.901
Blood culture0.85(0.30, 2.36)0.738
Mechanical ventilation   
Medications   
Macrolide therapy1.18(0.25, 5.45)0.837
Systemic corticosteroids1.04(0.276, 4.09)0.951
Chronic asthma medication1.66(0.71, 3.88)0.242
Beta‐agonist therapy0.66(0.16, 2.65)0.557
Vasoactive infusions   
Clindamycin or vancomycin1.00(0.10, 9.90)0.998
MULTIVARIATE ANALYSIS OF LENGTH OF STAY
VariableCoefficientConfidence IntervalP Value% ChangeConfidence Interval for % Change
Demographics     
Age0.287(0.012, 0.045)0.0012.9(1.2, 4.6)
Prior asthma hospitalization0.272(0.094, 0.45)0.00431.3(9.9, 56.8)
Intensive care unit admission1.015(0.802, 1.23)<0.001175.9(123.0, 241.3)
Therapies received     
Macrolide therapy0.379(0.59, 0.166)0.00131.6(44.6, 15.3)
Systemic corticosteroids0.264(0.391, 0.138)<0.00123.2(32.3, 12.9)
Chronic asthma medications0.056(0.255, 0.142)0.5685.5(22.5, 15.2)
Albuterol0.07(0.059, 0.199)0.2817.2(5.8, 22.0)
Clindamycin or vancomycin0.311(0.063, 0.559)0.01536.5(6.5, 74.9)
MULTIVARIATE ANALYSIS OF 28‐DAY READMISSION
VariableAdjusted Odds RatioConfidence IntervalP Value
Demographics   
Age0.910.72, 1.150.423
Prior asthma hospitalization1.940.42, 8.900.394
Intensive care unit admission5.732.03, 16.200.001
Therapies received   
Macrolide therapy1.120.22, 5.780.890
Systemic corticosteroids0.6960.10, 4.700.710
Chronic asthma medications1.980.32, 12.200.460
Albuterol0.5190.081, 3.310.488
Clindamycin or vancomycin0.9040.07, 11.130.937

Mycoplasma pneumoniae is a common cause of community‐acquired pneumonia (CAP), among school‐age children and adolescents.14 Though pneumonia caused by M. pneumoniae is typically self‐limited, severe illness may occur.5 M. pneumoniae has also been implicated in airway inflammation, which may lead to the onset and development of chronic pulmonary disease.610 Few studies have directly addressed appropriate treatment strategies for M. pneumoniae pneumonia,11 and, despite its high prevalence and potential for causing severe complications, treatment recommendations remain inconsistent.

The efficacy of macrolide therapy in particular for M. pneumoniae remains unclear. In vitro susceptibility studies have shown bacteriostatic activity of erythromycin, clarithromycin, and azithromycin against M. pneumoniae.1218 Additionally, several small retrospective studies have shown that among children with atypical CAP (including M. pneumoniae pneumonia), those treated with macrolides were less likely to have persistence or progression of signs and symptoms after 3 days of therapy.19, 20 Lu et al21 found a shorter duration of fever among macrolide recipients compared with non‐recipients. In adults, Shames et al22 found a shorter duration of fever and hospitalization among erythromycin recipients compared with controls. Other randomized controlled trials have also addressed the use of macrolides in treatment of M. pneumoniae, but the ability to draw meaningful conclusions is limited by small samples sizes and by lack of details about the number of patients with M. pneumoniae.11

In addition to their antimicrobial effect, macrolides also have anti‐inflammatory properties.2327 The importance of these anti‐inflammatory properties is supported by studies showing clinical cure in patients treated with macrolides despite persistence of M. pneumoniae organisms,2831 clinical improvement despite the administration of doses that provide tissue levels below the minimum inhibitory concentration of the organism,3234 and clinical cure in patients with macrolide‐resistant M. pneumoniae.18, 35

The objectives of the current study were to examine the impact of macrolide therapy on the length of stay (LOS) and short‐ and longer‐term readmissions, including longer‐term asthma‐related readmissions, in children hospitalized with M. pneumoniae pneumonia.

METHODS

Data Source

Data for this retrospective cohort study were obtained from the Pediatric Health Information System (PHIS), which contains administrative data from 38 freestanding children's hospitals. Data quality and reliability are assured through a joint effort by the Child Health Corporation of America (Shawnee Mission, KS) and PHIS‐participating hospitals as described previously.36, 37 Encrypted medical record numbers allow for tracking of individual patients across hospitalizations. This study was reviewed and approved by the Committees for the Protection of Human Subjects at The Children's Hospital of Philadelphia (Philadelphia, PA).

Patients

Children 6‐18 years of age with CAP were eligible if they were discharged from a participating hospital between January 1, 2006 and December 31, 2008. Subjects were included if they received antibiotic therapy on the first day of hospitalization and if they satisfied one of the following International Classification of Diseases, 9th revision (ICD‐9) discharge diagnosis code criteria: 1) Principal diagnosis of M. pneumoniae pneumonia (483.0); 2) Principal diagnosis of a pneumonia‐related symptom (eg, fever, cough) (780.6 or 786.00‐786.52 [except 786.1]) and a secondary diagnosis of M. pneumoniae pneumonia; or 3) Principal diagnosis of pneumonia (481‐483.8 [except 483.0], 485‐486) and a secondary diagnosis of Mycoplasma (041.81).

Children younger than 6 years of age were excluded due to the low prevalence of M. pneumoniae infection.2, 38 Patients with comorbid conditions predisposing to severe or recurrent pneumonia (eg, cystic fibrosis, malignancy) were excluded using a previously reported classification scheme.39 In addition, we excluded patient data from 2 hospitals due to incomplete reporting of discharge information; thus data from 36 hospitals were included in this study.

Validation of Discharge Diagnosis Codes for Mycoplasma pneumoniae

To assess for misclassification of the diagnosis of M. pneumoniae, we reviewed records of a randomly selected subset of subjects from The Children's Hospital of Philadelphia; 14 of 15 patients had signs of lower respiratory tract infection in conjunction with a positive M. pneumoniae polymerase chain reaction test from nasopharyngeal washings to confirm the diagnosis of M. pneumoniae pneumonia. Hence, the positive predictive value of our algorithm for diagnosing M. pneumoniae pneumonia was 93.3%.

Study Definitions

We identified children with asthma in 2 ways. Asthma‐related hospitalizations were identified by an ICD‐9 code for asthma (493.0‐493.92) in any discharge diagnosis field during any hospitalization in the 24 months prior to the current hospitalization. Baseline controller medications were identified by receipt of inhaled corticosteroids (eg, fluticasone) or leukotriene receptor antagonists on the first day of hospitalization.

Systemic corticosteroids (either oral or intravenous) included dexamethasone, hydrocortisone, methylprednisolone, prednisolone, and prednisone. Measures of disease severity included admission to the intensive care unit within 48 hours of hospitalization, and administration of vancomycin or clindamycin, vasoactive infusions (epinephrine, norepinephrine, dopamine, and dobutamine), and invasive (endotracheal intubation) and noninvasive (continuous positive airway pressure) mechanical ventilation within 24 hours of hospitalization, as previously described.40, 41 Viral respiratory season was defined as October through March.

Measured Outcomes

The primary outcomes of interest were hospital LOS and all‐cause readmission within 28 days and 15 months after index discharge. We examined readmissions for asthma 15 months after index discharge as a secondary outcome measure because of the potential role for M. pneumoniae infection in long‐term lung dysfunction, including asthma.42 The 15‐month time frame was selected based on longitudinal data available in PHIS for the entire study cohort.

Measured Exposures

The main exposure was early initiation of macrolide therapy, defined as receipt of erythromycin, clarithromycin, or azithromycin on the first day of hospitalization.

Data Analysis

Continuous variables were described using median and interquartile range (IQR) or range values, and compared using the Wilcoxon rank‐sum test. Categorical variables were described using counts and frequencies, and compared using the chi‐square test. Multivariable linear (for LOS) and logistic (for readmission) regression analyses were performed to assess the independent association of macrolide therapy with the primary outcomes. Because the LOS data had a skewed distribution, our analyses were performed using logarithmically transformed LOS values as the dependent variable. The resulting beta‐coefficients were transformed to reflect the percent difference in LOS between subjects receiving and not receiving macrolide therapy.

Building of the multivariable models began with the inclusion of macrolide therapy. Variables associated with primary outcomes on univariate analysis (P < 0.20) were also considered for inclusion as potential confounders.43 These variables were included in the final multivariable model if they remained significant after adjusting for other factors, or if their inclusion in the model resulted in a 15% or greater change in the effect size of the primary association of interest (ie, macrolide therapy).44 Because corticosteroids also have anti‐inflammatory properties, we assessed for interactions with macrolide therapy. There was no interaction between macrolide and systemic corticosteroid therapy (P = 0.26, Likelihood ratio test), therefore our primary model adjusted for systemic corticosteroids.

Despite adjusting for systemic corticosteroid therapy in our primary analysis, residual confounding by indication for corticosteroid therapy might exist. We therefore repeated the analysis after stratifying by receipt or non‐receipt of systemic corticosteroid therapy. Because the benefit of macrolides in preventing long‐term dysfunction may be limited to those without a prior diagnosis of asthma, we repeated the analysis of readmissions within 15 months of index discharge (any readmission and asthma‐related readmissions) while limiting the cohort to those without evidence of asthma (ie, no prior asthma‐related hospitalizations and no chronic asthma medications). Because children with underlying conditions or circumstances that would predispose to prolonged hospitalizations may have been included, despite our restriction of the cohort to those without an identified chronic complex condition, we also repeated the analysis while limiting the cohort to those with a LOS 7 days. Finally, all analyses were clustered on hospital using the robust standard errors of Huber and White to account for the correlation of exposures and outcomes among children within centers.

Data were analyzed using Stata version 11 (Stata Corporation, College Station, TX). Statistical significance was determined a priori as a two‐tailed P value <0.05.

RESULTS

Patient Characteristics

During the study, 690 children ages 6 to 18 years met inclusion criteria. Characteristics of these patients are shown in Table 1. The median age was 10 years (IQR, 7‐13 years). Ten patients (1.4%) also had a concomitant discharge diagnosis of pneumococcal pneumonia, while 19 patients (2.7%) had a concomitant discharge diagnosis of viral pneumonia; 1 of these patients had discharge diagnoses of both viral and pneumococcal pneumonia.

Demographic Information and Processes of Care for Children With a Discharge Diagnosis of Mycoplasma pneumoniae Pneumonia
  Empiric Macrolide Therapy 
VariableAll SubjectsYesNoP
  • NOTE: Values listed as number (percent).

  • Includes chest computed tomography or ultrasound.

Demographics    
Male sex356 (51.6)200 (49.4)156 (54.7)0.166
Race    
Black135 (19.6)81 (20.0)54 (19.0)0.506
White484 (70.1)287 (70.9)197 (69.1) 
Other62 (9.0)31 (7.7)31 (10.9) 
Missing9 (1.3)6 (1.5)3 (1.1) 
Presentation during viral respiratory season420 (60.9)242 (59.8)178 (62.5) 
Prior asthma hospitalization41 (5.9)31 (7.7)10 (3.5)0.023
Intensive care unit admission127 (18.4)74 (18.3)53 (18.6)0.914
Laboratory tests and procedures    
Additional radiologic imaging*24 (3.5)13 (3.2)11 (3.9)0.646
Arterial blood gas116 (17.3)72 (18.5)44 (15.6)0.316
Complete blood count433 (64.4)249 (64.0)184 (65.0)0.788
Blood culture280 (41.7)167 (42.9)113 (39.9)0.436
Mechanical ventilation16 (2.3)5 (1.2)11 (3.86)0.024
Medications    
Chronic asthma medication116 (16.8)72 (17.8)44 (15.4)0.419
Beta‐agonist therapy328 (47.5)215 (53.1)113 (39.7)0.001
Vasoactive infusions22 (3.2)13 (3.2)9 (3.2)0.969
Systemic corticosteroids252 (36.5)191 (47.2)61 (21.4)<0.001
Clindamycin or vancomycin86 (12.5)24 (5.9)62 (21.8)<0.001

Macrolide therapy was administered to 405 (58.7%) patients. Systemic corticosteroid therapy was administered to 252 (36.5%) patients. Overall, 191 (27.7%) of the 690 patients received both macrolides and systemic corticosteroids empirically, while 224 (32.5%) received neither; 61 (8.8%) received corticosteroids but not macrolides, while 214 (31.0%) received macrolides but not corticosteroids. Asthma hospitalization within the 24 months prior to admission was more common among those receiving macrolides (N = 60/405, 14.8%) than among those not receiving macrolides (N = 30/285, 10.5%) (P = 0.023). Macrolide recipients also more commonly received concomitant systemic corticosteroids (N = 191/405, 47.2%) than macrolide non‐recipients (N = 61/285, 21.4%) (P < 0.001) and more commonly received beta‐agonist therapy (N = 215/405, 53.1%) than macrolide non‐recipients (N = 113/285, 39.7%) (P = 0.001).

Length of Stay

The overall median LOS was 3 days (IQR, 2‐6 days); the median LOS was 3 days (IQR, 2‐5 days) for empiric macrolide recipients and 4 days (IQR, 2‐9 days) for non‐recipients (P < 0.001). Overall, 22.9% (N = 158) of children had an LOS 7 days and 8.8% (N = 61) of children had an LOS 14 days. The LOS was 7 days for 15.3% (N = 62) of macrolide recipients and 33.7% (N = 96) of non‐recipients. LOS was 7 days for 17.5% (N = 44) of systemic steroid recipients and 26% (N = 114) of non‐recipients. In unadjusted analysis, macrolide therapy (beta‐coefficient, 0.49; 95% confidence interval [CI]: 0.72 to 0.25; P < 0.001) and systemic corticosteroid administration (beta‐coefficient, 0.26; CI: 0.37 to 0.14; P < 0.001) were associated with shorter hospital LOS (Appendix 1).

In multivariable analysis, macrolide therapy remained associated with a shorter LOS (Table 2; Appendix 2). Systemic corticosteroid administration was associated with a 23% shorter LOS (adjusted beta‐coefficient, 0.26; 95% CI: 0.39 to 0.14; P < 0.001). In contrast, previous hospitalization for asthma was associated with a 31% longer LOS (adjusted beta‐coefficient, 0.27; 95% CI: 0.09‐0.045; P = 0.004). Receipt of beta‐agonist therapy or chronic asthma medications were not associated with significant differences in LOS. In analysis stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy, empiric macrolide therapy remained associated with a significantly shorter LOS in both systemic corticosteroid recipients and non‐recipient (Table 4). When the cohort was restricted to subjects with a LOS 7 days, macrolide therapy remained significantly associated with a shorter LOS (adjusted percent change, 20%; 95% CI: 32% to 5%; P = 0.015).

Adjusted Association of Empiric Macrolide Therapy With Outcomes
 Association of Empiric Macrolide Therapy With Outcomes*
  • All models adjusted for age, prior asthma hospitalization, intensive care unit admission, chronic asthma medications, albuterol, systemic corticosteroid therapy, and vancomcyin or clindamycin.

  • Abbreviation: CI, confidence interval.

Length of stay (days) 
Adjusted beta‐coefficient (95 % CI)0.38 (0.59 to 0.17)
Adjusted percent change (95% CI)32% (45% to 15%)
P value0.001
Any readmission within 28 days 
Adjusted odds ratio (95% CI)1.12 (0.22 to 5.78)
P value0.890
Any readmission within 15 mo 
Adjusted odds ratio (95% CI)1.00 (0.59 to 1.70)
P value0.991
Asthma hospitalization within 15 mo 
Adjusted odds ratio (95% CI)1.09 (0.54 to 2.17)
P value0.820

Readmission

Overall, 8 children (1.2%) were readmitted for pneumonia‐associated conditions within 28 days of index discharge. Readmission occurred in 1.2% of macrolide recipients and 1.1% of non‐recipients (P = 0.83) (Table 4). In unadjusted analysis, neither macrolide therapy (odds ratio [OR], 1.18; 95% CI: 0.25‐5.45; P = 0.84) nor systemic corticosteroid administration (OR, 1.04; 95% CI: 0.27‐4.10; P = 0.95) was associated with 28‐day readmission (Appendix 3). In multivariable analysis, empiric macrolide therapy was not associated with 28‐day readmission in the overall cohort (Table 2; Appendix 4)), or when the analysis was stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy (Table 3).

Multivariable Analysis of the Association Between Empiric Macrolide Therapy and Outcomes, Stratified by Receipt or Non‐Receipt of Systemic Corticosteroid Therapy
 Concomitant Systemic Corticosteroid Therapy*
 YesNo
  • All models adjusted for age, prior asthma hospitalization, intensive care unit admission, chronic asthma medications, albuterol, and vancomcyin or clindamycin.

  • Abbreviation: CI, confidence interval.

Length of stay  
Adjusted beta‐coefficient (95% CI)0.40 (0.74 to 0.07)0.37 (0.58 to 0.16)
Adjusted percent change (95% CI)33% (52% to 7%)31% (44% to 15%)
P value0.0200.001
Readmission within 28 days  
Adjusted odds ratio (95% CI)1.09 (0.05 to 26.7)1.50 (0.21 to 10.8)
P value0.9600.687
Readmission within 15 mo  
Adjusted odds ratio (95% CI)1.57 (0.65 to 3.82)0.81 (0.45 to 1.46)
P value0.320.49
Asthma hospitalization within 15 mo  
Adjusted odds ratio (95% CI)1.51 (0.58 to 3.93)0.85 (0.36 to 1.97)
P value0.3950.700
Readmissions Following Index Hospital Discharge Stratified by Receipt of Empiric Macrolide Therapy
 Empiric Macrolide Therapy
 N/Total (%)
ReadmissionYesNo
Any readmission within 28 days  
Overall5/405 (1.2)3/285 (1.1)
Systemic corticosteroid therapy2/186 (1.1)1/66 (1.5)
No systemic corticosteroid therapy3/177 (1.7)2/261 (0.8)
Any readmission within 15 mo  
Overall96/405 (23.7)64/285 (22.5)
Systemic corticosteroid therapy52/186 (28.0)17/66 (25.8)
No systemic corticosteroid therapy32/177 (18.1)59/261 (22.6)
Asthma hospitalization within 15 mo  
Overall61/405 (15.1)34/285 (11.9)
Systemic corticosteroid therapy39/186 (21.0)13/66 (19.7)
No systemic corticosteroid therapy14/177 (7.9)29/261 (11.1)

Overall, 160 children (23.2%) were readmitted within 15 months of index discharge; 95 were readmitted for asthma during this time (Table 3). Overall readmission occurred in 23.7% of macrolide recipients and 22.5% of macrolide non‐recipients (P = 0.702). Asthma readmission occurred in 15.1% of macrolide recipients and 11.9% of macrolide non‐recipients (P = 0.240). In unadjusted analysis, empiric macrolide therapy was not significantly associated with any readmission within 15 months (OR, 1.07; 95% CI: 0.69‐1.68; P = 0.759) or with asthma‐related readmission within 15 months (OR, 1.31; 95% CI: 0.73‐ 2.36; P = 0.369). In multivariable analysis, neither any readmission nor asthma readmission within 15 months was associated with empiric macrolide therapy overall (Table 2) or when stratified by receipt or non‐receipt of concomitant systemic corticosteroid therapy (Table 3).

The analyses for readmissions within 15 months of index discharge were repeated while limiting the cohort to those without prior asthma hospitalizations or chronic asthma medications. In this subset of patients, readmissions for any reason occurred in 55 (18.6%) of 295 macrolide recipients and 50 (22.0%) of 227 non‐recipients. The difference was not statistically significant in multivariable analysis (adjusted odds ratio, 0.79; 95% CI: 0.41‐1.51; P = 0.47). Readmissions for asthma occurred in 30 (10.2%) of 295 macrolide recipients and 26 (11.5%) of 227 non‐recipients; this difference was also not significant in multivariable analysis (adjusted odds ratio, 0.83; 95% CI: 0.36‐1.93; P = 0.83). The magnitude of the estimate of effect for 28‐day and 15‐month readmissions, and 15‐month asthma hospitalizations, was similar to the primary analysis when the cohort was restricted to subjects with a LOS 7 days.

DISCUSSION

This multicenter study examined the role of macrolide therapy in children hospitalized with M. pneumoniae pneumonia. Empiric macrolide therapy was associated with an approximately 30% shorter hospital LOS and, in stratified analysis, remained associated with a significantly shorter hospital LOS in both systemic corticosteroid recipients and non‐recipients. Empiric macrolide therapy was not associated with short‐ or longer‐term hospital readmission.

Previous small randomized trials have been inconclusive regarding the potential benefit of macrolide therapy in M. pneumoniae pneumonia.11 Our study, which demonstrated a shorter LOS among macrolides recipients compared with non‐recipients, has several advantages over prior studies including a substantively larger sample size and multicenter design. Animal models support our observations regarding the potential beneficial antimicrobial role of macrolides. M. pneumoniae concentrations in bronchoalveolar lavage specimens were significantly lower among experimentally infected mice treated with clarithromycin, a macolide‐class antibiotic, compared with either placebo or dexamethasone.45 Combination therapy with clarithromycin and dexamethasone reduced histopathologic inflammation to a greater degree than dexamethasone alone.45

While the relative importance of the antimicrobial and anti‐inflammatory properties of macrolides is not known, observational studies of children infected with macrolide‐resistant M. pneumoniae suggest that the antimicrobial properties of macrolides may provide disproportionate clinical benefit. The duration of fever in macrolide recipients with macrolide‐resistant M. pneumoniae (median duration, 9 days) reported by Suzuki et al46 was significantly longer than those with macrolide‐susceptible infections (median duration, 5 days), and similar to the duration of fever in patients with M. pneumoniae infection treated with placebo (median duration, 8 days) reported by Kingston et al.47 Additionally, macrolide therapy was associated with significant improvements in lung function in patients with asthma and concomitant M. pneumoniae infection, but not in patients with asthma without documented M. pneumoniae infection.9 As corticosteroids also have anti‐inflammatory properties, we expect that any anti‐inflammatory benefit of macrolide therapy would be mitigated by the concomitant administration of corticosteroids. The shorter LOS associated with empiric macrolide therapy in our study was comparable among corticosteroid recipients and non‐recipients.

Atypical bacterial pathogens, including M. pneumoniae, are associated with diffuse lower airway inflammation6, 48 and airway hyperresponsiveness,6 and have been implicated as a cause of acute asthma exacerbations.7, 4954 Among patients with previously diagnosed asthma, acute M. pneumoniae infection was identified in up to 20% of those having acute exacerbations.7, 54 Macrolide therapy has a beneficial effect on lung function and airway hyperresponsiveness in adults with asthma.9, 55 Among mice infected with M. pneumoniae, 3 days of macrolide therapy resulted in a significant reduction in airway hyperresponsiveness compared with placebo or dexamethasone; however, after 6 days of therapy, there was no significant difference in airway hyperresponsiveness between those receiving macrolides, dexamethasone, or placebo, suggesting that the benefit of macrolides on airway hyperresponsiveness may be brief. Our findings of a shorter LOS but no difference in readmissions at 28 days or longer, for macrolide recipients compared with non‐recipients, support the limited benefit of macrolide therapy beyond the initial reduction in bacterial load seen in the first few days of therapy.

M. pneumoniae infection has also been implicated as a cause of chronic pulmonary disease, including asthma.610 In the mouse model, peribronchial and perivascular mononuclear infiltrates, increased airway methacholine reactivity, and increased airway obstruction were observed 530 days after M. pneumoniae inoculation.6 M. pneumoniae has been identified in 26 (50%) of 51 children experiencing their first asthma attack,7 and 23 (42%) of 55 adults with chronic, stable asthma.9 Nevertheless, results of other studies addressing the issue are inconsistent, and the role of M. pneumoniae in the development of asthma remains unclear.56 In order to investigate the impact of macrolide therapy on the development of chronic pulmonary disease requiring hospitalization, we examined the readmission rates in the 15 months following index discharge. The proportion of children hospitalized with asthma following the hospitalization for M. pneumoniae pneumonia was higher for both macrolide recipients and non‐recipients compared with the 24‐months prior to infection. These results support a possible role for M. pneumoniae in chronic pulmonary disease. However, macrolide therapy was not associated with long‐term overall hospital readmission or long‐term asthma readmission, either in the entire cohort or in the subset of patients without prior asthma hospitalizations or medications.

This study had several limitations. First, because the identification of children with M. pneumoniae pneumonia relied on ICD‐9 discharge diagnosis codes, it is possible that there was misclassification of disease. We minimized the inclusion of children without M. pneumoniae by including only children who received antibiotic therapy on the first day of hospitalization and by excluding patients younger than 6 years of age, a group at relatively low‐risk for M. pneumoniae infection. Further, our algorithm for identification of M. pneumoniae pneumonia was validated through review of the medical records at 1 institution and was found to have a high positive predictive value. However, the positive predictive value of these ICD‐9 codes may vary across institutions. Additionally, the sensitivity of ICD‐9 codes for identifying children with M. pneumoniae pneumonia is not known. Also, not all children with pneumonia undergo testing for M. pneumoniae, and different tests have varying sensitivity and specificity.57, 58 Thus, some children with M. pneumoniae pneumonia were not diagnosed and so were not included in our study. It is not known how inclusion of these children would affect our results.

Second, the antibiotic information used in this study was limited to empiric antibiotic therapy. It is possible that some patients received macrolide therapy before admission. It is also likely that identification of M. pneumoniae during the hospitalization prompted the addition or substitution of macrolide therapy for some patients. If this therapy was initiated beyond the first day of hospitalization, these children would be classified as macrolide non‐recipients. Since macrolide administration was associated with a shorter hospital LOS, such misclassification would bias our results towards finding no difference in LOS between macrolide recipients and non‐recipients. It is therefore possible that the benefit of macrolide therapy is even greater than found in our study.

Third, there may be unmeasured confounding or residual confounding by indication for adjunct corticosteroid therapy related to clinical presentation. We expect that corticosteroid recipients would be sicker than non‐recipients. We included variables associated with a greater severity of illness (such as intensive care unit admission) in the multivariable analysis. Additionally, the shorter LOS among macrolide recipients remained when the analysis was stratified by receipt or non‐receipt of systemic corticosteroid therapy.

Fourth, we were only able to record readmissions occurring at the same hospital as the index admission; any readmission presenting to a different hospital following their index admission did not appear in our records, and was therefore not counted. It is thus possible that the true number of readmissions is higher than that represented here. Finally, despite the large number of patients included in this study, the number of short‐term readmissions was relatively small. Thus, we may have been underpowered to detect small but significant differences in short‐term readmission rates.

In conclusion, macrolide therapy was associated with shorter hospital LOS, but not with short‐term or longer‐term readmission in children presenting with M. pneumoniae pneumonia.

Appendix

0, 0, 0, 0

UNIVARIATE ANALYSIS OF LENGTH OF STAY
VariableBeta CoefficientConfidence IntervalP Value
Demographics   
Sex0.12(0.22, 0.02)0.022
Race   
Blackreference category   
White0.01(0.21, 0.23)0.933
Other0.13(0.39, 0.13)0.323
Missing0.46(0.81, 0.11)0.012
Presentation during viral respiratory season0.05(0.19, 0.09)0.462
Prior asthma hospitalization0.36(0.64, 0.08)0.015
Intensive care unit admission1.05(0.87, 1.23)<0.001
Labs and procedures performed   
Additional radiologic imaging0.23(0.20, 0.67)0.287
Arterial blood gas0.69(0.50, 0.87)<0.001
Complete blood count0.34(0.24, 0.45)<0.001
Blood culture0.17(0.98, 0.44)0.204
Mechanical ventilation1.15(0.68, 1.63)<0.001
Therapies received   
Empiric macrolide therapy0.49(0.72, 0.25)<0.001
Systemic steroids0.26(0.38, 0.14)<0.001
Chronic asthma medications0.20(0.38, 0.013)0.037
Beta‐agonist therapy0.07(0.21, 0.08)0.357
Vasoactive infusion1.08(0.727, 1.45)<0.001
Clindamycin or vancomycin0.55(0.34, 0.75)<0.001
UNIVARIATE ANALYSIS OF 28‐DAY READMISSION
VariableOdds Ratio*Confidence IntervalP Value
  • Ellipses indicate that variables correlated perfectly with the outcome in univariate analysis.

Demographics   
Sex0.56(0.23, 1.33)0.190
Race   
Blackreference category   
White0.46(0.19, 1.14)0.093
Other   
Missing   
Presentation during viral respiratory season0.64(0.09, 4.75)0.662
Prior asthma hospitalization   
Intensive care unit admission4.54(1.21, 17.03)0.025
Laboratory tests and procedures   
Additional radiologic imaging10.00(2.25, 44.47)0.002
Arterial blood gas   
Complete blood count0.92(0.24, 3.48)0.901
Blood culture0.85(0.30, 2.36)0.738
Mechanical ventilation   
Medications   
Macrolide therapy1.18(0.25, 5.45)0.837
Systemic corticosteroids1.04(0.276, 4.09)0.951
Chronic asthma medication1.66(0.71, 3.88)0.242
Beta‐agonist therapy0.66(0.16, 2.65)0.557
Vasoactive infusions   
Clindamycin or vancomycin1.00(0.10, 9.90)0.998
MULTIVARIATE ANALYSIS OF LENGTH OF STAY
VariableCoefficientConfidence IntervalP Value% ChangeConfidence Interval for % Change
Demographics     
Age0.287(0.012, 0.045)0.0012.9(1.2, 4.6)
Prior asthma hospitalization0.272(0.094, 0.45)0.00431.3(9.9, 56.8)
Intensive care unit admission1.015(0.802, 1.23)<0.001175.9(123.0, 241.3)
Therapies received     
Macrolide therapy0.379(0.59, 0.166)0.00131.6(44.6, 15.3)
Systemic corticosteroids0.264(0.391, 0.138)<0.00123.2(32.3, 12.9)
Chronic asthma medications0.056(0.255, 0.142)0.5685.5(22.5, 15.2)
Albuterol0.07(0.059, 0.199)0.2817.2(5.8, 22.0)
Clindamycin or vancomycin0.311(0.063, 0.559)0.01536.5(6.5, 74.9)
MULTIVARIATE ANALYSIS OF 28‐DAY READMISSION
VariableAdjusted Odds RatioConfidence IntervalP Value
Demographics   
Age0.910.72, 1.150.423
Prior asthma hospitalization1.940.42, 8.900.394
Intensive care unit admission5.732.03, 16.200.001
Therapies received   
Macrolide therapy1.120.22, 5.780.890
Systemic corticosteroids0.6960.10, 4.700.710
Chronic asthma medications1.980.32, 12.200.460
Albuterol0.5190.081, 3.310.488
Clindamycin or vancomycin0.9040.07, 11.130.937
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References
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  17. Okazaki N,Narita M,Yamada S, et al.Characteristics of macrolide‐resistant Mycoplasma pneumoniae strains isolated from patients and induced with erythromycin in vitro.Microbiol Immunol.2001;45:617620.
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  24. Beuther DA,Martin RJ.Antibiotics in asthma.Curr Allergy Asthma Rep.2004;4:132138.
  25. Rubin BK,Henke MO.Immunomodulatory activity and effectiveness of macrolides in chronic airway disease.Chest.2004;125:70S78S.
  26. Abe S,Nakamura H,Inoue S, et al.Interleukin‐8 gene repression by clarithromycin is mediated by the activator protein‐1 binding site in human bronchial epithelial cells.Am J Respir Cell Mol Biol.2000;22:5160.
  27. Ichiyama T,Nishikawa M,Yoshitomi T, et al.Clarithromycin inhibits NF‐kappaB activation in human peripheral blood mononuclear cells and pulmonary epithelial cells.Antimicrob Agents Chemother.2001;45:4447.
  28. Foy HM,Grayston JT,Kenny GE,Alexander ER,McMahan R.Epidemiology of Mycoplasma pneumoniae infection in families.JAMA.1966;197:859866.
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  31. Hahn DL.Is there a role for antibiotics in the treatment of asthma? Involvement of atypical organisms.BioDrugs.2000;14:349354.
  32. Keicho N,Kudoh S.Diffuse panbronchiolitis: role of macrolides in therapy.Am J Respir Med.2002;1:119131.
  33. Nagai H,Shishido H,Yoneda R,Yamaguchi E,Tamura A,Kurashima A.Long‐term low‐dose administration of erythromycin to patients with diffuse panbronchiolitis.Respiration.1991;58:145149.
  34. Yamamoto M,Kondo A,Tamura M,Izumi T,Ina Y,Noda M.[Long‐term therapeutic effects of erythromycin and newquinolone antibacterial agents on diffuse panbronchiolitis].Nihon Kyobu Shikkan Gakkai Zasshi.1990;28:13051313.
  35. Matsubara K,Morozumi M,Okada T, et al.A comparative clinical study of macrolide‐sensitive and macrolide‐resistant Mycoplasma pneumoniae infections in pediatric patients.J Infect Chemother.2009;15:380383.
  36. Mongelluzzo J,Mohamad Z,Ten Have TR,Shah SS.Corticosteroids and mortality in children with bacterial meningitis.JAMA.2008;299:20482055.
  37. Shah SS,Hall M,Srivastava R,Subramony A,Levin JE.Intravenous immunoglobulin in children with streptococcal toxic shock syndrome.Clin Infect Dis.2009;49:13691376.
  38. Heiskanen‐Kosma T,Korppi M,Jokinen C, et al.Etiology of childhood pneumonia: serologic results of a prospective, population‐based study.Pediatr Infect Dis J.1998;17:986991.
  39. Feudtner C,Hays RM,Haynes G,Geyer JR,Neff JM,Koepsell TD.Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services.Pediatrics.2001;107:E99.
  40. Weiss AK,Hall M,Lee GE,Kronman MP,Sheffler‐Collins S,Shah SS.Adjunct corticosteroids in children hospitalized with community‐acquired pneumonia.Pediatrics.2011;127:e255e263.
  41. Shah SS,Hall M,Newland JG, et al.Comparative effectiveness of pleural drainage procedures for the treatment of complicated pneumonia in childhood.J Hosp Med.2011;6:256263.
  42. Kraft M,Cassell GH,Henson JE, et al.Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma.Am J Respir Crit Care Med.1998;158:9981001.
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  44. Concato J,Feinstein AR,Holford TR.The risk of determining risk with multivariable models.Ann Intern Med.1993;118:201210.
  45. Tagliabue C,Salvatore CM,Techasaensiri C, et al.The impact of steroids given with macrolide therapy on experimental Mycoplasma pneumoniae respiratory infection.J Infect Dis.2008;198:11801188.
  46. Suzuki S,Yamazaki T,Narita M, et al.Clinical evaluation of macrolide‐resistant Mycoplasma pneumoniae.Antimicrob Agents Chemother.2006;50:709712.
  47. Kingston JR,Chanock RM,Mufson MA, et al.Eaton agent pneumonia.JAMA.1961;176:118123.
  48. Johnston SL.The role of viral and atypical bacterial pathogens in asthma pathogenesis.Pediatr Pulmonol Suppl.1999;18:141143.
  49. Berkovich S,Millian SJ,Snyder RD.The association of viral and mycoplasma infections with recurrence of wheezing in the asthmatic child.Ann Allergy.1970;28:4349.
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FDA Turns Down Novel Antidiabetes Drug

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Other contenders in a novel class of glucose-lowering agents are waiting in the wings, despite a negative reception by the Food and Drug Administration on dapagliflozin – the first in that class of agents – presumably because of concerns noted by an FDA advisory panel about potential increases in the risk of bladder and breast cancers associated with the drug.

On Jan. 19, the drug’s joint developers, Bristol-Myers Squibb and AstraZeneca, announced that it received a complete response from the FDA that asked for still more clinical data on dapagliflozin. Although the companies offered no specifics about the request, they said in a statement that they are working "closely with the FDA to determine the appropriate next steps for the dapagliflozin application."

Dapagliflozin lowers glucose by selectively inhibiting renal glucose reabsorption via inhibition of sodium-glucose cotransporter 2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy, or in combination with other diabetes drugs. Despite the initial FDA panel vote, interest in the drug persists, as it is believed to address a pathogenic defect that has yet to be addressed in diabetes.

Bristol-Myers Squibb and AstraZeneca submitted data from recently completed and ongoing phase III clinical trials of dapagliflozin in response to an FDA request for clarification on the drug’s cancer and hepatic risks, along with further data on efficacy and safety in special populations, including the elderly, minorities, and patients with moderate renal impairment.

"This data submission constitutes a major amendment to the original new drug application (NDA) for dapagliflozin," Dr. Brian Daniels, senior vice president of global development and medical affairs at Bristol-Myers Squibb, explained in a statement last fall.

In July 2011, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against its approval in a 9-6 vote. Despite the drug’s associated cardiovascular and weight-loss benefits, panel members were troubled by nine cases each of bladder and breast cancer among dapagliflozin-treated patients, compared with one of each type in control patients. Using these numbers, the FDA calculated risk ratios of 5.08 for the incidence of bladder cancer in dapagliflozin-treated men, compared with controls, and 4.04 for the incidence of breast cancer in women. The agency’s decision to deny marketing approval for dapagliflozin was widely expected.

Nevertheless, the pipeline of SGLT2-based drugs is full. At the European Association for the Study of Diabetes (EASD) meeting in September, data were presented on Boehringer Ingelheim’s empagliflozin, Astellas Pharma’s ipragliflozin, Taisho Pharmaceuticals’ TS-071, and Lexicon Pharmaceuticals’ LX4211, which is a dual inhibitor of both SGLT1 and SGLT2. All of these agents showed that they can successfully lower glucose levels and improve other metabolic parameters, with generally good short-term safety profiles. The largest of the study populations was 495 patients (for empagliflozin), and the longest of the study periods was 16 weeks (for ipragliflozin).

In an interview, Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon, noted that as a dual SGLT1/SGLT2 inhibitor, LX4211 is actually in a distinct class from dapagliflozin.

"This differentiates LX4211 from the SGLT2-specific inhibitors in several ways. For example, in patients with type 2 diabetes, LX4211 has been shown to cause a rapid reduction in blood sugar levels after meals, and an increase in GLP-1 [glucagonlike peptide–1] and the increase in PYY [peptide YY], effects that are associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract. Also, recent studies in healthy subjects have shown that LX4211 substantially decreases postprandial glucose levels without hypoglycemia, and in both diabetic patients and healthy subjects, LX4211 can substantially reduce triglycerides. These results have not been reported for SGLT2-selective inhibitors," he said.

With regard to safety, Dr. Lapuerta noted that the "issue for the FDA advisory committee had to do with the overall benefit/risk profile of dapagliflozin. We believe the solution will involve addressing both benefits and risks. On the benefit side, we believe that LX4211 is a cardiovascular drug, not just a diabetes drug. Dual inhibition of SGLT1/2 with LX4211 offers the potential benefit to combine strong [hemoglobin] A1c reduction with benefits in blood pressure, uric acid, weight loss, and triglycerides. Cardiovascular benefits will be relevant to approval," he said.

"On the risk side, there is the potential that reports of bladder cancer on dapagliflozin reflected an ascertainment bias. We can address this in the LX4211 clinical program by ensuring that we carefully document physician referral patterns and take steps to ensure [that] our studies identify as much as possible new conditions instead of preexisting ones."

 

 

Susan Holz, public relations manager at Boehringer Ingelheim Pharmaceuticals, said in an earlier interview, "We are aware of the advisory committee’s concerns with dapagliflozin and are working with the FDA to ensure [that] our filing package for empagliflozin is robust and comprehensive. Phase III trials for empagliflozin are underway, and we are continuing to evaluate the drug’s safety profile." Currently, there are 11 ongoing, multinational, phase III clinical trials, including a large cardiovascular outcomes safety trial, she said.

At the EASD meeting in September, Dr. Michaela Diamant, scientific director of the diabetes center at Free University Medical Center in Amsterdam, commented that SGLT2 inhibitors have "an interesting mechanism that addresses, to a certain extent, a pathogenic defect that has been largely overlooked in diabetes. ... I’m sure there is a huge group of patients who can profit from these novel agents."

Regarding the safety issue, she asked, "If you would have a trial of 2-5 years, would you definitely address causality of cancer? We know that cancer development takes 20 years. It’s very unlikely that the drug caused cancer. We have to do what is feasible. The industry is not going to develop any more of these drugs if they are required to do a trial of 10 years. It’s difficult to tease out [contributors] to the development of cancer," Dr. Diamant continued.

Dr. Diamant has been a board member, advisory panel member, consultant, research support recipient, and/or speakers bureau participant for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Abbott, AstraZeneca/BMS, Boehringer Ingelheim, Poxel Pharma, Sanofi-Aventis, Amylin Pharmaceuticals, Novartis, and Takeda.

Sue Sutter of "The Pink Sheet" contributed to this story. "The Pink Sheet" and this publication are both owned by Elsevier.

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Other contenders in a novel class of glucose-lowering agents are waiting in the wings, despite a negative reception by the Food and Drug Administration on dapagliflozin – the first in that class of agents – presumably because of concerns noted by an FDA advisory panel about potential increases in the risk of bladder and breast cancers associated with the drug.

On Jan. 19, the drug’s joint developers, Bristol-Myers Squibb and AstraZeneca, announced that it received a complete response from the FDA that asked for still more clinical data on dapagliflozin. Although the companies offered no specifics about the request, they said in a statement that they are working "closely with the FDA to determine the appropriate next steps for the dapagliflozin application."

Dapagliflozin lowers glucose by selectively inhibiting renal glucose reabsorption via inhibition of sodium-glucose cotransporter 2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy, or in combination with other diabetes drugs. Despite the initial FDA panel vote, interest in the drug persists, as it is believed to address a pathogenic defect that has yet to be addressed in diabetes.

Bristol-Myers Squibb and AstraZeneca submitted data from recently completed and ongoing phase III clinical trials of dapagliflozin in response to an FDA request for clarification on the drug’s cancer and hepatic risks, along with further data on efficacy and safety in special populations, including the elderly, minorities, and patients with moderate renal impairment.

"This data submission constitutes a major amendment to the original new drug application (NDA) for dapagliflozin," Dr. Brian Daniels, senior vice president of global development and medical affairs at Bristol-Myers Squibb, explained in a statement last fall.

In July 2011, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against its approval in a 9-6 vote. Despite the drug’s associated cardiovascular and weight-loss benefits, panel members were troubled by nine cases each of bladder and breast cancer among dapagliflozin-treated patients, compared with one of each type in control patients. Using these numbers, the FDA calculated risk ratios of 5.08 for the incidence of bladder cancer in dapagliflozin-treated men, compared with controls, and 4.04 for the incidence of breast cancer in women. The agency’s decision to deny marketing approval for dapagliflozin was widely expected.

Nevertheless, the pipeline of SGLT2-based drugs is full. At the European Association for the Study of Diabetes (EASD) meeting in September, data were presented on Boehringer Ingelheim’s empagliflozin, Astellas Pharma’s ipragliflozin, Taisho Pharmaceuticals’ TS-071, and Lexicon Pharmaceuticals’ LX4211, which is a dual inhibitor of both SGLT1 and SGLT2. All of these agents showed that they can successfully lower glucose levels and improve other metabolic parameters, with generally good short-term safety profiles. The largest of the study populations was 495 patients (for empagliflozin), and the longest of the study periods was 16 weeks (for ipragliflozin).

In an interview, Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon, noted that as a dual SGLT1/SGLT2 inhibitor, LX4211 is actually in a distinct class from dapagliflozin.

"This differentiates LX4211 from the SGLT2-specific inhibitors in several ways. For example, in patients with type 2 diabetes, LX4211 has been shown to cause a rapid reduction in blood sugar levels after meals, and an increase in GLP-1 [glucagonlike peptide–1] and the increase in PYY [peptide YY], effects that are associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract. Also, recent studies in healthy subjects have shown that LX4211 substantially decreases postprandial glucose levels without hypoglycemia, and in both diabetic patients and healthy subjects, LX4211 can substantially reduce triglycerides. These results have not been reported for SGLT2-selective inhibitors," he said.

With regard to safety, Dr. Lapuerta noted that the "issue for the FDA advisory committee had to do with the overall benefit/risk profile of dapagliflozin. We believe the solution will involve addressing both benefits and risks. On the benefit side, we believe that LX4211 is a cardiovascular drug, not just a diabetes drug. Dual inhibition of SGLT1/2 with LX4211 offers the potential benefit to combine strong [hemoglobin] A1c reduction with benefits in blood pressure, uric acid, weight loss, and triglycerides. Cardiovascular benefits will be relevant to approval," he said.

"On the risk side, there is the potential that reports of bladder cancer on dapagliflozin reflected an ascertainment bias. We can address this in the LX4211 clinical program by ensuring that we carefully document physician referral patterns and take steps to ensure [that] our studies identify as much as possible new conditions instead of preexisting ones."

 

 

Susan Holz, public relations manager at Boehringer Ingelheim Pharmaceuticals, said in an earlier interview, "We are aware of the advisory committee’s concerns with dapagliflozin and are working with the FDA to ensure [that] our filing package for empagliflozin is robust and comprehensive. Phase III trials for empagliflozin are underway, and we are continuing to evaluate the drug’s safety profile." Currently, there are 11 ongoing, multinational, phase III clinical trials, including a large cardiovascular outcomes safety trial, she said.

At the EASD meeting in September, Dr. Michaela Diamant, scientific director of the diabetes center at Free University Medical Center in Amsterdam, commented that SGLT2 inhibitors have "an interesting mechanism that addresses, to a certain extent, a pathogenic defect that has been largely overlooked in diabetes. ... I’m sure there is a huge group of patients who can profit from these novel agents."

Regarding the safety issue, she asked, "If you would have a trial of 2-5 years, would you definitely address causality of cancer? We know that cancer development takes 20 years. It’s very unlikely that the drug caused cancer. We have to do what is feasible. The industry is not going to develop any more of these drugs if they are required to do a trial of 10 years. It’s difficult to tease out [contributors] to the development of cancer," Dr. Diamant continued.

Dr. Diamant has been a board member, advisory panel member, consultant, research support recipient, and/or speakers bureau participant for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Abbott, AstraZeneca/BMS, Boehringer Ingelheim, Poxel Pharma, Sanofi-Aventis, Amylin Pharmaceuticals, Novartis, and Takeda.

Sue Sutter of "The Pink Sheet" contributed to this story. "The Pink Sheet" and this publication are both owned by Elsevier.

Other contenders in a novel class of glucose-lowering agents are waiting in the wings, despite a negative reception by the Food and Drug Administration on dapagliflozin – the first in that class of agents – presumably because of concerns noted by an FDA advisory panel about potential increases in the risk of bladder and breast cancers associated with the drug.

On Jan. 19, the drug’s joint developers, Bristol-Myers Squibb and AstraZeneca, announced that it received a complete response from the FDA that asked for still more clinical data on dapagliflozin. Although the companies offered no specifics about the request, they said in a statement that they are working "closely with the FDA to determine the appropriate next steps for the dapagliflozin application."

Dapagliflozin lowers glucose by selectively inhibiting renal glucose reabsorption via inhibition of sodium-glucose cotransporter 2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy, or in combination with other diabetes drugs. Despite the initial FDA panel vote, interest in the drug persists, as it is believed to address a pathogenic defect that has yet to be addressed in diabetes.

Bristol-Myers Squibb and AstraZeneca submitted data from recently completed and ongoing phase III clinical trials of dapagliflozin in response to an FDA request for clarification on the drug’s cancer and hepatic risks, along with further data on efficacy and safety in special populations, including the elderly, minorities, and patients with moderate renal impairment.

"This data submission constitutes a major amendment to the original new drug application (NDA) for dapagliflozin," Dr. Brian Daniels, senior vice president of global development and medical affairs at Bristol-Myers Squibb, explained in a statement last fall.

In July 2011, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against its approval in a 9-6 vote. Despite the drug’s associated cardiovascular and weight-loss benefits, panel members were troubled by nine cases each of bladder and breast cancer among dapagliflozin-treated patients, compared with one of each type in control patients. Using these numbers, the FDA calculated risk ratios of 5.08 for the incidence of bladder cancer in dapagliflozin-treated men, compared with controls, and 4.04 for the incidence of breast cancer in women. The agency’s decision to deny marketing approval for dapagliflozin was widely expected.

Nevertheless, the pipeline of SGLT2-based drugs is full. At the European Association for the Study of Diabetes (EASD) meeting in September, data were presented on Boehringer Ingelheim’s empagliflozin, Astellas Pharma’s ipragliflozin, Taisho Pharmaceuticals’ TS-071, and Lexicon Pharmaceuticals’ LX4211, which is a dual inhibitor of both SGLT1 and SGLT2. All of these agents showed that they can successfully lower glucose levels and improve other metabolic parameters, with generally good short-term safety profiles. The largest of the study populations was 495 patients (for empagliflozin), and the longest of the study periods was 16 weeks (for ipragliflozin).

In an interview, Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon, noted that as a dual SGLT1/SGLT2 inhibitor, LX4211 is actually in a distinct class from dapagliflozin.

"This differentiates LX4211 from the SGLT2-specific inhibitors in several ways. For example, in patients with type 2 diabetes, LX4211 has been shown to cause a rapid reduction in blood sugar levels after meals, and an increase in GLP-1 [glucagonlike peptide–1] and the increase in PYY [peptide YY], effects that are associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract. Also, recent studies in healthy subjects have shown that LX4211 substantially decreases postprandial glucose levels without hypoglycemia, and in both diabetic patients and healthy subjects, LX4211 can substantially reduce triglycerides. These results have not been reported for SGLT2-selective inhibitors," he said.

With regard to safety, Dr. Lapuerta noted that the "issue for the FDA advisory committee had to do with the overall benefit/risk profile of dapagliflozin. We believe the solution will involve addressing both benefits and risks. On the benefit side, we believe that LX4211 is a cardiovascular drug, not just a diabetes drug. Dual inhibition of SGLT1/2 with LX4211 offers the potential benefit to combine strong [hemoglobin] A1c reduction with benefits in blood pressure, uric acid, weight loss, and triglycerides. Cardiovascular benefits will be relevant to approval," he said.

"On the risk side, there is the potential that reports of bladder cancer on dapagliflozin reflected an ascertainment bias. We can address this in the LX4211 clinical program by ensuring that we carefully document physician referral patterns and take steps to ensure [that] our studies identify as much as possible new conditions instead of preexisting ones."

 

 

Susan Holz, public relations manager at Boehringer Ingelheim Pharmaceuticals, said in an earlier interview, "We are aware of the advisory committee’s concerns with dapagliflozin and are working with the FDA to ensure [that] our filing package for empagliflozin is robust and comprehensive. Phase III trials for empagliflozin are underway, and we are continuing to evaluate the drug’s safety profile." Currently, there are 11 ongoing, multinational, phase III clinical trials, including a large cardiovascular outcomes safety trial, she said.

At the EASD meeting in September, Dr. Michaela Diamant, scientific director of the diabetes center at Free University Medical Center in Amsterdam, commented that SGLT2 inhibitors have "an interesting mechanism that addresses, to a certain extent, a pathogenic defect that has been largely overlooked in diabetes. ... I’m sure there is a huge group of patients who can profit from these novel agents."

Regarding the safety issue, she asked, "If you would have a trial of 2-5 years, would you definitely address causality of cancer? We know that cancer development takes 20 years. It’s very unlikely that the drug caused cancer. We have to do what is feasible. The industry is not going to develop any more of these drugs if they are required to do a trial of 10 years. It’s difficult to tease out [contributors] to the development of cancer," Dr. Diamant continued.

Dr. Diamant has been a board member, advisory panel member, consultant, research support recipient, and/or speakers bureau participant for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Abbott, AstraZeneca/BMS, Boehringer Ingelheim, Poxel Pharma, Sanofi-Aventis, Amylin Pharmaceuticals, Novartis, and Takeda.

Sue Sutter of "The Pink Sheet" contributed to this story. "The Pink Sheet" and this publication are both owned by Elsevier.

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HM Should Prepare for Long-Term Changes with ACOs

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A hospitalist who works for one of the 32 organizations tapped in the inaugural cohort of Pioneer Accountable Care Organizations (ACOs) says HM should not expect major change in the short term from the new coordinated care model. But change will come in the long term.

"As we start to get data back and start to figure out where we can make the biggest positive impact on improving health for patients and also the impact of cost savings, then the hospitalist will be more involved," says Tierza Stephan, MD, FACP, SFHM, district medical director for hospitalists at Allina Hospitals & Clinics of Minneapolis.

The Pioneer designation was a Centers for Medicare & Medicaid Services (CMS) Innovation Center initiative crafted last summer for organizations and providers already experienced in providing coordinated care. A related model, the Medicare Shared Savings Program, does not require any previous experience with such contracts. The models set benchmarks for providers and institutions to qualify for shared shavings.

Dr. Stephan, a member of SHM's Practice Analysis Committee, helped the Allina Integrated Medical (AIM) Network become one of the Pioneer ACOs. The network includes 1,100 Allina doctors and 900 independent physicians from private clinics or practices. She says Allina has spent months preparing for the ACO: crafting its initial quality metrics, including generic drug utilization, timely turnaround of critical results, and patient satisfaction.

While all members of the network will share data to achieve better efficiency and cost savings, Dr. Stephan says it's too early in the process to say how well the program will work in practice. In the short term, she expects little daily change for HM physicians. Given the time it takes to get a program started, Dr. Stephan urges HM group leaders working on building an ACO, or those already in an approved program, to be a loud voice during the process.

"We're the primary care in the hospital, and primary care is really at the heart of accountable-care organizations," she says. "It really takes commitment by the entire healthcare community, and hospitalists interact with the entire healthcare community."

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A hospitalist who works for one of the 32 organizations tapped in the inaugural cohort of Pioneer Accountable Care Organizations (ACOs) says HM should not expect major change in the short term from the new coordinated care model. But change will come in the long term.

"As we start to get data back and start to figure out where we can make the biggest positive impact on improving health for patients and also the impact of cost savings, then the hospitalist will be more involved," says Tierza Stephan, MD, FACP, SFHM, district medical director for hospitalists at Allina Hospitals & Clinics of Minneapolis.

The Pioneer designation was a Centers for Medicare & Medicaid Services (CMS) Innovation Center initiative crafted last summer for organizations and providers already experienced in providing coordinated care. A related model, the Medicare Shared Savings Program, does not require any previous experience with such contracts. The models set benchmarks for providers and institutions to qualify for shared shavings.

Dr. Stephan, a member of SHM's Practice Analysis Committee, helped the Allina Integrated Medical (AIM) Network become one of the Pioneer ACOs. The network includes 1,100 Allina doctors and 900 independent physicians from private clinics or practices. She says Allina has spent months preparing for the ACO: crafting its initial quality metrics, including generic drug utilization, timely turnaround of critical results, and patient satisfaction.

While all members of the network will share data to achieve better efficiency and cost savings, Dr. Stephan says it's too early in the process to say how well the program will work in practice. In the short term, she expects little daily change for HM physicians. Given the time it takes to get a program started, Dr. Stephan urges HM group leaders working on building an ACO, or those already in an approved program, to be a loud voice during the process.

"We're the primary care in the hospital, and primary care is really at the heart of accountable-care organizations," she says. "It really takes commitment by the entire healthcare community, and hospitalists interact with the entire healthcare community."

A hospitalist who works for one of the 32 organizations tapped in the inaugural cohort of Pioneer Accountable Care Organizations (ACOs) says HM should not expect major change in the short term from the new coordinated care model. But change will come in the long term.

"As we start to get data back and start to figure out where we can make the biggest positive impact on improving health for patients and also the impact of cost savings, then the hospitalist will be more involved," says Tierza Stephan, MD, FACP, SFHM, district medical director for hospitalists at Allina Hospitals & Clinics of Minneapolis.

The Pioneer designation was a Centers for Medicare & Medicaid Services (CMS) Innovation Center initiative crafted last summer for organizations and providers already experienced in providing coordinated care. A related model, the Medicare Shared Savings Program, does not require any previous experience with such contracts. The models set benchmarks for providers and institutions to qualify for shared shavings.

Dr. Stephan, a member of SHM's Practice Analysis Committee, helped the Allina Integrated Medical (AIM) Network become one of the Pioneer ACOs. The network includes 1,100 Allina doctors and 900 independent physicians from private clinics or practices. She says Allina has spent months preparing for the ACO: crafting its initial quality metrics, including generic drug utilization, timely turnaround of critical results, and patient satisfaction.

While all members of the network will share data to achieve better efficiency and cost savings, Dr. Stephan says it's too early in the process to say how well the program will work in practice. In the short term, she expects little daily change for HM physicians. Given the time it takes to get a program started, Dr. Stephan urges HM group leaders working on building an ACO, or those already in an approved program, to be a loud voice during the process.

"We're the primary care in the hospital, and primary care is really at the heart of accountable-care organizations," she says. "It really takes commitment by the entire healthcare community, and hospitalists interact with the entire healthcare community."

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CMS Awards First Care-Transition Coalition Grants

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Piedmont Hospital in Atlanta is one of several hospitals participating in SHM’s care-transitions initiative Project BOOST (Better Outcomes for Older Adults through Safe Transitions) to be included in the first round of Community-Based Care Transitions Project (CCTP) awards.

Matthew Schreiber, MD, vice president and chief medical officer for Piedmont Hospital, says hospitalists should look for ways to participate in the community coalitions applying for CCTP awards, because managing their hospitals’ readmissions rates eventually will be essential to their job security.

“I said to my hospital, ‘Right now, people are giving out money for us to be in the figuring-it-out mode regarding readmissions,” Dr. Schreiber explains. “Eventually, we’ll just have to do it anyway.’”

CCTP is part of the government’s efforts (PDF) to reduce hospital readmissions by encouraging coalitions of health providers to collaborate on care transitions and ongoing care coordination after patients leave the hospital. The $500 million program initially dished out seven awards to community-based coalitions, not directly to hospitals. Most of these coalitions are housed at regional Agencies on Aging and involve multiple hospitals or health systems.

According to the Centers for Medicare & Medicaid Services (CMS), CCTP differs from a traditional grant program in that it pays community-based organizations an all-inclusive rate per eligible discharge, based on the cost of care transition services and of systemic changes at the hospital level.

The seven awardees also employ the Care Transitions Intervention program developed by Eric Coleman, MD, MPH, of the University of Colorado, co-chair of Project BOOST’s national advisory board. The intervention program is a recognized tool for improving care transitions and reducing preventable rehospitalizations through the use of social worker "transition coaches" to provide discharged patients with self-care education and encouragement.

Other BOOST site hospitals participating in CCTP-awarded coalitions include Northwestern Memorial in Chicago and Emory University Hospital Midtown in Atlanta.

Dr. Schreiber says being a Project BOOST site and using Dr. Coleman's Care Transitions Intervention should be complementary for any hospital striving to reduce readmissions. “Both together were greater than the sum of their parts,” he says, adding that Piedmont has reduced its readmission rate by 50%.

Summaries of the first seven sites and information on how to apply for ongoing CCTP grants can be found here.

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Piedmont Hospital in Atlanta is one of several hospitals participating in SHM’s care-transitions initiative Project BOOST (Better Outcomes for Older Adults through Safe Transitions) to be included in the first round of Community-Based Care Transitions Project (CCTP) awards.

Matthew Schreiber, MD, vice president and chief medical officer for Piedmont Hospital, says hospitalists should look for ways to participate in the community coalitions applying for CCTP awards, because managing their hospitals’ readmissions rates eventually will be essential to their job security.

“I said to my hospital, ‘Right now, people are giving out money for us to be in the figuring-it-out mode regarding readmissions,” Dr. Schreiber explains. “Eventually, we’ll just have to do it anyway.’”

CCTP is part of the government’s efforts (PDF) to reduce hospital readmissions by encouraging coalitions of health providers to collaborate on care transitions and ongoing care coordination after patients leave the hospital. The $500 million program initially dished out seven awards to community-based coalitions, not directly to hospitals. Most of these coalitions are housed at regional Agencies on Aging and involve multiple hospitals or health systems.

According to the Centers for Medicare & Medicaid Services (CMS), CCTP differs from a traditional grant program in that it pays community-based organizations an all-inclusive rate per eligible discharge, based on the cost of care transition services and of systemic changes at the hospital level.

The seven awardees also employ the Care Transitions Intervention program developed by Eric Coleman, MD, MPH, of the University of Colorado, co-chair of Project BOOST’s national advisory board. The intervention program is a recognized tool for improving care transitions and reducing preventable rehospitalizations through the use of social worker "transition coaches" to provide discharged patients with self-care education and encouragement.

Other BOOST site hospitals participating in CCTP-awarded coalitions include Northwestern Memorial in Chicago and Emory University Hospital Midtown in Atlanta.

Dr. Schreiber says being a Project BOOST site and using Dr. Coleman's Care Transitions Intervention should be complementary for any hospital striving to reduce readmissions. “Both together were greater than the sum of their parts,” he says, adding that Piedmont has reduced its readmission rate by 50%.

Summaries of the first seven sites and information on how to apply for ongoing CCTP grants can be found here.

Piedmont Hospital in Atlanta is one of several hospitals participating in SHM’s care-transitions initiative Project BOOST (Better Outcomes for Older Adults through Safe Transitions) to be included in the first round of Community-Based Care Transitions Project (CCTP) awards.

Matthew Schreiber, MD, vice president and chief medical officer for Piedmont Hospital, says hospitalists should look for ways to participate in the community coalitions applying for CCTP awards, because managing their hospitals’ readmissions rates eventually will be essential to their job security.

“I said to my hospital, ‘Right now, people are giving out money for us to be in the figuring-it-out mode regarding readmissions,” Dr. Schreiber explains. “Eventually, we’ll just have to do it anyway.’”

CCTP is part of the government’s efforts (PDF) to reduce hospital readmissions by encouraging coalitions of health providers to collaborate on care transitions and ongoing care coordination after patients leave the hospital. The $500 million program initially dished out seven awards to community-based coalitions, not directly to hospitals. Most of these coalitions are housed at regional Agencies on Aging and involve multiple hospitals or health systems.

According to the Centers for Medicare & Medicaid Services (CMS), CCTP differs from a traditional grant program in that it pays community-based organizations an all-inclusive rate per eligible discharge, based on the cost of care transition services and of systemic changes at the hospital level.

The seven awardees also employ the Care Transitions Intervention program developed by Eric Coleman, MD, MPH, of the University of Colorado, co-chair of Project BOOST’s national advisory board. The intervention program is a recognized tool for improving care transitions and reducing preventable rehospitalizations through the use of social worker "transition coaches" to provide discharged patients with self-care education and encouragement.

Other BOOST site hospitals participating in CCTP-awarded coalitions include Northwestern Memorial in Chicago and Emory University Hospital Midtown in Atlanta.

Dr. Schreiber says being a Project BOOST site and using Dr. Coleman's Care Transitions Intervention should be complementary for any hospital striving to reduce readmissions. “Both together were greater than the sum of their parts,” he says, adding that Piedmont has reduced its readmission rate by 50%.

Summaries of the first seven sites and information on how to apply for ongoing CCTP grants can be found here.

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Obesity in U.S. Appears to Be Leveling Off

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The prevalence of obesity in the United States appears to have plateaued, according to data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) conducted by the U.S. Centers for Disease Control and Prevention.

Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 figures in adults, and compared with 2007-2008 prevalence rates in children and adolescents.

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Data from the 2009-2010 National Health and Nutrition Examination Survey indicate that obesity in adults, children, and adolescents has not increased from previous figures.

For example, based on data from the 5,926 men and women with measured weight and height who participated in the 2009-2010 NHANES, the age-adjusted prevalence of obesity was roughly 35% for both men and women, which was not significantly different overall compared with the prevalence from 2003-2008, Katherine M. Flegal, Ph.D., and her colleagues from the National Center for Health Statistics, CDC, Hyattsville, Md., report online in the Jan. 17 JAMA.

Despite the lack of change overall, the analysis of adult data did indicate, however, that obesity increased in certain segments of the population. While no significant increase was seen among women overall (age- and race-adjusted annual change in odds ratio from 1999-2010, 1.01), statistically significant increases were seen among non-Hispanic black women (OR, 1.03) and Mexican American women (1.03), the investigators noted (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.39]).

A significant linear trend was also seen in men over the 12-year period (annual change in OR, 1.04).

As for BMI, the age-adjusted mean in both men and women was 28.7, and the trends over time in this study were similar to those seen with obesity, with a significant increase seen in men, but not in women, over the 12 years, the investigators said.

In a separate cross-sectional analysis of data from 4,111 children and adolescents who participated in NHANES, the 2009-2010 obesity prevalence of 9.7% in infants and toddlers up to age 2 years, and 16.9% for those aged 2-19 years, did not differ significantly from the 2007-2008 prevalence, and no difference was seen between males and females in regard to obesity prevalence, Cynthia L. Ogden, Ph.D., and her colleagues, also from the National Center for Health Statistics, CDC, reported in the same issue of JAMA.

A trend analysis over the 12-year study period did indicate, however, that the obesity prevalence among males aged 2-19 years increased significantly between 1999-2000 and 2009-2010 (OR, 1.05) per 2-year survey cycle, and that there was a significant increasing trend for non-Hispanic black males (OR, 1.10). Also, BMI increased significantly in males aged 12 through 19 years (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.40]).

NHANES data have been collected continuously since 1999, with reports released in 2-year cycles. Since no universally agreed upon definition of obesity exists for infants and toddlers up to age 2 years, high weight in this age group was defined as weight-for-recumbent length at or above the 95th percentile on the CDCs 2000 growth charts, the investigators explained.

Weight status in those aged 2 through 19 years is defined based on BMI; those at or above the sex-specific 85th percentile, but less than the 95th percentile, are considered overweight, and those at or above the sex-specific 95th percentile are considered obese. For adults, those with a BMI of 25.0 to 29.9 are considered overweight, and those with a BMI of 30.0 or higher are considered obese, with further subdivision into grades 1, 2, and 3 obesity based on BMI of 30.0 to less than 35.0, 35.0 to less than 40.0, and 40.0 or greater, respectively.

Investigators for both analyses noted that it is important to keep in mind that BMI is an "imperfect measure of body fat."

Since racial and ethnic differences in the level of body fat at specific BMIs exist, the differences in obesity prevalence by race and ethnicity in these studies may not represent actual differences in body fat, they said.

Overall, the findings in both adults and children/adolescents suggest that increases in the prevalence of obesity that have previously been observed are not continuing and have leveled off.

Although it’s difficult to predict whether these trends will continue in the same direction, the findings suggest that previous models that predict continuing increases in obesity prevalence in all age groups may be based on invalid assumptions.

None of the authors indicated having relevant conflicts of interest.

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The prevalence of obesity in the United States appears to have plateaued, according to data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) conducted by the U.S. Centers for Disease Control and Prevention.

Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 figures in adults, and compared with 2007-2008 prevalence rates in children and adolescents.

© okeyphotos/iStockphoto.com
Data from the 2009-2010 National Health and Nutrition Examination Survey indicate that obesity in adults, children, and adolescents has not increased from previous figures.

For example, based on data from the 5,926 men and women with measured weight and height who participated in the 2009-2010 NHANES, the age-adjusted prevalence of obesity was roughly 35% for both men and women, which was not significantly different overall compared with the prevalence from 2003-2008, Katherine M. Flegal, Ph.D., and her colleagues from the National Center for Health Statistics, CDC, Hyattsville, Md., report online in the Jan. 17 JAMA.

Despite the lack of change overall, the analysis of adult data did indicate, however, that obesity increased in certain segments of the population. While no significant increase was seen among women overall (age- and race-adjusted annual change in odds ratio from 1999-2010, 1.01), statistically significant increases were seen among non-Hispanic black women (OR, 1.03) and Mexican American women (1.03), the investigators noted (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.39]).

A significant linear trend was also seen in men over the 12-year period (annual change in OR, 1.04).

As for BMI, the age-adjusted mean in both men and women was 28.7, and the trends over time in this study were similar to those seen with obesity, with a significant increase seen in men, but not in women, over the 12 years, the investigators said.

In a separate cross-sectional analysis of data from 4,111 children and adolescents who participated in NHANES, the 2009-2010 obesity prevalence of 9.7% in infants and toddlers up to age 2 years, and 16.9% for those aged 2-19 years, did not differ significantly from the 2007-2008 prevalence, and no difference was seen between males and females in regard to obesity prevalence, Cynthia L. Ogden, Ph.D., and her colleagues, also from the National Center for Health Statistics, CDC, reported in the same issue of JAMA.

A trend analysis over the 12-year study period did indicate, however, that the obesity prevalence among males aged 2-19 years increased significantly between 1999-2000 and 2009-2010 (OR, 1.05) per 2-year survey cycle, and that there was a significant increasing trend for non-Hispanic black males (OR, 1.10). Also, BMI increased significantly in males aged 12 through 19 years (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.40]).

NHANES data have been collected continuously since 1999, with reports released in 2-year cycles. Since no universally agreed upon definition of obesity exists for infants and toddlers up to age 2 years, high weight in this age group was defined as weight-for-recumbent length at or above the 95th percentile on the CDCs 2000 growth charts, the investigators explained.

Weight status in those aged 2 through 19 years is defined based on BMI; those at or above the sex-specific 85th percentile, but less than the 95th percentile, are considered overweight, and those at or above the sex-specific 95th percentile are considered obese. For adults, those with a BMI of 25.0 to 29.9 are considered overweight, and those with a BMI of 30.0 or higher are considered obese, with further subdivision into grades 1, 2, and 3 obesity based on BMI of 30.0 to less than 35.0, 35.0 to less than 40.0, and 40.0 or greater, respectively.

Investigators for both analyses noted that it is important to keep in mind that BMI is an "imperfect measure of body fat."

Since racial and ethnic differences in the level of body fat at specific BMIs exist, the differences in obesity prevalence by race and ethnicity in these studies may not represent actual differences in body fat, they said.

Overall, the findings in both adults and children/adolescents suggest that increases in the prevalence of obesity that have previously been observed are not continuing and have leveled off.

Although it’s difficult to predict whether these trends will continue in the same direction, the findings suggest that previous models that predict continuing increases in obesity prevalence in all age groups may be based on invalid assumptions.

None of the authors indicated having relevant conflicts of interest.

The prevalence of obesity in the United States appears to have plateaued, according to data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) conducted by the U.S. Centers for Disease Control and Prevention.

Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 figures in adults, and compared with 2007-2008 prevalence rates in children and adolescents.

© okeyphotos/iStockphoto.com
Data from the 2009-2010 National Health and Nutrition Examination Survey indicate that obesity in adults, children, and adolescents has not increased from previous figures.

For example, based on data from the 5,926 men and women with measured weight and height who participated in the 2009-2010 NHANES, the age-adjusted prevalence of obesity was roughly 35% for both men and women, which was not significantly different overall compared with the prevalence from 2003-2008, Katherine M. Flegal, Ph.D., and her colleagues from the National Center for Health Statistics, CDC, Hyattsville, Md., report online in the Jan. 17 JAMA.

Despite the lack of change overall, the analysis of adult data did indicate, however, that obesity increased in certain segments of the population. While no significant increase was seen among women overall (age- and race-adjusted annual change in odds ratio from 1999-2010, 1.01), statistically significant increases were seen among non-Hispanic black women (OR, 1.03) and Mexican American women (1.03), the investigators noted (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.39]).

A significant linear trend was also seen in men over the 12-year period (annual change in OR, 1.04).

As for BMI, the age-adjusted mean in both men and women was 28.7, and the trends over time in this study were similar to those seen with obesity, with a significant increase seen in men, but not in women, over the 12 years, the investigators said.

In a separate cross-sectional analysis of data from 4,111 children and adolescents who participated in NHANES, the 2009-2010 obesity prevalence of 9.7% in infants and toddlers up to age 2 years, and 16.9% for those aged 2-19 years, did not differ significantly from the 2007-2008 prevalence, and no difference was seen between males and females in regard to obesity prevalence, Cynthia L. Ogden, Ph.D., and her colleagues, also from the National Center for Health Statistics, CDC, reported in the same issue of JAMA.

A trend analysis over the 12-year study period did indicate, however, that the obesity prevalence among males aged 2-19 years increased significantly between 1999-2000 and 2009-2010 (OR, 1.05) per 2-year survey cycle, and that there was a significant increasing trend for non-Hispanic black males (OR, 1.10). Also, BMI increased significantly in males aged 12 through 19 years (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.40]).

NHANES data have been collected continuously since 1999, with reports released in 2-year cycles. Since no universally agreed upon definition of obesity exists for infants and toddlers up to age 2 years, high weight in this age group was defined as weight-for-recumbent length at or above the 95th percentile on the CDCs 2000 growth charts, the investigators explained.

Weight status in those aged 2 through 19 years is defined based on BMI; those at or above the sex-specific 85th percentile, but less than the 95th percentile, are considered overweight, and those at or above the sex-specific 95th percentile are considered obese. For adults, those with a BMI of 25.0 to 29.9 are considered overweight, and those with a BMI of 30.0 or higher are considered obese, with further subdivision into grades 1, 2, and 3 obesity based on BMI of 30.0 to less than 35.0, 35.0 to less than 40.0, and 40.0 or greater, respectively.

Investigators for both analyses noted that it is important to keep in mind that BMI is an "imperfect measure of body fat."

Since racial and ethnic differences in the level of body fat at specific BMIs exist, the differences in obesity prevalence by race and ethnicity in these studies may not represent actual differences in body fat, they said.

Overall, the findings in both adults and children/adolescents suggest that increases in the prevalence of obesity that have previously been observed are not continuing and have leveled off.

Although it’s difficult to predict whether these trends will continue in the same direction, the findings suggest that previous models that predict continuing increases in obesity prevalence in all age groups may be based on invalid assumptions.

None of the authors indicated having relevant conflicts of interest.

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Major Finding: Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 in adults, and compared with 2007-2008 in children and adolescents.

Data Source: Two analyses of data from the 1999-2010 National Health and Nutrition Examination Surveys (NHANES).

Disclosures: The study authors reported having no relevant conflicts of interest.

Warnings issued for brentuximab vedotin

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Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

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Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

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Drowning Hospitalizations Halved Between 1993 and 2008

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Drowning Hospitalizations Halved Between 1993 and 2008

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

 

 

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

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Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

 

 

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

 

 

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

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Major Finding: Hospitalizations for drowning dropped 51% between 1993 and 2008. The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008.

Data Source: The results come from a study based on data from the Nationwide Inpatient Sample from 1993 to 2008.

Disclosures: The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.