BALTIMORE – Multiple studies based on phase 3 clinical trials of the investigational drug solriamfetol have found that it may be effective for improving next-day wakefulness and work productivity in people with narcolepsy and obstructive sleep apnea, and that the drug can maintain its effect throughout the day as well as for up to 6 months, investigators reported at the annual meeting of the Associated Professional Sleep Societies.

Solriamfetol, developed by Jazz Pharmaceuticals, is the subject of a new drug application accepted by the Food and Drug Administration in March of 2018 for the treatment of excessive sleepiness due to narcolepsy or obstructive sleep apnea (OSA). Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor.

The drug was the subject of four different studies presented at SLEEP 2018 that drilled down into its effect on specific aspects of narcolepsy or OSA, or both. One study explored results in narcoleptic patients with and without cataplexy. Another study investigated the drug’s maintenance of efficacy after 6 months of treatment. A third study looked at the drug’s impact on next-day function, work productivity, and quality of life in patients with narcolepsy. And the fourth study researched how solriamfetol helped maintain wakefulness throughout the day.

Yves Dauvilliers, MD, reported that the 150- and 300-mg doses of solriamfetol were effective in improving both sleep latency, as measured with maintenance of wakefulness test (MWT), and Epworth Sleepiness Scale (ESS) scores in both cataplexic (n = 117) and noncataplexic (n = 114) narcolepsy. The objective of the study was to reevaluate the safety of solriamfetol in these narcoleptic subgroups from the phase 3 trial, said Dr. Dauvilliers, a faculty member at Centre Hospitalier Universitaire de Montpellier (France).

In patients with cataplexy, the 150-mg dose increased sleep latency from a baseline of 0 to 7.9 after a week and sustained that for 12 weeks; doubling the dose raised that to 10.3 after a week, reaching 10.7 in week 12. Gains were even more dramatic in noncataplexic patients, with the 150-mg dose improving sleep latency to 12.8 at week 1 and 11.6 at week 12, and the 300-mg dose resulting in a gain of 16.8 after a week, trailing off to 13.8 after 12 weeks, Dr. Dauvilliers said.

The study also evaluated ESS scores for three dosing levels – 75, 150, and 300 mg – plus placebo. In the group with cataplexy, ESS at week 12 improved from a baseline of 0 to –3.1, –5.6, and –6.3 for the three dosing groups, respectively, vs. –1.8 for placebo. In the noncataplexy patients with narcolepsy, the improvements in ESS at week 12 were –4.5, –5.2 and –6.4, respectively, vs. –1.5 for placebo.

“At 150 mg and 300 mg, solriamfetol seems to be very effective in treating excessive sleepiness with narcolepsy, with the same efficacy in the group with and without cataplexy – with efficacy even after just 1 week of treatment,” Dr. Dauvilliers said.

Atul Malhotra, MD, and his coresearchers investigated the long-term safety and efficacy of solriamfetol out to 42 weeks in patients with narcolepsy or OSA who completed previous clinical trials, which were 6- and 12-week trials. The study involved an open-label phase from weeks 14 to 27, a 2-week randomized withdrawal phase and then safety follow-up after week 40. In the open-label phase, ESS scores for the overall treatment group (n = 519) improved from 15.9 at baseline to 8.3 at week 40, with variation between the OSA (n = 333) and narcolepsy (n = 186) groups: from 15.2 at baseline to 6.5 at week 40 for the former and from 17.3 to 11.4 for the latter.

In the randomized withdrawal phase, ESS scores for those on solriamfetol (n = 139) migrated upward from 7.3 to 8.5 – but for the placebo group (n = 141) ESS rose from 7.8 to 12.6, a difference of 3.7 favoring the treatment group, said Dr. Malhotra, chief of pulmonary and critical care medicine and the Kenneth M. Moser Professor in the department of medicine, University of California San Diego, La Jolla. Most patients in the placebo group had worsening of symptoms based on global impression of change – 64.5% vs. 28.2% in the treatment group in the self-reported cohort, and 63.8% vs. 28.7% in the clinician-evaluated cohort.

SOURCE: Dauvilliers Y et al. Abstract 0619; Malhotra A et al. Abstract 0620; Emsellem H et al. Abstract 0621; Schweitzer PK et al. Abstract 0622. Presented at Sleep 2018.

BALTIMORE – Multiple studies based on phase 3 clinical trials of the investigational drug solriamfetol have found that it may be effective for improving next-day wakefulness and work productivity in people with narcolepsy and obstructive sleep apnea, and that the drug can maintain its effect throughout the day as well as for up to 6 months, investigators reported at the annual meeting of the Associated Professional Sleep Societies.

Solriamfetol, developed by Jazz Pharmaceuticals, is the subject of a new drug application accepted by the Food and Drug Administration in March of 2018 for the treatment of excessive sleepiness due to narcolepsy or obstructive sleep apnea (OSA). Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor.

The drug was the subject of four different studies presented at SLEEP 2018 that drilled down into its effect on specific aspects of narcolepsy or OSA, or both. One study explored results in narcoleptic patients with and without cataplexy. Another study investigated the drug’s maintenance of efficacy after 6 months of treatment. A third study looked at the drug’s impact on next-day function, work productivity, and quality of life in patients with narcolepsy. And the fourth study researched how solriamfetol helped maintain wakefulness throughout the day.

Yves Dauvilliers, MD, reported that the 150- and 300-mg doses of solriamfetol were effective in improving both sleep latency, as measured with maintenance of wakefulness test (MWT), and Epworth Sleepiness Scale (ESS) scores in both cataplexic (n = 117) and noncataplexic (n = 114) narcolepsy. The objective of the study was to reevaluate the safety of solriamfetol in these narcoleptic subgroups from the phase 3 trial, said Dr. Dauvilliers, a faculty member at Centre Hospitalier Universitaire de Montpellier (France).

In patients with cataplexy, the 150-mg dose increased sleep latency from a baseline of 0 to 7.9 after a week and sustained that for 12 weeks; doubling the dose raised that to 10.3 after a week, reaching 10.7 in week 12. Gains were even more dramatic in noncataplexic patients, with the 150-mg dose improving sleep latency to 12.8 at week 1 and 11.6 at week 12, and the 300-mg dose resulting in a gain of 16.8 after a week, trailing off to 13.8 after 12 weeks, Dr. Dauvilliers said.

The study also evaluated ESS scores for three dosing levels – 75, 150, and 300 mg – plus placebo. In the group with cataplexy, ESS at week 12 improved from a baseline of 0 to –3.1, –5.6, and –6.3 for the three dosing groups, respectively, vs. –1.8 for placebo. In the noncataplexy patients with narcolepsy, the improvements in ESS at week 12 were –4.5, –5.2 and –6.4, respectively, vs. –1.5 for placebo.

“At 150 mg and 300 mg, solriamfetol seems to be very effective in treating excessive sleepiness with narcolepsy, with the same efficacy in the group with and without cataplexy – with efficacy even after just 1 week of treatment,” Dr. Dauvilliers said.

Atul Malhotra, MD, and his coresearchers investigated the long-term safety and efficacy of solriamfetol out to 42 weeks in patients with narcolepsy or OSA who completed previous clinical trials, which were 6- and 12-week trials. The study involved an open-label phase from weeks 14 to 27, a 2-week randomized withdrawal phase and then safety follow-up after week 40. In the open-label phase, ESS scores for the overall treatment group (n = 519) improved from 15.9 at baseline to 8.3 at week 40, with variation between the OSA (n = 333) and narcolepsy (n = 186) groups: from 15.2 at baseline to 6.5 at week 40 for the former and from 17.3 to 11.4 for the latter.

In the randomized withdrawal phase, ESS scores for those on solriamfetol (n = 139) migrated upward from 7.3 to 8.5 – but for the placebo group (n = 141) ESS rose from 7.8 to 12.6, a difference of 3.7 favoring the treatment group, said Dr. Malhotra, chief of pulmonary and critical care medicine and the Kenneth M. Moser Professor in the department of medicine, University of California San Diego, La Jolla. Most patients in the placebo group had worsening of symptoms based on global impression of change – 64.5% vs. 28.2% in the treatment group in the self-reported cohort, and 63.8% vs. 28.7% in the clinician-evaluated cohort.

SOURCE: Dauvilliers Y et al. Abstract 0619; Malhotra A et al. Abstract 0620; Emsellem H et al. Abstract 0621; Schweitzer PK et al. Abstract 0622. Presented at Sleep 2018.

BALTIMORE – Multiple studies based on phase 3 clinical trials of the investigational drug solriamfetol have found that it may be effective for improving next-day wakefulness and work productivity in people with narcolepsy and obstructive sleep apnea, and that the drug can maintain its effect throughout the day as well as for up to 6 months, investigators reported at the annual meeting of the Associated Professional Sleep Societies.

Solriamfetol, developed by Jazz Pharmaceuticals, is the subject of a new drug application accepted by the Food and Drug Administration in March of 2018 for the treatment of excessive sleepiness due to narcolepsy or obstructive sleep apnea (OSA). Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor.

The drug was the subject of four different studies presented at SLEEP 2018 that drilled down into its effect on specific aspects of narcolepsy or OSA, or both. One study explored results in narcoleptic patients with and without cataplexy. Another study investigated the drug’s maintenance of efficacy after 6 months of treatment. A third study looked at the drug’s impact on next-day function, work productivity, and quality of life in patients with narcolepsy. And the fourth study researched how solriamfetol helped maintain wakefulness throughout the day.

Yves Dauvilliers, MD, reported that the 150- and 300-mg doses of solriamfetol were effective in improving both sleep latency, as measured with maintenance of wakefulness test (MWT), and Epworth Sleepiness Scale (ESS) scores in both cataplexic (n = 117) and noncataplexic (n = 114) narcolepsy. The objective of the study was to reevaluate the safety of solriamfetol in these narcoleptic subgroups from the phase 3 trial, said Dr. Dauvilliers, a faculty member at Centre Hospitalier Universitaire de Montpellier (France).

In patients with cataplexy, the 150-mg dose increased sleep latency from a baseline of 0 to 7.9 after a week and sustained that for 12 weeks; doubling the dose raised that to 10.3 after a week, reaching 10.7 in week 12. Gains were even more dramatic in noncataplexic patients, with the 150-mg dose improving sleep latency to 12.8 at week 1 and 11.6 at week 12, and the 300-mg dose resulting in a gain of 16.8 after a week, trailing off to 13.8 after 12 weeks, Dr. Dauvilliers said.

The study also evaluated ESS scores for three dosing levels – 75, 150, and 300 mg – plus placebo. In the group with cataplexy, ESS at week 12 improved from a baseline of 0 to –3.1, –5.6, and –6.3 for the three dosing groups, respectively, vs. –1.8 for placebo. In the noncataplexy patients with narcolepsy, the improvements in ESS at week 12 were –4.5, –5.2 and –6.4, respectively, vs. –1.5 for placebo.

“At 150 mg and 300 mg, solriamfetol seems to be very effective in treating excessive sleepiness with narcolepsy, with the same efficacy in the group with and without cataplexy – with efficacy even after just 1 week of treatment,” Dr. Dauvilliers said.

Atul Malhotra, MD, and his coresearchers investigated the long-term safety and efficacy of solriamfetol out to 42 weeks in patients with narcolepsy or OSA who completed previous clinical trials, which were 6- and 12-week trials. The study involved an open-label phase from weeks 14 to 27, a 2-week randomized withdrawal phase and then safety follow-up after week 40. In the open-label phase, ESS scores for the overall treatment group (n = 519) improved from 15.9 at baseline to 8.3 at week 40, with variation between the OSA (n = 333) and narcolepsy (n = 186) groups: from 15.2 at baseline to 6.5 at week 40 for the former and from 17.3 to 11.4 for the latter.

In the randomized withdrawal phase, ESS scores for those on solriamfetol (n = 139) migrated upward from 7.3 to 8.5 – but for the placebo group (n = 141) ESS rose from 7.8 to 12.6, a difference of 3.7 favoring the treatment group, said Dr. Malhotra, chief of pulmonary and critical care medicine and the Kenneth M. Moser Professor in the department of medicine, University of California San Diego, La Jolla. Most patients in the placebo group had worsening of symptoms based on global impression of change – 64.5% vs. 28.2% in the treatment group in the self-reported cohort, and 63.8% vs. 28.7% in the clinician-evaluated cohort.

SOURCE: Dauvilliers Y et al. Abstract 0619; Malhotra A et al. Abstract 0620; Emsellem H et al. Abstract 0621; Schweitzer PK et al. Abstract 0622. Presented at Sleep 2018.

ABSTRACT

An increasing interest focuses on the rates and risk factors for hospital readmission. However, little is known regarding the readmission following total shoulder arthroplasty (TSA). This study aims to determine the rates, risk factors, and reasons for hospital readmission following primary TSA. Patients undergoing TSA (anatomic or reverse) as part of the American College of Surgeons National Surgical Quality Improvement Program in 2011 to 2013 were identified. The rate of unplanned readmission to the hospital within 30 postoperative days was characterized. Using multivariate regression, demographic and comorbidity factors were tested for independent association with readmission. Finally, the reasons for readmission were characterized. A total of 3627 patients were identified. Among the admitted patients, 93 (2.56%) were readmitted within 30 days of surgery. The independent risk factors for readmission included old age (for age 60-69 years, relative risk [RR] = 1.6; for age 70-79 years, RR = 2.3; for age ≥80 years, RR = 23.1; P = .042), male sex (RR = 1.6, P = .025), anemia (RR = 1.9, P = .005), and dependent functional status (RR = 2.8, P = .012). The reasons for readmission were available for 84 of the 93 readmitted patients. The most common reasons for readmission comprised pneumonia (14 cases, 16.7%), dislocation (7 cases, 8.3%), pulmonary embolism (7 cases, 8.3%), and surgical site infection (6 cases, 7.1%). Unplanned readmission occurs following about 1 in 40 cases of TSA. The most common causes of readmission include pneumonia, dislocation, pulmonary embolism, and surgical site infection. Patients with old age, male sex, anemia, and dependent functional status are at higher risk for readmission and should be counseled and monitored accordingly.

Continue to: Total shoulder arthroplasty...

Total shoulder arthroplasty (TSA) is performed with increasing frequency in the United States and is considered to be cost-effective.^1-4 Following the procedure, patients generally achieve shoulder function and pain relief.^5-8 Despite the success of the procedure, the growing literature on TSA has also reported rates of complications between 3.6% and 25% of the treated patients.^9-16

In recent years, an increasing interest has focused on the rates and risk factors for unplanned hospital readmissions; these variables may not only reflect the quality of patient care but also result in considerable costs to the healthcare system. For instance, among Medicare patients, readmissions within 30 days of discharge occur in almost 20% of cases, costing $17.4 billion per year.¹⁷ Readmission rates increasingly factor into hospital performance metrics and reimbursement, including the Hospital Readmissions Reduction Program of the Patient Protection and Affordable Care Act that reduces Centers for Medicare and Medicaid Services payments to hospitals with high 30-day readmission rates.¹⁸

To date, only a few studies have evaluated readmission following TSA, with 30- to 90-day readmission rates ranging from 4.5% to 7.3%.^19-23 These studies comprised single institution series^20,22 and analyses of administrative databases.^19,21,23 Most studies have shown that readmission occurs more often for medical than surgical reasons, with surgical reasons most commonly including infection and dislocation.^19-23 However, only limited analyses have been conducted regarding risk factors for readmission.^21,23 To date and to our knowledge, no study has investigated reasons for readmission following TSA using nationwide data.

This study aims to determine the rates, risk factors, and reasons for hospital readmission following primary TSA in the United States using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database.

METHODS

DATA SOURCE

The NSQIP database was utilized to address the study purpose. NSQIP is a nationwide prospective surgical registry established by the American College of Surgeons and reports data from academic and community hospitals across the United States.²⁴ Patients undertaking surgery at these centers are followed by the surgical clinical reviewers at the participating NSQIP sites prospectively for 30 days following the procedure to record complications including readmission. Preoperative and surgical data, such as demographics, medical comorbid diseases, and operative time, are also included. Previous studies have analyzed the complications of various orthopedic surgeries using the NSQIP data.^14,16,25-30

DATA COLLECTION

We retrospectively identified from NSQIP the patients who underwent primary TSA (anatomic or reverse) in 2013 to 2014. The timeframe 2013 to 2014 was used because NSQIP only began recording reasons for readmission in 2013. The inclusion criteria were as follows: Current Procedural Terminology (CPT) code for TSA (23472); preoperative diagnosis according to the International Classification of Diseases, Ninth Revision (ICD-9) codes 714.0, 715.11, 715.31, 715.91, 715.21, 715.89, 716.xx 718.xx, 719.xx, 726.x, 727.xx, and 733.41 (where x is a wild card digit); and no missing demographic, comorbidity, or outcome data. Anatomic and reverse TSA were analyzed together because they share the same CPT code, and the NSQIP database prevents searching by the ICD-9 procedure code.

The rate of unplanned readmission to the hospital within 30 postoperative days was characterized. The reasons for readmission in this 30-day period were only available in 2013 and were determined using the ICD-9 diagnosis codes. Patient demographics were recorded for use in identifying potential risk factors for readmission; the demographic data included sex, age, smoking status, body mass index (BMI), and comorbidities, including end-stage renal disease, dyspnea on exertion, congestive heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD).

Continue to: Statistical analysis...

STATISTICAL ANALYSIS

Statistical analyses were performed using Stata version 13.1 (StataCorp). First, using bivariate and multivariate regression, demographic and comorbidity factors were tested for independent association with readmission to the hospital within 30 days of surgery. Second, among the readmitted patients, the reasons for readmission were tabulated. Of note, the reasons for readmission were only documented for the procedures performed in 2013. All tests were 2-tailed and conducted at an α level of 0.05.

RESTULTS

A total of 3627 TSA patients were identified. The mean age (± standard deviation) was 69.4 ± 9.5 years, 55.8% of patients were female, and mean BMI was 30.1 ± 7.0 years. Table 1 provides the additional demographic data. Of the 3627 included patients, 93 (2.56%) were readmitted within 30 days of surgery. The 95% confidence interval for the estimated rate of readmission reached 2.05% to 3.08%.

Table 1. Patient Population

Abbreviation: COPD, chronic obstructive pulmonary disease.

In the bivariate analyses (Table 2), the following factors were positively associated readmission: older age (60-69 years, relative risk [RR] = 1.6; 70-79 years, RR = 2.2; ≥80 years, RR = 3.3; P = .011), dependent functional status (RR = 2.9, P = .008), and anemia (RR = 2.2, P < .001).

Table 2. Bivariate Analysis of Risk Factors for Readmission

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; RR, relative risk.

In the multivariate analyses (Table 3), the following factors were independent risk factors for readmission: older age (60-69 years, RR = 1.6; 70-79 years, RR = 2.3; ≥80 years, RR = 3.1; P =.027), male sex (RR = 1.6, P = .025), anemia (RR = 1.9, P = .005), and dependent functional status (RR = 2.8, P = .012). Interestingly, readmission showed no independent association with diabetes, dyspnea on exertion, BMI, COPD, hypertension, or current smoking status (P > .05 for each).

Table 3. Independent Risk Factors for Readmission on Multivariate Analysis

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; RR, relative risk.

Continue to: Table 4...

The reasons for readmission were available for 84 of the 93 readmitted patients. The most common reasons for readmission included pneumonia (14 cases, 16.7%), dislocation (7 cases, 8.3%), pulmonary embolism (7 cases, 8.3%), and surgical site infection (6 cases, 7.1%) (Table 4).

Table 4. Reasons for Readmission

DISCUSSION

Our analysis of 3042 TSAs from the NSQIP database suggests that unplanned readmission to the hospital occurs following about 1 in 40 cases of TSA. The study also suggests that the most common reasons for readmission encompass pneumonia, dislocation, pulmonary embolism, and surgical site infection. Old age, male sex, anemia, and dependent functional status serve as risk factors for readmission, and patients with such factors should be counseled and monitored accordingly.

In recent years, an increasing emphasis has centered on reducing rates of hospital readmission, with programs such as the Hospital Readmissions Reduction Program of the Affordable Care Act cutting reimbursements for hospitals with high 30-day readmission rates.^17,18 To date, only a few studies have evaluated the reasons for readmission and readmission rates for TSA.^19-23 Initial reports consisted of single-institution TSA registry reviews. For example, Mahoney and colleagues²⁰ retrospectively evaluated shoulder arthroplasty procedures at their institution to document the readmission rates, finding a 5.9% readmission rate at 30 days. Readmission occurred more frequently in the first 30 days following discharge than in the 30- to 90-day period, with the most common reasons for readmission including medical complications, infection, and dislocation. Streubel and colleagues²² evaluated reoperation rates from their institution’s TSA registry, finding a 0.6% reoperation rate for primary TSA at 30 days and 1.5% for revision TSA. Instability and infection were the most common indications for reoperation. Our findings confirm these single-institution results and demonstrate their application to a nationwide sample of TSA, not just to high-volume academic centers. We similarly observed that dislocation, surgical site infection, and medical complications (mostly pneumonia and pulmonary embolism) were common causes of readmission, and that the 30-day readmission rate was about 1 in 40.

Several authors have since used statewide databases to analyze and determine risk factors for readmission following TSA. Lyman and colleagues¹⁹ used the New York State Database to show that higher hospital TSA surgical volume was associated with a lower rate of readmission when age and comorbidities were controlled for in a multivariate model. Old age was also associated with an increased readmission rate in their multivariate analysis, but comorbidities (as measured by the Charlson comorbidity index) presented a nonsignificant associative trend. These authors opted not to determine specific causes of readmission. Schairer and colleagues²¹ used State Inpatient Databases from 7 states, finding a 90-day readmission rate of 7.3%, 82% of which were due to medical complications and 18% of which were due to surgical complications (mostly infection and dislocation). Their multivariate regression revealed that male sex, reverse TSA, Medicaid insurance, patients discharged to inpatient rehabilitation or nursing facilities, medical comorbidities, and low-volume TSA hospitals were associated with readmission. Zhang and colleagues²³ used the same source to show that the 90-day readmission rate reached 14% for surgically treated proximal humerus fractures and higher for patients who underwent open reduction internal fixation, were female, were African American, were discharged to a nursing facility, possessed Medicaid insurance, or experienced medical comorbidities. Most recently, Basques and colleagues³¹ analyzed 1505 TSA cases from 2011 and 2012 in the NSQIP database, finding a 3.3% rate of readmission, with heart disease and hypertension as risk factors for readmission. Although the limitations of the NSQIP database prevented us from analyzing surgeon and hospital TSA volume or reverse vs anatomic TSA, our results confirm that the findings from statewide database studies apply to the United States nationwide NSQIP database. Old patient age, male sex, and medical comorbidities (anemia and dependent functional status) are independent risk factors for TSA readmission. We identified pneumonia, dislocation, pulmonary embolism, and surgical site infection as the most common reasons for readmission.

This study features several limitations that should be considered when interpreting the results. Anatomic and reverse TSA share a CPT code and were not separated using NSQIP data. A number of studies have reported that reverse TSA may place patients at higher risk for readmission;^20,21 however, confounding by other patient factors could play a role in this finding. The 30-day timeframe for readmission is another potential limitation; however, this timeframe is frequently used in other studies and is the relevant timeframe for the reduced reimbursement penalties from the Hospital Readmissions Reduction Program of the Affordable Care Act.¹⁸ Furthermore, the NSQIP database contains no information on surgeon or hospital TSA volume, which is a result of safeguards for patient and provider privacy. Additionally, readmission data were only available for 2011 to 2013, with causes of readmission only present in 2013. Although provided with such current information, we cannot analyze readmission trends over time, such as in response to the Affordable Care Act of 2010. Finally, although NSQIP surgical clinical reviewers strive to identify readmissions to other hospitals during their reviews of outpatient medical records, proportions of these readmissions are possibly missed. Therefore, our 30-day readmission rate may slightly underestimate the true rate.

Despite these limitations, the NSQIP database offers a unique opportunity to examine risk factors and reasons for readmission following TSA. The prior literature on readmission following TSA stemmed either from limited samples or administrative data, which feature known limitations.³² By utilizing a large, prospective, non-administrative, nationwide sample, our findings are probably both more reliable and generalizable to the country as a whole.

CONCLUSION

Unplanned readmission occurs following about 1 in 40 cases of TSA. The most common causes of readmission include pneumonia, dislocation, pulmonary embolism, and surgical site infection. Patients with old age, male sex, anemia, and dependent functional status are at a higher risk for readmission and should be counseled and monitored accordingly.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

An increasing interest focuses on the rates and risk factors for hospital readmission. However, little is known regarding the readmission following total shoulder arthroplasty (TSA). This study aims to determine the rates, risk factors, and reasons for hospital readmission following primary TSA. Patients undergoing TSA (anatomic or reverse) as part of the American College of Surgeons National Surgical Quality Improvement Program in 2011 to 2013 were identified. The rate of unplanned readmission to the hospital within 30 postoperative days was characterized. Using multivariate regression, demographic and comorbidity factors were tested for independent association with readmission. Finally, the reasons for readmission were characterized. A total of 3627 patients were identified. Among the admitted patients, 93 (2.56%) were readmitted within 30 days of surgery. The independent risk factors for readmission included old age (for age 60-69 years, relative risk [RR] = 1.6; for age 70-79 years, RR = 2.3; for age ≥80 years, RR = 23.1; P = .042), male sex (RR = 1.6, P = .025), anemia (RR = 1.9, P = .005), and dependent functional status (RR = 2.8, P = .012). The reasons for readmission were available for 84 of the 93 readmitted patients. The most common reasons for readmission comprised pneumonia (14 cases, 16.7%), dislocation (7 cases, 8.3%), pulmonary embolism (7 cases, 8.3%), and surgical site infection (6 cases, 7.1%). Unplanned readmission occurs following about 1 in 40 cases of TSA. The most common causes of readmission include pneumonia, dislocation, pulmonary embolism, and surgical site infection. Patients with old age, male sex, anemia, and dependent functional status are at higher risk for readmission and should be counseled and monitored accordingly.

Continue to: Total shoulder arthroplasty...

Total shoulder arthroplasty (TSA) is performed with increasing frequency in the United States and is considered to be cost-effective.^1-4 Following the procedure, patients generally achieve shoulder function and pain relief.^5-8 Despite the success of the procedure, the growing literature on TSA has also reported rates of complications between 3.6% and 25% of the treated patients.^9-16

In recent years, an increasing interest has focused on the rates and risk factors for unplanned hospital readmissions; these variables may not only reflect the quality of patient care but also result in considerable costs to the healthcare system. For instance, among Medicare patients, readmissions within 30 days of discharge occur in almost 20% of cases, costing $17.4 billion per year.¹⁷ Readmission rates increasingly factor into hospital performance metrics and reimbursement, including the Hospital Readmissions Reduction Program of the Patient Protection and Affordable Care Act that reduces Centers for Medicare and Medicaid Services payments to hospitals with high 30-day readmission rates.¹⁸

To date, only a few studies have evaluated readmission following TSA, with 30- to 90-day readmission rates ranging from 4.5% to 7.3%.^19-23 These studies comprised single institution series^20,22 and analyses of administrative databases.^19,21,23 Most studies have shown that readmission occurs more often for medical than surgical reasons, with surgical reasons most commonly including infection and dislocation.^19-23 However, only limited analyses have been conducted regarding risk factors for readmission.^21,23 To date and to our knowledge, no study has investigated reasons for readmission following TSA using nationwide data.

This study aims to determine the rates, risk factors, and reasons for hospital readmission following primary TSA in the United States using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database.

METHODS

DATA SOURCE

The NSQIP database was utilized to address the study purpose. NSQIP is a nationwide prospective surgical registry established by the American College of Surgeons and reports data from academic and community hospitals across the United States.²⁴ Patients undertaking surgery at these centers are followed by the surgical clinical reviewers at the participating NSQIP sites prospectively for 30 days following the procedure to record complications including readmission. Preoperative and surgical data, such as demographics, medical comorbid diseases, and operative time, are also included. Previous studies have analyzed the complications of various orthopedic surgeries using the NSQIP data.^14,16,25-30

DATA COLLECTION

We retrospectively identified from NSQIP the patients who underwent primary TSA (anatomic or reverse) in 2013 to 2014. The timeframe 2013 to 2014 was used because NSQIP only began recording reasons for readmission in 2013. The inclusion criteria were as follows: Current Procedural Terminology (CPT) code for TSA (23472); preoperative diagnosis according to the International Classification of Diseases, Ninth Revision (ICD-9) codes 714.0, 715.11, 715.31, 715.91, 715.21, 715.89, 716.xx 718.xx, 719.xx, 726.x, 727.xx, and 733.41 (where x is a wild card digit); and no missing demographic, comorbidity, or outcome data. Anatomic and reverse TSA were analyzed together because they share the same CPT code, and the NSQIP database prevents searching by the ICD-9 procedure code.

The rate of unplanned readmission to the hospital within 30 postoperative days was characterized. The reasons for readmission in this 30-day period were only available in 2013 and were determined using the ICD-9 diagnosis codes. Patient demographics were recorded for use in identifying potential risk factors for readmission; the demographic data included sex, age, smoking status, body mass index (BMI), and comorbidities, including end-stage renal disease, dyspnea on exertion, congestive heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD).

Continue to: Statistical analysis...

STATISTICAL ANALYSIS

Statistical analyses were performed using Stata version 13.1 (StataCorp). First, using bivariate and multivariate regression, demographic and comorbidity factors were tested for independent association with readmission to the hospital within 30 days of surgery. Second, among the readmitted patients, the reasons for readmission were tabulated. Of note, the reasons for readmission were only documented for the procedures performed in 2013. All tests were 2-tailed and conducted at an α level of 0.05.

RESTULTS

A total of 3627 TSA patients were identified. The mean age (± standard deviation) was 69.4 ± 9.5 years, 55.8% of patients were female, and mean BMI was 30.1 ± 7.0 years. Table 1 provides the additional demographic data. Of the 3627 included patients, 93 (2.56%) were readmitted within 30 days of surgery. The 95% confidence interval for the estimated rate of readmission reached 2.05% to 3.08%.

Table 1. Patient Population

Abbreviation: COPD, chronic obstructive pulmonary disease.

In the bivariate analyses (Table 2), the following factors were positively associated readmission: older age (60-69 years, relative risk [RR] = 1.6; 70-79 years, RR = 2.2; ≥80 years, RR = 3.3; P = .011), dependent functional status (RR = 2.9, P = .008), and anemia (RR = 2.2, P < .001).

Table 2. Bivariate Analysis of Risk Factors for Readmission

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; RR, relative risk.

In the multivariate analyses (Table 3), the following factors were independent risk factors for readmission: older age (60-69 years, RR = 1.6; 70-79 years, RR = 2.3; ≥80 years, RR = 3.1; P =.027), male sex (RR = 1.6, P = .025), anemia (RR = 1.9, P = .005), and dependent functional status (RR = 2.8, P = .012). Interestingly, readmission showed no independent association with diabetes, dyspnea on exertion, BMI, COPD, hypertension, or current smoking status (P > .05 for each).

Table 3. Independent Risk Factors for Readmission on Multivariate Analysis

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; RR, relative risk.

Continue to: Table 4...

The reasons for readmission were available for 84 of the 93 readmitted patients. The most common reasons for readmission included pneumonia (14 cases, 16.7%), dislocation (7 cases, 8.3%), pulmonary embolism (7 cases, 8.3%), and surgical site infection (6 cases, 7.1%) (Table 4).

Table 4. Reasons for Readmission

DISCUSSION

Our analysis of 3042 TSAs from the NSQIP database suggests that unplanned readmission to the hospital occurs following about 1 in 40 cases of TSA. The study also suggests that the most common reasons for readmission encompass pneumonia, dislocation, pulmonary embolism, and surgical site infection. Old age, male sex, anemia, and dependent functional status serve as risk factors for readmission, and patients with such factors should be counseled and monitored accordingly.

In recent years, an increasing emphasis has centered on reducing rates of hospital readmission, with programs such as the Hospital Readmissions Reduction Program of the Affordable Care Act cutting reimbursements for hospitals with high 30-day readmission rates.^17,18 To date, only a few studies have evaluated the reasons for readmission and readmission rates for TSA.^19-23 Initial reports consisted of single-institution TSA registry reviews. For example, Mahoney and colleagues²⁰ retrospectively evaluated shoulder arthroplasty procedures at their institution to document the readmission rates, finding a 5.9% readmission rate at 30 days. Readmission occurred more frequently in the first 30 days following discharge than in the 30- to 90-day period, with the most common reasons for readmission including medical complications, infection, and dislocation. Streubel and colleagues²² evaluated reoperation rates from their institution’s TSA registry, finding a 0.6% reoperation rate for primary TSA at 30 days and 1.5% for revision TSA. Instability and infection were the most common indications for reoperation. Our findings confirm these single-institution results and demonstrate their application to a nationwide sample of TSA, not just to high-volume academic centers. We similarly observed that dislocation, surgical site infection, and medical complications (mostly pneumonia and pulmonary embolism) were common causes of readmission, and that the 30-day readmission rate was about 1 in 40.

Several authors have since used statewide databases to analyze and determine risk factors for readmission following TSA. Lyman and colleagues¹⁹ used the New York State Database to show that higher hospital TSA surgical volume was associated with a lower rate of readmission when age and comorbidities were controlled for in a multivariate model. Old age was also associated with an increased readmission rate in their multivariate analysis, but comorbidities (as measured by the Charlson comorbidity index) presented a nonsignificant associative trend. These authors opted not to determine specific causes of readmission. Schairer and colleagues²¹ used State Inpatient Databases from 7 states, finding a 90-day readmission rate of 7.3%, 82% of which were due to medical complications and 18% of which were due to surgical complications (mostly infection and dislocation). Their multivariate regression revealed that male sex, reverse TSA, Medicaid insurance, patients discharged to inpatient rehabilitation or nursing facilities, medical comorbidities, and low-volume TSA hospitals were associated with readmission. Zhang and colleagues²³ used the same source to show that the 90-day readmission rate reached 14% for surgically treated proximal humerus fractures and higher for patients who underwent open reduction internal fixation, were female, were African American, were discharged to a nursing facility, possessed Medicaid insurance, or experienced medical comorbidities. Most recently, Basques and colleagues³¹ analyzed 1505 TSA cases from 2011 and 2012 in the NSQIP database, finding a 3.3% rate of readmission, with heart disease and hypertension as risk factors for readmission. Although the limitations of the NSQIP database prevented us from analyzing surgeon and hospital TSA volume or reverse vs anatomic TSA, our results confirm that the findings from statewide database studies apply to the United States nationwide NSQIP database. Old patient age, male sex, and medical comorbidities (anemia and dependent functional status) are independent risk factors for TSA readmission. We identified pneumonia, dislocation, pulmonary embolism, and surgical site infection as the most common reasons for readmission.

This study features several limitations that should be considered when interpreting the results. Anatomic and reverse TSA share a CPT code and were not separated using NSQIP data. A number of studies have reported that reverse TSA may place patients at higher risk for readmission;^20,21 however, confounding by other patient factors could play a role in this finding. The 30-day timeframe for readmission is another potential limitation; however, this timeframe is frequently used in other studies and is the relevant timeframe for the reduced reimbursement penalties from the Hospital Readmissions Reduction Program of the Affordable Care Act.¹⁸ Furthermore, the NSQIP database contains no information on surgeon or hospital TSA volume, which is a result of safeguards for patient and provider privacy. Additionally, readmission data were only available for 2011 to 2013, with causes of readmission only present in 2013. Although provided with such current information, we cannot analyze readmission trends over time, such as in response to the Affordable Care Act of 2010. Finally, although NSQIP surgical clinical reviewers strive to identify readmissions to other hospitals during their reviews of outpatient medical records, proportions of these readmissions are possibly missed. Therefore, our 30-day readmission rate may slightly underestimate the true rate.

Despite these limitations, the NSQIP database offers a unique opportunity to examine risk factors and reasons for readmission following TSA. The prior literature on readmission following TSA stemmed either from limited samples or administrative data, which feature known limitations.³² By utilizing a large, prospective, non-administrative, nationwide sample, our findings are probably both more reliable and generalizable to the country as a whole.

CONCLUSION

Unplanned readmission occurs following about 1 in 40 cases of TSA. The most common causes of readmission include pneumonia, dislocation, pulmonary embolism, and surgical site infection. Patients with old age, male sex, anemia, and dependent functional status are at a higher risk for readmission and should be counseled and monitored accordingly.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

An increasing interest focuses on the rates and risk factors for hospital readmission. However, little is known regarding the readmission following total shoulder arthroplasty (TSA). This study aims to determine the rates, risk factors, and reasons for hospital readmission following primary TSA. Patients undergoing TSA (anatomic or reverse) as part of the American College of Surgeons National Surgical Quality Improvement Program in 2011 to 2013 were identified. The rate of unplanned readmission to the hospital within 30 postoperative days was characterized. Using multivariate regression, demographic and comorbidity factors were tested for independent association with readmission. Finally, the reasons for readmission were characterized. A total of 3627 patients were identified. Among the admitted patients, 93 (2.56%) were readmitted within 30 days of surgery. The independent risk factors for readmission included old age (for age 60-69 years, relative risk [RR] = 1.6; for age 70-79 years, RR = 2.3; for age ≥80 years, RR = 23.1; P = .042), male sex (RR = 1.6, P = .025), anemia (RR = 1.9, P = .005), and dependent functional status (RR = 2.8, P = .012). The reasons for readmission were available for 84 of the 93 readmitted patients. The most common reasons for readmission comprised pneumonia (14 cases, 16.7%), dislocation (7 cases, 8.3%), pulmonary embolism (7 cases, 8.3%), and surgical site infection (6 cases, 7.1%). Unplanned readmission occurs following about 1 in 40 cases of TSA. The most common causes of readmission include pneumonia, dislocation, pulmonary embolism, and surgical site infection. Patients with old age, male sex, anemia, and dependent functional status are at higher risk for readmission and should be counseled and monitored accordingly.

Continue to: Total shoulder arthroplasty...

Total shoulder arthroplasty (TSA) is performed with increasing frequency in the United States and is considered to be cost-effective.^1-4 Following the procedure, patients generally achieve shoulder function and pain relief.^5-8 Despite the success of the procedure, the growing literature on TSA has also reported rates of complications between 3.6% and 25% of the treated patients.^9-16

In recent years, an increasing interest has focused on the rates and risk factors for unplanned hospital readmissions; these variables may not only reflect the quality of patient care but also result in considerable costs to the healthcare system. For instance, among Medicare patients, readmissions within 30 days of discharge occur in almost 20% of cases, costing $17.4 billion per year.¹⁷ Readmission rates increasingly factor into hospital performance metrics and reimbursement, including the Hospital Readmissions Reduction Program of the Patient Protection and Affordable Care Act that reduces Centers for Medicare and Medicaid Services payments to hospitals with high 30-day readmission rates.¹⁸

To date, only a few studies have evaluated readmission following TSA, with 30- to 90-day readmission rates ranging from 4.5% to 7.3%.^19-23 These studies comprised single institution series^20,22 and analyses of administrative databases.^19,21,23 Most studies have shown that readmission occurs more often for medical than surgical reasons, with surgical reasons most commonly including infection and dislocation.^19-23 However, only limited analyses have been conducted regarding risk factors for readmission.^21,23 To date and to our knowledge, no study has investigated reasons for readmission following TSA using nationwide data.

This study aims to determine the rates, risk factors, and reasons for hospital readmission following primary TSA in the United States using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database.

METHODS

DATA SOURCE

The NSQIP database was utilized to address the study purpose. NSQIP is a nationwide prospective surgical registry established by the American College of Surgeons and reports data from academic and community hospitals across the United States.²⁴ Patients undertaking surgery at these centers are followed by the surgical clinical reviewers at the participating NSQIP sites prospectively for 30 days following the procedure to record complications including readmission. Preoperative and surgical data, such as demographics, medical comorbid diseases, and operative time, are also included. Previous studies have analyzed the complications of various orthopedic surgeries using the NSQIP data.^14,16,25-30

DATA COLLECTION

We retrospectively identified from NSQIP the patients who underwent primary TSA (anatomic or reverse) in 2013 to 2014. The timeframe 2013 to 2014 was used because NSQIP only began recording reasons for readmission in 2013. The inclusion criteria were as follows: Current Procedural Terminology (CPT) code for TSA (23472); preoperative diagnosis according to the International Classification of Diseases, Ninth Revision (ICD-9) codes 714.0, 715.11, 715.31, 715.91, 715.21, 715.89, 716.xx 718.xx, 719.xx, 726.x, 727.xx, and 733.41 (where x is a wild card digit); and no missing demographic, comorbidity, or outcome data. Anatomic and reverse TSA were analyzed together because they share the same CPT code, and the NSQIP database prevents searching by the ICD-9 procedure code.

The rate of unplanned readmission to the hospital within 30 postoperative days was characterized. The reasons for readmission in this 30-day period were only available in 2013 and were determined using the ICD-9 diagnosis codes. Patient demographics were recorded for use in identifying potential risk factors for readmission; the demographic data included sex, age, smoking status, body mass index (BMI), and comorbidities, including end-stage renal disease, dyspnea on exertion, congestive heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD).

Continue to: Statistical analysis...

STATISTICAL ANALYSIS

Statistical analyses were performed using Stata version 13.1 (StataCorp). First, using bivariate and multivariate regression, demographic and comorbidity factors were tested for independent association with readmission to the hospital within 30 days of surgery. Second, among the readmitted patients, the reasons for readmission were tabulated. Of note, the reasons for readmission were only documented for the procedures performed in 2013. All tests were 2-tailed and conducted at an α level of 0.05.

RESTULTS

A total of 3627 TSA patients were identified. The mean age (± standard deviation) was 69.4 ± 9.5 years, 55.8% of patients were female, and mean BMI was 30.1 ± 7.0 years. Table 1 provides the additional demographic data. Of the 3627 included patients, 93 (2.56%) were readmitted within 30 days of surgery. The 95% confidence interval for the estimated rate of readmission reached 2.05% to 3.08%.

Table 1. Patient Population

Abbreviation: COPD, chronic obstructive pulmonary disease.

In the bivariate analyses (Table 2), the following factors were positively associated readmission: older age (60-69 years, relative risk [RR] = 1.6; 70-79 years, RR = 2.2; ≥80 years, RR = 3.3; P = .011), dependent functional status (RR = 2.9, P = .008), and anemia (RR = 2.2, P < .001).

Table 2. Bivariate Analysis of Risk Factors for Readmission

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; RR, relative risk.

In the multivariate analyses (Table 3), the following factors were independent risk factors for readmission: older age (60-69 years, RR = 1.6; 70-79 years, RR = 2.3; ≥80 years, RR = 3.1; P =.027), male sex (RR = 1.6, P = .025), anemia (RR = 1.9, P = .005), and dependent functional status (RR = 2.8, P = .012). Interestingly, readmission showed no independent association with diabetes, dyspnea on exertion, BMI, COPD, hypertension, or current smoking status (P > .05 for each).

Table 3. Independent Risk Factors for Readmission on Multivariate Analysis

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; RR, relative risk.

Continue to: Table 4...

The reasons for readmission were available for 84 of the 93 readmitted patients. The most common reasons for readmission included pneumonia (14 cases, 16.7%), dislocation (7 cases, 8.3%), pulmonary embolism (7 cases, 8.3%), and surgical site infection (6 cases, 7.1%) (Table 4).

Table 4. Reasons for Readmission

DISCUSSION

Our analysis of 3042 TSAs from the NSQIP database suggests that unplanned readmission to the hospital occurs following about 1 in 40 cases of TSA. The study also suggests that the most common reasons for readmission encompass pneumonia, dislocation, pulmonary embolism, and surgical site infection. Old age, male sex, anemia, and dependent functional status serve as risk factors for readmission, and patients with such factors should be counseled and monitored accordingly.

In recent years, an increasing emphasis has centered on reducing rates of hospital readmission, with programs such as the Hospital Readmissions Reduction Program of the Affordable Care Act cutting reimbursements for hospitals with high 30-day readmission rates.^17,18 To date, only a few studies have evaluated the reasons for readmission and readmission rates for TSA.^19-23 Initial reports consisted of single-institution TSA registry reviews. For example, Mahoney and colleagues²⁰ retrospectively evaluated shoulder arthroplasty procedures at their institution to document the readmission rates, finding a 5.9% readmission rate at 30 days. Readmission occurred more frequently in the first 30 days following discharge than in the 30- to 90-day period, with the most common reasons for readmission including medical complications, infection, and dislocation. Streubel and colleagues²² evaluated reoperation rates from their institution’s TSA registry, finding a 0.6% reoperation rate for primary TSA at 30 days and 1.5% for revision TSA. Instability and infection were the most common indications for reoperation. Our findings confirm these single-institution results and demonstrate their application to a nationwide sample of TSA, not just to high-volume academic centers. We similarly observed that dislocation, surgical site infection, and medical complications (mostly pneumonia and pulmonary embolism) were common causes of readmission, and that the 30-day readmission rate was about 1 in 40.

Several authors have since used statewide databases to analyze and determine risk factors for readmission following TSA. Lyman and colleagues¹⁹ used the New York State Database to show that higher hospital TSA surgical volume was associated with a lower rate of readmission when age and comorbidities were controlled for in a multivariate model. Old age was also associated with an increased readmission rate in their multivariate analysis, but comorbidities (as measured by the Charlson comorbidity index) presented a nonsignificant associative trend. These authors opted not to determine specific causes of readmission. Schairer and colleagues²¹ used State Inpatient Databases from 7 states, finding a 90-day readmission rate of 7.3%, 82% of which were due to medical complications and 18% of which were due to surgical complications (mostly infection and dislocation). Their multivariate regression revealed that male sex, reverse TSA, Medicaid insurance, patients discharged to inpatient rehabilitation or nursing facilities, medical comorbidities, and low-volume TSA hospitals were associated with readmission. Zhang and colleagues²³ used the same source to show that the 90-day readmission rate reached 14% for surgically treated proximal humerus fractures and higher for patients who underwent open reduction internal fixation, were female, were African American, were discharged to a nursing facility, possessed Medicaid insurance, or experienced medical comorbidities. Most recently, Basques and colleagues³¹ analyzed 1505 TSA cases from 2011 and 2012 in the NSQIP database, finding a 3.3% rate of readmission, with heart disease and hypertension as risk factors for readmission. Although the limitations of the NSQIP database prevented us from analyzing surgeon and hospital TSA volume or reverse vs anatomic TSA, our results confirm that the findings from statewide database studies apply to the United States nationwide NSQIP database. Old patient age, male sex, and medical comorbidities (anemia and dependent functional status) are independent risk factors for TSA readmission. We identified pneumonia, dislocation, pulmonary embolism, and surgical site infection as the most common reasons for readmission.

This study features several limitations that should be considered when interpreting the results. Anatomic and reverse TSA share a CPT code and were not separated using NSQIP data. A number of studies have reported that reverse TSA may place patients at higher risk for readmission;^20,21 however, confounding by other patient factors could play a role in this finding. The 30-day timeframe for readmission is another potential limitation; however, this timeframe is frequently used in other studies and is the relevant timeframe for the reduced reimbursement penalties from the Hospital Readmissions Reduction Program of the Affordable Care Act.¹⁸ Furthermore, the NSQIP database contains no information on surgeon or hospital TSA volume, which is a result of safeguards for patient and provider privacy. Additionally, readmission data were only available for 2011 to 2013, with causes of readmission only present in 2013. Although provided with such current information, we cannot analyze readmission trends over time, such as in response to the Affordable Care Act of 2010. Finally, although NSQIP surgical clinical reviewers strive to identify readmissions to other hospitals during their reviews of outpatient medical records, proportions of these readmissions are possibly missed. Therefore, our 30-day readmission rate may slightly underestimate the true rate.

Despite these limitations, the NSQIP database offers a unique opportunity to examine risk factors and reasons for readmission following TSA. The prior literature on readmission following TSA stemmed either from limited samples or administrative data, which feature known limitations.³² By utilizing a large, prospective, non-administrative, nationwide sample, our findings are probably both more reliable and generalizable to the country as a whole.

CONCLUSION

Unplanned readmission occurs following about 1 in 40 cases of TSA. The most common causes of readmission include pneumonia, dislocation, pulmonary embolism, and surgical site infection. Patients with old age, male sex, anemia, and dependent functional status are at a higher risk for readmission and should be counseled and monitored accordingly.

This paper will be judged for the Resident Writer’s Award.

Vaccination costs surrounding Japanese encephalitis is high, according to an economic analysis presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

copyright itsmejust/Thinkstock

Vaccination costs surrounding Japanese encephalitis is high, according to an economic analysis presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

copyright itsmejust/Thinkstock

Vaccination costs surrounding Japanese encephalitis is high, according to an economic analysis presented at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

copyright itsmejust/Thinkstock

AMSTERDAM – Despite some “encouraging signs” seen in a cross-sectional study, it remains difficult to determine whether a patient with systemic lupus erythematosus (SLE) will respond to off-label rituximab therapy, according to David Isenberg, MD.

The presence of constitutional symptoms, which includes fatigue, at baseline were associated with a favorable response to rituximab at 6 months (odds ratio, 7.35; P = .01). Conversely, having more than one anti–extractable nuclear antigen (anti-ENA) antibody was associated with a worse response to rituximab at 12 months (OR, 0.33; P = .032).

“It’s not a cure for lupus, that’s obvious, but used at the appropriate time in the right sort of patients, it can be very helpful,” Dr. Isenberg said in an interview at the European Congress of Rheumatology. That’s both in terms of improving disease activity and reducing the use of glucocorticosteroids and immunosuppressive drugs, he noted.

“The great mystery, as with all drugs, is: Are there any markers which might tell us that the disease is going to do better with rituximab than perhaps with another form of medication, or is it just saying to us, ‘Whatever you do, it doesn’t make much difference’?” Dr. Isenberg said. He discussed the results of a study involving the first 121 patients treated with rituximab at his institution, University College London Hospital (UCLH); he noted this is one of the largest single-center cohorts of individuals with SLE who have used rituximab.

The aim of the study, which was presented at the congress by Hiurma Sánchez Pérez, MD, was therefore to try to find demographic, clinical, and serological markers that might help in predicting the response to rituximab in SLE patients.

Sara Freeman/MDedge News

SOURCE: Sánchez Pérez H and Isenberg D. Ann Rheum Dis. 2018;77(Suppl 2):177. EULAR 2018 Congress, Abstract OP0255.

AMSTERDAM – Despite some “encouraging signs” seen in a cross-sectional study, it remains difficult to determine whether a patient with systemic lupus erythematosus (SLE) will respond to off-label rituximab therapy, according to David Isenberg, MD.

The presence of constitutional symptoms, which includes fatigue, at baseline were associated with a favorable response to rituximab at 6 months (odds ratio, 7.35; P = .01). Conversely, having more than one anti–extractable nuclear antigen (anti-ENA) antibody was associated with a worse response to rituximab at 12 months (OR, 0.33; P = .032).

“It’s not a cure for lupus, that’s obvious, but used at the appropriate time in the right sort of patients, it can be very helpful,” Dr. Isenberg said in an interview at the European Congress of Rheumatology. That’s both in terms of improving disease activity and reducing the use of glucocorticosteroids and immunosuppressive drugs, he noted.

“The great mystery, as with all drugs, is: Are there any markers which might tell us that the disease is going to do better with rituximab than perhaps with another form of medication, or is it just saying to us, ‘Whatever you do, it doesn’t make much difference’?” Dr. Isenberg said. He discussed the results of a study involving the first 121 patients treated with rituximab at his institution, University College London Hospital (UCLH); he noted this is one of the largest single-center cohorts of individuals with SLE who have used rituximab.

The aim of the study, which was presented at the congress by Hiurma Sánchez Pérez, MD, was therefore to try to find demographic, clinical, and serological markers that might help in predicting the response to rituximab in SLE patients.

Sara Freeman/MDedge News

SOURCE: Sánchez Pérez H and Isenberg D. Ann Rheum Dis. 2018;77(Suppl 2):177. EULAR 2018 Congress, Abstract OP0255.

AMSTERDAM – Despite some “encouraging signs” seen in a cross-sectional study, it remains difficult to determine whether a patient with systemic lupus erythematosus (SLE) will respond to off-label rituximab therapy, according to David Isenberg, MD.

The presence of constitutional symptoms, which includes fatigue, at baseline were associated with a favorable response to rituximab at 6 months (odds ratio, 7.35; P = .01). Conversely, having more than one anti–extractable nuclear antigen (anti-ENA) antibody was associated with a worse response to rituximab at 12 months (OR, 0.33; P = .032).

“It’s not a cure for lupus, that’s obvious, but used at the appropriate time in the right sort of patients, it can be very helpful,” Dr. Isenberg said in an interview at the European Congress of Rheumatology. That’s both in terms of improving disease activity and reducing the use of glucocorticosteroids and immunosuppressive drugs, he noted.

“The great mystery, as with all drugs, is: Are there any markers which might tell us that the disease is going to do better with rituximab than perhaps with another form of medication, or is it just saying to us, ‘Whatever you do, it doesn’t make much difference’?” Dr. Isenberg said. He discussed the results of a study involving the first 121 patients treated with rituximab at his institution, University College London Hospital (UCLH); he noted this is one of the largest single-center cohorts of individuals with SLE who have used rituximab.

The aim of the study, which was presented at the congress by Hiurma Sánchez Pérez, MD, was therefore to try to find demographic, clinical, and serological markers that might help in predicting the response to rituximab in SLE patients.

Sara Freeman/MDedge News

SOURCE: Sánchez Pérez H and Isenberg D. Ann Rheum Dis. 2018;77(Suppl 2):177. EULAR 2018 Congress, Abstract OP0255.

Adults who use opioids are more likely to have “complicated health profiles and high levels of involvement in the criminal justice system” compared with adults who do not, according to a retrospective, cross-sectional analysis published July 6 in JAMA Network Open.

“The large proportion of individuals with opioid use disorders who have physical and mental health conditions and who contact the criminal justice system suggests that public health interventions to combat the opioid epidemic ... should coordinate treatment between the criminal justice and health care systems,” wrote Tyler N.A. Winkelman, MD, and his colleagues.

The investigators evaluated a representative sample of responses from 78,976 U.S. adults aged 18-64 who completed the 2015-2016 National Survey on Drug Use and Health, of which 31.3% reported use of prescription opioids, 4.3% reported misuse of opioids, 0.8% reported abuse of prescription opioids, and 0.4% reported heroin use.

The researchers also studied the health characteristics of each individual based on their level of opioid use, whether individuals used other substances in addition to prescription opioids, and the respondents’ recent and distant involvement in the criminal justice system, reported Dr. Winkelman, who is affiliated with the division of general internal medicine at Hennepin Healthcare in Minneapolis, and his colleagues.

After adjustment for health characteristic prevalence and co-occurring substance use across opioid use levels, compared with individuals who reported no opioid use, Dr. Winkelman and his associates found a higher prevalence of mental illness among individuals across four categories: prescription opioid use, prescription opioid misuse, prescription opioid use disorder, and heroin use. They also found a higher prevalence of self-reported chronic conditions such as diabetes, asthma, and high blood pressure across various levels of opioid use, compared with people who reported no opioid use.

Furthermore, Dr. Winkelman and his associates found that as the intensity of opioid use increased, individuals reported an increased prevalence of mild, moderate, and severe mental illness. Individuals who increased their intensity of opioid use also had a greater likelihood of co-occurring substance use with at least one other substance. For example, individuals who misused opioids or used heroin reported that they used tranquilizers or sedatives in more than 50% of cases. Of individuals who reported heroin use, 88.5% said they used prescription opioids within the past year, reported Dr. Winkelman, also a staff physician at the Adult Detention Center in Hennepin County, Minn., and his associates.

The researchers also found 22.4% of individuals (95% confidence interval, 21.7-23.1) who used prescription opioids, 33.2% of individuals who misused prescription opioids (95% CI, 30.9-35.6), 51.7% of individuals with prescription opioid use disorder (95% CI, 45.4-58.0), and 76.8% of individuals with heroin use (95% CI, 70.6-82.1) had any contact with the criminal justice system, compared with 15.9% (95% CI, 15.4-16.4) of individuals who did not report prescription opioid use.

“The overlap we found between involvement in the criminal justice system and opioid use suggests that access to opioid treatment within the criminal justice system is a critical public health issue,” the researchers wrote. They cited studies showing that strategies such as beginning or continuing methadone hydrochloride or buprenorphine hydrochloride during incarceration are tied to a reduction in postrelease mortality.

Among the limitations cited were the National Survey on Drug Use and Health’s cross-sectional design, which makes it difficult to determine whether opioid use preceded involvement in the criminal justice system, or vice versa.

Nevertheless, they said, the study provides the most comprehensive picture to date of the status across several domains of people who use opioids.

“Given the complex health and criminal justice profiles of individuals who use opioids, policy makers should carefully consider how changes to public health insurance programs and sentencing guidelines may aid or hinder a public health approach to the opioid epidemic,” wrote Dr. Winkelman and his colleagues.

Dr. Winkelman disclosed his affiliation with the Hennepin County detention center. Another author disclosed employment with the Colorado Permanente Medical Group and royalties from uptodate.com.

SOURCE: Winkelman TNA et al. JAMA Network Open. 2018 Jul 6. doi: 10.1001/jamanetworkopen.2018.0558.

Adults who use opioids are more likely to have “complicated health profiles and high levels of involvement in the criminal justice system” compared with adults who do not, according to a retrospective, cross-sectional analysis published July 6 in JAMA Network Open.

“The large proportion of individuals with opioid use disorders who have physical and mental health conditions and who contact the criminal justice system suggests that public health interventions to combat the opioid epidemic ... should coordinate treatment between the criminal justice and health care systems,” wrote Tyler N.A. Winkelman, MD, and his colleagues.

The investigators evaluated a representative sample of responses from 78,976 U.S. adults aged 18-64 who completed the 2015-2016 National Survey on Drug Use and Health, of which 31.3% reported use of prescription opioids, 4.3% reported misuse of opioids, 0.8% reported abuse of prescription opioids, and 0.4% reported heroin use.

The researchers also studied the health characteristics of each individual based on their level of opioid use, whether individuals used other substances in addition to prescription opioids, and the respondents’ recent and distant involvement in the criminal justice system, reported Dr. Winkelman, who is affiliated with the division of general internal medicine at Hennepin Healthcare in Minneapolis, and his colleagues.

After adjustment for health characteristic prevalence and co-occurring substance use across opioid use levels, compared with individuals who reported no opioid use, Dr. Winkelman and his associates found a higher prevalence of mental illness among individuals across four categories: prescription opioid use, prescription opioid misuse, prescription opioid use disorder, and heroin use. They also found a higher prevalence of self-reported chronic conditions such as diabetes, asthma, and high blood pressure across various levels of opioid use, compared with people who reported no opioid use.

Furthermore, Dr. Winkelman and his associates found that as the intensity of opioid use increased, individuals reported an increased prevalence of mild, moderate, and severe mental illness. Individuals who increased their intensity of opioid use also had a greater likelihood of co-occurring substance use with at least one other substance. For example, individuals who misused opioids or used heroin reported that they used tranquilizers or sedatives in more than 50% of cases. Of individuals who reported heroin use, 88.5% said they used prescription opioids within the past year, reported Dr. Winkelman, also a staff physician at the Adult Detention Center in Hennepin County, Minn., and his associates.

The researchers also found 22.4% of individuals (95% confidence interval, 21.7-23.1) who used prescription opioids, 33.2% of individuals who misused prescription opioids (95% CI, 30.9-35.6), 51.7% of individuals with prescription opioid use disorder (95% CI, 45.4-58.0), and 76.8% of individuals with heroin use (95% CI, 70.6-82.1) had any contact with the criminal justice system, compared with 15.9% (95% CI, 15.4-16.4) of individuals who did not report prescription opioid use.

“The overlap we found between involvement in the criminal justice system and opioid use suggests that access to opioid treatment within the criminal justice system is a critical public health issue,” the researchers wrote. They cited studies showing that strategies such as beginning or continuing methadone hydrochloride or buprenorphine hydrochloride during incarceration are tied to a reduction in postrelease mortality.

Among the limitations cited were the National Survey on Drug Use and Health’s cross-sectional design, which makes it difficult to determine whether opioid use preceded involvement in the criminal justice system, or vice versa.

Nevertheless, they said, the study provides the most comprehensive picture to date of the status across several domains of people who use opioids.

“Given the complex health and criminal justice profiles of individuals who use opioids, policy makers should carefully consider how changes to public health insurance programs and sentencing guidelines may aid or hinder a public health approach to the opioid epidemic,” wrote Dr. Winkelman and his colleagues.

Dr. Winkelman disclosed his affiliation with the Hennepin County detention center. Another author disclosed employment with the Colorado Permanente Medical Group and royalties from uptodate.com.

SOURCE: Winkelman TNA et al. JAMA Network Open. 2018 Jul 6. doi: 10.1001/jamanetworkopen.2018.0558.

Adults who use opioids are more likely to have “complicated health profiles and high levels of involvement in the criminal justice system” compared with adults who do not, according to a retrospective, cross-sectional analysis published July 6 in JAMA Network Open.

“The large proportion of individuals with opioid use disorders who have physical and mental health conditions and who contact the criminal justice system suggests that public health interventions to combat the opioid epidemic ... should coordinate treatment between the criminal justice and health care systems,” wrote Tyler N.A. Winkelman, MD, and his colleagues.

The investigators evaluated a representative sample of responses from 78,976 U.S. adults aged 18-64 who completed the 2015-2016 National Survey on Drug Use and Health, of which 31.3% reported use of prescription opioids, 4.3% reported misuse of opioids, 0.8% reported abuse of prescription opioids, and 0.4% reported heroin use.

The researchers also studied the health characteristics of each individual based on their level of opioid use, whether individuals used other substances in addition to prescription opioids, and the respondents’ recent and distant involvement in the criminal justice system, reported Dr. Winkelman, who is affiliated with the division of general internal medicine at Hennepin Healthcare in Minneapolis, and his colleagues.

After adjustment for health characteristic prevalence and co-occurring substance use across opioid use levels, compared with individuals who reported no opioid use, Dr. Winkelman and his associates found a higher prevalence of mental illness among individuals across four categories: prescription opioid use, prescription opioid misuse, prescription opioid use disorder, and heroin use. They also found a higher prevalence of self-reported chronic conditions such as diabetes, asthma, and high blood pressure across various levels of opioid use, compared with people who reported no opioid use.

Furthermore, Dr. Winkelman and his associates found that as the intensity of opioid use increased, individuals reported an increased prevalence of mild, moderate, and severe mental illness. Individuals who increased their intensity of opioid use also had a greater likelihood of co-occurring substance use with at least one other substance. For example, individuals who misused opioids or used heroin reported that they used tranquilizers or sedatives in more than 50% of cases. Of individuals who reported heroin use, 88.5% said they used prescription opioids within the past year, reported Dr. Winkelman, also a staff physician at the Adult Detention Center in Hennepin County, Minn., and his associates.

The researchers also found 22.4% of individuals (95% confidence interval, 21.7-23.1) who used prescription opioids, 33.2% of individuals who misused prescription opioids (95% CI, 30.9-35.6), 51.7% of individuals with prescription opioid use disorder (95% CI, 45.4-58.0), and 76.8% of individuals with heroin use (95% CI, 70.6-82.1) had any contact with the criminal justice system, compared with 15.9% (95% CI, 15.4-16.4) of individuals who did not report prescription opioid use.

“The overlap we found between involvement in the criminal justice system and opioid use suggests that access to opioid treatment within the criminal justice system is a critical public health issue,” the researchers wrote. They cited studies showing that strategies such as beginning or continuing methadone hydrochloride or buprenorphine hydrochloride during incarceration are tied to a reduction in postrelease mortality.

Among the limitations cited were the National Survey on Drug Use and Health’s cross-sectional design, which makes it difficult to determine whether opioid use preceded involvement in the criminal justice system, or vice versa.

Nevertheless, they said, the study provides the most comprehensive picture to date of the status across several domains of people who use opioids.

“Given the complex health and criminal justice profiles of individuals who use opioids, policy makers should carefully consider how changes to public health insurance programs and sentencing guidelines may aid or hinder a public health approach to the opioid epidemic,” wrote Dr. Winkelman and his colleagues.

Dr. Winkelman disclosed his affiliation with the Hennepin County detention center. Another author disclosed employment with the Colorado Permanente Medical Group and royalties from uptodate.com.

SOURCE: Winkelman TNA et al. JAMA Network Open. 2018 Jul 6. doi: 10.1001/jamanetworkopen.2018.0558.

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

[email protected]

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

[email protected]

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

[email protected]

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

The Food and Drug Administration has released revised guidance regarding testing blood donations for Zika virus, moving away from individual testing of donations and toward pooled testing.

“This [practice of pooled testing] is usually more cost effective and less burdensome for blood establishments,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement. “However, the FDA will continue to monitor the situation closely and, as appropriate, reconsider what measures are needed to maintain the safety of the blood supply.”

[email protected]

The Food and Drug Administration has released revised guidance regarding testing blood donations for Zika virus, moving away from individual testing of donations and toward pooled testing.

“This [practice of pooled testing] is usually more cost effective and less burdensome for blood establishments,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement. “However, the FDA will continue to monitor the situation closely and, as appropriate, reconsider what measures are needed to maintain the safety of the blood supply.”

[email protected]

The Food and Drug Administration has released revised guidance regarding testing blood donations for Zika virus, moving away from individual testing of donations and toward pooled testing.

“This [practice of pooled testing] is usually more cost effective and less burdensome for blood establishments,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement. “However, the FDA will continue to monitor the situation closely and, as appropriate, reconsider what measures are needed to maintain the safety of the blood supply.”

[email protected]

The Robotic Versus Laparoscopic Ventral Hernia Repair study is an interventional trial recruiting patients undergoing elective ventral hernia repair appropriate for minimally invasive surgery.

The trial will compare outcomes of laparoscopic and robotic approaches to ventral hernia repair. The robotic approach to ventral hernia repair previously had been associated with improved outcomes and reduced hospital stay times, compared with the laparoscopic approach, and has been endorsed by the American Hernia Society. However, this evidence is based on database and cohort studies, and more randomized, controlled trials are needed to assess the true effects of the robotic approach.

Patients will be included if they are scheduled for a ventral hernia repair that has been deemed appropriate for minimally invasive surgery. Exclusion criteria include being unlikely to survive for 2 years post surgery, being unlikely to follow up, having advanced chronic obstructive pulmonary disease or congestive heart failure, having a history of open abdomen or extensive lysis of adhesions, having ascites caused by cirrhosis or malignancy, having an active infection, and having a hernia defect size larger than 12 cm.

The primary outcome measure is total number of days spent in the hospital. Secondary outcomes include rates of surgical site infection, rates of surgical site occurrence, rates of hernia reoccurrence, patient-centered outcomes collected using HerQLes (a hernia quality of life measuring instrument), patient-centered outcomes collected using the EQ-5D questionnaire, and cost from a health care perspective.

The primary completion date is April 30, 2020, and the study completion date is April 30, 2023. About 120 people are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

[email protected]

The Robotic Versus Laparoscopic Ventral Hernia Repair study is an interventional trial recruiting patients undergoing elective ventral hernia repair appropriate for minimally invasive surgery.

The trial will compare outcomes of laparoscopic and robotic approaches to ventral hernia repair. The robotic approach to ventral hernia repair previously had been associated with improved outcomes and reduced hospital stay times, compared with the laparoscopic approach, and has been endorsed by the American Hernia Society. However, this evidence is based on database and cohort studies, and more randomized, controlled trials are needed to assess the true effects of the robotic approach.

Patients will be included if they are scheduled for a ventral hernia repair that has been deemed appropriate for minimally invasive surgery. Exclusion criteria include being unlikely to survive for 2 years post surgery, being unlikely to follow up, having advanced chronic obstructive pulmonary disease or congestive heart failure, having a history of open abdomen or extensive lysis of adhesions, having ascites caused by cirrhosis or malignancy, having an active infection, and having a hernia defect size larger than 12 cm.

The primary outcome measure is total number of days spent in the hospital. Secondary outcomes include rates of surgical site infection, rates of surgical site occurrence, rates of hernia reoccurrence, patient-centered outcomes collected using HerQLes (a hernia quality of life measuring instrument), patient-centered outcomes collected using the EQ-5D questionnaire, and cost from a health care perspective.

The primary completion date is April 30, 2020, and the study completion date is April 30, 2023. About 120 people are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

[email protected]

The Robotic Versus Laparoscopic Ventral Hernia Repair study is an interventional trial recruiting patients undergoing elective ventral hernia repair appropriate for minimally invasive surgery.

The trial will compare outcomes of laparoscopic and robotic approaches to ventral hernia repair. The robotic approach to ventral hernia repair previously had been associated with improved outcomes and reduced hospital stay times, compared with the laparoscopic approach, and has been endorsed by the American Hernia Society. However, this evidence is based on database and cohort studies, and more randomized, controlled trials are needed to assess the true effects of the robotic approach.

Patients will be included if they are scheduled for a ventral hernia repair that has been deemed appropriate for minimally invasive surgery. Exclusion criteria include being unlikely to survive for 2 years post surgery, being unlikely to follow up, having advanced chronic obstructive pulmonary disease or congestive heart failure, having a history of open abdomen or extensive lysis of adhesions, having ascites caused by cirrhosis or malignancy, having an active infection, and having a hernia defect size larger than 12 cm.

The primary outcome measure is total number of days spent in the hospital. Secondary outcomes include rates of surgical site infection, rates of surgical site occurrence, rates of hernia reoccurrence, patient-centered outcomes collected using HerQLes (a hernia quality of life measuring instrument), patient-centered outcomes collected using the EQ-5D questionnaire, and cost from a health care perspective.

The primary completion date is April 30, 2020, and the study completion date is April 30, 2023. About 120 people are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

[email protected]

Tranexamic Acid May Benefit Patients With Stroke

Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.

The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.

However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.

Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.

“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.

Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.

A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.

For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.

The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.

CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.

Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.

In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.

The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.

As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.

Combination Therapy May Prevent Stroke

Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.

Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.

The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.

Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.

“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.

POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.

More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.

Simple Scan Still Effective in Deciding Stroke Treatment

A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.

Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.

“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”

Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.

The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.

“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.

The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.

“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.

The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.

Thrombolysis May Be Appropriate in Wake-Up Stroke

The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.

The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.

The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”

“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.

Tranexamic Acid May Benefit Patients With Stroke

Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.

The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.

However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.

Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.

“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.

Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.

A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.

For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.

The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.

CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.

Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.

In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.

The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.

As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.

Combination Therapy May Prevent Stroke

Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.

Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.

The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.

Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.

“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.

POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.

More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.

Simple Scan Still Effective in Deciding Stroke Treatment

A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.

Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.

“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”

Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.

The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.

“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.

The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.

“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.

The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.

Thrombolysis May Be Appropriate in Wake-Up Stroke

The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.

The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.

The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”

“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.

Tranexamic Acid May Benefit Patients With Stroke

Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.

The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.

However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.

Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.

“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.

Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.

A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.

For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.

The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.

CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.

Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.

In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.

The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.

As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.

Combination Therapy May Prevent Stroke

Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.

Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.

The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.

Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.

“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.

POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.

More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.

Simple Scan Still Effective in Deciding Stroke Treatment

A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.

Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.

“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”

Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.

The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.

“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.

The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.

“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.

The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.

Thrombolysis May Be Appropriate in Wake-Up Stroke

The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.

The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.

The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”

“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.

The more sexual refusals men received in a virtual dating simulation, the more hostile the verbal comments men made to the women – regardless of the amount of alcohol the men had consumed, according to a study published in Aggressive Behavior.

“Contrary to our predictions [the relationship between sexual refusals and hostile comments] was not moderated by alcohol condition,” reported Jacqueline Woerner, PhD, and her colleagues. “Because participants had multiple opportunities to escalate their aggression or desist, this paradigm provides new insights into the mechanisms through which intoxication enhances the likelihood of sexual aggression in dating situations.”Dr. Woerner and her colleagues used a virtual dating simulation to compare the sexual aggression of 31 intoxicated men with that of an equal number sober controls. The men, aged 21-29 years and largely white, received either a mixed alcoholic drink adjusted to achieve a blood alcohol concentration of 0.08% or an alcohol-free beverage.

The men went on four computer-mediated dates with a virtual woman; the simulated dates covered a span of a couple of months during the session. The woman was programmed to always consent to some lower-level sexual activities (such as kissing), to consent to some medium-level activities (such as touching breasts) only during later dates, but to always refuse higher-level sexual activities (such as vaginal or oral sex).

As hypothesized, the number of consensual sexual activities correlated with the number of refusals, which suggested that, per expectancy confirmation theory, these men tended to focus on earlier cues that confirmed mutual sexual desire and to ignore those that suggested that the woman was no longer interested, according to the researchers. This correlation and the behaviors it suggests were significantly stronger among intoxicated men than they were among sober controls, reported Dr. Woerner, now affiliated with Yale University, New Haven, Conn., and her colleagues.

However, when the researchers examined the impact of alcohol on the relationship between sexual refusals and the number of hostile verbal comments, they got surprising results. The connection between sexual refusals and alcohol condition was not significant. Among the possible explanations for this unexpected finding were the “extremely high levels of hostility” of some men toward women and the sense of entitlement of some men toward women – whether the men are intoxicated or sober. “Perpetrators’ motives and situational triggers differ, thus multiple explanations need to be evaluated in further research,” Dr. Woerner and her colleagues wrote.

Dr. Woerner and her colleagues also recorded audio of participants as they interacted with the simulation. The intensity of the commentary – with comments like “You prude, we’ve been hanging out for months now” – suggested the participants took the simulation seriously, the researchers noted.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

[email protected]

SOURCE: Woerner J et al. Aggress Behav. 2018. doi: 10.1002/ab.21773.
 

The more sexual refusals men received in a virtual dating simulation, the more hostile the verbal comments men made to the women – regardless of the amount of alcohol the men had consumed, according to a study published in Aggressive Behavior.

“Contrary to our predictions [the relationship between sexual refusals and hostile comments] was not moderated by alcohol condition,” reported Jacqueline Woerner, PhD, and her colleagues. “Because participants had multiple opportunities to escalate their aggression or desist, this paradigm provides new insights into the mechanisms through which intoxication enhances the likelihood of sexual aggression in dating situations.”Dr. Woerner and her colleagues used a virtual dating simulation to compare the sexual aggression of 31 intoxicated men with that of an equal number sober controls. The men, aged 21-29 years and largely white, received either a mixed alcoholic drink adjusted to achieve a blood alcohol concentration of 0.08% or an alcohol-free beverage.

The men went on four computer-mediated dates with a virtual woman; the simulated dates covered a span of a couple of months during the session. The woman was programmed to always consent to some lower-level sexual activities (such as kissing), to consent to some medium-level activities (such as touching breasts) only during later dates, but to always refuse higher-level sexual activities (such as vaginal or oral sex).

As hypothesized, the number of consensual sexual activities correlated with the number of refusals, which suggested that, per expectancy confirmation theory, these men tended to focus on earlier cues that confirmed mutual sexual desire and to ignore those that suggested that the woman was no longer interested, according to the researchers. This correlation and the behaviors it suggests were significantly stronger among intoxicated men than they were among sober controls, reported Dr. Woerner, now affiliated with Yale University, New Haven, Conn., and her colleagues.

However, when the researchers examined the impact of alcohol on the relationship between sexual refusals and the number of hostile verbal comments, they got surprising results. The connection between sexual refusals and alcohol condition was not significant. Among the possible explanations for this unexpected finding were the “extremely high levels of hostility” of some men toward women and the sense of entitlement of some men toward women – whether the men are intoxicated or sober. “Perpetrators’ motives and situational triggers differ, thus multiple explanations need to be evaluated in further research,” Dr. Woerner and her colleagues wrote.

Dr. Woerner and her colleagues also recorded audio of participants as they interacted with the simulation. The intensity of the commentary – with comments like “You prude, we’ve been hanging out for months now” – suggested the participants took the simulation seriously, the researchers noted.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

[email protected]

SOURCE: Woerner J et al. Aggress Behav. 2018. doi: 10.1002/ab.21773.
 

The more sexual refusals men received in a virtual dating simulation, the more hostile the verbal comments men made to the women – regardless of the amount of alcohol the men had consumed, according to a study published in Aggressive Behavior.

“Contrary to our predictions [the relationship between sexual refusals and hostile comments] was not moderated by alcohol condition,” reported Jacqueline Woerner, PhD, and her colleagues. “Because participants had multiple opportunities to escalate their aggression or desist, this paradigm provides new insights into the mechanisms through which intoxication enhances the likelihood of sexual aggression in dating situations.”Dr. Woerner and her colleagues used a virtual dating simulation to compare the sexual aggression of 31 intoxicated men with that of an equal number sober controls. The men, aged 21-29 years and largely white, received either a mixed alcoholic drink adjusted to achieve a blood alcohol concentration of 0.08% or an alcohol-free beverage.

The men went on four computer-mediated dates with a virtual woman; the simulated dates covered a span of a couple of months during the session. The woman was programmed to always consent to some lower-level sexual activities (such as kissing), to consent to some medium-level activities (such as touching breasts) only during later dates, but to always refuse higher-level sexual activities (such as vaginal or oral sex).

As hypothesized, the number of consensual sexual activities correlated with the number of refusals, which suggested that, per expectancy confirmation theory, these men tended to focus on earlier cues that confirmed mutual sexual desire and to ignore those that suggested that the woman was no longer interested, according to the researchers. This correlation and the behaviors it suggests were significantly stronger among intoxicated men than they were among sober controls, reported Dr. Woerner, now affiliated with Yale University, New Haven, Conn., and her colleagues.

However, when the researchers examined the impact of alcohol on the relationship between sexual refusals and the number of hostile verbal comments, they got surprising results. The connection between sexual refusals and alcohol condition was not significant. Among the possible explanations for this unexpected finding were the “extremely high levels of hostility” of some men toward women and the sense of entitlement of some men toward women – whether the men are intoxicated or sober. “Perpetrators’ motives and situational triggers differ, thus multiple explanations need to be evaluated in further research,” Dr. Woerner and her colleagues wrote.

Dr. Woerner and her colleagues also recorded audio of participants as they interacted with the simulation. The intensity of the commentary – with comments like “You prude, we’ve been hanging out for months now” – suggested the participants took the simulation seriously, the researchers noted.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

[email protected]

SOURCE: Woerner J et al. Aggress Behav. 2018. doi: 10.1002/ab.21773.