Case

A 60-year-old male with a history of head & neck cancer, treated with radical neck dissection and radiation 5 years prior is admitted with community-acquired pneumonia and anasarca. Prior to admission, he was on a soft dysphagia diet and reports increased difficulty with solid foods and weight loss from 70 kg to 55 kg over 2.5 years. Should nutritional support be initiated?

Background

Malnutrition is associated with increased hospital mortality, decreased functional status and quality of life, infections, longer length of stay, higher hospital costs, and more frequent nonelective readmissions.^1,2

Identifying patients who are malnourished or at risk for malnutrition

An international consensus committee recommended the following criteria for the diagnosis of undernutrition if two of six are present³:

• Insufficient energy intake.
• Weight loss.
• Loss of muscle mass.
• Loss of subcutaneous fat.
• Localized or generalized fluid accumulation that may sometimes mask weight loss.
• Diminished functional status as measured by handgrip strength.

The joint commission requires that all patients admitted to acute care hospitals be screened for risk of malnutrition within 24 hours. The American College of Gastroenterologists recommends using a validated score to assess nutritional risk, such as the Nutritional Risk Score (NRS) 2002 or the NUTRIC (Nutrition Risk in the Critically Ill) Score, which use a combination of nutritional status and diet-related factors – weight loss, body mass index, and food intake – and also severity of illness measurements.⁴

• Starvation-related malnutrition, such as anorexia nervosa, presents with a deficiency in calories and protein without inflammation, .
• Chronic disease–related malnutrition, such as that caused chronic obstructive pulmonary disease, cancer, and obesity, presents with mild to moderate inflammation.
• Acute disease or injury–related malnutrition, such as that caused by sepsis, burns, and trauma, presents with acute and severe inflammation.

Laboratory indicators such as albumin, prealbumin, and transferrin are not recommended for the determination of nutritional status. Instead, as negative acute-phase reactants, they can be used as surrogate markers of nutritional risk and degree of inflammation.⁴

Overview of the data

What are the indications for initiating nutritional support, and what is the optimal timing for initiation?

Patients who are malnourished or at significant risk for becoming malnourished should receive specialized nutrition support. Early enteral nutrition should be initiated within 24-48 hours of admission in critically ill patients with high nutritional risk who are unable to maintain volitional intake.⁶ In the absence of preexisting malnutrition, nutritional support should be provided for patients with inadequate oral intake for 7-14 days or for those in whom inadequate oral intake is expected over the same time period.⁷
 

How should nutritional support be administered?

Dietary modification and supplementation

In patients who can tolerate an oral diet, dietary modifications may be made in order to facilitate the provision of essential nutrients in a well-tolerated form. Modifications may include adjusting the consistency of foods, energy value of foods, types of nutrients consumed, and number and frequency of meals.⁸ Commercial meal replacement beverages are widely used to support a standard oral diet, but there is no data to support their routine use.⁷

Enteral nutrition

Enteral nutrition (EN) is the method of choice for administering nutrition support. Contraindications to enteral feeding include diffuse peritonitis, intestinal obstruction, and gastrointestinal ischemia.⁹ The potential advantages of EN over parenteral nutrition (PN) include decreased infection rate, decreased total complications, and shorter length of stay, but there has been no observed difference in mortality. EN is also suggested to have nonnutritional benefits related to providing luminal nutrients – these include maintaining gut integrity, beneficial immune responses, and favorable metabolic responses that help maintain euglycemia and enhance more physiologic fuel utilization.⁴

Enteral feeding can be administered through the following routes of access:

• Nasogastric tubes: A nasogastric or orogastric tube with radiologic confirmation of positioning is the first line of enteral access. Gastric feeding is preferred because it is well tolerated in the majority of patients, is more physiological, requires a lower level of expertise, and minimizes any delay in initiation of feeding.
• Postpyloric tubes: Postpyloric feeding tubes are indicated if gastric feeding is poorly tolerated or if the patient is at high risk for aspiration because jejunal feedings decrease the incidence of reflux, regurgitation, and aspiration.
• Percutaneous access: When long-term enteral access is required – that is, for greater than 4 weeks – a percutaneous enteral access device should be placed. Prolonged use of a nasoenteric tube may be associated with erosion of the nares and an increase in the incidence of aspiration pneumonia, sinusitis, and esophageal ulceration or stricture. Patients who have had a stroke are the most likely to benefit from percutaneous endoscopic gastrostomy placement, as 40% of patients can have continued dysphagia as long as 1 year after.^4,10 Absolute contraindications for PEG placement include serious coagulation disorders (international normalized ratio greater than 1.5; fewer than 50,000 platelets/mcL), sepsis, abdominal wall infections, marked peritoneal carcinomatosis, peritonitis, severe gastroparesis, gastric outlet obstruction, or a history of total gastrectomy. Risks often outweigh benefits in patients who have cirrhosis with ascites, patients undergoing peritoneal dialysis, and patients who have portal hypertension with gastric varices, but PEG can be considered on a case-by-case basis.¹¹

Parenteral nutrition

Parenteral nutrition is reserved for patients in whom enteral feeding is contraindicated or who fail to meet their nutritional needs with enteral feedings. If EN is not feasible, then parenteral nutrition should be initiated as soon as possible in patients who had high nutritional risk on admission. Otherwise, PN should not be initiated during the first week of hospitalization because there is evidence to suggest net harm when initiated early. Supplemental PN may be considered for patients already on EN who are unable to meet more than 60% of their energy and protein requirements by the enteral route alone, but again, this should only be considered after 7-10 days on EN. PN is generally stopped when the patients achieve more than 60% of their energy and protein goals from EN.⁴

How should patients be monitored while receiving nutritional support?

If a patient is severely malnourished and refeeding is initiated, serious complications can occur, which are summarized in Table 1; these complications can include severe electrolyte disorders, fluid shifts, and even death.¹² Refeeding syndrome occurs in the first few days of initiating a diet in severely malnourished patients, and its severity is directly related to the severity of malnutrition prior to refeeding. The National Institute of Health and Clinical Excellence created criteria to identify patients at risk for refeeding syndrome; these criteria include having a BMI less than 18.5 kg/m²; unintentional weight loss of greater than 10% in the previous 3-6 months; little or no nutritional intake for more than 5 days; low levels of potassium, phosphorus, or magnesium before refeeding; and a history of alcohol misuse or taking certain drugs, such as insulin, chemotherapy, antacids, or diuretics.⁹

Gastric residual volume (GRV) is commonly monitored in patients receiving enteral nutrition. However, the American College of Gastroenterology does not recommend using GRVs to monitor EN feeding because it is a poor marker of clinically meaningful variables, such as gastric emptying, risk of aspiration, and risk of poor outcomes, and increases the risk of tube clogging and inadequate delivery of EN. If GRVs are being monitored, tube feedings should not be withheld because of high GRVs when there are no other signs of intolerance.⁴ Nausea may be managed by changing a patient from bolus to continuous feedings or by adding promotility agents such as metoclopramide or erythromycin.⁶
 

Special considerations in common conditions treated by hospitalists

The principles outlined above are general guidelines that are applicable to most patients requiring nutrition support. We have highlighted special considerations for common conditions in hospitalized patients who require nutritional support below.

Critical Illness

• Defer enteral nutrition until patient is fully resuscitated and hemodynamically stable.
• Severely malnourished or high nutritional-risk patients should be advanced toward goals as quickly as can be tolerated over 24-48 hours.
• Patients with acute respiratory distress syndrome or acute lung injury, or those expected to require mechanical ventilation for more than 72 hours, should receive trophic feeds or full nutrition by enteral route.⁶

Pancreatitis

• Oral feeding should be attempted as soon as abdominal pain is decreasing and inflammatory markers are improving.¹³
• A regular solid, low-fat diet should be initiated, rather than slowly advancing from a clear liquid diet.¹³
• In severe acute pancreatitis, initiation of enteral nutrition within 48 hours of presentation is associated with improved outcomes.¹³
• There is no difference in outcomes between gastric and postpyloric feeding.¹⁴
• Initiation of parenteral nutrition may be delayed for up to 5 days to allow for a trial of oral or enteral feeding.¹³

Surgical patients

• Consider postponing surgery to provide 7-10 days of preoperative nutrition supplementation in patients with risk of severe undernutrition.¹⁶
• Consider postoperative nutritional support if patients are at risk for severe undernutrition, are unable to eat for more than 7 days perioperatively, or are unable to maintain oral intake above 60% of recommended intake for more than 10 days.¹⁶
• Consider total parenteral nutrition in cases of impaired gastrointestinal function and absorption, high output enterocutaneous fistulae, obstructive lesions that do not allow enteral refeeding, or prolonged gastrointestinal failure.¹⁶

Prolonged Starvation

• Because of the high risk of refeeding syndrome, patients greater than 30% below ideal body weight should be hospitalized for close monitoring during refeeding.¹²
• Typical goal for weight gain is no greater than 2-3 pounds per week.¹⁰
• Total parenteral nutrition should be reserved for extreme cases, and if used, carbohydrate intake should not exceed 7 mg/kg/min.¹²

Stroke

• Enteral nutrition should be initiated within 24-48 hours of initial hospitalization if a patient is estimated to require feeding for more than 5 days and/or remain nil per os for 5-7 days.
• If a patient is intubated with increased intracranial pressure, this could delay gastric motility requiring a postpyloric tube placement.
• Initial placement of percutaneous endoscopic gastrostomy tubes can be considered if the hospitalized patient is expected to require nutritional support for greater than 30 days. Most patients will have improved dysphagia symptoms within 1 month of their acute stroke, although as many as 40% can have continued dysphagia up to 1 year.¹⁰

Back to the Case

The patient was admitted for a common general medical condition, but it is important to recognize that malnutrition was present on admission with weight loss and generalized fluid overload. Furthermore, he is at high nutritional risk because of his low body weight, poor oral intake, and dysphagia. Additionally, the acute inflammation from pneumonia places him in an increased catabolic state.

He was able to maintain some volitional oral intake, but after 7 days of close monitoring by a licensed dietician, it was determined that he was unable to meet his nutritional needs via the oral route. A percutaneous endoscopic gastrostomy tube was placed, and tube feeds were initiated, because his dysphagia – which was a significant factor contributing to his inability to meet his nutritional needs orally – was expected to persist for greater than 30 days.
 

Bottom Line

Nutrition support should be initiated in this patient with malnutrition on admission and high nutritional risk.

Dr. Abalos is an assistant professor at Georgetown University Medical Center in Washington. Dr. Corbett is an assistant professor at the University of Oklahoma Health Sciences Center in Oklahoma City.

References

1. Correia MI et al. The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. Clin Nutr. 2003 Jun;22(3):235-9.

2. Felder S et al. Association of nutritional risk and adverse medical outcomes across different medical inpatient populations. Nutrition. 2015 Nov-Dec;31(11-12):1385-93.

3. White JV et al. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: Characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet. 2012 May;112(5):730-8.

4. McClave SA et al. ACG clinical guideline: Nutrition therapy in the adult hospitalized patient. Am J Gastroenterol. 2016 Mar;111(3):315-334.

5. Mueller C et al. A.S.P.E.N. clinical guidelines: Nutrition screening, assessment, and intervention in adults. JPEN J Parenter Enter Nutr. 2011 Jan;35(1):16-24.

6. McClave SA et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN J Parenter Enter Nutr. 2016 Feb;40(2):159-211.

7. August D et al. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enter Nutr. 2002 Jan-Feb:26(1):SUPPL:1SA-138SA.

8. Kirkland LL et al. Nutrition in the hospitalized patient. J Hosp Med. 2013 Jan;8(1):52-8.

9. National Collaborating Centre for Acute Care, February 2006. Nutrition support in adults Oral nutrition support, enteral tube feeding and parenteral nutrition. National Collaborating Centre for Acute Care, London. Available from www.rcseng.ac.uk.

10. Corrigan ML et al. Nutrition in the stroke patient. Nutr Clin Pract. 2011 Jun;26(3):242-52.

11. Loser C et al. ESPEN guidelines on artificial enteral nutrition – Percutaneous endoscopic gastrostomy (PEG). Clin Nutr. 2005 Oct;24(5):848-61.

12. Mehler PS et al. Nutritional rehabilitation: Practical guidelines for refeeding the anorectic patient. J Nutr Metab. 2010. doi: 10.1155/2010/625782.

13. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

14. Singh N et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: A noninferiority randomized controlled trial. Pancreas. 2012 Jan;41(1):153-9.

15. Braga M et al. ESPEN guidelines on parenteral nutrition: Surgery. Clin Nutr. 2009 Aug;28(4):378-86.

16. Weimann A et al. ESPEN Guidelines on enteral nutrition: Surgery including organ transplantation. Clin Nutr. 2006 Apr;25(2):224-44.

Additional reading

• Kirkland LL et al. Nutrition in the Hospitalized Patient. J Hosp Med. 2013 Jan;8(1):52-8.
• McClave SA et al. ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient. Am J Gastroenterol. 2016 Mar;111(3):315-334.

Quiz: Recognizing Malnutrition

Which of the following is not a criteria for the diagnosis of malnutrition?

A. Weight loss

B. Insufficient energy intake

C. Prealbumin

D. Diminished handgrip strength

Answer: C. Prealbumin. Laboratory indicators of nutrition, such as albumin, prealbumin, and transferrin, and markers of infection or inflammation are not recommended for the determination of nutritional status. Because negative acute-phase reactants, they instead can be used as surrogate markers of nutritional risk and degree of inflammation

Key Points

• At the time of admission to the hospital, malnutrition is present in 20-50% of patients. All hospitalized patients should be screened for nutritional risk and nutritional support should be considered if patients are not expected to be able to meet nutritional needs for more than 7 days.
• Patients with severe malnutrition on admission, severe critical illness, or severe acute pancreatitis should be provided nutritional support within 24-48 hours.
• Use the gut! Nutritional support should be provided via the most physiologic route possible. Total parenteral nutrition (TPN) should be reserved for patients in whom adequate nutrition cannot be provided enterally.
• Consider a percutaneous endoscopic gastrostomy (PEG) tube if the patient is expected to require tube feedings for more than 30 days.
• Patients with severe malnutrition who are given nutritional support are at high risk of developing refeeding syndrome, which manifests as electrolyte depletions and heart failure or volume overload.

Case

A 60-year-old male with a history of head & neck cancer, treated with radical neck dissection and radiation 5 years prior is admitted with community-acquired pneumonia and anasarca. Prior to admission, he was on a soft dysphagia diet and reports increased difficulty with solid foods and weight loss from 70 kg to 55 kg over 2.5 years. Should nutritional support be initiated?

Background

Malnutrition is associated with increased hospital mortality, decreased functional status and quality of life, infections, longer length of stay, higher hospital costs, and more frequent nonelective readmissions.^1,2

Identifying patients who are malnourished or at risk for malnutrition

An international consensus committee recommended the following criteria for the diagnosis of undernutrition if two of six are present³:

• Insufficient energy intake.
• Weight loss.
• Loss of muscle mass.
• Loss of subcutaneous fat.
• Localized or generalized fluid accumulation that may sometimes mask weight loss.
• Diminished functional status as measured by handgrip strength.

The joint commission requires that all patients admitted to acute care hospitals be screened for risk of malnutrition within 24 hours. The American College of Gastroenterologists recommends using a validated score to assess nutritional risk, such as the Nutritional Risk Score (NRS) 2002 or the NUTRIC (Nutrition Risk in the Critically Ill) Score, which use a combination of nutritional status and diet-related factors – weight loss, body mass index, and food intake – and also severity of illness measurements.⁴

• Starvation-related malnutrition, such as anorexia nervosa, presents with a deficiency in calories and protein without inflammation, .
• Chronic disease–related malnutrition, such as that caused chronic obstructive pulmonary disease, cancer, and obesity, presents with mild to moderate inflammation.
• Acute disease or injury–related malnutrition, such as that caused by sepsis, burns, and trauma, presents with acute and severe inflammation.

Laboratory indicators such as albumin, prealbumin, and transferrin are not recommended for the determination of nutritional status. Instead, as negative acute-phase reactants, they can be used as surrogate markers of nutritional risk and degree of inflammation.⁴

Overview of the data

What are the indications for initiating nutritional support, and what is the optimal timing for initiation?

Patients who are malnourished or at significant risk for becoming malnourished should receive specialized nutrition support. Early enteral nutrition should be initiated within 24-48 hours of admission in critically ill patients with high nutritional risk who are unable to maintain volitional intake.⁶ In the absence of preexisting malnutrition, nutritional support should be provided for patients with inadequate oral intake for 7-14 days or for those in whom inadequate oral intake is expected over the same time period.⁷
 

How should nutritional support be administered?

Dietary modification and supplementation

In patients who can tolerate an oral diet, dietary modifications may be made in order to facilitate the provision of essential nutrients in a well-tolerated form. Modifications may include adjusting the consistency of foods, energy value of foods, types of nutrients consumed, and number and frequency of meals.⁸ Commercial meal replacement beverages are widely used to support a standard oral diet, but there is no data to support their routine use.⁷

Enteral nutrition

Enteral nutrition (EN) is the method of choice for administering nutrition support. Contraindications to enteral feeding include diffuse peritonitis, intestinal obstruction, and gastrointestinal ischemia.⁹ The potential advantages of EN over parenteral nutrition (PN) include decreased infection rate, decreased total complications, and shorter length of stay, but there has been no observed difference in mortality. EN is also suggested to have nonnutritional benefits related to providing luminal nutrients – these include maintaining gut integrity, beneficial immune responses, and favorable metabolic responses that help maintain euglycemia and enhance more physiologic fuel utilization.⁴

Enteral feeding can be administered through the following routes of access:

• Nasogastric tubes: A nasogastric or orogastric tube with radiologic confirmation of positioning is the first line of enteral access. Gastric feeding is preferred because it is well tolerated in the majority of patients, is more physiological, requires a lower level of expertise, and minimizes any delay in initiation of feeding.
• Postpyloric tubes: Postpyloric feeding tubes are indicated if gastric feeding is poorly tolerated or if the patient is at high risk for aspiration because jejunal feedings decrease the incidence of reflux, regurgitation, and aspiration.
• Percutaneous access: When long-term enteral access is required – that is, for greater than 4 weeks – a percutaneous enteral access device should be placed. Prolonged use of a nasoenteric tube may be associated with erosion of the nares and an increase in the incidence of aspiration pneumonia, sinusitis, and esophageal ulceration or stricture. Patients who have had a stroke are the most likely to benefit from percutaneous endoscopic gastrostomy placement, as 40% of patients can have continued dysphagia as long as 1 year after.^4,10 Absolute contraindications for PEG placement include serious coagulation disorders (international normalized ratio greater than 1.5; fewer than 50,000 platelets/mcL), sepsis, abdominal wall infections, marked peritoneal carcinomatosis, peritonitis, severe gastroparesis, gastric outlet obstruction, or a history of total gastrectomy. Risks often outweigh benefits in patients who have cirrhosis with ascites, patients undergoing peritoneal dialysis, and patients who have portal hypertension with gastric varices, but PEG can be considered on a case-by-case basis.¹¹

Parenteral nutrition

Parenteral nutrition is reserved for patients in whom enteral feeding is contraindicated or who fail to meet their nutritional needs with enteral feedings. If EN is not feasible, then parenteral nutrition should be initiated as soon as possible in patients who had high nutritional risk on admission. Otherwise, PN should not be initiated during the first week of hospitalization because there is evidence to suggest net harm when initiated early. Supplemental PN may be considered for patients already on EN who are unable to meet more than 60% of their energy and protein requirements by the enteral route alone, but again, this should only be considered after 7-10 days on EN. PN is generally stopped when the patients achieve more than 60% of their energy and protein goals from EN.⁴

How should patients be monitored while receiving nutritional support?

If a patient is severely malnourished and refeeding is initiated, serious complications can occur, which are summarized in Table 1; these complications can include severe electrolyte disorders, fluid shifts, and even death.¹² Refeeding syndrome occurs in the first few days of initiating a diet in severely malnourished patients, and its severity is directly related to the severity of malnutrition prior to refeeding. The National Institute of Health and Clinical Excellence created criteria to identify patients at risk for refeeding syndrome; these criteria include having a BMI less than 18.5 kg/m²; unintentional weight loss of greater than 10% in the previous 3-6 months; little or no nutritional intake for more than 5 days; low levels of potassium, phosphorus, or magnesium before refeeding; and a history of alcohol misuse or taking certain drugs, such as insulin, chemotherapy, antacids, or diuretics.⁹

Gastric residual volume (GRV) is commonly monitored in patients receiving enteral nutrition. However, the American College of Gastroenterology does not recommend using GRVs to monitor EN feeding because it is a poor marker of clinically meaningful variables, such as gastric emptying, risk of aspiration, and risk of poor outcomes, and increases the risk of tube clogging and inadequate delivery of EN. If GRVs are being monitored, tube feedings should not be withheld because of high GRVs when there are no other signs of intolerance.⁴ Nausea may be managed by changing a patient from bolus to continuous feedings or by adding promotility agents such as metoclopramide or erythromycin.⁶
 

Special considerations in common conditions treated by hospitalists

The principles outlined above are general guidelines that are applicable to most patients requiring nutrition support. We have highlighted special considerations for common conditions in hospitalized patients who require nutritional support below.

Critical Illness

• Defer enteral nutrition until patient is fully resuscitated and hemodynamically stable.
• Severely malnourished or high nutritional-risk patients should be advanced toward goals as quickly as can be tolerated over 24-48 hours.
• Patients with acute respiratory distress syndrome or acute lung injury, or those expected to require mechanical ventilation for more than 72 hours, should receive trophic feeds or full nutrition by enteral route.⁶

Pancreatitis

• Oral feeding should be attempted as soon as abdominal pain is decreasing and inflammatory markers are improving.¹³
• A regular solid, low-fat diet should be initiated, rather than slowly advancing from a clear liquid diet.¹³
• In severe acute pancreatitis, initiation of enteral nutrition within 48 hours of presentation is associated with improved outcomes.¹³
• There is no difference in outcomes between gastric and postpyloric feeding.¹⁴
• Initiation of parenteral nutrition may be delayed for up to 5 days to allow for a trial of oral or enteral feeding.¹³

Surgical patients

• Consider postponing surgery to provide 7-10 days of preoperative nutrition supplementation in patients with risk of severe undernutrition.¹⁶
• Consider postoperative nutritional support if patients are at risk for severe undernutrition, are unable to eat for more than 7 days perioperatively, or are unable to maintain oral intake above 60% of recommended intake for more than 10 days.¹⁶
• Consider total parenteral nutrition in cases of impaired gastrointestinal function and absorption, high output enterocutaneous fistulae, obstructive lesions that do not allow enteral refeeding, or prolonged gastrointestinal failure.¹⁶

Prolonged Starvation

• Because of the high risk of refeeding syndrome, patients greater than 30% below ideal body weight should be hospitalized for close monitoring during refeeding.¹²
• Typical goal for weight gain is no greater than 2-3 pounds per week.¹⁰
• Total parenteral nutrition should be reserved for extreme cases, and if used, carbohydrate intake should not exceed 7 mg/kg/min.¹²

Stroke

• Enteral nutrition should be initiated within 24-48 hours of initial hospitalization if a patient is estimated to require feeding for more than 5 days and/or remain nil per os for 5-7 days.
• If a patient is intubated with increased intracranial pressure, this could delay gastric motility requiring a postpyloric tube placement.
• Initial placement of percutaneous endoscopic gastrostomy tubes can be considered if the hospitalized patient is expected to require nutritional support for greater than 30 days. Most patients will have improved dysphagia symptoms within 1 month of their acute stroke, although as many as 40% can have continued dysphagia up to 1 year.¹⁰

Back to the Case

The patient was admitted for a common general medical condition, but it is important to recognize that malnutrition was present on admission with weight loss and generalized fluid overload. Furthermore, he is at high nutritional risk because of his low body weight, poor oral intake, and dysphagia. Additionally, the acute inflammation from pneumonia places him in an increased catabolic state.

He was able to maintain some volitional oral intake, but after 7 days of close monitoring by a licensed dietician, it was determined that he was unable to meet his nutritional needs via the oral route. A percutaneous endoscopic gastrostomy tube was placed, and tube feeds were initiated, because his dysphagia – which was a significant factor contributing to his inability to meet his nutritional needs orally – was expected to persist for greater than 30 days.
 

Bottom Line

Nutrition support should be initiated in this patient with malnutrition on admission and high nutritional risk.

Dr. Abalos is an assistant professor at Georgetown University Medical Center in Washington. Dr. Corbett is an assistant professor at the University of Oklahoma Health Sciences Center in Oklahoma City.

References

1. Correia MI et al. The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. Clin Nutr. 2003 Jun;22(3):235-9.

2. Felder S et al. Association of nutritional risk and adverse medical outcomes across different medical inpatient populations. Nutrition. 2015 Nov-Dec;31(11-12):1385-93.

3. White JV et al. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: Characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet. 2012 May;112(5):730-8.

4. McClave SA et al. ACG clinical guideline: Nutrition therapy in the adult hospitalized patient. Am J Gastroenterol. 2016 Mar;111(3):315-334.

5. Mueller C et al. A.S.P.E.N. clinical guidelines: Nutrition screening, assessment, and intervention in adults. JPEN J Parenter Enter Nutr. 2011 Jan;35(1):16-24.

6. McClave SA et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN J Parenter Enter Nutr. 2016 Feb;40(2):159-211.

7. August D et al. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enter Nutr. 2002 Jan-Feb:26(1):SUPPL:1SA-138SA.

8. Kirkland LL et al. Nutrition in the hospitalized patient. J Hosp Med. 2013 Jan;8(1):52-8.

9. National Collaborating Centre for Acute Care, February 2006. Nutrition support in adults Oral nutrition support, enteral tube feeding and parenteral nutrition. National Collaborating Centre for Acute Care, London. Available from www.rcseng.ac.uk.

10. Corrigan ML et al. Nutrition in the stroke patient. Nutr Clin Pract. 2011 Jun;26(3):242-52.

11. Loser C et al. ESPEN guidelines on artificial enteral nutrition – Percutaneous endoscopic gastrostomy (PEG). Clin Nutr. 2005 Oct;24(5):848-61.

12. Mehler PS et al. Nutritional rehabilitation: Practical guidelines for refeeding the anorectic patient. J Nutr Metab. 2010. doi: 10.1155/2010/625782.

13. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

14. Singh N et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: A noninferiority randomized controlled trial. Pancreas. 2012 Jan;41(1):153-9.

15. Braga M et al. ESPEN guidelines on parenteral nutrition: Surgery. Clin Nutr. 2009 Aug;28(4):378-86.

16. Weimann A et al. ESPEN Guidelines on enteral nutrition: Surgery including organ transplantation. Clin Nutr. 2006 Apr;25(2):224-44.

Additional reading

• Kirkland LL et al. Nutrition in the Hospitalized Patient. J Hosp Med. 2013 Jan;8(1):52-8.
• McClave SA et al. ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient. Am J Gastroenterol. 2016 Mar;111(3):315-334.

Quiz: Recognizing Malnutrition

Which of the following is not a criteria for the diagnosis of malnutrition?

A. Weight loss

B. Insufficient energy intake

C. Prealbumin

D. Diminished handgrip strength

Answer: C. Prealbumin. Laboratory indicators of nutrition, such as albumin, prealbumin, and transferrin, and markers of infection or inflammation are not recommended for the determination of nutritional status. Because negative acute-phase reactants, they instead can be used as surrogate markers of nutritional risk and degree of inflammation

Key Points

• At the time of admission to the hospital, malnutrition is present in 20-50% of patients. All hospitalized patients should be screened for nutritional risk and nutritional support should be considered if patients are not expected to be able to meet nutritional needs for more than 7 days.
• Patients with severe malnutrition on admission, severe critical illness, or severe acute pancreatitis should be provided nutritional support within 24-48 hours.
• Use the gut! Nutritional support should be provided via the most physiologic route possible. Total parenteral nutrition (TPN) should be reserved for patients in whom adequate nutrition cannot be provided enterally.
• Consider a percutaneous endoscopic gastrostomy (PEG) tube if the patient is expected to require tube feedings for more than 30 days.
• Patients with severe malnutrition who are given nutritional support are at high risk of developing refeeding syndrome, which manifests as electrolyte depletions and heart failure or volume overload.

Case

A 60-year-old male with a history of head & neck cancer, treated with radical neck dissection and radiation 5 years prior is admitted with community-acquired pneumonia and anasarca. Prior to admission, he was on a soft dysphagia diet and reports increased difficulty with solid foods and weight loss from 70 kg to 55 kg over 2.5 years. Should nutritional support be initiated?

Background

Malnutrition is associated with increased hospital mortality, decreased functional status and quality of life, infections, longer length of stay, higher hospital costs, and more frequent nonelective readmissions.^1,2

Identifying patients who are malnourished or at risk for malnutrition

An international consensus committee recommended the following criteria for the diagnosis of undernutrition if two of six are present³:

• Insufficient energy intake.
• Weight loss.
• Loss of muscle mass.
• Loss of subcutaneous fat.
• Localized or generalized fluid accumulation that may sometimes mask weight loss.
• Diminished functional status as measured by handgrip strength.

The joint commission requires that all patients admitted to acute care hospitals be screened for risk of malnutrition within 24 hours. The American College of Gastroenterologists recommends using a validated score to assess nutritional risk, such as the Nutritional Risk Score (NRS) 2002 or the NUTRIC (Nutrition Risk in the Critically Ill) Score, which use a combination of nutritional status and diet-related factors – weight loss, body mass index, and food intake – and also severity of illness measurements.⁴

• Starvation-related malnutrition, such as anorexia nervosa, presents with a deficiency in calories and protein without inflammation, .
• Chronic disease–related malnutrition, such as that caused chronic obstructive pulmonary disease, cancer, and obesity, presents with mild to moderate inflammation.
• Acute disease or injury–related malnutrition, such as that caused by sepsis, burns, and trauma, presents with acute and severe inflammation.

Laboratory indicators such as albumin, prealbumin, and transferrin are not recommended for the determination of nutritional status. Instead, as negative acute-phase reactants, they can be used as surrogate markers of nutritional risk and degree of inflammation.⁴

Overview of the data

What are the indications for initiating nutritional support, and what is the optimal timing for initiation?

Patients who are malnourished or at significant risk for becoming malnourished should receive specialized nutrition support. Early enteral nutrition should be initiated within 24-48 hours of admission in critically ill patients with high nutritional risk who are unable to maintain volitional intake.⁶ In the absence of preexisting malnutrition, nutritional support should be provided for patients with inadequate oral intake for 7-14 days or for those in whom inadequate oral intake is expected over the same time period.⁷
 

How should nutritional support be administered?

Dietary modification and supplementation

In patients who can tolerate an oral diet, dietary modifications may be made in order to facilitate the provision of essential nutrients in a well-tolerated form. Modifications may include adjusting the consistency of foods, energy value of foods, types of nutrients consumed, and number and frequency of meals.⁸ Commercial meal replacement beverages are widely used to support a standard oral diet, but there is no data to support their routine use.⁷

Enteral nutrition

Enteral nutrition (EN) is the method of choice for administering nutrition support. Contraindications to enteral feeding include diffuse peritonitis, intestinal obstruction, and gastrointestinal ischemia.⁹ The potential advantages of EN over parenteral nutrition (PN) include decreased infection rate, decreased total complications, and shorter length of stay, but there has been no observed difference in mortality. EN is also suggested to have nonnutritional benefits related to providing luminal nutrients – these include maintaining gut integrity, beneficial immune responses, and favorable metabolic responses that help maintain euglycemia and enhance more physiologic fuel utilization.⁴

Enteral feeding can be administered through the following routes of access:

• Nasogastric tubes: A nasogastric or orogastric tube with radiologic confirmation of positioning is the first line of enteral access. Gastric feeding is preferred because it is well tolerated in the majority of patients, is more physiological, requires a lower level of expertise, and minimizes any delay in initiation of feeding.
• Postpyloric tubes: Postpyloric feeding tubes are indicated if gastric feeding is poorly tolerated or if the patient is at high risk for aspiration because jejunal feedings decrease the incidence of reflux, regurgitation, and aspiration.
• Percutaneous access: When long-term enteral access is required – that is, for greater than 4 weeks – a percutaneous enteral access device should be placed. Prolonged use of a nasoenteric tube may be associated with erosion of the nares and an increase in the incidence of aspiration pneumonia, sinusitis, and esophageal ulceration or stricture. Patients who have had a stroke are the most likely to benefit from percutaneous endoscopic gastrostomy placement, as 40% of patients can have continued dysphagia as long as 1 year after.^4,10 Absolute contraindications for PEG placement include serious coagulation disorders (international normalized ratio greater than 1.5; fewer than 50,000 platelets/mcL), sepsis, abdominal wall infections, marked peritoneal carcinomatosis, peritonitis, severe gastroparesis, gastric outlet obstruction, or a history of total gastrectomy. Risks often outweigh benefits in patients who have cirrhosis with ascites, patients undergoing peritoneal dialysis, and patients who have portal hypertension with gastric varices, but PEG can be considered on a case-by-case basis.¹¹

Parenteral nutrition

Parenteral nutrition is reserved for patients in whom enteral feeding is contraindicated or who fail to meet their nutritional needs with enteral feedings. If EN is not feasible, then parenteral nutrition should be initiated as soon as possible in patients who had high nutritional risk on admission. Otherwise, PN should not be initiated during the first week of hospitalization because there is evidence to suggest net harm when initiated early. Supplemental PN may be considered for patients already on EN who are unable to meet more than 60% of their energy and protein requirements by the enteral route alone, but again, this should only be considered after 7-10 days on EN. PN is generally stopped when the patients achieve more than 60% of their energy and protein goals from EN.⁴

How should patients be monitored while receiving nutritional support?

If a patient is severely malnourished and refeeding is initiated, serious complications can occur, which are summarized in Table 1; these complications can include severe electrolyte disorders, fluid shifts, and even death.¹² Refeeding syndrome occurs in the first few days of initiating a diet in severely malnourished patients, and its severity is directly related to the severity of malnutrition prior to refeeding. The National Institute of Health and Clinical Excellence created criteria to identify patients at risk for refeeding syndrome; these criteria include having a BMI less than 18.5 kg/m²; unintentional weight loss of greater than 10% in the previous 3-6 months; little or no nutritional intake for more than 5 days; low levels of potassium, phosphorus, or magnesium before refeeding; and a history of alcohol misuse or taking certain drugs, such as insulin, chemotherapy, antacids, or diuretics.⁹

Gastric residual volume (GRV) is commonly monitored in patients receiving enteral nutrition. However, the American College of Gastroenterology does not recommend using GRVs to monitor EN feeding because it is a poor marker of clinically meaningful variables, such as gastric emptying, risk of aspiration, and risk of poor outcomes, and increases the risk of tube clogging and inadequate delivery of EN. If GRVs are being monitored, tube feedings should not be withheld because of high GRVs when there are no other signs of intolerance.⁴ Nausea may be managed by changing a patient from bolus to continuous feedings or by adding promotility agents such as metoclopramide or erythromycin.⁶
 

Special considerations in common conditions treated by hospitalists

The principles outlined above are general guidelines that are applicable to most patients requiring nutrition support. We have highlighted special considerations for common conditions in hospitalized patients who require nutritional support below.

Critical Illness

• Defer enteral nutrition until patient is fully resuscitated and hemodynamically stable.
• Severely malnourished or high nutritional-risk patients should be advanced toward goals as quickly as can be tolerated over 24-48 hours.
• Patients with acute respiratory distress syndrome or acute lung injury, or those expected to require mechanical ventilation for more than 72 hours, should receive trophic feeds or full nutrition by enteral route.⁶

Pancreatitis

• Oral feeding should be attempted as soon as abdominal pain is decreasing and inflammatory markers are improving.¹³
• A regular solid, low-fat diet should be initiated, rather than slowly advancing from a clear liquid diet.¹³
• In severe acute pancreatitis, initiation of enteral nutrition within 48 hours of presentation is associated with improved outcomes.¹³
• There is no difference in outcomes between gastric and postpyloric feeding.¹⁴
• Initiation of parenteral nutrition may be delayed for up to 5 days to allow for a trial of oral or enteral feeding.¹³

Surgical patients

• Consider postponing surgery to provide 7-10 days of preoperative nutrition supplementation in patients with risk of severe undernutrition.¹⁶
• Consider postoperative nutritional support if patients are at risk for severe undernutrition, are unable to eat for more than 7 days perioperatively, or are unable to maintain oral intake above 60% of recommended intake for more than 10 days.¹⁶
• Consider total parenteral nutrition in cases of impaired gastrointestinal function and absorption, high output enterocutaneous fistulae, obstructive lesions that do not allow enteral refeeding, or prolonged gastrointestinal failure.¹⁶

Prolonged Starvation

• Because of the high risk of refeeding syndrome, patients greater than 30% below ideal body weight should be hospitalized for close monitoring during refeeding.¹²
• Typical goal for weight gain is no greater than 2-3 pounds per week.¹⁰
• Total parenteral nutrition should be reserved for extreme cases, and if used, carbohydrate intake should not exceed 7 mg/kg/min.¹²

Stroke

• Enteral nutrition should be initiated within 24-48 hours of initial hospitalization if a patient is estimated to require feeding for more than 5 days and/or remain nil per os for 5-7 days.
• If a patient is intubated with increased intracranial pressure, this could delay gastric motility requiring a postpyloric tube placement.
• Initial placement of percutaneous endoscopic gastrostomy tubes can be considered if the hospitalized patient is expected to require nutritional support for greater than 30 days. Most patients will have improved dysphagia symptoms within 1 month of their acute stroke, although as many as 40% can have continued dysphagia up to 1 year.¹⁰

Back to the Case

The patient was admitted for a common general medical condition, but it is important to recognize that malnutrition was present on admission with weight loss and generalized fluid overload. Furthermore, he is at high nutritional risk because of his low body weight, poor oral intake, and dysphagia. Additionally, the acute inflammation from pneumonia places him in an increased catabolic state.

He was able to maintain some volitional oral intake, but after 7 days of close monitoring by a licensed dietician, it was determined that he was unable to meet his nutritional needs via the oral route. A percutaneous endoscopic gastrostomy tube was placed, and tube feeds were initiated, because his dysphagia – which was a significant factor contributing to his inability to meet his nutritional needs orally – was expected to persist for greater than 30 days.
 

Bottom Line

Nutrition support should be initiated in this patient with malnutrition on admission and high nutritional risk.

Dr. Abalos is an assistant professor at Georgetown University Medical Center in Washington. Dr. Corbett is an assistant professor at the University of Oklahoma Health Sciences Center in Oklahoma City.

References

1. Correia MI et al. The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. Clin Nutr. 2003 Jun;22(3):235-9.

2. Felder S et al. Association of nutritional risk and adverse medical outcomes across different medical inpatient populations. Nutrition. 2015 Nov-Dec;31(11-12):1385-93.

3. White JV et al. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: Characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet. 2012 May;112(5):730-8.

4. McClave SA et al. ACG clinical guideline: Nutrition therapy in the adult hospitalized patient. Am J Gastroenterol. 2016 Mar;111(3):315-334.

5. Mueller C et al. A.S.P.E.N. clinical guidelines: Nutrition screening, assessment, and intervention in adults. JPEN J Parenter Enter Nutr. 2011 Jan;35(1):16-24.

6. McClave SA et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN J Parenter Enter Nutr. 2016 Feb;40(2):159-211.

7. August D et al. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enter Nutr. 2002 Jan-Feb:26(1):SUPPL:1SA-138SA.

8. Kirkland LL et al. Nutrition in the hospitalized patient. J Hosp Med. 2013 Jan;8(1):52-8.

9. National Collaborating Centre for Acute Care, February 2006. Nutrition support in adults Oral nutrition support, enteral tube feeding and parenteral nutrition. National Collaborating Centre for Acute Care, London. Available from www.rcseng.ac.uk.

10. Corrigan ML et al. Nutrition in the stroke patient. Nutr Clin Pract. 2011 Jun;26(3):242-52.

11. Loser C et al. ESPEN guidelines on artificial enteral nutrition – Percutaneous endoscopic gastrostomy (PEG). Clin Nutr. 2005 Oct;24(5):848-61.

12. Mehler PS et al. Nutritional rehabilitation: Practical guidelines for refeeding the anorectic patient. J Nutr Metab. 2010. doi: 10.1155/2010/625782.

13. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

14. Singh N et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: A noninferiority randomized controlled trial. Pancreas. 2012 Jan;41(1):153-9.

15. Braga M et al. ESPEN guidelines on parenteral nutrition: Surgery. Clin Nutr. 2009 Aug;28(4):378-86.

16. Weimann A et al. ESPEN Guidelines on enteral nutrition: Surgery including organ transplantation. Clin Nutr. 2006 Apr;25(2):224-44.

Additional reading

• Kirkland LL et al. Nutrition in the Hospitalized Patient. J Hosp Med. 2013 Jan;8(1):52-8.
• McClave SA et al. ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient. Am J Gastroenterol. 2016 Mar;111(3):315-334.

Quiz: Recognizing Malnutrition

Which of the following is not a criteria for the diagnosis of malnutrition?

A. Weight loss

B. Insufficient energy intake

C. Prealbumin

D. Diminished handgrip strength

Answer: C. Prealbumin. Laboratory indicators of nutrition, such as albumin, prealbumin, and transferrin, and markers of infection or inflammation are not recommended for the determination of nutritional status. Because negative acute-phase reactants, they instead can be used as surrogate markers of nutritional risk and degree of inflammation

Key Points

• At the time of admission to the hospital, malnutrition is present in 20-50% of patients. All hospitalized patients should be screened for nutritional risk and nutritional support should be considered if patients are not expected to be able to meet nutritional needs for more than 7 days.
• Patients with severe malnutrition on admission, severe critical illness, or severe acute pancreatitis should be provided nutritional support within 24-48 hours.
• Use the gut! Nutritional support should be provided via the most physiologic route possible. Total parenteral nutrition (TPN) should be reserved for patients in whom adequate nutrition cannot be provided enterally.
• Consider a percutaneous endoscopic gastrostomy (PEG) tube if the patient is expected to require tube feedings for more than 30 days.
• Patients with severe malnutrition who are given nutritional support are at high risk of developing refeeding syndrome, which manifests as electrolyte depletions and heart failure or volume overload.

Click Here to Read Supplement. 

In a new supplement to Neurology Reviews, expert Richard J. Nowak, MD, MS, discusses the burden of myasthenia gravis and challenges in treating the disease.

Topics in this supplement include:

• Pathophysiology of Myasthenia Gravis
• Treatment Resistant Myasthenia Gravis
• Burden and Cost

Click Here to Read Supplement.

_{US/UNB-gMG/18/0033}

Click Here to Read Supplement. 

In a new supplement to Neurology Reviews, expert Richard J. Nowak, MD, MS, discusses the burden of myasthenia gravis and challenges in treating the disease.

Topics in this supplement include:

• Pathophysiology of Myasthenia Gravis
• Treatment Resistant Myasthenia Gravis
• Burden and Cost

Click Here to Read Supplement.

_{US/UNB-gMG/18/0033}

Click Here to Read Supplement. 

In a new supplement to Neurology Reviews, expert Richard J. Nowak, MD, MS, discusses the burden of myasthenia gravis and challenges in treating the disease.

Topics in this supplement include:

• Pathophysiology of Myasthenia Gravis
• Treatment Resistant Myasthenia Gravis
• Burden and Cost

Click Here to Read Supplement.

_{US/UNB-gMG/18/0033}

Pelvic inflammatory disease caused by chlamydia appears to significantly increase the risk of ovarian cancer, according to research to be presented at the annual meeting of the American Association for Cancer Research.

The finding, replicated in two large databases, suggests that promptly treating the infection might reduce the lifetime risk of developing ovarian cancer, Britton Trabert, PhD, said during a press briefing held in advance of the meeting.

“Ovarian cancer is typically diagnosed at a late stage and therefore has a poor prognosis,” said Dr. Mardis of The Nationwide Hospital, Columbus, Ohio. “Chlamydia will be an important point of study here, both because of the frequency of this infection, and because it is quite difficult to detect, due to its asymptomatic nature. But the most important take-home point is that we might be able to go a long way in terms of preventing ovarian cancer by routinely screening for infective agents.”

Pelvic inflammatory disease is known to be associated with ovarian cancer, and chlamydia is a leading cause of the disease, noted Dr. Trabert. “But chlamydia infections can be asymptomatic and persist for months or even years, so ascertainment of past chlamydia infections is challenging.”

To investigate the potential link between these infections and ovarian cancer, Dr. Trabert and her colleagues examined associations between antibodies to several infectious agents, including chlamydia, in two large ovarian cancer databases: a population-based case/control study in Poland and a case-control study nested into the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

The researchers screened for antibodies to chlamydia, Mycoplasma genitalium, Epstein-Barre virus, human papillomavirus, herpes simplex virus-1 and -2, polyomavirus, hepatitis B and C, and cytomegalovirus. The chlamydia antibody selected was plasmid-encoded Pgp3 protein, considered the gold standard measurement for prior or existing chlamydia infections.

The patient cohorts comprised 278 cases vs. 556 controls from the Polish study, and 160 cases vs. 159 controls from the PLCO study. Serum samples were collected at the time of ovarian cancer diagnosis in the Polish cohort, and before diagnosis in the PLCO cohort.

Dr. Trabert presented odds ratios for a Pgp3 antibody titer cut point indicative of past chlamydia infection, and a “more stringent” higher cut point indicative of current or chronic infection. She and her colleagues found statistically significant associations for each cut point in both studies.

In the Polish cohort, the lower Pgp3 cut point was associated with a 63% increased risk of ovarian cancer (odds ratio, 1.63). The higher cut point was associated with a doubling of risk (OR, 2.0).

In the PLCO cohort, the lower cut point was associated with a 43% increased risk (OR, 1.43). The higher cut point more than doubled the risk of ovarian cancer (OR, 2.25).

Neither cohort showed any significant association of ovarian cancer with any of the other antibodies, Dr. Trabert said.

The NCI Intramural Research Program supported the study. Dr. Trabert and her colleagues declared no conflicts of interest.

[email protected]

SOURCE: Trabert et al. Abstract 4942.

Pelvic inflammatory disease caused by chlamydia appears to significantly increase the risk of ovarian cancer, according to research to be presented at the annual meeting of the American Association for Cancer Research.

The finding, replicated in two large databases, suggests that promptly treating the infection might reduce the lifetime risk of developing ovarian cancer, Britton Trabert, PhD, said during a press briefing held in advance of the meeting.

“Ovarian cancer is typically diagnosed at a late stage and therefore has a poor prognosis,” said Dr. Mardis of The Nationwide Hospital, Columbus, Ohio. “Chlamydia will be an important point of study here, both because of the frequency of this infection, and because it is quite difficult to detect, due to its asymptomatic nature. But the most important take-home point is that we might be able to go a long way in terms of preventing ovarian cancer by routinely screening for infective agents.”

Pelvic inflammatory disease is known to be associated with ovarian cancer, and chlamydia is a leading cause of the disease, noted Dr. Trabert. “But chlamydia infections can be asymptomatic and persist for months or even years, so ascertainment of past chlamydia infections is challenging.”

To investigate the potential link between these infections and ovarian cancer, Dr. Trabert and her colleagues examined associations between antibodies to several infectious agents, including chlamydia, in two large ovarian cancer databases: a population-based case/control study in Poland and a case-control study nested into the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

The researchers screened for antibodies to chlamydia, Mycoplasma genitalium, Epstein-Barre virus, human papillomavirus, herpes simplex virus-1 and -2, polyomavirus, hepatitis B and C, and cytomegalovirus. The chlamydia antibody selected was plasmid-encoded Pgp3 protein, considered the gold standard measurement for prior or existing chlamydia infections.

The patient cohorts comprised 278 cases vs. 556 controls from the Polish study, and 160 cases vs. 159 controls from the PLCO study. Serum samples were collected at the time of ovarian cancer diagnosis in the Polish cohort, and before diagnosis in the PLCO cohort.

Dr. Trabert presented odds ratios for a Pgp3 antibody titer cut point indicative of past chlamydia infection, and a “more stringent” higher cut point indicative of current or chronic infection. She and her colleagues found statistically significant associations for each cut point in both studies.

In the Polish cohort, the lower Pgp3 cut point was associated with a 63% increased risk of ovarian cancer (odds ratio, 1.63). The higher cut point was associated with a doubling of risk (OR, 2.0).

In the PLCO cohort, the lower cut point was associated with a 43% increased risk (OR, 1.43). The higher cut point more than doubled the risk of ovarian cancer (OR, 2.25).

Neither cohort showed any significant association of ovarian cancer with any of the other antibodies, Dr. Trabert said.

The NCI Intramural Research Program supported the study. Dr. Trabert and her colleagues declared no conflicts of interest.

[email protected]

SOURCE: Trabert et al. Abstract 4942.

Pelvic inflammatory disease caused by chlamydia appears to significantly increase the risk of ovarian cancer, according to research to be presented at the annual meeting of the American Association for Cancer Research.

The finding, replicated in two large databases, suggests that promptly treating the infection might reduce the lifetime risk of developing ovarian cancer, Britton Trabert, PhD, said during a press briefing held in advance of the meeting.

“Ovarian cancer is typically diagnosed at a late stage and therefore has a poor prognosis,” said Dr. Mardis of The Nationwide Hospital, Columbus, Ohio. “Chlamydia will be an important point of study here, both because of the frequency of this infection, and because it is quite difficult to detect, due to its asymptomatic nature. But the most important take-home point is that we might be able to go a long way in terms of preventing ovarian cancer by routinely screening for infective agents.”

Pelvic inflammatory disease is known to be associated with ovarian cancer, and chlamydia is a leading cause of the disease, noted Dr. Trabert. “But chlamydia infections can be asymptomatic and persist for months or even years, so ascertainment of past chlamydia infections is challenging.”

To investigate the potential link between these infections and ovarian cancer, Dr. Trabert and her colleagues examined associations between antibodies to several infectious agents, including chlamydia, in two large ovarian cancer databases: a population-based case/control study in Poland and a case-control study nested into the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

The researchers screened for antibodies to chlamydia, Mycoplasma genitalium, Epstein-Barre virus, human papillomavirus, herpes simplex virus-1 and -2, polyomavirus, hepatitis B and C, and cytomegalovirus. The chlamydia antibody selected was plasmid-encoded Pgp3 protein, considered the gold standard measurement for prior or existing chlamydia infections.

The patient cohorts comprised 278 cases vs. 556 controls from the Polish study, and 160 cases vs. 159 controls from the PLCO study. Serum samples were collected at the time of ovarian cancer diagnosis in the Polish cohort, and before diagnosis in the PLCO cohort.

Dr. Trabert presented odds ratios for a Pgp3 antibody titer cut point indicative of past chlamydia infection, and a “more stringent” higher cut point indicative of current or chronic infection. She and her colleagues found statistically significant associations for each cut point in both studies.

In the Polish cohort, the lower Pgp3 cut point was associated with a 63% increased risk of ovarian cancer (odds ratio, 1.63). The higher cut point was associated with a doubling of risk (OR, 2.0).

In the PLCO cohort, the lower cut point was associated with a 43% increased risk (OR, 1.43). The higher cut point more than doubled the risk of ovarian cancer (OR, 2.25).

Neither cohort showed any significant association of ovarian cancer with any of the other antibodies, Dr. Trabert said.

The NCI Intramural Research Program supported the study. Dr. Trabert and her colleagues declared no conflicts of interest.

[email protected]

SOURCE: Trabert et al. Abstract 4942.

Look, I am not a burnout expert. And neither are you (presumably). None of us know much, but that won’t stop the regulations from coming. Program directors are already being asked to provide “wellness plans.” Through the SVS, experts have been enlisted to help, but it is now clear that what works for others won’t necessarily work for vascular surgeons. The next step is up to us. We are the only ones with detailed knowledge of our lives. I believe we are moving closer to answers but still face a few significant hurdles. Don’t worry, there are solutions. Hear me out …

Previously, I shared three studies with you, which found that vascular surgeons had the highest rates of suicidal ideation and career dissatisfaction among surgeons while spending more hours in the hospital than any other specialty. So what has been done to address these horrific numbers? Very little. We need answers now, but most of the data are over 10 years old. Much has changed in our specialty. The endovascular revolution created an entirely new working paradigm. A busy vascular surgeon used to perform 300 cases annually; now this number approaches 1,000. More procedures means more clerical work. Lead aprons and radiation exposure have added new ergonomic and medical concerns. Reimbursement dynamics now favor shorter, more frequent patient interactions over longer, more complex cases. We are benchmarked against old work standards while CPT bundling continuously lowers current RVU designations. EMR was supposed to make our lives better; it has done the opposite. Patient-centered health care has become a mantra, but the measures taken often backfire. Practicing medicine where the desired outcome is a high score on patient satisfaction surveys will likely lead to unnecessary tests, poor cost allocation, and low physician fulfillment. Quality of care is now measured scrupulously while the quality of our lives remains undocumented.

In the absence of organized reform, burnout appears to be increasing. A recent Mayo Clinic–AMA study found the current prevalence to be 54% among physicians. All of this has not happened overnight. I believe practicing vascular surgeons are resilient by default. The majority of us trained prior to the enforcement of duty hour restrictions. Out of high school, I enrolled in a 6-year BA/MD program (skipping 2 years of college seemed like a great idea in high school, less so when I got there). Half of my class never finished. In my intern year, six of the eight categorical residents dropped out. My odds of reaching PGY 2 were 12.5%. Fuzzy math aside, all of your stories are similar. We have proved our resilience over and over again. What is happening here is different.

Burnout is described as emotional exhaustion, low self-esteem, and depersonalization/cynicism. It develops slowly, progressively as stressors increase. A common thread seems to be the feeling that you alone are not enough. Examine your daily life. What are your most common stressors? For me, they relate to time management, clinical documentation, and whatever fresh hell my kids’ teachers have cooked up for “school projects.”

*****Scene*****

Wife: Can you help Luke (kindergarten) finish his diorama? It needs to be a scale depiction of his 3 favorite scenes from Wagner’s Ring cycle.

Me: Sure, I just need to complete the wind tunnel testing on Jack’s (3rd grade) carbon-neutral peanut-free alternative fuel source rocket booster.

Off stage – 7th Grade Son: The genetically modified spiders got loose again!

*****End Scene*****

We want to do a good job, but more hurdles are placed in our way. A recent AMA/Dartmouth Hitchcock study found that 50% of physicians’ time is spent performing data entry and other administrative work. Only 27% of time was spent on patient care. Every hour of face-to-face patient time requires 2 hours of EMR/clerical work. We are trapped in a bureaucratic prison. For years, every quality initiative was solved with a new form. To enter a simple note today, we must first “establish our relationship” with the patient, then ably click through a minefield of “warning boxes” signifying impending DVT prophylaxis catastrophes and antibiotic crimes and misdemeanors, next we scroll through a pre-populated postapocalyptic hellscape of minute- by-minute vital sign entries and lab values dating back to inception. Then, and only then, finally, ON PAGE 11, we can meagerly type: Patient at wound care, will come back on evening rounds.

Dr. Sheahan is the Claude C. Craighead Jr. Professor and Chair, Division of Vascular and Endovascular Surgery, Louisiana State University Health Sciences Center, New Orleans.

Look, I am not a burnout expert. And neither are you (presumably). None of us know much, but that won’t stop the regulations from coming. Program directors are already being asked to provide “wellness plans.” Through the SVS, experts have been enlisted to help, but it is now clear that what works for others won’t necessarily work for vascular surgeons. The next step is up to us. We are the only ones with detailed knowledge of our lives. I believe we are moving closer to answers but still face a few significant hurdles. Don’t worry, there are solutions. Hear me out …

Previously, I shared three studies with you, which found that vascular surgeons had the highest rates of suicidal ideation and career dissatisfaction among surgeons while spending more hours in the hospital than any other specialty. So what has been done to address these horrific numbers? Very little. We need answers now, but most of the data are over 10 years old. Much has changed in our specialty. The endovascular revolution created an entirely new working paradigm. A busy vascular surgeon used to perform 300 cases annually; now this number approaches 1,000. More procedures means more clerical work. Lead aprons and radiation exposure have added new ergonomic and medical concerns. Reimbursement dynamics now favor shorter, more frequent patient interactions over longer, more complex cases. We are benchmarked against old work standards while CPT bundling continuously lowers current RVU designations. EMR was supposed to make our lives better; it has done the opposite. Patient-centered health care has become a mantra, but the measures taken often backfire. Practicing medicine where the desired outcome is a high score on patient satisfaction surveys will likely lead to unnecessary tests, poor cost allocation, and low physician fulfillment. Quality of care is now measured scrupulously while the quality of our lives remains undocumented.

In the absence of organized reform, burnout appears to be increasing. A recent Mayo Clinic–AMA study found the current prevalence to be 54% among physicians. All of this has not happened overnight. I believe practicing vascular surgeons are resilient by default. The majority of us trained prior to the enforcement of duty hour restrictions. Out of high school, I enrolled in a 6-year BA/MD program (skipping 2 years of college seemed like a great idea in high school, less so when I got there). Half of my class never finished. In my intern year, six of the eight categorical residents dropped out. My odds of reaching PGY 2 were 12.5%. Fuzzy math aside, all of your stories are similar. We have proved our resilience over and over again. What is happening here is different.

Burnout is described as emotional exhaustion, low self-esteem, and depersonalization/cynicism. It develops slowly, progressively as stressors increase. A common thread seems to be the feeling that you alone are not enough. Examine your daily life. What are your most common stressors? For me, they relate to time management, clinical documentation, and whatever fresh hell my kids’ teachers have cooked up for “school projects.”

*****Scene*****

Wife: Can you help Luke (kindergarten) finish his diorama? It needs to be a scale depiction of his 3 favorite scenes from Wagner’s Ring cycle.

Me: Sure, I just need to complete the wind tunnel testing on Jack’s (3rd grade) carbon-neutral peanut-free alternative fuel source rocket booster.

Off stage – 7th Grade Son: The genetically modified spiders got loose again!

*****End Scene*****

We want to do a good job, but more hurdles are placed in our way. A recent AMA/Dartmouth Hitchcock study found that 50% of physicians’ time is spent performing data entry and other administrative work. Only 27% of time was spent on patient care. Every hour of face-to-face patient time requires 2 hours of EMR/clerical work. We are trapped in a bureaucratic prison. For years, every quality initiative was solved with a new form. To enter a simple note today, we must first “establish our relationship” with the patient, then ably click through a minefield of “warning boxes” signifying impending DVT prophylaxis catastrophes and antibiotic crimes and misdemeanors, next we scroll through a pre-populated postapocalyptic hellscape of minute- by-minute vital sign entries and lab values dating back to inception. Then, and only then, finally, ON PAGE 11, we can meagerly type: Patient at wound care, will come back on evening rounds.

Dr. Sheahan is the Claude C. Craighead Jr. Professor and Chair, Division of Vascular and Endovascular Surgery, Louisiana State University Health Sciences Center, New Orleans.

Look, I am not a burnout expert. And neither are you (presumably). None of us know much, but that won’t stop the regulations from coming. Program directors are already being asked to provide “wellness plans.” Through the SVS, experts have been enlisted to help, but it is now clear that what works for others won’t necessarily work for vascular surgeons. The next step is up to us. We are the only ones with detailed knowledge of our lives. I believe we are moving closer to answers but still face a few significant hurdles. Don’t worry, there are solutions. Hear me out …

Previously, I shared three studies with you, which found that vascular surgeons had the highest rates of suicidal ideation and career dissatisfaction among surgeons while spending more hours in the hospital than any other specialty. So what has been done to address these horrific numbers? Very little. We need answers now, but most of the data are over 10 years old. Much has changed in our specialty. The endovascular revolution created an entirely new working paradigm. A busy vascular surgeon used to perform 300 cases annually; now this number approaches 1,000. More procedures means more clerical work. Lead aprons and radiation exposure have added new ergonomic and medical concerns. Reimbursement dynamics now favor shorter, more frequent patient interactions over longer, more complex cases. We are benchmarked against old work standards while CPT bundling continuously lowers current RVU designations. EMR was supposed to make our lives better; it has done the opposite. Patient-centered health care has become a mantra, but the measures taken often backfire. Practicing medicine where the desired outcome is a high score on patient satisfaction surveys will likely lead to unnecessary tests, poor cost allocation, and low physician fulfillment. Quality of care is now measured scrupulously while the quality of our lives remains undocumented.

In the absence of organized reform, burnout appears to be increasing. A recent Mayo Clinic–AMA study found the current prevalence to be 54% among physicians. All of this has not happened overnight. I believe practicing vascular surgeons are resilient by default. The majority of us trained prior to the enforcement of duty hour restrictions. Out of high school, I enrolled in a 6-year BA/MD program (skipping 2 years of college seemed like a great idea in high school, less so when I got there). Half of my class never finished. In my intern year, six of the eight categorical residents dropped out. My odds of reaching PGY 2 were 12.5%. Fuzzy math aside, all of your stories are similar. We have proved our resilience over and over again. What is happening here is different.

Burnout is described as emotional exhaustion, low self-esteem, and depersonalization/cynicism. It develops slowly, progressively as stressors increase. A common thread seems to be the feeling that you alone are not enough. Examine your daily life. What are your most common stressors? For me, they relate to time management, clinical documentation, and whatever fresh hell my kids’ teachers have cooked up for “school projects.”

*****Scene*****

Wife: Can you help Luke (kindergarten) finish his diorama? It needs to be a scale depiction of his 3 favorite scenes from Wagner’s Ring cycle.

Me: Sure, I just need to complete the wind tunnel testing on Jack’s (3rd grade) carbon-neutral peanut-free alternative fuel source rocket booster.

Off stage – 7th Grade Son: The genetically modified spiders got loose again!

*****End Scene*****

We want to do a good job, but more hurdles are placed in our way. A recent AMA/Dartmouth Hitchcock study found that 50% of physicians’ time is spent performing data entry and other administrative work. Only 27% of time was spent on patient care. Every hour of face-to-face patient time requires 2 hours of EMR/clerical work. We are trapped in a bureaucratic prison. For years, every quality initiative was solved with a new form. To enter a simple note today, we must first “establish our relationship” with the patient, then ably click through a minefield of “warning boxes” signifying impending DVT prophylaxis catastrophes and antibiotic crimes and misdemeanors, next we scroll through a pre-populated postapocalyptic hellscape of minute- by-minute vital sign entries and lab values dating back to inception. Then, and only then, finally, ON PAGE 11, we can meagerly type: Patient at wound care, will come back on evening rounds.

Dr. Sheahan is the Claude C. Craighead Jr. Professor and Chair, Division of Vascular and Endovascular Surgery, Louisiana State University Health Sciences Center, New Orleans.

Closure of a patent foramen ovale (PFO) with an atrial septal aneurysm, hypermobility, or size of 2 mm or greater reduces the risk of stroke recurrence in patients with cryptogenic stroke, according to research published online ahead of print March 12 in the Journal of the American College of Cardiology.

“Considering the high prevalence of PFO in the general population and cryptogenic stroke patients, the key to appropriate use of this medical device is determining how to select optimal candidates for the procedure,” said Jae-Kwan Song, MD, PhD, a Professor in the Department of Medicine at Asan Medical Center, University of Ulsan College of Medicine, in Seoul, South Korea. “With our study and other recent trials, the criteria for selecting patients for the procedure are becoming clearer; in particular, the results suggest that closure is beneficial for those with high-risk PFO.”

A Multisite Superiority Trial

Previous research has not offered a definitive answer to the question of whether physicians can determine the potential benefit of PFO closure according to the PFO’s morphologic characteristics. In an earlier study, Dr. Song and colleagues found that high-risk PFO, as defined by transesophageal echocardiography (TEE), helped to predict stroke recurrence. The investigators then initiated the DEFENSE-PFO trial to evaluate whether restricting treatment to patients with cryptogenic stroke and PFO morphology associated with a higher rate of recurrent stroke would enhance the benefits of PFO closure.

Dr. Song and colleagues conducted DEFENSE-PFO, an open-label superiority trial, at two sites in South Korea from June 2011 through October 2017. Eligible patients had an ischemic stroke within the previous six months with no identifiable cause other than a high-risk PFO with left-to-right shunting. The researchers performed a standardized evaluation to rule out other identifiable mechanisms of stroke. The exclusion criteria were at least 50% stenosis of a major vessel, occlusion of a major vessel, and stroke resulting from small-vessel occlusive disease. Dr. Song and colleagues performed Holter monitoring or prolonged monitoring of cardiac rhythm to rule out paroxysmal atrial fibrillation.

A high-risk PFO was defined as one with an atrial septal aneurysm (ie, protrusion of the dilated segment of the septum at least 15 mm beyond the level surface of the atrial septum), hypermobility (ie, phasic septal excursion of 10 mm or more into either atrium), or size (ie, maximum separation of the septum primum from the secundum during the Valsalva maneuver) of 2 mm or greater on TEE.

Patients were randomized in equal groups to transcatheter PFO closure with the Amplatzer PFO Occluder plus medical therapy or medical therapy alone. All participants received antiplatelet therapy or anticoagulation chosen by the local investigator. During follow-up visits at one, three, six, 12, and 24 months, investigators recorded clinical data.

The primary end point was a composite of stroke, vascular death, or Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding during two years of follow-up. The secondary end point was asymptomatic ischemic stroke on follow-up MRI.

No End-Point Events After PFO Closure

Dr. Song and colleagues identified 450 patients with cryptogenic stoke and PFO, of whom 175 had high-risk PFO. They randomized 60 patients to each study arm. Participants’ mean age was 51.8. The groups were well balanced in terms of age, sex, medical history, qualifying event, modified Rankin scale score at discharge, and the anatomic characteristics of the PFO and atrial septum.

Seven patients randomized to PFO closure declined the treatment. Dual antiplatelet therapy was the most common medication in both groups at 30 days after randomization. This trend continued for as long as 12 months in the medication-only group, but single antiplatelet therapy became the most common strategy after six months in the PFO-closure group. About 17% of patients in the PFO-closure group stopped medication after the intervention. The median duration of follow-up was 2.8 years.

In the intention-to-treat analysis, no patient in the PFO-closure group had a primary end point event, compared with six patients in the medication-only group. Events recorded in the latter group included five ischemic strokes, one cerebral hemorrhage, two TIMI-defined major bleeding events, and one transient ischemic attack. The Kaplan-Meier two-year cumulative estimate of the probability of stroke was 10.5% in the medication-only group. The number of patients needed to treat with PFO closure to avoid one stroke at two years thus was 10.

Implications for Selection Criteria

The DEFENSE-PFO study differs from two previous trials that found benefits of PFO closure, but did not consider the anatomic features of the atrial septum or PFO. “The only trial with stringent entry criteria similar to ours is the CLOSE trial, which required that patients have a large interatrial right-to-left shunt (more than 30 microbubbles in the left atrium within three cardiac cycles after opacification of the right atrium) or an atrial septal aneurysm (a septum primum excursion greater than 10 mm),” said Dr. Song and colleagues. “Both the CLOSE trial and our trial showed no occurrence of stroke in patients who underwent PFO closure, suggesting that the beneficial effect of percutaneous device closure of PFO can be maximized by adding the morphologic characteristics of PFO, as evaluated by TEE, to the selection criteria for the procedure.”

Because the DEFENSE-PFO study was terminated early for patient safety, it was underpowered to provide a hazard ratio for its primary end point. In addition, selection bias may have affected the study, since it was conducted at a small number of centers.

—Erik Greb

Suggested Reading

Lee PH, Song J-K, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: The DEFENSE-PFO trial. J Am Coll Cardiol. 2018 Mar 12 [Epub ahead of print].

Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-1021.

Closure of a patent foramen ovale (PFO) with an atrial septal aneurysm, hypermobility, or size of 2 mm or greater reduces the risk of stroke recurrence in patients with cryptogenic stroke, according to research published online ahead of print March 12 in the Journal of the American College of Cardiology.

“Considering the high prevalence of PFO in the general population and cryptogenic stroke patients, the key to appropriate use of this medical device is determining how to select optimal candidates for the procedure,” said Jae-Kwan Song, MD, PhD, a Professor in the Department of Medicine at Asan Medical Center, University of Ulsan College of Medicine, in Seoul, South Korea. “With our study and other recent trials, the criteria for selecting patients for the procedure are becoming clearer; in particular, the results suggest that closure is beneficial for those with high-risk PFO.”

A Multisite Superiority Trial

Previous research has not offered a definitive answer to the question of whether physicians can determine the potential benefit of PFO closure according to the PFO’s morphologic characteristics. In an earlier study, Dr. Song and colleagues found that high-risk PFO, as defined by transesophageal echocardiography (TEE), helped to predict stroke recurrence. The investigators then initiated the DEFENSE-PFO trial to evaluate whether restricting treatment to patients with cryptogenic stroke and PFO morphology associated with a higher rate of recurrent stroke would enhance the benefits of PFO closure.

Dr. Song and colleagues conducted DEFENSE-PFO, an open-label superiority trial, at two sites in South Korea from June 2011 through October 2017. Eligible patients had an ischemic stroke within the previous six months with no identifiable cause other than a high-risk PFO with left-to-right shunting. The researchers performed a standardized evaluation to rule out other identifiable mechanisms of stroke. The exclusion criteria were at least 50% stenosis of a major vessel, occlusion of a major vessel, and stroke resulting from small-vessel occlusive disease. Dr. Song and colleagues performed Holter monitoring or prolonged monitoring of cardiac rhythm to rule out paroxysmal atrial fibrillation.

A high-risk PFO was defined as one with an atrial septal aneurysm (ie, protrusion of the dilated segment of the septum at least 15 mm beyond the level surface of the atrial septum), hypermobility (ie, phasic septal excursion of 10 mm or more into either atrium), or size (ie, maximum separation of the septum primum from the secundum during the Valsalva maneuver) of 2 mm or greater on TEE.

Patients were randomized in equal groups to transcatheter PFO closure with the Amplatzer PFO Occluder plus medical therapy or medical therapy alone. All participants received antiplatelet therapy or anticoagulation chosen by the local investigator. During follow-up visits at one, three, six, 12, and 24 months, investigators recorded clinical data.

The primary end point was a composite of stroke, vascular death, or Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding during two years of follow-up. The secondary end point was asymptomatic ischemic stroke on follow-up MRI.

No End-Point Events After PFO Closure

Dr. Song and colleagues identified 450 patients with cryptogenic stoke and PFO, of whom 175 had high-risk PFO. They randomized 60 patients to each study arm. Participants’ mean age was 51.8. The groups were well balanced in terms of age, sex, medical history, qualifying event, modified Rankin scale score at discharge, and the anatomic characteristics of the PFO and atrial septum.

Seven patients randomized to PFO closure declined the treatment. Dual antiplatelet therapy was the most common medication in both groups at 30 days after randomization. This trend continued for as long as 12 months in the medication-only group, but single antiplatelet therapy became the most common strategy after six months in the PFO-closure group. About 17% of patients in the PFO-closure group stopped medication after the intervention. The median duration of follow-up was 2.8 years.

In the intention-to-treat analysis, no patient in the PFO-closure group had a primary end point event, compared with six patients in the medication-only group. Events recorded in the latter group included five ischemic strokes, one cerebral hemorrhage, two TIMI-defined major bleeding events, and one transient ischemic attack. The Kaplan-Meier two-year cumulative estimate of the probability of stroke was 10.5% in the medication-only group. The number of patients needed to treat with PFO closure to avoid one stroke at two years thus was 10.

Implications for Selection Criteria

The DEFENSE-PFO study differs from two previous trials that found benefits of PFO closure, but did not consider the anatomic features of the atrial septum or PFO. “The only trial with stringent entry criteria similar to ours is the CLOSE trial, which required that patients have a large interatrial right-to-left shunt (more than 30 microbubbles in the left atrium within three cardiac cycles after opacification of the right atrium) or an atrial septal aneurysm (a septum primum excursion greater than 10 mm),” said Dr. Song and colleagues. “Both the CLOSE trial and our trial showed no occurrence of stroke in patients who underwent PFO closure, suggesting that the beneficial effect of percutaneous device closure of PFO can be maximized by adding the morphologic characteristics of PFO, as evaluated by TEE, to the selection criteria for the procedure.”

Because the DEFENSE-PFO study was terminated early for patient safety, it was underpowered to provide a hazard ratio for its primary end point. In addition, selection bias may have affected the study, since it was conducted at a small number of centers.

—Erik Greb

Suggested Reading

Lee PH, Song J-K, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: The DEFENSE-PFO trial. J Am Coll Cardiol. 2018 Mar 12 [Epub ahead of print].

Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-1021.

Closure of a patent foramen ovale (PFO) with an atrial septal aneurysm, hypermobility, or size of 2 mm or greater reduces the risk of stroke recurrence in patients with cryptogenic stroke, according to research published online ahead of print March 12 in the Journal of the American College of Cardiology.

“Considering the high prevalence of PFO in the general population and cryptogenic stroke patients, the key to appropriate use of this medical device is determining how to select optimal candidates for the procedure,” said Jae-Kwan Song, MD, PhD, a Professor in the Department of Medicine at Asan Medical Center, University of Ulsan College of Medicine, in Seoul, South Korea. “With our study and other recent trials, the criteria for selecting patients for the procedure are becoming clearer; in particular, the results suggest that closure is beneficial for those with high-risk PFO.”

A Multisite Superiority Trial

Previous research has not offered a definitive answer to the question of whether physicians can determine the potential benefit of PFO closure according to the PFO’s morphologic characteristics. In an earlier study, Dr. Song and colleagues found that high-risk PFO, as defined by transesophageal echocardiography (TEE), helped to predict stroke recurrence. The investigators then initiated the DEFENSE-PFO trial to evaluate whether restricting treatment to patients with cryptogenic stroke and PFO morphology associated with a higher rate of recurrent stroke would enhance the benefits of PFO closure.

Dr. Song and colleagues conducted DEFENSE-PFO, an open-label superiority trial, at two sites in South Korea from June 2011 through October 2017. Eligible patients had an ischemic stroke within the previous six months with no identifiable cause other than a high-risk PFO with left-to-right shunting. The researchers performed a standardized evaluation to rule out other identifiable mechanisms of stroke. The exclusion criteria were at least 50% stenosis of a major vessel, occlusion of a major vessel, and stroke resulting from small-vessel occlusive disease. Dr. Song and colleagues performed Holter monitoring or prolonged monitoring of cardiac rhythm to rule out paroxysmal atrial fibrillation.

A high-risk PFO was defined as one with an atrial septal aneurysm (ie, protrusion of the dilated segment of the septum at least 15 mm beyond the level surface of the atrial septum), hypermobility (ie, phasic septal excursion of 10 mm or more into either atrium), or size (ie, maximum separation of the septum primum from the secundum during the Valsalva maneuver) of 2 mm or greater on TEE.

Patients were randomized in equal groups to transcatheter PFO closure with the Amplatzer PFO Occluder plus medical therapy or medical therapy alone. All participants received antiplatelet therapy or anticoagulation chosen by the local investigator. During follow-up visits at one, three, six, 12, and 24 months, investigators recorded clinical data.

The primary end point was a composite of stroke, vascular death, or Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding during two years of follow-up. The secondary end point was asymptomatic ischemic stroke on follow-up MRI.

No End-Point Events After PFO Closure

Dr. Song and colleagues identified 450 patients with cryptogenic stoke and PFO, of whom 175 had high-risk PFO. They randomized 60 patients to each study arm. Participants’ mean age was 51.8. The groups were well balanced in terms of age, sex, medical history, qualifying event, modified Rankin scale score at discharge, and the anatomic characteristics of the PFO and atrial septum.

Seven patients randomized to PFO closure declined the treatment. Dual antiplatelet therapy was the most common medication in both groups at 30 days after randomization. This trend continued for as long as 12 months in the medication-only group, but single antiplatelet therapy became the most common strategy after six months in the PFO-closure group. About 17% of patients in the PFO-closure group stopped medication after the intervention. The median duration of follow-up was 2.8 years.

In the intention-to-treat analysis, no patient in the PFO-closure group had a primary end point event, compared with six patients in the medication-only group. Events recorded in the latter group included five ischemic strokes, one cerebral hemorrhage, two TIMI-defined major bleeding events, and one transient ischemic attack. The Kaplan-Meier two-year cumulative estimate of the probability of stroke was 10.5% in the medication-only group. The number of patients needed to treat with PFO closure to avoid one stroke at two years thus was 10.

Implications for Selection Criteria

The DEFENSE-PFO study differs from two previous trials that found benefits of PFO closure, but did not consider the anatomic features of the atrial septum or PFO. “The only trial with stringent entry criteria similar to ours is the CLOSE trial, which required that patients have a large interatrial right-to-left shunt (more than 30 microbubbles in the left atrium within three cardiac cycles after opacification of the right atrium) or an atrial septal aneurysm (a septum primum excursion greater than 10 mm),” said Dr. Song and colleagues. “Both the CLOSE trial and our trial showed no occurrence of stroke in patients who underwent PFO closure, suggesting that the beneficial effect of percutaneous device closure of PFO can be maximized by adding the morphologic characteristics of PFO, as evaluated by TEE, to the selection criteria for the procedure.”

Because the DEFENSE-PFO study was terminated early for patient safety, it was underpowered to provide a hazard ratio for its primary end point. In addition, selection bias may have affected the study, since it was conducted at a small number of centers.

—Erik Greb

Suggested Reading

Lee PH, Song J-K, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: The DEFENSE-PFO trial. J Am Coll Cardiol. 2018 Mar 12 [Epub ahead of print].

Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-1021.

Jeffrey Glasheen, MD, had not considered focusing on quality improvement (QI) while studying at the University of Wisconsin, Madison. It was not until a medical error led to the death of a family member that his eyes were opened to the potential consequences of a system not invested in care quality.

“I couldn’t square with it because I had spent the last two to three years of my life working with some of the most dedicated, passionate, hard working people who all were trying to improve lives, and the fact that what I was seeing could result in a family member dying just didn’t make sense,” said Dr. Glasheen. “At the time I thought ‘This must be one of those unfortunate things that happens once in a lifetime,’ and I put it on the back burner.”

As more research on medical errors emerged, however, Dr. Glasheen realized his family’s experience was not as unique as he had thought.

It was after reading the now famous Institute of Medicine report, “To err is human,” which found that medical errors were responsible for 44,000-98,000 deaths a year, that Dr. Glasheen resolved to pursue a career in quality improvement.

[email protected]

Jeffrey Glasheen, MD, had not considered focusing on quality improvement (QI) while studying at the University of Wisconsin, Madison. It was not until a medical error led to the death of a family member that his eyes were opened to the potential consequences of a system not invested in care quality.

“I couldn’t square with it because I had spent the last two to three years of my life working with some of the most dedicated, passionate, hard working people who all were trying to improve lives, and the fact that what I was seeing could result in a family member dying just didn’t make sense,” said Dr. Glasheen. “At the time I thought ‘This must be one of those unfortunate things that happens once in a lifetime,’ and I put it on the back burner.”

As more research on medical errors emerged, however, Dr. Glasheen realized his family’s experience was not as unique as he had thought.

It was after reading the now famous Institute of Medicine report, “To err is human,” which found that medical errors were responsible for 44,000-98,000 deaths a year, that Dr. Glasheen resolved to pursue a career in quality improvement.

[email protected]

Jeffrey Glasheen, MD, had not considered focusing on quality improvement (QI) while studying at the University of Wisconsin, Madison. It was not until a medical error led to the death of a family member that his eyes were opened to the potential consequences of a system not invested in care quality.

“I couldn’t square with it because I had spent the last two to three years of my life working with some of the most dedicated, passionate, hard working people who all were trying to improve lives, and the fact that what I was seeing could result in a family member dying just didn’t make sense,” said Dr. Glasheen. “At the time I thought ‘This must be one of those unfortunate things that happens once in a lifetime,’ and I put it on the back burner.”

As more research on medical errors emerged, however, Dr. Glasheen realized his family’s experience was not as unique as he had thought.

It was after reading the now famous Institute of Medicine report, “To err is human,” which found that medical errors were responsible for 44,000-98,000 deaths a year, that Dr. Glasheen resolved to pursue a career in quality improvement.

[email protected]

Herpes zoster, also known as shingles, is caused by a reactivation of varicella-zoster virus. Once an individual has been exposed to varicella-zoster virus, either from primary infection (chickenpox) or vaccination, the virus remains dormant in dorsal root ganglion cells. It may become reactivated at a later time, which results in herpes zoster. Typically, immunosuppression (hematologic malignancy and HIV infection) and age are factors that play a role in reactivation, although young people may develop shingles as well. Older age increases the incidence of herpes zoster.

Courtesy Dr. Donna Bilu Martin

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected]. This case and photo were submitted by Dr. Bilu Martin.

Herpes zoster, also known as shingles, is caused by a reactivation of varicella-zoster virus. Once an individual has been exposed to varicella-zoster virus, either from primary infection (chickenpox) or vaccination, the virus remains dormant in dorsal root ganglion cells. It may become reactivated at a later time, which results in herpes zoster. Typically, immunosuppression (hematologic malignancy and HIV infection) and age are factors that play a role in reactivation, although young people may develop shingles as well. Older age increases the incidence of herpes zoster.

Courtesy Dr. Donna Bilu Martin

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected]. This case and photo were submitted by Dr. Bilu Martin.

Herpes zoster, also known as shingles, is caused by a reactivation of varicella-zoster virus. Once an individual has been exposed to varicella-zoster virus, either from primary infection (chickenpox) or vaccination, the virus remains dormant in dorsal root ganglion cells. It may become reactivated at a later time, which results in herpes zoster. Typically, immunosuppression (hematologic malignancy and HIV infection) and age are factors that play a role in reactivation, although young people may develop shingles as well. Older age increases the incidence of herpes zoster.

Courtesy Dr. Donna Bilu Martin

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected]. This case and photo were submitted by Dr. Bilu Martin.

Counseling alone is unlikely to combat tanning addiction in adolescents; treatment that addresses the comorbid substance abuse and psychiatric issues is necessary, said Kimberly A. Miller, PhD, of the University of Southern California, Los Angeles, and her associates.

©Vidmantas Goldbergas/iStockphoto.com

Of a multiethnic sample of 2,637 high school students aged 16-17 years from Los Angeles, 7% met the modified CAGE criteria for tanning addiction, a compulsive drive to use indoor tanning beds frequently. The rate was similar in Hispanic teens and non-Hispanic white adolescents (7.6% versus 7.9%, respectively). Asian and Asian American teens had the lowest prevalence of tanning addiction (4.3%), while Native Hawaiian/Pacific Islanders had the highest (10.5%). Slightly more females than males met the criteria (9% vs. 5%), Dr. Miller and her associates reported in the Journal of Investigative Dermatology.

Past 30-day tobacco and marijuana use was significantly associated with tanning addiction, and teens with problem drinking were 3.4 times as likely to meet tanning addiction criteria as were those without problem drinking. Adolescents with panic disorder symptoms were two times more likely to meet tanning addiction criteria than were those without symptoms, and those with obsessive-compulsive disorder symptoms were three times more likely, Dr. Miller and associates said.

“With each additional problem use of substances, the likelihood of tanning addiction was increased by 67% for adolescents; for each additional psychological symptom, this figure was 30%,” the researchers said.

Dr. Miller and her associates cited several limitations. One was the cross-sectional design of the study. Another was the study’s focus on adolescents from Los Angeles, which limits the generalizability of the findings.

The authors declared no conflicts of interest.

SOURCE: Miller KA et al. J Investig Dermatol. 2018. doi: 10.1016/j.jid.2018.02.018.

Counseling alone is unlikely to combat tanning addiction in adolescents; treatment that addresses the comorbid substance abuse and psychiatric issues is necessary, said Kimberly A. Miller, PhD, of the University of Southern California, Los Angeles, and her associates.

©Vidmantas Goldbergas/iStockphoto.com

Of a multiethnic sample of 2,637 high school students aged 16-17 years from Los Angeles, 7% met the modified CAGE criteria for tanning addiction, a compulsive drive to use indoor tanning beds frequently. The rate was similar in Hispanic teens and non-Hispanic white adolescents (7.6% versus 7.9%, respectively). Asian and Asian American teens had the lowest prevalence of tanning addiction (4.3%), while Native Hawaiian/Pacific Islanders had the highest (10.5%). Slightly more females than males met the criteria (9% vs. 5%), Dr. Miller and her associates reported in the Journal of Investigative Dermatology.

Past 30-day tobacco and marijuana use was significantly associated with tanning addiction, and teens with problem drinking were 3.4 times as likely to meet tanning addiction criteria as were those without problem drinking. Adolescents with panic disorder symptoms were two times more likely to meet tanning addiction criteria than were those without symptoms, and those with obsessive-compulsive disorder symptoms were three times more likely, Dr. Miller and associates said.

“With each additional problem use of substances, the likelihood of tanning addiction was increased by 67% for adolescents; for each additional psychological symptom, this figure was 30%,” the researchers said.

Dr. Miller and her associates cited several limitations. One was the cross-sectional design of the study. Another was the study’s focus on adolescents from Los Angeles, which limits the generalizability of the findings.

The authors declared no conflicts of interest.

SOURCE: Miller KA et al. J Investig Dermatol. 2018. doi: 10.1016/j.jid.2018.02.018.

Counseling alone is unlikely to combat tanning addiction in adolescents; treatment that addresses the comorbid substance abuse and psychiatric issues is necessary, said Kimberly A. Miller, PhD, of the University of Southern California, Los Angeles, and her associates.

©Vidmantas Goldbergas/iStockphoto.com

Of a multiethnic sample of 2,637 high school students aged 16-17 years from Los Angeles, 7% met the modified CAGE criteria for tanning addiction, a compulsive drive to use indoor tanning beds frequently. The rate was similar in Hispanic teens and non-Hispanic white adolescents (7.6% versus 7.9%, respectively). Asian and Asian American teens had the lowest prevalence of tanning addiction (4.3%), while Native Hawaiian/Pacific Islanders had the highest (10.5%). Slightly more females than males met the criteria (9% vs. 5%), Dr. Miller and her associates reported in the Journal of Investigative Dermatology.

Past 30-day tobacco and marijuana use was significantly associated with tanning addiction, and teens with problem drinking were 3.4 times as likely to meet tanning addiction criteria as were those without problem drinking. Adolescents with panic disorder symptoms were two times more likely to meet tanning addiction criteria than were those without symptoms, and those with obsessive-compulsive disorder symptoms were three times more likely, Dr. Miller and associates said.

“With each additional problem use of substances, the likelihood of tanning addiction was increased by 67% for adolescents; for each additional psychological symptom, this figure was 30%,” the researchers said.

Dr. Miller and her associates cited several limitations. One was the cross-sectional design of the study. Another was the study’s focus on adolescents from Los Angeles, which limits the generalizability of the findings.

The authors declared no conflicts of interest.

SOURCE: Miller KA et al. J Investig Dermatol. 2018. doi: 10.1016/j.jid.2018.02.018.

Alcohol dependence ages your brain. Artificial intelligence comes to glucose monitoring. There’s a promising combo treatment for allergic rhinitis. And evidence mounts for the importance of thrombectomy in stroke.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Alcohol dependence ages your brain. Artificial intelligence comes to glucose monitoring. There’s a promising combo treatment for allergic rhinitis. And evidence mounts for the importance of thrombectomy in stroke.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Alcohol dependence ages your brain. Artificial intelligence comes to glucose monitoring. There’s a promising combo treatment for allergic rhinitis. And evidence mounts for the importance of thrombectomy in stroke.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”