ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology

Parenteral nutrition offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate and enteral nutrition is not feasible, is contraindicated or is not accepted by the patient.These guidelines are intended to provide evidence-based recommendations for the use of parenteral nutrition in cancer patients. They were developed by an interdisciplinary expert group in accordance with accepted standards, are based on the most relevant publications of the last 30 years and share many of the conclusions of the ESPEN guidelines on enteral nutrition in oncology.Under-nutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis and, per se, responsible for excess morbidity and mortality. Many indications for parenteral nutrition parallel those for enteral nutrition (weight loss or reduction in food intake for more than 7–10 days), but only those who, for whatever reason cannot be fed orally or enterally, are candidates to receive parenteral nutrition. A standard nutritional regimen may be recommended for short-term parenteral nutrition, while in cachectic patients receiving intravenous feeding for several weeks a high fat-to-glucose ratio may be advised because these patients maintain a high capacity to metabolize fats. The limited nutritional response to the parenteral nutrition reflects more the presence of metabolic derangements which are characteristic of the cachexia syndrome (or merely the short duration of the nutritional support) rather than the inadequacy of the nutritional regimen. Perioperative parenteral nutrition is only recommended in malnourished patients if enteral nutrition is not feasible. In non-surgical well-nourished oncologic patients routine parenteral nutrition is not recommended because it has proved to offer no advantage and is associated with increased morbidity. A benefit, however, is reported in patients undergoing hematopoietic stem cell transplantation. Short-term parenteral nutrition is however commonly accepted in patients with acute gastrointestinal complications from chemotherapy and radiotherapy, and long-term (home) parenteral nutrition will sometimes be a life-saving maneuver in patients with sub acute/chronic radiation enteropathy. In incurable cancer patients home parenteral nutrition may be recommended in hypophagic/(sub)obstructed patients (if there is an acceptable performance status) if they are expected to die from starvation/under nutrition prior to tumor spread.

Summary of statements: Non-surgical Oncology
Subject	Recommendations	Grade	Number
Nutritional status	Nutritional assessment of all cancer patients should begin with tumor diagnosis and be repeated at every visit in order to initiate nutritional intervention early, before the general status is severely compromised and chances to restore a normal condition are few	C	1.1
	Total daily energy expenditure in cancer patients may be assumed to be similar to healthy subjects, or 20–25 kcal/kg/day for bedridden and 25–30 kcal/kg/day for ambulatory patients	C	1.4
	The majority of cancer patients requiring PN for only a short period of time do not need a special formulation. Using a higher than usual percentage of lipid (e.g. 50% of non-protein energy), may be beneficial for those with frank cachexia needing prolonged PN (Grade C)	C	1.5
Indications	Therapeutic goals for PN in cancer patients are the improvement of function and outcome by:	C	2.1
	• preventing and treating under-nutrition/cachexia,
	• enhancing compliance with anti-tumor treatments,
	• controlling some adverse effects of anti-tumor therapies,
	• improving quality of life
	PN is ineffective and probably harmful in non-aphagic oncological patients in whom there is no gastrointestinal reason for intestinal failure	A	2.1
	PN is recommended in patients with severe mucositis or severe radiation enteritis	C	2.1
Nutritional provision	Supplemental PN is recommended in patients if inadequate food and enteral intake (<60% of estimated energy expenditure) is anticipated for more than 10 days	C	2.2
	PN is not recommended if oral/enteral nutrient intake is adequate	A	2.2
	In the presence of systemic inflammation it appears to be extremely difficult to achieve whole body protein anabolism in cancer patients. In this situation, in addition to nutritional interventions, pharmacological efforts are recommended to modulate the inflammatory response	C	2.3
	Preliminary data suggest a potential positive role of insulin (Grade C). There are no data on n-3 fatty acids	C	2.4
Peri-operative care	Peri-operative PN is recommended in malnourished candidates for artificial nutrition, when EN is not possible	A	3.1
	Peri-operative PN should not be used in the well-nourished	A	3.1
During non-surgical therapy	The routine use of PN during chemotherapy, radiotherapy or combined therapy is not recommended	A	3.2
	If patients are malnourished or facing a period longer than one week of starvation and enteral nutritional support is not feasible, PN is recommended	C	3.2
Incurable patients	In intestinal failure, long-term PN should be offered, if (1) enteral nutrition is insufficient, (2) expected survival due to tumor progression is longer than 2–3 months),(3) it is expected that PN can stabilize or improve performance status and quality of life, and (4) the patient desires this mode of nutritional support	C	3.3
	There is probable benefit in supporting incurable cancer patients with weight loss and reduced nutrient intake with “supplemental” PN	B	3.4
Hematopoietic stem cell transplantation (HSCT)	In HSCT patients PN should be reserved for those with severe mucositis, ileus, or intractable vomiting	B	3.5
	No clear recommendation can be made as to the time of introduction of PN in HSCT patients. Its withdrawal should be considered when patients are able to tolerate approximately 50% of their requirements enterally	C	3.6
	HSCT patients may benefit from glutamine-supplemented PN	B	3.7
Tumor growth	Although PN supplies nutrients to the tumor, there is no evidence that this has deleterious effects on the outcome. This consideration should therefore have no influence on the decision to feed a cancer patient when PN is clinically indicated	C	4.1

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ESPEN Guidelines on Parenteral Nutrition: Surgery

In modern surgical practice it is advisable to manage patients within an enhanced recovery protocol and thereby have them eating normal food within 1–3 days. Consequently, there is little room for routine perioperative artificial nutrition. Only a minority of patients may benefit from such therapy. These are predominantly patients who are at risk of developing complications after surgery. The main goals of perioperative nutritional support are to minimize negative protein balance by avoiding starvation, with the purpose of maintaining muscle, immune, and cognitive function and to enhance postoperative recovery.Several studies have demonstrated that 7–10 days of preoperative parenteral nutrition improves postoperative outcome in patients with severe undernutrition who cannot be adequately orally or enterally fed. Conversely, its use in well-nourished or mildly undernourished patients is associated with either no benefit or with increased morbidity.Postoperative parenteral nutrition is recommended in patients who cannot meet their caloric requirements within 7–10 days orally or enterally. In patients who require postoperative artificial nutrition, enteral feeding or a combination of enteral and supplementary parenteral feeding is the first choice.The main consideration when administering fat and carbohydrates in parenteral nutrition is not to overfeed the patient. The commonly used formula of 25 kcal/kg ideal body weight furnishes an approximate estimate of daily energy expenditure and requirements. Under conditions of severe stress requirements may approach 30 kcal/kg ideal body weights.In those patients who are unable to be fed via the enteral route after surgery, and in whom total or near total parenteral nutrition is required, a full range of vitamins and trace elements should be supplemented on a daily basis.

Summary of statements: Surgery
Subject	Recommendations	Grade	Number
Indications	Preoperative fasting from midnight is unnecessary in most patients	A	Preliminary remarks
	Interruption of nutritional intake is unnecessary after surgery in most patients	A	Preliminary remarks
Application	Preoperative parenteral nutrition is indicated in severely undernourished patients who cannot be adequately orally or enterally fed	A	1
	Postoperative parenteral nutrition is beneficial in undernourished patients in whom enteral nutrition is not feasible or not tolerated	A	2
	Postoperative parenteral nutrition is beneficial in patients with postoperative complications impairing gastrointestinal function who are unable to receive and absorb adequate amounts of oral/enteral feeding for at least 7 days	A	2
	In patients who require postoperative artificial nutrition, enteral feeding or a combination of enteral and supplementary parenteral feeding is the first choice	A	2
	Combinations of enteral and parenteral nutrition should be considered in patients in whom there is an indication for nutritional support and in whom >60% of energy needs cannot be met via the enteral route, e.g. in high output enterocutaneous fistulae or in patients in whom partly obstructing benign or malignant gastro-intestinal lesions do not allow enteral refeeding. In completely obstructing lesions surgery should not be postponed because of the risk of aspiration or severe bowel distension leading to peritonitis	C	2
	In patients with prolonged gastrointestinal failure parenteral nutrition is life-saving	C	2
	Preoperative carbohydrate loading using the oral route is recommended in most patients. In the rare patients who cannot eat or are not allowed to drink preoperatively for whatever reasons the intravenous route can be used	A	3
Type of formula	The commonly used formula of 25 kcal/kg ideal body weight furnishes an approximate estimate of daily energy expenditure and requirements. Under conditions of severe stress requirements may approach 30 kcal/kg ideal body weight	B	4
	In illness/stressed conditions a daily nitrogen delivery equivalent to a protein intake of 1.5 g/kg ideal body weight (or approximately 20% of total energy requirements) is generally effective to limit nitrogen losses	B	4
	The Protein:Fat:Glucose caloric ratio should approximate to 20:30:50%	C	4
	At present, there is a tendency to increase the glucose:fat calorie ratio from 50:50 to 60:40 or even 70:30 of the non-protein calories, due to the problems encountered regarding hyperlipidemia and fatty liver, which is sometimes accompanied by cholestasis and in some patients may progress to non-alcoholic steatohepatitis	C	5
	Optimal nitrogen sparing has been shown to be achieved when all components of the parenteral nutrition mix are administered simultaneously over 24 hours	A	6
	Individualized nutrition is often unnecessary in patients without serious co-morbidity	C	7
	The optimal parenteral nutrition regimen for critically ill surgical patients should probably include supplemental n-3 fatty acids. The evidence-base for such recommendations requires further input from prospective randomised trials	C	8
	In well-nourished patients who recover oral or enteral nutrition by postoperative day 5 there is a little evidence that intravenous supplementation of vitamins and trace elements is required	C	9
	After surgery, in those patients who are unable to be fed via the enteral route, and in whom total or near total parenteral nutrition is required, a full range of vitamins and trace elements should be supplemented on a daily basis	C	9
	Weaning from parenteral nutrition is not necessary	A	10

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ESPEN Guidelines on Parenteral Nutrition: Hepatology

Parenteral nutrition (PN) offers the possibility to increase or to ensure nutrient intake in patients, in whom sufficient nutrition by oral or enteral alone is insufficient or impossible. Complementary to the ESPEN guideline on enteral nutrition of liver disease (LD) patients the present guideline is intended to give evidence-based recommendations for the use of PN in LD. For this purpose three paradigm conditions of LD were chosen: alcoholic steatohepatitis (ASH), liver cirrhosis and acute liver failure. The guideline was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was presented on the ESPEN website and visitors' criticism and suggestions were welcome and included in the final revision. PN improves nutritional state and liver function in malnourished patients with ASH. PN is safe and improves mental state in patients with cirrhosis and severe HE. Perioperative (including liver transplantation) PN is safe and reduces the rate of complications. In acute liver failure PN is a safe second-line option to adequately feed patients in whom enteral nutrition is insufficient or impossible.

Summary of statements: Alcoholic Steatohepatitis
Subject	Recommendations	Grade	Number
General	Use simple bedside methods such as the Subjective Global Assessment (SGA) or anthropometry to identify patients at risk of undernutrition.	C	1
	Start PN immediately in moderately or severely malnourished ASH patients, who cannot be fed sufficiently either orally or enterally.	A	1
	Give i.v. glucose (2–3 g kg−1 d−1) when patients have to abstain from food for more than 12 h.	C	1
	Give PN when the fasting period lasts longer than 72 h.	C	1
Energy	Provide energy to cover 1.3 × REE	C	2
	Give glucose to cover 50–60 % of non-protein energy requirements.	C	3
	Use lipid emulsions with a content of n-6 unsaturated fatty acids lower than in traditional pure soybean oil emulsions.	C	3
Amino acids	Provide amino acids at 1.2–1.5 g kg−1 d−1.	C	3
Micronutrients	Give water soluble vitamins and trace elements daily from the first day of PN.	C	3
	Administer vitamin B1 prior to starting glucose infusion to reduce the risk of Wernicke's encephalopathy.	C	3
Monitoring	Employ repeat blood sugar determinations in order to detect hypoglycemia and to avoid PN related hyperglycemia.	C	6
	Monitor phosphate, potassium and magnesium levels when refeeding malnourished patients.	C	3
Summary of statements: Liver Cirrhosis
Subject	Recommendations	Grade	Number
General	Use simple bedside methods such as the Subjective Global Assessment (SGA) or anthropometry to identify patients at risk of undernutrition.	C	4
	Start PN immediately in moderately or severely malnourished cirrhotic patients, who cannot be fed sufficiently either orally or enterally.	A	4
	Give i.v. glucose (2–3 g kg−1 d−1) when patients have to abstain from food for more than 12 h.	C	4
	Give PN when the fasting period lasts longer than 72 h.	C	4
	Consider PN in patients with unprotected airways and encephalopathy when cough and swallow reflexes are compromised.	C	4
	Use early postoperative PN if patients cannot be nourished sufficiently by either oral or enteral route.	A	4
	After liver transplantation, use early postoperative nutrition; PN is second choice to EN.	C	4
Energy	Provide energy to cover 1.3 x REE	C	5
	Give glucose to cover 50 % - 60 % of non-protein energy requirements.	C	6
	Reduce glucose infusion rate to 2–3 g kg−1 d−1 in case of hyperglycemia and use consider the use of i.v. insulin.	C	6
	Use lipid emulsions with a content of n-6 unsaturated fatty acids lower than in traditional pure soybean oil emulsions.	C	6
Amino acids	Provide amino acids at 1.2–1.5 g kg−1 d−1.	C	7
	In encephalopathy III° or IV°, consider the use of solutions rich in BCAA and low in AAA, methionine and tryptophane.	A	7
Micronutrients	Give water soluble vitamins and trace elements daily from the first day of PN.	C	8
	In alcoholic liver disease, administer vitamin B1 prior to starting glucose infusion to reduce the risk of Wernicke's encephalopathy.	C	3, 8
Monitoring	Employ repeat blood sugar determinations in order to avoid PN related hyperglycemia.	A	6
	Monitor phosphate, potassium and magnesium levels when refeeding malnourished patients.	C	8
Summary of statements: Acute Liver Failure
Subject	Recommendations	Grade	Number
General	Commence artificial nutrition when patient is unlikely to resume normal oral nutrition within the next 5–7 days.	C	9
	Use PN when patients cannot be fed adequately by EN.	C	9
Energy	Provide energy to cover 1.3 × REE.	C	10
	Consider using indirect calorimetry to measure individual energy expenditure.	C	10
	Give i.v. glucose (2–3 g kg−1 d−1) for prophylaxis or treatment of hypoglycaemia.	C	11
	In case of hyperglycaemia, reduce glucose infusion rate to 2–3 g kg−1 d−1 and consider the use of i.v. insulin.	C	11, 6
	Consider using lipid (0.8 – 1.2 g kg−1 d−1) together with glucose to cover energy needs in the presence of insulin resistance.	C	11
Amino acids	In acute or subacute liver failure, provide amino acids at 0.8–1.2 g kg−1 d−1.	C	11
Monitoring	Employ repeat blood sugar determinations in order to detect hypoglycaemia and to avoid PN related hyperglycaemia.	C	11
	Employ repeat blood ammonia determinations in order to adjust amino acid provision.	C	11

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ESPEN Guidelines on Parenteral Nutrition: Gastroenterology

Undernutrition as well as specific nutrient deficiencies has been described in patients with Crohn's disease (CD), ulcerative colitis (UC) and short bowel syndrome. In the latter, water and electrolytes disturbances may be a major problem.The present guidelines provide evidence-based recommendations for the indications, application and type of parenteral formula to be used in acute and chronic phases of illness.Parenteral nutrition is not recommended as a primary treatment in CD and UC. The use of parenteral nutrition is however reliable when oral/enteral feeding is not possible.There is a lack of data supporting specific nutrients in these conditions.Parenteral nutrition is mandatory in case of intestinal failure, at least in the acute period.In patients with short bowel, specific attention should be paid to water and electrolyte supplementation. Currently, the use of growth hormone, glutamine and GLP-2 cannot be recommended in patients with short bowel.

Summary of statements: Parenteral nutrition in Crohn's disease
Subject	Recommendations	Grade	Number
Indication	PN is indicated for patients who are malnourished or at risk of becoming malnourished and who have an inadequate or unsafe oral intake, a non (or poorly) functioning or perforated gut, or in whom the gut is inaccessible. Specific reasons in patients with CD include an obstructed gut, a short bowel, often with a high intestinal output or an enterocutaneous fistula.	B	4.1
Active disease	Parenteral nutrition (PN) should not be used as a primary treatment of inflammatory luminal CD.	A	3.5
	Bowel rest has not been proven to be more efficacious than nutrition per se.
Maintenance of remission	In case of persistent intestinal inflammation there is rarely a place for long-term PN.	B	3.7
	The most common indication for long-term PN is the presence of a short bowel.
Perioperative	Use of PN in the perioperative period in CD patients is similar to that of other surgical procedures.	B	3.6
Application	When indicated, PN improves nutritional status and reduces the consequences of undernutrition, providing there is not continuing intra-abdominal sepsis	B	1
	Specific deficits (trace elements, vitamins) should be corrected by appropriate supplementation.	B	1
	The use of PN in patients with CD should follow general recommendations for parenteral nutrition.	B	1
Route	Parenteral nutrition is usually combined with oral/enteral food unless there is continuing intra-abdominal sepsis or perforation. Central and peripheral routes may be selected according to the expected duration of PN	C	3.2
Type of formula	Although there are encouraging experimental data, the present clinical studies are insufficient to permit the recommendation of glutamine, n-3 fatty acids or other pharmaconutrients in CD.	B	4.3
Undernutrition	Parenteral nutrition may improve the quality of life in undernourished CD patients.	C	3.4
Summary of statements: PN in ulcerative colitis
Subject	Recommendations	Grade	Number
Indication	Parenteral nutrition should only be used in patients with UC who are malnourished or at risk of becoming malnourished before or after surgery if they cannot tolerate food or an enteral feed	B	9
Active disease	There is no place for PN in acute inflammatory UC as means of enabling bowel rest.	B	10
Maintenance of remission	Parenteral nutrition is not recommended.	B	11
Application	Treat specific deficiencies when oral route is not possible.	C	5
Type of formula	The value of specific substrates (n-3 fatty acids, glutamine) is not proven.	B	10.2
Summary of statements: Short bowel syndrome (intestinal failure)
Subject	Recommendations	Grade	Number
Indication	Maintenance and/or improvement of nutritional status, correction of water and electrolyte balance, improvement in quality of life.	B	15
Route
Post-op period	Predictions on the route of nutritional support needed can be made from knowledge of the remaining length of small bowel and the presence or absence of the colon. PN is likely to be needed if the remaining small bowel length is very short (e.g., less than 100 cm with a jejunostomy and less than 50 cm with a remaining colon in continuity). With longer lengths parenteral nutrition, water and electrolytes may be needed until oral/enteral intake is adequate to maintain nutrition, water and electrolyte status.	B	17.1
Adaptation phase	Patients with a jejunostomy have little change in their nutritional/fluid requirements with time. Patients with a colon in continuity with the small bowel have an improvement in absorption over 1–3 years and parenteral nutrition can often be reduced or stopped.	B	17.2
	Dietary counseling is important for those with a retained colon and may facilitate intestinal adaptation. In patients with a jejunostomy and a high output stoma advice on oral fluid intake and drug treatments are vital.
Maintenance/Stabilization	Parenteral nutrition, water and electrolytes (especially sodium and magnesium should be continued when oral/enteral intake is insufficient to maintain a normal body weight/hydration or when the intestinal/stool output is so great as to severely reduce the patient's quality of life. Assuming strict compliance with dietary/water and electrolyte advice, after 2 years, dependency on PN is likely to be long-term.	B	17.3
Type of formula	No specific substrate composition of PN is required per se.	B	16
	Specific attention should be paid to electrolyte supplementation (especially sodium and magnesium).	B	16, 17
	Currently, the use of growth hormone, glutamine or GLP-2 cannot be recommended.	B	18

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ESPEN Guidelines on Parenteral Nutrition: Geriatrics

Older subjects are at increased risk of partial or complete loss of independence due to acute and/or chronic disease and often of concomitant protein caloric malnutrition. Nutritional care and support should be an indispensable part of their management. Enteral nutrition is always the first choice for nutrition support. However, when patients cannot meet their nutritional requirements adequately via the enteral route, parenteral nutrition (PN) is indicated.PN is a safe and effective therapeutic procedure and age per se is not a reason to exclude patients from this treatment. The use of PN should always be balanced against a realistic chance of improvement in the general condition of the patient. Lower glucose tolerance, electrolyte and micronutrient deficiencies and lower fluid tolerance should be assumed in older patients treated by PN. Parenteral nutrition can be administered either via peripheral or central veins. Subcutaneous administration is also a possible solution for basic hydration of moderately dehydrated subjects. In the terminal, demented or dying patient the use of PN or hydration should only be given in accordance with other palliative treatments.

Summary of statements: Geriatrics
Subject	Recommendations	Grade	Number
Indications	Age per se is not a reason to exclude patients from PN.	C [IV]	1.1.
	PN is indicated and may allow adequate nutrition in patients who cannot meet their nutritional requirements via the enteral route.	C [IV]	1.1.
	PN support should be instituted in the older person facing a period of starvation of more than 3 days or if intake is likely to be insufficient for more than 7–10 days, and when oral or enteral nutrition is impossible.	C [IV]	1.1.
	Pharmacological sedation or physical restraining to make PN possible is not justified.	C [IV]	1.1.
	PN is a useful and effective method of nutritional support in older persons but compared to EN and oral nutritional supplements are much less often justified.	B [III]	1.2.
Metabolic/physiological features in older subjects	Insulin resistance and hyperglycaemia together with impairment of cardiac and renal function are the most relevant features. They may warrant the use of formulae with higher lipid content.	C [IV]	2
	Deficiencies in vitamins, trace elements and minerals should be suspected in older subjects.	B [IIb]	2
	The effect of nutritional support on restoration of depleted body cell mass is lower in elderly patients than in younger subjects. The oxidation capacity for lipid emulsions is not negatively influenced by age.	B [IIa]	2
Peripheral PN	Both central and peripheral nutrition can be used in geriatric patients.	C [IV]	3
	Osmolarity of peripheral parenteral nutrition should not be higher than 850 mOsmol/l.	B [III]	3
Subcutaneous fluid administration	The subcutaneous route is possible for fluid administration in order to correct mild to moderate dehydration but not to meet other nutrient requirements.	A [Ia]	4
PN and nutritional status	PN can improve nutritional status in older as well as in younger adults. However, active physical rehabilitation is essential for muscle gain.	B [IIb]	5
Functional status	PN can support improvement of functional status, but the margin of improvement is lower than in younger patients.	C [IV]	6
Morbidity and mortality	PN can reduce mortality and morbidity in older as well as in middle-aged subjects.	C [IV]	7
Length of hospital stay	No studies have assessed length of hospital stay in older patients on PN.		8
Quality of life	Long-term parenteral nutrition does not influence quality of life of older patients more negatively than it does in younger subjects.	C [IV]	9
Specific complications	There are no specific complications of PN in geriatric patients compared to other ages, but complications tend to be more frequent due to associated comorbidities.	C [IV]	10
Specific situations	Indications for PN are similar in younger and older adults in the hospital and at home.	B [III]	11
Ethical problems	PN or parenteral hydration should be considered as medical treatments rather than as basic care. Therefore their use should be balanced against a realistic chance of improvement in the general condition.	C [IV]	12

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ESPEN Guidelines on Parenteral Nutrition: On Cardiology and Pneumology

Nutritional support is becoming a mainstay of the comprehensive therapeutic approach to patients with chronic diseases. Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are frequently associated with the progressive development of malnutrition, due to reduced energy intake, increased energy expenditure and impaired anabolism. Malnutrition and eventually cachexia have been shown to have a negative influence on the clinical course of CHF and COPD, and to impinge on patients' quality of life. Nutritional support in these patients should be therefore considered, particularly to prevent progressive weight loss, since restoration of lean and fat body mass may not be achievable. In CHF and COPD patients, the gastrointestinal tract is normally accessible and functioning. Although recent reports suggest that heart failure is associated with modifications of intestinal morphology, permeability and absorption, the clinical relevance of these are still not clear. Oral supplementation and enteral nutrition should represent the first choices when cardiopulmonary patients need nutritional support, particularly given the potential complications and economic burden of parenteral nutrition. This appropriately preferential enteral approach partly explains the lack of robust clinical trials of the role of parenteral nutrition in CHF and COPD patients. Based on the available evidence collected via PubMed, Medline, and SCOPUS searches, it is recommended that parenteral nutrition is reserved for those patients in whom malabsorption has been documented and in those in whom enteral nutrition has failed.

Summary of statements: Parenteral Nutrition in Cardiology
Subject	Recommendations	Grade	Number
Background	The prevalence of cardiac cachexia, defined from weight loss of at least 6% in 6 months, has been estimated at about 12–15% in patients in New York Heart Association (NYHA) classes II–IV. The incidence of weight loss >6% in CHF patients with NYHA class III/IV is approximately 10% per year. CHF affects nutritional state, energy and substrate metabolism.	B	1.1
	The mortality in CHF patients with cardiac cachexia is 2–3 times higher than in non-cachectic CHF patients.	B	1.2
	Although there is limited evidence that gut function is impaired in CHF, decreased cardiac function can reduce bowel perfusion and lead to bowel wall oedema, resulting in malabsorption.	B	1.3
Indications	Although there is no evidence available from well-designed studies, PN is recommended to stop or reverse weight loss in patients with evidence of malabsorption, on the basis that it improves outcome in other similar conditions and there is a plausible physiological argument for it.	C	1.4
	Currently there is no indication for PN in the prophylaxis of cardiac cachexia. Further studies are needed to assess the impact of the parenteral administration of specific substrates on cardiac function.	C	1.5
Contra-indications	There are no specific contraindications to PN in CHF patients. However, considering that cardiac function is decreased and water retention is frequently found in CHF patients, it is recommended that PN should be avoided, other than in patients with evidence of malabsorption in whom enteral nutrition has been shown, or is strongly expected, to be ineffective.	B	1.6
Implementation	When feeding CHF patients, either enterally or parenterally, fluid overload must be avoided.	C	1.6
Summary of statements: Parenteral Nutrition in Respiratory Medicine
Subject	Recommendations	Grade	Number
Background	Between 25% and 40% of patients with advanced COPD are malnourished.	B	2.1
	Being underweight and having low fat-free mass are independently associated with a poor prognosis in patients with chronic respiratory insufficiency, especially in COPD.	B	2.2
Indications	There is no evidence showing that gut function is impaired in COPD patients. Therefore, considering that enteral nutrition is less expensive and associated with fewer and less severe complications than parenteral nutrition, enteral nutrition should represent the first approach to patients with COPD in need of nutritional support.	B	2.3
	There is limited evidence that COPD patients intolerant of EN profit from PN. Small studies do however suggest that, in combination with exercise and anabolic pharmacotherapy, PN has the potential to improve nutritional status and function.	C	2.4
Effect of PN	Loss of body weight is correlated with increased morbidity and mortality. However, due to the lack of studies of its effects, it is not possible to be sure if prognosis is influenced by the provision of PN.	B	2.5
Regimen selection	In patients with stable COPD, glucose-based PN causes an increase in the respiratory CO2 load. PN composition should accordingly be orientated towards lipids as the energy source. There is not sufficient evidence to recommend specific lipid substrates.	B	2.6

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Duration of Immunity to Norovirus Gastroenteritis

The duration of immunity to norovirus (NoV) gastroenteritis has been believed to be from 6 months to 2 years. However, several observations are inconsistent with this short period. To gain better estimates of the duration of immunity to NoV, we developed a mathematical model of community NoV transmission. The model was parameterized from the literature and also fit to age-specific incidence data from England and Wales by using maximum likelihood. We developed several scenarios to determine the effect of unknowns regarding transmission and immunity on estimates of the duration of immunity. In the various models, duration of immunity to NoV gastroenteritis was estimated at 4.1 (95% CI 3.2–5.1) to 8.7 (95% CI 6.8–11.3) years. Moreover, we calculated that children (<5 years) are much more infectious than older children and adults. If a vaccine can achieve protection for duration of natural immunity indicated by our results, its potential health and economic benefits could be substantial.Key words: Norovirus, modeling, mathematical model, immunity, incidence, vaccination, vaccine development, viruses, enteric infections, acute gastroenteritisNoroviruses (NoVs) are the most common cause of acute gastroenteritis (AGE) in industrialized countries. In the United States, NoV causes an estimated 21 million cases of AGE (1), 1.7 million outpatient visits (2), 400,000 emergency care visits, 70,000 hospitalizations (3), and 800 deaths annually across all age groups (4). Although the highest rates of disease are in young children, infection and disease occur throughout life (5), despite an antibody seroprevalence >50%, and infection rates approach 100% in older adults (6,7).Frequently cited estimates of the duration of immunity to NoV are based on human challenge studies conducted in the 1970s. In the first, Parrino et al. challenged volunteers with Norwalk virus (the prototype NoV strain) inoculum multiple times. Results suggested that the immunity to Norwalk AGE lasts from ≈2 months to 2 years (8). A subsequent study with a shorter challenge interval suggested that immunity to Norwalk virus lasts for at least 6 months (9). In addition, the collection of volunteer studies together demonstrate that antibodies against NoV may not confer protection and that protection from infection (serologic response or viral shedding) is harder to achieve than protection from disease (defined as AGE symptoms) (10–14). That said, most recent studies have reported some protection from illness and infection in association with antibodies that block binding of virus-like particles to histo-blood group antigen (HBGA) (13,14). Other studies have also associated genetic resistance to NoV infections with mutations in the 1,2-fucosyltransferase (FUT2) gene (or “secretor” gene) (15). Persons with a nonsecretor gene (FUT2−/−) represent as much as 20% of the European population. Challenge studies have also shown that recently infected volunteers are susceptible to heterologous strains sooner than to homotypic challenge, indicating limited cross-protection (11).One of many concerns with all classic challenge studies is that the virus dose given to volunteers was several thousand–fold greater than the small amount of virus capable of causing human illness (estimated as 18–1,000 virus particles) (16). Thus, immunity to a lower challenge dose, similar to what might be encountered in the community, might be more robust and broadly protective than the protection against artificial doses encountered in these volunteer studies. Indeed, Teunis et al. have clearly demonstrated a dose-response relationship whereby persons challenged with a higher NoV dose have substantially greater illness risk (16).Furthermore, in contrast with results of early challenge studies, several observations can be made that, when taken together, are inconsistent with a duration of immunity on the scale of months. First, the incidence of NoV in the general population has been estimated in several countries as ≈5% per year, with substantially higher rates in children (5). Second, Norwalk virus (GI.1) volunteer studies conducted over 3 decades, indicate that approximately one third of genetically susceptible persons (i.e., secretor-positive persons with a functional FUT2 gene) are immune (18,20,22). The point prevalence of immunity in the population (i.e., population immunity) can be approximated by the incidence of infection (or exposure) multiplied by the duration of immunity. If duration of immunity is truly <1 year and incidence is 5%, <5% of the population should have acquired immunity at any given time. However, challenge studies show population immunity levels on the order of 30%–45%, suggesting that our understanding of the duration of immunity is incomplete (8,11,17,18). HBGA–mediated lack of susceptibility may play a key role, but given the high seroprevalence of NoV antibodies and broad diversity of human HBGAs and NoV, HBGA–mediated lack of susceptibility cannot solely explain the discrepancy between estimates of duration of immunity and observed NoV incidence. Moreover, population immunity levels may be driven through the acquisition of immunity of fully susceptible persons or through boosting of immunity among those previously exposed.

Table 1

Summary of literature review of Norwalk virus volunteer challenge studies*

Evaluation of Cholera and Other Diarrheal Disease Surveillance System,Niger State,Nigeria-2012

Objective

To determine how the cholera and other diarrheal disease surveillance system in Niger state is meeting its surveillance objectives, to evaluate its performance and attributes and to describe its operation to make recommendations for improvement.

Introduction

Cholera causes frequent outbreaks in Nigeria, resulting in mortality. In 2010 and 2011, 41,936 cases (case fatality rate [CFR]-4.1%) and 23,366 cases (CFR-3.2%) were reported (1). Reported cases in Nigeria by week 26, 2012 was 309 (CFR-1.29%) involving 20 Local Government Areas in 6 States. In Nigeria, there are currently eleven (11) States including Niger state at high risk for cholera/bloodless diarrhea outbreaks.In 2011, Niger state had 2472 cholera cases (CFR-2%) and 45,111 other diarrhea diseases cases, recorded in more than half of state Purpose of surveillance system is to ensure early detection of cholera and other diarrheal cases and to monitor trends towards evidence-based decision for management, prevention and control.

Methods

We conducted evaluation in July, 2012. We used CDC guideline on surveillance system evaluation (2001) as guide to assess operation, performance and attributes (2). We conducted key informant/in-depth interviews with stakeholders. We examined cholera action plans for preparedness and response, conducted laboratory assessment, extracted and analyzed cholera surveillance (2005–2012) for frequencies/proportions using Microsoft Excel. Thematic analysis was done for qualitative data. We shared findings with stakeholders at all levels.

Results

Surveillance system was setup for early detection and monitoring towards evidence-based decision. State government funds system. Case definition used is highly sensitive and is any patient aged 5 years or more who develops acute watery diarrhea, with/without vomiting. Though simple case definition, laboratory confirmation makes surveillance complex. A passive system, active during outbreaks; has formal and informal sources of information and part of Integrated Disease Surveillance and Response (IDSR) system and flow(fig.1). It takes 24–48 hours between outbreaks onset, confirmation and response.Line list showed undefined/poorly labeled outcomes. Of 2472 cases in 2011 1320 (49%) were found in line list. 2011 monthly data completeness was 75%. So far in 2012, 5(0.02%) of all diarrhea cases were cholera. System captures only age as sociodemographics.Of 11 suspected cholera cases tested during 2011 epidemic, 7 confirmed as cholera (PPV-63%). Of 3 rumours of cholera outbreaks (January 2011-July 2012), one (PPV-33%) was true. Acceptability of system is high among all stakeholders interviewed. Timeliness of monthly reporting was 68.7% (

Computerized Text Analysis to Enhance Automated Pneumonia Detection

Objective

To improve the surveillance for pneumonia using the free-text of electronic medical records (EMR).

Introduction

Information about disease severity could help with both detection and situational awareness during outbreaks of acute respiratory infections (ARI). In this work, we use data from the EMR to identify patients with pneumonia, a key landmark of ARI severity. We asked if computerized analysis of the free-text of clinical notes or imaging reports could complement structured EMR data to uncover pneumonia cases.

Methods

A previously validated ARI case-detection algorithm (CDA) (sensitivity, 99%; PPV, 14%) [1] flagged VAMHCS outpatient visits with associated chest imaging (n = 2737). Manually categorized imaging reports (Non-Negative if they could support the diagnosis of pneumonia, Negative otherwise; kappa = 0.88), served as a reference for the development of an automated report classifier through machine-learning [2]. EMR entries related to visits with Non-Negative chest imaging were manually reviewed to identify cases with Possible Pneumonia (new symptom(s) of cough, sputum, fever/chills/night sweats, dyspnea, pleuritic chest pain) or with Pneumonia-in-Plan (pneumonia listed as one of two most likely diagnoses in a physician’s note). These cases were used as reference for the development of the EMR-based CDAs. CDA components included ICD-9 codes for the full spectrum of ARI [1] or for the pneumonia subset, text analysis aimed at non-negated ARI symptoms in the clinical note [1] and the above-mentioned imaging report text classifier.

Results

The manual review identified 370 reference cases with Possible Pneumonia and 250 with Pneumonia-in-Plan. Statistical performance for illustrative CDAs that combined structured EMR parameters with or without text analyses are shown in the ConclusionsAutomated text analysis of chest imaging reports can improve our ability to separate outpatients with pneumonia from those with a milder form of ARI.

CDA Number	1	2	3	4	5	6	7	8	9	10	11	12
	Possible Pneumonia						Pneumonia-in-Plan
CDA Components
(Pneumonia ICD-9 Codes	•	•					•	•
(ARI ICD-9 Codes			•	•	•	•			•	•	•	•
OR Text of Clinical Notes)					•	•					•	•
AND Chest Imaging Obtained	•	•	•	•	•	•	•	•	•	•	•	•
AND Text of Imaging Reports		•		•		•		•		•		•
Sensitivity (%)	36.8	28.4	85.9	58.4	99.7	66.2	52	40.8	93.6	68.8	100	74.8
Specificity (%)	95.4	99.7	29.8	98.5	2.2	98	95.4	99.6	29.8	96.8	2.3	95.7
PPV (%)	55.3	93.8	16	86.1	13.7	83.3	52.8	91.1	12	68.5	9.3	63.6
NPV (%)	91	90	93.2	93.8	98.1	95	95.2	94.4	98	97	100	97.4
F-Measure	44.2	43.6	27	69.6	24.1	73.8	52.4	56.4	21	68.6	17	68.7

Open in a separate window     

Selecting Targeted Symptoms/Syndromes for Syndromic Surveillance in Rural China

Objective

To select the potential targeted symptoms/syndromes as early warning indicators for epidemics or outbreaks detection in rural China.

Introduction

Patients’ chief complaints (CCs) as a common data source, has been widely used in syndromic surveillance due to its timeliness, accuracy and availability (1). For automated syndromic surveillance, CCs always classified into predefined syndromic categories to facilitate subsequent data aggregation and analysis. However, in rural China, most outpatient doctors recorded the information of patients (e.g. CCs) into clinic logs manually rather than computers. Thus, more convenient surveillance method is needed in the syndromic surveillance project (ISSC). And the first and important thing is to select the targeted symptoms/syndromes.

Methods

Epidemiological analysis was conducted on data from case report system in Jingmen City (one study site in ISSC) from 2004 to 2009. Initial symptoms/syndromes were selected by literature reviews. And finally expert consultation meetings, workshops and field investigation were held to confirm the targeted symptoms/syndromes.

Results

10 kinds of infectious diseases, 6 categories of emergencies, and 4 bioterrorism events (i.e. plague, anthrax, botulism and hemorrhagic fever) were chose as specific diseases/events for monitoring (Respiratory casesGastrointestinal casesEmergenciesName%Name%NameEvents (No.)^*Pulmonary tuberculosis82.38^†Hand-foot-mouth diseases41.73^†A(H1N1)10^†Mumps9.14^†Bacillary dysentery28.56^†Mumps5^†Measles3.35^†Hepatitis A15.36^†Hand-foot-mouth diseases1^†Varicella2.00^† Infectious diarrhea6.58^†Bacillary dysentery1^†Influenza/A(H1N1)1.79^†Hepatitis E4.30^†Food poisoning2^†Rubella0.72Typhoid3.03^†Unknown reason dermatitis1Scarlet fever0.44Paratyphoid0.22Pertussis0.15Amebic dysentery0.22Meningococcal meningitis0.03Total100.00Total100.00Total20Open in a separate window^*Chronic infectious diseases (excluded).^†Selected specific diseases (top 5) or events (non-infectious excluded).

Table 2

List of symptoms/syndromes

A Review of Evaluations of Electronic Event-based Biosurveillance Systems

Objective

To assess evaluations of electronic event-based biosurveillance systems (EEBS’s) and define priorities for EEBS evaluations.

Introduction

EEBS’s that use near real-time information from the Internet are an increasingly important source of intelligence for public health organizations (1, 2). However, there has not been a systematic assessment of EEBS evaluations, which could identify uncertainties about current systems and guide EEBS development to effectively exploit digital information for surveillance.

Methods

We searched PubMed and consulted EEBS experts to identify EEBS’s that met the following criteria: uses publicly-available Internet info sources, includes events that impact humans, and has global scope. We constructed a list of 17 key evaluation variables using guidelines for evaluating health surveillance systems, and identified the key variables included in evaluations per EEBS, as well as the number of EEBS’s evaluated for each key variable (3,4).

Results

We identified 10 EEBS’s and 17 evaluations (EEBSYear startedNo. evaluationsNo. key variables assessedArgus200557BioCaster200659EpiSpider200624Gcni-Db201214GODSn200613GPHIN1997710Health Map2006712MedlSys200624ProMed1994512PULS200625Open in a separate window

Conclusions

While EEBS’s have demonstrated their usefulness and accuracy for early outbreak detection, no evaluations have cited specific examples of public health decisions or outcomes resulting from the EEBS. Future evaluations should discuss these critical indicators of public health utility. They also should assess the novel aspects of EEBS and include variables such as policy readiness, system redundancy, input/output geography (5); and test the effects of combining EEBS’s into a “super system”.     

Potential use of multiple surveillance data in the forecast of hospital admissions

Objective

This paper describes the potential use of multiple influenza surveillance data to forecast hospital admissions for respiratory diseases.

Introduction

A sudden surge in hospital admissions in public hospital during influenza peak season has been a challenge to healthcare and manpower planning. In Hong Kong, the timing of influenza peak seasons are variable and early short-term indication of possible surge may facilitate preparedness which could be translated into strategies such as early discharge or reallocation of extra hospital beds. In this study we explore the potential use of multiple routinely collected syndromic data in the forecast of hospital admissions.

Methods

A multivariate dynamic linear time series model was fitted to multiple syndromic data including influenza-like illness (ILI) rates among networks of public and private general practitioners (GP), and school absenteeism rates, plus drop-in fever count data from designated flu clinics (DFC) that were created during the pandemic. The latent process derived from the model has been used as a measure of the influenza activity [1]. We compare the cross-correlations between estimated influenza level based on multiple surveillance data and GP ILI data, versus accident and emergency hospital admissions with principal diagnoses of respiratory diseases and pneumonia & influenza (P&I).

Results

The estimated influenza activity has higher cross-correlation with respiratory and P&I admissions (ρ=0.66 and 0.73 respectively) compared to that of GP ILI rates (Surveillance dataCross correlations / lags^*−2−1012Respiratory disease admissionsGP ILI0.480.530.550.500.45Estimated influenza activity0.590.660.660.580.46P&I admissionsGP ILI0.570.620.650.590.49Estimated influenza activity0.660.730.730.650.53Open in a separate window^*negative lags refer to correlations between lagged surveillance data and hospital admissions

Conclusions

The use of a multivariate method to integrate information from multiple sources of influenza surveillance data may have the potential to improve forecasting of admission surge of respiratory diseases.     

Mental Illness and Co-morbid Conditions: BioSense 2008 – 2011

Objective

The purpose of this paper was to analyze the associated burden of mental illness and medical comorbidity using BioSense data 2008–2011.

Introduction

Understanding the relationship between mental illness and medical comorbidity is an important aspect of public health surveillance. In 2004, an estimated one fourth of the US adults reported having a mental illness in the previous year (1). Studies showed that mental illness exacerbates multiple chronic diseases like cardiovascular diseases, diabetes and asthma (2). BioSense is a national electronic public health surveillance system developed by the Centers for Disease Control and Prevention (CDC) that receives, analyzes and visualizes electronic health data from civilian hospital emergency departments (EDs), outpatient and inpatient facilities, Veteran Administration (VA) and Department of Defense (DoD) healthcare facilities. Although the system is designed for early detection and rapid assessment of all-hazards health events, BioSense can also be used to examine patterns of healthcare utilization.

Methods

We used 4 years (2008 – 2011) of BioSense civilian hospitals’ EDs visit data to perform the analysis. We searched final diagnoses for ICD-9 CM codes related to mental illness (290 – 312), schizophrenia (295), major depressive disorder (296.2 – 296.3), mood disorder (296, 300.4 and 311) and anxiety, stress & adjustment disorders (300.0, 300.2, 300.3, 308, and 309). We used BioSense syndromes/sub-syndromes based on chief complaints and final diagnoses for comorbidity. For the purpose of this study, comorbidity was defined broadly as the co-occurrence of mental and physical illness in the same person regardless of the chronological order. The proportion was calculated as the number of mental health visits associated with comorbidity divided by the total number of mental illness relevant visits. We ranked the top 10 proportions of comorbidity for adult mental illness by year.

Results

From 2008–2011, there were 4.6 million visits where mental illness was reported in the EDs visits. Average age of those reported mental illness was 44 years, 55% were women and 45% were men. More women were reported with anxiety (67%), mood (66%), and major depressive disorders (59%) than men; while men were reported more with schizophrenia (56%) than women (44%). The most common comorbid condition was hypertension, followed by chest pain, abdominal pain, diabetes, nausea & vomiting and dyspnea (Rank20082009201020111HypertensionHypertensionHypertensionHypertension2Chest PainChest PainChest PainChest Pain3Abdominal painAbdominal painAbdominal painAbdominal pain4Diabetes mellitusDiabetes mellitusDiabetes mellitusDiabetes mellitus5Nausea & vomitingNausea &. vomitingNausea & vomitingNausea & vomiting6DyspneaDyspneaDyspneaDyspnea7Injury, NOSTailshallshalls8FallsAsthmaHeadacheHeadache9HeadacheHeadacheAsthmaInjury, NOS10AsthmaInjury, NOSInjury, NOSAsthmaOpen in a separate window

Conclusions

This study supports prior findings that adult mental illness is associated with substantial medical burden. We identified 10 most common comorbid condition associated with mental illness. The major limitation of this work was that electronic data does not allow determination of the causal pathway between mental illness and some medical comorbidity. In addition, data represents only those who have access to healthcare or those with health seeking behaviors. Familiarity with comorbid conditions affecting persons with adult mental illness may assist programs aimed at providing medical care for the mentally ill.     

Monitoring the Impact of Heat Waves with Emergency Service Utilization Data in Los Angeles County

Objective

To assess current indicators for situational awareness during heat waves derived from electronic emergency department (ED) and 911 emergency dispatch call (EDC) center data.

Introduction

Los Angeles County’s (LAC) early event detection system captures over 60% of total ED visits, as well as 800 to 1,000 emergency dispatch calls from Los Angeles City Fire (LACF) daily. Both ED visits and EDC calls are classified into syndrome categories, and then analyzed for aberrations in count and spatial distribution. During periods of high temperatures, a heat report is generated and sent to stakeholders upon request. We describe how syndromic surveillance serves as an important near real-time, population-based instrument for measuring the impact of heat waves on emergency service utilization in LAC.

Methods

Daily electronic ED registration data, EDC calls, and high temperatures from Palmdale, California were queried from January 1, 2010 to August 26, 2012 and aggregated into Centers for Disease Control (CDC) weeks. A custom “heat exposure” category was created by searching ED chief complaints for key terms such as “Heat stroke,” “hyperthermia,” “overheat,” and relevant ICD9 diagnosis codes. Similarly, EDC calls were classified if related to “heat exposure.” Pearson correlation tests were used to determine correlation between total ED visits, heat-related ED visits, heat-related EDC calls, and daily maximum temperatures.

Results

Thus far 2012 has exceeded counts cumulative to August 26th for the past two years in the number of heat-related ED visits, heat-related EDC calls, and hot days (2010 to 8/26 (year end total)2011 to 8/26 (year end total)2012 to 8/26Heat-related FD visits214(319)195(304)246Heat-related 911 calls102(169)73(128)163Number of days > 80F102(148)99(152)123Number of days > 90F72(100)67(96)87Number of days > 100F18(23)14(17)27Number of days > 105F3(3)4(4)7Open in a separate windowAge groups were similarly distributed in total ED visits, heat-related ED visits and EDC calls, with a 18 to 44 year old majority (37%, 37%, and 42% respectively), followed by 45 to 64 year olds (23%, 21%, 23%). Total ED visits did not increase during summer months, and were therefore not found to be correlated to temperature (ρ=−0.06, p=0.46) or heat-related EDC calls (ρ=0.07, p=0.4). Heat-related ED visits however, were positively correlated with both EDC calls (ρ=0.85, p< 0.001) and temperatures (ρ=0.59, p<0.001). Heat-related EDC calls were also correlated with temperature (ρ=0.56, p<0.001).

Conclusions

Due to small numbers of heat-related visits relative to total ED visits, any effects that increased temperatures may have on total ED visits are undetectable. Total ED volume should therefore not be used as an indicator for measuring the impact of heat on LAC’s population. Filtering chief complaints to obtain heat-specific ED visits, however, enables patterns of increase to emerge which correlate with higher temperatures and heat-related emergency dispatch calls. About 35% of the week to week variation in heat-related ED visits, and 32% of the week to week variation in heat-related EDC calls can be explained by week to week variations in temperature. That heat-related visits were similarly distributed in age as all visitors suggests that heat does not disproportionately affect children and the elderly any more than the other acute health conditions that bring visitors to the ED. Syndromic analysis of ED data and EDC can provide baselines for health conditions such as hyperthermia that are otherwise difficult to obtain.     

A System for Surveillance Directly from the EMR

Objective

Our objective was to conduct surveillance of nosocomial infections directly from multiple EMR data streams in a large multi-location Canadian health care facility. The system developed automatically triggers bed-day-level-location-aware reports and detects and tracks the incidents of nosocomial infections in hospital by ward.

Introduction

Hospital acquired infections are a major cause of morbidity, mortality and increased resource utilization. CDC estimates that in the US alone, over 2 million patients are affected by nosocomial infections costing approximately $34.7 billion to $45 billion annually (1). The existing process of detection and reporting relies on time consuming manual processing of records and generation of alerts based on disparate definitions that are not comparable across institutions or even physicians.

Methods

A multi-stakeholder team consisting of experts from medicine, infection control, epidemiology, privacy, computing, artificial intelligence, data fusion and public health conducted a proof of concept from four complete years of admission records of all patients at the University of Ottawa Heart Institute. Figure 1 lists the data elements investigated. Our system uses an open source enterprise bus ‘Mirth Connect’ to receive and store data in HL7 format. The processing of information is handled by individual components and alerts are pushed back to respective locations. The free text components were classified using natural language processing. Negation detection was performed using NegEx (2). Data-fusion algorithms were used to merge information to make it meaningful and allow complex syndrome definitions to be mapped onto the data.

Results

The system monitors: Ventilator Associated Pneumonia (VAP), Central Line Infections (CLI), Methicillin Resistant Staph Aureus (MRSA), Clostridium difficile (C. Diff) and Vancomycin resistant Enterococcus (VRE).21452 hospital admissions occurred in 17670 unique patients over four years. There were 41720 CXRs performed in total, of which 10546 were classified as having an infiltrate. 4575 admissions were associated with at least one CXR showing an infiltrate, 2266 of which were hospital-acquired. Hospital acquired infiltrates were associated with an increased hospital mortality (6.3% vs 2.6%)* and length of stay (19.5 days vs 6.5 days)*. 253 patients had at least one positive blood culture. This was also associated with an increased hospital mortality (23,3% vs. 2.8%)* and length of stay (10.8 vs 40.9 days)*. (* all p values < 0.00001)

Conclusions

This proof of concept system demonstrates the capability of monitoring and analyzing multiple available data streams to automatically detect and track infections without the need for manual data capture and entry. It acquires directly from the EMR data to identify and classify health care events, which can be used to improve health outcomes and costs. The standardization of definitions used for detection will allow for generalization across institutions.

Current Therapies and Emerging Drugs in the Pipeline for Type 2 Diabetes

Background

Diabetes is a global epidemic that affects 347 million people worldwide and 25.8 million adults in the United States. In 2007, the total estimated cost associated with diabetes in the United States in 2007 was $174 billion. In 2009, $16.9 billion was spent on drugs for diabetes. The global sales of diabetes pharmaceuticals totaled $35 billion in 2010, and these are expected to rise to $48 billion by 2015. Despite such considerable expenditures, in 2000 only 36% of patients with type 2 diabetes in the United States achieved glycemic control, defined as hemoglobin A1c <7%.

Objective

To review some of the most important drug classes currently in development for the treatment of type 2 diabetes.

Discussion

Despite the 13 classes of antidiabetes medications currently approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes, the majority of patients with this chronic disease do not achieve appropriate glycemic control with these medications. Many new drug classes currently in development for type 2 diabetes appear promising in early stages of development, and some of them represent novel approaches to treatment, with new mechanisms of action and a low potential for hypoglycemia. Among these promising pharmacotherapies are agents that target the kidney, liver, and pancreas as a significant focus of treatment in type 2 diabetes. These investigational agents may potentially offer new approaches to controlling glucose levels and improve outcomes in patients with diabetes. This article focuses on several new classes, including the sodium-glucose cotransporter-2 inhibitors (which are furthest along in development); 11beta-hydroxysteroid dehydrogenase (some of which are now in phase 2 trials); glycogen phosphorylase inhibitors; glucokinase activators; G protein–coupled receptor 119 agonists; protein tyrosine phosphatase 1B inhibitors; and glucagon-receptor antagonists.

Conclusion

Despite the abundance of FDA-approved therapeutic options for type 2 diabetes, the majority of American patients with diabetes are not achieving appropriate glycemic control. The development of new options with new mechanisms of action may potentially help improve outcomes and reduce the clinical and cost burden of this condition.Diabetes is a chronic, progressive disease that affects approximately 347 million people worldwide.1 In the United States, 25.8 million Americans have diabetes, and another 79 million US adults aged ≥20 years are considered to have prediabetes.2 Diabetes is the leading cause of kidney failure, nontraumatic lower-limb amputations, and new cases of blindness among adults in the United States. It is a major cause of heart disease and stroke and is the seventh leading cause of death among US adults.2The total estimated cost for diabetes in the United States in 2007 was $174 billion,2 and between 2007 and 2009, the estimated cost attributable to pharmacologic intervention in the treatment of diabetes increased from $12.5 billion to $16.9 billion.3–5 Global sales for diabetes medications totaled $35 billion in 2010 and could rise to $48 billion by 2015, according to the drug research company IMS Health.6,7 In 2009, $1.1 billion was spent on diabetes research by the National Institutes of Health.8 Despite these staggering costs, currently there are still no proved strategies to prevent this disease or its serious complications.

KEY POINTS

• ▸ Approximately 25.8 million adult Americans have diabetes. In 2007, diabetes cost the United States an estimated $174 billion, and in 2009, $16.9 billion was spent on antidiabetes medications.
• ▸ Nevertheless, the majority of American patients with diabetes do not achieve glycemic control with the currently available pharmacotherapies.
• ▸ Several novel and promising medications are currently in development, targeting the kidney, liver, and pancreas in the treatment of type 2 diabetes.
• ▸ Many of these investigational agents involve new mechanisms of action that offer new therapeutic targets and may help improve glucose control in patients with diabetes.
• ▸ The new drug classes in development include the sodium-glucose cotransporter-2 inhibitors (which are furthest along in development); the 11beta-hydroxysteroid dehydrogenase; glycogen phosphorylase inhibitors; glucokinase activators; G protein-coupled receptor 119 agonists; protein tyrosine phosphatase 1B inhibitors; glucagon-receptor antagonists.
• ▸ Several of these new classes are associated with low potential for hypoglycemia, representing a potentially new approach to diabetes drug therapy.
• ▸ The development of new options with new mechanisms of action may potentially help improve patient outcomes and reduce the clinical and cost burden of this chronic disease.

According to the 1999–2000 National Health and Nutrition Examination Survey, only 36% of patients with type 2 diabetes achieve glycemic control—defined as hemoglobin (Hb) A_1c <7%—with currently available therapies.9 Lifestyle modification remains the most important and effective way to treat diabetes; however, the majority of patients with type 2 diabetes are unable to maintain such a rigid lifestyle regimen. For most patients with type 2 diabetes, pharmacologic intervention will therefore be needed to maintain glycemic control.2​and22 list the 13 classes of medication currently approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes. Despite this abundance of pharmacotherapies, new medications with different mechanisms of action or new approaches to therapy are needed to improve patient outcomes and reduce the clinical and cost burden of this serious condition.

Table 1

FDA-Approved Antidiabetic Agents for the Treatment of Type 2 Diabetes