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1.
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
SubjectRecommendationsGradeNumber
IndicationPN 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.B4.1
Active diseaseParenteral nutrition (PN) should not be used as a primary treatment of inflammatory luminal CD.A3.5
Bowel rest has not been proven to be more efficacious than nutrition per se.
Maintenance of remissionIn case of persistent intestinal inflammation there is rarely a place for long-term PN.B3.7
The most common indication for long-term PN is the presence of a short bowel.
PerioperativeUse of PN in the perioperative period in CD patients is similar to that of other surgical procedures.B3.6
ApplicationWhen indicated, PN improves nutritional status and reduces the consequences of undernutrition, providing there is not continuing intra-abdominal sepsisB1
Specific deficits (trace elements, vitamins) should be corrected by appropriate supplementation.B1
The use of PN in patients with CD should follow general recommendations for parenteral nutrition.B1
RouteParenteral 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 PNC3.2
Type of formulaAlthough 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.B4.3
UndernutritionParenteral nutrition may improve the quality of life in undernourished CD patients.C3.4
Summary of statements: PN in ulcerative colitis
SubjectRecommendationsGradeNumber
IndicationParenteral 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 feedB9
Active diseaseThere is no place for PN in acute inflammatory UC as means of enabling bowel rest.B10
Maintenance of remissionParenteral nutrition is not recommended.B11
ApplicationTreat specific deficiencies when oral route is not possible.C5
Type of formulaThe value of specific substrates (n-3 fatty acids, glutamine) is not proven.B10.2
Summary of statements: Short bowel syndrome (intestinal failure)
SubjectRecommendationsGradeNumber
IndicationMaintenance and/or improvement of nutritional status, correction of water and electrolyte balance, improvement in quality of life.B15
Route
Post-op periodPredictions 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.B17.1
Adaptation phasePatients 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.B17.2
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/StabilizationParenteral 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.B17.3
Type of formulaNo specific substrate composition of PN is required per se.B16
Specific attention should be paid to electrolyte supplementation (especially sodium and magnesium).B16, 17
Currently, the use of growth hormone, glutamine or GLP-2 cannot be recommended.B18
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2.
ESPEN Guidelines on Parenteral Nutrition: Hepatology   总被引:2,自引:0,他引:2  
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
SubjectRecommendationsGradeNumber
GeneralUse simple bedside methods such as the Subjective Global Assessment (SGA) or anthropometry to identify patients at risk of undernutrition.C1
Start PN immediately in moderately or severely malnourished ASH patients, who cannot be fed sufficiently either orally or enterally.A1
Give i.v. glucose (2–3 g kg−1 d−1) when patients have to abstain from food for more than 12 h.C1
Give PN when the fasting period lasts longer than 72 h.C1
EnergyProvide energy to cover 1.3 × REEC2
Give glucose to cover 50–60 % of non-protein energy requirements.C3
Use lipid emulsions with a content of n-6 unsaturated fatty acids lower than in traditional pure soybean oil emulsions.C3
Amino acidsProvide amino acids at 1.2–1.5 g kg−1 d−1.C3
MicronutrientsGive water soluble vitamins and trace elements daily from the first day of PN.C3
Administer vitamin B1 prior to starting glucose infusion to reduce the risk of Wernicke's encephalopathy.C3
MonitoringEmploy repeat blood sugar determinations in order to detect hypoglycemia and to avoid PN related hyperglycemia.C6
Monitor phosphate, potassium and magnesium levels when refeeding malnourished patients.C3
Summary of statements: Liver Cirrhosis
SubjectRecommendationsGradeNumber
GeneralUse simple bedside methods such as the Subjective Global Assessment (SGA) or anthropometry to identify patients at risk of undernutrition.C4
Start PN immediately in moderately or severely malnourished cirrhotic patients, who cannot be fed sufficiently either orally or enterally.A4
Give i.v. glucose (2–3 g kg−1 d−1) when patients have to abstain from food for more than 12 h.C4
Give PN when the fasting period lasts longer than 72 h.C4
Consider PN in patients with unprotected airways and encephalopathy when cough and swallow reflexes are compromised.C4
Use early postoperative PN if patients cannot be nourished sufficiently by either oral or enteral route.A4
After liver transplantation, use early postoperative nutrition; PN is second choice to EN.C4
EnergyProvide energy to cover 1.3 x REEC5
Give glucose to cover 50 % - 60 % of non-protein energy requirements.C6
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.C6
Use lipid emulsions with a content of n-6 unsaturated fatty acids lower than in traditional pure soybean oil emulsions.C6
Amino acidsProvide amino acids at 1.2–1.5 g kg−1 d−1.C7
In encephalopathy III° or IV°, consider the use of solutions rich in BCAA and low in AAA, methionine and tryptophane.A7
MicronutrientsGive water soluble vitamins and trace elements daily from the first day of PN.C8
In alcoholic liver disease, administer vitamin B1 prior to starting glucose infusion to reduce the risk of Wernicke's encephalopathy.C3, 8
MonitoringEmploy repeat blood sugar determinations in order to avoid PN related hyperglycemia.A6
Monitor phosphate, potassium and magnesium levels when refeeding malnourished patients.C8
Summary of statements: Acute Liver Failure
SubjectRecommendationsGradeNumber
GeneralCommence artificial nutrition when patient is unlikely to resume normal oral nutrition within the next 5–7 days.C9
Use PN when patients cannot be fed adequately by EN.C9
EnergyProvide energy to cover 1.3 × REE.C10
Consider using indirect calorimetry to measure individual energy expenditure.C10
Give i.v. glucose (2–3 g kg−1 d−1) for prophylaxis or treatment of hypoglycaemia.C11
In case of hyperglycaemia, reduce glucose infusion rate to 2–3 g kg−1 d−1 and consider the use of i.v. insulin.C11, 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.C11
Amino acidsIn acute or subacute liver failure, provide amino acids at 0.8–1.2 g kg−1 d−1.C11
MonitoringEmploy repeat blood sugar determinations in order to detect hypoglycaemia and to avoid PN related hyperglycaemia.C11
Employ repeat blood ammonia determinations in order to adjust amino acid provision.C11
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3.
4.
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
SubjectRecommendationsGradeNumber
IndicationsAge 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 subjectsInsulin 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 PNBoth 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 administrationThe 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 statusPN 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 statusPN can support improvement of functional status, but the margin of improvement is lower than in younger patients.C [IV]6
Morbidity and mortalityPN can reduce mortality and morbidity in older as well as in middle-aged subjects.C [IV]7
Length of hospital stayNo studies have assessed length of hospital stay in older patients on PN.8
Quality of lifeLong-term parenteral nutrition does not influence quality of life of older patients more negatively than it does in younger subjects.C [IV]9
Specific complicationsThere 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 situationsIndications for PN are similar in younger and older adults in the hospital and at home.B [III]11
Ethical problemsPN 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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5.
ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology   总被引:1,自引:0,他引:1  
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
SubjectRecommendationsGradeNumber
Nutritional statusNutritional 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 fewC1.1
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 patientsC1.4
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)C1.5
IndicationsTherapeutic goals for PN in cancer patients are the improvement of function and outcome by:C2.1
• 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 failureA2.1
PN is recommended in patients with severe mucositis or severe radiation enteritisC2.1
Nutritional provisionSupplemental PN is recommended in patients if inadequate food and enteral intake (<60% of estimated energy expenditure) is anticipated for more than 10 daysC2.2
PN is not recommended if oral/enteral nutrient intake is adequateA2.2
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 responseC2.3
Preliminary data suggest a potential positive role of insulin (Grade C). There are no data on n-3 fatty acidsC2.4
Peri-operative carePeri-operative PN is recommended in malnourished candidates for artificial nutrition, when EN is not possibleA3.1
Peri-operative PN should not be used in the well-nourishedA3.1
During non-surgical therapyThe routine use of PN during chemotherapy, radiotherapy or combined therapy is not recommendedA3.2
If patients are malnourished or facing a period longer than one week of starvation and enteral nutritional support is not feasible, PN is recommendedC3.2
Incurable patientsIn 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 supportC3.3
There is probable benefit in supporting incurable cancer patients with weight loss and reduced nutrient intake with “supplemental” PNB3.4
Hematopoietic stem cell transplantation (HSCT)In HSCT patients PN should be reserved for those with severe mucositis, ileus, or intractable vomitingB3.5
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 enterallyC3.6
HSCT patients may benefit from glutamine-supplemented PNB3.7
Tumor growthAlthough 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 indicatedC4.1
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6.
When planning parenteral nutrition (PN), the proper choice, insertion, and nursing of the venous access are of paramount importance. In hospitalized patients, PN can be delivered through short-term, non-tunneled central venous catheters, through peripherally inserted central catheters (PICC), or – for limited period of time and with limitation in the osmolarity and composition of the solution – through peripheral venous access devices (short cannulas and midline catheters). Home PN usually requires PICCs or – if planned for an extended or unlimited time – long-term venous access devices (tunneled catheters and totally implantable ports).The most appropriate site for central venous access will take into account many factors, including the patient's conditions and the relative risk of infective and non-infective complications associated with each site. Ultrasound-guided venepuncture is strongly recommended for access to all central veins. For parenteral nutrition, the ideal position of the catheter tip is between the lower third of the superior cava vein and the upper third of the right atrium; this should preferably be checked during the procedure.Catheter-related bloodstream infection is an important and still too common complication of parenteral nutrition. The risk of infection can be reduced by adopting cost-effective, evidence-based interventions such as proper education and specific training of the staff, an adequate hand washing policy, proper choices of the type of device and the site of insertion, use of maximal barrier protection during insertion, use of chlorhexidine as antiseptic prior to insertion and for disinfecting the exit site thereafter, appropriate policies for the dressing of the exit site, routine changes of administration sets, and removal of central lines as soon as they are no longer necessary.Most non-infective complications of central venous access devices can also be prevented by appropriate, standardized protocols for line insertion and maintenance. These too depend on appropriate choice of device, skilled implantation and correct positioning of the catheter, adequate stabilization of the device (preferably avoiding stitches), and the use of infusion pumps, as well as adequate policies for flushing and locking lines which are not in use.
Summary of statements: Central Venous Catheters
SubjectRecommendationsGradeNumber
Choice of route for intravenous nutritionCentral venous access (i.e., venous access which allows delivery of nutrients directly into the superior vena cava or the right atrium) is needed in most patients who are candidates for parenteral nutrition (PN).C1
In some situations however PN may be safely delivered by peripheral access (short cannula or midline catheter), as when using a solution with low osmolarity, with a substantial proportion of the non-protein calories given as lipid.
It is recommended that peripheral PN (given through a short peripheral cannula or through a midline catheter) should be used only for a limited period of time, and only when using nutrient solutions whose osmolarity does not exceed 850 mOsm/L.
Home PN should not normally be given via short cannulas as these carry a high risk of dislocation and complications.
Peripheral PN, whether through short cannulas or midline catheters, demands careful surveillance for thrombophlebitis.
Choice of PN catheter deviceShort-term: many non-tunneled central venous catheters (CVCs), as well as peripherally inserted central catheters (PICCs), and peripheral catheters are suitable for in-patient PN.B2
Medium-term: PICCs, Hohn catheters, and tunneled catheters and ports are appropriate. Non-tunneled central venous catheters are discouraged in HPN, because of high rates of infection, obstruction, dislocation, and venous thrombosis.
Prolonged use and HPN (>3 months) usually require a long-term device. There is a choice between tunneled catheters and totally implantable devices. In those requiring frequent (daily) access a tunneled device is generally preferable.
Choice of vein for PNThe choice of vein is affected by several factors including venepuncture technique, the risk of related mechanical complications, the feasibility of appropriate nursing of the catheter site, and the risk of thrombotic and infective complications.C3
The use of the femoral vein for PN is relatively contraindicated, since this is associated with a high risk of contamination at the exit site in the groin, and a high risk of venous thrombosis.
High approaches to the internal jugular vein (either anterior or posterior to the sternoclavicular muscle) are not recommended, since the exit site is difficult to nurse, and there is thus a high risk of catheter contamination and catheter-related infection.
Insertion of CVCsThere is compelling evidence that ultrasound-guided venepuncture (by real-time ultrasonography) is associated with a lower incidence of complications and a higher rate of success than ‘blind’ venepuncture. Ultrasound support is therefore strongly recommended for all CVC insertions. Placement by surgical cutdown is not recommended, in terms of cost-effectiveness and risk of infection.A4
In placement of PICCs, percutaneous cannulation of the basilic vein or the brachial vein in the midarm, utilizing ultrasound guidance and the micro-introducer technique, is the preferred optionB4
Position of CVC tipHigh osmolarity PN requires central venous access and should be delivered through a catheter whose tip is in the lower third of the superior vena cava, at the atrio-caval junction, or in the upper portion of the right atrium (Grade A). The position of the tip should preferably be checked during the procedure, especially when an infraclavicular approach to the subclavian vein has been used.C, B5
Postoperative X-ray is mandatory (a) when the position of the tip has not been checked during the procedure, and/or (b) when the device has been placed using blind subclavian approach or other techniques which carry the risk of pleuropulmonary damage.
Choice of material for CVCThere is limited evidence to suggest that the catheter material is important in the etiology of catheter-related sepsis. Teflon, silicone and polyurethane (PUR) have been associated with fewer infections than polyvinyl chloride or polyethylene. Currently all available CVCs are made either of PUR (short-term and medium-term) or silicone (medium-term and long-term); no specific recommendation for clinical practice is made.B6
Reducing the risk of catheter-related infectionEvidence indicates that the risk of catheter-related infection is reduced by:
• Using tunneled and implanted catheters (value only confirmed in long-term use)
• Using antimicrobial coated catheters (value only shown in short-term use)
• Using single-lumen catheters
• Using peripheral access (PICC) when possible
• Appropriate choice of the insertion site
• Ultrasound-guided venepuncture
• Use of maximal barrier precautions during insertion
• Proper education and specific training of the staff
• An adequate policy of hand washing
• Use of 2% chlorhexidine as skin antiseptic
• Appropriate dressing of the exit site
• Disinfection of hubs, stopcocks and needle-free connectors
• Regular change of administration sets
Some interventions are not effective in reducing the risk of infection, and should not be adopted for this purpose; these include:
• in-line filters
• routine replacement of central lines on a scheduled basis
• antibiotic prophylaxis
• the use of heparin
B6
Diagnosis of catheter-related sepsisDiagnosis of CRBSI is best achieved (a) by quantitative or semi-quantitative culture of the catheter (when the CVC is removed or exchanged over a guide wire), or (b) by paired quantitative blood cultures or paired qualitative blood cultures from a peripheral vein and from the catheter, with continuously monitoring of the differential time to positivity (if the catheter is left in place).A7
Treatment of catheter-related sepsis (short-term lines)A short-term central line should be removed in the case of (a) evident signs of local infection at the exit site, (b) clinical signs of sepsis, (c) positive culture of the catheter exchanged over guide wire, or (d) positive paired blood cultures (from peripheral blood and blood drawn from the catheter). Appropriate antibiotic therapy should be continued after catheter removal.B8
Treatment of catheter-related sepsis (long-term lines)Removal of the long-term venous access is required in case of (a) tunnel infection or port abscess, (b) clinical signs of septic shock, (c) paired blood cultures positive for fungi or highly virulent bacteria, and/or (d) complicated infection (e.g., evidence of endocarditis, septic thrombosis, or other metastatic infections). In other cases, an attempt to save the device may be tried, using the antibiotic lock technique.B9
Routine care of central cathetersMost central venous access devices for PN can be safely flushed and locked with saline solution when not in use.C10
Heparinized solutions may be used as a lock (after flushing with saline), when recommended by the manufacturer, in the case of implanted ports or opened-ended catheter lumens which are scheduled to remain closed for more than 8 h.
Prevention of line occlusionIntraluminal obstruction of the central venous access can be prevented by appropriate nursing protocols in maintenance of the line, including the use of nutritional pumps.C11
Prevention of catheter-related central venous thrombosisThrombosis is avoided by the use of insertion techniques designed to limit damage to the vein, including
• Ultrasound guidance at insertion
• choice of a catheter with the smallest caliber compatible with the infusion therapy needed
• position of the tip of the catheter at or near to the atrio-caval junction
Prophylaxis with a daily subcutaneous dose of low molecular weight heparin is effective only in patients at high risk for thrombosis.
B12
Keywords: Guidelines; Evidence-based; Clinical practice; Parenteral nutrition; Central venous access; Venous access devices; Midline catheters; PICC; Central venous catheters; Totally implantable ports; Tunneled catheters; Peripheral parenteral nutrition; Home parenteral nutrition; Ultrasound guidance; Catheter-related bloodstream infection; Needle-free connectors; Chlorhexidine; Antibiotic lock therapy; Exchange over guide wire; Heparin lock; Sutureless securing devices; Catheter-related venous thrombosis; Pinch-off syndrome; Fibrin sleeve  相似文献   

7.
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
SubjectRecommendationsGradeNumber
IndicationsPreoperative fasting from midnight is unnecessary in most patientsAPreliminary remarks
Interruption of nutritional intake is unnecessary after surgery in most patientsAPreliminary remarks
ApplicationPreoperative parenteral nutrition is indicated in severely undernourished patients who cannot be adequately orally or enterally fedA1
Postoperative parenteral nutrition is beneficial in undernourished patients in whom enteral nutrition is not feasible or not toleratedA2
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 daysA2
In patients who require postoperative artificial nutrition, enteral feeding or a combination of enteral and supplementary parenteral feeding is the first choiceA2
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 peritonitisC2
In patients with prolonged gastrointestinal failure parenteral nutrition is life-savingC2
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 usedA3
Type of formulaThe 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 weightB4
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 lossesB4
The Protein:Fat:Glucose caloric ratio should approximate to 20:30:50%C4
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 steatohepatitisC5
Optimal nitrogen sparing has been shown to be achieved when all components of the parenteral nutrition mix are administered simultaneously over 24 hoursA6
Individualized nutrition is often unnecessary in patients without serious co-morbidityC7
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 trialsC8
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 requiredC9
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 basisC9
Weaning from parenteral nutrition is not necessaryA10
  相似文献   

8.
9.
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) (1014). 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*
StudyAll
Secretor positive
Secretor negative
Strain
No. challengedNo. (%) infectedNo. (%) AGE No. challengedNo. (%) infected No. (%) AGENo. challengedNo. (%) infected
Dolin 1971 (10)129 (75)SM
Wyatt 1974 (11)†2316 (70)NV, MC, HI
Parrino 1977 (8)†126 (50)NV
Johnson 1990 (17)†4231 (74)25 (60)NV
Graham 1994 (12)5041 (82)34 (68)NV
Lindesmith 2003 (18)7734 (44)21 (27)5535 (64)21 (38)210NV
Lindesmith 2005 (19)159 (60)7 (47)128 (67)31 (33)SM
Atmar 2008 (20)2116 (76)11 (52)2116 (76)11 (52)NV
Leon 2011 (21)‡157 (47)5 (33)157 (47)5 (33)NV
Atmar 2011 (14)‡4134 (83)29 (71)4134 (83)29 (71)NV
Seitz 2011 (22)1310 (77)10 (77)1310 (77)10 (77)1 (5.6)NV
Frenck 2012 (23)4017 (42)12 (30)2316 (70)12 (52.1)17GII.4
Open in a separate window*AGE, acute gastroenteritis; SM, Snow Mountain virus; NV, Norwalk virus; MC, Montgomery County virus; HI, Hawaii virus; GII.4, genogroup 2 type 4.
†Only includes initial challenge, not subsequent re-challenge.
‡Only includes placebo or control group.In this study, we aimed to gain better estimates of the duration of immunity to NoV by developing a community-based transmission model that represents the transmission process and natural history of NoV, including the waning of immunity. The model distinguishes between persons susceptible to disease and those susceptible to infection but not disease. We fit the model to age-specific incidence data from a community cohort study. However, several factors related to NoV transmission remain unknown (e.g., the role asymptomatic persons who shed virus play in transmission). Therefore, we constructed and fit a series of 6 models to represent the variety of possible infection processes to gain a more robust estimate of the duration of immunity. This approach does not consider multiple strains or the emergence of new variants, so we are effectively estimating minimum duration of immunity in the absence of major strain changes.  相似文献   

10.

Objective

To analyze Influenza surveillance data from 2009 to 2010 the Northern, Southern, and Western zones in Nigeria and determined co-morbidity factors associated with influenza in Nigeria.

Introduction

Influenza is viral illness that affects mainly the nose, throat, bronchi and occasionally, the lungs. Influenza viruses have been an under-appreciated contributor to morbidity and mortality in Nigeria. They are a substantial contributor to respiratory disease burden in Nigeria and other developing countries. Nigeria started influenza sentinel surveillance in 2008 to inform disease control and prevention efforts.

Methods

We conducted a cross sectional study on secondary data analysis of Influenza surveillance data from January 2009 to December 2010 obtained from Nigeria’s Federal Ministry of Health. Epidemiological data were obtained for suspected ILI and SARI cases defined in accordance with WHO Regional Office for Africa’s guidelines. Laboratory confirmation for presence of influenza viruses was done using real time PCR assays.Standardized case investigation forms used for sample collection were analyzed using Epi-Info software to generate frequency and proportions.

Results

Of the 5,860 suspected influenza cases reported between 2007 and 2011 from all the influenza sites in Nigeria, 1104 (18.8%) and 2,510 (42.8%) of the total cases were recorded in 2009 and 2010 respectively. A total of 296 (7.3%) were positive for Flu A, while 147 (2.9%) for Flu B. The Northern zone recorded a total of 1908(AR: 2.6/100,000) suspected cases while the Southern zone recorded 554(AR: 1.48/100,000) and the Western zone reported 549(2/100,000) suspected cases. Of the 443 that were positive 43 (1.5%) were health workers, 446 (8.0%) had co infection of chronic respiratory tract disease, 50(3.7%) had co infection with heart disease. Exposure to poultry was 2797(98.2%).

Conclusions

Co-morbidity factors associated with influenza viruses are an important contribution to the burden of respiratory illnesses in Nigeria predominantly affecting children less than 5years and adults 25years and above. Additional years of data are needed to better understand the co-morbidity factors associated epidemiology of influenza viruses in Nigeria.INFLUENZA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
INFLUENZA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)Influenza with COPD N (%)Influenza only N(%)Total
A/H10 (0.0)12(100.0)12(100.0)
A/H310(11.2)79(88.8)89 (100.0)
All Negative551 (11.1)4392 (88.9)4943 (100.0)
pdmA/H1N114 (9.3)137 (90.7)151 (100.0)
pdmA/H1N110(5.6)170(99.4)180 (100.0)
Total585(10.9)4790(89.1)5375(100.0)
Open in a separate windowOnly 585 (10.9%) had chest indrawing, with majority of the influenza subtype pdm A/H1N1 cases 14 (9.3%) had chest indrawing.INFLUENZA AND CHRONIC CHEST DISEASE
Influenza Sub-typeInfluenza with Chronic Shortness of Breath N (%)Influenza cases without Chronic Shortness of Breath N(%)Total
A/H10 (0.0)16 (100.0)16 (100.0)
A/H31 (0.91115 (99.1)116 (100.0)
All Negative56 (1.1)5204 (98.9)5204 (100.0)
pdm A/H1N10 (1.3)152 (98.7)152 (100.0)
Un-suptype-able0 (0.0)181 (100.0)181 (100.0)
Total57 (1.0)5668 (99.0)5725 (100.0)
Open in a separate windowLess than 5% of the respondents with influenza cases had chronic shortness of breath  相似文献   

11.

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 casesEmergencies
Name%Name%NameEvents (No.)
*Pulmonary tuberculosis82.38Hand-foot-mouth diseases41.73A(H1N1)10
Mumps9.14Bacillary dysentery28.56Mumps5
Measles3.35Hepatitis A15.36Hand-foot-mouth diseases1
Varicella2.00 Infectious diarrhea6.58Bacillary dysentery1
Influenza/A(H1N1)1.79Hepatitis E4.30Food poisoning2
Rubella0.72Typhoid3.03Unknown reason dermatitis1
Scarlet fever0.44Paratyphoid0.22
Pertussis0.15Amebic dysentery0.22
Meningococcal meningitis0.03
Total100.00Total100.00Total20
Open in a separate window*Chronic infectious diseases (excluded).Selected specific diseases (top 5) or events (non-infectious excluded).

Table 2

List of symptoms/syndromes
*Scheme 1**Scheme 2
No.SymptomsNo.SymptomsNo.Syndromes
1Abdominal pain11 Headache1Coma/sudden death
2Bone/muscle/joint Pain12Hematochezia2Fever
3Chills13Jaundice3Gastrointestinal
4Conjunctival hyperemia14Mucocutaneous hemorrhage4Hemorrhagic
5Convulsion15Nasal congestion/Rhinorrhea5Influenza like illness
6Cough16Nausea/Vomitting6Neurological
7Diarrhea17Rach7Rash
8Disturbance of consciousness18Sore throat8Respiratory
9Fatigue19Tenesmus
10Fever
Open in a separate window*The incidence of symptom was >= 20% of specific disease(s)/event(s).**The number of times of syndromes monitored was >= 4 times. Asthma (4 times) and diarrhea (5 times) were excluded due to study objectives.Final targeted symptoms.

Conclusions

We should take the simple, stability and feasibility of operation, and also the local conditions into account before establishing a surveillance system. Symptoms were more suitable for monitoring compared to syndromes in resource-poor settings. Further evaluated and validated would be conducted during implementation. Our study might provide methods and evidences for other developing countries with limited conditions in using automated syndromic surveillance system, to construct similar early warning system.  相似文献   

12.
Improving ILI Surveillance using Hospital Staff Influenza-like Absence (ILA)     
Lydia Drumright  Simon D. Frost  Mike Catchpole  John Harrison  Mark Atkins  Penny Parker  Alex J. Elliot  Douglas M. Fleming  Alison H. Holmes 《Online Journal of Public Health Informatics》2013,5(1)

Objective

To address the feasibility and efficiency of a novel syndromic surveillance method, monitoring influenza-like absence (ILA) among hospital staff, to improve national ILI surveillance and inform local hospital preparedness.

Introduction

Surveillance of influenza in the US, UK and other countries is based primarily on measures of influenza-like illness (ILI), through a combination of syndromic surveillance systems, however, this method may not capture the full spectrum of illness or the total burden of disease. Care seeking behaviour may change due to public beliefs, for example more people in the UK sought care for pH1N1 in the summer of 2009 than the winters of 2009/2010 and 2010/2011, resulting in potential inaccurate estimates from ILI (1). There may also be underreporting of or delays in reporting ILI in the community, for example in the UK those with mild illness are less likely to see a GP (2), and visits generally occur two or more days after onset of symptoms (3). Work absences, if the reason is known, could fill these gaps in detection.

Methods

Weekly counts and rates of hospital staff ILA (attributed to colds or influenza) were compared to GP ILI consultation rates (Royal College of General Practitioners Weekly Returns Service)(4) for 15–64 year olds, and positive influenza A test results (PITR) for all inpatients hospitalised in the three London hospitals for which staff data were collected using both retrospective time series and prospective outbreak detection methods implemented in the surveillance package in R (5)

Results

Rates of ILA were about six times higher than rates of ILI. Data on hospital staff ILA demonstrated seasonal trends as defined by ILI. Compared to the ILI rates, ILA demonstrated a more realistic estimate of the relative burden of pandemic H1N1 during July 2009 (1) (Figure). ILA provides potentially earlier warnings than GP ILI as indicated by its ability to predict ILI data for the local region (p < 0.001), as well as its potential for daily ‘real time’ updates. Using outbreak detection methods and examining peak weeks, alarms and thresholds, ILA alarmed, reached threshold rates and peaked consistently earlier or in the same week as ILI and PITR, with the exception of the July 2009, suggesting that it may be predictive of both community and patient cases of influenza (Open in a separate windowFigure:Weekly counts of ILA among hospital staff (blue), PITR among hospital patients (orange), and ILI in the community (red) from April 2008 to March 2011 and prospective alarms for elevated counts (circles) using a Bayesian subsystem algorithm, using the previous six weeks as the reference for prediction. Data plotted by counts rather than rates for clarity.

Table:

Week of the year that alarms commenced and peaks were reached for each of the four official influenza events from March 2008 to April 2011.
Winter 2008/2009Winter 2009/2010Winter 2010/2011Summer 2009
CommenceThresholdPeakCommenceThresholdPeakCommenceThresholdPeakCommenceThresholdPeak
ILA33.17.11383644474751272429
II.I364951394049494951262629
PITR49NA5139NA4447NA5225NA31
Open in a separate windowILA = influenza like absences among hospital staff; ILI = influenza like illness from RCGP data in London, ages 15–64; PITR = positive influenza A test results among patients from the same hospital as staff contributing ILA data; Threshold for ILI data was set at 30/100,000 as defined by the Health Protection Agency. The ILA threshold set at 60/100,000, such that all ILI above a threshold of 30/100000 were also above a threshold for ILA.

Conclusions

This study has demonstrated the potential to further explore the usefulness of using ILA data to complement existing national influenza surveillance systems. This work could improve our accuracy in monitoring of influenza and has the potential to improve emergency response to influenza for individual hospitals.  相似文献   

13.
Potential use of multiple surveillance data in the forecast of hospital admissions     
Eric H.Y. Lau  Dennis K.M. Ip  Benjamin J. Cowling 《Online Journal of Public Health Informatics》2013,5(1)

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.  相似文献   

14.
Applying Zero-inflated Mixed Model to School Absenteeism Surveillance in Rural China     
Xiaoxiao Song  Tao Tao  Qi Zhao  Fuqiang Yang  Palm Lars  Diwan Vinod  Hui Yuan  Biao Xu 《Online Journal of Public Health Informatics》2013,5(1)

Objective

To describe and explore the spatial and temporal variability via ZIMM for absenteeism surveillance in primary school for early detection of infectious disease outbreak in rural China.

Introduction

Absenteeism has great advantages in promoting the early detection of epidemics1. Since August 2011, an integrated syndromic surveillance project (ISSC) has been implemented in China2. Distribution of the absenteeism generally are asymmetry, zero inflation, truncation and non-independence3. For handling these encumbrances, we should apply the Zero-inflated Mixed Model (ZIMM).

Methods

Data for this study was obtained from the web-based data of ISSC in 62 primary schools in two counties of Jiangxi province, China from April 1th, 2012 to June 30st, 2012. The ZIMM was used to explore: 1)the temporal and spatial variability regarding occurrence and intensity of absenteeism simultaneously, and 2) the heterogeneity among the reporting primary schools by introducing random effects into the intercepts. The analyse was processed in the SAS procedure NLMIXED4.

Results

The total 4914 absenteeism events were reported in the 62 primary schools in the study period. The rate of zero report was 49.88% (Fig. 1). According to ZIMM, there are fixed and random effect parameters in this model (Open in a separate windowFig. 1Absenteeism from Apr. 1st to Jun. 30th 2012

Table 1

Fixed parameters and variance components estimates for the absenteeism using ZIMM
Logistic regression parameter with occurrencelognormal regression parameter with intensity
parametersβStd Errp valueβStd Errp value
Fixed parametersIntercept−0.7330.2620.0050.7180.0390.000
county−0.1880.1030.068−0.0200.0420.632
month−0.1650.0740.026−0.0730.0270.007
Variance componentsVar (Ranndm Effect)0.5481.9060.7740.3160.1200.009
Residual0.1200.1190.313
Open in a separate window

Conclusions

School absenteeism data has greater uncertain than many other sources and easier fluctuate by some factors such as holiday, season, family status and geographic distribution. Thus, the spatial and temporal dynamics should be taken into account in controlling fluctuate of absenteeism. Moreover, school absenteeism data are correlated within each school due to repeated measures. Applying the ZIMM, the occurrences and intensity of absenteeism could be evaluated to reduce the bias and improve the prediction precision. The ZIMM is an appropriate tool for health authorities in decision making for public health events.  相似文献   

15.
Computerized Text Analysis to Enhance Automated Pneumonia Detection     
Sylvain DeLisle  Tariq Siddiqui  Adi Gundlapalli  Matthew Samore  Leonard D’Avolio 《Online Journal of Public Health Informatics》2013,5(1)

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 Number123456789101112
Possible PneumoniaPneumonia-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 (%)36.828.485.958.499.766.25240.893.668.810074.8
Specificity (%)95.499.729.898.52.29895.499.629.896.82.395.7
PPV (%)55.393.81686.113.783.352.891.11268.59.363.6
NPV (%)919093.293.898.19595.294.4989710097.4
F-Measure44.243.62769.624.173.852.456.42168.61768.7
Open in a separate window  相似文献   

16.
Evaluation of Cholera and Other Diarrheal Disease Surveillance System,Niger State,Nigeria-2012     
Adebobola T. Bashorun  Anthony Ahumibe  Saliman Olugbon  Patrick Nguku  Kabir Sabitu 《Online Journal of Public Health Informatics》2013,5(1)

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% (Performance attributesExcellent (>90%)Very good (80–89%)Good (70–79%)Average (60–69%)Fair (50–59%)Poor (<50%)Simplicity•Flexibility•Data Quality•Acceptability•Sensitivity•Positive Predictive Value•Representativeness•Timeliness•Stability•Open in a separate windowLaboratory can isolate Vibro cholerae isolation but has no Cary Blair transport medium and cholera rapid test kits.

Conclusions

Evaluation revealed that surveillance system is meeting its objectives by early detection and response to cholera outbreaks. System is simple, stable, flexible, sensitive with poor data quality, low PPV, fair laboratory capacity and moderate timeliness. We recommended electronic and internet-based reporting for timeliness and data quality improvement; and provision of laboratory consumables.Open in a separate window  相似文献   

17.
A Review of Evaluations of Electronic Event-based Biosurveillance Systems     
Kimberly Gajewski  Jean-Paul Chretien  Amy Peterson  Julie Pavlin  Rohit Chitale 《Online Journal of Public Health Informatics》2013,5(1)

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”.  相似文献   

18.
Category-Specific Comparison of Univariate Alerting Methods for Biosurveillance Decision Support     
Yevgeniy Elbert  Vivian Hung  Howard Burkom 《Online Journal of Public Health Informatics》2013,5(1)
  相似文献   

19.
Mental Illness and Co-morbid Conditions: BioSense 2008 – 2011     
Achintya N. Dey  Anna Grigoryan  Soyoun Park  Stephen Benoit  Taha Kass-Hout 《Online Journal of Public Health Informatics》2013,5(1)

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.  相似文献   

20.
Current Therapies and Emerging Drugs in the Pipeline for Type 2 Diabetes     
Quang T. Nguyen  Karmella T. Thomas  Katie B. Lyons  Loida D. Nguyen  Raymond A. Plodkowski 《American Health & Drug Benefits》2011,4(5):303-311

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.35 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) A1c <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.2and22 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
ClassDrug (brand)Mechanism of actionaHbA1c reduction, %bEffect on weightAdverse effectsaPrecautions/Comments
Alpha-glucosidase inhibitorsAcarbose (Precose) Miglitol (Glyset)Delay complex carbohydrate absorption0.5–0.8Weight neutralFlatulence, diarrhea, abdominal painTitrate slowly to minimize gastrointestinal effects
Amylin analogPramlintide (Symlin)Acts in conjunction with insulin to prolong gastric emptying, reduce postprandial glucose secretion, promote appetite suppression0.5–1Weight lossNausea, vomitingBlack box warning: Coadministration with insulin may induce severe hypoglycemia Injectable drug
BiguanideMetformin (Glucophage)Decrease hepatic glucose output Increase peripheral glucose uptake1–2Weight neutralNausea, vomiting, diarrhea, flatulenceTaken with meals Avoid use in patients with renal or hepatic impairment or with CHF, because of increased risk for lactic acidosis
Bile acid sequestrantColesevelam (Welchol)Binds to intestinal bile acids Mechanism of action for diabetes control unknown0.5Weight neutralConstipation, dyspepsia, nausea 
DPP-4 inhibitorsSitagliptin (Januvia) Saxagliptin (Onglyza) Linagliptin (Tradjenta)Slow inactivation of incretin hormones0.5–0.8Weight neutralNot clinically significant 
Dopamine agonistBromocriptine (Parlodel)Mechanism of action for diabetes control unknown0.5–0.7Weight neutralNausea, vomiting dizziness, headache, diarrhea 
Incretin mimeticsExanetide (Byetta)
Liraglutide (Victoza)
Stimulate insulin secretion, slows gastric emptying, suppresses glucagon release, induces satiety0.5–1Weight lossNausea, vomiting, diarrheaAcute pancreatitis has been reported during postmarketing experience
Injectable drug
Insulin preparations: rapid-, short-, intermediate-, long-acting, premixedRefer to Exogenous insulinUp to 3.5Weight gainHypoglycemia 
Nonsulfonylurea secretagoguesNateglinide (Starlix)
Repaglinide (Prandin)
Stimulate insulin secretion from the pancreas1–1.5Weight gainHypogylcemiaTaken with meals to control rapid onset
First-generation sulfonylureasChlorpropamide (Diabinese)
Tolazamide (Tolinase)
Tolbutamide (Orinase)
Stimulate insulin secretion from the pancreas1–2Weight gainHypoglycemiaUse of these agents has declined in response to adverse effects and unpredictable results
Second-generation sulfonylureasGlimepiride (Amaryl)
Glipizide (Glucotrol)
Glyburide (Micronase, Diabeta, Glynase)
Stimulate insulin secretion from the pancreas1–2Weight gainHypoglycemia 
ThiazolidinedionesPioglitazone (Actos)
Rosiglitazone (Avandia)
Increase peripheral tissue insulin sensitivity0.5–1.4Weight gainEdemaBlack box warning: These agents can cause or exacerbate CHF Contraindicated in patients with NYHA class III or IV heart failure
Open in a separate windowaLacy CF, et al, eds. Drug Information Handbook. 18th ed. Hudson, OH: Lexi-Comp; 2009–2010.bNathan DM, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2006;29:1963–1972.CHF indicates congestive heart failure; DPP, dipeptidyl peptidase; HbA1c, glycated hemoglobin; NYHA, New York Heart Association.

Table 2

Insulin Preparations
Drug (brand)Onset timeaPeak timeaDurationaComments
Rapid-acting
Insulin aspart (NovoLog)10–20 min1–3 hr3–5 hrAdminister within
Insulin glulisine (Apidra)25 min45–48 min4–5 hr15 min before or immediately after
Insulin lispro (Humalog)15–30 min0.5–2.5 hr3–6.5 hrmeals
Short-acting
Insulin regular (Novolin R, Humulin R)30–60 min1–5 hr6–10 hrAdminister 30 min before meals
Intermediate-acting
Insulin NPH (Novolin N, Humulin N)1–2 hr6–14 hr16–24+ hrCloudy appearance
Long-acting
Insulin detemir (Levemir)1.1–2 hr3.2–9.3 hr5.7–24 hrDo not mix with (dose-dependent) other insulins
Insulin glargine (Lantus)1.1 hrNone24 hr 
Premixed
70% Insulin aspart protamine/30% insulin aspart (NovoLog Mix 70/30)10–20 min1–4 hr24 hrCloudy appearance Administer within 15 min before meals
75% Insulin lispro protamine/25% insulin lispro protamine (Humalog Mix 75/25)15–30 min2 hr22 hr 
50% Insulin lispro protamine/50% insulin lispro protamine (Humalog Mix 50/50)15–30 min2 hr22 hr 
70% Insulin NPH/30% insulin regular (Humulin 70/30, Novolin 70/30)30 min1.5–12 hr24 hrCloudy appearance Administer within 30 min before meals
50% Insulin NPH/50% insulin regular (Humulin 50/50)30–60 min1.5–4.5 hr7.5–24 hr 
Open in a separate windowaMcEvoy GK, ed. American Society of Health-System Pharmacists Drug Information. Bethesda, MD; 2008.NPH indicates neutral protamine Hagedorn.Indeed, the number of diabetes medications for type 2 diabetes is expected to grow in the next few years, considering the many promising investigational therapeutic options currently in development that may gain FDA approval in the future. This article reviews some of the therapies that are currently being tested and may soon become new options for the treatment of type 2 diabetes (Drug categoryMechanism of actionCommentsSodium-glucose cotransporter-2 inhibitorsInhibit reabsorption of glucose at the proximal tubule of the kidney, thereby decreasing systemic hyperglycemiaLow potential for hypoglycemia Furthest along in clinical trials11beta-hydroxysteroid dehydrogenase type 1 inhibitorsInhibit an enzyme responsible for activating cortisone to cortisol, which minimizes antiglycemic effects of cortisolLow potential for hypoglycemia All drugs currently in phase 2 clinical trialsGlycogen phosphorylase inhibitorsInhibit enzymes responsible for hepatic gluconeogenesisStill very early in development Oral agents have shown promising results in animals and humansGlucokinase activatorsActivate key enzyme to increase hepatic glucose metabolismSeveral drugs are currently in phase 2 clinical trialsG protein–coupled receptor 119 agonistsMechanisms unknown Activation induces insulin release and increases secretion of glucagon-like peptide 1 and gastric inhibitory peptideStill very early in development Animal data are availableProtein tyrosine phosphatase 1B inhibitorsIncrease leptin and insulin releaseStill very early in development A potential weight-loss medicationGlucagon-receptor antagonistsBlock glucagon from binding to hepatic receptors, thereby decreasing gluconeogenesisLow potential for hypoglycemiaOpen in a separate window  相似文献   

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