Hennepin County Medical Center

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy. METHODS: A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease. RESULTS: A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo). CONCLUSIONS: Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.

Transjugular intrahepatic portosystemic shunts (TIPS) may worsen liver function and decrease survival in some patients. The Child-Pugh classification has several drawbacks when used to determine survival in such patients. The survival of 231 patients at 4 medical centers within the United States who underwent elective TIPS was studied to develop statistical models to (1) predict patient survival and (2) identify those patients whose liver-related mortality post-TIPS would be 3 months or less. Among these elective TIPS patients, 173 had the procedure for prevention of variceal rebleeding and 58 for treatment of refractory ascites. Death related to liver disease occurred in 110 patients, 70 within 3 months. Cox proportional-hazards regression identified serum concentrations of bilirubin and creatinine, international normalized ratio for prothrombin time (INR), and the cause of the underlying liver disease as predictors of survival in patients undergoing elective TIPS, either for prevention of variceal rebleeding or for treatment of refractory ascites. These variables can be used to calculate a risk score (R) for patients undergoing elective TIPS. Patients with R > 1.8 had a median survival of 3 months or less. This model was superior to both the Child-Pugh classification, as well as the Child-Pugh score, in predicting survival. Using logistic regression and the same variables, we also developed a nomogram that indicates which patients survive less than 3 months. Finally, the model was validated among an independent set of 71 patients from the Netherlands. This Mayo TIPS model may predict early death following elective TIPS for either prevention of variceal rebleeding or for treatment of refractory ascites.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

INTRODUCTION Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection (1). Sepsis and septic shock are major healthcare problems, impacting millions of people around the world each year and killing between one in three and one in six of those it affects (2–4). Early identification and appropriate management in the initial hours after the development of sepsis improve outcomes. The recommendations in this document are intended to provide guidance for the clinician caring for adult patients with sepsis or septic shock in the hospital setting. Recommendations from these guidelines cannot replace the clinician’s decision-making capability when presented with a unique patient’s clinical variables. These guidelines are intended to reflect best practice (Table 1). TABLE 1. - Table of Current Recommendations and Changes From Previous 2016 Recommendations Recommendations 2021 Recommendation Strength and Quality of Evidence Changes From 2016 Recommendations 1. For hospitals and health systems, we recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment. Strong , moderate-quality evidence (for screening) Changed from Best practice statement “We recommend that hospitals and hospital systems have a performance improvement program for sepsis including sepsis screening for acutely ill, high-risk patients.” Strong , very low-quality evidence (for standard operating procedures) 2. We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a single-screening tool for sepsis or septic shock. Strong , moderate-quality evidence NEW 3. For adults suspected of having sepsis, we suggest measuring blood lactate. Weak , low quality of evidence INITIAL RESUSCITATION 4. Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately. Best practice statement 5. For patients with sepsis induced hypoperfusion or septic shock we suggest that at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hr of resuscitation. Weak, low quality of evidence DOWNGRADE from Strong , low quality of evidence “We recommend that in the initial resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first 3 hr” 6. For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation, over physical examination, or static parameters alone. Weak , very low quality of evidence 7. For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate. Weak , low quality of evidence 8. For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion. Weak , low quality of evidence NEW MEAN ARTERIAL PRESSURE 9. For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets. Strong , moderate-quality evidence ADMISSION TO INTENSIVE CARE 10. For adults with sepsis or septic shock who require we suggest the patients to the within Weak , low quality of evidence For adults with suspected sepsis or septic shock we recommend and for and an of is or Best practice statement For adults with septic shock or a for sepsis, we recommend within hr of Strong , low quality of evidence from “We recommend that of should be as as after and within one for septic shock and sepsis Strong , very low quality of evidence , quality of evidence For adults with sepsis shock, we recommend of the of of Best practice statement For adults with sepsis shock, we suggest a of and for infection the of within 3 hr from the time when sepsis first Weak , very low quality of evidence NEW from “We recommend that of IV should be as as after and within hr for septic shock and sepsis , quality of evidence For adults with a low of infection and shock, we suggest to the Weak , very low quality of evidence NEW from “We recommend that of IV should be as as after and within hr for septic shock and sepsis , quality of evidence For adults with suspected sepsis or septic shock, we suggest against using clinical to when to as compared to clinical alone. Weak , very low quality of evidence For adults with sepsis or septic shock at of we recommend using with over using Best practice statement NEW from “We recommend with one or for patients with sepsis or septic shock to and or Strong , quality of evidence For adults with sepsis or septic shock at low of we suggest against using with as compared with using Weak , low quality of evidence NEW from “We recommend with one or for patients with sepsis or septic shock to and or Strong , quality of evidence For adults with sepsis or septic shock and for we suggest using with for treatment over one Weak , very low quality of evidence For adults with sepsis or septic shock and low for we suggest against using for as compared to one Weak , very low quality of evidence For adults with sepsis or septic shock, we suggest against using the and the are Weak , very low quality of evidence For adults with sepsis or septic shock at of we suggest using over Weak , low quality of evidence NEW from “We recommend with one or for patients with sepsis or septic shock to and or Strong , quality of evidence For adults with sepsis or septic shock at low of we suggest against of Weak , low quality of evidence NEW from “We recommend with one or for patients with sepsis or septic shock to and or Strong , quality of evidence We on the of For adults with sepsis or septic shock, we suggest using of for an initial over Weak , moderate-quality evidence For adults with sepsis or septic shock, we recommend of on and Best practice statement For adults with sepsis or septic shock, we recommend or a of infection that and as as and Best practice statement For adults with sepsis or septic shock, we recommend of that are a of sepsis or septic shock after other Best practice statement For adults with sepsis or septic shock, we suggest for of over using of for Weak , very low quality of evidence For adults with an initial of sepsis or septic shock and we suggest using over of Weak , very low quality of evidence For adults with an initial of sepsis or septic shock and of is we suggest using clinical to when to over clinical alone. Weak , low quality of evidence For adults with sepsis or septic shock, we recommend using as fluid for resuscitation. Strong , moderate-quality evidence For adults with sepsis or septic shock, we suggest using of for resuscitation. Weak , low quality of evidence from , low quality of “We suggest using or for fluid resuscitation of patients with sepsis or septic For adults with sepsis or septic shock, we suggest using in patients who of Weak , moderate-quality evidence For adults with sepsis or septic shock, we recommend against using for resuscitation. Strong , evidence For adults with sepsis and septic shock, we suggest against using for resuscitation. Weak , moderate-quality evidence from , low quality of evidence “We suggest using over when patients with sepsis or septic For adults with septic shock, we recommend using as the over other Strong evidence evidence quality of evidence quality of evidence low-quality evidence For adults with septic shock on with mean arterial pressure we suggest of the of Weak , quality evidence For adults with septic shock and mean arterial pressure and we suggest Weak , low quality of evidence For adults with septic shock, we suggest against using Weak , low quality of evidence For adults with septic shock and dysfunction with hypoperfusion and arterial blood we suggest to or using alone. Weak , low quality of evidence For adults with septic shock and dysfunction with hypoperfusion and arterial blood we suggest against using Weak , low quality of evidence NEW For adults with septic shock, we suggest of arterial blood pressure over as as and are Weak , very low quality of evidence For adults with septic shock, we suggest to mean arterial pressure a is Weak , very low quality of evidence NEW is evidence to a on the of fluid in the first hr of resuscitation in patients with sepsis and septic shock who have of hypoperfusion and after the initial resuscitation. NEW “We suggest using or for fluid resuscitation of patients with sepsis or septic Weak , low quality of evidence “We suggest using over when patients with sepsis or septic Weak , low quality of evidence is evidence to a on the of in adults with sepsis-induced For adults with sepsis-induced we suggest the of over Weak , low quality of evidence NEW is evidence to a on the of in to for adults with sepsis-induced For adults with sepsis-induced we recommend using a low over a Strong , evidence For adults with sepsis-induced we recommend using an for of 30 over higher Strong , moderate-quality evidence For adults with to sepsis-induced we suggest using higher over Weak , moderate-quality evidence For adults with sepsis-induced we suggest using low as compared with Weak , low quality of evidence For adults with sepsis-induced we suggest using Weak , moderate-quality evidence using we recommend against using Strong , moderate-quality evidence For adults with sepsis-induced we recommend using for hr Strong , moderate-quality evidence For adults with sepsis induced we suggest using over Weak , moderate-quality evidence For adults with sepsis-induced we suggest using when in with the in to Weak , low quality of evidence NEW For adults with septic shock and an for we suggest using IV Weak , moderate-quality evidence from Weak , low quality of evidence “We suggest against using IV to septic shock patients fluid resuscitation and are to for this is not we suggest IV at a of For adults with sepsis or septic shock we suggest against using Weak , low quality of evidence NEW from “We the of blood is evidence to a on the of other blood For adults with sepsis or septic shock we recommend using a Strong , moderate-quality evidence For adults with sepsis or septic shock we suggest against using IV Weak , low quality of evidence For adults with sepsis or septic shock, and who have for we suggest using Weak , moderate-quality evidence For adults with sepsis or septic shock, we recommend using a to Strong , moderate-quality evidence For adults with sepsis or septic shock, we recommend using low over for Strong , moderate-quality evidence For adults with sepsis or septic shock, we suggest against using in to over alone. Weak , low quality of evidence adults with sepsis or septic shock and we suggest using or Weak , low quality of evidence adults with sepsis or septic shock and with for we suggest against using Weak , moderate-quality evidence For adults with sepsis or septic shock, we recommend at a of Strong , moderate-quality evidence For adults with sepsis or septic shock we suggest against using IV Weak , low quality of evidence NEW For adults with septic shock and we suggest against using to improve or to Weak , low quality of evidence For adults with septic shock and and or we suggest using Weak , low quality of evidence For adult patients with sepsis or septic shock who be we suggest of Weak , very low quality of evidence CARE For adults with sepsis or septic shock, we recommend of and with patients and over Best practice statement For adults with sepsis or septic shock, we suggest of over hr or Weak , low quality of evidence For adults with sepsis or septic shock, is evidence to a on to of For adults with sepsis or septic shock, we recommend that the of on clinician be the treatment when to and and Best practice statement For adults with sepsis or septic shock, we suggest against for patients over on clinician Weak , low quality of evidence For adult of sepsis or septic shock and we suggest to over Weak , very low quality of evidence For adults with sepsis or septic shock, we suggest using a of at of over Weak , very low quality of evidence For adults with sepsis or septic shock, is evidence to a on the of tool over For adults with sepsis or septic shock and we recommend screening for and and and to these Best practice statement For adults with sepsis or septic shock and we suggest and sepsis and to hospital and in the setting. Weak , very low quality of evidence For adults with sepsis or septic shock and we recommend the clinical provide the to in in and hospital to are and Best practice statement For adults with sepsis and septic shock and we suggest using a compared with to the Weak , very low quality of evidence For adults with sepsis and septic shock, we recommend at and hospital Best practice statement For adult of sepsis and septic shock and we recommend including the sepsis and and after sepsis in the and hospital Best practice statement For adults with sepsis or septic shock who we recommend hospital with to and and Best practice statement For adults with sepsis or septic shock and is evidence to a on compared with For adults with sepsis or septic shock, is evidence to a for or against For adult of sepsis or septic shock, we recommend and for and after hospital Best practice statement For adult of sepsis or septic shock, we suggest to a program Weak , very low quality of evidence For adult of sepsis or septic shock for or an of we suggest to a Weak , very low quality of evidence are to in the be at for Sepsis and - Recommendation 1. For hospitals and health systems, we recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment. Strong quality of evidence for Strong very low-quality evidence for standard operating Sepsis performance improvement of sepsis of sepsis and for a of on the of performance improvement that these with to sepsis with a in in patients with sepsis and septic shock The of performance improvement not to be as as the of a program that sepsis screening and Sepsis screening are to identification of sepsis and of or of the health is in of these with having the of with in of clinical and are for sepsis as response of or Early or Early improve performance of screening and in a of patients from for hospital sepsis the the operating and higher for the for screening as MEWS and target patients in as or of three not a of screening is in and of sepsis screening are an of sepsis for operating procedures are a of that a response to clinical Sepsis standard operating as Early have to a standard with of the sepsis and the between of sepsis and of sepsis to hospitals in the in a and after of sepsis with a from other this time in hospitals with higher with the sepsis a of in higher with standard operating procedures compared with it in one - Recommendation 2. We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a screening tool for sepsis or septic shock. Strong moderate-quality The qSOFA three to and in patients with or suspected a a and a blood pressure mm of these are the is qSOFA to the recommendations of the on the of Sepsis qSOFA as a of in patients with or suspected to as a screening tool that time have the of the qSOFA as a screening tool for sepsis The have as to have that qSOFA is having of for identification of infection induced organ dysfunction qSOFA are screening for sepsis and the clinician to the of the that of patients a qSOFA or these patients for of have when against the Early and the Early the of a qSOFA should the clinician to the of sepsis in given the of the the a against as a screening - Recommendation 3. For adults suspected of having sepsis, we suggest measuring blood lactate. Weak low-quality The of lactate with in patients with suspected infection and sepsis is is as of the sepsis for those patients with sepsis and an elevated lactate is of the of septic shock that lactate be to for the of sepsis adult patients with suspected not have the of lactate in this The lactate an elevated from of the from with from and from the three are and an between the of lactate at and the are the of an elevated or lactate or the of a of sepsis in patients with suspected lactate is to or the on not be in we a the of serum lactate as an to the of sepsis in patients with suspected not - Recommendations 4. Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately. Best practice 5. For patients with sepsis induced hypoperfusion or septic shock we suggest that at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hours of resuscitation. Weak low-quality 6. For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation over physical or static parameters alone. Weak very low-quality parameters response to a or a fluid using pressure or 7. For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate. Weak low-quality resuscitation, serum lactate should be the clinical and other of elevated lactate. 8. For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion. Weak low-quality fluid resuscitation is for the of sepsis-induced hypoperfusion in sepsis and septic shock. Previous guidelines recommend appropriate resuscitation of sepsis or septic shock and having a low for it in those patients sepsis is not is the evidence from this is a best practice and are that a is The 2016 a for using a of 30 mL/kg of IV in initial fluid resuscitation. of initial resuscitation on evidence are for initial resuscitation in sepsis or septic shock. of adults to an with sepsis or septic shock that to 30 mL/kg of crystalloid fluid within 3 hours of sepsis with of of and of in of including and the and the of fluid in the of 30 that this fluid in clinical practice patients require fluid initial resuscitation. to be with the of fluid and with fluid of and of the of septic patients is the for a initial and of the response to treatment. and fluid the initial resuscitation should be by of and organ perfusion. pressure and blood pressure are of fluid measures have at fluid compared with static measures with fluid against pressure or and of in response to in a and dynamic to guide fluid with to of to and of to in one other in between septic patients with a compared with standard from and a of evidence in to guide of fluid resuscitation as as the appropriate in patients with sepsis and in that resuscitation with of IV by and arterial with fluid in the first hours and higher hospital standard fluid the initial 30 mL/kg is by measures of fluid of mL/kg compared to to 3 mL/kg the of fluid and on of of or not be a in pressure that the is fluid a for lactate is an of and is not a of of septic shock in lactate as evidence of to (1). Previous of these guidelines have using lactate as a target of resuscitation in the of sepsis and septic shock, on to and of in serum lactate in with or in The that serum lactate are not in patients with septic shock, these that decrease lactate lactate should be the clinical and other of elevated lactate. with sepsis lactate not be in is not measures of organ be to the and of of the and capillary refill time have and to be of The a resuscitation a resuscitation at or lactate by hours in the first hours of septic shock the organ dysfunction as by in the and in the lactate this not the of a on using resuscitation and is and this should be by and to or fluid are of the or to the should management - Recommendation 9. For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets. Strong moderate-quality MAP is a of mean in is the major of and MAP in blood and the of perfusion. as the and have the to blood a to be mm are with organ with MAP Previous guidelines a MAP of 65 mm Hg for initial resuscitation. The on a in septic shock patients who given to target a MAP of mm a target of mm Hg in a a in with higher MAP patients with higher MAP with with a higher of of this that the MAP in the of on this that higher MAP not improve in septic shock to and MAP target compared a mm with a that and MAP by the in patients 65 and with septic shock The in this a mean MAP of mm compared with mm Hg in the to in the by of and in in the and the of with higher MAP and the of patients with MAP of mm the a MAP of 65 mm Hg in the initial resuscitation of patients with septic shock who require to - Recommendation 10. For adults with sepsis or septic shock who require we suggest the patients to the within Weak low-quality The of patients on of in an appropriate the septic patients are in the and hospital of patients from are with sepsis and and and hospital of on the time for to the from and an of an in of for each of to of patients in the a higher hospital for the higher to time hr and compared with the to time for of an to time hr with hospital in patients with higher of with sepsis not patients to when hours hospital the a hospital higher and higher of and of patients in hospitals in the that to to higher and on of patients to an in outcomes. is evidence of and are best in an are of patients with sepsis to an not be in in and be this and appropriate treatment should not be of of - Recommendation For adults with suspected sepsis or septic shock we recommend and for and an of is or Best practice of these we the of a for to it is to in a a best practice we that appropriate should be in patients with suspected sepsis and septic shock it in in the of not in this as as The and of sepsis are and other is to sepsis, the cannot have a of sepsis in a with organ a or of patients with sepsis to have Best practice is to the to other are or a patient’s clinical after hospital or the of a of this be in when it is to or major is a that to on the that the is each as in and of the that by or in each in of or that the for a in the or a We not or evidence this are to a an that not from is or this is not of the should the of patients and patients that is not to - Recommendations For adults with septic shock or a for sepsis, we recommend within one of Strong low quality of evidence very low quality of evidence For adults with sepsis shock, we recommend of the of of Best practice and clinical examination, for and of and treatment for that this should be within 3 hours of that a be as to the of an of the patient’s and the of sepsis is to be For adults with sepsis shock, we suggest a of and for infection the of within 3 hours from the time when sepsis first Weak very low quality of For adults with a low of infection and shock, we suggest to the Weak very low quality of Early of appropriate is one of the to in patients with sepsis to patients with sepsis or septic shock should be as an The to provide as as be against the with to patients infection These a of as or and sepsis is as sepsis in and that first to be sepsis to be the of infection and of for each with suspected sepsis should the and of The with in patients with septic shock, have a between time to and in patients with septic shock in patients septic shock a of patients at each of time from to of with of for patients for patients not on a of patients at each of time from to of with of for patients with sepsis at least one of or or organ and for patients with septic to a for sepsis and a for septic shock in a of patients in each in time from to of with of and of in patients with in patients not an between and should be that the and at of to the of with or other patients with sepsis shock, the between time to and within the first hours from is have one to a in between and the other in a in time to suggest that after hours from hospital sepsis We suggest in patients with sepsis shock as as sepsis to be the and 3 hours after sepsis first suspected for sepsis at that given the of with septic shock and the of and the a to and within one in patients with septic shock. for patients with sepsis, we recommend be 1). For patients with sepsis shock, we recommend a of and of be to within 3 should be or should be to the Recommendations on of from suggest that of in patients with sepsis and septic shock is and and of a of in The and time for by and the of and of on is to recommendations to the of in patients with sepsis and septic shock in are in with the recommendations to - Recommendation For adults with suspected sepsis or septic shock, we suggest against using clinical to when to as compared to clinical alone. Weak very low quality of is in in response to in with clinical the of and of a of 30 a of and of for sepsis in patients We evidence from three that compared for of the three in to of to or of to and not in of the and on the with of the and the quality of evidence very guidelines for the management of recommend of for patients with of and in including the a against using to guide in to clinical - Recommendations For adults with sepsis or septic shock at of we recommend using with over using Best practice For adults with sepsis or septic shock at low of we suggest against using with as compared with using Weak low quality of The on to an against in an treatment for sepsis and septic shock the that the patient’s infection is caused by the of with treatment for in a with and the of with treatment in a for of patients and be to The of by from in to in and by for of infection or IV of or of hospital and of on the of including in on patients with the of in patients with of hours are with in not in patients with or sepsis, including against with higher patients The with are by an between of and in patients with or to for in a with be in a be from including the of to for are and on and clinical for are - Recommendations For adults with sepsis or septic shock and for we suggest using with for treatment over one Weak very low quality of For adults with sepsis or septic shock and low for we suggest against using for compared with one Weak very low quality of For adults with sepsis or septic shock, we suggest against using the and the are Weak very low quality of the of in of the world and between in and the initial of is to the at least one that is against the the and are the of on the of for and the of the and are is for patients with in a with of in or other between in adult patients with sepsis or septic shock when from the in the of of and in a low with the from the Recommendations the of one for treatment over one are given clinical including of and the of the of sepsis is to the appropriate For this we from recommendations in patients with sepsis or septic shock recommend the of on of to guide this infection or with within the of within the to a within the and within the the and are is not for patients with with and quality of evidence very and the of with the of for treatment. have an in in patients at for we suggest using for treatment to the of in patients with a low for we suggest using a for as are of using and the a of including infection and development of of is in patients at for with septic shock. - Recommendations For adults with sepsis or septic shock at of we suggest using over Weak low quality of For adults with sepsis or septic shock at low of we suggest against of Weak low quality of Sepsis and septic shock to are in and are with that of appropriate

BACKGROUND: Endoscopic sphincterotomy is commonly used to remove bile-duct stones and to treat other problems. We prospectively investigated risk factors for complications of this procedure and their outcomes. METHODS: We studied complications that occurred within 30 days of endoscopic biliary sphincterotomy in consecutive patients treated at 17 institutions in the United States and Canada from 1992 through 1994. RESULTS: Of 2347 patients, 229 (9.8 percent) had a complication, including pancreatitis in 127 (5.4 percent) and hemorrhage in 48 (2.0 Percent). There were 55 deaths from all causes within 30 days; death was directly or indirectly related to the procedure in 10 cases. Of five significant risk factors for complications identified in a multivariate analysis, two were characteristics of the patients (suspected dysfunction of the sphincter of Oddi as an indication for the procedure and the presence of cirrhosis) and three were related to the endoscopic technique (difficulty in cannulating the bile duct achievement of access to the bile duct by "precut" sphincterotomy, and use of a combined percutaneous-endoscopic procedure). The overall risk of complications was not related to the patient's age, the number of coexisting illnesses, or the diameter of the bile duct. The rate of complications was highest when the indication for the procedure was suspected dysfunction of the sphincter of Oddi (21.7 percent) and lowest when the indication was removal of bile-duct stones within 30 days of laparoscopic cholecystectomy (4.9 percent). As compared with those who performed fewer procedures, endoscopists who performed more than one sphincterotomy per week had lower rates of all complications (8.4 percent vs. 11.1 percent, P=0.03) and severe complications (0.9 percent vs. 2.3 percent, P=0.01). CONCLUSIONS: The rate of complications after endoscopic biliary sphincterotomy can vary widely in different circumstances and is primarily related to the indication for the procedure and to endoscopic technique, rather than to the age or general medical condition of the patients.

Between 1976-1979, 87 Type III open fractures (in 75 patients) were treated at the Hennepin County Medical Center. Factors leading to increased morbidity in Type III fractures were: massive soft-tissue damage; compromised vascularity; severe wound contamination; and marked fracture instability. This study demonstrates, because of varied severity and prognosis, that the current designation of Type III open fracture is too inclusive. We recommend, therefore, that Type III open fractures be divided, in order of worsening prognosis, into three subtypes. Type IIIA--Adequate soft-tissue coverage of a fractured bone despite extensive soft-tissue laceration or flaps, or high-energy trauma irrespective of the size of the wound. Type IIIB--Extensive soft-tissue injury loss with periosteal stripping and bone exposure. This is usually associated with massive contamination. Type IIIC--Open fracture associated with arterial injury requiring repair. Wound sepsis in the three subtypes were: Type IIIA, 4%, IIIB, 52%; and IIIC, 42%; while amputation rates were, respectively, 0%, 16%, and 42%. Only two patients developed osteomyelitis, and 12 patients had delayed or nonunions. Five patients died, all as a result of multisystem trauma. The bacterial pathogens in infected open fractures have changed dramatically over the years. In the present series (1976-1979), 77% of infections were due to Gram-negative bacteria, compared with 24% previously (1961-1975). A change of antibiotic therapy from a first-generation cephalosporin alone to a combination of a cephalosporin and an aminoglycoside, or a third-generation cephalosporin, is currently indicated in Type III open fractures.

INTRODUCTION Guidelines for the diagnosis and treatment of acute pancreatitis were published by the American College of Gastroenterology in 1997 (1). These and subsequent guidelines (2–7) have undergone periodic review (6, 8–13) in accordance with advances that have been made in the diagnosis and treatment of acute pancreatitis. Guidelines for clinical practice are intended to apply to all health-care providers who take care of patients with acute pancreatitis and are intended to be flexible, and to suggest preferable (but not the only) approaches. Because there is a wide range of choices in any health-care situation, the physician should select the course best suited to the individual patient and the clinical situation. These guidelines have been developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee, and approved by the Board of Trustees. The world literature in English was reviewed using a MEDLINE search and also using the Cochrane Library. The ratings of levels of evidence for these guidelines are indicated in Table 1. The final recommendations are based on the data available at the time of the publication of this document and may be updated with appropriate scientific development at a later time. The following guidelines are intended for adult and not pediatric patients. The main diagnostic guidelines include an assessment of risk factors of severity at admission and determination of severity. The major treatment guidelines include supportive care, fluid resuscitation, transfer to intensive care unit, enteral feeding, use of antibiotics, treatment of infected pancreatic necrosis, treatment of sterile pancreatic necrosis, treatment of associated pancreatic duct disruptions, and role of magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy for detection and treatment of choledocholithiasis in biliary pancreatitis.Table 1: Ratings of Evidence Used for This GuidelinePATHOPHYSIOLOGY The pathophysiology of acute pancreatitis is generally considered in three phases. In the first phase, there is premature activation of trypsin within pancreatic acinar cells. A variety of mechanisms have been proposed including disruption of calcium signaling in acinar cells (14–18), cleavage of trypsinogen to trypsin by the lysosomal hydrolase cathepsin-B, and decreased activity of the intracellular pancreatic trypsin inhibitor (17, 18). Once trypsin is activated, it activates a variety of injurious pancreatic digestive enzymes. In the second phase, there is intrapancreatic inflammation through a variety of mechanisms and pathways (16, 18–28). In the third phase, there is extrapancreatic inflammation including acute respiratory syndrome (ARDS) (16, 19–21, 29). In both phases, there are four important steps mediated by cytokines and other inflammatory mediators: 1) activation of inflammatory cells, 2) chemoattraction of activated inflammatory cells to the microcirculation, 3) activation of adhesion molecules allowing the binding of inflammatory cells to the endothelium, and 4) migration of activated inflammatory cells into areas of inflammation. In the majority of patients, acute pancreatitis is mild. In 10–20%, the various pathways that contribute to increased intrapancreatic and extrapancreatic inflammation result in what is generally termed systemic inflammatory response syndrome (SIRS) (Table 2). In some instances, SIRS predisposes to multiple organ dysfunction and/or pancreatic necrosis. The factors that determine severity are not clearly understood, but appear to involve a balance between proinflammatory and anti-inflammatory factors. Recent evidence suggests that the balance may be tipped in favor of proinflammatory factors by genetic polymorphisms of inflammatory mediators that increase severity of acute pancreatitis (27, 30, 31).Table 2: Systemic Inflammatory Response Syndrome (SIRS)CLINICAL CONSIDERATIONS Clinical Diagnosis It has been estimated that in the United States there are 210,000 admissions for acute pancreatitis each year (13). Most patients with acute pancreatitis experience abdominal pain that is located generally in the epigastrium and radiates to the back in approximately half of cases. The onset may be swift with pain reaching maximum intensity within 30 min, is frequently unbearable, and characteristically persists for more than 24 h without relief. The pain is often associated with nausea and vomiting. Physical examination usually reveals severe upper abdominal tenderness at times associated with guarding (32). is that a diagnosis of acute pancreatitis of the following three 1) abdominal pain of acute 2) and/or times the upper of and 3) of acute pancreatitis on This for the that an and/or be times the upper of in acute pancreatitis. In a patient with abdominal pain of acute pancreatitis and levels that are than times the upper of a be to a diagnosis of acute pancreatitis. In this for the that of abdominal pain be in some patients with to acute In both and are the course of acute pancreatitis. The may than The of the and/or not with the severity of acute pancreatitis. It is usually not to both and may be preferable it in some that increase including and some In is to be more and than in the diagnosis of acute pancreatitis. of the diagnosis of acute pancreatitis has in the clinical of the (32). and/or for include of the pancreatic development of a The diagnosis of acute pancreatitis is and biliary and In severe the patients appear and In the patients generally appear but not (32). A of the to the of acute pancreatitis is the of this the for acute to determine are and in that may acute include any diagnosis of biliary other biliary pancreatic acute pancreatitis use of and the of abdominal other a a of pancreatitis. within the first 24 h should include and ultrasound is usually at the time of admission to for the than to the diagnosis of acute pancreatitis. of duct by ultrasound is by is are of the duct is for the detection of duct the is by abdominal ultrasound to that are with the diagnosis of acute pancreatitis including of the of and in a is the best to that acute to the severity of acute and to of pancreatitis on that the diagnosis of acute pancreatitis include of the with of pancreatic and fluid the use of a diagnosis of pancreatic be In may to the of acute for a duct may be pancreatic may pancreatitis to other a pancreatic may suggest and of the pancreatic duct a may suggest The role of magnetic resonance and in the diagnosis of acute pancreatitis and of severity is These are to in pancreatic and choledocholithiasis The in in a based for acute pancreatitis The was to of of acute pancreatitis and its to of severity of and of and also to for patient in to the acute pancreatitis was an acute inflammatory of the that may also involve and/or organ for severity organ and and/or pancreatic but also including and of severity within h of and (Table by pancreatitis was of the with of the that is in response to may be inflammatory in by a was areas of pancreatic that was associated with necrosis. The for the diagnosis of of pancreatic than in than of the It was that pancreatic be sterile infected and that infected was by the of within the extrapancreatic fluid was pancreatic fluid that of the acute pancreatitis into the and other areas may both with and pancreatitis. Most fluid sterile and the A pancreatic was a of pancreatic by a that a result of acute pancreatic pancreatitis. It is generally that a of at is the onset of acute pancreatitis to a of and pancreatic and are usually to the an infected pancreatic should be termed a pancreatic A pancreatic may also an of pancreatic and acute pancreatitis was pancreatitis associated with organ dysfunction and an pancreatitis was pancreatitis associated with organ and/or was (Table were a of systemic that were of severe acute pancreatitis including a severe calcium by was an important in a based it is some of the in the was to and that of severity by the have not been in a in In there is scientific that should be in a of major are In the a was not for and/or for the diagnosis of acute pancreatitis. In published the times to times the upper of In the for severe pancreatitis organ and/or (Table This a of patients with levels of severity. the of pancreatic is more than a pancreatic all patients with pancreatitis without organ with organ have a of was between and organ with organ have a more than with organ for organ that were have not been in a have organ to and have for organ have have A of the is in acute and and the important of organ In a include of the for organ that are In the pancreatic was considered than of the than in These in Because of the in the for the of necrosis, it is to A of the a for the diagnosis of pancreatic necrosis. the pancreatic a was not made between The first is a of pancreatic by a that the the may also include the are usually The second of pancreatic is that within the of the and pancreatic with of pancreatic This frequently termed is a clinical that be to these of of patients have have pancreatitis patients with have infected of patients with pancreatitis experience organ but in the majority it is with a of organ in pancreatitis is of organ is the in infected than in sterile The in acute pancreatitis is approximately in in pancreatitis in infected necrosis, in sterile (Table in in the of organ is with organ is with organ literature that of of a result of infected necrosis, more have with a of later a the majority of within the first and the majority of the first These a variety of including of patients to a to patients within the first are generally to organ this are generally by infected of sterile necrosis. organ at and and/or are risk factors for severity that should be at with these may treatment in a a an intensive care of The of risk factors of severity of acute pancreatitis at admission is to transfer patients who are to have a severe to a an intensive care for to to of and to the of patients for in A variety of risk factors have been It is that have more severe pancreatitis of In but not all of has with a more severe have been a variety of that have to determine is a risk for severity in acute pancreatitis A that patients with a more systemic and but not In the of and termed within the first 24 h of admission the of severity in patients with acute pancreatitis have that patients with organ at admission have a than who not experience organ at admission The of organ to organ is a major in the associated with organ at admission patients with organ at admission has also been to with the of organ organ is within was to organ for more than was have that a on within the first 24 h of admission with severity in of organ the of on within 24 h has been associated with have indicated that has has also been to have other than that indicated that patients with pancreatitis in first of pancreatitis have a for and of pancreatic In three all in acute pancreatitis the first in the third in the should patients on the of of to this In but not in a between onset of and with more severe abdominal pain was patients with of inflammatory in the and that third The that are at admission in severe acute pancreatitis are and It is that be the first of and to in this It is also that be at h and 24 h admission to of fluid of The severity of a variety of and be at admission and to patients with severe pancreatitis Table A variety of have a at admission and the first h with a with an and with an are some in the of the to patients for severity. in there was between and pancreatitis In three were not patients with sterile and infected In within the first 24 h a of and of for severe acute pancreatitis to the of and The of the was the of this within the first 24 h and In an that the first h is of the development of severe an that within the first h suggests pancreatitis.Table have been for to severity of acute pancreatitis but have the of a h for a In are is a more of that of severity of acute pancreatitis In the was the in sterile and infected have been that have to severity of pancreatitis with more that are available at In at admission and a were associated with a and In within 24 h of admission was also associated with a In at admission with a variety of including but not organ of intensive care, The of an to the to increase of for severity. In this a is to the the is and are the is than 30 In severe acute there is of fluid into third a result of inflammatory mediators inflammation by pancreatic The in be by an increased to in the of the of the and result in pancreatic necrosis. has been proposed a of pancreatitis In this at admission and of admission to at 24 h were the best of pancreatitis. In patients who with and a increase in at 24 h were at risk of pancreatic necrosis, of patients decreased by 24 h not pancreatic have not that at admission at 24 h is a risk for severe acute pancreatitis there is that the of pancreatitis is in the of at admission the of at admission the first 24 h is of a clinical is an acute levels than within the first h of with the of with a and that are both Because the is generally h this is not at admission in severity (16, A variety of including trypsinogen activation and have at admission in severe pancreatitis in but not all of these is available and organ are the important of severity in acute pancreatitis. The between and pancreatitis be made of by of patients with acute pancreatitis not a at admission at any time the a is usually not in patients with pancreatitis by A for a at admission (but not a with is to acute pancreatitis a A for a a admission is to pancreatitis there is clinical evidence of increased severity. The between and pancreatitis be made more a is on the second third admission than at the time of admission may be at the to and the course of of acute the development of necrosis, and including in is the best available to pancreatitis. pancreatitis is by an and of the pancreatitis is by disruption of the that areas not areas of intrapancreatic fluid than necrosis, areas of clearly a disruption of and pancreatic there is a than of to should be without the use of the between and pancreatitis be made in the of a some important in accordance with for severity (Table In the severe acute both in of organ and in the development of pancreatic necrosis, in pancreatitis. is a severity be This on the of the and the of than than with pancreatitis have a and than patients with for have been in some that the use of the severity of acute pancreatitis. there have been that have this evidence that in of on subsequent The determination that a patient has pancreatic has clinical the and of pancreatitis is than that of pancreatitis. the determination that a patient has pancreatitis may to treatment that is not in pancreatitis. the of may not be important in the and of pancreatitis was some have a between of and of organ have not some have a between the of and the of infected have not has a of of with have not In patients with than necrosis, was the in sterile to infected It is to these with in the care of patients with acute pancreatitis. is that there is in the of patients with severe pancreatitis who are to individual for In the of patients with severe pancreatitis who were for in the of patients was In some but not all patients who were were more than who were to the The should in that organ organ than the of to be a more important in the and of acute pancreatitis. in acute pancreatitis that be on abdominal include pancreatic fluid and biliary of inflammation of the and biliary organ with and pancreatic magnetic resonance has not been in the care of patients with acute pancreatitis. the to patients with acute have indicated that has some the of of to an for the of to to and the of to in the severity of acute pancreatitis and its In of duct and pancreatic duct of include of in and the of a patient It has been that patients with organ at admission have a than who not have organ at admission It has also been that for patients who organ for the first time may be organ is at admission the development of organ at admission a The are patients with organ and organ organ more than Because it is not at the onset of organ it is to be patients who of organ in accordance with the (Table 4) more care in a unit, an intensive care unit, there is It is that a organ that for severity for for for and for be to the severity of organ and of care with on that and of fluid is a in the care of patients with acute pancreatitis. of supportive care is in the treatment of acute pancreatitis. It is important to at and to of are These are of the first 24 h of admission the care of the patient be in it is not for patients to be in an for of time a these are usually to patients, and may be on patients with acute pancreatitis who appear to be a The should that and fluid may be for of time and fluid balance are the first 24 h and each It is that be the first are to should be the is that there is of should be is other clinical suggest the of to a of is of that with a fluid is of to by third and by inflammatory the of the and is a major to the development of pancreatitis. to and is evidence that fluid and of pancreatic and have not been in clinical there is of the of fluid in acute pancreatitis. In all patients who at admission and increased the first 24 h a result of fluid developed pancreatic the of fluid should be by and of at and 24 h admission for patients with at of is generally not A second important of is is evidence that to of and of is an important of pancreatic of and are also of and in that contribute both to pancreatic and also to organ respiratory It is important to abdominal pain with a is evidence to suggest an of any of The of and the of should be by have a pain by abdominal pain is be It is important to of frequently are to transfer to an intensive care should take for organ to an intensive care a care should be considered there are that suggest that the pancreatitis is severe is to be of Evidence of organ dysfunction is the important for transfer to an intensive care In to a of and that not to a fluid a transfer to an intensive care are other than organ that should of transfer to an intensive care is the for fluid to in an who may have that care be to the of a patient not have but is of transfer should be considered to in of a for with that by and in a but not transfer to an intensive care include with with evidence of and of to The of a an intensive care is the of care under the of a with care, and an intensive care the best supportive including fluid resuscitation, for of organ for and for respiratory and for there is treatment to organ enteral than is for patients who of In is usually within of and is not The of and the of have not been to In of of is usually abdominal pain has that are abdominal tenderness has nausea and have are and the assessment of the physician is that the patient has It has not been patients pancreatitis a at the onset of than a of to a The for of at the onset of has also not been In there is role for pancreatic the patient an in severe pancreatitis all of the is but also the of the is that a of the to the it is to pancreatic and an later in the not the patient has pancreatic in pancreatic necrosis, it is to use a inhibitor on a of the that by the is the patient to a In severe should be it that the patient not be to by for This assessment usually be made within the first of is to that enteral is preferable to there is evidence that in severe acute pancreatitis is in to may to infected and and that contribute to organ is also evidence that there is a of with in severe that may also contribute to Because enteral there has been in the of enteral not to appropriate but also to systemic and and there are associated with the use of that be by use of enteral have been a of but not that have enteral with have patients range that have in have been other that have been in In it is to that enteral is and than but there is not that there are major in and of acute pancreatitis. The of the of on and the other on of the were In enteral was in the the was that there were data to the and of enteral to be to determine the of In was to be to in of and be to determine the role of for A major to of pancreatic is into the is evidence that increase pancreatic and The result may be an of abdominal pain associated with a A of enteral is that some patients not the of a of time. the of be to the individual and on the response and The use of to pancreatic is not at this time patients with pancreatitis. of In there have been but not that have the role of in pancreatic The of patients in each was range of these and of the digestive these three a in infected with the use of antibiotics, and not a in have been three of these and a that was published in the other and the published in The in was that and in the other that pancreatic a on the of and in and that there was in the of infected necrosis, systemic in the the in this were also patients in this the that has this important A that a with in to the of of and based on of severity The also an that the use of may to a This risk to with use of the of patients with pancreatitis in has been it is there is a not It also patients should with evidence is are not in pancreatitis. is for in patients with pancreatitis. It should be that the first patients with pancreatic may appear with and/or organ this is appropriate an for a of is Once and other of are to be and of is is to It should also be that patients with pancreatitis may appear at various a is appropriate for these patients a for a of appropriate including of pancreatic necrosis, are to be should be with and is infected is of in infected is may be in of of patients with pancreatitis infected necrosis, usually of Most patients with infected have systemic and that is the time of admission at some time of patients with infected have organ at admission admission Because the in and may be in sterile and infected and organ may in a of patients with both sterile and infected in it is to these evidence of in the The between sterile and infected is an important the course of but the second and third at of of infected are The of by has to be and in sterile infected the first of this infected is on the of systemic and/or organ for and is The is usually the second third of this is for it is generally that patients with of systemic to of infected that at a later time may have developed but were not at the time of a reveals the of choices for treatment include a a a third of and reveals the of a is of and are The of care for infected pancreatic is patients are to Guidelines and review have generally that be have the of that be for patients with infected who are In a review that the treatment for infected for patients who were should be a course of to to the inflammatory to and the infected to The role of to in infected The of of a of is generally by the pancreatic The that infected pancreatic has also been by of patients who have been by and by of patients with infected with than In this there were patients who and also patients who were with without It is also that in of patients with without be to determine the of without The of that have generally been have with and with without have not been these are generally considered to in have been that are than of infected necrosis. These have generally been for patients with infected pancreatic who are to with organ and/or The first is a to to the of the to a an for of with and of for This and has not been in a to more is with of under This has and may have than This has not been in a to A third is of infected The this have been a the patient has to that infected This has not been to and a of who are to at more be available at all times for of of of of of infected and of endoscopic to sterile necrosis, may be to patients with infected necrosis, but should be with A pancreatic in the of an infected of an of pancreatic generally in a patient who is in the of acute pancreatitis. of a pancreatic is include endoscopic is best the first this abdominal pain persists and should be This is usually but endoscopic is a in with the appropriate duct and are and may endoscopic of in at of patients with sterile the was in patients with sterile with organ with the that of the of is an that patients with sterile should to be the first for the following there have been that a in and at times a of in and than sterile is a is the development of infected and the for In at patients a in that to in a of patients with sterile necrosis, there was a to on within The of in severe sterile in an to organ may be a is a is has been in sterile infected within the first of severe sterile has not been with the of and is an that has been to is for at the inflammatory in the and to an that the and This has frequently been necrosis. this organ has usually and patients are and not that are generally have in and the of infected necrosis, nausea of abdominal pain a result of within by of fluid pancreatic in the of the who of necrosis, by endoscopic than is often in an individual of patients with pancreatic is and is by a at a with in all with pancreatic of the of the fluid within the necrosis, and a is of an to the of the to a of This be by by a of be but including of more and of and in some be considered the is to the of the and endoscopic ultrasound reveals The of the with an through a by endoscopic to the of and of often endoscopic into the and of and of between the and the to endoscopic and/or

OBJECTIVES: To develop a brief screen to identify families at risk for food insecurity (FI) and to evaluate the sensitivity, specificity, and convergent validity of the screen. PATIENTS AND METHODS: Caregivers of children (age: birth through 3 years) from 7 urban medical centers completed the US Department of Agriculture 18-item Household Food Security Survey (HFSS), reports of child health, hospitalizations in their lifetime, and developmental risk. Children were weighed and measured. An FI screen was developed on the basis of affirmative HFSS responses among food-insecure families. Sensitivity and specificity were evaluated. Convergent validity (the correspondence between the FI screen and theoretically related variables) was assessed with logistic regression, adjusted for covariates including study site; the caregivers' race/ethnicity, US-born versus immigrant status, marital status, education, and employment; history of breastfeeding; child's gender; and the child's low birth weight status. RESULTS: The sample included 30,098 families, 23% of which were food insecure. HFSS questions 1 and 2 were most frequently endorsed among food-insecure families (92.5% and 81.9%, respectively). An affirmative response to either question 1 or 2 had a sensitivity of 97% and specificity of 83% and was associated with increased risk of reported poor/fair child health (adjusted odds ratio [aOR]: 1.56; P < .001), hospitalizations in their lifetime (aOR: 1.17; P < .001), and developmental risk (aOR: 1.60; P < .001). CONCLUSIONS: A 2-item FI screen was sensitive, specific, and valid among low-income families with young children. The FI screen rapidly identifies households at risk for FI, enabling providers to target services that ameliorate the health and developmental consequences associated with FI.

BACKGROUND: The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. METHODS: We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up. RESULTS: A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. CONCLUSIONS: A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

Resilience in human development is defined in relation to positive adaptation in the context of significant adversity, emphasizing a developmental systems approach. A brief history and glossary on the central concepts of resilience research in developmental science are provided, and the fundamental models and strategies guiding the research are described. Major findings of the first four decades of research are summarized in terms of protective and promotive factors consistently associated with resilience in diverse situations and populations of young people. These factors—such as self-regulation skills, good parenting, community resources, and effective schools—suggest that resilience arises from ordinary protective processes, common but powerful, that protect human development under diverse conditions. The greatest threats posed to children may be adversities that damage or undermine these basic human protective systems. Implications of these findings for theory and practice are discussed, highlighting three strategies of fostering resilience, focused on reducing risk, building strengths or assets, and mobilizing adaptive systems that protect and restore positive human development. The concluding section outlines future directions of resilience research and its applications, including rapidly growing efforts to integrate research and prevention efforts across disciplines, from genetics to ecology, and across level of analysis, from molecules to media.

BACKGROUND: Levels of MBCK can be increased in patients with skeletal muscle injury or renal failure in the absence of myocardial injury, causing diagnostic confusion. This study was designed to determine whether measurement of cardiac troponin I (cTnI), a myocardial regulatory protein with comparable sensitivity to MBCK, has sufficient specificity to clarify the etiology of MBCK elevations in patients with acute or chronic skeletal muscle disease or renal failure. METHODS AND RESULTS: Of the patients (n = 215) studied, 37 had acute skeletal muscle injury, 10 had chronic muscle disease, nine were marathon runners, and 159 were chronic dialysis patients. Patients were evaluated clinically, by ECG, and by two-dimensional echocardiography. Total creatine kinase (normal, < 170 IU/L) was determined spectrophotometrically, and cTnI (normal, < 3.1 ng/mL) and MBCK (normal, < 6.7 ng/mL) were determined with specific monoclonal antibodies. Values above the upper reference limit were considered "elevated." Elevations of total creatine kinase were common, and elevations of MBCK occurred in 59% of patients with acute muscle injury, 78% of patients with chronic muscle disease and marathon runners, and 3.8% of patients with chronic renal failure. Some of the patients were critically ill; five patients were found to have had myocardial infarctions and one had a myocardial contusion. cTnI was elevated only in these patients. CONCLUSIONS: Elevations of cTnI are highly specific for myocardial injury. Use of cTnI should facilitate distinguishing whether elevations of MBCK are due to myocardial or skeletal muscle injury.

Four men, aged 67-72 years, had 4-month to 6-year histories of injuring themselves or their spouses with aggressive behaviors during sleep, often during attempted dream enactment. A 60-year-old woman had disruptive though nonviolent sleep and dream behaviors. Polysomnography did not detect seizures but did document REM sleep pathology with variable loss of chin atonia, extraordinarily increased limb-twitch activity, and increased REM ocular activity and density. A broad range of REM sleep behaviors was recorded on videotape, including stereotypical hand motions, reaching and searching gestures, punches, kicks, and verified dream movements. Stage 3-4 slow wave sleep was elevated for age in all patients. NREM sleep was devoid of harmful behaviors, although three men had periodic myoclonus. There was no associated psychiatric disorder, whereas serious neurologic disorder was closely associated in four cases: olivo-ponto-cerebellar degeneration, Guillain-Barré syndrome, subarachnoid hemorrhage, and an atypical dementia. Two patients had immediate and lasting sleep behavioral suppression induced by clonazepam, and another patient had the same response with desipramine. All instances of drug discontinuation prompted immediate relapse. In four cases there was associated dream hyperactivity, which resolved with behavioral control. These REM sleep neurobehavioral disorders constitute another category of parasomnia, replicate findings from 21 years ago in cats receiving pontine tegmental lesions, and offer additional perspectives on human behavior, neurophysiology, pharmacology, and dream phenomenology.

For both children and adults with neurological, neurodevelopmental, medical, or psychiatric disorders, neuropsychological assessment can be a valuable tool in determining diagnosis, prognosis, and functional abilities as well as informing clinical management. This review summarizes the contributions of neuropsychological assessment to clinical care across diagnostic categories, with the goal of helping clinicians determine its utility for individual patients.

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.

BACKGROUND: Despite recommendations for annual vaccination against influenza, more than half of elderly Americans do not receive this vaccine. In a serial cohort study, we assessed the efficacy and cost effectiveness of influenza vaccine administered to older persons living in the community. METHODS: Using administrative data bases, we studied men and women over 64 years of age who were enrolled in a large health maintenance organization in the Minneapolis-St. Paul area. We examined the rate of vaccination and the occurrence of influenza and its complications in each of three seasons: 1990-1991, 1991-1992, and 1992-1993. Outcomes were adjusted for age, sex, diagnoses indicating a high risk, use of medications, and previous use of health care services. RESULTS: Each cohort included more than 25,000 persons 65 years of age or older. Immunization rates ranged from 45 percent to 58 percent. Although the vaccine recipients had more coexisting illnesses at base line than those who did not receive the vaccine, during each influenza season vaccination was associated with a reduction in the rate of hospitalization for pneumonia and influenza (by 48 to 57 percent, P < or = 0.002) and for all acute and chronic respiratory conditions (by 27 to 39 percent, P < or = 0.01). Vaccination was also associated with a 37 percent reduction (P = 0.04) in the rate of hospitalization for congestive heart failure during the 1991-1992 season, when influenza A was epidemic. The costs of hospitalization for all types of illness studied were lower in the vaccinated group during 1991-1992 (range of reduction, 47 to 66 percent; P < 0.005) and for acute and chronic respiratory conditions and congestive heart failure in 1990-1991 (reductions of 37 percent and 43 percent, respectively; P < or = 0.05). Direct savings per year averaged $117 per person vaccinated (range, $21 to $235), with cumulative savings of nearly $5 million. Vaccination was also associated with reductions of 39 to 54 percent in mortality from all causes during the three influenza seasons (P < 0.001). CONCLUSIONS: For elderly citizens living in the community, vaccination against influenza is associated with reductions in the rate of hospitalization and in deaths from influenza and its complications, as compared with the rates in unvaccinated elderly persons, and vaccination produces direct dollar savings.

BACKGROUND: Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. METHODS: We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. RESULTS: Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P=0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was -0.04±0.53 mg per deciliter (-3.5±46.9 μmol per liter) in the pharmacologic-therapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 μmol per liter) in the ultrafiltration group (P=0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P=0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P=0.03). CONCLUSIONS: In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.).

Knowledge of the excess risk posed by specific cardiovascular syndromes could help in the development of strategies to reduce premature mortality among patients with chronic kidney disease (CKD). The rates of atherosclerotic vascular disease, congestive heart failure, renal replacement therapy, and death were compared in a 5% sample of the United States Medicare population in 1998 and 1999 (n = 1,091,201). Patients were divided into the following groups: 1, no diabetes, no CKD (79.7%); 2, diabetes, no CKD (16.5%); 3, CKD, no diabetes (2.2%); and 4, both CKD and diabetes (1.6%). During the 2 yr of follow-up, the rates (per 100 patient-years) in the four groups were as follows: atherosclerotic vascular disease, 14.1, 25.3, 35.7, and 49.1; congestive heart failure, 8.6, 18.5, 30.7, and 52.3; renal replacement therapy, 0.04, 0.2, 1.6, and 3.4; and death, 5.5, 8.1, 17.7, and 19.9, respectively (P < 0.0001). With use of Cox regression, the corresponding adjusted hazards ratios were as follows: atherosclerotic vascular disease, 1, 1.30, 1.16, and 1.41 (P < 0.0001); congestive heart failure, 1, 1.44, 1.28, and 1.79 (P < 0.0001); renal replacement therapy, 1, 2.52, 23.1, and 38.9 (P < 0.0001); and death, 1, 1.21, 1.38, and 1.56 (P < 0.0001). On a relative basis, patients with CKD were at a much greater risk for the least frequent study outcome, renal replacement therapy. On an absolute basis, however, the high death rates of patients with CKD may reflect accelerated rates of atherosclerotic vascular disease and congestive heart failure.

We evaluated the results of treatment for ninety-seven patients (106 infections in ninety-eight hips) who had had either an infection after a total hip arthroplasty or positive intraoperative cultures of specimens obtained during revision of a total hip arthroplasty for presumed aseptic loosening. The patients were managed according to various protocols on the basis of the clinical setting (positive intraoperative cultures, early postoperative infection, late chronic infection, or acute hematogenous infection). Aerobic gram-positive cocci accounted for 109 (74 per cent) of the 147 microbial isolates; gram-negative bacilli, for twenty-one (14 per cent); and anaerobes, for twelve (8 per cent). The white blood-cell count and erythrocyte sedimentation rate were elevated in association with seventeen (16 per cent) and sixty-seven (63 per cent) of the 106 infections, respectively. The mean duration of follow-up was 3.8 years (range, 0.3 to eleven years). A good result was noted after the initial treatment of twenty-eight (90 per cent) of the thirty-one infections that had been diagnosed on the basis of positive intraoperative cultures at the time of the revision, twenty-five (71 per cent) of the thirty-five early postoperative infections, twenty-nine (85 per cent) of the thirty-four late chronic infections, and three of the six acute hematogenous infections. Of the twenty++-one infections for which the initial therapy failed, twelve eventually were eradicated after additional treatment and the hip had a functional prosthesis at the time of follow-up. Of the ninety-seven infections that were treated successfully (there was a functional retained or exchange prosthesis in place at the time of the most recent follow-up and infection had not recurred at least two years after the discontinuation of antibiotic therapy), nine were associated with subsequent aseptic loosening of the prosthesis. The factors associated with recurrent infection were retained bone cement, the number of previous operations, potential immunocompromise, and early postoperative infection after arthroplasty without cement.

BACKGROUND: The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy. METHODS: In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death. RESULTS: There was no significant difference between the two treatment groups in the rate of embolic events (five embolic events among 619 patients in the transesophageal-echocardiography group [0.8 percent]) vs. three among 603 patients in the conventional-treatment group [0.5 percent], P=0.50). However, the rate of hemorrhagic events was significantly lower in the transesophageal-echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent], P=0.03). Patients in the transesophageal-echocardiography group also had a shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days, P<0.001) and a greater rate of successful restoration of sinus rhythm (440 patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status. CONCLUSIONS: The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.

BACKGROUND: Patients who are members of minority groups may be more likely than others to consult physicians of the same race or ethnic group, but little is known about the relation between patients' race or ethnic group and the supply of physicians or the likelihood that minority-group physicians will care for poor or black and Hispanic patients. METHODS: We analyzed data on physicians' practice locations and the racial and ethnic makeup and socioeconomic status of communities in California in 1990. We also surveyed 718 primary care physicians from 51 California communities in 1993 to examine the relation between the physicians' race or ethnic group and the characteristics of the patients they served. RESULTS: Communities with high proportions of black and Hispanic residents were four times as likely as others to have a shortage of physicians, regardless of community income. Black physicians practiced in areas where the percentage of black residents was nearly five times as high, on average, as in areas where other physicians practiced. Hispanic physicians practiced in areas where the percentage of Hispanic residents was twice as high as in areas where other physicians practiced. After we controlled for the racial and ethnic makeup of the community, black physicians cared for significantly more black patients (absolute difference, 25 percentage points; P < 0.001) and Hispanic physicians for significantly more Hispanic patients (absolute difference, 21 percentage points; P < 0.001) than did other physicians. Black physicians cared for more patients covered by Medicaid (P = 0.001) and Hispanic physicians for more uninsured patients (P = 0.03) than did other physicians. CONCLUSIONS: Black and Hispanic physicians have a unique and important role in caring for poor, black, and Hispanic patients in California. Dismantling affirmative-action programs as is currently proposed, may threaten health care for both poor people and members of minority groups.