***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction In this prospect i ve , r and omized controlled study , we aim ed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis . Material s and methods Forty-two patients with severe sepsis were enrolled in the study . Patients in the study group ( n = 21 ) received an intravenous immunoglobulin preparation ( Pentaglobin ® ) in addition to st and ard therapy . Pentaglobin ® therapy was commenced on the day of diagnosis of severe sepsis : 5 ml/kg per day Pentaglobin ® ( 38 g/l IgG , 6 g/l IgM , and 6 g/l IgA ) was infused over 6 hours and repeated for 3 consecutive days . Patients in the control group ( n = 18 ) received st and ard sepsis therapy , but no immunoglobulin administration . Blood sample s for procalcitonin ( PCT ) measurements were taken daily for 8 days . Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation ( APACHE ) II and sequential organ failure assessment ( SOFA ) scores . Results and discussion Procalcitonin levels showed a statistically significant decrease in the Pentaglobin ® group ( P < 0.001 ) ; however , an improvement in SOFA scores could not be demonstrated . Procalcitonin levels and SOFA scores did not change significantly in the control group . Septic shock incidence ( 38 % versus 57 % ) and 28-day mortality rate ( 23.8 % versus 33.3 % ) were found to be similar between the Pentaglobin ® and control groups . The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin ® and control groups either . Conclusion Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin ® on organ morbidity , septic shock incidence and mortality rate in patients with severe sepsis The objective of this prospect i ve , r and omized , double-blind , placebo-controlled clinical trial was to evaluate the efficacy of adjunctive therapy with iv human immunoglobulin G in reducing the morbidity and mortality associated with acute renal failure . Forty patients greater than or equal to 18 yr of age who were identified within 48 h of the onset of acute renal failure and who met the enrollment criteria were enrolled in the study . Thirty-five patients were considered evaluable . Patients were grouped according to the admitting service ( medical or surgical/trauma ) and were r and omized to receive either immunoglobulin G ( 400 mg/kg body wt ) or placebo ( normal saline ; 8 mL/kg body wt ) at study entry and then weekly thereafter for a maximum of 4 doses . The groups were well balanced with respect to demographics , clinical presentation , and severity of illness ( APACHE II scores ) . A significant reduction in mortality at 42 days after study entry was observed . Two of 17 ( 12 % ) patients in the immunoglobulin G-treated group compared with 8 of 18 ( 44 % ) patients in the placebo-treated group died ( P = 0.025 ) . No differences were observed in the frequency of major complications that occurred in association with acute renal failure . However , in patients who manifested infection , greater survival was observed in the immunoglobulin G treatment group . The results suggest that immunoglobulin G administered at the onset of acute renal failure reduced mortality possibly by decreasing the severity of infectious complications associated with the occurrence of of acute renal failure . ( ABSTRACT TRUNCATED AT 250 WORDS Background Recombinant human activated protein C ( rhAPC ) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal r and omized trial . We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice . Methods We conducted a prospect i ve observational study involving adult patients recruited before and after licensure of rhAPC in France . Inclusion criteria were applied according to the label approved in Europe . The expected recruitment bias was controlled by building a sample of patients matched for propensity score . Complete hospitalization costs were quantified using a regression equation involving intensive care units variables . rhAPC acquisition costs were added , assuming that all costs associated with rhAPC were already included in the equation . Cost comparisons were conducted using the nonparametric bootstrap method . Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio . Results In the initial cohort ( n = 1096 ) , post-license patients were younger , had less co-morbid conditions and had failure of more organs than did pre-license patients ( for all : P < 0.0001 ) . In the matched sample ( n = 840 ) the mean age was 62.4 ± 14.9 years , Simplified Acute Physiology Score II was 56.7 ± 18.5 , and the number of organ failures was 3.20 ± 0.83 .  When rhAPC was used , 28-day mortality tended to be reduced ( 34.1 % post-license versus 37.4 % pre-license , P = 0.34 ) , bleeding events were more frequent ( 21.7 % versus 13.6 % , P = 0.002 ) and hospital costs were higher ( € 47,870 versus € 36,717 , P < 0.05 ) . The incremental cost-effectiveness ratios gained were as follows : € 20,278 per life-year gained and € 33,797 per quality -adjusted life-year gained . There was a 74.5 % probability that rhAPC would be cost-effective if there were willingness to pay € 50,000 per life-year gained . The probability was 64.3 % if there were willingness to pay € 50,000 per quality -adjusted life-year gained . Conclusion This study , conducted in matched patient population s , demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay € 50,000 per life-year gained is 74.5 % OBJECTIVE To evaluate the long-term survival of critically ill patients with sepsis and to assess the factors predictive of long-term survival ( > 1 month after admission date ) . DESIGN Prospect i ve , cohort study . SETTING Medical/surgical intensive care unit ( ICU ) in a multidisciplinary community hospital . PATIENTS All patients admitted to the ICU from January 1 , 1987 to March 31 , 1991 who both demonstrated clinical evidence of the systemic inflammatory response syndrome and yielded blood cultures positive for a bacterium or fungus ( n = 153 ) . INTERVENTIONS R and om set of procedures normally performed in an ICU setting . MEASUREMENTS AND MAIN RESULTS Patient characteristics , including age , blood culture results , comorbid conditions , and severity of illness as estimated by the Acute Physiology Score of the Acute Physiology and Chronic Health Evaluation II prognostic system were recorded . Follow-up evaluation utilizing the National Death Index provided survival outcome for all patients 1 yr after hospital discharge . The mortality rate at hospital discharge was 51.0 % , and mortality rates at 1 month , 6 months , and 1 yr after admission date were 40.5 % , 64.7 % , and 71.9 % , respectively . A total of 33 patients survived beyond the period of observation . The analyses demonstrated the following findings : a ) the survival rate was negatively correlated with the Acute Physiology Score up to 1 month after hospital admission date , but uncorrelated thereafter ; b ) fungal infections , such as C and ida , had the shortest survival prospect s of any blood-borne infection ; and c ) both malignancy and human immunodeficiency virus infection contributed to poorer outcomes , but differed in their patterns of long-term survival . CONCLUSIONS The most critical period for surveillance of bacteremic patients was in months 2 through 6 after discharge , during which time , the percentage of patients surviving decreased dramatically . The degree of physiologic derangement , as measured by the Acute Physiology Score , was a useful measure of prognosis within the first month after the score was assessed at ICU admission . However , beyond this period , prognostic utility decreased significantly . Healthcare providers should use caution concerning the expected survival of hospitalized patients with human immunodeficiency virus , based on experience with distinct conditions , such as malignancies OBJECTIVES To assess the clinical and cost-effectiveness of drotrecogin alfa ( activated ) for the treatment of adults with severe sepsis in a UK context . DATA SOURCES Electronic data bases . Data from the commercial use of the drug up to April 2002 . Data from the manufacturer su bmi ssion to the National Institute for Clinical Excellence ( NICE ) . REVIEW METHODS A systematic review of the literature and an economic evaluation were undertaken . Data were synthesis ed through a narrative review with full tabulation of results from included studies . RESULTS The evidence on the effectiveness of drotrecogin alfa ( activated ) for the treatment of severe sepsis came primarily from one large pivotal r and omised controlled trial , the PROWESS study . This study demonstrated a statistically significant absolute reduction in 28-day mortality of 6.5 % . Longer term survival benefit was maintained to 90 days . By 9 months , the trend towards increased median survival was non-significant , although the survival curves did not cross . Results presented by the number of organ dysfunctions were not statistically significant , but when mortality rates for those with two or more organ failures were combined , the relative risk of death was significantly lower in those treated with drotrecogin alfa ( activated ) compared with placebo . However , this report highlights a number of considerations relevant to the subgroup analyses reported for the PROWESS study . Published cost-effectiveness studies of treatment with drotrecogin alfa ( activated ) have applied a range of methods to the estimation of benefits , estimating an incremental gain per treated patient of between 0.38 and 0.68 life-years ( for patients with severe sepsis ) . For patients with severe sepsis and multiple organ dysfunction , the manufacturer ( Eli Lilly ) estimated an incremental gain of 1.115 life-years per treated patient , compared to 1.351 life-years per treated patient estimated by the Southampton Health Technology Assessment s Centre ( SHTAC ) . These latter UK analyses are based on a patient group that is more severely affected by disease , where effectiveness is greater and the baseline risk of all-cause mortality is much higher ( SHTAC analysis ) , these factors are associated with the noted difference in effect . The three published cost-effectiveness studies report cost for US and Canadian patient groups ; for those patients with severe sepsis they report the additional cost per patient treated in a range around 10,000 - 16,000 dollars . The manufacturer 's su bmi ssion reports analysis for the UK , based on 28-day survival data in patients with severe sepsis and multiple organ dysfunction ( the European licence indication ) , with the additional mean cost per treated patient estimated to be 5106 pounds . The analysis undertaken by SHTAC , for a UK group of patients with severe sepsis and multiple organ dysfunction , estimates an additional mean cost per patient treated of 6661 pounds . The manufacturer 's su bmi ssion to NICE presents cost-effectiveness estimates for drotrecogin alfa ( activated ) in the UK , in patients with severe sepsis and multiple organ dysfunction , at 6637 pounds per quality -adjusted life-year ( QALY ) based on 28-day effectiveness data , and 10,937 pounds per QALY based on longer term follow-up data . SHTAC developed an independent cost-effectiveness model and estimated a base-case cost per QALY of 8228 pounds in patients with severe sepsis and multiple organ failure ( based on 28-day survival data ) . Simulation results indicate that where the NHS is willing to pay 20,000 pounds per QALY , drotrecogin alfa ( activated ) is a cost-effective use of re sources in 98.7 % of cases . Published economic evaluations report various sensitivity analyses , with results sensitive to changes in the measure of treatment effect , but otherwise studies reported that results were robust to variations in most assumptions used in the cost-effectiveness analysis . CONCLUSIONS Drotrecogin alfa ( activated ) plus best supportive care appears clinical ly and cost-effective compared with best supportive care alone , in a UK cohort of severe sepsis patients , and in the subgroup of more severely affected patients with severe sepsis and multiple organ failure . The introduction of drotrecogin alfa ( activated ) will involve a substantial additional cost to the NHS . The treatment-eligible population in Engl and and Wales may comprise up to 16,570 patients , with an estimated annual drug acquisition cost of over 80 million pounds , excluding VAT . Further research is required on the longer term impact of drotrecogin alfa ( activated ) on both mortality and morbidity in UK patients with severe sepsis , on the clinical and cost-effectiveness of drotrecogin alfa ( activated ) in children ( under 18 years ) with severe sepsis , and on the effect of the timing of dosage and duration of treatment on outcomes in severe sepsis Objective : To determine long-term survival for subjects with severe sepsis enrolled in the previous multiple-center trial ( PROWESS ) of drotrecogin alfa ( activated ) ( DrotAA ) vs. placebo . Design : Retrospective , cross-sectional , blinded follow-up of subjects enrolled in a previous r and omized , controlled trial . Setting : One hundred 
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RESULTS Our meta- analysis , the first to simultaneously allow for type of IVIG ( IVIG or immunoglobulin M-enriched polyclonal IVIG ) , choice of control ( no treatment or albumin ) , study quality /publication bias and other potential covariates , indicated that the treatment effect of IVIG on mortality for patients with severe sepsis  is borderline significant with a large degree of heterogeneity in treatment effect between individual studies .
Modelling indicated that there were issues with bias associated with trial methodology , publication and small- study effects with the current evidence .
The large degree of heterogeneity in treatment effects between studies , however , could be explained ( best-fitting model ) by a measure of study quality ( i.e. use of albumin as control - as an indicator of proper blinding to treatment as a proxy for study quality - associated with decreased effect ) and duration of IVIG therapy ( longer duration associated with increased effect ) .
In-depth discussion within the Expert Group on duration of IVIG therapy , with daily dose and total dose also clearly inter-related , indicated no clear clinical rationale for this association and exposed a lack of evidence on the underst and ing of the mechanism of action of IVIG in severe sepsis .
Although the EVI analyses suggested substantial expected net benefit from a large , multicentre r and omised controlled trial ( RCT ) evaluating the clinical effectiveness of IVIG , the remaining uncertainties around the design of such a study mean that we are unable to recommend it at this time .