Absolute Risk Reduction In Mortality Research Articles

Does proactive care in care homes improve survival? A quality improvement project

BackgroundNHS England’s ‘Enhanced Health in Care Homes’ specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches...

Estimated mortality with early empirical antibiotic coverage of methicillin-resistant Staphylococcus aureus in hospitalized patients with bacterial infections: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis to estimate the effect of early active empirical antibiotics for MRSA on mortality, both in patients admitted with MRSA infections and in patients admitted with common infectious syndromes, for whom the causative pathogen may not have been MRSA. A systematic literature search was conducted using Embase, MEDLINE, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from the earliest entry through to 26 April 2022. We included studies of patients hospitalized with culture-proven MRSA infections that compared mortality rates depending on whether patients received active empirical antibiotics. The primary outcome was the adjusted OR for mortality with early active empirical antibiotics. After performing random-effects meta-analysis, we estimated the absolute risk reduction in mortality with initial empirical MRSA coverage for common infectious syndromes based on the prevalence of MRSA and baseline mortality rate for each syndrome, as reported in the medical literature. Of an initial 2136 unique manuscripts, 37 studies (11 661 participants) met our inclusion criteria. Fifteen studies (6066 participants) reported adjusted OR of mortality. The pooled adjusted OR for mortality was 0.64 (95% CI, 0.48-0.84), favouring active empirical antibiotics. The estimated absolute mortality benefit was 0% for patients with pneumonia, 0.1% (95% CI, 0.04-0.2) for non-critically ill patients with soft tissue infections, 0.04% (95% CI, 0.01-0.05) for non-critically ill patients with urinary tract infections, 0.6% (95% CI, 0.2-1.0) for patients with septic shock, and 1.0% (95% CI, 0.3-1.4) for patients with catheter-related infections admitted to ICUs. For the three most common infections in the hospital, the absolute benefit on mortality of empirical antibiotics against MRSA is 0.1% or less. Meaningful benefit of empirical antimicrobials against MRSA is limited to patients with approximately 30% mortality and 10% prevalence of MRSA. Avoiding empirical antibiotics against MRSA for low-risk infections would substantially reduce the use of anti-MRSA therapy.

CLIF-C AD score predicts survival benefit from pre-emptive TIPS in individuals with Child-Pugh B cirrhosis and acute variceal bleeding

Among individuals with Child-Pugh B cirrhosis and acute variceal bleeding (AVB), the Baveno VII workshop recommended pre-emptive TIPS in those with a Child-Pugh score of 8-9 and active bleeding at initial endoscopy (Child B8-9 + AB criteria). Nevertheless, whether this criterion is superior to the CLIF-Consortium acute decompensation score (CLIF-C ADs) remains unclear. Data on 1,021 consecutive individuals with Child-Pugh B cirrhosis and AVB from 13 university hospitals in China who were treated with pre-emptive TIPS (n= 297) or drug plus endoscopic treatment (n= 724) between 2010 to 2019 were retrospectively analysed. A competing risk regression model was used to compare the outcomes between the two groups after adjusting for confounders. The concordance-statistic for benefit (c-for-benefit) was used to evaluate a models' ability to predict treatment benefit (risk difference between treatment groups). Pre-emptive TIPS was associated with reduced mortality compared to drug plus endoscopic treatment (adjusted hazard ratio 0.62, 95% CI 0.44 to 0.88). A higher baseline CLIF-C AD score was associated with greater survival benefit (i.e., larger absolute mortality risk reduction). After adjusting for confounders, a survival benefit was observed in individuals with CLIF-C ADs ≥48 or Child-Pugh B8-9 with active bleeding, but not in those with CILF-C ADs <48, no active bleeding or Child-Pugh B7 with active bleeding. The c-for-benefit of CILF-C ADs for predicting survival benefit was higher than that of Child B8-9+AB criteria. In individuals with Child-Pugh B cirrhosis and AVB, CLIF-C ADs predicts survival benefit from pre-emptive TIPS and outperforms the Child B8-9+AB criteria. Prospective validation should be performed to confirm this result, especially for other aetiologies of cirrhosis. In this study, among individuals with Child-Pugh B cirrhosis and acute variceal bleeding, the CLIF-Consortium acute decompensation (CLIF-C AD) score could predict the survival benefit from pre-emptive TIPS, with patients with higher CLIF-C AD scores benefiting more from pre-emptive TIPS. Furthermore, the CLIF-C AD score outperformed the Child B8-9 plus active bleeding criteria in terms of discriminating between those who obtained more benefit vs. less benefit from pre-emptive TIPS. Depending on prospective validation, the CLIF-C AD score could be used as the model of choice to determine who should undergo pre-emptive TIPS.

LB3. Baricitinib plus Standard of Care for Hospitalized Adults with COVID-19 on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation: Results of a Randomized, Placebo-Controlled Trial

BackgroundInterventions to reduce mortality in critically ill patients with COVID-19 are a crucial unmet medical need. Baricitinib (BARI) is an oral, selective Janus kinase (JAK)1/JAK2 inhibitor with efficacy in hospitalized adults with COVID-19. Treatment with BARI 4-mg was evaluated in critically ill adult patients with COVID-19 with baseline need for invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO).MethodsCOV-BARRIER (NCT04421027) was a randomized double-blind, placebo-controlled trial in patients with confirmed SARS-CoV-2 infection and elevation of ≥ 1 serum inflammatory marker. In this newly completed substudy, enrolled participants (not previously reported) from 4 countries on IMV or ECMO at study entry were randomly assigned 1:1 to once-daily BARI 4-mg or placebo (PBO) for up to 14 days plus standard of care (SOC), which included baseline systemic corticosteroid use in 86% of patients. The prespecified exploratory endpoints included all-cause mortality and number of ventilator-free days (VFDs) through Day 28.ResultsCharacteristics for 101 participants are shown in Table 1.Treatment with BARI significantly reduced all-cause mortality by Day 28 compared to PBO [39.2% vs 58.0%, respectively; hazard ratio (HR) = 0.54 (95%CI 0.31, 0.96), p=0.030, relative risk (RR) = 0.68 (95%CI 0.45, 1.02); Figure 1A]. One additional death was prevented for every six BARI-treated patients. Significant reduction in mortality was also observed by Day 60 [45.1% vs 62.0%; HR = 0.56 (95%CI 0.33, 0.97), p=0.027, RR = 0.73 (95%CI 0.50, 1.06); Figure 1B].Patients treated with BARI showed a numerical reduction in the duration of IMV and duration of hospitalization vs PBO and more BARI treated patients recovered (Table 2). No new safety findings were observed (Table 2). ConclusionTreatment with BARI+SOC (corticosteroids) resulted in an absolute risk reduction in mortality of 19% at Day 28 and 17% at Day 60 in patients with COVID-19 who were on IMV or ECMO at enrollment. These results are consistent with the reduction in mortality observed in the less severely ill hospitalized patients in the primary COV-BARRIER study population. Disclosures E. Wesley Ely, MD, CDC (Grant/Research Support)Eli Lilly (Other Financial or Material Support, Unpaid consultant)NIH (Grant/Research Support)VA (Grant/Research Support) Athimalaipet V. Ramanan, FRCP, AbbVie (Consultant, Speaker’s Bureau)Eli Lilly and Company (Consultant, Grant/Research Support, Speaker’s Bureau)Novartis (Consultant, Speaker’s Bureau)Pfizer (Consultant, Speaker’s Bureau)Roche (Consultant, Speaker’s Bureau)Sobi (Consultant, Speaker’s Bureau)UCB (Consultant, Speaker’s Bureau) Cynthia E. Kartman, RN BSN, Eli Lilly and Company (Employee, Shareholder) Stephanie de Bono, MD PhD, Eli Lilly and Company (Employee, Shareholder) Ran Liao, PhD, Eli Lilly and Company (Employee, Shareholder) Maria Lucia B Piruzeli, MD, Eli Lilly and Company (Employee, Shareholder) Sujatro Chakladar, PhD, Eli Lilly and Company (Employee, Shareholder) Vincent Marconi, MD, Bayer (Consultant, Scientific Research Study Investigator)Eli Lilly (Consultant, Scientific Research Study Investigator)Gilead Sciences (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator)

Baricitinib reduces 30-day mortality in older adults with moderate-to-severe COVID-19 pneumonia.

BackgroundOlder adults are at the highest risk of severe disease and death due to COVID‐19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID‐19 moderate‐to‐severe pneumonia.MethodsThis is a propensity score [PS]‐matched retrospective cohort study. Patients from the COVID‐AGE and Alba‐Score cohorts, hospitalized for moderate‐to‐severe COVID‐19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS‐matched controls) or ≥70 years old (78 on baricitinib and 78 PS‐matched controls). Thirty‐day mortality rates were analyzed with Kaplan–Meier and Cox proportional hazard models.ResultsMean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30‐day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS‐matched controls, p < 0.001) and a lower 30‐day adjusted fatality rate (HR 0.21; 95% CI 0.09–0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30‐day absolute mortality risk; HR 0.14; 95% CI 0.03–0.64; p = 0.011).ConclusionsBaricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID‐19 pneumonia.

Remdesivir for COVID-19 in Europe: will it provide value for money?

Remdesivir for COVID-19 in Europe: will it provide value for money?

Cost to Save a Life in Heart Failure: Health Disparity Costs Lives.

ObjectiveThe purpose of this paper is to assign a dollar value to life-saving medication, surgical procedures, and medical devices. The knowledge of the wide variation in the cost of drugs, surgery, and devices allows providers and patients to choose higher-valued therapies. Cost is a significant barrier to health. The current reimbursement system is complicated, representing a significant barrier to saving lives by promoting health disparity.BackgroundThe cost analysis of heart failure therapies is an important tool in the education of physicians, patients, and vendors of the intervention. The analysis demonstrates disparities between heart failure therapies. The cost to save a single life is calculated from annualized absolute mortality risk reduction, trial length, and estimated 10-year costs. The method allows comparisons of drugs, devices, and surgery.MethodsThe 10-year cost of drugs is 120 months times the cost of a drug/month as listed by the website GoodRX.com. The 10-year cost of surgery or device therapy was determined from a cost analysis found by a Google search of the literature. When wide ranges were reported, the mean value was selected.1/absolute mortality risk reduction X 100 is the number needed to treat to save a life annualized for the mean length of the study. The cost to save a life can then be computed by the following formula:Cost/life saved = (10-year cost/annualized absolute mortality risk reduction) X (100)ResultsBeta-blockers and spironolactone had the lowest cost per life saved at $13,333 and $21,818, respectively. Defibrillators are the most expensive at $6,417,856. Valsartan/sacubitril has a cost of $1,127,733. Dapagliflozin, the newest class of heart failure drug, costs $4,853,200. ConclusionsCalculating the cost to save a life gives insight into the value of therapies and demonstrates disparities. It is a means of comparing drugs and devices. New drug therapies are costly, not affordable, and serve as a barrier to the successful treatment of heart failure.

Long-term mortality in the Intermediate care after emergency abdominal surgery (InCare) trial-A post-hoc follow-up study.

Patients undergoing emergency abdominal surgery are at high risk of post-operative complications. Although post-operative treatment at an intermediate care unit may improve early outcome, there is a lack of studies on the long-term effects of such therapy. The aim of this study was to assess the long-term effect of intermediate care versus standard surgical ward care on mortality in the Intermediate Care After Emergency Abdominal Surgery (InCare) trial. We included adult patients undergoing emergency major laparoscopy or laparotomy with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 10 or more, who participated in the InCare trial from October 2010 to November 2012. In the InCare trial, patients were randomized to either post-operative intermediate care or standard surgical ward care. The primary outcome was time to death within 6years after surgery. We assessed mortality with Coxregression analysis. A total of 286 patients were included. The all-cause 6-year landmark mortality was 52.8% (76 of 144 patients) in the intermediate care group and 47.9% (68 of 142 patients) in the ward care group. There was no statistically significant difference in mortality risk between the two groups (hazard ratio 1.06 (95% confidence interval 0.76-1.47), P=.73). We found no statistically significant difference in 6-year mortality between patients randomized to post-operative intermediate care or ward care after emergency abdominal surgery. However, we detected an absolute mortality risk reduction of 5% in favour of ward care, possibly due to random error.

Graphing and reporting heterogeneous treatment effects through reference classes

BackgroundExploration and modelling of heterogeneous treatment effects as a function of baseline covariates is an important aspect of precision medicine in randomised controlled trials (RCTs). Randomisation generally guarantees the internal validity of an RCT, but heterogeneity in treatment effect can reduce external validity. Estimation of heterogeneous treatment effects is usually done via a predictive model for individual outcomes, where one searches for interactions between treatment allocation and important patient baseline covariates. However, such models are prone to overfitting and multiple testing and typically demand a transformation of the outcome measurement, for example, from the absolute risk in the original RCT to log-odds of risk in the predictive model.MethodsWe show how reference classes derived from baseline covariates can be used to explore heterogeneous treatment effects via a two-stage approach. We first estimate a risk score which captures on a single dimension some of the heterogeneity in outcomes of the trial population. Heterogeneity in the treatment effect can then be explored via reweighting schemes along this axis of variation. This two-stage approach bypasses the search for interactions with multiple covariates, thus protecting against multiple testing. It also allows for exploration of heterogeneous treatment effects on the original outcome scale of the RCT. This approach would typically be applied to multivariable models of baseline risk to assess the stability of average treatment effects with respect to the distribution of risk in the population studied.Case studyWe illustrate this approach using the single largest randomised treatment trial in severe falciparum malaria and demonstrate how the estimated treatment effect in terms of absolute mortality risk reduction increases considerably in higher risk strata.Conclusions‘Local’ and ‘tilting’ reweighting schemes based on ranking patients by baseline risk can be used as a general approach for exploring, graphing and reporting heterogeneity of treatment effect in RCTs.Trial registrationISRCTN clinical trials registry: ISRCTN50258054. Prospectively registered on 22 July 2005.

Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae bacteremia and pneumonia.

Background: Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown.Methods: We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY.Results: In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively.Conclusion: CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor-recipient combination.

The impact of donor quality on post-kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post-KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n=120818) and waitlisted candidates (n=376272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5-year post-KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTSscore of80, 5-year waitlist survival was 47.6%, and 5-year post-KT survival was 78.9% after receiving kidneys with a KDPIof20 and was 70.7% after receiving kidneys with a KDPIof80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPIof100 (>16 percentage points). Our prediction tool (www.transplantmodels.com/kdpi-epts) can support individualized decision-making on kidney offers in clinical practice.

Transcatheter Aortic Valve Replacement: OPTIMIZING OUTCOMES FOR HEALTHY RECOVERY.

Transcatheter aortic valve replacement (TAVR) has been approved in the United States for intermediate and high-risk patients with severe symptomatic aortic stenosis. More than 80 000 TAVR procedures have been performed in the United States and the number is growing every year. Two valve designs are approved in the United States including the balloon expandable Edwards Sapien prosthesis and self-expanding CoreValve prosthesis. The PARTNER trial of the Sapien valve, involving patients who were considered inoperable, reported a 19% absolute risk reduction in mortality compared with medical therapy, with a number needed to treat of 5. Randomized controlled trials in patients with high and intermediate risk of inhospital mortality based on the Society of Thoracic Surgeons score showed noninferiority of TAVR compared with surgical aortic valve replacement. Major complications associated with TAVR include a 2% to 3% risk of stroke at 30 d, 8% to 25% risk of permanent pacemaker implantation depending on valve design, and 6% risk of major vascular complications. There are some concerns regarding valve durability as this technology is extended to younger patients with lower risk. Five-year follow-up data from the initial PARTNER trials noted appropriate valve performance and hemodynamics in survivors; however, longer follow-up is required to assess the true incidence of structural deterioration. Approximately one-third of TAVR patients are transferred to a transitional care facility after TAVR, and more than 50% of the patients are frail. Cardiac rehabilitation has been reported to be safe in post-TAVR patients and was associated with significant improvements in exercise capacity, functional independence, and frailty.

Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis.

Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU. Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles. Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU. Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was mortality at longest duration of follow-up. Our secondary outcomes were ICU and hospital length of stay, duration of mechanical ventilation, and frequency of renal complications. The internal validity of trials was assessed in duplicate using the Cochrane Collaboration's Risk of Bias tool. We included 13 trials enrolling 1,652 patients. Methods used to assess fluid responsiveness included stroke volume variation (nine trials), pulse pressure variation (one trial), and stroke volume change with passive leg raise/fluid challenge (three trials). In 12 trials reporting mortality, the risk ratio for death associated with dynamic assessment of fluid responsiveness was 0.59 (95% CI, 0.42-0.83; I = 0%; n = 1,586). The absolute risk reduction in mortality associated with dynamic assessment of fluid responsiveness was -2.9% (95% CI, -5.6% to -0.2%). Dynamic assessment of fluid responsiveness was associated with reduced duration of ICU length of stay (weighted mean difference, -1.16 d [95% CI, -1.97 to -0.36]; I = 74%; n = 394, six trials) and mechanical ventilation (weighted mean difference, -2.98 hr [95% CI, -5.08 to -0.89]; I = 34%; n = 334, five trials). Three trials were adjudicated at unclear risk of bias; the remaining trials were at high risk of bias. In adult patients admitted to intensive care who required acute volume resuscitation, goal-directed therapy guided by assessment of fluid responsiveness appears to be associated with reduced mortality, ICU length of stay, and duration of mechanical ventilation. High-quality clinical trials in both medical and surgical ICU populations are warranted to inform routine care.

Thromboprophylaxis and mortality among patients who developed venous thromboembolism in seven major hospitals in Saudi Arabia.

INTRODUCTION:Venous thromboembolism (VTE) during hospitalization is a serious and potentially fatal condition. Despite its effectiveness, evidence-based thromboprophylaxis is still underutilized in many countries including Saudi Arabia.OBJECTIVE OF THE STUDY:Our objectives were to determine how often hospital-acquired VTE patients received appropriate thromboprophylaxis, VTE-associated mortality, and the percentage of patients given anticoagulant therapy and adherence to it after discharged.METHODS:This study was conducted in seven major hospitals in Saudi Arabia. From July 1, 2009, till June 30, 2010, all recorded deep vein thrombosis (DVT) and pulmonary embolism (PE) cases were noted. Only patients with confirmed VTE diagnosis were included in the analysis.RESULTS:A total of 1241 confirmed VTE cases occurred during the 12-month period. Most (58.3%) of them were DVT only, 21.7% were PE, and 20% were both DVT and PE. 21.4% and 78.6% of confirmed VTE occurred in surgical and medical patients, respectively. Only 40.9% of VTE cases received appropriate prophylaxis (63.2% for surgical patients and 34.8% for medical patients; P < 0.001). The mortality rate was 14.3% which represented 1.6% of total hospital deaths. Mortality was 13.5% for surgical patients and 14.5% for medical patients (P > 0.05). Appropriate thromboprophylaxis was associated with 4.11% absolute risk reduction in mortality (95% confidence interval: 0.24%–7.97%). Most (89.4%) of the survived patients received anticoagulation therapy at discharge and 71.7% of them were adherent to it on follow-up.CONCLUSION:Thromboprophylaxis was underutilized in major Saudi hospitals denoting a gap between guideline and practice. This gap was more marked in medical than surgical patients. Hospital-acquired VTE was associated with significant mortality. Efforts to improve thromboprophylaxis utilization are warranted.

Acute Respiratory Distress Syndrome Measurement Error. Potential Effect on Clinical Study Results.

Identifying patients with acute respiratory distress syndrome (ARDS) is a recognized challenge. Experts often have only moderate agreement when applying the clinical definition of ARDS to patients. However, no study has fully examined the implications of low reliability measurement of ARDS on clinical studies. To investigate how the degree of variability in ARDS measurement commonly reported in clinical studies affects study power, the accuracy of treatment effect estimates, and the measured strength of risk factor associations. We examined the effect of ARDS measurement error in randomized clinical trials (RCTs) of ARDS-specific treatments and cohort studies using simulations. We varied the reliability of ARDS diagnosis, quantified as the interobserver reliability (κ-statistic) between two reviewers. In RCT simulations, patients identified as having ARDS were enrolled, and when measurement error was present, patients without ARDS could be enrolled. In cohort studies, risk factors as potential predictors were analyzed using reviewer-identified ARDS as the outcome variable. Lower reliability measurement of ARDS during patient enrollment in RCTs seriously degraded study power. Holding effect size constant, the sample size necessary to attain adequate statistical power increased by more than 50% as reliability declined, although the result was sensitive to ARDS prevalence. In a 1,400-patient clinical trial, the sample size necessary to maintain similar statistical power increased to over 1,900 when reliability declined from perfect to substantial (κ = 0.72). Lower reliability measurement diminished the apparent effectiveness of an ARDS-specific treatment from a 15.2% (95% confidence interval, 9.4-20.9%) absolute risk reduction in mortality to 10.9% (95% confidence interval, 4.7-16.2%) when reliability declined to moderate (κ = 0.51). In cohort studies, the effect on risk factor associations was similar. ARDS measurement error can seriously degrade statistical power and effect size estimates of clinical studies. The reliability of ARDS measurement warrants careful attention in future ARDS clinical studies.

Value of Internal Thoracic Artery Grafting to the Left Anterior Descending Coronary Artery at Coronary Reoperation

The study sought to determine if left internal thoracic artery (LITA) grafting of the left anterior descending (LAD) at reoperative coronary artery bypass grafting (CABG) improves patient outcomes. LITA grafting to the LAD is the gold standard for primary CABG, but its value for reoperative CABG is unknown. From January 1985 to January 2007, reoperative CABG was performed in 3,473 patients who did not receive a LITA during their primary CABG and whose anterior myocardium (LAD) was at risk at reoperation: 2,389 had LITA grafting and 1,084 saphenous vein (SV) grafting to the LAD. Propensity matching (908 matched pairs) was used for balanced comparison of outcomes. Follow-up was continued to 20 years post-operatively, with a mean follow-up of 11 ± 8.2 years. Unadjusted hospital mortality was 2.2% and 6.5% in the LITA and SV groups, respectively (p < 0.001), but 3.1% and 5.6% in propensity-matched groups (p = 0.008). Unadjusted survival at 1, 5, 10, 15, and 20 years was 94%, 82%, 64%, 46%, and 32% for the LITA group, but 88%, 73%, 50%, 32%, and 18% for the SV group (p <.0001), respectively. For propensity-matched groups, both early (p = 0.01) and late survival was greater (p = 0.005) in the LITA group. At 20 years, LITA grafting of the LAD at reoperation resulted in an absolute mortality risk reduction of 6.0% and a hazard ratio of 0.85, with number needed to treat of 16 patients. LITA-to-LAD grafting at reoperation is safe and confers a risk-adjusted survival advantage. When appropriate, a LITA should be used to revascularize the LAD at coronary reoperations.

Decompressive Surgery for Malignant Middle Cerebral Artery Infarcts: The Results of Randomized Trials Can Be Reproduced in Daily Practice

Background: In clinical randomized controlled trials (RCTs), decompressive surgery (DS) for malignant middle cerebral artery (MMCA) infarcts leads to a 50% absolute risk reduction in mortality, and improves the 1-year functional outcome. The reproducibility of these results in routine practice has never been evaluated. The purpose of this study was to test the hypothesis that the results of DS for MMCA in practice are similar to those observed in the surgical group of RCTs. Methods: We prospectively included the first 31 patients who underwent DS for MMCA. They were screened based on similar criteria as in the meta-analysis. The primary outcome was a modified Rankin Scale (mRS) score of ≤4, and secondary outcomes were mRS of ≤3 and death at 1 year. Results: Thirty-one patients underwent DS for MMCA. The 1-year mRS was ≤4 in 22 patients (71.0%) and ≤3 in 16 (51.6%). Seven patients died (22.6%). Conclusion: This observational study showed that DS for MMCA in a center without previous experience provides similar results as those obtained in the surgical arm of RCTs.

To screen or not to screen

To screen or not to screen

Prospective association between self-reported life satisfaction and mortality: Results from the MONICA/KORA Augsburg S3 survey cohort study

BackgroundTo identify factors which determine high life satisfaction (LS) and to analyse the prognostic influence of LS on mortality.MethodsData collection was conducted on 2,675 participants, age 25-74 years, as part of the MONICA Augsburg Project 1994-95. Multivariate logistic regression analyses were used to determine factors associated with high LS (measured with one item, 6-level Likert scale, where "high" = very satisfied/most of the time very satisfied with ones personal life). After 12 years mean follow-up, a total of 245 deaths occurred. We calculated age- and sex-adjusted incident mortality rates per 10,000. Hazard ratios (HRs) were estimated from Cox proportional hazards models.ResultsIndependent determinants of LS were income, health-perception, and social support, as well as somatisation, anger or depressive symptoms (all p < 0.05). Participants with higher LS (n = 721, 27%) benefited the most with respect to absolute mortality risk reduction (higher LS = 67; mid = 98; low = 140 per 10,000). The sex-stratified analyses indicated an independent association of higher LS and survival for men (HR 0.55; 95% CI 0.37 - 0.81) but not for women.ConclusionsBaseline assessment demonstrated that psychological, social and life-style factors, but not somatic co-morbidities, were relevant determinants of LS. Moreover, the analysis showed that men with higher LS have a substantial long-term survival benefit. The observed association between LS and mortality may be attributed to common underlying causes such as social network integration and/or self-rated health.

Assessing the Feasibility of the American College of Surgeons' Benchmarks for the Triage of Trauma Patients

To test the feasibility of accomplishing the American College of Surgeons Committee on Trauma benchmarks of less than 5% undertriage (treatment of patients with moderate to severe injuries at nontrauma centers [NTCs]) and less than 50% overtriage (transfer of patients with minor injuries to trauma centers [TCs]) given current practice patterns by describing transfer patterns for patients taken initially to NTCs and estimating volume shifts and potential lives saved if full implementation were to occur. Retrospective cohort study of adult trauma patients initially evaluated at NTCs in Pennsylvania (between April 1, 2001, and March 31, 2005). We used published estimates of mortality risk reduction associated with treatment at TCs. Undertriage and overtriage rates, estimated patient volume shifts, and number of lives saved. A total of 93,880 adult trauma patients were initially evaluated at NTCs in Pennsylvania between 2001 and 2005. Undertriage was 69%; overtriage was 53%. Achieving less than 5% undertriage would require the transfer of 18,945 patients per year, a 5-fold increase from current practice (3650 transfers per year). Given an absolute mortality risk reduction of 1.9% for patients with moderate to severe injuries treated at TCs, this change in practice would save 99 potential lives per year or would require 191 transfers per year to save 1 potential life. Given current practice patterns, American College of Surgeons Committee on Trauma recommendations for the regionalization of trauma patients may not be feasible. To achieve 5% undertriage, TCs must increase their capacity 5-fold, physicians at NTCs must increase their capacity to discriminate between moderate to severe and other injuries, or the guidelines must be modified.