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Biomedical subjects

Neill K J Adhikari

Publications and source records attributed to Neill K J Adhikari.

14 recordsLinked to original sources
PubMed2006

Drotrecogin alfa (activated): does current evidence support treatment for any patients with severe sepsis?

Two international multicentre randomised controlled trials of drotrecogin alfa (activated) (DrotAA), the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) trials, have produced inconsistent results. When 28-day mortality data from these trials for patients with severe sepsis and at high risk of death are pooled using a standard random-effects meta-analysis technique, there is no statistically significant survival benefit (for patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more), or a borderline significant benefit (for patients with multi-organ failure). We argue that two important methodological issues might explain the disparate results between the two trials. These issues centre on early trial stopping, which exaggerates treatment effects, and reliance on subgroup analyses, which for DrotAA yields inconsistent results across different definitions of high risk. These concerns call into question the effectiveness of DrotAA in any patients with severe sepsis. Consequently, further randomised trials of this agent in prospectively defined high-risk patients are required to clarify its role in the management of severe sepsis.

Humans↗
PubMed2006

A meta-analysis of noninvasive weaning to facilitate liberation from mechanical ventilation.

PURPOSE: To summarize the evidence comparing noninvasive positive pressure ventilation (NPPV) and invasive positive pressure ventilation (IPPV) weaning on mortality, ventilator associated pneumonia and the total duration of mechanical ventilation among invasively ventilated adults with respiratory failure. SOURCE: Meta-analysis of randomized and quasi-randomized studies comparing early extubation with immediate application of NPPV to IPPV weaning. We selected randomized studies that 1) included adults, with respiratory failure, invasively ventilated for at least 24 hr; 2) compared extubation with immediate application of NPPV to weaning using IPPV; and 3) reported at least one clinically important outcome. PRINCIPAL FINDINGS: We searched MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) for randomized controlled trials comparing NPPV and IPPV weaning. Additional data sources included personal files, conference proceedings and author contact. Two reviewers independently assessed trial quality and abstracted data. Five studies enrolling 171 patients demonstrated that compared to IPPV, noninvasive weaning decreased mortality (relative risk, 0.41 [95% confidence interval [CI] 0.22-0.76]), ventilator associated pneumonia (relative risk, 0.28 [95% CI 0.09-0.85]) and the total duration of mechanical ventilation (weighted mean difference, -7.33 days [95% CI -11.45 to -3.22 days]). CONCLUSIONS: In the absence of a large randomized controlled trial, this meta-analysis demonstrated a consistent positive effect of noninvasive weaning on mortality. Notwithstanding, the use of NPPV to facilitate weaning, in mechanically ventilated patients, with predominantly chronic obstructive pulmonary disease, is associated with promising, but insufficient, evidence of net clinical benefit at present.

Humans↗
PubMed2006

The evolution of intensive care unit performance assessment.

Intensive care units (ICUs) share the problems experienced by the health care system at large. Various approaches to define and manage the quality of care patients receive in the ICU have been proposed. Performance measurement involves the collection of data to evaluate an ICU's performance against itself (over time), other ICUs, or other appropriate benchmarks. Successful performance assessment requires the quantification of relevant indexes of performance. Although these indexes are increasingly being developed, it will be some time before widely recognized, validated systems are available.

Benchmarking↗
PubMed2006

Mortality predictions in the intensive care unit: comparing physicians with scoring systems.

OBJECTIVE: Risk-prediction models offer potential advantages over physician predictions of outcomes in the intensive care unit (ICU). Our systematic review compared the accuracy of ICU physicians' and scoring system predictions of ICU or hospital mortality of critically ill adults. DATA SOURCE: MEDLINE (1966-2005), CINAHL (1982-2005), Ovid Healthstar (1975-2004), EMBASE (1980-2005), SciSearch (1980-2005), PsychLit (1985-2004), the Cochrane Library (Issue 1, 2005), PubMed "related articles," personal files, abstract proceedings, and reference lists. STUDY SELECTION: We considered all studies that compared physician predictions of ICU or hospital survival of critically ill adults to an objective scoring system, computer model, or prediction rule. We excluded studies if they focused exclusively on the development or economic evaluation of a scoring system, computer model, or prediction rule. DATA EXTRACTION AND ANALYSIS: We independently abstracted data and assessed study quality in duplicate. We determined summary receiver operating characteristic curves and areas under the summary receiver operating characteristic curves+/-se and summary diagnostic odds ratios. DATA SYNTHESIS: We included 12 observational studies of moderate methodological quality. The area under the summary receiver operating characteristic curves for seven studies was 0.85+/-0.03 for physician predictions compared with 0.63+/-0.06 for scoring system predictions (p=.002). Physicians' summary diagnostic odds ratios derived from the area under the summary receiver operating characteristic curves were significantly higher (12.43; 95% confidence interval 5.47, 27.11) than scoring systems' summary diagnostic odds ratios (2.25; 95% confidence interval 0.78, 6.52, p=.001). Combined results of all 12 studies indicated that physicians predict mortality more accurately than do scoring systems: ratio of diagnostic odds ratios (95% confidence interval) 1.92 (1.19, 3.08) (p=.007). CONCLUSIONS: Observational studies suggest that ICU physicians discriminate between survivors and nonsurvivors more accurately than do scoring systems in the first 24 hrs of ICU admission. The overall accuracy of both predictions of patient mortality was moderate, implying limited usefulness of outcome prediction in the first 24 hrs for clinical decision making.

Critical Illness↗
PubMed2006

Outcomes of interfacility critical care adult patient transport: a systematic review.

INTRODUCTION: We aimed to determine the adverse events and important prognostic factors associated with interfacility transport of intubated and mechanically ventilated adult patients. METHODS: We performed a systematic review of MEDLINE, CENTRAL, EMBASE, CINAHL, HEALTHSTAR, and Web of Science (from inception until 10 January 2005) for all clinical studies describing the incidence and predictors of adverse events in intubated and mechanically ventilated adult patients undergoing interfacility transport. The bibliographies of selected articles were also examined. RESULTS: Five studies (245 patients) met the inclusion criteria. All were case-series and two were prospective in design. Due to the paucity of studies and significant heterogeneity in study population, outcome events, and results, we synthesized data in a qualitative manner. Pre-transport severity of illness was reported in only one study. The most common indication for transport was a need for investigations and/or specialist care (three studies, 220 patients). Transport modalities included air (fixed or rotor wing; 66% of patients) and ground (31%) ambulance, and commercial aircraft (3%). Transport teams included a physician in three studies (220 patients). Death during transfer was rare (n = 1). No other adverse events or significant therapeutic interventions during transport were reported. One study reported a 19% (28/145) incidence of respiratory alkalosis on arrival and another study documented a 30% overall intensive care unit mortality, while no adverse events or outcomes were reported after arrival in the three other studies. CONCLUSION: Insufficient data exist to draw firm conclusions regarding the mortality, morbidity, or risk factors associated with the interfacility transport of intubated and mechanically ventilated adult patients. Further study is required to define the risks and benefits of interfacility transfer in this patient population. Such information is important for the planning and allocation of resources related to transporting critically ill adults.

Adult↗
PubMed2006

Statins, bugs and prophylaxis: intriguing possibilities.

Statin therapy may represent a potential prophylactic intervention in certain high-risk scenarios, for example in pandemic influenza and in those undergoing aggressive medical treatments. Emerging data indicate a potential prophylactic role in these high-risk groups.

Humans↗
PubMed2005

Randomized trials stopped early for benefit: a systematic review.

CONTEXT: Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown. OBJECTIVE: To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit. DATA SOURCES: Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit. STUDY SELECTION: Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria. DATA EXTRACTION: Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping. DATA SYNTHESIS: Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73). CONCLUSIONS: RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

Clinical Trials Data Monitoring Committees↗
PubMed2005

Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: a systematic review.

CONTEXT: Developers of health care software have attributed improvements in patient care to these applications. As with any health care intervention, such claims require confirmation in clinical trials. OBJECTIVES: To review controlled trials assessing the effects of computerized clinical decision support systems (CDSSs) and to identify study characteristics predicting benefit. DATA SOURCES: We updated our earlier reviews by searching the MEDLINE, EMBASE, Cochrane Library, Inspec, and ISI databases and consulting reference lists through September 2004. Authors of 64 primary studies confirmed data or provided additional information. STUDY SELECTION: We included randomized and nonrandomized controlled trials that evaluated the effect of a CDSS compared with care provided without a CDSS on practitioner performance or patient outcomes. DATA EXTRACTION: Teams of 2 reviewers independently abstracted data on methods, setting, CDSS and patient characteristics, and outcomes. DATA SYNTHESIS: One hundred studies met our inclusion criteria. The number and methodologic quality of studies improved over time. The CDSS improved practitioner performance in 62 (64%) of the 97 studies assessing this outcome, including 4 (40%) of 10 diagnostic systems, 16 (76%) of 21 reminder systems, 23 (62%) of 37 disease management systems, and 19 (66%) of 29 drug-dosing or prescribing systems. Fifty-two trials assessed 1 or more patient outcomes, of which 7 trials (13%) reported improvements. Improved practitioner performance was associated with CDSSs that automatically prompted users compared with requiring users to activate the system (success in 73% of trials vs 47%; P = .02) and studies in which the authors also developed the CDSS software compared with studies in which the authors were not the developers (74% success vs 28%; respectively, P = .001). CONCLUSIONS: Many CDSSs improve practitioner performance. To date, the effects on patient outcomes remain understudied and, when studied, inconsistent.

Clinical Pharmacy Information Systems↗
PubMed2005

Bilevel noninvasive positive pressure ventilation for acute respiratory failure: survey of Ontario practice.

OBJECTIVE: To determine physicians' stated practices regarding the use of bilevel noninvasive ventilation (NIV) for acute respiratory failure and the predictors of practice variation. DESIGN: Cross-sectional postal survey. SETTING: Province of Ontario, Canada. PARTICIPANTS: Attending physicians and residents in four specialties at 15 teaching hospitals. INTERVENTIONS: We used literature searches and focus groups to design questions related to NIV utilization with respect to frequency, location of and indications for use, awareness of supporting literature, and perceived efficacy. We assessed the survey's clinical sensibility and reliability. We used regression analyses to evaluate practice variation among hospitals and specialties and to determine predictors of more frequent NIV use, initiation of and continued use in nonmonitored settings, and use for specific indications. MEASUREMENTS AND MAIN RESULTS: Three hundred eighty-five (48%) of 808 physicians responded; 242 used NIV. The two most common indications for NIV use were chronic obstructive pulmonary disease and congestive heart failure. NIV guidelines, protocols, or policies were available in 12 of 15 hospitals. We found variation in NIV utilization among specialties but not hospitals. Specialty (critical care and respirology versus internal and emergency medicine), fewer years of postgraduate experience, and a greater number of noninvasive ventilators were predictors of more frequent NIV use (all p < or = .001). Only 6% of respondents reported initiation of use and continued use most frequently in nonmonitored settings, which increased with the number of noninvasive ventilators (p = .02). Physician characteristics such as awareness of the literature were predictive of NIV use for exacerbations of chronic obstructive pulmonary disease, whereas perceived NIV efficacy was predictive of use for many indications, including congestive heart failure. CONCLUSIONS: Self-reported practice variation for bilevel NIV exists among specialties but not hospitals and differs with respect to frequency, location of use, and use for specific indications. Some factors associated with variation in NIV use may be suitable targets for utilization improvement interventions.

Acute Disease↗
PubMed2005

Abstract reporting in randomized clinical trials of acute lung injury: an audit and assessment of a quality of reporting score.

OBJECTIVES: To evaluate the quality of reporting among abstracts of randomized controlled trials (RCTs) in acute lung injury and to highlight important trial information for abstract inclusion. DESIGN: Audit of published RCT abstracts. SAMPLE: A total of 56 RCTs, identified in MEDLINE, EMBASE, HEALTHSTAR, CINAHL, and the Cochrane Central Register of Controlled Trials. MEASUREMENTS AND MAIN RESULTS: We used a research focus group and published literature on suggested content for abstracts of original articles to generate a list of 32 recommended items. The focus group reduced this list to a 20-item long form list of highly relevant criteria and a 12-item short form list of essential criteria for inclusion in abstracts of RCTs in acute lung injury. After pilot testing the abstract appraisal form, we evaluated abstracts independently and in duplicate. We scored the quality of reporting of each abstract by dividing the number of criteria fulfilled by the number applicable. Although abstracts described the study objectives and interventions well and the participants, outcomes, and conclusions to an intermediate extent, key deficiencies were noted in reporting the study methods, setting, and results. Mean quality of reporting scores were significantly higher for structured compared with unstructured abstracts using the 32-item, 20-item, and 12-item lists (p = .008, .014, and <.0001, respectively), especially for abstracts published after 1990 (p = .004, .017, and .001, respectively). The 20-item and 12-item lists correlated well with the 32-item list (r = .89 and .62, respectively) and with one another (r = .73). CONCLUSIONS: Key design features and results are frequently under-reported in RCT abstracts, particularly among unstructured abstracts. Checklists may aid authors and editors in prioritizing important criteria for inclusion in RCT abstracts.

Abstracting and Indexing↗