Outcomes of ICU patients with and without perceptions of excessive care:a comparison between cancer and non-cancer patients

BACKGROUND: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer.METHODS: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer.RESULTS: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p &lt; 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60-1.72 and HR 0.87, 95% CI 0.49-1.54) and TLDs (HR 0.81, 95% CI 0.33-1.99 and HR 0.70, 95% CI 0.27-1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58-3.15 and 1.66, 95% CI 1.28-2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups.CONCLUSIONS: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU.</p

Impact of Reporting Bias in Network Meta-Analysis of Antidepressant Placebo-Controlled Trials

BACKGROUND: Indirect comparisons of competing treatments by network meta-analysis (NMA) are increasingly in use. Reporting bias has received little attention in this context. We aimed to assess the impact of such bias in NMAs. METHODS: We used data from 74 FDA-registered placebo-controlled trials of 12 antidepressants and their 51 matching publications. For each dataset, NMA was used to estimate the effect sizes for 66 possible pair-wise comparisons of these drugs, the probabilities of being the best drug and ranking the drugs. To assess the impact of reporting bias, we compared the NMA results for the 51 published trials and those for the 74 FDA-registered trials. To assess how reporting bias affecting only one drug may affect the ranking of all drugs, we performed 12 different NMAs for hypothetical analysis. For each of these NMAs, we used published data for one drug and FDA data for the 11 other drugs. FINDINGS: Pair-wise effect sizes for drugs derived from the NMA of published data and those from the NMA of FDA data differed in absolute value by at least 100% in 30 of 66 pair-wise comparisons (45%). Depending on the dataset used, the top 3 agents differed, in composition and order. When reporting bias hypothetically affected only one drug, the affected drug ranked first in 5 of the 12 NMAs but second (n = 2), fourth (n = 1) or eighth (n = 2) in the NMA of the complete FDA network. CONCLUSIONS: In this particular network, reporting bias biased NMA-based estimates of treatments efficacy and modified ranking. The reporting bias effect in NMAs may differ from that in classical meta-analyses in that reporting bias affecting only one drug may affect the ranking of all drugs

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life

The Effects of Fructose Intake on Serum Uric Acid Vary among Controlled Dietary Trials1234

Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I2. A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 μmol/L (95% CI: −6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213–219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at “real world” doses are needed

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(&gt; MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of &gt;= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700