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Combination antibiotic therapy improves survival and clinical response of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients.

ObjectivePrevious observational studies suggest that the use of proton pump inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired pneumonia (HCAP). However, the potential presence of confounding and protopathic biases limits the conclusions that can be drawn from these studies. Our objective was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically in new users of non-steroidal anti-inflammatory drugs (NSAIDs).DesignWe formed eight restricted cohorts of new users of NSAIDs, aged ≥40 years, using a common protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, US MarketScan and the UK's General Practice Research Database (GPRD)). This specific patient population was studied to minimise bias due to unmeasured confounders. High-dimensional propensity scores were used to estimate site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared with unexposed patients. Fixed-effects meta-analytic models were used to estimate overall effects across databases.ResultsOf the 4 238 504 new users of NSAIDs, 2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to 1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI  0.75 to 1.21).ConclusionsOur study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP.

IntroductionDespite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.MethodsUtilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis.ResultsIn total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P = 0.313) and only a trend to longer duration of ventilator support (P = 0.055) among survivors.ConclusionMarked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.

Background Catheter related bloodstream infections (CRBSI) are associated with significant morbidity and mortality and effective methods for their prevention are needed. Objective To assess the efficacy of a chlorhexidine-impregnated dressing for prevention of central venous catheter-related colonization and CRBSI using meta-analysis. Data Sources Multiple computerized database searches supplemented by manual searches including relevant conference proceedings. Study Selection Randomized controlled trials (RCT) evaluating the efficacy of a chlorhexidine-impregnated dressing compared with conventional dressings for prevention of catheter colonization and CRBSI. Data Extraction Data were extracted on patient and catheter characteristics and outcomes. Data Synthesis Pooled estimates of the relative risk (RR) and 95% confidence intervals (CI) were obtained using the DerSimonian and Laird random effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was assessed using the Cochran Q statistic and I2. Subgroup analyses were used to explore heterogeneity. Results Nine RCTs met the inclusion criteria. Use of a chlorhexidine-impregnated dressing resulted in a reduced incidence of CRBSI (random effects RR 0.57, 95% CI 0.42–0.79, P=0.002). The incidence of catheter colonization was also markedly reduced in the chlorhexidine-impregnated dressing group (random effects RR 0.51, 95% CI 0.39–0.67, P< 0.001). There was significant benefit for prevention of catheter colonization and CRBSI, including arterial catheters used for hemodynamic monitoring. Other than in low birth weight infants, adverse effects were rare and minor. Conclusions Our analysis shows that a chlorhexidine-impregnated dressing is beneficial in preventing catheter colonization and, more importantly, CRBSI and warrants routine use in patients at high risk of CRBSI and CVC or arterial catheter colonization in ICUs.

People diagnosed with cancer are at increased risk of suicide, especially in the 3 months following initial diagnosis. Increased support and psychiatric involvement should be considered for the first year after cancer diagnosis.

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