The role of statins in prevention and treatment of community acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications. PURPOSE: Performed a systematic review to address the role of statins in the prevention or treatment of CAP. DATA SOURCE: Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies. STUDY SELECTION: Two authors independently reviewed studies that examined the role of statins in CAP. DATA EXTRACTION: Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted. DATA SYNTHESIS: Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74-0.95), I(2) = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59-0.78), I(2) = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77-0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder. CONCLUSIONS: Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Temporal trends of infective endocarditis in North America from 2000 to 2017 – a systematic review

Objectives To examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. Patients and Methods A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews™, Ovid Embase™, Ovid Medline™, Scopus™, and Web of Science™ were searched for studies published between January 1, 2000 and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. Results Of 8,588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for two studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7-14.4%, while the percentage of patients who underwent surgery ranged from 6.4-16.0%. Conclusion Overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations have been highlighted for use in subsequent systematic reviews of IE

The association between prior statin usage and long-term outcomes after critical care admission

Background: Statins may have immunomodulatory effects that benefit critically ill patients. Therefore we retrospectively examined the association between survival and the prescription of statins prior to admission to an intensive care unit (ICU), or high dependency unit (HDU), as a result of major elective surgery, or as an emergency with a presumed diagnosis of sepsis. Methods: We retrospectively studied critical care patients (ICU or HDU) from a tertiary referral UK teaching hospital. Nottingham University Hospitals has over 2200 beds, of which 39 are critical care beds. Over a five-year period (2000–2005) 414 patients were identified with a presumed diagnosis of sepsis, and 672 patients were identified with a planned ICU/HDU admission following elective major surgery. Patients prescribed statins prior to hospital admission were compared with those who were not. Demographics, past medical history, drug history, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were examined. Univariate and multivariate analyses were applied using the primary endpoint of survival at five years after admission. Results: Patients prescribed statins prior to critical care admission were, on average, older, with higher initial APACHE II scores and more pre-existing comorbidities. Statins were almost invariably stopped following admission to critical care. Statin usage was not associated with significantly altered survival during hospital admission, or at five years, for either patients with sepsis (9% v 15%, P=0.121; 73% v 84%, P=0.503 respectively), or post-operative patients (55% v 58%, P=0.762; 57% v 63%, P=0.390). Conclusions: Prior statin usage was not associated with improved or worsening outcomes in patients admitted to critical care after elective surgical cases or with a presumed diagnosis of sepsis

Increasing incidence and mortality of infective endocarditis: a population-based study through a record-linkage system

<p>Abstract</p> <p>Background</p> <p>Few population-based studies provide epidemiological data on infective endocarditis (IE). Aim of the study is to analyze incidence and outcomes of IE in the Veneto Region (North-Eastern Italy).</p> <p>Methods</p> <p>Residents with a first hospitalization for IE in 2000-2008 were extracted from discharge data and linked to mortality records to estimate 365-days survival. Etiology was retrieved in subsets of this cohort by discharge codes and by linkage to a microbiological database. Risk factors for mortality were assessed through logistic regression.</p> <p>Results</p> <p>1,863 subjects were hospitalized for IE, with a corresponding crude rate of 4.4 per 100,000 person-years, increasing from 4.1 in 2000-2002 to 4.9 in 2006-2008 (p = 0.003). Median age was 68 years; 39% of subjects were hospitalized in the three preceding months. 23% of patients underwent a cardiac valve procedure in the index admission or in the following year. Inhospital mortality was 14% (19% including hospital transfers); 90-days and 365-days mortality rose through the study years. Mortality increased with age and the Charlson comorbidity index, in subjects with previous hospitalizations for heart failure, and (in the subcohort with microbiological data) in IE due to Staphylococci (40% of IE).</p> <p>Conclusions</p> <p>The study demonstrates an increasing incidence and mortality for IE over the last decade. Analyses of electronic archives provide a region-wide picture of IE, overcoming referral biases affecting single clinic or multicentric studies, and therefore represent a first fundamental step to detect critical issues related to IE.</p

Non prescribed sale of antibiotics in Riyadh, Saudi Arabia: A Cross Sectional Study

Background Antibiotics sales without medical prescriptions are increasingly recognized as sources of antimicrobial misuse that can exacerbate the global burden of antibiotic resistance. We aimed to determine the percentage of pharmacies who sell antibiotics without medical prescriptions, examining the potential associated risks of such practice in Riyadh, Saudi Arabia, by simulation of different clinical scenarios. Methods A cross sectional study of a quasi-random sample of pharmacies stratified by the five regions of Riyadh. Each pharmacy was visited once by two investigators who simulated having a relative with a specific clinical illness (sore throat, acute bronchitis, otitis media, acute sinusitis, diarrhea, and urinary tract infection (UTI) in childbearing aged women). Results A total of 327 pharmacies were visited. Antibiotics were dispensed without a medical prescription in 244 (77.6%) of 327, of which 231 (95%) were dispensed without a patient request. Simulated cases of sore throat and diarrhea resulted in an antibiotic being dispensed in (90%) of encounters, followed by UTI (75%), acute bronchitis (73%), otitis media (51%) and acute sinusitis (40%). Metronidazole (89%) and ciprofloxacin (86%) were commonly given for diarrhea and UTI, respectively, whereas amoxicillin/clavulanate was dispensed (51%) for the other simulated cases. None of the pharmacists asked about antibiotic allergy history or provided information about drug interactions. Only 23% asked about pregnancy status when dispensing antibiotics for UTI-simulated cases. Conclusions We observed that an antibiotic could be obtained in Riyadh without a medical prescription or an evidence-based indication with associated potential clinical risks. Strict enforcement and adherence to existing regulations are warranted

Prognostic factors in left-sided endocarditis: results from the andalusian multicenter cohort

<p>Abstract</p> <p>Background</p> <p>Despite medical advances, mortality in infective endocarditis (IE) is still very high. Previous studies on prognosis in IE have observed conflicting results. The aim of this study was to identify predictors of in-hospital mortality in a large multicenter cohort of left-sided IE.</p> <p>Methods</p> <p>An observational multicenter study was conducted from January 1984 to December 2006 in seven hospitals in Andalusia, Spain. Seven hundred and five left-side IE patients were included. The main outcome measure was in-hospital mortality. Several prognostic factors were analysed by univariate tests and then by multilogistic regression model.</p> <p>Results</p> <p>The overall mortality was 29.5% (25.5% from 1984 to 1995 and 31.9% from 1996 to 2006; Odds Ratio 1.25; 95% Confidence Interval: 0.97-1.60; p = 0.07). In univariate analysis, age, comorbidity, especially chronic liver disease, prosthetic valve, virulent microorganism such as <it>Staphylococcus aureus</it>, <it>Streptococcus agalactiae </it>and fungi, and complications (septic shock, severe heart failure, renal insufficiency, neurologic manifestations and perivalvular extension) were related with higher mortality. Independent factors for mortality in multivariate analysis were: Charlson comorbidity score (OR: 1.2; 95% CI: 1.1-1.3), prosthetic endocarditis (OR: 1.9; CI: 1.2-3.1), <it>Staphylococcus aureus </it>aetiology (OR: 2.1; CI: 1.3-3.5), severe heart failure (OR: 5.4; CI: 3.3-8.8), neurologic manifestations (OR: 1.9; CI: 1.2-2.9), septic shock (OR: 4.2; CI: 2.3-7.7), perivalvular extension (OR: 2.4; CI: 1.3-4.5) and acute renal failure (OR: 1.69; CI: 1.0-2.6). Conversely, <it>Streptococcus viridans </it>group etiology (OR: 0.4; CI: 0.2-0.7) and surgical treatment (OR: 0.5; CI: 0.3-0.8) were protective factors.</p> <p>Conclusions</p> <p>Several characteristics of left-sided endocarditis enable selection of a patient group at higher risk of mortality. This group may benefit from more specialised attention in referral centers and should help to identify those patients who might benefit from more aggressive diagnostic and/or therapeutic procedures.</p

A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes.</p> <p>Methods/Design</p> <p>A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates.</p> <p>Discussion</p> <p>Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic.</p> <p>Trial Registration Number</p> <p><a href="http://www.controlled-trials.com/ISRCTN45190901">ISRCTN45190901</a></p

SpxA1 Involved in Hydrogen Peroxide Production, Stress Tolerance and Endocarditis Virulence in Streptococcus sanguinis

Streptococcus sanguinis is one of the most common agents of infective endocarditis. Spx proteins are a group of global regulators that negatively or positively control global transcription initiation. In this study, we characterized the spxA1 gene in S. sanguinis SK36. The spxA1 null mutant displayed opaque colony morphology, reduced hydrogen peroxide (H2O2) production, and reduced antagonistic activity against Streptococcus mutans UA159 relative to the wild type strain. The ΔspxA1 mutant also demonstrated decreased tolerance to high temperature, acidic and oxidative stresses. Further analysis revealed that ΔspxA1 also exhibited a ∼5-fold reduction in competitiveness in an animal model of endocarditis. Microarray studies indicated that expression of several oxidative stress genes was downregulated in the ΔspxA1 mutant. The expression of spxB and nox was significantly decreased in the ΔspxA1 mutant compared with the wild type. These results indicate that spxA1 plays a major role in H2O2 production, stress tolerance and endocarditis virulence in S. sanguinis SK36. The second spx gene, spxA2, was also found in S. sanguinis SK36. The spxA2 null mutant was found to be defective for growth under normal conditions and showed sensitivity to high temperature, acidic and oxidative stresses