Jennie Johnstone

Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis.

Objective To evaluate risk factors for severe outcomes in patients with seasonal and pandemic influenza. Design Systematic review. Study selection Observational studies reporting on risk factor-outcome combinations of interest in participants with influenza. Outcomes included death, ventilator support, admission to hospital, admission to an intensive care unit, pneumonia, and composite outcomes. Data sources Medline, Embase, CINAHL, Global Health, and the Cochrane Central Register of Controlled Trials to March 2011. Risk of bias assessment Newcastle-Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality of evidence. Results 63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence supporting risk factors for severe outcomes of influenza ranged from being limited to absent. This was particularly relevant for the relative lack of data for non-2009 H1N1 pandemics and for seasonal influenza studies. Limitations in the published literature included lack of power and lack of adjustment for confounders was widespread: adjusted risk estimates were provided for only 5% of risk factor-outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for “any risk factor” (odds ratio for mortality 2.77, 95% confidence interval 1.90 to 4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza), obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68, 1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all other risk factors. Some well accepted risk factors such as pregnancy and belonging to an ethnic minority group could not be identified as risk factors. In contrast, women who were less than four weeks post partum had a significantly increased risk of death from pandemic influenza (4.43, 1.24 to 15.81). Conclusion The level of evidence to support risk factors for influenza related complications is low and some well accepted risk factors, including pregnancy and ethnicity, could not be confirmed as risks. Rigorous and adequately powered studies are needed.

Blood CD33(+)HLA‐DR(−) myeloid‐derived suppressor cells are increased with age and a history of cancer

As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA‐DR(−) MDSCs across three cohorts: healthy adults (19–59 years old), community‐dwelling seniors (61–76 years old), and frail elderly (67–99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF‐α, IL‐6, and IL‐1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age‐related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age‐related pathologies.

The Loss of Topography in the Microbial Communities of the Upper Respiratory Tract in the Elderly

RATIONALE The microbial communities inhabiting the upper respiratory tract protect from respiratory infection. The maturity of the immune system is a major influence on the composition of the microbiome and, in youth, the microbiota and immune system are believed to mature in tandem. With age, immune function declines and susceptibility to respiratory infection increases. Whether these changes contribute to the microbial composition of the respiratory tract is unknown. OBJECTIVES Our goal was to determine whether the microbes of the upper respiratory tract differ between mid-aged adults (18-40 yr) and the elderly (>65 yr). METHODS Microbiomes of the anterior nares and oropharynx of elderly individuals were evaluated by 16S rRNA gene sequencing. These communities were compared with data on mid-aged adults obtained from the Human Microbiome Project. MEASUREMENTS AND MAIN RESULTS The microbiota of the elderly showed no associations with sex, comorbidities, residence, or vaccinations. Comparisons of mid-aged adults and the elderly demonstrated significant differences in the composition of the anterior nares and oropharynx, including a population in the anterior nares of the elderly that more closely resembled the oropharynx than the anterior nares of adults. The elderly oropharyngeal microbiota were characterized by increased abundance of streptococci, specifically, Streptococcus salivarius group species, but not Streptococcus pneumoniae, carriage of which was low (<3% of participants), as demonstrated by PCR (n = 4/123). CONCLUSIONS Microbial populations of the upper respiratory tract in mid-aged adults and the elderly differ; it is possible that these differences contribute to the increased risk of respiratory infections experienced by the elderly.

Probiotics in the critically ill: A systematic review of the randomized trial evidence

Objective:Critical illness results in changes to the microbiology of the gastrointestinal tract, leading to a loss of commensal flora and an overgrowth of potentially pathogenic bacteria. Administering certain strains of live bacteria (probiotics) to critically ill patients may restore balance to the microbiota and have positive effects on immune function and gastrointestinal structure and function. The purpose of this systematic review was to evaluate the effect of probiotics in critically ill patients on clinical outcomes. Design:Systematic review. Interventions:None. Measurements and Main Results:We searched computerized databases, reference lists of pertinent articles, and personal files from 1980 to 2011. We included randomized controlled trials enrolling critically ill adults, which evaluated probiotics compared to a placebo and reported clinically important outcomes (infections, mortality, and length of stay). A total of 23 randomized controlled trials met inclusion criteria. Probiotics were associated with reduced infectious complications as documented in 11 trials (risk ratio 0.82; 95% confidence interval 0.69–0.99; p = .03; test for heterogeneity p = .05; I2 44%). When data from the seven trials reporting ventilator-associated pneumonia were pooled, ventilator-associated pneumonia rates were also significantly reduced with probiotics (risk ratio 0.75; 95% confidence interval 0.59–0.97; p = .03; test for heterogeneity p = .16; I2 35%). Probiotics were associated with a trend toward reduced intensive care unit mortality (risk ratio 0.80; 95% confidence interval 0.59–1.09; p = .16; test for heterogeneity p = .89; I2 0%) but did not influence hospital mortality. Probiotics had no effect on intensive care unit or hospital length of stay. Compared to trials of higher methodological quality, greater treatment effects were observed in trials of a lower methodological quality. Conclusions:Probiotics appear to reduce infectious complications including ventilator-associated pneumonia and may influence intensive care unit mortality. However, clinical and statistical heterogeneity and imprecise estimates preclude strong clinical recommendations. Further research on probiotics in the critically ill is warranted.

Impact of the Pneumococcal Vaccine on Long-Term Morbidity and Mortality of Adults at High Risk for Pneumonia

BACKGROUND There is debate surrounding the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV). We determined whether PPV was associated with reduced mortality or additional hospitalization for vaccine-preventable infections in patients previously hospitalized for community-acquired pneumonia (CAP). METHODS From 2000 through 2002, adults with CAP admitted to the hospital in Edmonton, Alberta, Canada, were enrolled in a population-based cohort. Postdischarge outcomes during 5 years were ascertained using administrative databases. The primary outcome was the composite of all-cause mortality or additional hospitalization for vaccine-preventable infections. Proportional hazards analysis was used to determine the association between PPV use and outcomes. RESULTS A total of 2950 patients were followed up for a median of 3.8 years. The mean patient age was 68 years; 52% were male. One-third (n = 956) received PPV: 667 (70%) before and 289 (30%) during hospitalization. After discharge, 1404 patients (48%) died, 504 (17%) were admitted with vaccine-preventable infections, and 1626 (55%) reached the composite outcome of death or infection. PPV was not associated with reduced risk of the composite outcome (589 [62%] vs 1037 [52%] for those unvaccinated; adjusted hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.79-1.04). Results were not altered in sensitivity analyses using propensity scores (adjusted HR, 0.91; 95% CI, 0.79-1.04), restricting the sample to patients 65 years or older (adjusted HR, 0.90; 95% CI, 0.77-1.04), or considering only those who received PPV at discharge (adjusted HR, 0.84; 95% CI, 0.71-1.00). CONCLUSIONS One-half of patients discharged from the hospital after pneumonia die or are subsequently hospitalized with a vaccine-preventable infection within 5 years. PPV was not associated with a reduced risk of death or hospitalization. Better pneumococcal vaccination strategies are urgently needed.

Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials

Background: Results of randomized controlled trials evaluating zinc for the treatment of the common cold are conflicting. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for such use. Methods: We searched electronic databases and other sources for studies published through to Sept. 30, 2011. We included all randomized controlled trials comparing orally administered zinc with placebo or no treatment. Assessment for study inclusion, data extraction and risk-of-bias analyses were performed in duplicate. We conducted meta-analyses using a random-effects model. Results: We included 17 trials involving a total of 2121 participants. Compared with patients given placebo, those receiving zinc had a shorter duration of cold symptoms (mean difference −1.65 days, 95% confidence interval [CI] −2.50 to −0.81); however, heterogeneity was high (I2 = 95%). Zinc shortened the duration of cold symptoms in adults (mean difference −2.63, 95% CI −3.69 to −1.58), but no significant effect was seen among children (mean difference −0.26, 95% CI −0.78 to 0.25). Heterogeneity remained high in all subgroup analyses, including by age, dose of ionized zinc and zinc formulation. The occurrence of any adverse event (risk ratio [RR] 1.24, 95% CI 1.05 to 1.46), bad taste (RR 1.65, 95% CI 1.27 to 2.16) and nausea (RR 1.64, 95% CI 1.19 to 2.27) were more common in the zinc group than in the placebo group. Interpretation: The results of our meta-analysis showed that oral zinc formulations may shorten the duration of symptoms of the common cold. However, large high-quality trials are needed before definitive recommendations for clinical practice can be made. Adverse effects were common and should be the point of future study, because a good safety and tolerance profile is essential when treating this generally mild illness.

Vaccine herd effect

Abstract Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines.

Human rabies encephalitis following bat exposure: failure of therapeutic coma

The case: A healthy 73-year-old man had pain in his left shoulder. He presented to a regional hospital 1 week later with fever, dysphagia, muscle spasms and progressive generalized weakness. His neurologic status deteriorated, which prompted transfer to a tertiary care hospital. Upon the patients

Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial

Background: A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture. Methods: Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization. Results: Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26–1.39). Interpretation: These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial. Trial registration: ClinicalTrials.gov, no. NCT01344343.

Does duration of perioperative antibiotic prophylaxis matter in cardiac surgery? A systematic review and meta-analysis

Objective:We aimed to compare the efficacy of short-term (<24 hours) versus longer-term antibiotic prophylaxis (≥24 hours) in open heart surgery. Background:The optimal duration of antibiotic prophylaxis for adults undergoing cardiac surgery is unknown and guideline recommendations are inconsistent. Methods:We searched MEDLINE, EMBASE, CINAHL, and CENTRAL for parallel-group randomized trials comparing any antibiotic prophylaxis administered for <24 hours to any antibiotic prophylaxis for ≥24 hours in adult patients undergoing open heart surgery. Reference lists of selected articles, clinical practice guidelines, review articles, and congress abstracts were searched. Study selection, data extraction and assessment of risk of bias were performed independently by 2 reviewers. Results:Of the 1338 citations identified by our search strategy, 12 studies involving 7893 patients were selected. Compared with short-term antibiotic prophylaxis, longer-term antibiotic prophylaxis reduced the risk of sternal surgical site infection (SSI) by 38% (risk ratio 1.38, 95% confidence interval (CI) 1.13–1.69, P = 0.002) and deep sternal SSI by 68% (risk ratio 1.68, 95% CI 1.12–2.53, P = 0.01). There were no statistically significant differences in mortality, infections overall and adverse events. Eleven of the trials were at high risk for bias due to limitations in study design. Conclusions:Perioperative antibiotic prophylaxis of ≥24 hours may be more efficacious in preventing sternal SSIs in patients undergoing cardiac surgery compared to shorter regimens. The findings however are limited by the heterogeneity of antibiotic regimens used and the risk of bias in the published studies.