Vaccines for preventing herpes zoster in older adults.

BACKGROUND: Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. MAIN RESULTS: We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated zoster vaccine and one study compared zoster vaccine versus pneumococcal polysaccharide vaccine (pneumo 23).Confirmed cases of herpes zoster were less frequent in patients who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49 (95% confidence interval (CI) 0.43 to 0.56), with a risk difference (RD) of 2%, and number needed to treat to benefit (NNTB) of 50. Analyses according to age groups indicated a greater benefit in participants aged 60 to 69 years, RR 0.36 (95% CI 0.30 to 0.45) and in participants aged 70 years and over, RR 0.63 (95% CI 0.53 to 0.75). Vaccine-related systemic adverse effects were more frequent in the vaccinated group (RR 1.29, 95% CI 1.05 to 1.57, number needed to treat to harm (NNTH) = 100). The pooled data risk ratio for adverse effects for participants with one or more inoculation site adverse effect was RR 4.51 (95% CI 2.35 to 8.68), and the NNTH was 2.8 (95% CI 2.3 to 3.4). Side effects were more frequent in younger (60 to 69 years) than in older (70 years and over) participants. AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years), this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.

Early versus late tracheostomy for critically ill patients.

BACKGROUND: Long-term mechanical ventilation is the most common situation where tracheostomy is indicated for patients in intensive care units (ICU). 'Early' and 'late' tracheostomies are two categories of the timing of tracheostomy. The evidence on the advantages attributed to early over late tracheostomy is somewhat conflicting but includes shorter hospital stays and lower mortality rates. OBJECTIVES: To evaluate the effectiveness and safety of early (≤ 10 days after intubation) versus late tracheostomy (> 10 days after intubation) in critically ill adult patients predicted to be on prolonged mechanical ventilation and with different clinical conditions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 12); MEDLINE (via PubMed) (1966 to December 2010); EMBASE (via Ovid) (from 1974 to December 2010); LILACS (1986 to December 2010); PEDro (Physiotherapy Evidence Database) at www.pedro.fhs.usyd.edu.au (1999 to December 2010) and CINAHL (1982 to December 2010). SELECTION CRITERIA: We included all randomized or quasi-randomized controlled trials which compared early tracheostomy (two to10 days after intubation) against late tracheostomy (> 10 days after intubation) for critically ill adult patients expected to be on prolonged mechanical ventilation. There was no language restriction. DATA COLLECTION AND ANALYSIS: Two authors extracted data and conducted a quality assessment. Meta-analyses using the random-effects model were conducted for mortality and pneumonia. MAIN RESULTS: We included four studies, with a high risk of bias, in which a total of 673 patients were randomized to either early or late tracheostomy. We could not pool data in a meta-analysis because of clinical, methodological and statistical heterogeneity between the included studies. There is no strong evidence for real differences between early and late tracheostomy in the primary outcome of mortality. In one study a statistically significant result favouring early tracheostomy was observed in the outcome measuring time spent on ventilatory support (mean difference (MD) -9.80 days, 95% CI -11.48 to -8.12, P < 0.001). AUTHORS' CONCLUSIONS: Updated evidence is of low quality, and potential differences between early and late tracheostomy need to be better investigated by means of randomized controlled trials. At present there is no specific information about any subgroup or individual characteristics potentially associated with better outcomes with either early or late tracheostomy.

De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock.

BACKGROUND: Mortality rates among patients with sepsis, severe sepsis or septic shock ranges from 27% to 54%. Empirical broad-spectrum antimicrobial treatment is aimed at achieving adequate antimicrobial therapy and thus reducing mortality. However, there is a risk that empirical broad-spectrum antimicrobial treatment can expose patients to overuse of antimicrobials. De-escalation has been proposed as a strategy to replace empirical broad-spectrum antimicrobial treatment with a narrower antimicrobial therapy. This is done by either changing the pharmacological agent or discontinuing a pharmacological combination according to the patient's microbial culture results. OBJECTIVES: To evaluate the effectiveness and safety of de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock caused by any micro-organism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 8); MEDLINE via PubMed (from inception to August 2010); EMBASE (from inception to August 2010); LILACS (from inception to August 2010); Current Controlled Trials and bibliographic references of relevant studies. We also contacted the main authors in the area. We applied no language restriction. SELECTION CRITERIA: We planned to include randomized controlled trials comparing de-escalation (based on culture results) versus standard therapy for adults with sepsis, severe sepsis or septic shock. The primary outcome was mortality (at 28 days, hospital discharge or the end of the follow-up period). Studies including patients initially treated with an empirical but not adequate antimicrobial therapy were not considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors planned to independently select and extract data and evaluate methodological quality of all studies. We planned to use relative risk (risk ratio) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals. We planned to use the random-effects statistical model when the estimate effects of two or more studies could be combined in a meta-analysis. MAIN RESULTS: We retrieved 436 references via the search strategy. No randomized controlled trials testing de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock could be included in this review. AUTHORS' CONCLUSIONS: There is no adequate, direct evidence as to whether de-escalation of antimicrobial agents is effective and safe for adults with sepsis, severe sepsis or septic shock. Therefore, it is not possible to either recommend or not recommend the de-escalation of antimicrobial agents in clinical practice for septic patients. This uncertainty warrants further research via randomized controlled trials or cohort studies.