Network meta-analysis of direct-acting antivirals in combination with peginterferon-ribavirin for previously untreated patients with hepatitis C genotype 1 infection.

AIM: To conduct a network meta-analysis (NMA) to determine the comparative efficacy, as measured by sustained virological response (SVR), between boceprevir (BOC), telaprevir (TEL), faldaprevir (FAL), simeprevir (SIM) and sofosbuvir (SOF) in combination with peginterferon-ribavirin (PR) against a control of PR. DESIGN: A literature search was conducted to identify randomized controlled trials (RCTs) including adult patients with hepatitis C virus genotype 1 who were naive to any prior therapy. RCTs assessing standard duration therapy (SDT) or response-guided therapy (RGT) BOC, TEL, FAL, SIM or SOF in combination with PR against a control of PR were eligible for inclusion. All RCTs must have provided SVR at either 12 or 24 weeks post-therapy cessation. RESULTS: We included nine RCTs. All direct-acting antivirals (DAAs) were found to perform better than PR. Additionally, SDT FAL was found to be better than the 240 mg RGT FAL regimen with the PR lead-in. A sensitivity analysis excluding RCTs with only SVR at 12 weeks was consistent with the results of the primary analysis. A sensitivity analysis removing an RCT assessing SIM that reported SVR of >60% in the PR control group additionally found that RGT SIM was superior to the 240 mg RGT FAL regimen with the PR lead-in. DISCUSSION: Our analyses indicate that SDT and RGT regimens of DAAs plus PR do not differ greatly in terms of SVR among treatment-naive hepatitis C genotype 1 patients. More advanced Bayesian network meta-analyses are likely needed to incorporate a comprehensive evidence base, expanding beyond randomized clinical trials.

Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis.

BACKGROUND: New direct-acting antiviral agents for hepatitis C genotype 1 infection, boceprevir and telaprevir, offer enhanced sustained virologic response (SVR) among both treatment-naïve and treatment-experienced patients. AIM: To determine the relative efficacy of the new direct-acting antiviral agents by applying a multiple treatment comparison meta-analysis. DESIGN: We included published Phase II and III randomized controlled trials evaluating head-to-head comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment comparison meta-analysis. RESULTS: We included data from four boceprevir, three telaprevir and six peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin randomized controlled trials. Both boceprevir and telaprevir offer statistically superior outcomes for SVR, relapse and discontinuation due to adverse events than either peg-interferons among both treatment-naïve and treatment-experienced patients. Among treatment-naïve patients, clinical outcomes were similar for boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval (95% CrI) 0.41-1.91] and for relapse (OR 1.09, 95% CrI 0.19-4.84). Similarly, among treatment-experienced patients, clinical outcomes were similar for boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70-3.08) and for relapse (OR 0.35, 95% CrI 0.13-1.02). For treatment-naïve patients receiving standard-duration therapy, telaprevir yielded lower rates of anemia and neutropenia, but higher rates of rash and pruritus. For treatment-experience patients, all adverse event rates were higher with telaprevir. DISCUSSION: Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1 treatment-naïve and treatment-experienced patients.

Adverse events associated with individual statin treatments for cardiovascular disease: an indirect comparison meta-analysis.

BACKGROUND: Statins are the most widely prescribed drug available. Due to this reason, it is important to understand the risks involved with the drug class and individual statins. AIM: We conducted a meta-analysis and employed indirect comparisons to identify differing risk effects across statins. DESIGN: We included any randomized clinical trial (RCT) of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin used for cardiovascular disease event prevention. The main outcome was adverse events [all-cause mortality, cancers, rhabdomylosis, diabetes, aspartate and alanine aminotransferase (AST/ALT), and creatinine kinase (CK) increases beyond the upper limit of normal]. In order to evaluate the relative effects of each drug on adverse events, we calculated adjusted indirect comparisons of the adverse-event outcomes. RESULTS: Seventy-two trials involving 159,458 patients met our inclusion criteria. Overall, statin treatments significantly increased the rate of diabetes when compared to controls (OR: 1.09; 95% CI: 1.02-1.16) and elevated AST (OR: 1.31; 95% CI: 1.04-1.66) and ALT (OR: 1.28; 95% CI: 1.11-1.48) levels when compared to controls. Using indirect comparisons, we also found that atorvastatin significantly elevated AST levels compared to pravastatin (OR: 2.21; 95% CI: 1.13-4.29) and simvastatin significantly increased CK levels when compared to rosuvastatin (OR: 4.39; 95% CI: 1.01-19.07). Higher dose studies had increased risk of AST elevations. DISCUSSION: Although statins are generally well tolerated, there are risks associated with almost all drugs. With few exceptions, statins appear to exert a similar risk across individual drugs.

An assessment of global Internet-based HIV/AIDS media coverage: implications for United Nations Programme on HIV/AIDS' Global Media HIV/AIDS initiative.

No studies to date have assessed the quantity of HIV/AIDS-related media on the Internet. We assessed the quantity of language-specific HIV/AIDS Internet-based news coverage, and the correlation between country-specific HIV/AIDS news coverage and HIV/AIDS prevalence. Internet-based HIV/AIDS news articles were queried from Google News Archives for 168 countries, for the year 2007, in the nine most commonly spoken languages worldwide. English, French and Spanish sources had the greatest number of HIV/AIDS-related articles, representing 134,000 (0.70%), 11,200 (0.65%) and 24,300 (0.49%) of all news articles, respectively. A strong association between country-specific HIV/AIDS news coverage and HIV/AIDS prevalence was found, Spearman's rank correlation: 0.6 (P < 0.001). Among countries with elevated HIV/AIDS prevalence (> or =10%), the volume of HIV/AIDS-specific media was highest in Swaziland (15.9%) and Malawi (13.2%), and lowest in South Africa (4.8%) and Namibia (4.9%). Increased media attention should be placed on countries with high HIV/AIDS prevalence and limited HIV/AIDS-specific news coverage.

Mortality is influenced by locality in a major HIV/AIDS epidemic.

OBJECTIVES: The aim of the study was to compare the risks of death among HIV-infected patients on highly active antiretroviral therapy (HAART) in two proximate, yet distinct neighbourhoods: a neighbourhood with a high concentration of gay men, and a neighbourhood with a high concentration of injecting drug users. METHODS: We compared the clinical and socioeconomic characteristics of HIV-infected patients from the two neighbourhoods entering the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program from 1 September 1997 to 30 November 2005, using contingency table statistics. Cox survival models and Kaplan-Meier methods were used to estimate the cumulative mortality rates. RESULTS: We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV-experienced physician and be less adherent. Patients in the neighbourhood with a high concentration of gay men were more likely to have AIDS. Mortality was significantly higher for patients in the neighbourhood with a high concentration of injecting drug users [hazard ratio (HR) 3.01; 95% confidence interval (CI) 1.73, 5.24]. CONCLUSIONS: A threefold increase was observed in the risk of death among HIV-infected individuals on HAART in the neighbourhood with a high concentration of injecting drug users relative to the neighbourhood with a high concentration of gay men. The implications of this study should be assessed in similar HIV/AIDS epicentres.

Health care services utilization stratified by virological and immunological markers of HIV: evidence from a universal health care setting.

OBJECTIVE: The aim of the study was to determine rates of utilization of in-patient, out-patient and laboratory services stratified by virological and immunological markers of HIV disease among patients on antiretroviral treatment in British Columbia, Canada. METHODS: We estimated resource utilization for in-patient visits, out-patient visits, and laboratory tests among patients initiating antiretroviral treatment between 1 April 1994 and 31 December 2000, with follow-up to 31 March 2001. Resource use was stratified by CD4 cell count and plasma HIV viral load (pVL) at the time of utilization and rates per 100 patient-years were calculated for each health care resource. RESULTS: A total of 2718 patients were included in our analyses. The overall rates of in-patient visits, out-patient visits, and laboratory tests were 902, 3001 and 840 per 100 patient-years, respectively. Utilization was higher for patients with low CD4 cell counts and high pVLs when compared with patients with high CD4 cell counts and low pVLs. CONCLUSIONS: Patients with low CD4 cell counts and high pVLs had the highest use of health care services. Regular follow-up with health care providers in an out-patient setting, allowing for proper monitoring and maintenance of HIV care, is important in minimizing unnecessary and potentially costly in-patient care.

Hospital treatment and diagnosis of Mycoplasma pneumoniae pneumonia.

A study was started in 1972 in order to determine the true etiology of patients who presented with obscure pulmonary infiltrates. Patients who were included in this study had sera drawn on two occasions. Complete testing was performed for the various viruses and also for Mycoplasma pneumoniae antibodies. The study continued through 1975 and a total of 159 patients were included. Of these 159 patients, 28 had positive complement fixation tests for M. pneumoniae antibodies. The clinical profile and treatment course is outlined and discussed.

Mycoplasma pneumoniae as a cause of pneumonia, lung abscess and pleural effusion: a case report.

A case report of a 26 year-old asthmatic male is outlined in order to show the clinical features and unusual development pattern of pulmonary disorders and pleural effusion with a Mycoplasma pneumoniae pneumonia. A literature review is included in order to put this unusual case into perspective.

Myocarditis and severe bilateral bronchopneumonia caused by Mycoplasma pneumoniae.

A man with severe bilateral bronchopneumonia and a right lobar consolidation caused by Mycoplasma pneumoniae, had a concurrent myocarditis. The possible aetiology of the patchy pulmonary opacities is discussed. A literature review of cases of myocarditis associated with M.pneumoniae is presented.