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To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic. We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty). The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

ObjectiveTo assess the association between low-dose aspirin and the incidence of colorectal cancer (CRC), gastric cancer (GC), oesophageal cancer (EC) and gastrointestinal bleeding (GIB) in adults without established atherosclerotic cardiovascular disease.DesignCohort study with propensity score matching of new-users of aspirin to non-users.SettingClinical Data Analysis and Reporting System database, Hong Kong.ParticipantsAdults ≥40 years with a prescription start date of either low-dose aspirin (75–300 mg/daily) or paracetamol (non-aspirin users) between 1 January 2004 to 31 December 2008 without a history of atherosclerotic cardiovascular disease.Main outcome measuresThe primary outcome was the first diagnosis of gastrointestinal cancer (either CRC, GC or EC) and the secondary outcome was GIB. Individuals were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any type of cancer besides the outcome, death or until 31 December 2017. A competing risk survival analysis was used to estimate HRs and 95% CIs with death as the competing risk.ResultsAfter matching, 49 679 aspirin and non-aspirin users were included. The median (IQR) follow-up was 10.0 (6.4) years. HRs for low-dose aspirin compared with non-aspirin users were 0.83 for CRC (95% CI, 0.76 to 0.91), 0.77 for GC (95% CI, 0.65 to 0.92) and 0.88 for EC (95% CI, 0.67 to 1.16). Patients prescribed low-dose aspirin had an increased risk of GIB (HR 1.15, 95% CI, 1.11 to 1.20), except for patients prescribed proton pump inhibitors or histamine H2-receptor antagonists (HR 1.03, 95% CI, 0.96 to 1.10).ConclusionIn this cohort study of Chinese adults, patients prescribed low-dose aspirin had reduced risks of CRC and GC and an increased risk of GIB. Among the subgroup of patients prescribed gastroprotective agents at baseline, however, the association with GIB was attenuated.

Background Understanding the trend of global antifungal agent consumption could assist with identification of global healthcare policy inadequacies and promote accessibility and availability of antifungal agents. Methods Using pharmaceutical sales data from the IQVIA-multinational integrated data analysis system database, we assessed use of systemic antifungal agents in humans in 27 middle- and 38 high-income countries from 2008 through 2018. Results Consumption of systemic antifungal agents increased from 0.50 (in 2008) to 0.92 defined daily dose (DDD)/1000 inhabitants/day (in 2018), with a compound annual growth rate of 6.2%. High-income countries remain major consumers of antifungal agents with large variance in quantities consumed, with a gradual decline in consumption in recent years. Consumption in middle-income countries increased. Itraconazole (0.32 DDD/1000 inhabitants/day), terbinafine (0.30 DDD/1000 inhabitants/day), and fluconazole (0.23 DDD/1000 inhabitants/day) were the most commonly used antifungal agents in middle- and high-income countries in 2018. Following incorporation into the World Health Organization Essential Medicines List, itraconazole consumption in middle-income countries surged. Consumption of ketoconazole slowly declined, with 5.04% annual decrease, probably due to labelling changes in 2013 to reflect hepatotoxicity concerns. The use of polyenes (0.004 DDD/1000 inhabitants/day) and echinocandins (0.003 DDD/1000 inhabitants/day) were lowest among all the antifungal drug classes. Conclusion Global consumption of triazoles and terbinafine has gradually increased in middle- and high-income countries. Life-saving antifungal agents, including echinocandins and polyenes, are available only parenterally and may be underutilized, mainly in middle-income countries. Future research on country-specific epidemiology is warranted to guide health policy coordination to ensure equitable access to appropriate use of antifungal agents.

Introduction Obesity prevalence has increased in Japan in recent years. Given the strong association of obesity with poor glycemic control, and increased risk of type 2 diabetes (T2D) with central obesity, this study describes the current trends and relationships between glycated hemoglobin (HbA1c), body mass index (BMI), and waist circumference in the Japanese people with T2D. Methods This was a retrospective, cross-sectional study of people with T2D who had at least one recorded HbA1c and BMI (or waist circumference) value in the Japan Medical Data Center Claims database. Five annual cohorts of the study population were formed between January 2017 and December 2021. Annual trends of HbA1c across BMI categories (obesity class I [≥ 25 ~  < 30 kg/m 2 ]–IV [≥ 40 kg/m 2 ]) and in people with central obesity (waist circumference: ≥ 85 cm in men; ≥ 90 cm in women) were described by sex and age groups. Results Overall, 106,089 people with T2D (HbA1c and BMI data: 106,079; HbA1c and waist circumference data: 105,424) were included, with the majority of people belonging to obesity class I (range: 39.7–40.6%) and obesity class II (range: 16.2–17.7%) categories across all annual cohorts. People in higher BMI categories had higher mean HbA1c, with > 50% of people with T2D in obesity class I–IV (54.8–56.5%) having HbA1c ≥ 7%. Between 2017 and 2021, BMI and waist circumference increased in the age group 18–44 years. More than 50% of people with T2D and central obesity in both sexes and people of age group 18–44 years across obesity class I–IV or with central obesity had HbA1c ≥ 7%. Conclusion More than half of the people with T2D belonging to obesity class I–IV or central obesity had poor glycemic control (HbA1c ≥ 7%), especially in the 18–44 age group. This highlights the need for body weight management for better glycemic control in relatively young Japanese people with T2D and obesity.

Introduction Recent data on the prevalence of metabolic syndrome in Japanese patients with type 2 diabetes (T2D) are limited. Methods This retrospective, cross-sectional, observational study investigated the prevalence of metabolic syndrome in patients with T2D using a Japanese administrative claims database. Patients with a T2D diagnosis, prescription of a hypoglycemic agent, and one or more annual health checkups in 2020 were included. Trends in the prevalence of metabolic syndrome by sex and body mass index (BMI) subgroup were assessed. Results The study cohort consisted of 155,653 patients (men, 81.6%; mean age 54.6 ± 8.5 years). Patients with metabolic syndrome had a higher mean BMI (29.1 ± 4.5 kg/m 2 versus 25.2 ± 4.5 kg/m 2 ) and mean waist circumference (98.3 ± 10.0 cm versus 87.9 ± 11.2 cm) compared to those without metabolic syndrome. Overall, the prevalence of metabolic syndrome was 43.0% in patients with T2D, with prevalence higher in men (46.6%) than women (27.0%). The prevalence increased across BMI subgroups from 17.3% in the < 25 kg/m 2 subgroup, to 54.6% and 66.1% in the 25 to < 30 and ≥ 30 kg/m 2 subgroups, respectively. A greater proportion of patients with metabolic syndrome had cardiovascular or renal comorbidities (BMI < 25, 0.3–2.0%; BMI 25 to < 30, 0.7–6.2%; BMI ≥ 30 kg/m 2 , 0.7–6.8%) and cardiovascular drug usage (BMI < 25, 1.3–9.0%; BMI 25 to < 30, 3.8–31.1%; BMI ≥ 30 kg/m 2 , 3.5–37.0%) in the higher BMI subgroups compared to the BMI < 25 kg/m 2 subgroup. Conclusion The prevalence of metabolic syndrome in Japanese patients with T2D was 43.0% and increased with higher BMI. In patients with T2D and metabolic syndrome, cardiovascular drug usage and comorbidities increased in patients with a higher BMI. These data highlight the importance of managing metabolic parameters in addition to glycemic control in Japanese patients with T2D, particularly in patients with metabolic syndrome and BMI ≥ 25 kg/m 2 .

Other randomised studies of acute stage ABPA itraconazole versus corticosteroids from India [8] and all severe asthma also comparing itraconazole with (lower dose) corticosteroid from Iran [9] probably came too late to influence the consumption of itraconazole that the authors documented to 2018, and Iran is not included amongst the 38 middleincome countries. Sincerely David W. Denning Professor of Infectious Diseases in Global Health, Manchester Fungal Infection Group, The University of Manchester, UK Chief Executive, Global Action for Fungal Infections, Geneva, Switzerland Declarations Funding No funding to declare. In his letter [1], Prof. Denning postulated reasons for the increased consumption of itraconazole, preceding its listing in the World Health Organization (WHO)'s Essential Medicine List (EML) in 2017. Conflicts of interest EWC has received research grants from the Research Grants Council (RGC, Hong Kong), Narcotics Division of the Security Bureau of the Government of the Hong Kong SAR, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, and Takeda, outside the submitted work.

Introduction Outcomes associated with suboptimal use of antithrombotic treatments (antiplatelets, warfarin, direct oral anticoagulants [DOACs]) are unclear in Chinese patients with atrial fibrillation (AF). Objectives Our objective was to assess the prescription patterns, quality, effectiveness, and safety of antithrombotic treatments. Methods This was a population-based cohort study using electronic health records in Hong Kong. Patients newly diagnosed with AF during 2010–2016 were followed up until 2017. Patients at high stroke risk (CHA2DS2-VASc score ≥ 2) and receiving antithrombotic treatments were matched using propensity scoring. We used Cox proportional hazards regression to compare the risks of ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between groups. Results Of the 52,178 high-risk patients with AF, 27,614 (52.9%) received antithrombotic treatment and were included in the analyses. Between 2010 and 2016, prescribing of antiplatelets and warfarin declined and that of DOACs increased dramatically (from 1 to 32%). Two-thirds of warfarin users experienced poor anticoagulation control. Warfarin and DOACs were associated with lower risks of ischemic stroke (warfarin, hazard ratio [HR] 0.51 [95% confidence interval (CI) 0.36–0.71]; DOACs, HR 0.69 [95% CI 0.51–0.94]) and all-cause mortality (warfarin, HR 0.47 [95% CI 0.39–0.57]; DOACs, HR 0.45 [95% CI 0.37–0.55]) than were antiplatelets. DOACs were associated with a lower risk of ICH than was warfarin (HR 0.53 [95% CI 0.34–0.83]). GIB risks were similar among all groups. Conclusion Antiplatelet prescribing and suboptimal warfarin management remain common in Chinese patients with AF at high risk of stroke. DOAC use may be associated with a lower risk of ischemic stroke and all-cause mortality when compared with antiplatelets and with a lower risk of ICH when compared with warfarin.

Orphaned because of low prevalence and barely recoverable medical costs, patients with rare diseases are disproportionately deprived of life-saving treatment. In China, an estimated 16·8 million patients suffer from rare diseases. This substantial burden could potentially be addressed through policies that optimise research and development, licensing, pricing, and reimbursement of orphan drugs. We aimed to review existing international orphan drug frameworks to inform policy formulation in China. Pharmaceutical legislation, regulation, or policies related to the access and regulation of orphan drugs were examined from 194 WHO member countries and six regions. Relevant policies were identified through an internet search for governmental policy documents, email contacts to national pharmacovigilance centres participating in the WHO Programme for International Drug Monitoring, and a systematic literature search from academic publication databases. English publications were searched from PubMed, MEDLINE, Embase, Web of Science, and the Cochrane Library, and the search was updated to July 31, 2019. 171 drug regulation documents from 156 countries or regions and 77 full-text academic publications were retrieved and read in full. 89 (44·5%) of 200 countries or regions had documentation on orphan drug policy. 34 subthemes from content analysis were categorised into six policy themes: orphan drug designation, marketing authorisation, safety and efficacy requirements, price regulation, incentives that encourage market access, and incentives that encourage research and development. In the past 5 years, surges in the establishment of orphan drug policy were found in non-high income countries (ie, lower-middle-income countries, upper-middle-income countries, and low-income countries). Globally, patient access to orphan drugs has been boosted by government regulatory efforts and incentives. In China, priority review and tax reduction on orphan drug regulation are being initiated, along with the establishment of a national registry system for rare diseases, which are expected to positively effect patient access to orphan drugs. However, the current drug regulatory and insurance scheme in China still needs substantial improvement to achieve the accessibility and affordability of orphan drugs across the nation. A need for solid nation-wide epidemiological data on rare diseases, orphan drug designation, and systematic policy support is timely. None.

As the first approved oral kinase inhibitor, tofacitinib is effective and well-tolerated, but more expensive than conventional treatments for uncontrolled rheumatoid arthritis. Public formulary listing typically exerts a positive impact on the uptake of new drugs. We aimed to assess the budgetary impact of introducing tofacitinib into the Hospital Authority Drug Formulary as a fully subsidised drug in Hong Kong. We applied a population-based budget impact model to trace the number of eligible patients receiving biologics or tofacitinib treatment, then estimated the 5-year healthcare expenditure on rheumatoid arthritis treatments, with or without tofacitinib (2017-2021). We used linear regression to estimate the number of target patients and compound annual growth rate to estimate market share. Competing treatments included abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and tofacitinib. Retail price was used for drug costs, valued in Hong Kong dollars (HK$) in 2017 and discounted at 4% per year. The annual treatment cost of tofacitinib was HK$74 214 per patient, and the costs of biologics ranged from HK$64 350 to HK$115 700. Without tofacitinib, the annual government health expenditures for rheumatoid arthritis treatment were estimated to increase from HK$147.9 million (2017) to HK$190.6 million (2021). The introduction of tofacitinib to the formulary would reduce healthcare expenditures by 17.3% to 20.3% per year, with cumulative savings of HK$192.8 million; this change was estimated to provide consistent savings (HK$66.4 million to HK$196.8 million) in all tested scenarios. Introduction of tofacitinib to the formulary will provide 5-year savings, given the current drug price and patient volume.