The effect of carvedilol on mortality risk in heart failure patients with diabetes: results of a meta-analysis

BACKGROUND: Although beta-blocker therapy has been shown to improve survival in patients with chronic heart failure, this class of drugs tends to be underutilized in diabetic patients due to concerns about adverse metabolic effects, especially on glycemic control. No randomized clinical trial has specifically evaluated the effect of beta-blocker therapy on mortality in diabetic patients with heart failure. Previous meta-analyses combining results of heart failure trials with pharmacologically diverse beta-blockers suggest that the survival benefit in diabetic patients may be diminished compared to benefits in non-diabetic patients. However, some trial results indicate that carvedilol, which blocks beta1-, beta2-, and alpha1-receptors and is a potent antioxidant, may produce at least comparable effects in both patient groups. OBJECTIVES: To evaluate the effect of carvedilol in patients with heart failure and diabetes, specifically to determine if the survival benefit of carvedilol demonstrated in heart failure trials was as great in the subgroups of patients with diabetes. METHODS: A meta-analysis was performed that included 5757 patients with heart failure, 25% of whom had diabetes, from seven large placebo-controlled randomized trials with carvedilol. All large (> 100 patients) placebo-controlled, randomized trials with carvedilol in heart failure were included. The endpoint of all-cause mortality was examined in the overall population, patients without diabetes, and patients with diabetes. The number of patients needed to treat (NNT) for 1 year to prevent one death associated with carvedilol use in diabetic versus non-diabetic patients was also calculated. The log-rank test and the Cox proportional hazards regression were used to compare the event time distributions of carvedilol versus placebo with respect to the outcome of mortality. RESULTS: Similar survival benefits were seen with carvedilol use in diabetic and non-diabetic patients (relative risk reductions of 28% [95% confidence interval (CI) 3-46%; p = 0.03] and 37% [95% CI 22-48%; p < 0.001], respectively). There were no significant differences between the relative mortality risk reductions or the NNT with carvedilol use in diabetic versus non-diabetic patients. The NNT for 1 year to prevent one death was 23 for all patients, as well as for non-diabetic patients, and 25 for the diabetic group. CONCLUSIONS: This meta-analysis provides evidence that the same survival benefit may occur with carvedilol in heart failure patients with and without diabetes. The low NNT in the severe heart failure trial, COPERNICUS, and the diabetic subgroup in this meta-analysis suggests that severe heart failure patients and heart failure patients with diabetes may particularly derive benefit from therapy with carvedilol.     

The effect of carvedilol on mortality risk in heart failure patients with diabetes: results of a meta-analysis

ABSTRACT

Background: Although β.blocker therapy has been shown to improve survival in patients with chronic heart failure, this class of drugs tends to be underutilized in diabetic patients due to concerns about adverse metabolic effects, especially on glycemic control. No randomized clinical trial has specifically evaluated the effect of β.blocker therapy on mortality in diabetic patients with heart failure. Previous meta. analyses combining results of heart failure trials with pharmacologically diverse β.blockers suggest that the survival benefit in diabetic patients may be diminished compared to benefits in non.diabetic patients. However, some trial results indicate that carvedilol, which blocks β₁., β₂., and α₁.receptors and is a potent antioxidant, may produce at least comparable effects in both patient groups.

Objectives: To evaluate the effect of carvedilol in patients with heart failure and diabetes, specifically to determine if the survival benefit of carvedilol demon- strated in heart failure trials was as great in the subgroups of patients with diabetes.

Methods: A meta-analysis was performed that included 5757 patients with heart failure, 25% of whom had diabetes, from seven large placebo-controlled randomized trials with carvedilol. All large (> 100 patients) placebo-controlled, randomized trials with carvedilol in heart failure were included. The endpoint of all-cause mortality was examined in the overall population, patients without diabetes, and patients with diabetes. The number of patients needed to treat (NNT) for 1 year to prevent one death associated with carvedilol use in diabetic versus non-diabetic patients was also calculated. The log-rank test and the Cox proportional hazards regression were used to compare the event time distributions of carvedilol versus placebo with respect to the outcome of mortality.

Results: Similar survival benefits were seen with carvedilol use in diabetic and non-diabetic patients (relative risk reductions of 28% [95% confidence interval (CI) 3-46%; p = 0.03] and 37% [95% CI 22-48%; p < 0.001], respectively). There were no significant differences between the relative mortality risk reductions or the NNT with carvedilol use in diabetic versus non- diabetic patients. The NNT for 1 year to prevent one death was 23 for all patients, as well as for non-diabetic patients, and 25 for the diabetic group.

Conclusions: This meta-analysis provides evidence that the same survival benefit may occur with carvedilol in heart failure patients with and without diabetes. The low NNT in the severe heart failure trial, COPERNICUS, and the diabetic subgroup in this meta-analysis suggests that severe heart failure patients and heart failure patients with diabetes may particularly derive benefit from therapy with carvedilol.     

NSAIDs and COVID-19: A Systematic Review and Meta-analysis

Drug Safety - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been discouraged for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, fearing that they...     

新型冠状病毒肺炎患者继发感染的危险因素分析

摘要：目的　探讨新型冠状病毒肺炎（COVID-19）患者继发细菌感染的危险因素。方法　回顾性分析天津市海河医院收治的136例COVID-19患者的临床资料,根据临床诊断结果分为继发细菌性肺炎（继发感染组,44例）和非继发感染组（92例）。比较2组患者临床特征、治疗、疾病转归等差异,Logistic回归分析患者继发感染的危险因素。结果　继发感染组患者年龄、合并基础疾病比例高于非继发感染组（P＜0.01）,入院的氧合指数（OI）＜400 mmHg、高热（体温>39 ℃）、重症、合并急性呼吸窘迫综合征（ARDS）、低蛋白血症、心功能不全比例也均高于非继发感染组,接受机械通气治疗、有创操作、激素治疗比例及住院时间均高于非继发感染组（P＜0.05）。Logistics 回归分析显示,合并基础疾病（OR=4.613,95%CI：1.756~12.118）、激素治疗（OR=2.403,95%CI：1.012~6.422）、入院OI＜400 mmHg（OR=6.534,95%CI：2.064~20.691）、低蛋白血症（OR=12.949,95%CI：3.284~51.067）是继发细菌感染的独立危险因素。结论　COVID-19继发感染与患者入院氧合指数低于400 mmHg、低蛋白血症、激素治疗、基础疾病关系密切,临床尽早干预可预防患者继发感染,有利于改善预后。     

Outcome of COVID-19 patients with use of Tocilizumab: A single center experience

COVID-19 pandemic has become a global concern. Cytokine release syndrome (CRS) complicates acute respiratory distress syndrome (ARDS) and causes multi-organ failure which can subsequently lead to mortality in COVID-19 patients. Tocilizumab, an interleukin-6 antagonist, has shown to salvage patients with cytokine release storm. In this study, we aim to evaluate therapeutic response of Tocilizumab in COVID-19 patients. A single-arm retrospective review of 40 patients with COVID-19, admitted to The Aga Khan University Hospital Karachi, from March 2020 to May 2020 was performed. Selection of patients for use of Tocilizumab was based on severity of disease, rapid clinical deterioration, presence of CRS and absence of any absolute contraindication to Tocilizumab. Improvement after Tocilizumab was defined as improvement in oxygen requirement and inflammatory parameters. Serum levels of inflammatory cytokines like C-reactive protein, ferritin, D-dimer and lactate dehydrogenase levels were monitored before and after administering Tocilizumab. Mean age was 62.4 years and 33 (82.5%) were male. 19 (47.5%) patients were critically sick, 18 (45%) were severely sick and 3 (7.5%) were moderately sick. 29 (77.5%) patients showed significant improvement in oxygen requirement, inflammatory parameters and chest x-rays, out of which 28 patients were discharged home. The mean duration between administration of Tocilizumab and overall improvement was 4.3 ± 3.2 days. Hence, Tocilizumab can be used as a possible treatment option in patients with COVID-19 induced CRS but needs monitoring for its adverse effects.     

The effect of oseltamivir use in critically ill patients with COVID-19: A multicenter propensity score-matched study

BackgroundOseltamivir has been used as adjunctive therapy in the management of patients with COVID-19. However, the evidence about using oseltamivir in critically ill patients with severe COVID-19 remains scarce. This study aims to evaluate the effectiveness and safety of oseltamivir in critically ill patients with COVID-19.MethodsThis multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care unit (ICU). Patients were categorized into two groups based on oseltamivir use within 48 hours of ICU admission (Oseltamivir vs. Control). The primary endpoint was viral load clearance.ResultsA total of 226 patients were matched into two groups based on their propensity score. The time to COVID-19 viral load clearance was shorter in patients who received oseltamivir (11 vs. 16 days, p = 0.042; beta coefficient: −0.84, 95%CI: (−1.33, 0.34), p = 0.0009). Mechanical ventilation (MV) duration was also shorter in patients who received oseltamivir (6.5 vs. 8.5 days, p = 0.02; beta coefficient: −0.27, 95% CI: [−0.55,0.02], P = 0.06). In addition, patients who received oseltamivir had lower odds of hospital/ventilator-acquired pneumonia (OR:0.49, 95% CI:(0.283,0.861), p = 0.01). On the other hand, there were no significant differences between the groups in the 30-day and in-hospital mortality.ConclusionOseltamivir was associated with faster viral clearance and shorter MV duration without safety concerns in critically ill COVID-19 patients.     

Azvudine reduces the in-hospital mortality of COVID-19 patients:A retrospective cohort study

In our retrospective cohort study, we aim to explore whether Azvudine modifies the risk of death in COVID-19 patients. It was conducted on the medical records of patients, consecutively admitted for COVID-19 pneumonia to two hospitals in Chongqing, China. Based on Azvudine treatment exposure,the patients were divided into Azvudine group and non-Azvudine group. We used 1:2 ratio propensity score matching(PSM) in our study to adjust for confounding factors and differences between Azvudine and non-...     

基于骨关节炎患者的胃肠道和心血管风险评估非甾体抗炎药的使用

摘要 目的：了解我院骨关节炎住院患者非甾体抗炎药（NSAIDs）应用的现状,为临床合理使用该类药物提供建议。 方法：采用回顾性调查方法,对2013年5月-2014年5月间因骨关节炎（osteoarthritis,OA）住院患者的胃肠道（gastrointestinal, GI ）风险因素,心血管（cardiovascular,CV）病史和住院期间NSAIDs的使用情况进行分析。 结果：306名入选的OA患者中,42.2%的患者无任何GI风险因素,55.6%属于中度GI风险,2.2%的患者属于高GI风险,16.3%（50/306）的患者至少有一个CV病史。随着GI风险的逐渐增加,非选择性NSAIDs抑制剂的用药比例逐渐增加,特异性COX-2抑制剂的用药比例逐渐减少,胃粘膜保护药物则更频繁用于有GI风险的患者。5例有高GI风险,同时无CV病史的口服NSAIDs的患者无一例采用特异性COX-2抑制剂联合PPI的治疗方案。 结论：我院OA患者NSAIDs应用与文献推荐不符,临床药师可在促进其合理应用方面发挥积极作用。该结果能为临床合理用药提供参考、充分发挥临床药师作为治疗团队成员的作用,并为国家将来规范NSAIDs使用的指南或专家共识提供参考。     

Increased risk of hyperglycemia associated with the use of everolimus in patients with cancer: a systematic review and meta-analysis

Everolimus is an orally administered rapamycin analogue that has been approved to treat several types of solid tumors. However, some patients develop hyperglycemia after being treated with everolimus. In this meta-analysis, we aimed to evaluate the incidence and risk of hyperglycemia in patients with cancer who received everolimus. We searched the medical literature, as index in the Cochrane Library, PubMed, EMBASE, and abstracts from the top scientific meetings (AACR, ASCO, and ESMO). Our meta-analysis included the randomly controlled trials published before November 2014. We calculated overall incidence, relative risk (RR) and 95% confidence intervals (CI) using fixed-effects or random-effects models, depending on the heterogeneity among the trials. A total of 3377 patients (everolimus: 1971; control: 1406) from 8 randomized clinical trials were included in the meta-analysis. In the everolimus groups, the incidence of all grades of hyperglycemia was 20.0% (95% CI: 11.0%–29.0%), while the incidence of high-grade hyperglycemia was 6.0% (95% CI: 3.0%–8.0%). Patients treated with everolimus had an increased risk of hyperglycemia as compared with that of controls (all-grade RR: 2.94, 95% CI: 2.34–3.70; high-grade RR: 4.66, 95% CI: 2.75–7.89). Everolimus significantly increased the risk of hyperglycemia. This risk may depend on the tumor type and the everolimus dosage.     

Paracetamol use and risk of ovarian cancer: a meta-analysis

AIM: Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. METHODS: A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. RESULTS: Eight studies (four case-control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random-effects model (RR=0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed-effects model (RR=0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; 'regular use' was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non-use (RR=0.70, 95% CI 0.51, 0.95). CONCLUSIONS: Our meta-analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol's potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance.     

The use of NSAIDs in rheumatic disorders 2005: a global perspective

Population studies and World Health Organisation (WHO) statistics indicate that 10-50% of individuals suffer from musculoskeletal disorders. Up to 3% will be classified as disabled due to their bone and joint condition, and the majority will suffer from pain. Almost all will require non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics for their management. The large majority of this population is elderly and, hence, at greater risk of adverse effects to the NSAIDs. The NSAIDs are a necessary choice in pain management because of the integrated role of the cyclo-oxygenase (COX) pathway in the generation of inflammation and in the biochemical recognition of pain. For over 80 years the management of musculoskeletal pain was hampered by NSAID toxicity problems related to the traditional NSAIDs. In the early 1990s, paracetamol was recommended as the first-choice analgesic for osteoarthritis, but subsequent studies have shown that paracetamol has a significant gastrointestinal (GI) toxicity profile. In addition, it has lower analgesic efficacy than NSAIDs and is, thus, not an effective alternative to NSAIDs in any of the inflammatory arthritides. The identification of cyclo-oxygenase 2 (COX-2) and the subsequent introduction of the COX-2-selective inhibitor NSAID drugs was thought to be a major breakthrough with the expectation of a significant reduction in G/I side-effects. This has not been the case for celecoxib, and indeed for all COX-2-selective inhibitors when given with ASA. The COX-2-selective inhibitors also inhibit renal COX-2 with the potential for problems of fluid retention, oedema, hypertension and congestive heart failure. The major controversy with respect to the COX-2-selective inhibitors as a class has been the increase in myocardial infarction and other cardiovascular events observed in some studies. Thus, the initial expected global benefits of the COX-2-selective inhibitors may be outweighed by their potential for toxicity. Recent studies have shown that the use of a proton-pump inhibitor drug with traditional NSAIDs and with COX-2-selective inhibitors has been shown to significantly reduce GI symptoms and peptic ulceration. Thus, the traditional NSAIDs have been re-established as the preferred choice in the management of arthritis and musculoskeletal disorders.     

间苯三酚联合非甾体抗炎药治疗肾绞痛的荟萃分析

目的系统评价间苯三酚联合非甾体抗炎药(NSAIDs)治疗肾绞痛的临床价值。方法电子检索中英文数据库中关于间苯三酚联合NSAIDs对比山莨菪碱联合NSAIDs治疗肾绞痛的随机或半随机对照研究,采用Rev Man 5.2软件对数据进行分析。结果共纳入6篇研究,共1437名患者,其中间苯三酚组765例,山莨菪碱组672例。Meta分析结果显示:2组在治疗肾绞痛30 min疼痛缓解率上差异无统计学意义(P=0.07),但结果稳健性欠佳。间苯三酚联合NSAIDs比山莨菪碱联合NSAIDs治疗肾绞痛的疼痛缓解速度更快(P=0.0002),总不良反应发生率更低(P=0.0003),其中口干、皮肤潮红、排尿困难、尿潴留等常见不良反应发生率也明显更低(P<0.05)。结论与山莨菪碱联合NSAIDs相比,间苯三酚联合NSAIDs治疗肾绞痛的起效速度更快,不良反应更少。该结论仍需更多高质量大样本的随机对照研究予以论证。     

All-cause and cause-specific mortality rates of patients treated for alcohol use disorders: A meta-analysis

Background: Although alcohol use disorders (AUDs) are known to increase the relative risk of all-cause and some cause-specific mortality, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritizing the identification and/or treatment of diseases likely to cause their death. Methods: We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUDs. Number of deaths by cause and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analyzed assuming random effects. Results: Thirty-one studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. A total of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded, and the pooled all-cause mortality rate was 27.67/1000 person-years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95% CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1, 7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms, respiratory diseases, and substance use disorders. Conclusions: Patients with AUDs have increased rates of all-cause and cause-specific mortality compared with the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning health care services for patients with AUDs.