Differences between statins on clinical endpoints: a population-based cohort study

OBJECTIVE: Many studies have shown differences between statins based on surrogate endpoints, but few have studied differences in reaching clinical endpoints.This study compares the risk of cardiovascular and cerebrovascular events between atorvastatin users and other statin users in daily general practice. RESEARCH DESIGN AND METHODS: A cohort study was performed in the Integrated Primary Care Information project database, a longitudinal general practice research database with electronic patient records of more than 500,000 individuals in The Netherlands. All new statin users in the period 1st September 1999 to 31st December 2002 were included. Multivariate Cox-regression analysis was used to compare the occurrence of the primary endpoint between atorvastatin users and other statin users. MAIN OUTCOME MEASURES: The primary endpoint was the composite outcome of fatal or non-fatal myocardial infarction, admission for unstable angina pectoris, fatal or non-fatal cerebrovascular accidents, or transient ischaemic events. RESULTS: 3499 new statin users were identified, including 797 patients with a history of cardiovascular disease. 1341 persons started with simvastatin (38.3%), 1154 with atorvastatin (33.0%), 811 with pravastatin (23.2%) and 193 with other statins (5.5%). The median follow-up was 1.9 years. Two hundred and thirty three patients (6.7%) experienced a primary endpoint. Atorvastatin users had a significantly lower risk of cardiovascular and cerebrovascular events than users of other statins (relative risk [RR]: 0.70, 95% confidence interval [CI]: 0.55-0.96). The relative risks of atorvastatin users compared to simvastatin and pravastatin users individually were 0.70 (95% CI: 0.48-1.02) and 0.78 (95% CI: 0.52-1.16), respectively. The protective effect of atorvastatin was more pronounced in persons without a history of cardiovascular or cerebrovascular events. CONCLUSION: Atorvastatin showed a more favourable effect on fatal and non-fatal cardiovascular and cerebrovascular events in the general population than other statins.     

Comparison of incidences of cardiovascular events among new users of different statins: a retrospective observational cohort study

Abstract

Objective:

To compare incidences of cardiovascular disease (CVD) in general and myocardial infarction (MI) specifically between new users of different statins in daily practice.     

Cancer risk in patients with osteoporosis: a population-based cohort study

Background: Osteoporosis has been associated with cancer development. We conducted a nationwide population-based cohort study in Taiwan to evaluate this possible association of osteoporosis with subsequent cancer development.

Methods: A total of 35,979 patients diagnosed with osteoporosis between 2000 and 2010 identified from the National Health Insurance Research Database comprised the osteoporosis cohort, and each patient was randomly frequency matched with one individual from the general population (without osteoporosis) based on age, sex, and year of osteoporosis diagnosis to form the non-osteoporosis (control) cohort. Cox proportional hazard regression analysis was used to calculate adjusted hazard ratios and 95% confidence intervals and determine the effect of osteoporosis on cancer risk.

Results: Patients with osteoporosis showed a significantly higher risk of developing liver and thyroid cancers and lower risk of colorectal cancer than did individuals without osteoporosis. Male patients with osteoporosis had a significantly increased risk for liver cancer, whereas female patients with osteoporosis had a significantly increased risk for thyroid cancer, but a significantly decreased risk for overall and colorectal cancers. In addition, more significant findings were observed when age ≤64 years or the follow-up duration was ≤5 years; however, a significantly lower risk for colorectal cancer was observed when follow-up duration was >5 years. Study limits including lack of data for some health-related behaviors, inclusion criteria of osteoporosis and potential selection bias have been discussed.

Conclusion: Patients with osteoporosis showed a higher risk for liver and thyroid cancers and a lower risk for colorectal cancer than did control individuals. Stratified analyses by sex, age, and follow-up duration showed various patterns in different cancers.     

Frequency and risk factors for mental disorders following pancreatitis: a nationwide cohort study

Objective: To investigate the frequency and risk factors for mental disorders following pancreatitis.

Methods: Patients with acute pancreatitis (AP) and chronic pancreatitis (CP) were identified (n?=?18,074) from a nationwide database in New Zealand (1998–2015). They were followed from their first hospital admissions for AP or CP to incident mental disorders. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression analyses.

Results: CP (vs AP) was associated with a significantly higher risk of mental disorders (adjusted HR?=?2.00 [95% CI?=?1.53–2.62]). Pre-existing diabetes (adjusted HR?=?8.99 [95% CI?=?6.23–12.96] for AP and adjusted HR?=?3.42 [95% CI?=?2.37–4.96] for CP) and post-pancreatitis diabetes mellitus (adjusted HR?=?7.10 [95% CI?=?4.14–12.19] for AP and adjusted HR?=?2.97 [95% CI?=?1.83–4.82] for CP) were risk factors for mental disorders in individuals following pancreatitis. Severe (adjusted HR?=?2.07 [95% CI?=?1.39–3.06] vs mild) and recurrent (adjusted HR?=?1.62 [95% CI?=?1.07–2.45] vs single episode) attacks were associated with significantly higher risks of mental disorders following AP.

Conclusions: Patients following CP, recurrent AP, severe AP, and those with diabetes are at high risk for developing mental disorders.     

Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study

Objective Several case-control studies have reported that the use of fluoroquinolone increases the risk of rupture of the Achilles tendon. Our aim was to estimate this risk by means of a population-based cohort approach. Setting Data on Achilles tendon ruptures and fluoroquinolone use were retrieved from three population-based databases that include information on residents of Funen County (population: 470,000) in primary and secondary care during the period 1991–1999. A study cohort of all 28,262 first-time users of fluoroquinolone and all incident cases of Achilles tendon ruptures were identified. Main outcome measures The incidence rate of Achilles tendon ruptures among users and non-users of fluoroquinolones and the standardised incidence rate ratio associating fluoroquinolon use with Achilles tendon rupture were the main outcome measures. Results Between 1991 and 2002 the incidence of Achilles tendon rupture increased from 22.1 to 32.6/100,000 person-years. Between 1991 and 1999 the incidence of fluoroquinolone users was 722/100,000 person-years, with no apparent trend over time. Within 90 days of their first use of fluoroquinolone, five individuals had a rupture of the Achilles tendon; the expected number was 1.6, yielding an age- and sex-standardised incidence ratio of 3.1 [(95% confidence interval (95%CI): 1.0–7.3). The 90-day cumulative incidence of Achilles tendon ruptures among fluoroquinolone users was 17.7/100,000 (95%CI: 5.7–41.3), which is an increase of 12.0/100,000 (95%CI: 0.0–35.6) compared to the background population. Conclusion Fluoroquinolone use triples the risk of Achilles tendon rupture, but the incidence among users is low. Grant support: there is no funding.     

临床药师提供的药学服务对他汀类药物治疗服务系统建设的影响研究

目的探讨临床药师主导的药学服务对他汀类药物治疗服务系统构建及评价的影响。方法200例服用他汀类药物治疗的老年(62~88岁)患者,按随机原则分为药师干预组和对照组,每组100例。对照组通过传统用药护理、发放宣教手册、电话回访实施干预;药师干预组在对照组基础上结合药师小组在临床前行讨论模式,经由本社区居委会领导精选交流及协调,每周按时由合格教师或临床药师构建成服务小组,为社区提供免费药学服务和充分培训,进而可更好完成药品使用审评数据分析及收集。对比两组干预前后用药相关问题(DRP)发生情况及药物治疗收益(安全性、有效性、经济性、适当性)。结果干预后,药师干预组DRP发生率30.0%低于对照组的70.0%,差异有统计学意义(P<0.05)。干预后,两组的DRP出现条目数、DRP总药物数量、DRP处方药数量均较干预前减少,且药师干预组减少量更多。干预后,药师干预组药品不良反应(ADR)、重复用药、相互作用、潜在不适当用药(PIM)、其他用药问题发生率分别为13.0%、1.0%、1.0%、2.0%、25.0%,均低于对照组的26.0%、7.0%、7.0%、10.0%、40.0%,差异有统计学意义(P<0.05);药师干预组用药信念好、用药认知好的占比和近3个月就诊率均高于对照组,欧洲视觉模拟标尺法(QOL EQ-VAS)评分低于对照组,医保用药数量、用药数量、月药费均少于对照组,剂量不当、治疗不足的占比均低于对照组,差异有统计学意义(P<0.05)。两组干预后用药依从性好、超适应证、无适应证的占比和欧洲五维健康量表(QOL EQ-5D)评分比较差异均无统计学意义(P>0.05)。结论以临床药师为主导的药学服务,能显著提高老年患者用药安全性、有效性、经济性和适当性,临床药师地位得到提高以及公众的认同。     

Long-term risk of colorectal cancer by gender after positive colonoscopy: population-based cohort study

Background: Evidence for surveillance intervals of colonoscopy are primarily based on adenoma recurrence rate rather than on colorectal cancer (C.R.C.) incidence. Little is known about long-term risk of C.R.C. after positive colonoscopy. In view of men have significantly higher C.R.C. risk than women, we aimed to estimate the gender-specific C.R.C. incidence after positive colonoscopy (adenoma or malignant lesion) at follow-up colonoscopy.

Methods: A retrospective cohort study was conducted using data from a database of colonoscopy screening and surveillance. Patients having had a colonoscopy (January 2010–March 2014) were selected as study subjects and the history of prior colonoscopies was reviewed. Multivariable Weibull regression models were used to estimate the incidence of C.R.C. at follow-up colonoscopy for subjects who were assigned a stratified risk level. The benchmark risk was defined according to a national survey.

Results: The interval incidence of C.R.C. at a 10 year follow-up was 164 (95% C.I. 63–343) and 79 (95% C.I. 26–188) per 100,000 person-years for low-risk men and women respectively, which tallied with our benchmark risk. Men exceeded the benchmark risk in 3–5 years if they had an incomplete polyp removal, ≥3 adenomas during their last colonoscopy or a personal C.R.C. history, and in 7–8 years if they only had familial C.R.C. history. Women had a lower risk of C.R.C., and reached a same risk level 3–5 years later than men. Coexisting above risk factors resulted in a sharp increase in the incidence of C.R.C. at follow-up exceeding the benchmark much earlier.

Conclusion: Surveillance intervals for men based on incidence of C.R.C. are in line with that recommended by the current guidelines for colonoscopy. However, an extension of 3–5 years may be appropriate for women. To target personalized medicine, a risk predictive model could be used to identify an appropriate surveillance interval for each individual in the future.     

膝关节镜下治疗盘状半月板疗效分析

目的总结在膝关节镜下治疗盘状半月板临床应用效果。方法本组22例，男16例，女6例，年龄6—35岁。应用美国Stryker关节镜对22例膝关节盘状软骨进行了检查、确诊及手术。结果盘状半月板全切除术7例，部分切除术15例。随访2个月～5年，优19例，良2例，差1例，优良率95．5％。结论膝关节镜检查及手术在诊断和治疗膝关节盘状半月板是一种有效的方法。     

溃疡性结肠炎活动期的临床疗效评价

目的分析溃疡性结肠炎（UC）活动期的临床疗效及治疗转归,评价预后相关因素。方法回顾性分析216例住院患者的病例资料,记录临床表现及诊疗经过,对柳氮磺吡啶（SASP）或5-氨基水杨酸（5-ASA）、糖皮质激素、免疫抑制剂、灌肠、外科手术等治疗方法的疗效进行评价。结果活动期UC患者中,轻度占25.0%（54/216）,中度占50.9%（110/216）,重度占24.1%（52/216）;SASP或5-ASA是控制症状的主要药物,对于中度UC患者,联合用药治疗效果较为理想。而发病年龄轻、结肠病变范围大、低血红蛋白、大便以血为主、低血清白蛋白、病变伴有溃疡是提示疗效差的相关因素。结论对于UC病变处于活动期时,应及时评估病情严重程度,选择疗效相对较好的治疗方案,并分析影响疗效相关因素。     

Association between neurodegenerative diseases and pneumonia: a retrospective population-based study

Purpose: The association between pneumonia and neurodegenerative diseases (NDs) has never been reported in detail. We address this relationship with reference to the general population.

Methods: Using Taiwan’s National Health Insurance Research Database to identify a pneumonia cohort (including the typical and atypical), we established an ND cohort of 19,062 patients and a non-ND cohort of 76,227 people. In both cohorts, the risk of pneumonia was measured using multivariable Cox proportional hazards models.

Results: The adjusted hazard ratio (aHR) (95% confidence interval [CI]) for the pneumonia cohort was 2.10 (1.96–2.24), regardless of age, sex, comorbidities or drug use in the ND cohort. The aHR (95% CI) for adults aged 20–49 years was 2.08 (1.58–2.75), men 2.20 (2.01–2.40). However, older subjects were at greatest risk of pneumonia, (3.41 [2.99–3.88]) if the 20–49 years age group is used as the reference. For the ND and non-ND cohorts, those with comorbidities (with the exception of hyperlipidemia) had higher risk; aHR (95% CI) 2.35 (2.30–2.52). The aHR (95% CI) for those without comorbidities is 3.28 (2.52–4.26). No significant difference was observed in incidence of pneumonia between those who were and were not using statin medications; the aHR (95% CI) was 1.03 (0.93–1.14).

Conclusion: The ND cohort had a higher risk of pneumonia, regardless of age, sex, comorbidities or statin use. The risk of pneumonia was higher in elderly and male patients in the ND cohort.     

Effect of statins on total cholesterol concentrations and cardiovascular outcomes in patients with diabetes mellitus: a population-based cohort study

Background

In the UK, clinicians usually make treatment decisions based on total cholesterol (TC) at the same time supplemented with high-density lipoprotein cholesterol (HDL-C) measurements. We evaluated statin-associated TC concentration change and its impact on cardiovascular (CV) risk reduction in diabetic patients in the setting of usual care.

Methods

In a population-based cohort study using a record-linkage database in Tayside, Scotland. we studied 6,697 diabetic patients who had at least two separate TC measurements between 1993 and 2007. Patients were categorized into statin-exposed and statin-unexposed groups according to statin use status during the follow-up. The main outcomes were TC concentration change from baseline, CV events, and all-cause mortality during the follow-up. Multivariate Cox regression models with a time-dependent variable for statins were employed to assess outcome risk.

Results

Statin-associated TC concentrations decreased by 1.64 mmol/L (28%) in patients without CV disease (CVD) (5,984) and 1.19 mmol/L (23%) in patients with CVD (713) from 5.90 mmol/L and 5.20 mmol/L at baselines, respectively. Statin use reduced incident and recurrent CV events by 39% and 41%, respectively [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.57–0.66; 0.59 95% CI 0.47–0.76) per millimole of TC reduction. For all-cause mortality, the adjusted HRs were 0.39 (95% CI 0.32–0.47) in primary prevention and 0.58 (95% CI 0.42–0.80) in secondary prevention.

Conclusion

Statin use was as effective in diabetic patients in the setting of usual care, as in the clinical trials, in both primary and secondary prevention. TC changes can be used as a measure of statin efficacy in the absence of low-density lipoprotein cholesterol (LDL-C) in diabetic patients.     

Patterns of drug use and abuse among aging adults with and without HIV: A latent class analysis of a US Veteran cohort

This study characterized the extent and patterns of self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV-infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and socio-demographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22–86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non-users were most prevalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV-infected. While problems of obesity marked those not currently using drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV-infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV.     

Factors associated with mortality among heroin users after seeking treatment with methadone: A population-based cohort study in Taiwan

Data concerning factors associated with mortality among heroin users under methadone maintenance treatment (MMT) in the Han Chinese population are limited. This study examined mortality risk among heroin users after seeking treatment with methadone in a catchment area using a cohort of 1616 Taiwanese heroin users between October 2006 and December 2008. During the study period, 26 (1.6%) people died, with an all-cause mortality rate per 100 person years of 3.42. The primary cause of death among our patients was accidents, followed by suicide and drug overdose. Older age, HIV infection, psychiatric treatment history, and alcohol abuse/dependence were risk factors for all-cause mortality; remaining on MMT was protective for survival. Our findings suggest that although mortality is mainly associated with medical and psychiatric comorbidities, continuing with the MMT program is still an important predictor for survival.     

A multicentre,open study to assess the effect of individualizing starting doses of atorvastatin according to baseline LDL-C levels on achieving cholesterol targets: the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST-2) study

ABSTRACT

Objectives: ACTFAST-2 was designed to match the starting dose of a statin to the baseline low density lipoprotein-cholesterol (LDL-C) value, to allow high-risk European subjects to achieve LDL-C targets within 12 weeks with the initial dose or one up-titration.

Research design and methods: This was a 12-week, prospective, open-label trial that enrolled 610 high-risk subjects from 8 European countries. Subjects with LDL-C > 2.6?mmol/L (> 100?mg/dL),but ≤ 5.7?mmol/L (≤ 220?mg/dL) were assigned a starting dose of atorvastatin (10, 20, 40, 80?mg/day) according to LDL-C level and status of statin use at baseline (either statin-free or statin-treated), with a single up-titration at 6 weeks if needed.

Results: At 12 weeks, 68.0% of subjects overall, including 73.5% of statin-free and 60.5% of statin-treated subjects, achieved LDL-C target (< 2.6?mmol/L (< 100?mg/dL). The total cholesterol/high density lipoprotein-cholesterol (TC/HDL-C) ratio target was achieved by 75.2% of subjects overall, including 78.1% of statin-free and 71.2% of statin-treated subjects. In the statin-free group, LDL-C decreased by a mean of 42%. In the statin-treated group, atorvastatin led to an additional 31% reduction in LDL-C over the statin used at baseline. Mean decreases in TC/HDL-C ratio were 30% and 20% in the statin-free and statin-treated groups, respectively. The incidence of AST/ALT greater than 3 times of upper limit of normal range in all patients was 0.8% and no rhabdomyolysis was reported.

Conclusion: This study confirms that use of a flexible starting dose of atorvastatin allows the large majority of high-risk subjects to achieve their LDL-C target safely within 12 weeks with an initial dose or just a single up-titration.