An education-behavioural intervention improves adherence to statins

Purpose

Effective treatment of hyperlipidemia is an important precondition for cardiovascular diseases. Unfortunately, adherence to lipid-lowering treatment is unsatisfactory. In order to improve adherence to statins, an intervention combining educational and behavioural components was tested in general practice settings.

Methods

A total of 198 outpatients with untreated hyperlipidemia were enrolled in this open-label, prospective, randomised study. Patients were prescribed simvastatin, in initial dosage of 20 mg daily, and followed for 48 weeks. Intervention group received educational counseling at each visit (that is every 8 weeks); and were also asked to adopt a routine evening activity of their choice for a reminder. Control group obtained usual care. Primary outcome measure was patient adherence, expressed as medication possession ratio (MPR).

Results

Patients’ mean age was 59.6 +/- 9.1 years. Study arms differed in their level of adherence: mean ± SD MPR was 95.4±53.7% and 81.7±31.0%, for intervention and control group, respectively (P<0.05). Patients from intervention group found a reminder activity useful in over 90% of cases.

Conclusions

Simple inexpensive educational-behavioural intervention proved to be effective in enhancing adherence to statins in hyperlipidemia. Given the health and economic consequences of non-adherence, these results may have high clinical, and practical usefulness.     

Use of medications amongst older persons in Kaunas, Lithuania

Aim

To evaluate the associations between socio-economical factors and the use of medications in the elderly.

Methods

The data was collected in a cross-sectional study in 2009. We received 624 completed questionnaires (response rate — 48.9%) from elderly people aged 60–84 years living in Kaunas (Lithuania). For an evaluation of the impact of explanatory variables on the analyzed events (binary dependent variable), an Enter model of logistic regression was used.

Results

Our findings suggest that 50.8% (n=317) of respondents used at least one drug daily. 18.3% (n=114) of respondents indicated that they use medications regularly, but not on a day-by-day basis. One quarter (25.6%; n=160) used medication only on an “at need” basis. Only 5.3% (n=33) of older persons did not use any medications at all. Logistic regression showed that being male (OR=0.67; 95%CI:0.45–0.98) was associated with using medications “regularly + daily.” For the use of “daily” medications, older age (OR=1.33; 95%CI:1.15–1.53) was associated with using medications daily. An opposite association was observed for respondents having no paid work (OR=0.48; 95%CI:0.26–0.82).

Conclusions

Our study suggests that more than half of older persons in Lithuania use medications every day. Use was associated with socioeconomic factors (gender, age, and employment status).     

Influence of refill adherence method when comparing level of adherence for different dosing regimens

Purpose

To examine the impact of two methods when estimating refill adherence in patients using bisphosphonates with different dosing regimens.

Methods

In the Swedish Prescribed Drug Register, 18,203 new users of bisphosphonates aged 18–85 years were identified between 1 July 2006 and 30 June 2007 and followed for a maximum of 2 years. The patients were categorised based on dosing regimen: one tablet daily, one tablet weekly, switching between these regimens, and other regimens. Refill adherence was estimated with Continuous measure of Medication Acquisition (CMA, adherent if CMA?≥?80 %) and the maximum gap method (adherent if gaps <45 days). Differences in adherence between patients in the groups were assessed with logistic regression models controlling for confounding factors.

Results

The proportion of patients classified as adherent was higher using CMA compared with patients classified as adherent using the maximum gap method. Patients on one tablet weekly had significantly lower adherence compared with patients on one tablet daily in the main analyses of both methods (the maximum gap method: 73 % vs. 80 %; adjusted OR?=?0.71; 95 % CI 0.57–0.89 and CMA: 84 % vs. 88 %, adjusted OR?=?0.75; 95 % CI 0.57–0.99). Patients using the other two dosing regimens had significantly lower adherence compared with patients on one tablet daily using both methods.

Conclusion

Choice of method has an impact on the estimates of refill adherence to bisphosphonates. Patients on one tablet weekly dosing had lower adherence compared with patients on one tablet daily dosing using both methods.     

Benzodiazepine therapy in psychiatric outpatients is associated with deliberate self-poisoning events at emergency departments—a population-based nested case–control study

Rationale

Deliberate self-poisoning (DSP), the most common form of deliberate self-harm, is closely associated with suicide. Identifying risk factors of DSP is necessary for implementing prevention strategies.

Objectives

This study aimed to evaluate the relationship between benzodiazepine (BZD) treatment in psychiatric outpatients and DSP cases at emergency departments (EDs).

Methods

We performed a retrospective nested case–control study of psychiatric patients receiving BZD therapy to evaluate the relationship between BZD use and the diagnosis of DSP at EDs using data from the nationwide Taiwan National Health Insurance Research Database.

Results

Regression analysis yielded an odds ratio (OR) and 95 % confidence interval (95 % CI) indicating that the use of BZDs in psychiatric outpatients was significantly associated with DSP cases at EDs (OR?=?4.46, 95 % CI?=?3.59–5.53). Having a history of DSP, sleep disorders, anxiety disorders, schizophrenia, depression, or bipolar disorder was associated with a DSP diagnosis at EDs (OR?=?13.27, 95 % CI?=?8.28–21.29; OR?=?5.04, 95 % CI?=?4.25–5.98; OR?=?3.95, 95 % CI?=?3.32–4.70; OR?=?7.80, 95 % CI?=?5.28–11.52; OR?=?15.20, 95 % CI?=?12.22–18.91; and OR?=?18.48, 95 % CI?=?10.13–33.7, respectively). After adjusting for potential confounders, BZD use remained significantly associated with a subsequent DSP diagnosis (adjusted OR?=?2.47, 95 % CI?=?1.93–3.17). Patients taking higher average cumulative BZD doses were at greater risk of DSP.

Conclusion

Vigilant evaluation of the psychiatric status of patients prescribed with BZD therapy is critical for the prevention of DSP events at EDs.     

The Impact of Upper Gastrointestinal Symptoms on Nonadherence to, and Discontinuation of, Low-Dose Acetylsalicylic Acid in Patients with Cardiovascular Risk

Background

While low-dose acetylsalicylic acid (ASA [aspirin]; 75–325 mg) is a mainstay of cardiovascular (CV) protection in patients at high risk of CV events, such protection may be compromised due to poor adherence (or discontinuation) resulting from gastrointestinal (GI) adverse events. To date, however, the link between GI adverse events and nonadherence to, and discontinuation of, low-dose ASA is not well established in the literature.

Objective

The aim of this study was to characterize the real-world impact of upper GI symptoms on low-dose ASA nonadherence and discontinuation in patients with CV risk taking low-dose ASA for CV protection.

Study Design

Multicenter, observational, noninterventional study.

Setting

Primary-care, cardiology, and practice group centers in the US, Canada, and France.

Patients

Subjects aged ≥18 years at risk of, or with confirmed, CV disease, and who had been prescribed or recommended low-dose ASA (75–325 mg daily) by a physician.

Main Outcome Measure

Adherence to low-dose ASA was assessed using 3 months of data prospectively collected using an electronic diary (completed at least three times/day). Adherence was defined as low-dose ASA intake of ≥75% over the 3-month eDiary phase. Discontinuation was defined as no reported low-dose ASA intake for ≥7 continuous days. The odds of daily adherence were calculated using a mixed-model analysis for repeated measures, and a Cox-proportional hazard model was used to assess the association between upper GI symptoms and time to discontinuation of low-dose ASA.

Results

Overall, 340 patients (mean age 50 years; 59% women) participated in the analysis. Most patients (75%) were low-dose ASA naíve at inclusion, and had not experienced upper GI symptoms within the previous 14 days. Among these patients, the onset of upper GI symptoms was rapid; symptoms were reported by 19% of patients on the first day of the study, rising to 46% of patients at the end of the first week. Over the 3-month study period, 18% of patients were nonadherent to low-dose ASA treatment. The occurrence of upper GI symptoms negatively affected low-dose ASA adherence, in both the overall patient population (odds ratio [OR] = 0.84; 95% CI 0.70, 1.0) and among patients who were low-dose ASA naíve at baseline (OR = 0.76; 95% CI 0.57, 1.0). A total of 13% of patients discontinued low-dose ASA therapy. For the overall cohort and for the low-dose ASA-naíve patients at baseline, more than three episodes of upper GI symptoms during the previous week was associated with an increased risk of low-dose ASA discontinuation compared with no episodes of upper GI symptoms during the previous week (hazard ratio [HR] = 2.60; 95% CI 1.00, 6.80, and HR = 7.52; 95% CI 2.57, 22.04, respectively).

Conclusions

Upper GI symptoms can lead to nonadherence to, and discontinuation of, low-dose ASA CV-protective therapy. Patients who initiate low-dose ASA may experience an early onset of upper GI symptoms. (Trial registration number: NCT00681759 [ClinicalTrials.gov Identifier]; AstraZeneca study code: D961FC00004)     

Does a Single-Pill Antihypertensive/Lipid-Lowering Regimen Improve Adherence in US Managed Care Enrollees?

Background

A previous study in 4703 patients suggested that a single-pill combination of amlodipine and atorvastatin is associated with greater adherence to therapy than a two-pill calcium channel antagonist (calcium channel blocker [CCB]) and HMG-CoA reductase inhibitor (statin) regimen. However, the impact of prior medication use on the potential adherence benefits of single-pill amlodipine/atorvastatin has not been studied.

Objective

To compare adherence to single-pill amlodipine/atorvastatin versus two-pill CCB + statin regimens in a large managed care population, stratified according to prior CCB and statin use.

Methods

This retrospective study was conducted among managed care enrollees in the US. Patients included in the analysis had to have a pharmacy claim for single-pill amlodipine/atorvastatin or claims for both a CCB and a statin within any 30-day window between April 2004 and April 2005. Adherence was measured over 6 months following the index date (the date of the first single-pill amlodipine/atorvastatin claim or of the claim for the second medication class for any two-pill CCB + statin regimen) as the proportion of days covered (PDC) by both CCB and statin therapy; patients were considered ‘adherent’ if PDC was ≥80%. Patients were divided into four cohorts based on pre-index CCB and statin use: (i) naive (CCB)/naive (statin); (ii) experienced (CCB)/naive (statin); (iii) naive (CCB)/experienced (statin); and (iv) experienced (CCB)/experienced (statin). Within each cohort, adherence was compared for patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin or other two-pill CCB + statin regimens (including amlodipine or atorvastatin but not both) at index. Multivariable logistic regression with propensity score weighting was used to adjust for covariates, including age, sex and co-morbidities.

Results

In total, 35 430 patients were included in the analysis. At month 6 (after adjusting for covariates), patients in the experienced (CCB)/naive (statin) cohort receiving single-pill amlodipine/atorvastatin were more than twice as likely to be adherent as those receiving two-pill amlodipine + atorvastatin (odds ratio [OR] 2.20; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.75; p < 0.0001). Similarly, patients in the naive (CCB)/experienced (statin) cohort receiving single-pill amlodipine/atorvastatin were more likely to be adherent than those receiving two-pill amlodipine + atorvastatin (OR 1.72; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.81; p < 0.0001). In contrast, in the naive (CCB)/naive (statin) cohort there was no significant difference in adherence between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.00), although patients receiving single-pill amlodipine/atorvastatin were slightly more likely to be adherent than those receiving other two-pill CCB + statin regimens (OR 1.29; p < 0.01). In the experienced (CCB)/experienced (statin) cohort there was also no significant difference between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.08), and only a slightly greater likelihood of achieving adherence to single-pill amlodipine/ atorvastatin versus other two-pill CCB + statin regimens (OR 1.19; p < 0.01).

Conclusions

This large retrospective study confirms previous observations that single-pill amlodipine/ atorvastatin can help improve adherence versus two-pill CCB + statin regimens. However, greater improvements in adherence are likely to be observed in patients with prior experience of either CCB or statin therapy than in those either naive to, or experienced with, both therapies.     

Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis

Purpose

To assess the efficacy and safety of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor—canagliflozin for type 2 diabetes (T2DM).

Methods

A search of Medline (1946–January 2014), Embase (1950–January 2014), and The Cochrane Library for randomized controlled trials of canagliflozin compared to placebo or active comparator in T2DM was performed. Clinical Trials website and unpublished U.S. Food and Drug Administration data were also searched.

Results

Ten trials including 6,701 patients were analyzed. Compared with placebo, canagliflozin produced absolute reductions in glycated hemoglobin A_1c levels when used as monotherapy (weighted mean difference (WMD) ?1.08 %, 95 % confidence interval (CI) [?1.25 to ?0.90], p?p?HbA1c by ?0.21 % (WMD, 95 %CI [?0.33 to ?0.08], p?=?0.001). Canagliflozin led to greater body weight loss (vs. placebo, WMD ?2.81 kg, 95 %CI [?3.26 to ?2.37]; vs. active comparators, WMD ?3.49 kg, 95 %CI [?4.86 to ?2.12]). Hypoglycemia with canagliflozin was similar to placebo or sitagliptin, and was lower than glimepiride (risk ratio (RR) 0.15, 95 %CI [0.10 to 0.22]). Genital tract infections were more common with canagliflozin (vs. placebo, RR 3.76, 95 %CI [2.23 to 6.35]; vs. active comparators, RR 4.95, 95 %CI [3.25 to 7.52]). Similar incidences of urinary tract infections were noted with canagliflozin compared with control groups.

Conclusion

Canagliflozin led to improvements in reducing glycated hemoglobin A_1c levels and body weight with low risk of hypoglycemia in patients with T2DM. Common adverse effects including genital tract infections and osmotic diuresis-related AEs were identified and reviewed. Risks of cardiovascular events are even less certain, and more data on long-term effects are needed.     

Combined effect of common gene variants on response to drug withdrawal therapy in medication overuse headache

Purpose

No information is currently available on genetic determinants of short-term response to drug withdrawal in medication overuse headache (MOH). In the present study, we aimed to evaluate the role of 14 polymorphisms in 8 candidate genes potentially relevant for drug addiction (OPRM1, DRD2, DBH, COMT, BDNF, SLC6A4, 5HT2A, and SLC1A2) as predictors for detoxification outcome of MOH patients at 2 months of follow-up.

Methods

Genotyping was conducted by PCR, PCR-RFLP analysis, or real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. The association between gene variants and risk of unsuccessful detoxification was evaluated by univariate and multivariate logistic regression analyses.

Results

One hundred and eight MOH patients with effective drug withdrawal therapy and 65 MOH patients with unsuccessful detoxification were available for the analysis. In the multivariable logistic regression analysis, triptan overuse (odds ratio (OR) 0.271, 95 % confidence interval (CI) 0.083–0.890, P?=?0.031) and TT genotype carriage of DRD2 NcoI (OR 0.115, 95 % CI 0.014–0.982, P?=?0.048) emerged as independent predictors for unsuccessful detoxification. In addition, carriers of at least four of the six top-ranked gene variants (P?P?=?0.001).

Conclusion

This exploratory study suggests that DRD2 NcoI may be a genetic determinant of detoxification outcome in MOH patients. Our findings also show that an approach based on the combination of multiple genetic markers could be clinically useful for identification of MOH patients at higher risk for unsuccessful detoxification.     

Accuracy of general practitioners’ readings of ECG in primary care

Background

The electrocardiogram (ECG) is a diagnostic test commonly used in daily Primary Care practice. General Practitioners (GP) often feel unsure about their interpretation of ECGs, so they engage external services to provide it.

Aim

To evaluate accuracy of ECG readings done by GPs by comparison with those done by a cardiologist as the gold standard.

Methods

We studied 195 ECGs collected consecutively during first semester of 2010 in an urban Health Centre of Portugal. Each ECG was read by each physician and inter-observer agreement was evaluated. After coding by Novacode, sensitivity and specificity of GP’s readings were calculated.

Results

Inter-observer agreement between GP readings was “good” with an intraclass correlation coefficient of 0.727 (CI 95%: 0.670–0.779). When compared with gold standard, GP achieved a “good” agreement with an intraclass correlation coefficient of 0.712 (CI 95%: 0.659–0.762). The overall accuracy of GP for detecting abnormalities was 81.0% (95%CI: 75.7–85.6%), with a sensitivity of 84.8% (95%CI: 77.3–90.6%) and a specificity of 77.5% (95%CI: 69.7–84.2%). For normal tests, accuracy was 79.9% (95%CI: 74.7–84.3). In the most prevalent classes of abnormalities, accuracy was higher than 90%.

Conclusion

GP showed good skills in reading ECGs in their practice of Primary Care. Better attention should be given to ischemic abnormalities present on ECGs. Key message: General Practitioners demonstrate good skills for reading the ECGs of patients on a primary care centre when compared to the gold standard defined by a cardiologist reading.     

Bevacizumab increases the risk of gastrointestinal perforation in cancer patients: a meta-analysis with a focus on different subgroups

Background

The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event.

Materials and methods

We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies.

Results

A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95 % CI 2.35–4.79, P?<?0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04–9.08, P?=?0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43–5.61, P?=?0.003), gynecologic cancer (RR 3.37, 95% CI 1.71–6.62, P?<?0.001) and prostate cancer (RR 6.01, 95% CI 1.78–20.28, P?=?0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92–4.96, P?<?0.001) or oxaliplatin (RR 2.85, 95% CI 1.07–7.57, P?=?0.036).

Conclusions

Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients.     

Usefulness of Reynolds Risk Score in men with stable angina

Introduction

Recently several risk scores have been proposed that, beyond traditional risk factors, also include additional inflammatory biomarkers underlying atherothrombosis. The Reynolds Risk Score (RRS) is a point scale assessing the risk of cardiovascular events over 10 years, which takes into account for the first time high-sensitivity C-reactive protein. The aim of this study was to establish clinical usefulness of RRS in men with stable coronary artery disease and preserved left ventricular systolic function.

Material and Methods

In total, 119 symptomatic non-diabetic man (mean age 63.9±9.23) who were directed for an elective coronary arteriography were enrolled in the study. Clinical data were collected including the elevated heart rate ≥70 bpm/min, basic laboratory results, placental growth factor and results of coronary angiography. Patients were analyzed related to RRS: low risk <10% (n=50), moderate risk 10-19% (n=46) and high risk >20% (n=23).

Results

Opposite to high RRS patients, in the low risk group more often occurred marginal or none atherosclerotic coronary arteries (13% vs. 44%, P=0.0214). The findings have revealed the relationship between the higher risk score and the lower frequency of marginal or no atherosclerotic coronary arteries (OR=0.19, 95%CI 0.05–0.67).

Conclusions

The Reynolds Risk Score appears to be useful in men with stable coronary artery disease and preserved left ventricular systolic function in stratifying the severity of coronary atherosclerosis.     

Anaphylactoid Reactions to Intravenous <Emphasis Type="Italic">N</Emphasis>-Acetylcysteine during Treatment for Acetaminophen Poisoning

Background

Anaphylactoid reactions to intravenous (IV) N-acetylcysteine (NAC) are well-recognized adverse events during treatment for acetaminophen (APAP) poisoning. Uncertainty exists regarding their incidence, severity, risk factors, and management. We sought to determine the incidence, risk factors, and treatment of anaphylactoid reactions to IV NAC in a large, national cohort of patients admitted to hospital for acetaminophen overdose.

Methods

This retrospective medical record review included all patients initiated on the 21-h IV NAC protocol for acetaminophen poisoning in 34 Canadian hospitals between February 1980 and November 2005. The primary outcome was any anaphylactoid reaction, defined as cutaneous (urticaria, pruritus, angioedema) or systemic (hypotension, respiratory symptoms). We examined the incidence, severity and timing of these reactions, and their association with patient and overdose characteristics using multivariable analysis.

Results

An anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses, of which 398 (75.4%) were cutaneous. Five hundred four (95.4%) reactions occurred during the first 5 h. Of 403 patients administered any medication for these reactions, 371 (92%) received an antihistamine. Being female (adjusted OR 1.24 [95%CI 1.08, 1.42]) and having taken a single, acute overdose (1.24 [95%CI 1.10, 1.39]) were each associated with more severe reactions, whereas higher serum APAP concentrations were associated with fewer reactions (0.79 [95%CI 0.68, 0.92]).

Conclusion

Anaphylactoid reactions to the 21-h IV NAC protocol were uncommon and involved primarily cutaneous symptoms. While the protective effects of higher APAP concentrations are of interest in understanding the pathophysiology, none of the associations identified are strong enough to substantially alter the threshold for NAC initiation.