Evaluation of a multicomponent intervention consisting of education and feedback to reduce benzodiazepine prescriptions by general practitioners: The BENZORED hybrid type 1 cluster randomized controlled trial.

BACKGROUND: Current benzodiazepine (BZD) prescription guidelines recommend short-term use to minimize the risk of dependence, cognitive impairment, and falls and fractures. However, many clinicians overprescribe BZDs and chronic use by patients is common. There is limited evidence on the effectiveness of interventions delivered by general practitioners (GPs) on reducing prescriptions and long-term use of BZDs. We aimed to evaluate the effectiveness of a multicomponent intervention for GPs that seeks to reduce BZD prescriptions and the prevalence of long-term users. METHODS AND FINDINGS: We conducted a multicenter two-arm, cluster randomized controlled trial in 3 health districts in Spain (primary health centers [PHCs] in Balearic Islands, Catalonia, and Valencian Community) from September 2016 to May 2018. The 81 PHCs were randomly allocated to the intervention group (n = 41; 372 GPs) or the control group (n = 40; 377 GPs). GPs were not blinded to the allocation; however, pharmacists, researchers, and trial statisticians were blinded to the allocation arm. The intervention consisted of a workshop about the appropriate prescribing of BZDs and tapering-off long-term BZD use using a tailored stepped dose reduction with monthly BZD prescription feedback and access to a support web page. The primary outcome, based on 700 GPs (351 in the control group and 349 in the intervention group), compared changes in BZD prescriptions in defined daily doses (DDDs) per 1,000 inhabitants per day after 12 months. The 2 secondary outcomes were the proportion of long-term users (≥6 months) and the proportion of long-term users over age 65 years. Intention-to-treat (ITT) analysis was used to assess all clinical outcomes. Forty-nine GPs (21 intervention group and 28 control group) were lost to follow-up. However, all GPs were included in the ITT analysis. After 12 months, there were a statistically significant decline in total BZD prescription in the intervention group compared to the control group (mean difference: -3.24 DDDs per 1,000 inhabitants per day, 95% confidence interval (CI): -4.96, -1.53, p < 0.001). The intervention group also had a smaller number of long-term users. The adjusted absolute difference overall was -0.36 (95% CI: -0.55, -0.16, p > 0.001), and the adjusted absolute difference in long-term users over age 65 years was -0.87 (95% CI: -1.44, -0.30, p = 0.003). A key limitation of this clustered design clinical trial is the imbalance of some baseline characteristics. The control groups have a higher rate of baseline BZD prescription, and more GPs in the intervention group were women, GPs with a doctorate degree, and trainers of GP residents. CONCLUSIONS: A multicomponent intervention that targeted GPs and included educational meeting, feedback about BZD prescriptions, and a support web page led to a statistically significant reduction of BZD prescriptions and fewer long-term users. Although the effect size was small, the high prevalence of BZD use in the general population suggests that large-scale implementation of this intervention could have positive effects on the health of many patients. TRIAL REGISTRATION: ISRCTN ISRCTN28272199.

Evaluating the Implementation of a Multicomponent Intervention Consisting of Education and Feedback on Reducing Benzodiazepine Prescriptions by General Practitioners: BENZORED Hybrid Type I Cluster Randomized Controlled Trial.

BACKGROUND: General practitioners (GPs) in developed countries widely prescribe benzodiazepines (BZDs) for their anxiolytic, hypnotic, and muscle-relaxant effects. Treatment duration, however, is rarely limited, and this results in a significant number of chronic users. Long-term BZD use is associated with cognitive impairment, falls with hip fractures, traffic accidents, and increased mortality. The BENZORED IV trial was a hybrid type-1 trial conducted to evaluate the effectiveness and implementation of an intervention to reduce BZD prescription in primary care. The purpose of this qualitative study was to analyze the facilitators and barriers regarding the implementation of the intervention in primary care settings. METHODS: A qualitative interview study with 40 GPs from three Spanish health districts. Focus group meetings with GPs from the intervention arm of the BENZORED IV trial were held at primary healthcare centers in the three districts. For sampling purposes, the GPs were classified as high or low implementers according to the success of the intervention measured at 12 months. The Consolidated Framework for Implementation Research (CFIR) was used to conduct the meetings and to code, rate, and analyze the data. RESULTS: Three of the 41 CFIR constructs strongly distinguished between high and low implementers: the complexity of the intervention, the individual Stage of Change, and the key stakeholder's engagement. Seven constructs weakly discriminated between the two groups: adaptability in the intervention, external policy and incentives, implementation climate, relative priority, self-efficacy, compatibility, and engaging a formally appointed implementation leader. Fourteen constructs did not discriminate between the two groups, six had insufficient data for evaluation, and eleven had no data for evaluation. CONCLUSIONS: We identified constructs that could explain differences in the efficacy in implementation of the intervention. This information is relevant for the design of successful strategies for implementation of the intervention.

Cost-effectiveness of brief structured interventions to discontinue long-term benzodiazepine use: an economic analysis alongside a randomised controlled trial.

Background: In Spain, long-term use of benzodiazepine is prevalent in 7% of the population; however, this longer-term use lacks clinical benefits, costs €90million per year and side-effects further add extra cost through adverse health outcomes. This study aims to estimate the cost-effectiveness of primary care services stepped dose reduction of long-term benzodiazepines using either Structured Interview with Follow-up (SIF) or Without Follow-up (SIW), compared to Treatment as Usual (TAU). Design: Cost-effectiveness analysis was conducted alongside randomised control utilizing data from three arm cluster randomized trial. Setting: Primary care. Participants: 75 general practitioners were randomised to one of the three arms (TAU, SIW, SIF). Measurements: Cost and Cost per Quality-Adjusted Life Year (QALY) Results: Compared to usual care, providing SIW per participant costs an additional €117.94 and adding patient follow-up, €218.4. As a result of intervention, participants showed a gain of, on average, for SIW 0.0144 QALY (95% CI -0.0137 to 0.0425) and for SIF 0.0340 QALYs (0.0069 to 0.0612). The Incremental Cost Effectiveness Ratio was €8190.28/QALY (SIW) and €6423.53/QALY (SIF). At the Spanish reimbursement threshold (€45,000 per QALY) the chance interventions are cost effective is 79.8% for SIW and 97.7% for SIF. Conclusions: Brief structured interventions to discontinue long-term benzodiazepine use represent value for money, particularly with scheduled follow-up appointments, and would represent a cost-effective investment by the Spanish healthcare to reduce prevalence of long-term use.

Intervention to reduce benzodiazepine prescriptions in primary care, study protocol of a hybrid type 1 cluster randomised controlled trial: the BENZORED study.

INTRODUCTION: Benzodiazepines (BZDs) are mainly used to treat anxiety and sleep disorders, and are often prescribed for long durations, even though prescription guidelines recommend short-term use due to the risk of dependence, cognitive impairment, and falls and fractures. Education of general practitioners (GPs) regarding the prescription of BZDs may reduce the overuse and of these drugs.The aims of this study are to analyse the effectiveness of an intervention targeted to GPs to reduce BZD prescription and evaluate the implementation process. METHODS AND ANALYSIS: The healthcare centres in three regions of Spain (Balearic Islands, Catalonia and Community of Valencia) will be randomly allocated to receive a multifactorial intervention or usual care (control). GPs in the intervention group will receive a 2-hour workshop about best-practice regarding BZD prescription and BZD deprescribing, monthly feedback about their BZD prescribing practices and access to a support web page. Outcome measures for each GP are the defined daily dosage per 1000 inhabitants per day and the proportion of long-term BZD users at 12 months. Data will be collected from the electronic prescription database of the public health system, and will be subjected to intention-to-treat analysis. Implementation will be evaluated by mixed methods following the five domains of the Consolidated Framework For Implementation Research. ETHICS AND DISSEMINATION: This study was approved by the Balearic Islands Ethical Committee of Clinical Research (IB3065/15), l'IDIAP Jordi Gol Ethical Committee of Clinical Research (PI 15/0148) and Valencia Primary Care Ethical Committee of Clinical Research (P16/024). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN28272199.

Efficacy of two interventions on the discontinuation of benzodiazepines in long-term users: 36-month follow-up of a cluster randomised trial in primary care.

BACKGROUND: Primary care interventions that promote cessation of benzodiazepine (BZD) use in long-term users are effective at 1 year, but their efficacy at 3 years is uncertain. AIM: To assess the 3-year efficacy of two primary care interventions delivered by GPs on cessation of BZD use in long-term users. DESIGN AND SETTING: Multicentre, three-arm, cluster randomised, controlled trial, with random allocation at the GP level. METHOD: Seventy-five GPs and 532 patients were randomly allocated to three groups: usual care (control), structured intervention with stepped-dose reduction and follow-up visits (SIF), or structured intervention with written stepped-dose reduction (SIW). The primary outcome was BZD use at 36 months. RESULTS: At 36 months, 66/168 patients (39.2%) in the SIW group, 79/191 patients (41.3%) in the SIF group, and 45/173 patients (26.0%) in the control group had discontinued BZD use. The relative risks (RR) adjusted by cluster were 1.51 (95% CI = 1.10 to 2.05; P = 0.009) in the SIW group and 1.59 (95% CI = 1.15 to 2.19; P = 0.005) in the SIF group. A total of 131/188 patients (69.7%) who successfully discontinued BZD use at 12 months remained abstinent at 36 months. The groups showed no significant differences in anxiety, depression, or sleep dissatisfaction at 36 months. CONCLUSION: The interventions were effective on cessation of BZD use; most patients who discontinued at 12 months remained abstinent at 3 years. Discontinuation of BZD use did not have a significant effect on anxiety, depression, or sleep quality.

Safety during the monitoring of diabetic patients: trial teaching course on health professionals and diabetics - SEGUDIAB study.

BACKGROUND: Safety for diabetic patients means providing the most suitable treatment for each type of diabetic in order to improve monitoring and to prevent the adverse effects of drugs and complications arising from the disease. The aim of this study is to analyze the effect of imparting educational interventions to health professionals regarding the safety of patients with Diabetes Mellitus (DM). DESIGN: A cluster randomized trial with a control group. SETTING AND SAMPLE: The study analyzed ten primary healthcare centres (PHC) covering approximately 150,000 inhabitants. Two groups of 5 PHC were selected on the basis of their geographic location (urban, semi-urban and rural), their socio-economic status and the size of their PHC, The interventions and control groups were assigned at random. The study uses computerized patient records to individually assess subjects aged 45 to 75 diagnosed with type 1 and type 2 DM, who met the inclusion conditions and who had the variables of particular interest to the study. Trial: The educational interventions consisted of a standardized teaching course aimed at doctors and nurses. The course lasted 6 hours and was split into three 2-hour blocks with subsequent monthly refresher courses. MEASUREMENT: For the health professionals, the study used the Diabetes Attitude Scale (DAS-3) to assess their attitudes and motivation when monitoring diabetes. For the patients, the study assessed factors related to their degree of control over the disease at onset, 6, 12 and 24 months. MAIN VARIABLES: levels of HbA1c. ANALYSIS: The study analyzed the effect of the educational interventions both on the attitudes and motivations of health professionals and on the degree of control over the diabetes in both groups. DISCUSSION: Imparting educational interventions to health professionals would improve the monitoring of diabetic patients. The most effective model involves imparting the course to both doctors and nurses. However, these models have not been tested on our Spanish population within the framework of primary healthcare. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01087541.

Comparative efficacy of two primary care interventions to assist withdrawal from long term benzodiazepine use: a protocol for a clustered, randomized clinical trial.

BACKGROUND: Although benzodiazepines are effective, long-term use is not recommended because of potential adverse effects; the risks of tolerance and dependence; and an increased risk of hip fractures, motor vehicle accidents, and memory impairment. The estimated prevalence of long-term benzodiazepine use in the general population is about 2,2 to 2,6%, is higher in women and increases steadily with age. Interventions performed by General Practitioners may help patients to discontinue long-term benzodiazepine use. We have designed a trial to evaluate the effectiveness and safety of two brief general practitioner-provided interventions, based on gradual dose reduction, and will compare the effectiveness of these interventions with that of routine clinical practice. METHODS/DESIGN: In a three-arm cluster randomized controlled trial, general practitioners will be randomly allocated to: a) a group in which the first patient visit will feature a structured interview, followed by visits every 2-3 weeks to the end of dose reduction; b) a group in which the first patient visit will feature a structured interview plus delivery of written instructions to self-reduce benzodiazepine dose, or c) routine care. Using a computerized pharmaceutical prescription database, 495 patients, aged 18-80 years, taking benzodiazepine for at least 6 months, will be recruited in primary care health districts of three regions of Spain (the Balearic Islands, Catalonia, and Valencia). The primary outcome will be benzodiazepine use at 12 months. The secondary outcomes will include measurements of anxiety and depression symptoms, benzodiazepine dependence, quality of sleep, and alcohol consumption. DISCUSSION: Although some interventions have been shown to be effective in reducing benzodiazepine consumption by long-term users, the clinical relevance of such interventions is limited by their complexity. This randomized trial will compare the effectiveness and safety of two complex stepped care interventions with that of routine care in a study with sufficient statistical power to detect clinically relevant differences. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN13024375.

Effects of annual influenza vaccination on winter mortality in elderly people with chronic heart disease.

AIMS: Although there is general agreement for the recommendation of the influenza vaccine to elderly and high-risk adults, the magnitude of clinical effectiveness and benefit from the annual vaccination is controversial. In this study, we have assessed the effects of annual influenza vaccination on winter mortality in older adults with chronic heart disease. METHODS AND RESULTS: Cohort study that included 1340 Spanish community-dwelling individuals 65 years or older who had chronic heart disease (congestive heart failure or coronary artery disease) followed from January 2002 to April 2005. Annual influenza vaccine status was a time-varying condition and primary outcome was all-cause death during the study period. Multivariable Cox proportional-hazard models adjusted by age, sex, and comorbidity were used to evaluate vaccine effectiveness. Influenza vaccination was associated with a significant reduction of 37% in the adjusted risk of winter mortality during the overall period 2002-2005. The attributable mortality risk reduction in vaccinated people was 8.2 deaths per 1000 person-winters. We estimated that one death was prevented for every 122 annual vaccinations (ranging between 49 in Winter 2005 and 455 in Winter 2003). CONCLUSION: Our results suggest a benefit from the influenza vaccination and support an annual vaccination strategy for elderly people with cardiac diseases.