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.

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study.

BACKGROUND: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. METHODS: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. RESULTS: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). CONCLUSIONS: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Longitudinal association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators.

BACKGROUND & AIMS: The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year. METHODS: We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial. Dietary intake information was obtained at baseline, 6- and 12-months from a validated 143-item semi-quantitative food-frequency questionnaire, and CQI (range: 4 to 20) was calculated based on four dietary criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio. Overall and regional adiposity (total body fat, visceral fat and android-to-gynoid fat ratio) was quantified using dual-energy X-ray absorptiometry at all three time points. Multiple adjusted linear mixed-effects models were used to assess associations between concurrent changes in repeatedly measured CQI and adiposity over time. RESULTS: After controlling for potential confounding factors, a 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (ß -0.067 z-score, 95% CI -0.088; -0.046, p < 0.001), android-to-gynoid fat ratio (-0.038, -0.059; -0.017, p < 0.001), and total fat (-0.064, -0.080; -0.047, p < 0.001). Fibre intake and the ratio of wholegrain/total grain showed the strongest inverse associations with all adiposity indicators. CONCLUSIONS: In this prospective cohort of older adults with overweight/obesity and MetS, we found that improvements in dietary carbohydrate quality over a year were associated with concurrent favorable changes in visceral and overall fat deposition. These associations were mostly driven by dietary fibre and the wholegrain/total grain ratio. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized. CONTROLLED TRIAL: (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

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.

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.

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.

Withdrawal from long-term benzodiazepine use: randomised trial in family practice.

BACKGROUND: The long-term use of benzodiazepines is highly prevalent in developed societies and is not devoid of risks. Withdrawing patients from these drugs is often difficult. Tapering off benzodiazepines has been shown to be a good strategy for discontinuing their long-term use. AIM: To establish the efficacy of an intervention programme for reducing the chronic use of benzodiazepines. DESIGN OF STUDY: Randomised, two-arm, parallel, non-blinded controlled trial. SETTING: Three urban healthcare centres covering a population of 50,000 inhabitants (Mallorca, Spain). METHOD: Adult patients (n = 139) taking benzodiazepines daily for more than a year and visited by their family physician were randomised into an intervention group (n = 73) that received standardised advice and a tapering off schedule with biweekly follow-up visits, or into a control group (n = 66), that was managed following routine clinical practice. Both were followed for a year. RESULTS: Patients achieved withdrawal or reduced their dose by at least 50% after 6 and 12 months. Abstinence and withdrawal symptoms were also measured. Both groups were homogeneous for personal, clinical and psychological characteristics and for benzodiazepine use. Only two patients from each group were lost to follow-up. After 12 months, 33 (45.2%) patients in the intervention group and six (9.1%) in the control group had discontinued benzodiazepine use; relative risk = 4.97 (95% confidence interval [CI] = 2.2 to 11.1), absolute risk reduction = 0.36 (95% CI = 0.22 to 0.50). For every three interventions, one patient achieved withdrawal. Sixteen (21.9%) subjects from the intervention group and 11 (16.7%) controls reduced their initial dose by more than 50%. CONCLUSION: Standardised advice given by the family physician, together with a tapering off schedule, is effective for withdrawing patients from long-term benzodiazepine use and is feasible in primary care.

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.