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.

Multiple health behaviour change primary care intervention for smoking cessation, physical activity and healthy diet in adults 45 to 75 years old (EIRA study): a hybrid effectiveness-implementation cluster randomised trial.

BACKGROUND: This study aimed to evaluate the effectiveness of a) a Multiple Health Behaviour Change (MHBC) intervention on reducing smoking, increasing physical activity and adherence to a Mediterranean dietary pattern in people aged 45-75 years compared to usual care; and b) an implementation strategy. METHODS: A cluster randomised effectiveness-implementation hybrid trial-type 2 with two parallel groups was conducted in 25 Spanish Primary Health Care (PHC) centres (3062 participants): 12 centres (1481 participants) were randomised to the intervention and 13 (1581 participants) to the control group (usual care). The intervention was based on the Transtheoretical Model and focused on all target behaviours using individual, group and community approaches. PHC professionals made it during routine care. The implementation strategy was based on the Consolidated Framework for Implementation Research (CFIR). Data were analysed using generalised linear mixed models, accounting for clustering. A mixed-methods data analysis was used to evaluate implementation outcomes (adoption, acceptability, appropriateness, feasibility and fidelity) and determinants of implementation success. RESULTS: 14.5% of participants in the intervention group and 8.9% in the usual care group showed a positive change in two or all the target behaviours. Intervention was more effective in promoting dietary behaviour change (31.9% vs 21.4%). The overall adoption rate by professionals was 48.7%. Early and final appropriateness were perceived by professionals as moderate. Early acceptability was high, whereas final acceptability was only moderate. Initial and final acceptability as perceived by the participants was high, and appropriateness moderate. Consent and recruitment rates were 82.0% and 65.5%, respectively, intervention uptake was 89.5% and completion rate 74.7%. The global value of the percentage of approaches with fidelity ≥50% was 16.7%. Eight CFIR constructs distinguished between high and low implementation, five corresponding to the Inner Setting domain. CONCLUSIONS: Compared to usual care, the EIRA intervention was more effective in promoting MHBC and dietary behaviour change. Implementation outcomes were satisfactory except for the fidelity to the planned intervention, which was low. The organisational and structural contexts of the centres proved to be significant determinants of implementation effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03136211 . Registered 2 May 2017, "retrospectively registered".

Assessing the feasibility and acceptability of a cluster-randomized study of cognitive behavioral therapy for chronic insomnia in a primary care setting.

BACKGROUND: Cognitive behavioral therapy for chronic insomnia (CBT-i) is the treatment of choice for this condition but is underutilized in patients who attend primary care. The purpose of the present feasibility-pilot study was to assess the feasibility and acceptability of a cluster-randomized study of CBT-i in a primary care setting. METHODS: This study, performed at two primary health care centers in Majorca, Spain, was a mixed methods feasibility-pilot study of a parallel cluster-randomized design comparing CBT-i and usual care (UC). Patients were included if they were 18 to 65 years-old; had diagnoses of chronic insomnia according to the Insomnia Severity Index (ISI ≥ 8); had insomnia for more than 3 months. Twenty-five GPs and nurses and 32 patients were randomly allocated to two groups. The main outcome of the intervention was improvement of dimensions of sleep quality, measured using the Spanish version of the Pittsburgh Sleep Quality Index, at baseline and at 3 months after the intervention. Other primary outcomes of the study were the feasibility and applicability of the intervention, collected through nominal groups. A thematic analysis was performed to classify primary care provider (PCP) proposals. Additionally, we assessed the recruitment process, compliance with the intervention sessions, and patient retention. RESULTS: We adapted the CBT-i approach of Morin to a primary care context. After intervention training, PCPs expressed the need for more extensive training in the different aspects of the therapy and the discussion of more cases. PCPs considered the intervention as adequate but wanted fewer but longer sessions as well as to discard the cognitive restructuring component. PCPs considered it crucial to prepare each session in advance and to establish a specific agenda for the CBT-i. Regular reminders given to PCPs and patients were suggested to improve study participation. Compared to the UC group, higher proportions of patients in the intervention group had short sleep latency, slept for longer than 5 h, and had fewer sleep disruptions. CONCLUSIONS: This feasibility-pilot study identified several key issues that must be addressed before performing a CBT-i intervention in future clinical trial in a primary care setting. TRIAL REGISTRATION: NCT04565223 . (Clinical trials.gov) Registered 1 September 2020-Retrospectively registered.

Correction to: Complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in primary health care (EIRA study): study protocol for a hybrid trial.

It has been highlighted the original article (1) contained a typesetting mistake in the authorship, and that author Caterine Vicens was omitted.

Complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in primary health care (EIRA study): study protocol for a hybrid trial.

BACKGROUND: Health promotion is a key process of current health systems. Primary Health Care (PHC) is the ideal setting for health promotion but multifaceted barriers make its integration difficult in the usual care. The majority of the adult population engages two or more risk behaviours, that is why a multiple intervention might be more effective and efficient. The primary objectives are to evaluate the effectiveness, the cost-effectiveness and an implementation strategy of a complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in PHC. METHODS: This study is a cluster randomised controlled hybrid type 2 trial with two parallel groups comparing a complex multiple risk behaviour intervention with usual care. It will be carried out in 26 PHC centres in Spain. The study focuses on people between 45 and 75 years who carry out two or more of the following unhealthy behaviours: tobacco use, low adherence to the Mediterranean dietary pattern or insufficient physical activity level. The intervention is based on the Transtheoretical Model and it will be made by physicians and nurses in the routine care of PHC practices according to the conceptual framework of the "5A's". It will have a maximum duration of 12 months and it will be carried out to three different levels (individual, group and community). Incremental cost per quality-adjusted life year gained measured by the tariffs of the EuroQol-5D questionnaire will be estimated. The implementation strategy is based on the "Consolidated Framework for Implementation Research", a set of discrete implementation strategies and an evaluation framework. DISCUSSION: EIRA study will determine the effectiveness and cost-effectiveness of a complex multiple risk intervention and will provide a better understanding of implementation processes of health promotion interventions in PHC setting. It may contribute to increase knowledge about the individual and structural barriers that affect implementation of these interventions and to quantify the contextual factors that moderate the effectiveness of implementation. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03136211 .Retrospectively registered on May 2, 2017.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review.

PURPOSE: Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS: We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS: The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). CONCLUSIONS: Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care.

LESS-PHARMA Study: Identifying and Deprescribing Potentially Inappropriate Medication in the Elderly Population with Excessive Polypharmacy in Primary Care.

Potentially inappropriate medication (PIM) increases adverse drug reactions and mortality, especially in excessively polymedicated patients. General practitioners are often in charge of this process. Some tools have been created to support them in this matter. This study aimed to measure the amount of potentially inappropriate medication among excessively polymedicated patients using several supporting tools and assess the feasibility of these tools in primary care. Several explicit deprescribing criteria were used to identify potentially inappropriate medications. The level of agreement between all the criteria and the acceptance by the general practitioner (GP) was also measured. We analysed whether the drugs proposed for deprescribing were eventually withdrawn after twelve months. The total number of drugs prescribed was 2038. Six hundred and forty-nine drugs (31.8%) were considered potentially inappropriate by at least one of the tools. GPs agreed with the tools in 56.7% of the cases. In a 12-month period, 109 drugs, representing 29.6% of the drugs that GPs agreed to deprescribe, were withdrawn. Elderly excessively polymedicated patients accumulated a great number of PIMs. The use of deprescribing supporting tools, such as explicit criteria, is feasible in primary care, and these tools are well accepted by the GPs. However, eventual withdrawal was carried out in less than half of the cases.

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.

Young woman diagnosed with paraganglioma in primary care.

A 15-year-old young woman was referred to the emergency room for admission by her general practitioner after receiving the results of urinary metanephrines and catecholamines requested to study the tachycardia, sweating and headaches that she had been presenting progressively last year. Imaging tests showed a large right supraumbilical para-aortic paraganglioma that was successfully removed with surgery after previous medical preparation with adrenergic blockers. Genetic testing showed a heterozygous mutation of the gene succinate dehydrogenase-B. The classic triad of symptoms in these disorders consists of headaches, sweating and tachycardia, usually accompanied by hypertension. We wanted to present this case, a challenging diagnosis of paraganglioma in primary care.

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.

Cognitive function after clinical remission in patients with melancholic and non-melancholic depression: a 6 month follow-up study.

BACKGROUND: Cognitive symptoms are core symptoms with an impact on functioning in depression. Remission is considered as the main objective of the management and treatment of depression. This study was aimed to compare cognitive performance between melancholic (MelD) and non-melancholic depression (NMelD) and to determine whether these cognitive alterations remain after clinical remission. METHODS: We performed a 6 month follow-up study of 88 melancholic and non-melancholic depressive patients. Sociodemographic and clinical characteristics were recorded. Depression was examined using the Hamilton Depression Rating Scale and the CORE Index for Melancholia. Cognitive performance was assessed with the Trail Making Test (TMT), the Digit Span subtest of the WAIS-III, Stroop Colour Word Test (SCWT), the Tower of London (TOL DX), the Controlled Oral Word Association Test (FAS), Semantic Verbal Fluency and Finger Tapping Test (FTT). RESULTS: MelD patients show worse performance than N-MelD at baseline, with significant differences at Digit Span subtest of WAIS Part I and Part II, SCWT Part I and Part II, TOL DX, Total Problem Solving, Total Execution Time and FTT- Preferred hand. Cognitive impairment remains at six months follow-up after clinical remission in MelD. In the comparison between remitted and non-remitted patients, cognitive impairment in Trail Making Test Part B and Verbal and Semantic Fluency (Animals) remains after clinical remission in MelD group but not in non-melancholic patients. LIMITATIONS: The use of psychopharmacological treatment and the small sample of melancholic patients. CONCLUSIONS: Patients with MelD do not improve cognitive performance despite clinical remission compared with remitted NMelD patients. The persistence of some cognitive dysfunctions in MelD remitted patients could represent a trait marker of a different depressive subtype and not be secondary to disease severity.