FlowUTI: An interactive web-application for optimizing the use of flow cytometry as a screening tool in urinary tract infections.

Due to the high prevalence of patients attending with urinary tract infection (UTI) symptoms, the use of flow-cytometry as a rapid screening tool to avoid unnecessary cultures is becoming a widely used system in clinical practice. However, the recommended cut-points applied in flow-cytometry systems differ substantially among authors, making it difficult to obtain reliable conclusions. Here, we present FlowUTI, a shiny web-application created to establish optimal cut-off values in flow-cytometry for different UTI markers, such as bacterial or leukocyte counts, in urine from patients with UTI symptoms. This application provides a user-friendly graphical interface to perform robust statistical analysis without a specific training. Two datasets are analyzed in this manuscript: one composed of 204 urine samples from neonates and infants (≤3 months old) attended in the emergency department with suspected UTI; and the second dataset including 1174 urines samples from an elderly population attended at the primary care level. The source code is available on GitHub (https://github.com/GuillermoMG-HUVR/Microbiology-applications/tree/FlowUTI/FlowUTI). The web application can be executed locally from the R console. Alternatively, it can be freely accessed at https://covidiario.shinyapps.io/flowuti/. FlowUTI provides an easy-to-use environment for evaluating the efficiency of the urinary screening process with flow-cytometry, reducing the computational burden associated with this kind of analysis.

Prognostic Significance of the Relative Load of KPC-Producing Klebsiella pneumoniae within the Intestinal Microbiota in a Prospective Cohort of Colonized Patients.

Increased relative bacterial load of KPC-producing Klebsiella pneumoniae (KPC-KP) within the intestinal microbiota has been associated with KPC-KP bacteremia. Prospective observational study of KPC-KP adult carriers with a hospital admission at recruitment or within the three prior months (January 2018 to February 2019). A qPCR-based assay was developed to measure the relative load of KPC-KP in rectal swabs (RLKPC, proportion of blaKPC relative to 16S rRNA gene copy number). We generated Fine-Gray competing risk and Cox regression models for survival analysis of all-site KPC-KP infection and all-cause mortality, respectively, at 90 and 30 days. The median RLKPC at baseline among 80 KPC-KP adult carriers was 0.28% (range 0.001% to 2.70%). Giannella Risk Score (GRS) was independently associated with 90-day and 30-day all-site infection (adjusted subdistribution hazard ratio [aHR] 1.23, 95% CI = 1.15 to 1.32, P < 0.001). RLKPC (adjusted hazard ratio [aHR] 1.04, 95% CI = 1.01 to 1.07, P = 0.008) and age (aHR 1.05, 95% CI = 1.01 to 1.10, P = 0.008) were independent predictors of 90-day all-cause mortality in a Cox model stratified by length of hospital stay (LOHS) ≥20 days. An adjusted Cox model for 30-day all-cause mortality, stratified by LOHS ≥14 days, included RLKPC (aHR 1.03, 95% CI = 1.00 to 1.06, P = 0.027), age (aHR 1.10, 95% CI = 1.03 to 1.18, P = 0.004), and severe KPC-KP infection (INCREMENT-CPE score >7, aHR 2.96, 95% CI = 0.97 to 9.07, P = 0.057). KPC-KP relative intestinal load was independently associated with all-cause mortality in our clinical setting, after adjusting for age and severe KPC-KP infection. Our study confirms the utility of GRS to predict infection risk in patients colonized by KPC-KP. IMPORTANCE The rapid dissemination of carbapenemase-producing Enterobacterales represents a global public health threat. Increased relative load of KPC-producing Klebsiella pneumoniae (KPC-KP) within the intestinal microbiota has been associated with an increased risk of bloodstream infection by KPC-KP. We developed a qPCR assay for quantification of the relative KPC-KP intestinal load (RLKPC) in 80 colonized patients and examined its association with subsequent all-site KPC-KP infection and all-cause mortality within 90 days. Giannella Risk Score, which predicts infection risk in colonized patients, was independently associated with the development of all-site KPC-KP infection. RLKPC was not associated with all-site KPC-KP infection, possibly reflecting the large heterogeneity in patient clinical conditions and infection types. RLKPC was an independent predictor of all-cause mortality within 90 and 30 days in our clinical setting. We hypothesize that KPC-KP load may behave as a surrogate marker for the severity of the patient's clinical condition.

Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.

Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals.

Use of a personalised depression intervention in primary care to prevent anxiety: a secondary study of a cluster randomised trial.

BACKGROUND: In the predictD-intervention, GPs used a personalised biopsychosocial programme to prevent depression. This reduced the incidence of major depression by 21.0%, although the results were not statistically significant. AIM: To determine whether the predictD-intervention is effective at preventing anxiety in primary care patients without depression or anxiety. DESIGN AND SETTING: Secondary study of a cluster randomised trial with practices randomly assigned to either the predictD-intervention or usual care. This study was conducted in seven Spanish cities from October 2010 to July 2012. METHOD: In each city, 10 practices and two GPs per practice, as well as four to six patients every recruiting day, were randomly selected until there were 26-27 eligible patients for each GP. The endpoint was cumulative incidence of anxiety as measured by the PRIME-MD screening tool over 18 months. RESULTS: A total of 3326 patients without depression and 140 GPs from 70 practices consented and were eligible to participate; 328 of these patients were removed because they had an anxiety syndrome at baseline. Of the 2998 valid patients, 2597 (86.6%) were evaluated at the end of the study. At 18 months, 10.4% (95% CI = 8.7% to 12.1%) of the patients in the predictD-intervention group developed anxiety compared with 13.1% (95% CI = 11.4% to 14.8%) in the usual-care group (absolute difference = -2.7% [95% CI = -5.1% to -0.3%]; P = 0.029). CONCLUSION: A personalised intervention delivered by GPs for the prevention of depression provided a modest but statistically significant reduction in the incidence of anxiety.

Patterns of primary care among persons with schizophrenia: the role of patients, general practitioners and centre factors.

BACKGROUND: Patients with schizophrenia and related disorders have more physical problems than the general population. Primary care professionals play an important role in the care of these patients as they are the main entry point into the healthcare system. We aimed to identify patient, general practitioner, and primary care centre factors associated with the number of visits of patients with schizophrenia and related disorders to general practitioners. METHODS: A descriptive, cross-sectional study was conducted in 13 primary care centres belonging to the Clinical Management Unit of Mental Health of the Regional Hospital of Málaga, Spain. The eligible population was composed of patients with schizophrenia and related disorders attending the primary care centres in the study area, and the general practitioners who attend these patients. Our dependent variable was the total number of general practitioner visits made by patients with schizophrenia and related disorders during the 3.5-year observation period. The independent variables were grouped into three: (a) patient variables (sociodemographic and clinical), (b) general practitioner variables, and (c) primary care centre characteristics. Descriptive, bivariate, and multivariate analyses using the random forest method were performed. RESULTS: A total of 259 patients with schizophrenia and related disorders, 96 general practitioners, and 13 primary care centres were included. The annual mean was 3.9 visits per patient. The results showed that younger general practitioners, patients who were women, patients who were married, some primary care centres to which the patient belonged, taking antipsychotic medication, presenting any cardiovascular risk factor, and more frequency of mental health training sessions at the primary care centre were associated with an increased number of visits to general practitioners. CONCLUSIONS: The only general practitioner variable that was associated with the number of visits was age, the older the less contact. There were also patient variables involved in the number of visits. Finally, mental health training for general practitioners was important for these professionals to manage patients with schizophrenia and related disorders.

Recording of cardiovascular risk factors by general practitioners in patients with schizophrenia.

BACKGROUND: Patients with schizophrenia and related disorders (SRD) are more predisposed to having cardiovascular risk factors (CVRFs) compared to the general population due to a combination of lifestyle factors and exposure to antipsychotic medications. We aimed to analyse the documentation practices of CVRFs by general practitioners (GPs) and its associations with patient variables in a sample of persons with SRD. METHODS: An observational, cross-sectional study was conducted in 13 primary care centres (PCCs) in Malaga (Spain). The population comprised all patients with SRD who were in contact with a GP residing in the study area. The number of CVRFs (type 2 diabetes mellitus, hypertension, hypercholesterolaemia, obesity and smoking) recorded by GPs were analysed by considering patients' demographic and clinical variables and use of primary care services. We performed descriptive, bivariate and multivariate regression analyses. RESULTS: A total of 494 patients were included; CVRFs were not recorded in 59.7% of the patients. One CVRF was recorded in 42.1% of patients and two or more CVRFs were recorded in 16.1% of patients. Older age, living in an urban area and a higher number of visits to the GP were associated with a higher number of CVRFs recorded. CONCLUSION: The main finding in this study is that both patients' demographic variables as well as use of primary care services were found to be related to the documentation of CVRFs in patients with SRD by GPs.

Family physicians' views on participating in prevention of major depression. The predictD-EVAL qualitative study.

BACKGROUND: The predictD intervention, a multicomponent intervention delivered by family physicians (FPs), reduced the incidence of major depression by 21% versus the control group and was cost-effective. A qualitative methodology was proposed to identify the mechanisms of action of these complex interventions. PURPOSE: To seek the opinions of these FPs on the potential successful components of the predictD intervention for the primary prevention of depression in primary care and to identify areas for improvement. METHOD: Qualitative study with FPs who delivered the predictD intervention at 35 urban primary care centres in seven Spanish cities. Face-to-face semi-structured interviews adopting a phenomenological approach. The data was triangulated by three investigators using thematic analysis and respondent validation was carried out. RESULTS: Sixty-seven FPs were interviewed and they indicated strategies used to perform the predictD intervention, including specific communication skills such as empathy and the activation of patient resources. They perceived barriers such as lack of time and facilitators such as prior acquaintance with patients. FPs recognized the positive consequences of the intervention for FPs, patients and the doctor-patient relationship. They also identified strategies for future versions and implementations of the predictD intervention. CONCLUSIONS: The FPs who carried out the predictD intervention identified factors potentially associated with successful prevention using this program and others that could be improved. Their opinions about the predictD intervention will enable development of a more effective and acceptable version and its implementation in different primary health care settings.

Severe Mental Illness in Community Mental Health Care in Spain: Prevalence and Related Factors.

The aims of this study were to determine the prevalence of severe mental illness (SMI) in patients in contact with mental health services and to determine the factors associated with SMI. A total of 260 patients who met diagnostic criteria for SMI were assessed using the Global Assessment of Functioning (GAF) scale and Health of the Nation Outcome Scales. The overall prevalence of SMI was 6.08 per thousand. According to the three different cutoff points with GAF, the prevalence of SMI ranged from 5.38 per thousand under the weak criterion (GAF < 70) to 1.01 per thousand under the strict criterion (GAF < 50). In the regression model, the dependent variable (presence of SMI) was defined using a GAF < 60, and the variables independently associated with the dependent variable were years of disease duration since diagnose, mental health service use, alcohol or other substance abuse, and depressive anxiety and other psychological symptoms.

A personalized intervention to prevent depression in primary care: cost-effectiveness study nested into a clustered randomized trial.

BACKGROUND: Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care. METHODS: Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months. RESULTS: With a willingness-to-pay threshold of €10,000 (£8568) the probability of cost-effectiveness oscillated from 83% (societal perspective) to 89% (health perspective). If the threshold was increased to €30,000 (£25,704), the probability of being considered cost-effective was 94% (societal perspective) and 96%, respectively (health perspective). The sensitivity analysis confirmed these results. CONCLUSIONS: Compared with usual care, an intervention based on personal predictors of risk of depression implemented by GPs is a cost-effective strategy to prevent depression. This type of personalized intervention in primary care should be further developed and evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01151982. Registered on June 29, 2010.

Effectiveness of Psychological and/or Educational Interventions in the Prevention of Anxiety: A Systematic Review, Meta-analysis, and Meta-regression.

Importance: To our knowledge, no systematic reviews or meta-analyses have been conducted to assess the effectiveness of preventive psychological and/or educational interventions for anxiety in varied populations. Objective: To evaluate the effectiveness of preventive psychological and/or educational interventions for anxiety in varied population types. Data Sources: A systematic review and meta-analysis was conducted based on literature searches of MEDLINE, PsycINFO, Web of Science, EMBASE, OpenGrey, Cochrane Central Register of Controlled Trials, and other sources from inception to March 7, 2017. Study Selection: A search was performed of randomized clinical trials assessing the effectiveness of preventive psychological and/or educational interventions for anxiety in varying populations free of anxiety at baseline as measured using validated instruments. There was no setting or language restriction. Eligibility criteria assessment was conducted by 2 of us. Data Extraction and Synthesis: Data extraction and assessment of risk of bias (Cochrane Collaboration's tool) were performed by 2 of us. Pooled standardized mean differences (SMDs) were calculated using random-effect models. Heterogeneity was explored by random-effects meta-regression. Main Outcomes and Measures: Incidence of new cases of anxiety disorders or reduction of anxiety symptoms as measured by validated instruments. Results: Of the 3273 abstracts reviewed, 131 were selected for full-text review, and 29 met the inclusion criteria, representing 10 430 patients from 11 countries on 4 continents. Meta-analysis calculations were based on 36 comparisons. The pooled SMD was -0.31 (95% CI, -0.40 to -0.21; P < .001) and heterogeneity was substantial (I2 = 61.1%; 95% CI, 44% to 73%). There was evidence of publication bias, but the effect size barely varied after adjustment (SMD, -0.27; 95% CI, -0.37 to -0.17; P < .001). Sensitivity analyses confirmed the robustness of effect size results. A meta-regression including 5 variables explained 99.6% of between-study variability, revealing an association between higher SMD, waiting list (comparator) (ß = -0.33 [95% CI, -0.55 to -0.11]; P = .005) and a lower sample size (lg) (ß = 0.15 [95% CI, 0.06 to 0.23]; P = .001). No association was observed with risk of bias, family physician providing intervention, and use of standardized interviews as outcomes. Conclusions and Relevance: Psychological and/or educational interventions had a small but statistically significant benefit for anxiety prevention in all populations evaluated. Although more studies with larger samples and active comparators are needed, these findings suggest that anxiety prevention programs should be further developed and implemented.

Effectiveness of Psychological and Educational Interventions to Prevent Depression in Primary Care: A Systematic Review and Meta-Analysis.

PURPOSE: Although evidence exists for the efficacy of psychosocial interventions to prevent the onset of depression, little is known about its prevention in primary care. We aimed to evaluate the effectiveness of psychological and educational interventions to prevent depression in primary care. METHODS: We conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs) examining the effect of psychological and educational interventions to prevent depression in nondepressed primary care attendees. We searched MEDLINE, PsycINFO, Web of Science, OpenGrey Repository, Cochrane Central Register of Controlled Trials, and other sources up to May 2016. At least 2 reviewers independently evaluated the eligibility criteria, extracted data, and assessed the risk of bias. We calculated standardized mean differences (SMD) using random-effects models. RESULTS: We selected 14 studies (7,365 patients) that met the inclusion criteria, 13 of which were valid to perform a meta-analysis. Most of the interventions had a cognitive-behavioral orientation, and in only 4 RCTs were the intervention clinicians primary care staff. The pooled SMD was -0.163 (95%CI, -0.256 to -0.070; P = .001). The risk of bias and the heterogeneity (I2 = 20.6%) were low, and there was no evidence of publication bias. Meta-regression detected no association between SMD and follow-up times or SMD and risk of bias. Subgroup analysis suggested greater effectiveness when the RCTs used care as usual as the comparator compared with those using placebo. CONCLUSIONS: Psychological and educational interventions to prevent depression had a modest though statistically significant preventive effect in primary care. Further RCTs using placebo or active comparators are needed.

Time to positivity of blood cultures in patients with bloodstream infections: A useful prognostic tool.

OBJECTIVE: The time to positivity (TTP) of blood cultures in patients with bloodstream infections (BSIs) has been considered to be a possible prognostic tool for some bacterial species. However, notable differences have been found between sampling designs and statistical methods in published studies to date, which makes it difficult to compare results or to derive reliable conclusions. Our objective was to evaluate the clinical and microbiological implications of TTP among patients with BSI caused by the most common pathogens. METHODS: A total of 361 episodes of BSI were reported for 332 patients. The survival of the entire cohort was measured from the time of blood culture sampling. In order to compare our results with those of previous studies, TTP was divided in three different groups based on log rank (short TTP <12h; medium TTP ≥12h to ≤27h, and long TTP >27h). Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HR). RESULTS: The Cox proportional hazard model revealed that TTP is an independent predictor of mortality (HR=1.00, p=0.031) in patients with BSIs. A higher mortality was found in the group of patients with the shortest TTP (<12h) (HR=2.100, p=0.047), as well as those with longest TTP (>27h) (HR=3.277, p=0.031). CONCLUSIONS: It seems that TTP may provide a useful prognostic tool associated with a higher risk of mortality, not only in patients with shorter TTP, but also in those with longer TTP.

Intervention to Prevent Major Depression in Primary Care: A Cluster Randomized Trial.

BACKGROUND: Not enough is known about universal prevention of depression in adults. OBJECTIVE: To evaluate the effectiveness of an intervention to prevent major depression. DESIGN: Multicenter, cluster randomized trial with sites randomly assigned to usual care or an intervention. (ClinicalTrials.gov: NCT01151982). SETTING: 10 primary care centers in each of 7 cities in Spain. PARTICIPANTS: Two primary care physicians (PCPs) and 5236 nondepressed adult patients were randomly sampled from each center; 3326 patients consented and were eligible to participate. INTERVENTION: For each patient, PCPs communicated individual risk for depression and personal predictors of risk and developed a psychosocial program tailored to prevent depression. MEASUREMENTS: New cases of major depression, assessed every 6 months for 18 months. RESULTS: At 18 months, 7.39% of patients in the intervention group (95% CI, 5.85% to 8.95%) developed major depression compared with 9.40% in the control (usual care) group (CI, 7.89% to 10.92%) (absolute difference, -2.01 percentage points [CI, -4.18 to 0.16 percentage points]; P = 0.070). Depression incidence was lower in the intervention centers in 5 cities and similar between intervention and control centers in 2 cities. LIMITATION: Potential self-selection bias due to nonconsenting patients. CONCLUSION: Compared with usual care, an intervention based on personal predictors of risk for depression implemented by PCPs provided a modest but nonsignificant reduction in the incidence of major depression. Additional study of this approach may be warranted. PRIMARY FUNDING SOURCE: Institute of Health Carlos III.

Evaluation and optimization of the Sysmex UF1000i system for the screening of urinary tract infection in primary health care elderly patients.

OBJECTIVE: Urinary tract infections (UTIs) are a common problem in the elderly population. Urine culture is still considered the "gold standard" to diagnose infection in this population. However, urine cultures are laborious and costly, and most samples will yield no growth. METHODS: An evaluation was made of the Sysmex UF-1000i flow cytometer as a screening tool for UTI in an elderly population older than 65 years who lived in the community, using 346 urine samples submitted for culture. RESULTS: The Receiver Operating Characteristic (ROC) analysis showed a significant difference (P<0.01) between 0.98 bacteria area under the curve value and 0.82 of white blood cells (WBC). The combination of both counts for screening did not show any improvement in specificity or sensitivity. According to our data, the use of a single cut-off point of 200bacteria/µL is suggested, in which the sensitivity and specificity were 99.11% and 91.59%, respectively, with a NPV of 99.49%. Moreover, this cut-off value could avoid 60.24% of the samples to be cultured, with a minimal false negative results rate of 0.87%. CONCLUSIONS: The stratification of age groups stratification helps in selecting a more adjusted Sysmex UF1000i cut-off limit, leading to an improvement in the screening parameters that would imply a better management of these infections, as well as a high reduction in the workload and cost savings.

Preventing the onset of major depression based on the level and profile of risk of primary care attendees: protocol of a cluster randomised trial (the predictD-CCRT study).

BACKGROUND: The 'predictD algorithm' provides an estimate of the level and profile of risk of the onset of major depression in primary care attendees. This gives us the opportunity to develop interventions to prevent depression in a personalized way. We aim to evaluate the effectiveness, cost-effectiveness and cost-utility of a new intervention, personalized and implemented by family physicians (FPs), to prevent the onset of episodes of major depression. METHODS/DESIGN: This is a multicenter randomized controlled trial (RCT), with cluster assignment by health center and two parallel arms. Two interventions will be applied by FPs, usual care versus the new intervention predictD-CCRT. The latter has four components: a training workshop for FPs; communicating the level and profile of risk of depression; building up a tailored bio-psycho-family-social intervention by FPs to prevent depression; offering a booklet to prevent depression; and activating and empowering patients. We will recruit a systematic random sample of 3286 non-depressed adult patients (1643 in each trial arm), nested in 140 FPs and 70 health centers from 7 Spanish cities. All patients will be evaluated at baseline, 6, 12 and 18 months. The level and profile of risk of depression will be communicated to patients by the FPs in the intervention practices at baseline, 6 and 12 months. Our primary outcome will be the cumulative incidence of major depression (measured by CIDI each 6 months) over 18 months of follow-up. Secondary outcomes will be health-related quality of life (SF-12 and EuroQol), and measurements of cost-effectiveness and cost-utility. The inferences will be made at patient level. We shall undertake an intention-to-treat effectiveness analysis and will handle missing data using multiple imputations. We will perform multi-level logistic regressions and will adjust for the probability of the onset of major depression at 12 months measured at baseline as well as for unbalanced variables if appropriate. The economic evaluation will be approached from two perspectives, societal and health system. DISCUSSION: To our knowledge, this will be the first RCT of universal primary prevention for depression in adults and the first to test a personalized intervention implemented by FPs. We discuss possible biases as well as other limitations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01151982.