Papers by David Prieto-Merino
Additional file 1 of Estimating proportion of days covered (PDC) using real-world online medicine suppliers' datasets
Additional file 1: Figure S1. Comparison of PDCs by patient characteristics.

Microorganisms, 2021
Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a high impact on the... more Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a high impact on the comfort of those who are affected and long-term treated with corticosteroids with limited efficacy and a high prevalence of relapses. Because of the limited effectiveness of these treatments, new strategies for recovery from AD lesions are continually being explored. In this article, we describe the gut microbiome changes achieved in a recently published clinical trial with the probiotic formulation Bifidobacterium animalis subsp. lactis CECT 8145, Bifidobacterium longum CECT 7347, and Lacticaseibacillus casei CECT 9104 (formerly Lactobacillus casei CECT 9104), showing a significant improvement in SCORAD (scoring atopic dermatitis) index in children (4–17 years) with AD (Clinicaltrials.gov identifier: NCT02585986). The present gut microbiome post hoc study showed no significant changes in diversity (Shannon and Simpson indexes) after probiotic consumption. In the probiotic group, genera...
Project submitted to Health Technology Assessment programme

Animals, 2020
The aim of this work is to establish the most suitable proteolysis conditions to obtain bovine ca... more The aim of this work is to establish the most suitable proteolysis conditions to obtain bovine casein hydrolysates containing peptides with antioxidant and antihypertensive capacity. To this end, the proteolytic activity of Cynara scolymus L. flower extracts was characterized on whole bovine casein, evaluating the effect of several factors (pH, temperature, substrate concentration, enzyme concentration, and hydrolysis time). The optimal conditions to carry out the hydrolysis with the C. scolymus L. extract were as follows: pH 6.2, 50 °C, and 0.023 mg·mL−1 of extract-protein concentration. A Michaelis constant (Km) value of 5.66 mg·mL−1 and a maximum rate of reaction (Vmax) of 8.47 mUAbs∙min−1 were observed. The optimal hydrolysis time was 17 h. The casein hydrolysates obtained with these conditions contained peptides with antioxidant activity (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity: 30.89%; Trolox equivalent antioxidant capacity (TEAC) against 2,2’-azino-bi...

Lancet (London, England), Jan 13, 2018
Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined t... more Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics. We did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155. We obtained data for 40 138 patients from two randomised trials of tranexamic acid i...

Nutrients, 2022
Background: Evidence suggests that bioactive peptides reduce hypertension and affect certain meta... more Background: Evidence suggests that bioactive peptides reduce hypertension and affect certain metabolic pathways. Methods: Fifty-four volunteers with stage 1 prehypertension and/or hypercholesterolemia and/or basal glucose >100 mg/dL were recruited and randomized to pork dry-cured ham (n = 35) or cooked ham (placebo group; n = 19) for 28 days. After a wash-out period, meat products were changed for 28 additional days. Bioactive peptides composition and enzyme inhibitory activities of both products were characterized. Treatment comparisons for the main effects were made using a two (treatment) × two (times) repeated measures minus the effect of cooked ham (placebo). Results: 24 h mean systolic and diastolic pressures decreased up to 2.4 mmHg in the dry-cured ham period (treatment effect, p = 0.0382 y p = 0.0233, respectively) as well as the number of systolic pressure measures > 135 mmHg (treatment effect, p = 0.0070). Total cholesterol levels also decreased significantly after ...

Cureus
Chronic pelvic pain syndrome (CPPS) is permanent pelvic pain of unknown etiology. Current theorie... more Chronic pelvic pain syndrome (CPPS) is permanent pelvic pain of unknown etiology. Current theories suggest a multifactorial origin for CPPS, including urinary pathologies, psychosocial factors, prostate inflammation, infection, central sensitization of the nervous system, and muscular contractures or fibrosis. As there are no defined treatment protocols for CPPS, a multimodal approach is recommended. The objective of this study was to evaluate the impact of a manual therapy treatment protocol on pain, urinary symptoms, and overall quality of life. Materials and Methods Twenty-three men aged 47.36 ± 10.11 years were recruited consecutively by urologists practicing at two hospitals. All men presented prostatic tenderness with no other positive clinical history, urine cultures, or echography studies. Patients underwent six manual therapy sessions (three during the first week and three every two weeks after that) performed by a single osteopath or physiotherapist. The intervention protocol addressed the treatment of muscle structures, fascial mechanics, vascularization, innervation, emotional factors, and the need for information. The questionnaires used to evaluate outcomes included the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptoms Score (IPSS), and a Visual Analog Scale (VAS) for pain, and the Hospital Anxiety and Depression Scale (HADS). Data were evaluated using Chi-squared or paired difference tests by an external researcher. Results The mean NIH-CPSI scores recorded for our study cohort decreased by 7.69 points (30.92%; p<0.0005; 95% CI 4.02-10.52). IPSS measurements decreased by 3.20 points (22.18%; p=0.009; 95% CI 1.00-6.09), although the item addressing quality of life decreased by 1.67 points only (31.99%; p<0.0005; 95% CI 0.94-2.33). The VAS score also decreased by 2.20 points (38.6%; p<0.0005; 95% CI 1.45-2.73). Changes in HADS scores were not statistically significant. Conclusions Based on patient responses, this case series revealed that manual therapy improved urinary symptoms, pain, and quality of life.
Additional file 1: of Cardiovascular Disease among Syrian refugees: a descriptive study of patients in two Médecins Sans Frontières clinics in northern Lebanon
Annex 1. Extracts from "Integrated Clinical Pathway for Patients at High Cardiovascular Risk... more Annex 1. Extracts from "Integrated Clinical Pathway for Patients at High Cardiovascular Risk", MSF. (DOCX 82 kb)

Journal of Global Health Science, 2021
Background: We evaluated the impact of an integrated community-based hypertension intervention on... more Background: We evaluated the impact of an integrated community-based hypertension intervention on hypertension awareness (defined as prior diagnosis of hypertension among persons with elevated blood pressure), prevalence of hypertension, and behavioural risk factors for hypertension. Methods: The community-based hypertension improvement program implements an integrated package of interventions in one health district in Ghana. The project is evaluated using a quasi-experimental design consisting of population-based cross-sectional surveys (the focus of this paper) in an intervention and a comparison districts, plus a cohort study in the intervention district-only. The cohort study determined hypertension control. Results: At baseline, we interviewed 2,400 respondents (1,200 each from the Lower Manya Krobo (intervention district) and Akuapim South (comparison district) and interviewed 2,533 adults aged 30 years or older from same districts at endline-1,306 from the Lower Manya Krobo and 1,227 from Akuapim South districts. Hypertension awareness significantly increased in the intervention district from 47.7%; 95% confidence interval (CI) (42.0-53.7) at baseline to 59.2%; 95% CI (53.8-64.6) at endline, while in the comparison district, there was a small, non-significant decrease from 44.7%; 95% CI (38.8-50.8) to 36.6%; 95% CI (31.3-42.2). There is strong evidence of difference between these two districts OR (P = 0.005). There were no significant differences in changes of hypertension prevalence or treatment from baseline to endline between the two districts The proportion of people that know more than 2 risk factors increased in the control groups (odds ratio [OR], 1.770; 95% CI, 1.242-2.5142) while this does not change significantly in the intervention group (OR, 0.865; 95% CI, 0.61-1.210). Conclusion: This integrated community-based program improved hypertension awareness, and some behavioural risk factors, but not hypertension prevalence at the community level.
Integration of diabetes care and associated costs: MSF experience in Democratic Republic of Congo and Swaziland
F1000Research, 2018

Nutrients, 2021
Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit ... more Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit and vegetable (FV) consumption usually report intention-to-treat (ITT) analysis as the main outcome. These analyses compare the randomly assigned groups and accept that some individuals may not follow the recommendations received in their group. The ITT analysis is useful to quantify the global effect of promoting the consumption of FV in a population (effectiveness) but, if non-adherence is significant in the RCT, they cannot estimate the specific effect in the individuals that increased their FV consumption (efficacy). To calculate the efficacy of FV consumption, a per protocol analysis (PP) would have to be carried out, in which groups of individuals are compared according to their actual adherence to FV consumption, regardless of the group to which they were assigned; unfortunately, many RCTs do not report the PP analysis. The objective of this article is to apply a new method to est...

Conflict and Health, 2019
Background: Literature on the burden and management of atherosclerotic cardiovascular disease (AS... more Background: Literature on the burden and management of atherosclerotic cardiovascular disease (ASCVD) in humanitarian settings is limited. This study aimed to describe patient characteristics and explore both service use and use of recommended secondary prevention drugs in Syrian refugee patients with ASCVD attending two Médecins Sans Frontières (MSF) clinics in Lebanon. Methods: This study comprised a cross-sectional survey of ASCVD patients attending either MSF clinic over a fourweek period in early 2017. Using descriptive statistics, we explored patient demographic characteristics, cardiovascular risk factors and assessed ASCVD secondary prevention medication prescription and patient adherence with a 7-day self-report scale. A retrospective study of routine clinical data explored workload and trends in patient loss to follow-up. We performed logistic regression modelling to explore risk factors for loss to follow-up. Results: We included 514 patients with ASCVD in the cross-sectional study, performed in 2017. Most (61.9%) were male and mean age was 60.4 years (95% CI, 59.6-61.3). Over half (58.8%) underwent revascularization and 26.1% had known cerebrovascular disease. ASCVD risk factors included 51.8% with diabetes and 72.2% with hypertension. While prescription (75.7 to 98.2%) and self-reported adherence rates (78.4 to 93.9%) for individual ASCVD secondary prevention drugs (ACE-inhibitor, statin and antiplatelet) were high, the use of all three was low at 41.3% (CI 95% : 37.0-45.6). The 5-year retrospective cohort study (ending April 2017) identified 1286 patients with ASCVD and 16, 618 related consultations (comprising 24% of all NCD consultations). Over one third (39.7%) of patients were lost to follow-up, with lower risk among men. Conclusions: The burden of ASCVD within MSF clinics in Lebanon is substantial. Although prescription and adherence of individual secondary prevention drugs is acceptable, overall use of the three recommended drugs is suboptimal. Loss to follow-up rates were high. Further studies are needed to evaluate innovative strategies to increase the use of the multiple recommended drugs, and to increase the retention of patients with ASCVD in the care system.

Nephrology Dialysis Transplantation, 2019
INTRODUCTION: Pneumonia is a leading cause of hospitalization and mortality worldwide, and a comm... more INTRODUCTION: Pneumonia is a leading cause of hospitalization and mortality worldwide, and a common infection in patients with manifest CKD. Little is known about the acute and long-term adverse health events of pneumonia in persons with chronic kidney disease (CKD). METHODS: We studied adults with CKD accessing healthcare in Stockholm, during 2006-11, and who had not previously been diagnosed with lower-respiratory tract infections. We used Cox regression with pneumonia as a time-varying exposure, adjusted for socio-demographics, comorbidities and medications to estimate hazard ratios [HRs (95% confidence intervals)] for the events of death, major adverse cardiovascular events (MACE), acute kidney injury (AKI), CKD progression, or subsequent hospitalization for urinary tract infections (UTIs)/sepsis. Cataract and knee/joint replacement served as negative control outcomes. RESULTS: We identified 71,931 adults with confirmed CKD (mean age 77 years, 59% women); Of these, 8,440 (24%) were subsequently diagnosed with pneumonia; Incident pneumonia was associated with ten times higher adjusted mortality risk during the first 90 days (HR 9.9; 95%CI 9.4-10.4) and double the mortality beyond 90 days from pneumonia diagnosis (2.0; 1.9-2.1). Incident pneumonia was similarly associated with higher adjusted risk of MACE (<90 days: 12.6;12.0-13.3; 90 days: 1.5; 1.4-1.6). The adjusted risk of CKD progression and UTI/sepsis hospitalization was highest within 90 days from pneumonia but remained elevated thereafter. For AKI, the association with incident pneumonia was only seen within 90 days. Neither risk of cataract nor knee/joint replacement was related to pneumonia. CONCLUSIONS: Incident pneumonia was strongly associated with increased risks of MACE, CKD progression, severe UTI/sepsis and death, with risks highest soon after pneumonia diagnosis but extending beyond 90 days. Our findings highlight the susceptibility for adverse outcomes of CKD patients following pneumonia diagnosis, and may inform clinical decisions regarding vaccination strategies.

JAMA Dermatology, 2018
IMPORTANCE Oral intake of new probiotic formulations may improve the course of atopic dermatitis ... more IMPORTANCE Oral intake of new probiotic formulations may improve the course of atopic dermatitis (AD) in a young population. OBJECTIVE To determine whether a mixture of oral probiotics is safe and effective in the treatment of AD symptoms and to evaluate its influence on the use of topical steroids in a young population. DESIGN, SETTING, AND PARTICIPANTS A 12-week randomized, double-blind, placebo-controlled intervention trial, from March to June 2016, at the outpatient hospital Centro Dermatológico Estético de Alicante, Alicante, Spain. Observers were blinded to patient groupings. Participants were children aged 4 to 17 years with moderate atopic dermatitis. The groups were stratified and block randomized according to sex, age, and age of onset. Patients were ineligible if they had used systemic immunosuppressive drugs in the previous 3 months or antibiotics in the previous 2 weeks or had a concomitant diagnosis of intestinal bowel disease or signs of bacterial infection. INTERVENTIONS Twelve weeks with a daily capsule containing freeze-dried powder with 10 9 total colony-forming units of the probiotic strains Bifidobacterium lactis CECT 8145, B longum CECT 7347, and Lactobacillus casei CECT 9104 and maltodextrin as a carrier, or placebo (maltodextrin-only capsules). MAIN OUTCOMES AND MEASURES SCORAD index score and days of topical steroid use were analyzed. RESULTS Fifty children (26 [50%] female; mean [SD] age, 9.2 [3.7] years) participated. After 12 weeks of follow-up, the mean reduction in the SCORAD index in the probiotic group was 19.2 points greater than in the control group (mean difference, −19.2; 95% CI, −15.0 to −23.4). In relative terms, we observed a change of −83% (95% CI, −95% to −70%) in the probiotic group and −24% (95% CI, −36% to −11%) in the placebo group (P < .001). We found a significant reduction in the use of topical steroids to treat flares in the probiotic arm (161 of 2084 patient-days [7.7%]) compared with the control arm (220 of 2032 patient-days [10.8%]; odds ratio, 0.63; 95% CI, 0.51 to 0.78). CONCLUSIONS AND RELEVANCE The mixture of probiotics was effective in reducing SCORAD index and reducing the use of topical steroids in patients with moderate AD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02585986

Scientific reports, Jan 23, 2017
We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk ... more We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk among Japanese men of working age (25-64 years) using the 2010 Japanese national survey data for occupation and industry-specific death rates. Poisson regression models were used to estimate the age-adjusted incident rate ratios by lung, gastric, and colorectal cancers, with manufacturing used as the referent occupation or industry. Unemployed Japanese men and those in manufacturing had an 8-11-fold increased risk of lung, gastric and colorectal cancer. The highest mortality rates for lung and colorectal cancer by occupation were "administrative and managerial" (by occupation) and "mining" (by industry). For gastric cancer, the highest mortality rate was "agriculture" (by occupation) and "mining" (by industry). By occupation; Japanese men in service occupations, those in administrative and managerial positions, those in agriculture, forestry and fi...
Development of an electronic clinical decision support system: “mWellcare - an Integrated mHealth System for Prevention and Care of Chronic Diseases”
Endocrine Abstracts, 2016

Lancet (London, England), Dec 17, 2017
Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Mille... more Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000-15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival. We increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1-59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of model...

JACC: Clinical Electrophysiology, 2021
The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS)... more The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 AE 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverterdefibrillator prescription.

Journal of Pharmaceutical Policy and Practice, 2021
Background The proportion of days covered (PDC) is used to estimate medication adherence by looki... more Background The proportion of days covered (PDC) is used to estimate medication adherence by looking at the proportion of days in which a person has access to the medication, over a given period of interest. This study aimed to adapt the PDC algorithm to allow for plausible assumptions about prescription refill behaviour when applied to data from online pharmacy suppliers. Methods Three PDC algorithms, the conventional approach (PDC1) and two alternative approaches (PDC2 and PDC3), were used to estimate adherence in a real-world dataset from an online pharmacy. Each algorithm has different denominators and increasing levels of complexity. PDC1, the conventional approach, is the total number of days between first dispensation and a defined end date. PDC2 counts the days until the end of supply date. PDC3 removes from the denominator specifically defined large gaps between refills, which could indicate legitimate reasons for treatment discontinuation. The distribution of the three PDCs...

UNSTRUCTURED With over five million covid-19 positive cases declared, more than 30,000 deaths and... more UNSTRUCTURED With over five million covid-19 positive cases declared, more than 30,000 deaths and more than two million patients recovered, we would expect that the highly digitalised health systems of the high-income countries would have collected, processed and ana-lysed large quantities of clinical data from COVID-19 patients. Those analysis should have served to answer important clinical questions such as: what are the risk factors for becoming infected? What are good clinical variables to predict prognosis? What kind of patients are more likely to survive mechanical ventilation? Are there clinical sub-phenotypes of the disease? All these, and many more, are crucial questions to improve our clinical strategies against the epidemic and save as many lives as possible until we find a vaccine and effective treatments. One might assume that in the era of Big Data and Machine Learning there would be an army of scientist crunching petabytes of clinical data to solve these questions. Ho...
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Papers by David Prieto-Merino