COVID-19 and pregnancy: A European study on pre- and post-infection medication use.

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

Home Blood Pressure Self-monitoring plus Self-titration of Antihypertensive Medication for Poorly Controlled Hypertension in Primary Care: the ADAMPA Randomized Clinical Trial.

BACKGROUND: Patient empowerment through pharmacological self-management is a common strategy in some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure. OBJECTIVE: This study aimed to assess self-monitoring plus self-titration of antihypertensive medication versus usual care for reducing systolic blood pressure (SBP) at 12 months in poorly controlled hypertensive patients. DESIGN: The ADAMPA study was a pragmatic, controlled, randomized, non-masked clinical trial with two parallel arms in Valencia, Spain. PARTICIPANTS: Hypertensive patients older than 40 years, with SBP over 145 mmHg and/or diastolic blood pressure (DBP) over 90 mmHg, were recruited from July 2017 to June 2018. INTERVENTION: Participants were randomized 1:1 to usual care versus an individualized, pre-arranged plan based on self-monitoring plus self-titration. MAIN MEASURE: The primary outcome was the adjusted mean difference (AMD) in SBP between groups at 12 months. KEY RESULTS: Primary outcome data were available for 312 patients (intervention n=156, control n=156) of the 366 who were initially recruited. The AMD in SBP at 12 months (main analysis) was -2.9 mmHg (95% CI, -5.9 to 0.1, p=0.061), while the AMD in DBP was -1.9 mmHg (95% CI, -3.7 to 0.0, p=0.052). The results of the subgroup analysis were consistent with these for the main outcome measures. More patients in the intervention group achieved good blood pressure control (<140/90 mmHg) at 12 months than in the control group (55.8% vs 42.3%, difference 13.5%, 95% CI, 2.5 to 24.5%, p=0.017). At 12 months, no differences were observed in behavior, quality of life, use of health services, or adverse events. CONCLUSION: Self-monitoring plus self-titration of antihypertensive medication based on an individualized pre-arranged plan used in primary care may be a promising strategy for reducing blood pressure at 12 months compared to usual care, without increasing healthcare utilization or adverse events. TRIAL REGISTRATION: EudraCT, number 2016-003986-25 (registered 17 March 2017) and clinicaltrials.gov , NCT03242785.

Estimating disease incidence rates and transition probabilities in elderly patients using multi-state models: a case study in fragility fracture using a Bayesian approach.

BACKGROUND: Multi-state models are complex stochastic models which focus on pathways defined by the temporal and sequential occurrence of numerous events of interest. In particular, the so-called illness-death models are especially useful for studying probabilities associated to diseases whose occurrence competes with other possible diseases, health conditions or death. They can be seen as a generalization of the competing risks models, which are widely used to estimate disease-incidences among populations with a high risk of death, such as elderly or cancer patients. The main advantage of the aforementioned illness-death models is that they allow the treatment of scenarios with non-terminal competing events that may occur sequentially, which competing risks models fail to do. METHODS: We propose an illness-death model using Cox proportional hazards models with Weibull baseline hazard functions, and applied the model to a study of recurrent hip fracture. Data came from the PREV2FO cohort and included 34491 patients aged 65 years and older who were discharged alive after a hospitalization due to an osteoporotic hip fracture between 2008-2015. We used a Bayesian approach to approximate the posterior distribution of each parameter of the model, and thus cumulative incidences and transition probabilities. We also compared these results with a competing risks specification. RESULTS: Posterior transition probabilities showed higher probabilities of death for men and increasing with age. Women were more likely to refracture as well as less likely to die after it. Free-event time was shown to reduce the probability of death. Estimations from the illness-death and the competing risks models were identical for those common transitions although the illness-death model provided additional information from the transition from refracture to death. CONCLUSIONS: We illustrated how multi-state models, in particular illness-death models, may be especially useful when dealing with survival scenarios which include multiple events, with competing diseases or when death is an unavoidable event to consider. Illness-death models via transition probabilities provide additional information of transitions from non-terminal health conditions to absorbing states such as death, what implies a deeper understanding of the real-world problem involved compared to competing risks models.

Clinical outcomes of nonvitamin K oral anticoagulants and acenocoumarol for stroke prevention in contemporary practice: A population-based propensity-weighted cohort study.

AIMS: Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice. METHODS: This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed. RESULTS: We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2). CONCLUSIONS: No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.

Group-based Trajectory Models to Assess Quality of INR Control and Its Association With Clinical Outcomes.

BACKGROUND: The Time in Therapeutic Range (TTR) is the gold-standard measure used to assess the quality of oral anticoagulation with vitamin K antagonists. However, TTR is a static measure, and International Normalized Ratio (INR) control is a dynamic process. Group-based Trajectory Models (GBTM) can address this dynamic nature by classifying patients into different trajectories of INR control over time. OBJECTIVES: The objective of this study was to assess the quality of INR control in a population-based cohort of new users of vitamin K antagonist with a diagnosis of atrial fibrillation using GBTM. METHODS: We classified patients into different trajectories according to their propensity for being adequately anticoagulated over their first year of treatment using GBTM, and we evaluated the association between trajectories and relevant clinical outcomes over the following year. RESULTS: We included 8024 patients in the cohort who fulfilled the inclusion criteria; the mean number of INR determinations over the first year of treatment was 13.9. We identified 4 differential trajectories of INR control: Optimal (9.7% of patients, TTR: 83.8%), Improving (27.4% of patients, TTR: 61.2%), Worsening (28%; TTR: 69.1%), and Poor control (34.9%; TTR: 41.5%). In adjusted analysis, Poor and Worsening control patients had a higher risk of death than Optimal control patients (hazard ratio: 1.79; IC 95%, 1.36-2.36 and hazard ratio: 1.36; IC 95%, 1.02-1.81, respectively). Differences in other outcomes did not achieve statistical significance, except for a reduced risk of transient ischemic attack in the Improving Control group. CONCLUSIONS: GBTM may contribute to a better understanding and assessment of the quality of oral anticoagulation and may be used in addition to traditional, well-established measures such as TTR.

Antipsychotic utilization patterns among patients with schizophrenic disorder: a cross-national analysis in four countries.

PURPOSE: The aim of the present study was to describe antipsychotic utilization patterns among patients with schizophrenic disorder in Italy, Spain, the UK, and the USA. METHODS: A retrospective cohort study was conducted. Patients aged 15 and over with schizophrenic disorder were identified in the Caserta claims database (Italy), the Valencia electronic medical record (EMR) database (Spain), in The Health Improvement Network EMR database (UK), and in databases of publicly and privately insured populations in the United States (US). RESULTS: The frequency of first-generation or second-generation antipsychotic use and of long-acting or other formulations was described. Persistence to antipsychotics was estimated. Overall, 1,403,240 patients with schizophrenic disorder having a total of 765,573 new antipsychotic treatment episodes were identified. The median follow-up time ranged from 0.8 (IQR 0.2-1.9) years in the US commercially-insured population to 1.2 (IQR 0.1-1.7) years in the Spanish population. Second-generation antipsychotics were more frequently used than first-generation antipsychotics in all countries (on average, from 64.4% in the UK to 87% in US): the use of this class increased over time in Italy, Spain, and US (Medicaid). The use of long-acting formulations was heterogeneous across countries, but generally much lower than other formulations. Persistence to antipsychotic treatment at 1 year was low in all countries, ranging from 40 in Spain to 30% in Italy. CONCLUSIONS: Antipsychotic utilization was heterogeneous among persons with schizophrenic disorder. Nevertheless, low persistence was an issue in all the countries, as less than half of the patients continued their treatment beyond 1 year.

Rationale and design of a pragmatic clinical trial to assess the impact of self-monitoring blood pressure at home and self-titration of antihypertensive medication in poorly controlled hypertension: the ADAMPA study protocol.

BACKGROUND: Lack of control of hypertension is one of the most prevalent problems encountered by general practitioners (GPs). Self-measured blood pressure monitoring at home (SMBP) and self-titration of medication could be a good strategy to improve hypertension management, however, evidence is limited and not conclusive. We aimed to assess the effectiveness, in the primary care setting, of an intervention that includes educational components, SMBP and self-titration of antihypertensive medication to decrease systolic blood pressure compared to usual care, in a population with poorly controlled hypertension, during a 12-month period. METHODS: Pragmatic, controlled, randomized, unblinded clinical trial with two parallel groups assigned in a ratio of 1:1 to self-management (which includes educational components, SBMP and self-titration of antihypertensive medication based on a patient's GP's pre-established adjustment plan) or to usual care (with educational components too). DISCUSSION: If the data from this trial show positive results, the study may contribute to a change of strategy in the treatment of hypertension, focusing on the patient as the main actor to achieve blood pressure control. Furthermore, this approach might contribute to the financial sustainability of the National Health Service. TRIAL REGISTRATION: This trial has been registered in the database with reference number EudraCT: 2016-003986-25. Registered 05 May 2017, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-003986-25.

Antibiotic Use in Children - A Cross-National Analysis of 6 Countries.

OBJECTIVES: To describe the rates of pediatric antibiotic use across 6 countries on 3 continents. STUDY DESIGN: Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries. RESULTS: A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population. CONCLUSIONS: We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.

Did HEDIS get it right? Evaluating the quality of a quality measure: adherence to ß-blockers and cardiovascular outcomes after myocardial infarction.

BACKGROUND: As an example of the process that could be used to evaluate and optimize the performance of quality measures in routine practice, we evaluated whether the Healthcare Effectiveness Data and Information Set (HEDIS) measure assessing the "persistence of ß-blocker treatment after a heart attack" correlates with post-myocardial infarction (MI) outcomes and whether or not there are alternative specifications of this construct which are better predictors and/or may be more easily applied. RESEARCH DESIGN: The study included a retrospective cohort of 8672 post-MI patients 18 years old and above. We assessed the strength of the association between the different adherence measures and the composite clinical outcome using multivariable Cox models. We compared the predictive capacity of each adherence definition model to one that did not contain adherence by computing the change in C-statistics and the continuous net reclassification improvement indices (NRIs). RESULTS: Adherence was associated with clinical outcome reductions, with hazard ratios ranging from 0.48 (95% CI, 0.27-0.85) to 0.81 (95% CI, 0.67-0.99). None of the adherence measures, including the HEDIS definition, significantly changed the C-statistic relative to a model that did not include adherence. However, the short-term adherence measure (having 72 d covered during the first 90 d postdischarge) showed a large change in NRI (correctly reclassifying 12% of cases and 16% of noncases; NRI: 28%; 95% CI, 22%-38%), although did not significantly differ from the change in NRI with the HEDIS measure. CONCLUSIONS: We identified an adherence measure that showed a predictive ability as good as that of the HEDIS definition to measure ß-blocker use after MI, halving the time of assessment required, and thus, allowing for the implementation of quality improvement interventions in a more timely manner.

[Translated article] Therapeutic management, adherence, and clinical outcomes of heart failure in Andalucía. ANDALIC Protocol.

Heart failure is a prevalent syndrome with high mortality rates, representing a significant economic burden in terms of healthcare. The lack of systematic information about the treatment and adherence of patients with heart failure limits the understanding of these aspects and potentially the improvement of clinical outcomes. OBJECTIVE: To describe the clinical characteristics, therapeutic management, adherence, persistence, and clinical results, as well as the association between these variables, in a cohort of patients with heart failure in Andalusia. DESIGN: This study will be an observational, population-based, retrospective cohort study. Data of patients discharged from an Andalusian hospital with a diagnosis of heart failure between 2014 and 2023 will be extracted from the Andalusian population health database. ANALYSIS: The statistical analysis will incorporate the following strategies: (1) Descriptive analysis of the characteristics of the population cohort, adherence measures, and clinical outcomes. (2) Bivariate analyses to study the association of covariates with adherence, persistence, and clinical results. (3) Multivariate logistic regression and Cox regression analysis including relevant covariates. (4) To evaluate changes over time, multivariate Poisson regression models will be used. By conducting this comprehensive study, we aim to gain valuable insights into the clinical characteristics, treatment management, and adherence of heart failure patients in Andalusia, as well as to identify factors that may influence clinical outcomes. These findings could be critical both for the development of optimised strategies that improve medical care and quality of life of patients and for mitigating the health burden of HF in the region.

Therapeutic management, adherence, and clinical outcomes of heart failure in Andalucía. ANDALIC Protocol. / Manejo terapéutico, adherencia y resultados clínicos de la insuficiencia cardiaca en Andalucía. Protocolo ANDALIC.

Heart failure is a prevalent syndrome with high mortality rates, representing a significant economic burden in terms of healthcare. The lack of systematic information about the treatment and adherence of patients with heart failure limits the understanding of these aspects and potentially the improvement of clinical outcomes. OBJECTIVE: To describe the clinical characteristics, therapeutic management, adherence, persistence and clinical results, as well as the association between these variables, in a cohort of patients with heart failure in Andalusia. DESIGN: This study will be an observational, population-based, retrospective cohort study. Data of patients discharged from an Andalusian hospital with a diagnosis of heart failure between 2014 and 2023 will be extracted from the Andalusian population health database. ANALYSIS: The statistical analysis will incorporate the following strategies: 1) Descriptive analysis of the characteristics of the population cohort, adherence measures, and clinical outcomes. 2) Bivariate analyses to study the association of covariates with adherence, persistence and clinical results. 3) Multivariate logistic regression and Cox regression analysis including relevant covariates. 4) To evaluate changes over time, multivariate Poisson regression models will be used. By conducting this comprehensive study, we aim to gain valuable insights into the clinical characteristics, treatment management, and adherence of heart failure patients in Andalusia, as well as to identify factors that may influence clinical outcomes. These findings could be critical both for the development of optimized strategies that improve medical care and quality of life of patients and for mitigating the health burden of HF in the region.

Long-Term Effect of Home Blood Pressure Self-Monitoring Plus Medication Self-Titration for Patients With Hypertension: A Secondary Analysis of the ADAMPA Randomized Clinical Trial.

Importance: Patient empowerment through pharmacologic self-management is a common strategy for some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure (BP). Several trials have shown its potential for reducing BP in the short term, but evidence in the longer term is scarce. Objective: To evaluate the longer-term effectiveness of BP self-monitoring plus self-titration of antihypertensive medication vs usual care for patients with poorly controlled hypertension, with passive follow-up and primary-care nursing involvement. Design, Setting, and Participants: The ADAMPA (Impact of Self-Monitoring of Blood Pressure and Self-Titration of Medication in the Control of Hypertension) study was a randomized, unblinded clinical trial with 2 parallel arms conducted in Valencia, Spain. Included participants were patients 40 years or older, with systolic BP (SBP) over 145 mm Hg and/or diastolic BP (DBP) over 90 mm Hg, recruited from July 21, 2017, to June 30, 2018 (study completion, August 25, 2020). Statistical analysis was conducted on an intention-to-treat basis from August 2022 to February 2024. Interventions: Participants were randomized 1:1 to usual care vs an individualized, prearranged plan based on BP self-monitoring plus medication self-titration. Main Outcomes and Measures: The main outome was the adjusted mean difference (AMD) in SBP between groups at 24 months of follow-up. Secondary outcomes were the AMD in DBP between groups at 24 months of follow-up, proportion of patients reaching the BP target (SBP <140 mm Hg and DBP <90 mm Hg), change in behaviors, quality of life, health service use, and adverse events. Results: Among 312 patients included in main trial, data on BP measurements at 24 months were available for 219 patients (111 in the intervention group and 108 in the control group). The mean (SD) age was 64.3 (10.1) years, and 120 patients (54.8%) were female; the mean (SD) SBP was 155.6 (13.1) mm Hg, and the mean (SD) diastolic BP was 90.8 (7.7) mm Hg. The median follow-up was 23.8 months (IQR, 19.8-24.5 months). The AMD in SBP at the end of follow-up was -3.4 mm Hg (95% CI, -4.7 to -2.1 mm Hg; P < .001), and the AMD in DBP was -2.5 mm Hg (95% CI, -3.5 to -1.6 mm Hg; P < .001). Subgroup analysis for the main outcome showed consistent results. Sensitivity analyses confirmed the robustness of the main findings. No differences were observed between groups in behaviors, quality of life, use of health services, or adverse events. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, BP self-monitoring plus self-titration of antihypertensive medication based on an individualized prearranged plan used in primary care reduced BP in the longer term with passive follow-up compared with usual care, without increasing health care use or adverse events. These results suggest that simple, inexpensive, and easy-to-implement self-management interventions have the potential to improve the long-term control of hypertension in routine clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03242785.

Group-based trajectory models: a new approach to classifying and predicting long-term medication adherence.

BACKGROUND: Classifying medication adherence is important for efficiently targeting adherence improvement interventions. The purpose of this study was to evaluate the use of a novel method, group-based trajectory models, for classifying patients by their long-term adherence. RESEARCH DESIGN: We identified patients who initiated a statin between June 1, 2006 and May 30, 2007 in prescription claims from CVS Caremark and evaluated adherence over the subsequent 15 months. We compared several adherence summary measures, including proportion of days covered (PDC) and trajectory models with 2-6 groups, with the observed adherence pattern, defined by monthly indicators of full adherence (defined as having ≥24 d covered of 30). We also compared the accuracy of adherence prediction based on patient characteristics when adherence was defined by either a trajectory model or PDC. RESULTS: In 264,789 statin initiators, the 6-group trajectory model summarized long-term adherence best (C=0.938), whereas PDC summarized less well (C=0.881). The accuracy of adherence predictions was similar whether adherence was classified by PDC or by trajectory model. CONCLUSIONS: Trajectory models summarized adherence patterns better than traditional approaches and were similarly predicted by covariates. Group-based trajectory models may facilitate targeting of interventions and may be useful to adjust for confounding by health-seeking behavior.

A Bayesian multivariate spatial approach for illness-death survival models.

Illness-death models are a class of stochastic models inside the multi-state framework. In those models, individuals are allowed to move over time between different states related to illness and death. They are of special interest when working with non-terminal diseases, as they not only consider the competing risk of death but also allow us to study the progression from illness to death. The intensity of each transition can be modelled including both fixed and random effects of covariates. In particular, spatially structured random effects or their multivariate versions can be used to assess spatial differences between regions and among transitions. We propose a Bayesian methodological framework based on an illness-death model with a multivariate Leroux prior for the random effects. We apply this model to a cohort study regarding progression after an osteoporotic hip fracture in elderly patients. From this spatial illness-death model, we assess the geographical variation in risks, cumulative incidences and transition probabilities related to recurrent hip fracture and death. Bayesian inference is done via the integrated nested Laplace approximation.

Initial opioid prescription characteristics and risk of opioid misuse, poisoning and dependence: retrospective cohort study.

OBJECTIVE: To identify individual and initial prescription-related factors associated with an increased risk for opioid-related misuse, poisoning and dependence (MPD) in patients with non-cancer pain. METHODS: Cohort study linking several databases covering 5 million inhabitants of the region of Valencia, Spain, including all adults initiating prescription opioids in the period 2012-2018. To ascertain the association between the characteristics of the initial prescription choice and the risk of opioid MPD, we used shared frailty Cox regression models. We additionally considered death as a competing risk in sensitivity analyses. RESULTS: 958 019 patients initiated opioid prescription from 2012 to 2018, of which 0.13% experienced MPD. Most patients were prescribed tramadol as initial opioid (76.7%) followed by codeine (16.3%), long-acting opioids (6.7%), short-acting opioids (0.2%) and ultrafast opioids (0.1%). Initiation with ultrafast (HR 7.2; 95% CI 4.1 to 12.6), short-acting (HR 4.8; 95% CI 2.3 to 10.2) and long-acting opioids (HR 1.5; 95% CI 1.2 to 1.9) were associated with a higher risk of MPD when compared with tramadol. Initial prescriptions covering 4-7 days (HR 1.3; 95% CI 1.0 to 1.8), 8-14 days (HR 1.4; 95% CI 1.0 to 1.9), 15-30 days (HR 1.7; 95% CI 1.2 to 2.3) and more than one a month (HR 1.8; 95% CI 1.3 to 2.5) were associated with more MPD risk than initial prescriptions for 1-3 days. Treatments with >120 daily morphine milligram equivalents (MME) increased MPD risk (vs <50 MME, HR 1.6; 95% CI 1.1 to 2.2). Main individual factors associated with increased risk of MPD risk were male sex (HR 2.4; 95% CI 2.1 to 2.7), younger age (when compared with patients aged 18-44 years, patients aged 45-64 years, HR 0.4; 95% CI 0.4 to 0.5; patients aged 65-74 years, HR 0.4; 95% CI 0.3 to 0.5 and patients aged 75 years old and over, HR 0.7; 95% CI 0.6 to 0.8), lack of economic resources (2.1; 95% CI 1.8 to 2.5) and registered misuse of alcohol (2.9; 95% CI 2.4 to 3.5). Sensitivity analyses yielded overall comparable results. CONCLUSIONS: Our study identifies riskier patterns of opioid prescription initiation for non-cancer indications, as well as patient subgroups with higher risk of misuse, poisoning and dependence.

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.

Prevalence of attention deficit hyperactivity disorder among children and adolescents in Spain: a systematic review and meta-analysis of epidemiological studies.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in childhood, but the frequency of the condition is not well established in many countries. The aim of the present study was to quantify the overall prevalence of ADHD among children and adolescents in Spain by means of a systematic review and meta-analysis. METHODS: PubMed/MEDLINE, IME, IBECS and TESEO were comprehensively searched. Original reports were selected if they provided data on prevalence estimates of ADHD among people under 18 years old in Spain and were cross-sectional, observational epidemiological studies. Information from included studies was systematically extracted and evaluated. Overall pooled-prevalence estimates of ADHD were calculated using random-effects models. Sources of heterogeneity were explored by means sub-groups analyses and univariate meta-regressions. RESULTS: Fourteen epidemiological studies (13,026 subjects) were selected. The overall pooled-prevalence of ADHD was estimated at 6.8% [95% confidence interval (CI) 4.9 - 8.8%] representing 361,580 (95% CI 260,550 - 467,927) children and adolescents in the community. There was significant heterogeneity (P < 0.001), which was incompletely explained by subgroup analyses and meta-regressions. CONCLUSIONS: Our findings suggest that the prevalence of ADHD among children and adolescents in Spain is consistent with previous studies conducted in other countries and regions. This study represents a first step in estimating the national burden of ADHD that will be essential to building evidence-based programs and services.

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System.

BACKGROUND: While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair. METHODS: A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors. RESULTS: Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis. CONCLUSIONS: Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not.

Predictive Performance of the FRAX Tool Calibrated for Spain vs. an Age and Sex Model: Prospective Cohort Study with 9082 Women and Men Followed for up to 8 Years.

In Spain, the Fracture Risk Assessment Tool (FRAX) was adapted using studies with a small number of patients, and there are only a few external validation studies that present limitations. In this prospective cohort study, we compared the performance of FRAX and a simple age and sex model. We used data from the ESOSVAL cohort, a cohort composed of a Mediterranean population of 11,035 women and men aged 50 years and over, followed for up to 8 years, to compare the discrimination, calibration, and reclassification of FRAX calibrated for Spain and a logistic model including only age and sex as variables. We found virtually identical AUC, 83.55% for FRAX (CI 95%: 80.46, 86.63) and 84.10% for the age and sex model (CI 95%: 80.91, 87.29), and there were similar observed-to-predicted ratios. In the reclassification analyses, patients with a hip fracture that were reclassified correctly as high risk by FRAX, compared to the age and sex model, were -2.86%, using either the 3% threshold or the observed incidence, 1.54% (95%CI: -8.44, 2.72 for the 3% threshold; 95%CI: -7.68, 1.97 for the incidence threshold). Remarkably simple and inexpensive tools that are easily transferable into electronic medical record environments may offer a comparable predictive ability to that of FRAX.

Assessing Concurrent Adherence to Combined Essential Medication and Clinical Outcomes in Patients With Acute Coronary Syndrome. A Population-Based, Real-World Study Using Group-Based Trajectory Models.

Aim: Adherence to multiple medications recommended for secondary prevention of cardiovascular conditions represents a challenge. We aimed to identify patterns of concurrent adherence to combined therapy and assess their impact on clinical outcomes in a cohort of patients with acute coronary syndrome (ACS). Methods: Population-based retrospective cohort of all patients discharged after hospitalization for ACS (2009-2011), prescribed ≥3 therapeutic groups within the first month. We assessed monthly concurrent adherence (≥24 days of medication out of 30) to ≥3 medications during the first year, and patterns were identified through group-based trajectory models. A composite clinical outcome during the second year was constructed. The association between adherence patterns and traditional refill adherence metrics [e.g., the proportion of days covered (PDC)], and outcomes were assessed through a multivariable Cox proportional hazards model. Results: Among 15,797 patients discharged alive, 12,057 (76.32%) initiated treatment with ≥3 therapeutic groups after discharge. We identified seven adherence trajectories to ≥3 medications: Adherent (52.94% of patients); Early Gap (6.64%); Middle Gap (5.67%); Late Decline (10.93%); Occasional Users (5.45%); Early Decline (8.79%); Non-Adherent (9.58%). Compared to the Adherent group, patients belonging to Early Gap (HR:1.30, 95%CI 1.07;1.60), Late decline (hazards ratio (HR): 1.31, 95% CI 1.1; 1.56), and Non-Adherent trajectories (HR: 1.36, 95% CI 1.14; 1.63) had a greater risk of adverse clinical outcomes, which was also different to the risk ascertained through concurrent PDC < 80 (HR: 1.13, 95% CI 1.01; 1.27). Conclusion: Overall, seven adherence trajectories to ≥3 drugs were identified, with three distinct adherence patterns being at higher risk of adverse outcomes. The identification of patterns of concurrent adherence, a more comprehensive approach than traditional measurements, may be useful to target interventions to improve adherence to multiple medications.