Medication economic burden of antidepressant non-adherence in Spain.

Introduction: Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and costs. Methods: A population-based registry study was conducted to assess non-adherence and to analyze the economic burden of treatment and from non-adherence to antidepressants in 2021. Non-adherence was measured by the Medication Possession Ratio and those below 80% were classified as non-adherent. Results: In 2021, 246,718 patients (10.60% [95% CI: 10.48-10.72]) received antidepressants at a cost of €29 million. The median antidepressant cost per patient/year was €70.08€, ranging from €7.58 for amitriptyline to €396.66 for agomelatine. Out-of-pocket costs represented 6.09% of total expenditures, with a median copayment of €2.78 per patient. The 19.87% [95% CI 19.52-20.22)] of patients were non-adherent to antidepressants, costing €3.9 million (13.30% of total antidepressant costs). Non-adherence rates exceeded 20% for the tricyclic antidepressants, fluoxetine (23.53%), fluvoxamine (22.42%), and vortioxetine (20.58%). Venlafaxine (14.64%) and citalopram (14.88%) had the lowest non-adherence rates, of less than 15%. The median cost of non-adherent medications per patient/year was €18.96 and ranged from €2.50 (amitriptyline) to €133.42 (agomelatine). Conclusion: Reducing non-adherence to antidepressants is critical to improving clinical and economic outcomes. The implementation of interventions and standardized measures, including early detection indicators, is urgently needed. Antidepressants differ with regard to non-adherence and their cost, and this should be considered when prescribing this medication. The Medication Possession Ratio could be used by the healthcare provider and clinician to identify non-adherent patients for monitoring, and to take necessary corrective actions.

Prevalence and cost of hospitalized patients with asymptomatic COVID-19 in 2020 in Spain.

Introduction: COVID-19 transmission has been characterized by the presence of asymptomatic patients. Additionally, most studies evaluating costs focus on symptomatic COVID-19 cases. Objective: To describe the prevalence, characteristics, and costs of asymptomatic COVID-19 cases at admission in Spanish hospitals in 2020. Methods: A nationwide study was performed, and data of hospitalized patients were collected of the Minimum Basic Data Set in Spain during 2020. Patients with COVID-19 codes as a primary and as a secondary diagnosis at admission were selected. Variables collected included age, sex, length of stay, in-hospital death, admission, length of stay and death in intensive care unit, mechanical ventilation and ventilatory assistance. COVID-19 related hospital costs were calculated using diagnosis-related groups from the Minimum Basic Data Set. Patients and costs were disaggregated by sex, age group, intensive care unit admission and epidemic wave (first or second) and main diagnosis. Results: A total of 14,742 patients were admitted with asymptomatic COVID-19 in Spanish hospitals representing 6.35% of all COVID-19 admitted patients. The total cost of admissions with asymptomatic COVID-19 was €105,933,677.6 with a mean cost per patient of €7,185.8 with higher mean cost in the first wave despite only 2.7% of cases were found during that time. Based on primary diagnosis, the higher number of cases of asymptomatic COVID-19 were found in "Pregnancy, childbirth and the puerperium" followed by "diseases of the circulatory system". Conclusions: There was a high prevalence of asymptomatic cases during screening at admission process in Spanish hospitals in 2020. The highest number of cases was found among the group of "pregnancy, childbirth, and puerperium" followed by "diseases of the circulatory system." The higher costs might be due not only to the main pathology at admission but to the associated healthcare provisions needed in case of positive COVID-19 testing.

Increase in driving after cocaine use in Spain: a cross-sectional dataset analysis for 2021.

Objective: Driving under the influence of alcohol and/or drugs impairs skills essential for safe driving, increases the risk of being involved in a traffic accident and is particularly prevalent in Spain. The aim is to assess the prevalence of positive substance driving cases, what factors may be associated with driving after substance use, and the evolution of the progress in the prevalence of drug use among drivers in drivers based on the 2008, 2013, 2018, and 2021 studies. Study design and setting: The present study was conducted in a representative sample of Spanish drivers in 2021 for alcohol (breath) and psychoactive substances [oral fluid (OF)]. The sample size was 2980 drivers, mostly males (76.5%) with a mean age of 41.35 ± 13.34 years. Results: In 2021, 9.3% of drivers tested positive for alcohol and/or drugs. The presence of alcohol alone was observed in 4.2% of drivers, alcohol and another substance in 0.3%, a single drug in 4.4%, and two or drugs other than alcohol in 0.4%. Overall, cocaine cases were the highest registered in 2021 (2.4%), while cannabis (1.9%) and polydrug cases (0.7%) were the lowest, with respect to the 2008/2013/2018 studies. Conclusions: According to our research, in 2021, 9 out of 100 drivers were detected to have some substance in their system. This prevalence remains unacceptably high in Spain, with a marked increase in the frequency of driving after cocaine use. Further interventions and measures must be taken to avoid driving under the influence of alcohol and/or drugs.

Trends in the Use of Driving-Impairing Medicines According to the DRUID Category: A Population-Based Registry Study with Reference to Driving in a Region of Spain between 2015 and 2019.

The European DRUID (Drive Under the Influence of drugs, alcohol, and medicines) program classifies medications into three categories according to their effect on one's fitness to drive. The trend in the use of driving-impairing medicines (DIMs) in a region of Spain between 2015 and 2019 was analyzed through a population-based registry study. Pharmacy dispensing records for DIMs are provided. The use of DIMs on drivers was weighted according to the national driver's license census. The analysis was performed considering the population distribution by age and sex, treatment length, and the three DRUID categories. DIMs were used by 36.46% of the population and 27.91% of drivers, mainly chronically, with considerable daily use (8.04% and 5.34%, respectively). Use was more common in females than in males (42.28% vs. 30.44%) and increased with age. Among drivers, consumption decreases after 60 years of age for females and after 75 years of age for males. There was a 34% increase in the use of DIMs between 2015 and 2019, with a focus on daily use (>60%). The general population took 2.27 ± 1.76 DIMs, fundamentally category II (moderate influence on fitness to drive) (20.3%) and category III (severe influence on fitness to drive) (19.08%). The use of DIMs by the general population and drivers is significant and has increased in recent years. The integration of the DRUID classification into electronic prescription tools would assist physicians and pharmacists in providing adequate information to the patient about the effects of prescribed medications on their fitness to drive.

Environmental factors are associated to hospital outcomes in COVID-19 patients during lockdown and post-lockdown in 2020: A nationwide study.

OBJECTIVE: This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown and post-lockdown 2020 period in Spain. METHODS: We performed a nationwide population-based retrospective study on 208,744 patients admitted to Spanish hospitals due to COVID-19 based on the Minimum Basic Data Set (MBDS) during the first two waves of the pandemic in 2020. Environmental data were obtained from Copernicus Atmosphere Monitoring Service. The association was assessed by a generalized additive model. RESULTS: PM2.5 was the most critical environmental factor related to hospital admissions and hospital mortality due to COVID-19 during the lockdown in Spain, PM10, NO2, and SO2and also showed associations. The effect was considerably reduced during the post-lockdown period. ICU admissions in COVID-19 patients were mainly associated with PM2.5, PM10, NO2, and SO2 during the lockdown as well. During the lockdown, exposure to PM2.5 and PM10 were the most critical environmental factors related to ICU mortality in COVID-19. CONCLUSION: Short-term exposure to air pollutants impacts COVID-19 out-comes during the lockdown, especially PM2.5, PM10, NO2, and SO2. These pollutants are associated with hospital admission, hospital mortality and ICU admission, while ICU mortality is mainly associated with PM2.5 and PM10. Our findings reveal the importance of monitoring air pollutants in respiratory infectious diseases.

Economic Burden of the 2020 COVID-19 Hospitalizations in Spain.

This economic evaluation reports the total and per patient costs of inpatient care for COVID-19 in Spain in 2020.

Non-Adherence to Antidepressant Treatment and Related Factors in a Region of Spain: A Population-Based Registry Study.

Antidepressants are a commonly prescribed psychotropic medication, and their use has increased in recent years. Medication non-adherence in patients with mental disorders is associated with worse health outcomes. A population-based registry study to assess antidepressant non-adherence during 2021 has been carried out. An indirect method based on the medication possession ratio (MPR) has been utilized. Patients with a MPR under 80% were classified as non-adherent. A multivariate logistic regression to identify non-adherence predictors has been used, considering sociodemographic (age, sex, institutionalization and urbanicity) and health related variables (diagnostics, antidepressant class, multiple prescribers, and polypharmacy). In 2021, 10.6% of the Castile and Leon population used antidepressants. These patients were institutionalized (7.29%), living in urban areas (63.44%), polymedicated with multiple prescribers (57.07%), and using serotonin selective reuptake inhibitors (SSRIs) (54.77%), other antidepressants (46.82%) or tricyclic antidepressants (TCAs) (13.76%). Antidepressants were prescribed mainly for depression (36.73%) and anxiety (29.24%). Non-adherence to antidepressants was more frequent in men (20.56%) than in woman (19.59%) and decreased with increasing age (32% up to 17 years old vs. 13.76% over 80 years old). TCAs were associated with the highest prevalence of non-adherence (23.99%), followed by SSRIs (20.19%) and other antidepressants (18.5%). Predictors of non-adherence in patients on antidepressants were: living in urban areas, using TCAs, and pain occurrence. Non-adherence to antidepressants decreases with aging. Being female, institutionalization, being polymedicated and having depression/anxiety alongside another psychiatric diagnosis are protective factors against non-adherence. The MPR is a robust indicator for the clinician to identify non-adherent patients for monitoring, and adopt any necessary corrective actions.

Hospitalized COVID-19 Patients with Severe Acute Respiratory Syndrome: A Population-Based Registry Analysis to Assess Clinical Findings, Pharmacological Treatment and Survival.

Background and Objectives: One of the most serious clinical outcomes in hospitalized patients with COVID-19 is severe acute respiratory syndrome (SARS). The aim is to analyze pharmacological treatment, survival and the main mortality predictors. Materials and Methods: A real-world data study from COVID-19-hospitalized patients with SARS from 1 March to 31 May 2020 has been carried out. Variables such as hospital length of stay, ventilation type and clinical outcomes have been taken into account. Results: In Castile and Leon, 14.03% of the 7307 in-hospital COVID-19 patients developed SARS, with a mortality rate of 42.53%. SARS prevalence was doubled in males compared to females, and 78.54% had an age of 65 years or more. The most commonly used medicines were antibiotics (89.27%), antimalarials (68.1%) and corticosteroids (55.9%). Survival of patients developing SARS was lower compared to patients without this complication (12 vs. 13 days). The main death predictors were disseminated intravascular coagulation (DIC) (OR: 13.87) and age (>65 years) (OR: 7.35). Conclusions: Patients older than 65 years who develop DIC have a higher probability of hospital death. Tocilizumab and steroids have been linked to a lower incidence of hospital death, being the main treatment for COVID-19 hospitalized patients with SARS.

Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality.

BACKGROUND: Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. METHODS: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. RESULTS: In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39-0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. CONCLUSIONS: Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study.

Economic recession has dire consequences on overall health. None have explored the impact of economic crisis (EC) on infective endocarditis (IE) mortality. We conducted a retrospective, nationwide, temporal trend study analyzing mortality trends by age, sex, and adverse outcomes in patients diagnosed with IE in Spain from 1997 to 2014. Data were divided into two subperiods: pre-EC (January 1997-August 2008) and post-EC (September 2008-December 2014). A total of 25 952 patients presented with IE. The incidence increased from 301.4 to 365.1 per 10 000 000 habitants, and the mortality rate rose from 24.3% to 28.4%. Those aged >75 years experienced more adverse outcomes. Complications due to sepsis, shock, acute kidney injury requiring dialysis, and heart failure increased after the EC onset, and expenditures soared to €16 216. Expenditure per community was related to mortality (P < .001). The EC resulted as an independent predictor for mortality (hazard ratio 1.06; 95% confidence interval 1.01-1.11). Incidence and mortality rate in patients with IE after the onset of the EC have increased as a result of rising adverse outcomes despite an overall increased investment.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

Clinical Profile, Pharmacological Treatment, and Predictors of Death Among Hospitalized COVID-19 Patients With Acute Kidney Injury: A Population-Based Registry Analysis.

Introduction: One of the worst clinical outcomes of the coronavirus disease 2019 (COVID-19) pandemic was acute kidney injury (AKI). Methods: This manuscript presents results from a population-based registry study assessing treatment, comorbidities, and predictors of hospital death among COVID-19 patients with AKI from March 1st to May 31th, 2020. Death, oxygen delivery and ventilation, acute dialysis need, use of medications, and various clinical outcomes, in addition to the length of stay in the hospital and intensive care unit (ICU), were evaluated. Results: In Castile and Leon, the largest region of Spain, 10.87% of the patients admitted for COVID-19 (n = 7,307) developed AKI. These patients were known by having hypertension (57.93%), cardiovascular disease (48.99%), diabetes (26.7%) and chronic kidney disease (14.36%), and they used antibiotics (90.43%), antimalarials (60.45%), steroids (48.61%), antivirals (33.38%), anti-systemic inflammatory response syndrome (SIRS) drugs (9.45%), and tocilizumab (8.31%). Mortality among patients with AKI doubled that observed in patients without AKI (46.1 vs. 21.79%). Predictors of hospital death in COVID-19 patients with AKI were ventilation needs (OR = 5.9), treatment with steroids (OR = 1.7) or anti-SIRS (OR = 2.4), severe acute respiratory syndrome (SARS) occurrence (OR = 2.8), and SIRS occurrence (OR = 2.5). Conclusions: Acute kidney injury is a frequent and serious complication among COVID-19 patients, with a very high mortality, that requires more attention by treating physicians, when prescribing medications, by looking for manifestations particular to the disease, such as SARS or SIRS.

Positivity to Cocaine and/or Benzoylecgonine in Confirmation Analyses for On-Road Tests in Spain.

We are using real-life data in order to determine the prevalence of driving with the presence of cocaine and/or benzoylecgonine (BZE), their concentrations, and their use in combination with other drugs. This study assessed data on Spanish drivers with confirmed drug-positive results recorded by the Spanish National Traffic Agency from 2011-2016. Frequencies of positivity for cocaine and/or BZE and concentration of such substances were obtained. Comparisons and univariate and multivariate regression analyses were performed. Drivers who tested positive for cocaine and/or BZE accounted for 48.59% of the total positive results for drugs. In positive cases for both cocaine and BZE, other substances were detected in 81.74%: delta-9-tetrahydrocannabinol (THC) (68.19%), opioids (20.78%) and amphetamine-like substances (16.76%). In the multivariate logistic regression analysis, the frequency of cocaine and/or BZE positive cases decreased with age (OR:0.97) and were less likely among women (OR:0.63). Concentrations (ng/mL) of cocaine (249.30) and BZE (137.90) were higher when both substances were detected together than when detected alone. Positivity to cocaine represented an important proportion among Spanish drivers who tested positive for drugs, and polysubstance use was especially observed in more than 8 out of 10 positive cases for cocaine and/or BZE.

Healthcare Data for Achieving a More Personalized Treatment of Chronic Kidney Disease.

The current concept of healthcare incites a more personalized treatment of diseases. To this aim, biomarkers are needed to improve decision-making facing chronic kidney disease (CKD) patients. Prognostic markers provided by real-world (observational) evidence are proposed in this Special Issue entitled "Biomarkers in Chronic Kidney Disease", with the intention to identify high-risk patients. These markers do not target measurable parameters in patients but clinical endpoints that may be in turn transformed to benefits under the effect of future interventions.

Clinical Profile, Treatment and Predictors during the First COVID-19 Wave: A Population-Based Registry Analysis from Castile and Leon Hospitals.

The first wave of the COVID-19 pandemic collapsed the hospitals in Castile and Leon (Spain). An analysis of the clinical characteristics, drug therapies and principal outcome predictors in the COVID-19 hospitalized patients from 1 March to 31 May 2020 is presented through a population-based registry study. Hospital stay variables, ventilation mode data and clinical outcomes were observed. In Castile and Leon hospitals, 7307 COVID-19 patients were admitted, with 57.05% being male and a median of 76 years. The mortality rate was 24.43%, with a high incidence of severe acute respiratory syndrome (SARS) (14.03%) and acute kidney injury (AKI) (10.87%). The most used medicines were antibiotics (90.83%), antimalarials (42.63%), steroids (44.37%) and antivirals, such as lopinavir/ritonavir (42.63%). The use of tocilizumab (9.37%) and anti-SIRS (systemic inflammatory response syndrome) medicines (7.34%) were remarkable. Fundamentally, death occurred more likely over 65 years of age (OR: 9.05). In addition, the need for ventilation was associated with a higher probability of death (OR: 3.59), SARS (OR: 5.14) and AKI (OR: 2.31). The drug-use pattern had been modified throughout the COVID-19 first wave. Multiple factors, such as age, gender and the need for mechanical ventilation, were related to the worst evolution prognosis of the disease.

[Differential health effects of alcoholic beverages: an umbrella review of observational studies.] / Tipos de bebidas alcohólicas y efectos diferenciados en la salud: una revisión paraguas de estudios observacionales.

BACKGROUND: There is great controversy about whether the consumption of different types of alcoholic beverages has different effects on health. The objective was to carry out an umbrella review of the studies that described the association between the consumption of different types of alcoholic beverages and various health indicators. METHODS: Search through PubMed (from January 2000 to February 2019) of systematic reviews and meta-analysis that reported quantitative results of the association between the consumption of different types of alcoholic beverages and health effects. 26 studies were identified: 21 related to cancer, three to cardiometabolic diseases, two to neurodegenerative diseases, and one to general mortality. RESULTS: The results were heterogeneous. The great methodological differences in the estimation of alcohol intake, control of confounding variables, and the evaluation of statistical difference between types of beverages, made it very difficult to conclude whether they cause an unequal effect on health. In general mortality and cardiometabolic diseases, it was suggested that beer and spirits appear to have a greater negative effect than wine, but the differences were not statistically significant. Regarding cancer, in those types where the causal evidence is totally consistent: oropharynx, colorectal and breast (women), the reviews did not show a differentiated effect according to the type of alcoholic beverages. Regarding neurodegenerative diseases, the available information did not allow clear conclusions to be drawn. CONCLUSIONS: The reviewed evidence does not allow to conclude that the consumption of wine, beer or spirits, has a differential effect on cardiometabolic, cancer or neurodegenerative diseases.

OBJETIVO: Existe gran controversia sobre si el consumo de diversos tipos de bebidas alcohólicas tiene efectos diferenciados en la salud. El objetivo de este estudio fue realizar una revisión paraguas de los estudios que describían la asociación del consumo de diferentes tipos de bebidas alcohólicas con diversos indicadores de salud. METODOS: Se realizó una búsqueda a través de PubMed (entre enero de 2000 y febrero de 2019) de revisiones sistemáticas y metaanálisis que reportaban resultados cuantitativos de la asociación entre el consumo de diferentes tipos de bebidas alcohólicas y efectos en salud. Se identificaron 26 estudios: veintiuno estaban relacionados con cáncer, tres con enfermedades cardiometabólicas, dos con neurodegenerativas y uno con mortalidad general. RESULTADOS: Los resultados fueron heterogéneos. Las grandes diferencias metodológicas en la estimación de la ingesta de alcohol, el control de las variables confusoras y el contraste de las estimaciones entre el tipo de bebidas hacían muy difícil concluir sobre si provocaban un efecto desigual en la salud. En la mortalidad general y las enfermedades cardiometabólicas, aunque parece que la cerveza y los licores tenían un mayor efecto negativo que el vino, las diferencias entre tipos de bebidas no eran estadísticamente significativas. Respecto al cáncer, en aquellos tipos cuya evidencia causal era totalmente consistente (orofaringe, colorrectal y de mama [mujeres]), las revisiones no mostraban un efecto diferenciado según los tipos de bebidas alcohólicas. Respecto a las enfermedades neurodegenerativas, la información disponible tampoco permitía establecer claras conclusiones. CONCLUSIONES: La evidencia revisada no permite afirmar que el consumo de vino, cerveza o licores tenga un efecto diferencial en las enfermedades cardiometabólicas, las neurodegenerativas o el cáncer.

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies.

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

Population-Based Registry Analysis of Antidiabetics Dispensations: Trend Use in Spain between 2015 and 2018 with Reference to Driving.

Insulins and some oral antidiabetics are considered to be driving-impairing medicines (DIM) and they belong to the Driving under the Influence of Drugs, alcohol, and medicines (DRUID) category I (minor influence on fitness to drive). The trend of antidiabetics use in Castilla y León from 2015 to 2018 is presented through a population-based registry study. Treatment duration with these medicines and the concomitant use of other DIMs were observed. An adjustment method was used with information from the drivers' license census. For all calculations, age and gender were taken into account. 3.98% of the general population used at least one antidiabetic, as well as 2.92% of drivers. The consumption of antidiabetics in men was higher than in women (4.35% vs. 3.61%, p = 0.001), and the use increases with age, especially from 35-39 years to 75-79 years in men and 85-89 years in women. Antidiabetics were consumed chronically, specifically 100% in the case of insulins and 95% in the case of oral antidiabetics. In addition to antidiabetics, 2.5 ± 1.86 DIMs were consumed, mainly anxiolytics (25.53%), opioids (23.03%), other analgesics and antipiretics (19.13%), and antidepressants (17.73%). Collaboration between pharmacists and physicians is a priority to clearly transmitting risks to patients. It is necessary that the health authorities include information on DIMs, such as the DRUID classification, in the prescription and dispensing software.

Prevalence of alcohol and other psychoactive substances in motor vehicle drivers in Spain, 2018: Cross-sectional dataset analysis with studies from 2008 and 2013.

Driving under the influence of substances is particularly common in developed countries. In Spain, in 2010, roadside oral fluid drug screening became mandatory, and in 2014, the zero tolerance legal system was established. The aim of the current study is to analyze the prevalence of alcohol (in breath) and drugs (in oral fluids) in a representative sample of motor vehicle drivers in Spain in 2018. This study focuses specifically on multiple substance use (i.e., polysubstance use), and seeks to analyze the factors associated with driving after consumption of substances, as well as the evolution of the presence of drugs in drivers from 2008, 2013 and 2018 studies. A total of 2881 drivers were included in this study. In 2018, alcohol was detected in 3.9 % of the cases, alcohol plus another substance(s) was found in 0.8 % of the cases, only one drug (excluding alcohol) made up 5.1 % of the cases and drivers testing positives to more than one drug at a time (apart from alcohol) constituted 1.1 %. There were less cases of positives for any drugs or alcohol in 2018 and 2013 (2018: 10.9 %, z=3.6, p=0.0003; 2013: 9.3 %, z=5.7, p<0.0001) than in 2008 (14.0 %), yet the frequency observed in 2018 is more than that of 2013 (z=2, p=0.05). Multiple drug use (without alcohol), increased from 0.5 % in 2008 to 1.1 % in 2018 (z=2.2, p=0.03). Alcohol/drug driving continues to be frequent in Spain, leading to the need for intervention in this field, particularly on polydrug use and driving.

The Impact of Iron Supplementation for Treating Anemia in Patients with Chronic Kidney Disease: Results from Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to be superior to per os (PO) iron supplementation. The differences between the available formulations are poorly characterized. This report presents results from pairwise and network meta-analyses carried out after a comprehensive search in sources of published and unpublished studies, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations (International prospective register of systematic reviews PROSPERO reference ID: CRD42020148155). Meta-analytic calculations were performed for the outcome of non-response to iron supplementation (i.e., hemoglobin (Hgb) increase of <0.5-1.0 g/dL, or initiation/intensification of erythropoiesis-stimulating agent (ESA) therapy, or increase/change of iron supplement, or requirements of blood transfusion). A total of 34 randomized controlled trials (RCT) were identified, providing numerical data for analyses covering 93.7% (n = 10.097) of the total study population. At the network level, iron supplementation seems to have a more protective effect against the outcome of non-response before the start of dialysis than once dialysis is initiated, and some preparations seem to be more potent (e.g., ferumoxytol, ferric carboxymaltose), compared to the rest of iron supplements assessed (surface under the cumulative ranking area (SUCRA) > 0.8). This study provides parameters for adequately following-up patients requiring iron supplementation, by presenting the most performing preparations, and, indirectly, by making it possible to identify good responders among all patients treated with these medicines.