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Due to the role that schools play in determining the status of the future occupations of their children (i.e., the selection function of education), high socioeconomic status (SES) parents may not always be supportive of interventions that would reduce the SES achievement gap. In four experiments, we measured the support of parents (Ntotal = 1966) for implementing an equalizing (and, in Experiments 2 and 3, an inequality‐maintaining) intervention. In Experiments 1 and 2, a negative association between subjective SES and support for the equalizing intervention was found when the selection function was made salient, an effect that was also observed in Experiment 4 but only for Right‐leaning participants. In Experiment 3, where the salience of selection was held constant, we found a negative association between subjective SES and support for the equalizing intervention, but not the inequality‐maintaining intervention. [ABSTRACT FROM AUTHOR]

Background: While advances in endovascular thrombectomy (EVT) have led to high reperfusion rates, most patients treated with EVT do not avoid disability. Post‐reperfusion hemorrhagic transformation (HT) is a potential target for improving outcomes. This study examined pretreatment blood–brain barrier (BBB) disruption in tissue that would subsequently become part of the final infarct to evaluate its role in post‐EVT HT. Methods: This post hoc analysis of the FRAME study, which enrolled patients with anterior large vessel occlusion who received EVT within 6 hours of onset, included patients if they had successful pretreatment MRI perfusion weighted imaging (PWI) and underwent successful EVT. BBB disruption was measured as the percent signal change due to gadolinium leakage on the PWI source images prior to thrombectomy. Mean permeability derangement (MPD) was defined as the average of all voxels in the stroke core that are two standard deviations above normal. The primary outcome was hemorrhagic transformation with parenchymal hematoma (PH). Results: In total, 164 patients were included; mean age was 71 and 48% were female. PH occurred in 57 patients. Median MPD was 13.5% for patients with PH versus 3.6% for patients without (p < 0.0001). Elevated MPD was independently associated with PH with a 20% increased risk of PH for each 5% increase in MPD (OR 1.206; 95% CI 1.037:1.405; p = 0.0147, adjusted for NIHSS and procedure duration). Conclusions: Even in patients who are successfully recanalized in an early time window, pretreatment BBB disruption in regions that go on to infarct is associated with an increased risk of post‐EVT HT. [ABSTRACT FROM AUTHOR]

In 2018, a significant neural tube defects (NTD) signal was reported after pre‐conceptional exposure to dolutegravir, but was not confirmed in further analysis. Since 2019, dolutegravir‐based regimen, an integrase inhibitor (INI), is recommended by WHO as the most‐effective first‐line therapy in all patients living with HIV. To explore the potential INI‐related teratogenic effect, we searched disproportionate signals between exposure to INI‐class drugs and congenital anomalies, compared to non‐INI drugs, using the international pharmacovigilance database, VigiBase®. We selected all the reports registered in VigiBase® between 01/01/2007 and 30/03/2021 on any antiretroviral drug‐related fetal or neonatal adverse drug reactions, declared either in children (<2 years) exposed in utero or in pregnant women (12–50 years). A case/non‐case study was conducted to detected signals between congenital anomalies and prenatal exposure to any INI‐class drug, compared to non‐INI drugs, by estimating adjusted reporting odds ratios (aROR) with 95% confidence intervals (95%CI). We identified 2521 unique reports, among which 664 (26.3%) were related to INI‐class use. Overall, 520 congenital anomalies were cited from 327 unique reports, of whom 31.0% were INI‐related. Compared to non‐INI drugs, no significant disproportionate reporting signal between prenatal exposure to INI‐class drugs and congenital anomalies was found (aROR 1.13; 95% CI:0.85–1.51). However, specific significant signals were reported for raltegravir/elvitegravir/dolutegravir drug exposure and urinary malformations (aROR 2.43; 95%CI:1.08–5.43), digestive malformations (aROR 3.09; 95%CI:1.22–7.84), and NTDs (aROR 3.02; 95%CI:1.09–8.37). Although specific congenital anomalies signals associated with raltegravir/elvitegravir/dolutegravir exposure were notified, causal relationship needs to be further investigated in prospective studies. [ABSTRACT FROM AUTHOR]

This article introduces the Perceived Economic Scarcity Scale (PESS), a novel instrument measuring the subjective evaluation and experience of economic scarcity (the feeling of having insufficient financial resources to meet one's needs). We conducted three high‐powered preregistered studies (total N = 1900) to rigorously evaluate the PESS's psychometric properties. In Study 1, we generated a pool of items and used both Principal Component Analysis and Exploratory Factor Analysis to select the most appropriate items. In Study 2, we examined the PESS's construct validity, demonstrating that it measures a distinct construct from related constructs such as subjective social class. In Study 3, we examined the PESS's predictive validity, demonstrating that it is a robust predictor of both affective outcomes (e.g. anxiety‐depressive symptoms) and cognitive outcomes (e.g. economic risk‐taking). Critically, we found that the PESS not only has incremental validity over and above income but also has greater predictive utility than income. We also found that the PESS score varies depending on the distance‐to‐pay and has excellent test–retest reliability. Overall, the PESS appears to be a valid and reliable instrument for assessing perceived economic scarcity, and we encourage researchers to use it to better understand the psychological consequences of 'not having enough'. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the real‐world rates of non‐adherence and non‐persistence to antiretroviral therapy (ART) among treatment‐naïve adult patients with HIV after a 12‐month follow‐up period in Belgium. Methods: A retrospective analysis of longitudinal pharmacy claims was conducted using the Pharmanet database from January 1, 2018, to December 31, 2021. Non‐adherence was assessed over 12 months and reported as the proportion of days covered below the 80% threshold. Non‐persistence was defined as the first 90‐day gap in treatment between the two types of ART dispensed. Poisson regression with robust standard error and Cox proportional hazard models were used to assess the factors associated with non‐adherence and non‐persistence, respectively. Results: Overall, 2999 patients were initiated on ART between 2018 and 2021. After a 12‐month follow‐up, the proportions of non‐adherence and non‐persistence were 35.6% and 15.9%, respectively in 2018, and decreased to 18.7% and 6.8%, respectively in 2021. Non‐adherence was higher among women, Brussels residents, and those receiving multiple‐tablet regimens (MTRs). Similarly, the prevalence of non‐persistence was higher among women and MTR recipients. Conclusion: Among treatment‐naïve adults with HIV in Belgium, non‐adherence, and non‐persistence to ART showed improvement over the study period but remained at high levels. Disparities were observed by sex and between geographical regions. Prioritizing strategies targeting women in Brussels and facilitating the transition from MTRs to single‐tablet regimens should be emphasized optimize adherence to ART in Belgium. [ABSTRACT FROM AUTHOR]

Income inequality is commonly posited to elevate concerns about social status that undermine psychological health, but the empirical evidence is inconsistent. Here we propose that these inconsistencies conceal opposing processes: Income inequality prompts perceived competitiveness, which can both negatively predict psychological health via avoidance motivation and positively predict psychological health via approach motivation. First, we conducted a two‐year longitudinal study (1,700+ participants from 500+ county identifiers) and provided support for our opposing processes model. Second, we conducted three pre‐preregistered studies using an experimental‐causal‐chain design. We sequentially showed that induced income inequality increased perceived competitiveness (Study 2a; 444 participants), induced perceived competitiveness increased avoidance and approach motivation (Study 2b; 1,018 participants), and induced avoidance/approach motivation decreased/increased psychological health (Study 2c; 562 participants). These findings suggest that scholars should shift from studying the main effects of income inequality on psychological health to studying the psychological processes involved in the inequality‐health relation. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to assess the real‐world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML). Methods: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add‐on to standard of care. One‐year follow‐up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1‐year survival. Results: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One‐year survival was 51.9% (41/79). PML–immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death‐1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow‐up magnetic resonance imaging at least once during follow‐up (OR = 3.16, 95% confidence interval = 1.20–8.72, p = 0.02) was associated with 1‐year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1‐month follow‐up in survivors compared to nonsurvivors (p < 0.0001). Thirty‐two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%). Interpretation: In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML‐IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257–270 [ABSTRACT FROM AUTHOR]

Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as "biological." Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3‐ to 4‐month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their mothers in large, outdoor, half‐acre cages. Maternal rank was defined as the proportion of animals outranked by each female, and the two genes of interest to us were monoamine oxidase and serotonin transporter, both of which are polymorphic in their promoter regions (MAOA‐LPR and 5‐HTTLPR, respectively), with one allele of each gene considered a "plasticity" allele, conferring increased sensitivity to environmental events. Our large sample size (n = 2014–3140) enabled us to examine the effects of individual genotypes rather than combining genotypes as is often done. Rank was positively associated with Confident temperament, but only for animals with the 5‐repeat allele for MAOA‐LPR. Rank had no other effect on temperament. In contrast, genotype had many different effects, with 5‐HTTLPR associated with behavioral inhibition, and MAOA‐LPR associated with ratings‐based measures of temperament. We also examined the joint effect of the two genotypes and found some evidence for a dose‐response: animals with the plasticity alleles for both genes were more likely to be behaviorally inhibited. Our results suggest phenotypic differences between animals possessing alleles for MAOA‐LPR that show functional equivalence based on in vitro tests, and our data for 5‐HTTLPR revealed differences between short/short homozygotes and long/short heterozygotes, strongly suggesting that combining genotypes for statistical analysis should be avoided if possible. Our analysis also provides evidence of sex differences in temperament, and, to our knowledge, the only evidence of differences in temperament based on specific pathogen‐free status. We suggest several directions for future research. Highlights: Maternal rank has minimal impact on infant temperament, influencing Confident temperament only for animals with the 5‐repeat allele for MAOA‐LPR.Animals with the short/short genotype (but not the long/short genotype) for 5‐HTTLPR are less likely to be behaviorally inhibited.Sex differences, and differences between specific‐pathogen‐free (SPF) and non‐SPF animals, were also found for all measures of temperament. [ABSTRACT FROM AUTHOR]

Objective: Restoring anti‐JC virus (JCV) immunity is the only treatment of progressive multifocal leukoencephalopathy (PML). Interleukin‐7 is a cytokine that increases number and function of T cells. We analyzed a population of PML patients who received recombinant human IL‐7 (rhIL‐7) to estimate survival and its determinants. Methods: After exclusion of patients with missing data or receiving other immunotherapies, findings from 64 patients with proven PML who received rhIL‐7 between 2007 and 2020 were retrospectively analyzed. Logistic regression was used to analyze variables associated with one‐year survival. Results: Underlying conditions were HIV/AIDS (n = 27, 42%), hematological malignancies (n = 16, 25%), primary immunodeficiencies (n = 13, 20%), solid organ transplantation (n = 4, 6%) and chronic inflammatory diseases (n = 4, 6%). One‐year survival was 54.7% and did not differ by underlying condition. Survival was not associated with baseline characteristics, but with a >50% increase in blood lymphocytes (OR 4.1, 95%CI 1.2–14.9) and CD4+ T cells (OR 5.9, 95%CI 1.7–23.3), and a > 1 log copies/mL decrease in cerebrospinal fluid JCV DNA (OR 7.6, 95%CI 1.6–56.1) during the first month after rhIL‐7 initiation. Side effects were mainly local and flu‐like symptoms (n = 8, 12.5%) and PML‐immune reconstitution inflammatory syndrome (IRIS) (n = 5, 8%). Interpretation: In this non‐controlled retrospective study, survival did not differ from that expected in HIV/AIDS patients, but might have been improved in those with hematological malignancies, primary immunodeficiencies and transplant recipients. RhIL‐7 might have contributed to the increase in blood lymphocytes and decrease in CSF JCV replication that were associated with better survival. ANN NEUROL 2022;91:496–505 [ABSTRACT FROM AUTHOR]

Introduction: Topical sertaconazole is indicated in the treatment of vaginal or mucocutaneous fungal infections due to Candida and dermatophytosis. To our knowledge, there is no data available in the literature on the potential effects of sertaconazole during pregnancy. The aim of this study was to evaluate the potential risks of topical sertaconazole use during pregnancy for the foetus and pregnancy. Materials and methods: The EFEMERIS database was used, which contained medications prescribed and dispensed to pregnant women in the Haute‐Garonne region whose pregnancy ended between July 2004 and December 2018. We compared pregnant women exposed to sertaconazole at least once during pregnancy to unexposed. Crude and adjusted odds ratios (OR) of major congenital anomalies and small gestational age at birth were estimated using logistic regression models. For other outcomes, hazard ratios (HR) were estimated by Cox regression models. Results: The study included 16,222 pregnant women (15.0%) who were given sertaconazole and 91,976 who were not. Exposure to sertaconazole during pregnancy was not associated with increased risks of any of the investigated outcomes, including natural pregnancy termination (HRa = 0.92 [0.78–1.08]), preterm birth (HRa = 1.06 [0.95–1.17]) and small for gestational age at birth (ORa = 0.78 [0.66–0.92]). No association between risk of major congenital anomalies overall and maternal exposure to sertaconazole during the first trimester was observed (ORa = 1.01 [0.84–1.21]). Discussion: This is the first study involving a large number of pregnant women to assess the potential risks of sertaconazole during pregnancy. This study does not indicate an increased risk of adverse pregnancy outcome and major congenital anomalies from exposure to topical sertaconazole. [ABSTRACT FROM AUTHOR]

Aims: In 2018, 1.07 million pregnant women received antiretroviral drugs, raising whether this affects pregnancy outcomes. We assessed the adverse pregnancy outcomes associated with prenatal antiretroviral drug exposure, notified to the French ANRS pharmacovigilance system. Methods: An exhaustive case report series has been performed using the ANRS pharmacovigilance database. All ANRS‐sponsored HIV clinical research studies using antiretroviral drugs either in pregnant women or women of childbearing age were eligible from 2004 to 2019. We analysed the following pregnancy outcomes: abortion, ectopic pregnancy, stillbirth, prematurity (<37 weeks of gestational age), low birth weight (<2500 g) and congenital abnormalities. A logistic regression was performed to assess the odds ratio (OR) for each outcome separately (if occurrence >50) compared to the outcome observed when exposed to non‐nucleoside‐reverse‐transcriptase‐inhibitor (NNRTI)‐based regimen as the reference. Results: Among the 34 studies selected, 918 deliveries occurred, of whom 88% had pregnancy outcomes documented. Pregnant women were mainly exposed to PI (n = 387, 48.6%), NNRTI (n = 331, 41.5%) and INI‐based combinations (n = 40, 5.0%, 18 on dolutegravir). Compared to NNRTI‐based combinations, there was no significant association observed with exposure to other antiretroviral combination for spontaneous abortion, prematurity or low birth weight, except an increased risk of low birth weight in new‐born exposed to exclusive nucleoside‐reverse‐transcriptase‐inhibitor (NRTI) combinations (n = 4; OR 7.50 [1.49–37.83]). Conclusions: Our study, mainly based on protease inhibitor (PI) and NNRTI‐based regimens, is overall reassuring on the risk of adverse pregnancy outcomes, except for NRTI which should be interpreted cautiously (small number, indication bias). In this study, the number of integrase inhibitor (INI)‐based combinations was too low to draw any conclusions. [ABSTRACT FROM AUTHOR]

A puzzle has emerged amidst rising inequality: why do people profess high levels of belief in meritocracy even as income gains are increasingly concentrated at the top? In light of contradictory theories and evidence, we undertake the first assessment of the relationship between local income inequality and meritocratic beliefs outside the United States, using data from the UK Household Longitudinal Study. We find that the positive relationship between country‐level income inequality and meritocratic beliefs identified in the recent literature does not translate straightforwardly below country level: there is no robust relationship between local income inequality and meritocratic beliefs in England. However, there is a robust—and somewhat paradoxical—positive association between high local income inequality and meritocratic beliefs among those with the lowest incomes. On average, respondents with annual household incomes of £10,000 are five points more likely (on a 100‐point scale) to believe their hard work will pay off if they live in the most rather than the least unequal places in England. We also show that this applies beyond the specific case of meritocratic beliefs: low‐income respondents in unequal places are also notably more satisfied with their own (low) income than similar respondents in more equal localities. In line with system justification theory, we argue that belief in meritocracy serves as an important tool of psychological resilience for low‐income individuals who regularly come into contact with others more economically fortunate than themselves: though it legitimates their current position at the bottom of the status hierarchy, this belief also offers the promise of future advancement. While this reduces concern about the psychological effects of growing local income inequality on the most economically vulnerable, it also suggests that there is little prospect of demand for systemic economic change emerging from what might have been considered the most likely places. [ABSTRACT FROM AUTHOR]

A fifth vaccine against Covid‐19, NVX‐CoV2373 Nuvavoxid® (Novavax), a protein‐based adjuvanted vaccine, was recently marketed in Europe. The main clinical trial before marketing concluded to a 'vaccine efficacy' of 89.7% without talking about other validated efficacy parameters. We further analysed the data of this clinical trial using the different validated methods of risk expression: absolute risks (AR), AR reduction (ARR) and number needed to treat (NNT). ARR and NNT values were 1.22% and 82, respectively, for an RR value of 0.10. Description of these parameters allowed defining some interesting characteristics of NVX‐CoV2373 efficacy according to age, race, variant and coexisting illness. Finally, we ask that the results of clinical trials be systematically presented, using not only RR but also including AR, ARR and NNT. [ABSTRACT FROM AUTHOR]

Aims: Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death‐related drugs recorded in a large pharmacovigilance database during the last 10 years. Methods: A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval. Results: Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years. Conclusion: Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries. [ABSTRACT FROM AUTHOR]

Summary: We aimed to assess the risk factors of venous thrombosis (VT) and arterial thrombosis (AT) in adults with primary immune thrombocytopenia (ITP), particularly in relation to treatments. The population comprised all incident primary ITP adults in France between 2009 and 2017 (FAITH cohort; NCT03429660) built in the national health database. Outcomes were the first hospitalisation for VT and AT. Multivariable Cox regression models included baseline risk factors, time‐varying exposure to ITP drugs, splenectomy and to cardiovascular drugs. The cohort included 10 039 patients. A higher risk of hospitalisation for VT was observed with older age, history of VT, history of cancer, splenectomy [hazard ratio (HR) 3·23, 95% confidence interval (CI) 2·26–4·61], exposure to corticosteroids (HR 3·55, 95% CI 2·74–4·58), thrombopoietin‐receptor agonists (TPO‐RAs; HR 2·28, 95% CI 1·59–3·26) and intravenous immunoglobulin (IVIg; HR 2·10, 95% CI 1·43–3·06). A higher risk of hospitalisation for AT was observed with older age, male sex, a history of cardiovascular disease, splenectomy (HR 1·50, 95% CI 1·12–2·03), exposure to IVIg (HR 1·85, 95% CI 1·36–2·52) and TPO‐RAs (HR 1·64, 95% CI 1·26–2·13). Rituximab was not associated with an increased risk. These findings help to estimate the risk of thrombosis in adult patients with ITP and to select treatment. [ABSTRACT FROM AUTHOR]

Several papers have reported that tramadol can induce hypoglycemia. However, in some reports, confounding factors can be found, like coadministration of hypoglycemic drugs. We used the WHO pharmacovigilance database (VigiBase®) to investigate whether tramadol alone could be associated with hyponatremia. All 2010–2019 ICSRs (Individual Case Safety Reports) with the PT term "hyponatremia" and tramadol were included. Two disproportionality analyses were performed: 1/after inclusion of all reports, 2/after exclusion of concomitant hypoglycemic drugs. Results are expressed as Reporting Odds Ratios (ROR; 95% CI). Among 10 038 436 ICSRs, 97 639 were included. In comparison with codeine, a significant association was found between tramadol use and reports of hypoglycemia before [ROR = 1.54 (1.43–1.66)] or after [ROR = 1.43 (1.31–1.56)] exclusion of hypoglycemic drugs. Tramadol use is associated with a higher risk of hypoglycemia reports than codeine, the other step 2 analgesic, in the presence as well as in the absence of other hypoglycemic drugs. We concluded that hypoglycemia is an adverse drug reaction of tramadol, which can be observed in diabetic as well as in non‐diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. Methods: We compared two cohorts of LVO‐related patients with large core (>50 ml on diffusion‐weighted‐imaging or CT‐perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre‐MT era from a prospective registry. Primary outcome was 90‐day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). Results: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72–131) and MMRatio 1.4 (IQR: 1.0–1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7–27.0] vs 0.7 [0.1–6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow‐up imaging was more frequent in the MT + BMM group regardless of the MMRatio. Interpretation: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417–427 [ABSTRACT FROM AUTHOR]

Background: There are no effective treatments for multiple system atrophy (MSA). Objective: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. Methods: This was a double‐blind, parallel‐group, placebo‐controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease–Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA‐Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. Results: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (−2.13 units [95% confidence interval, CI, −4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12‐week in UMSARS Part II (exploratory outcome: −1.41 units [95% CI, −2.84; 0.03]; p = 0.05) and in MSA‐QoL emotional/social dimension (secondary outcome: −6.99 units [95% CI, −13.40; −0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). Conclusion: The MSA‐FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID‐19 with hypertension/cardiovascular disease, particularly in Europe. The ACE‐CoV study was designed to assess this question. The study was conducted in the Covid‐Clinic‐Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS‐CoV‐2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid‐Clinic‐Toul included 263 patients. Among them, 111 were included in the ACE‐CoV study population. In OW‐PS‐adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73–3.33). It was 0.99 (95% CI: 0.68–1.45) for ACEIs and 1.64 (95% CI: 0.77–3.50) for ARBs. Analyses with weighting by the IPTW‐PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE‐CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID‐19 with a history of cardiovascular disease/arterial hypertension. [ABSTRACT FROM AUTHOR]

Several vaccines are being developed as part of the COVID‐19 pandemic. The results of clinical trials for these vaccines were published with efficacy values of more than 90%, using mainly relative risk (RR). In this paper, we decided to reanalyse the data using the different validated methods of risk expression. Using main publications, absolute risks (AR), AR reduction (ARR), number needed to treat (NNT) were calculated for five COVID‐19 vaccines (tozinameran Comirnaty®, Moderna, Vaxzevria®, Janssen, and Sputnik V vaccines). AR, ARR, NNT, and RR values varied according to COVID‐19 vaccines. The order of the different vaccines was not the same according to the chosen efficacy parameters. This is a further example of the need to express results of clinical trials, using not only RR, but also AR, ARR, and NNT in order to clearly present the clinical interest of drugs. [ABSTRACT FROM AUTHOR]

Social capital interventions for the mental health of older adults have been inconclusive to date, and have rarely investigated the psychological resources that are important to having social capital. This study focused on the "Neighborhoods in Solidarity" (NS), which are a series of Swiss community‐based interventions that aim to empower older adults to participate in their communities. Our goal was to understand whether the NS were associated with collaborative competence, social capital, and subsequently, symptoms of depression. Cross‐sectional data were collected from 947 individuals aged 55 and over (Mage = 68.66, SD = 9.04) in 10 Swiss neighbourhoods (five with the NS [n = 479] and five control neighbourhoods [n = 468]). Structural equation modelling was used to model the relationship between the NS intervention, collaborative competence, cognitive and structural dimensions of social capital, and symptoms of depression (measured by the CESD‐R‐10). Individual participation in the NS had total and indirect effects on symptoms of depression via collaborative competence and both social capitals. These findings suggest that existing community‐based interventions can be indirectly associated with better mental health outcomes in the ageing population. [ABSTRACT FROM AUTHOR]

Patients with COVID‐19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID‐19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug–drug interactions. Here, we analyzed the potential or proven risk of the co‐administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID‐19. Practical recommendations are offered, where possible. [ABSTRACT FROM AUTHOR]

No increased risk of cataract in adult patients with primary immune thrombocytopenia treated with eltrombopag. During a total follow-up of 31 448 patient-years, 573 patients had a surgery for cataract and 1089 (12-9%) were exposed to eltrombopag (309 with >=365 DDDs). II TableRisk of cataract surgery associated with exposure to eltrombopag in patients with immune thrombocytopenia (ITP). (2017) Occurrence and management of cataracts in adult patients (pts) with chronic immune thrombocytopenia (cITP) during long-term treatment with eltrombopag (EPAG): Results from the extend study. [Extracted from the article]

Objective: Scholars disagree on whether income inequality has incentive or disincentive effects. In the present research, we move beyond such debate and focus on the motivational processes that income inequality predicts. First, income inequality makes economic stratification salient; therefore, it should promote perceived competitiveness. Second, competitiveness can be appraised as both a challenge and a threat; therefore, it should promote both approach and avoidance motivation.Method: In three studies (N = 2,543), U.S. residents from various ZIP codes reported the extent to which they perceived competitiveness in their town/city (Studies 1-3), as well as their economic achievement goals, achievement motives, and self-regulatory foci (Studies 2-3).Results: Level of local income inequality was found to be a positive predictor-via increased perceived competitiveness-of other-approach economic goals, need for achievement, and promotion focus, as well as other-avoidance economic goals, fear of failure (specifically, the shame/embarrassment component), and prevention focus. Furthermore, actual and perceived income inequality were positively correlated.Conclusions: The conceptual and empirical work herein is the first to show how the economic environment predicts individuals' perceptions of competitiveness, influencing personal goals, motives, and orientations. It provides a more nuanced perspective on the implications of income inequality than perspectives currently available. [ABSTRACT FROM AUTHOR]

Background and purpose: Diffusion‐weighted imaging (DWI) commonly detects acute ischaemic lesions in patients with acute intracerebral hemorrhage (ICH), especially with cerebral amyloid angiopathy (CAA). We investigated the relationship between cortical superficial siderosis (cSS), a neuroimaging marker of CAA, and DWI lesions in patients with acute ICH. Methods: We conducted a retrospective analysis of prospectively collected data from consecutive patients with acute supratentorial ICH who underwent brain magnetic resonance imaging within 10 days after symptom onset. Magnetic resonance imaging scans were analyzed for DWI lesions, cSS and other markers for small‐vessel disease. Univariate and multivariate analyses were performed to assess the association between cSS and DWI lesions. Results: Among 246 ICH survivors (mean age 71.4 ± 12.6 years) who were enrolled, 126 had lobar ICH and 120 had deep ICH. Overall, DWI lesions were observed in 38 (15.4%) patients and were more common in patients with lobar ICH than deep ICH (22.2% vs. 8.3%; P = 0.003). In multivariate logistic regression analysis, the extent of white matter hyperintensities [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05–1.58; P = 0.02] and cSS severity (focal cSS: OR, 3.54; 95% CI, 1.28–9.84; disseminated cSS: OR, 4.41; 95% CI, 1.78–10.97; P = 0.001) were independently associated with the presence of DWI lesions. Conclusions: Diffusion‐weighted imaging lesions are more frequently observed in patients with acute lobar ICH than in those with deep ICH. cSS severity and white matter hyperintensity extent are independent predictors for the presence of DWI lesions, suggesting that CAA may be involved in the pathogenesis of DWI lesions associated with acute ICH. [ABSTRACT FROM AUTHOR]

In contrast to statins, the risk of diabetes with fibrates was not clearly studied. This study investigates a putative signal of diabetes associated with the use of fibrates using the World Health Organization (WHO) global individual case safety reports database, VigiBase®. We included all reports registered until the 31st December 2017 in VigiBase® to measure the risk of reporting 'hyperglycemia or new onset of diabetes' (SMQ term) compared with all other reports [as a reporting odds ratio (ROR 95% CI)] for fibrates, statins, and the combination fibrates + statins. The likelihood that diabetes resulted from statin–fibrate interaction was also estimated. According to the interaction additive model, a ROR value for coexposure exceeding the sum of the RORs estimated for each individual class of drug supports a potential drug–drug interaction (DDI). To assess the stability of our results, we performed several sensitivity analyses, according to outcome definition and after exclusion of putative competitive (hyperglycemic) drugs. We included 19 149 patients exposed to fibrates (without statins), 177 323 to statins (without fibrates) and 3 247 to statins plus fibrates. In contrast to statins (ROR = 1.75, 95% CI 1.72–1.78), no association was found for fibrates (ROR = 0.76, 95% CI 0.71–0.82). The ROR value was lower for the combination statins plus fibrates (ROR = 1.46, 95% CI 1.28–1.67). Similar trends were found in sensitivity analyses. This study, performed in the real conditions of use, failed to find a signal of diabetes with fibrates. It strengths the association previously described with statin without any evidence for a statin–fibrate DDI. [ABSTRACT FROM AUTHOR]

Abstract: Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV‐infected patients. This study aimed to compare adherence to generic multi‐tablet regimens (MTR) vs. brand MTR likely to incorporate ARV drugs without breaking fixed‐dose combinations (FDC) and brand single‐tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over exposed to one of the generic or the brand of lamivudine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Adherence was measured by medication possession ratio (MPR) using both defined daily dose (DDD) and daily number of tablet recommended for adults (DNT). Adherence to generic MTR vs. brand MTR and brand STR was compared using Kruskal–Wallis. The overall median adherence was 0.97 (IQR 0.13) by DNT method and 0.97 (0.14) by DDD method. Adherence in patients exposed to generic MTR (n = 165) vs. brand MTR (n = 481) and brand STR (n = 470) was comparable by DNT and DDD methods. In conclusion, adherence to generic MTR was high and comparable with adherence to brand MTR and to STR. Utilization of DDD instead DNT to measure the MPR led to small but nonsignificant difference that has no clinical impact. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by biological drugs (BD) and a group treated by traditional systemic treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi‐Pyrénées area (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between ‘exposed’ patients treated with BD (adalimumab, etanercept, infliximab, or ustekinumab) and ‘unexposed’ patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine). We realized a survival analysis on the first infectious event, defined as an anti‐infective drug delivery or a hospital diagnosis of infection. We selected 101 ‘exposed’ and 788 ‘unexposed’ patients. In our multivariate Cox model, ‘exposure’ did not seem to decrease the time frame of the first infectious event compared with ‘nonexposure’ (HR = 0.94, P = 0.62). Among all treatment, the safest seemed to be ustekinumab while the least safe was etanercept. We found factors statistically associated with the risk of infection: gender (female vs. male), economic deprivation, chronic hepatitis B or C, history of cancer, at least one infectious event, and the number of different drugs during the 6‐month period before the study. We did not find any difference of infective risk between the BD and the TST. This result enhances the recent PSONET registries conclusions. [ABSTRACT FROM AUTHOR]

Background and purpose: Acute convexity subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS) are neuroimaging markers of cerebral amyloid angiopathy (CAA) that may arise through similar mechanisms. The prevalence of cSS in patients with CAA presenting with acute cSAH versus lobar intracerebral hemorrhage (ICH) was compared and the physiopathology of cSS was explored by examining neuroimaging associations. Methods: Data from 116 consecutive patients with probable CAA (mean age, 77.4 ± 7.3 years) presenting with acute cSAH (n = 45) or acute lobar ICH (n = 71) were retrospectively analyzed. Magnetic resonance imaging scans were analyzed for cSS and other imaging markers. The two groups’ clinical and imaging data were compared and the associations between cSAH and cSS were explored. Results: Patients with cSAH presented mostly with transient focal neurological episodes. The prevalence of cSS was higher amongst cSAH patients than amongst ICH patients (88.9% vs. 57.7%; P < 0.001). In multivariable logistic regression analysis, focal [odds ratio (OR) 6.73; 95% confidence interval (CI) 1.75–25.81; P = 0.005] and disseminated (OR 11.68; 95% CI 3.55–38.35; P < 0.001) cSS were independently associated with acute cSAH, whereas older age (OR 0.93; 95% CI 0.87–0.99; P = 0.025) and chronic lobar ICH count (OR 0.45; 95% CI 0.25–0.80; P = 0.007) were associated with acute lobar ICH. Conclusions: Amongst patients with CAA, cSS is independently associated with acute cSAH. These findings suggest that cSAH may be involved in the pathogenesis of the cSS observed in CAA. Longitudinal studies are warranted to assess this potential causal relationship. [ABSTRACT FROM AUTHOR]

Aims Apelin is a recently identified adipokine known to improve glucose tolerance and insulin sensitivity in murine models. This study was dedicated to the proof of concept that apelin administration also enhances insulin sensitivity in humans. Materials and Methods Healthy overweight men were enrolled in this randomized, double-blind, placebo-controlled, cross-over study that successively considered the efficacy and the tolerance of 2 doses of (pyr1)- Apelin-13. A first group of subjects received 9 nmol/kg ( n = 8) of (pyr1)- Apelin-13 and, after examination of safety data, a second group received 30 nmol/kg ( n = 8). Each volunteer underwent 2 hyperinsulinaemic-euglycaemic clamps where the basal level of glucose infusion rate ( GIR) was measured from the 90th to the 120th minute (level 1). Continuous intravenous administration of apelin or placebo was ongoing for 2 hours and GIR was finally evaluated from the 210th to the 240th minute (level 2). Primary evaluation endpoint was the difference in GIR between level 2 and level 1 (Δ GIR). Results A slight increase in Δ GIR was observed with the low apelin dose (0.65 ± 0.71 mg/kg/min, P = .055) whereas the highest dose significantly improved insulin sensitivity (0.82 ± 0.71 mg/kg/min, P = .033). Cardiovascular monitoring and safety reports did not reveal any side effect of apelin administration. Conclusion As the first demonstration of the insulin-sensitizing action of apelin in humans, alongside numerous studies in rodents, this trial confirms that the apelin/ APJ pathway should be considered as a new target to design alternative therapeutic strategies to control insulin resistance in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Catholics and Protestants differ in terms of social autonomy versus heteronomy. We propose that the regulation of behavior in accordance with social norms depends on the social control exercised by an authority for Catholics more than it does for Protestants. Two experiments measured cheating behavior (the transgression of a social norm) as a function of the religious group (Protestant vs. Catholic) and social control (with vs. without). Catholics were found to be more responsive to social control, that is, to cheat less when social control was salient, whereas Protestants' behavior did not depend on this dimension. In Study 2, intrinsic-extrinsic religiousness was found to mediate this difference. Results are discussed in the context of the effects of public policies based on social control. [ABSTRACT FROM AUTHOR]

The potential favorizing role of drugs in sleep apnea syndrome ( SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions ( ADRs) in VigiBase®, the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case-noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37-year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were 'serious' in around 82% of cases. The case-noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS. [ABSTRACT FROM AUTHOR]

Background: Chronic exchange transfusion is effective for primary and secondary prevention of stroke in children with sickle cell anemia (SCA). Erythrocytapheresis is recognized to be the most efficient approach; however, it is not widely implemented and is not suitable for all patients. The aim of our study was to compare automated exchange transfusion (AET) with our manual method of exchange transfusion and, in particular, to evaluate the efficacy, safety, and cost of our manual method.Study Design and Methods: Thirty-nine SCA children with stroke and/or abnormal findings on transcranial Doppler were included in the study. We retrospectively analyzed 1353 exchange sessions, including 333 sessions of AET and 1020 sessions of manual exchange transfusion (MET).Results: Both methods were well tolerated. The median decrease in hemoglobin (Hb)S per session was 21.5% with AET and 18.8% with our manual method (p < 0.0001) with no major increase in red blood cell consumption. Iron overload was well controlled, even with the manual method, with a median (interquartile range) ferritin level of 312 (152-994) µg/L after 24 months of transfusions. The main differences in annual cost relate to equipment costs, which were 74 times higher with the automated method.Conclusion: Our study shows that continuous MET has comparable efficacy to the automated method in terms of stroke prevention, decrease in HbS, and iron overload prevention. It is feasible in all hospital settings and is often combined with AET successively over time. [ABSTRACT FROM AUTHOR]

Children with sickle cell disease ( SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy ( CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre ( n = 375 SS/Sβ0). Median follow-up was 6·8 years (2677 patient-years). Among the 59 children presenting with CV, seven had a stroke. Overall, the incidence of CV was 2·20/100 patient-years [95% confidence interval (95% CI): 1·64-2·76] and the incidence of stroke was 0·26/100 patient-years (95% CI: 0·07-0·46). The cumulative risk of CV by age 14 years was 26·0% (95% CI: 20·0-33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper-airway obstruction [Hazard ratio ( HR) = 1·47; 95% CI: 1·05-2·06] or bronchial obstruction ( HR = 1·76; 95% CI: 1·49-2·08) and reticulocyte count ( HR = 1·82 per 50 × 109/l increase; 95% CI: 1·10-3·01) were independent risk factors whereas fetal haemoglobin level ( HR = 0·68 per 5% increase; 95% CI: 0·48-0·96) was protective. Alpha-thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower-airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV. [ABSTRACT FROM AUTHOR]

Background Biological drugs have dramatically improved the management of moderate to severe psoriasis. Little is known about their economic impact in daily clinical practice. Objective The aim of this study was to estimate the costs of biological drugs, in term of health resources consumption, and to compare it with costs induced by traditional systemic treatments. Methods This cohort study was built from the French health insurance database in the Midi Pyrénées area (2.8 million inhabitants, South West of France). We compared health care costs between 'exposed' patients treated with biological drugs (adalimumab, etanercept, infliximab or ustekinumab) and 'unexposed' patients defined as patients who received traditional systemic treatments (phototherapy, acitretin, methotrexate or cyclosporin) during a 6-month period. Results A total of 1924 patients met the inclusion criteria. Sixty-nine patients were 'exposed', whereas 1855 patients were 'unexposed'. 'Exposed' patients had a mean total healthcare cost of 8107€ vs. 1678€ ( P < 0.001) for 'unexposed' patients. They had higher costs concerning inpatient admission, medication and consultations including dermatology consultations, laboratory, non-medical care and transportation. Biological drug prescription was associated with an increase in the use of anti-infective drugs and with a reduction in the use of psychoactive drugs. Conclusion The mean total health care expenditure in patients treated with biological drugs was five times higher as compared with patients treated with traditional systemic treatments. The limitation of the study is the short duration of follow-up comprising a loading dose period for some biological drugs. This may have contributed to an overestimation of drug-related costs. [ABSTRACT FROM AUTHOR]

Drug-drug interactions ( DDIs) between antihypertensive drugs and non-steroidal anti-inflammatory drugs ( NSAIDs) can lead to adverse drug reactions ( ADRs). Guidelines are available to help prescribers deal with these drug associations, but their implementation is not well evaluated. The aims of this study were to assess the prevalence of NSAIDs exposure in patients treated with antihypertensive drugs, using the French Pharmacovigilance database, and explore the ADRs related to DDIs between antihypertensive drugs and NSAIDs. Over the 11, 442 notifications of ADRs recorded in this database in patients treated with oral antihypertensive drugs between 2008 and 2010, 517 (4.5 and 95% CI: 4.1-4.9) also included exposure to NSAIDs. These subjects were more frequently women, took more drugs in general, and were younger and less frequently treated with antiplatelet drugs. In 24.2% of them (125 patients), a DDI between NSAIDs and antihypertensive drugs was potentially the cause of the reported ADR. Acute renal failure caused by DDIs between NSAIDs and angiotensin-converting enzyme inhibitors ( ACEIs), angiotensin receptor blockers ( ARBs), or diuretics was the most frequently reported ADR (20.7%). Finally, in the French Pharmacovigilance database, around one-fourth of associations NSAIDs + antihypertensive drugs are associated with a 'serious' ADR (mainly acute renal failure), suggesting that this well-known DDI is not enough taken into account by prescribers. [ABSTRACT FROM AUTHOR]

Socio-cognitive conflict has been defined as a situation of confrontation with a disagreeing other. Previous research suggests that individuals can regulate conflict in a relational way, namely by focusing on social comparison between relative levels of competences. Relational conflict regulation has been described as yielding particularly negative effects on social interactions and learning, but has been understudied. The present research addresses the question of the origin of relational conflict regulation by introducing a fundamental distinction between two types of regulation, one based on the affirmation of one's own point of view and the invalidation of the other's (i.e., 'competitive' regulation), the other corresponding to the protection of self-competence via compliance (i.e., 'protective' regulation). Three studies show that these modes of relational conflict regulation result from the endorsement of distinct performance goals, respectively, performance-approach goals (trying to outperform others) and performance-avoidance goals (avoiding performing more poorly than others). Theoretical implications for the literature on both conflict regulation and achievement goals are discussed. [ABSTRACT FROM AUTHOR]

The article presents a case study related to 4-year-old boy has presented to the emergency department for asthenia, leg pain, and anuria. Topics include the abdominal ultrasound has showed marked bilateral kidney enlargement, the contrast-enhanced computed has performed for differential diagnosis of the metabolic disorders were controlled demonstrated bilateral enlargement, and the heterogenous hypodensity of the kidneys with decreased corticomedullary differentiation but no lymphadenopathy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Several factors are known to influence spontaneous reporting of adverse drug reactions (ADRs). Among them, 'seriousness' of the reaction is one of the most important. • However, evolution in the reporting of 'serious' vs.'non-serious' ADRs over time for the same drug remains unknown. WHAT THIS STUDY ADDS • Spontaneous reports mainly involve 'non-serious' ADRs during the first years of marketing and 'serious' ADRs later, particularly for drugs with non-hospital use. AIM To investigate trends in spontaneous reporting to the French Pharmacovigilance system of 'serious' (SADRs) and 'non-serious' (NSADRs) adverse drug reactions over time. METHODS Annual SADR : NSADR ratios were calculated for each drug and their evolution tested with linear trend tests. RESULTS Among the 39 new active substances commercialized in France in 2000, 16 had sufficient data to perform linear trend tests. An increasing linear relation was found for five widely prescribed drugs, a non-significant increasing trend for eight others, i.e. drugs mostly used in hospitals. CONCLUSION ADR reports mainly concern NSADRs during first years of marketing. Reports of SADRs are proportionally more frequent later. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose Risk factors for intravenous immunoglobulin-induced renal failure (IVIg-RF) were suspected from case series studies. This study was aimed at quantifying the risk of IVIg-RF associated with exposure to drugs that modify intrarenal hemodynamics. Methods We conducted a case-control study in the French Pharmacovigilance Database (FPVD). Adult IVIg-RF cases registered in the FPVD from 1996 to 2009 were reviewed. Controls were patients included in the FPVD for another IVIg adverse effect. Controls were matched for sucrose content of the preparation, year of adverse event and age. The predictors of IVIg-RF were exposure to angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor antagonists (ARA), diuretics, age, gender and weight, IVIg delivered dose and infusion duration, chronic kidney disease, hypertension and diabetes mellitus. Acute IVIg-RF was defined as a calculated creatinine clearance less than 60 mL/min and, in the event of chronic kidney disease, (i) a more than 50% increase of serum creatinine, (ii) an indication of oligo-anuria or (iii) a requirement for dialysis. Results We selected 71 cases and 71 controls. Forty-nine percent of the cases required transient hemodialysis. In the final multivariate model, exposure to ACE-I and/or ARA was the sole independent predictor associated with IVIg-RF (OR = 7.9, 95%CI = 1.3-49.2). There was an interaction between 'diabetes mellitus' (OR = 7.7, 95%CI = 2.3-25.5) and 'chronic kidney disease' (OR = 13.0, 95%CI = 3.1-54.7), both being strong risk factors in univariate models ( p < 0.001). Chronic hypertension was a risk factor for hemodialysis. Conclusions Temporary interruption of ACE-I and ARA may be considered at the time of IVIg infusion. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose Heat waves could reveal or aggravate several 'serious' adverse drug reactions (ADRs) in elderly. Thus, we wanted to describe the main characteristics of heat-related 'serious' ADRs occurred in patients older than 70 years during these two events in France (2003 and 2006). Methods We analysed 'serious' ADRs reported to the network of French pharmacovigilance centres in summer 2003 and 2006 and suspected to be heat related. 'Serious' ADRs occurred during summers with heat waves (2003 and 2006) were compared with ADRs occurred during the same months in the summers of 2004 and 2005 (reference period). Results Patients' characteristics and number of 'serious' ADRs were similar whatever the year of the study. Number of drug-related deaths seemed higher in 2003 than in 2004-2005. More 'serious' heat-related ADRs were reported in the summers of 2003 and 2006 (68 in 2003 and 72 in 2006). Comparing with the reference period, metabolic ADRs were less frequent during the summers of 2003 (29%, p = 0.0001) and 2006 (39%, p = 0.003). Occurrence of other ADRs was similar whatever the period. Drugs more frequently involved during heat waves were diuretics, serotonic antidepressants, angiotensin converting inhibitors and proton pump inhibitors. Differences between 2003 and 2006 were found for non-dopaminergic (atropinic) antiparkinsonians or antiepileptics (most frequently involved in 2006) and beta-blockers or proton pump inhibitors (less frequently involved in 2006). Conclusion The present study underlines the interest of a National Pharmacovigilance Database to follow each year the role of drugs in heat-related ADRs. This survey should be associated with other pharmacoepidemiological methods, such as case-control or population-based studies. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss the benefits and strengths of disproportionality analysis as a method to identify adverse drug reactions (ADRs). They provide a brief historical background of the method as well as its principles and applications. They add that the said approach is a validated method in research of drug safety and surveillance and must be considered as exploratory in a situation of signal detection.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Dilated cardiomyopathy is a frequent disease, responsible for 40–50% of cases of heart failure. • Several aetiologies have been reported: idiopathic, familial/genetic, viral and/or immune but also toxic agents (alcohol, cobalt, carbon monoxide, lead, cocaine, mercury or drugs). • Among drugs, anthracyclines are well known to induce such an adverse drug reaction. WHAT THIS STUDY ADDS • This study describes an association with already suspected drugs (anthracyclines, antiretrovirals). • It also found a signal with other drugs (antipsychotics, lithium, antidepressants, retinoids). • This pharmacovigilance signal should be confirmed by further prospective studies. AIMS To evaluate putative associations between drugs and dilated cardiomyopathy. METHODS We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals. RESULTS Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were ‘suspect’. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs. CONCLUSIONS The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors . . .), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Three ‘weak’ opioid analgesics are marketed in France and other European countries in association with paracetamol. • They are very largely used, but to our knowledge there is no large study comparing the reporting rate of adverse drug reactions (ADRs) between these different step 2 analgesic combinations to determine the safest one. WHAT THIS STUDY ADDS • The aim of this study was to compare reporting rate of ADRs with three step 2 combinations according to their consumption in France. • The results show that among these combinations, reporting rate and ‘seriousness’ of reported ADRs are the highest with tramadol/paracetamol (TRM+P) and the lowest with codeine/paracetamol. • The safety of TRM+P needs to be urgently investigated with more methodologically rigorous studies. AIMS Three ‘weak’ opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare the reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol (COD+P) and dextropropoxyphene/paracetamol (DXP+P). METHODS All spontaneous reports submitted to the French Pharmacovigilance Database from 1 January 1987 to 31 December 2006 suspected to be induced by one of the three step 2 analgesic combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same period was obtained from the French Drug Agency. The number of ADRs, serious ADRs and different organ classes of ADRs were compared according to their consumption. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each variable using DXP+P as reference. RESULTS The reporting rate of ADRs was calculated as 24.9/100 000 person-years for DXP+P, 44.5/100 000 person-years for TRM+P and 12.5/100 000 person-years for COD+P. The reporting rate (OR 0.56, 95% CI 0.50, 0.63) and ‘seriousness»’ (OR 0.65, 95% CI 0.53, 0.80) of ADRs were significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59, 4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and ‘seriousness’ (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with DXP+P than with COD+P. CONCLUSIONS Among the three step 2 analgesic combinations, reporting rate and ‘seriousness’ of ADRs are the highest with TRM+P and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is worst than that of COD+P. [ABSTRACT FROM AUTHOR]

Objective To review the cardiovascular adverse drug reactions (ADRs) with memantine reported to the French PharmacoVigilance Database. Methods We reviewed all the observations of cardiovascular ADRs with memantine reported to the French PharmacoVigilance Database up to May 2007. We recorded the characteristics of patients (age, sex and underlying disease) and of ADRs (nature, seriousness, delay in occurrence, evolution, imputability). Results After exclusion of 16 cases, the cardiac origin of which was not clearly assessed, 36 cardiac ADRs with memantine were recorded between its commercialisation in France (July 2003) and May 2007. These ADRs consisted of 18 reports of bradycardia and 18 reports of various cardiovascular ADRs (orthostatic hypotension with fall[6] electrocardiogram perturbations[4] fainting[2] malaise with arterial hypotension[2] arterial hypotension and acute renal failure[1] fatal heart failure[1] sudden death[2]). Among the 18 reports of bradycardia, 7 cases occurred with memantine as the sole suspected drug and all but one resolved after memantine's discontinuation. Conclusion Cardiovascular properties of memantine seem to be complex and remain quite unclear. Despite its drawbacks and its descriptive design, our study suggests that memantine could determine some cardiac ADRs, especially bradycardia; the mechanism of which remains unexplained. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]