Unravelling the alcohol harm paradox: a population-based study of social gradients across very heavy drinking thresholds

Background: There is consistent evidence that individuals in higher socioeconomic status groups are more likely to report exceeding recommended drinking limits, but those in lower socioeconomic status groups experience more alcohol-related harm. This has been called the ‘alcohol harm paradox’. Such studies typically use standard cut-offs to define heavy drinking, which are exceeded by a large proportion of adults. Our study pools data from six years (2008–2013) of the population-based Health Survey for England to test whether the socioeconomic distribution of more extreme levels of drinking could help explain the paradox. Methods: The study included 51,498 adults from a representative sample of the adult population of England for a cross-sectional analysis of associations between socioeconomic status and self-reported drinking. Heavy weekly drinking was measured at four thresholds, ranging from 112 g+/168 g + (alcohol for women/men, or 14/21 UK standard units) to 680 g+/880 g + (or 85/110 UK standard units) per week. Heavy episodic drinking was also measured at four thresholds, from 48 g+/64 g + (or 6/8 UK standard units) to 192 g+/256 g + (or 24/32 UK standard units) in one day. Socioeconomic status indicators were equivalised household income, education, occupation and neighbourhood deprivation. Results: Lower socioeconomic status was associated with lower likelihoods of exceeding recommended limits for weekly and episodic drinking, and higher likelihoods of exceeding more extreme thresholds. For example, participants in routine or manual occupations had 0.65 (95 % CI 0.57–0.74) times the odds of exceeding the recommended weekly limit compared to those in ‘higher managerial’ occupations, and 2.15 (95 % CI 1.06–4.36) times the odds of exceeding the highest threshold. Similarly, participants in the lowest income quintile had 0.60 (95 % CI 0.52–0.69) times the odds of exceeding the recommended weekly limit when compared to the highest quintile, and 2.30 (95 % CI 1.28–4.13) times the odds of exceeding the highest threshold. Conclusions: Low socioeconomic status groups are more likely to drink at extreme levels, which may partially explain the alcohol harm paradox. Policies that address alcohol-related health inequalities need to consider extreme drinking levels in some sub-groups that may be associated with multiple markers of deprivation. This will require a more disaggregated understanding of drinking practice

Interventions that enhance health services for parents and infants to improve child development and social and emotional well-being in high-income countries: A systematic review

Background: Experiences in the first 1000 days of life have a critical influence on child development and health. Health services that provide support for families need evidence about how best to improve their provision. Methods: We systematically reviewed the evidence for interventions in high-income countries to improve child development by enhancing health service contact with parents from the antenatal period to 24 months postpartum. We searched 15 databases and trial registers for studies published in any language between 01 January 1996 and 01 April 2016. We also searched 58 programme or organisation websites and the electronic table of contents of eight journals. Results: Primary outcomes were motor, cognitive and language development, and social-emotional well-being measured to 39 months of age (to allow the interventions time to produce demonstrable effects). Results: were reported using narrative synthesis due to the variation in study populations, intervention design and outcome measurement. 22 of the 12 986 studies identified met eligibility criteria. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group criteria, the quality of evidence overall was moderate to low. There was limited evidence for intervention effectiveness: positive effects were seen in 1/6 studies for motor development, 4/11 for language development, 4/8 for cognitive development and 3/19 for social-emotional well-being. However, most studies showing positive effects were at high/unclear risk of bias, within-study effects were inconsistent and negative effects were also seen. Intervention content and intensity varied greatly, but this was not associated with effectiveness. Conclusions: There is insufficient evidence that interventions currently available to enhance health service contacts up to 24 months postpartum are effective for improving child development. There is an urgent need for robust evaluation of existing interventions and to develop and evaluate novel interventions to enhance the offer to all families

Arterially Perfused Neurosphere-Derived Cells Distribute Outside the Ischemic Core in a Model of Transient Focal Ischemia and Reperfusion In Vitro

BACKGROUND: Treatment with neural stem cells represents a potential strategy to improve functional recovery of post-ischemic cerebral injury. The potential benefit of such treatment in acute phases of human ischemic stroke depends on the therapeutic viability of a systemic vascular delivery route. In spite of the large number of reports on the beneficial effects of intracerebral stem cells injection in experimental stroke, very few studies demonstrated the effectiveness of the systemic intravenous delivery approach. METODOLOGY/PRINCIPAL FINDINGS: We utilized a novel in vitro model of transient focal ischemia to analyze the brain distribution of neurosphere-derived cells (NCs) in the early 3 hours that follow transient occlusion of the medial cerebral artery (MCA). NCs obtained from newborn C57/BL6 mice are immature cells with self-renewal properties that could differentiate into neurons, astrocytes and oligodendrocytes. MCA occlusion for 30 minutes in the in vitro isolated guinea pig brain preparation was followed by arterial perfusion with 1x10(6) NCs charged with a green fluorescent dye, either immediately or 60 minutes after reperfusion onset. Changes in extracellular pH and K(+) concentration during and after MCAO were measured through ion-sensitive electrodes. CONCLUSION/SIGNIFICANCE: It is demonstrated that NCs injected through the vascular system do not accumulate in the ischemic core and preferentially distribute in non-ischemic areas, identified by combined electrophysiological and morphological techniques. Direct measurements of extracellular brain ions during and after MCA occlusion suggest that anoxia-induced tissue changes, such as extracellular acidosis, may prevent NCs from entering the ischemic area in our in vitro model of transitory focal ischemia and reperfusion suggesting a role played by the surrounding microenviroment in driving NCs outside the ischemic core. These findings strongly suggest that the potential beneficial effect of NCs in experimental focal brain ischemia is not strictly dependent on their homing into the ischemic region, but rather through a bystander mechanism possibly mediated by the release of neuroprotective factors in the peri-infarct region

Do consequences of a given pattern of drinking vary by socioeconomic status? A mortality and hospitalisation follow-up for alcohol-related causes of the Finnish Drinking Habits Surveys

Background: Socioeconomic differences in alcohol-related mortality and hospitalisations, as based on register data, are larger than socioeconomic differences in various types of harmful drinking, as based on survey data. Objective: The aim was to use a follow-up study to examine whether differential drinking patterns between socioeconomic groups explain the observed differences in alcohol-related mortality and hospitalisations, or whether similar drinking patterns predict higher mortality among lower socioeconomic groups. Method: The study population included Finns who participated in cross-sectional surveys on drinking habits in 1969, 1976 or 1984 when aged 25–69 (n = 6406). They were followed up for alcohol-related mortality and hospitalisations (n = 180) for 16 years. Drinking patterns were measured by total consumption, frequency of subjective intoxication and of drinking different amounts of alcohol at a time, and by volume of consumption that was drunk in heavy drinking occasions and non-heavy drinking occasions. Results: Compared with non-manual workers, manual workers had a 2.06-fold hazard of alcohol-related death or hospitalisation. Adjustment for drinking patterns explained only a small fraction of the excess hazard among manual workers. Additionally, in each category of total consumption and in each level of the volume drunk in heavy drinking occasions, the risk of alcohol-related death and hospitalisation was higher for manual than for non-manual workers. Conclusions: Consequences of similar drinking patterns are more severe for those with lower socioeconomic status. Future studies are needed to explain how higher socioeconomic groups manage to escape the consequences of drinking that others have to face

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Supplemental tables to Neuropsychiatric diagnoses after isotretinoin initiation in pediatric acne patients: a retrospective cohort study published in the Journal of the American Academy of Dermatology.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Associations between antipsychotics and risk of violent crimes and suicidal behaviour in personality disorder.

BACKGROUND: Despite uncertain benefits, people with personality disorder are commonly treated with antipsychotic medication. OBJECTIVE: To investigate the association between antipsychotics and violent crimes and suicidal behaviour in individuals with personality disorder. METHODS: We used nationwide Danish registries to identify all individuals with diagnosed personality disorder aged 18-64 years during 2007 to 2016. Antipsychotics were recorded in dispensed prescriptions, and individuals were followed up for police-recorded suspicions for violent crimes and healthcare presentations of suicidal behaviour. We applied a within-individual design where outcome rates for individuals with personality disorder during medicated periods were compared with rates during non-medicated periods. FINDINGS: The cohort included 166 328 people with diagnosed personality disorder, of whom 79 253 were prescribed antipsychotics, presented at least one outcome and were thus included in the within-individual analyses. Compared with periods when individuals were not on antipsychotic medication, violent crime suspicions were 40% lower (incident rate ratio (IRR) 0.60, 95% CI 0.55 to 0.63) in men and 10% lower (IRR 0.90, 95% CI 0.79 to 1.01) in women, while rates of suicidal behaviour were 32% lower both in men (IRR 0.68, 95% CI 0.66 to 0.71) and in women (IRR 0.68, 95% CI 0.65 to 0.70). In subgroup analyses, the magnitude of the association varied across specific personality disorders for criminal outcomes but less for suicidal behaviour, with largest association in dissocial personality disorder for violent criminality (IRR 0.53, 95% CI 0.47 to 0.59). CONCLUSIONS: Treatment with antipsychotics was associated with reduced risks for violent crime suspicions and suicidal behaviour among individuals with personality disorder. CLINICAL IMPLICATIONS: Potential effects of antipsychotics on suicidal behaviour and violence should be taken into account when considering treatment options for people with personality disorders

Isotretinoin and adverse neuropsychiatric outcomes: retrospective cohort study using routine data

Background Severe neuropsychiatric outcomes have been reported in individuals exposed to isotretinoin, but the evidence is inconclusive and complicated by several methodological limitations. Objectives To establish and quantify the association between isotretinoin use for acne and 1-year incident neuropsychiatric adverse outcomes. Methods A propensity score-matched cohort study of electronic medical records between the years 2013 and 2019 with patients followed up for 1 year after their index dispensed prescription was conducted. The database included over 12 million patients aged 12&ndash;27&thinsp;years. We analysed data for individuals with acne in this age range with a dispensed prescription for isotretinoin or a control prescription. Outcomes included diagnoses of any incident sleep or mental health disorder, or nonfatal self-harm within 1 year of the index prescription. Results We included 30&thinsp;866 patients prescribed isotretinoin for their acne, 44&thinsp;748 prescribed oral antibiotics, 108&thinsp;367 prescribed topical anti-acne agents and 78&thinsp;666 patients with acne but without an anti-acne prescription. After propensity score matching for baseline confounders, the odds ratio (OR) for any incident neuropsychiatric outcomes in patients with acne exposed to isotretinoin was 0&middot;80 [95% confidence interval (CI) 0&middot;74&ndash;0&middot;87] compared with those on oral antibiotics; 0&middot;94 (95% CI 0&middot;87&ndash;1&middot;02) compared with those using topical anti-acne medicines; and 1&middot;06 (95% CI 0&middot;97&ndash;1&middot;16) compared with those without a prescription for anti-acne medicines. Patients exposed to isotretinoin experienced significantly more incident physical symptoms than patients in any of the three comparison cohorts. Conclusions Isotretinoin was not independently associated with excess adverse neuropsychiatric outcomes at the population level. When monitoring potential adverse outcomes during isotretinoin treatment, clinicians should also consider the high mental health burden associated with treatment-resistant acne and the potential contribution of physical side-effects of prescribed medication on mental health. What is already known about this topic? Severe neuropsychiatric outcomes have been reported in individuals exposed to isotretinoin, but the evidence is inconclusive and complicated by several methodological limitations. The neuropsychiatric risks potentially associated with isotretinoin treatment are an ongoing concern to clinicians and individuals with treatment-resistant acne. Current isotretinoin prescribing guidelines recommend close monitoring for adverse mental health outcomes during isotretinoin treatment. What does this study add? After controlling for various potential sources of bias, isotretinoin was associated with a reduced incidence of adverse psychiatric outcomes (odds ratio 0&middot;80, 95% confidence interval 0&middot;74&ndash;0&middot;87) compared with oral antibiotics. Isotretinoin appeared to reduce the excess psychiatric risk associated with treatment-resistant moderate-to-severe acne. In monitoring potential adverse outcomes during isotretinoin treatment, clinicians should also consider the high mental health burden associated with treatment-resistant acne and the potential contribution of physical side-effects of the prescribed medication on mental health. </section

Associations between antipsychotics and risk of violent crimes and suicidal behaviour in personality disorder

Background Despite uncertain benefits, people with personality disorder are commonly treated with antipsychotic medication. Objective To investigate the association between antipsychotics and violent crimes and suicidal behaviour in individuals with personality disorder. Methods We used nationwide Danish registries to identify all individuals with diagnosed personality disorder aged 18–64 years during 2007 to 2016. Antipsychotics were recorded in dispensed prescriptions, and individuals were followed up for police-recorded suspicions for violent crimes and healthcare presentations of suicidal behaviour. We applied a within-individual design where outcome rates for individuals with personality disorder during medicated periods were compared with rates during non-medicated periods. Findings The cohort included 166 328 people with diagnosed personality disorder, of whom 79 253 were prescribed antipsychotics, presented at least one outcome and were thus included in the within-individual analyses. Compared with periods when individuals were not on antipsychotic medication, violent crime suspicions were 40% lower (incident rate ratio (IRR) 0.60, 95% CI 0.55 to 0.63) in men and 10% lower (IRR 0.90, 95% CI 0.79 to 1.01) in women, while rates of suicidal behaviour were 32% lower both in men (IRR 0.68, 95% CI 0.66 to 0.71) and in women (IRR 0.68, 95% CI 0.65 to 0.70). In subgroup analyses, the magnitude of the association varied across specific personality disorders for criminal outcomes but less for suicidal behaviour, with largest association in dissocial personality disorder for violent criminality (IRR 0.53, 95% CI 0.47 to 0.59). Conclusions Treatment with antipsychotics was associated with reduced risks for violent crime suspicions and suicidal behaviour among individuals with personality disorder. Clinical implications Potential effects of antipsychotics on suicidal behaviour and violence should be taken into account when considering treatment options for people with personality disorders

Abuse-deterrent extended-release oxycodone and risk of opioid-related harm

Aim: To establish and quantify the association between abuse-deterrent formulation (ADF) oxycodone and 1-year risk of opioid-related harm. Design: Propensity score-matched cohort study of electronic medical records for years 2014–18, with patients followed up for 1 year after their index health-care visit. Setting: More than 70 million patients from 56 US health-care organizations. Participants: Patients aged 18–64 years at index health-care visit with any indication for an oral opioid analgesic, with no past 12-month history of oral oxycodone use or substance use disorder, and who were alive at the end of the 1-year follow-up (new episode of prescription oral ADF oxycodone [OxyContin], n = 45 045; new episode of non-ADF oxycodone opioid preparation, n = 1 377 359). Measurements: International Classification of Diseases diagnoses of any opioid-related disorder or non-fatal opioid poisoning within 1 year of the index health-care visit. Pooled odds ratios (OR) with 95% confidence intervals (95% CI). Findings: After propensity score matching, 89 802 patients with a mean age of 44 [standard deviation (SD) = 11] years (62% women, 68% white) were included. During 1-year follow-up, 1445 diagnoses of opioid use disorder or opioid poisoning occurred in the ADF oxycodone cohort (34.8/1000 person-years) and 765 occurred in the non-ADF oxycodone cohort (18.2/1000 person-years). The odds of opioid-related adverse outcomes were increased in the ADF oxycodone cohort compared with the non-ADF oxycodone opioid cohort, including for opioid use disorders (OR = 2.02; 95% CI = 1.83, 2.23) and opioid poisoning (OR = 1.64 95% CI = 1.35, 1.99). Conclusions: Patients with a new prescription of abuse-deterrent formulation oxycodone may be at increased risk of opioid-related harm.</p

Analysis of neuropsychiatric diagnoses after montelukast initiation

Importance The evidence base for the association between montelukast and adverse neuropsychiatric outcomes is mixed and inconclusive. Several methodological limitations have been identified in the evidence base on the safety of montelukast in observational studies. Objective To investigate the association between new montelukast exposure and 1-year incident neuropsychiatric diagnoses with improved precision and control for baseline confounders. Design, Setting, and Participants This propensity score–matched cohort study was conducted using electronic health records from 2015 to 2019 in the TriNetX Analytics Network patient repository of more than 51 million patients from 56 health care organizations, mainly in the US. Included patients were those aged 15 to 64 years at index prescription for montelukast or for control prescription who had a history of asthma or allergic rhinitis. After propensity score matching for various baseline confounders, including comorbidities and dispensed prescription medicines, we included 154 946 patients, of whom 77 473 individuals were exposed to montelukast. Patients were followed up for 12 months. Data were analyzed from June through November 2021. Exposures New dispensed prescription for leukotriene receptor antagonist montelukast or control medication. Main Outcomes and Measures Incident neuropsychiatric diagnoses at 12 months identified using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Results There were 72 490 patients with asthma (44 726 [61.7%] women; mean [SD] age at index prescription, 35 [15] years) and 82 456 patients with allergic rhinitis (54 172 [65.7%] women; mean [SD] age at index prescription, 40 [14] years). In patients exposed to montelukast, the odds ratio [OR] for any incident neuropsychiatric outcome was 1.11 (95% CI, 1.04-1.19) in patients with asthma and 1.07 (95% CI, 1.01-1.14) in patients with allergic rhinitis compared with patients who were unexposed. The highest OR was for anxiety disorders (OR, 1.21; 95% CI, 1.05-1.20) among patients with asthma exposed to montelukast and insomnia (OR, 1.15; 95% CI, 1.05-1.27) among patients with allergic rhinitis exposed to montelukast. Conclusions and Relevance This study found that patients with asthma or allergic rhinitis had increased odds of adverse neuropsychiatric outcomes after montelukast initiation. These findings suggest that clinicians should consider monitoring potential adverse mental health symptoms during montelukast treatment, particularly in individuals with a history of mental health or sleep problems