Patient reported preferences for sleep interventions among women receiving buprenorphine for opioid use disorder

AimAmong individuals receiving medication for OUD (MOUD), insomnia is highly prevalent and increases the risk for negative OUD outcomes. However, little is known about MOUD patient-reported preferences for insomnia treatments among women with OUD. This mixed-methods study explored acceptability of and patient preferences for sleep interventions among women in OUD treatment.MethodsThis is an analysis from an ongoing cross-sectional survey and interview study investigating the relationship between sleep and OUD recovery. The parent study is actively enrolling non-pregnant women between 18–45 years stabilized on buprenorphine from an outpatient program. Participants complete measures including the Insomnia Severity Index (ISI), with scores of ≥10 identifying clinically significant insomnia symptoms. A sub-sample who met this threshold completed semi-structured interviews. Descriptive statistics were generated for survey responses, and applied thematic analysis was used for interview data.ResultsParticipants selected for the qualitative interview (n = 11) highlighted prior positive and negative experiences with sleep treatments, challenges with employing non-pharmacological sleep strategies, and preferences for both medical and behavioral sleep interventions while in recovery. Women emphasized the need for flexibility of sleep therapy sessions to align with ongoing social determinants (e.g., caregiving responsibilities) as well as for sleep medications without sedating effects nor risk of dependency.ConclusionsMany women receiving MOUD have concomitant insomnia symptoms, and desire availability of both pharmacologic and behavioral sleep interventions within the OUD treatment setting. Qualitative findings underscore the need for evidence-based sleep interventions that account for the unique socioenvironmental factors that may impact strategy implementation in this population

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Addiction curriculum design for medical students

Background: As mortality and morbidity due to substance use disorder (SUD) are increasing for women, especially during pregnancy and postpartum, it is imperative to equip medical providers with skills to identify SUD and initiate treatments. We designed a curriculum to provide third-year medical students with clinical exposure to SUD during pregnancy. Approach: This novel, experience-based SUD curriculum was focused on providing adequate knowledge, skills and confidence to provide compassionate, patient-centred care to women with SUD. Obstetrics and Gynecology clerkship third-year medical students rotated 1 day through a clinic that provides Obstetrics and Gynecology and addiction medicine services. Congruent with COVID-19 limitations, students completed pre-clinic assignments and in-clinic tasks (e.g., screening, brief intervention, referral to treatment [SBIRT]) under supervision. Evaluation: After implementation of this pilot curriculum, 20 students and 10 teachers completed surveys (100% response rate) with open-ended response items. Quantitative data and open-ended responses using electronic surveys were sequentially analysed to evaluate the curriculum's feasibility and acceptability. Implications: We designed a novel curriculum that focused on SUD learning objectives and providing exposure to third-year medical students, and our findings indicate that it is feasible and acceptable to both students and teachers. In the future, we plan to provide this curriculum to both our third- and fourth-year medical students, and we encourage teachers and providers at other institutions to utilise it during their clinical training.</p

Addiction curriculum design for medical students

Background: As mortality and morbidity due to substance use disorder (SUD) are increasing for women, especially during pregnancy and postpartum, it is imperative to equip medical providers with skills to identify SUD and initiate treatments. We designed a curriculum to provide third-year medical students with clinical exposure to SUD during pregnancy. Approach: This novel, experience-based SUD curriculum was focused on providing adequate knowledge, skills and confidence to provide compassionate, patient-centred care to women with SUD. Obstetrics and Gynecology clerkship third-year medical students rotated 1 day through a clinic that provides Obstetrics and Gynecology and addiction medicine services. Congruent with COVID-19 limitations, students completed pre-clinic assignments and in-clinic tasks (e.g., screening, brief intervention, referral to treatment [SBIRT]) under supervision. Evaluation: After implementation of this pilot curriculum, 20 students and 10 teachers completed surveys (100% response rate) with open-ended response items. Quantitative data and open-ended responses using electronic surveys were sequentially analysed to evaluate the curriculum's feasibility and acceptability. Implications: We designed a novel curriculum that focused on SUD learning objectives and providing exposure to third-year medical students, and our findings indicate that it is feasible and acceptable to both students and teachers. In the future, we plan to provide this curriculum to both our third- and fourth-year medical students, and we encourage teachers and providers at other institutions to utilise it during their clinical training.</p

Fine-Scale Human Population Structure in Southern Africa Reflects Ecogeographic Boundaries.

Recent genetic studies have established that the KhoeSan populations of southern Africa are distinct from all other African populations and have remained largely isolated during human prehistory until ∼2000 years ago. Dozens of different KhoeSan groups exist, belonging to three different language families, but very little is known about their population history. We examine new genome-wide polymorphism data and whole mitochondrial genomes for &gt;100 South Africans from the ≠Khomani San and Nama populations of the Northern Cape, analyzed in conjunction with 19 additional southern African populations. Our analyses reveal fine-scale population structure in and around the Kalahari Desert. Surprisingly, this structure does not always correspond to linguistic or subsistence categories as previously suggested, but rather reflects the role of geographic barriers and the ecology of the greater Kalahari Basin. Regardless of subsistence strategy, the indigenous Khoe-speaking Nama pastoralists and the N|u-speaking ≠Khomani (formerly hunter-gatherers) share ancestry with other Khoe-speaking forager populations that form a rim around the Kalahari Desert. We reconstruct earlier migration patterns and estimate that the southern Kalahari populations were among the last to experience gene flow from Bantu speakers, ∼14 generations ago. We conclude that local adoption of pastoralism, at least by the Nama, appears to have been primarily a cultural process with limited genetic impact from eastern Africa