Antipsychotic polypharmacy and adverse drug reactions among adults in a London mental health service, 2008-2018.

BACKGROUND: Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25]. METHODS: We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively. RESULTS: We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87-3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33-2.31) in the period following the APP prescribing. CONCLUSIONS: Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

Fluorine on fluorenes.

A practical synthesis of 1,8-difluorofluorenone and of its (2,7)-dibromo and (2,4,5,7)-tetrabromo derivatives has been developed. Fluorinated fluorenones are the starting materials for polyhalogenated dibenzochrysenes as well as for geodesic hydrocarbons. 2,7-Dibromo-1,8-difluoro-9H-fluoren-9-one was converted to 3,14-dibromo-4,13-difluorodibenzo[g,p]chrysene through a novel strategy.

Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the USA.

OBJECTIVES: To investigate SARS-CoV-2 (the virus causing COVID-19) infection and exposure risks among grocery retail workers, and to investigate their mental health state during the pandemic. METHODS: This cross-sectional study was conducted in May 2020 in a single grocery retail store in Massachusetts, USA. We assessed workers' personal/occupational history and perception of COVID-19 by questionnaire. The health outcomes were measured by nasopharyngeal SARS-CoV-2 reverse transcriptase PCR (RT-PCR) results, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULTS: Among 104 workers tested, 21 (20%) had positive viral assays. Seventy-six per cent positive cases were asymptomatic. Employees with direct customer exposure had an odds of 5.1 (95% CI 1.1 to 24.8) being tested positive for SARS-CoV-2 after adjustments. As to mental health, the prevalence of anxiety and depression (ie, GAD-7 score >4 or PHQ-9 score >4) was 24% and 8%, respectively. After adjusting for potential confounders, those able to practice social distancing consistently at work had odds of 0.3 (95% CI 0.1 to 0.9) and 0.2 (95% CI 0.03 to 0.99) screening positive for anxiety and depression, respectively. Workers commuting by foot, bike or private cars were less likely to screen positive for depression (OR 0.1, 95% CI 0.02 to 0.7). CONCLUSIONS: In this single store sample, we found a considerable asymptomatic SARS-CoV-2 infection rate among grocery workers. Employees with direct customer exposure were five times more likely to test positive for SARS-CoV-2. Those able to practice social distancing consistently at work had significantly lower risk of anxiety or depression.

Amyloid ß chaperone - lipocalin-type prostaglandin D synthase acts as a peroxidase in the presence of heme.

The extracellular transporter, lipocalin-type prostaglandin D synthase (L-PGDS) binds to heme and heme metabolites with high affinity. It has been reported that L-PGDS protects neuronal cells against apoptosis induced by exposure to hydrogen peroxide. Our study demonstrates that when human WT L-PGDS is in complex with heme, it exhibits a strong peroxidase activity thus behaving as a pseudo-peroxidase. Electron paramagnetic resonance studies confirm that heme in the L-PGDS-heme complex is hexacoordinated with high-spin Fe(III). NMR titration of heme in L-PGDS points to hydrophobic interaction between heme and several residues within the ß-barrel cavity of L-PGDS. In addition to the transporter function, L-PGDS is a key amyloid ß chaperone in human cerebrospinal fluid. The presence of high levels of bilirubin and its derivatives, implicated in Alzheimer's disease, by binding to L-PGDS may reduce its chaperone activity. Nevertheless, our ThT binding assay establishes that heme and heme metabolites do not significantly alter the neuroprotective chaperone function of L-PGDS. Guided by NMR data we reconstructed the heme L-PGDS complex using extensive molecular dynamics simulations providing a platform for mechanistic interpretation of the catalytic and transporting functions and their modulation by secondary ligands like Aß peptides and heme metabolites.

20S Proteasome as a Drug Target in Trichomonas vaginalis.

Trichomoniasis is a sexually transmitted disease with hundreds of millions of annual cases worldwide. Approved treatment options are limited to two related nitro-heterocyclic compounds, yet resistance to these drugs is an increasing concern. New antimicrobials against the causative agent, Trichomonas vaginalis, are urgently needed. We show here that clinically approved anticancer drugs that inhibit the proteasome, a large protease complex with a critical role in degrading intracellular proteins in eukaryotes, have submicromolar activity against the parasite in vitro and on-target activity against the enriched T. vaginalis proteasome in cell-free assays. Proteomic analysis confirmed that the parasite has all seven α and seven ß subunits of the eukaryotic proteasome although they have only modest sequence identities, ranging from 28 to 52%, relative to the respective human proteasome subunits. A screen of proteasome inhibitors derived from a marine natural product, carmaphycin, revealed one derivative, carmaphycin-17, with greater activity against T. vaginalis than the reference drug metronidazole, the ability to overcome metronidazole resistance, and reduced human cytotoxicity compared to that of the anticancer proteasome inhibitors. The increased selectivity of carmaphycin-17 for T. vaginalis was related to its >5-fold greater potency against the ß1 and ß5 catalytic subunits of the T. vaginalis proteasome than against the human proteasome subunits. In a murine model of vaginal trichomonad infection, proteasome inhibitors eliminated or significantly reduced parasite burden upon topical treatment without any apparent adverse effects. Together, these findings validate the proteasome of T. vaginalis as a therapeutic target for development of a novel class of trichomonacidal agents.

Demographic, socioeconomic, and health correlates of unmet need for mental health treatment in the United States, 2002-16: evidence from the national surveys on drug use and health.

BACKGROUND: Unmet need for mental health services remains high in the United States and is disproportionately concentrated in some groups. The scale and nature of these disparities have not been fully elucidated and bear further scrutiny. As such, in this study, we examine the demographic, socioeconomic, and health correlates of unmet need for mental health treatment as well as the reasons for unmet need. METHODS: We draw upon the National Survey for Drug Use and Health (NSDUH) from 2002 to 16 for adults aged 18 and over in the United States (n = 579,017). Using multivariable logistic regression, we simultaneously model the demographic, socioeconomic, and health correlates of unmet need for mental health treatment from 2002 to 16. We also analyse the reasons for unmet need expressed by these populations, reasons which include cost, perceived stigma, minimisation of symptoms, low perceived effectiveness of treatment, and structural barriers. RESULTS: Major characteristics associated with increased odds of unmet need include past year substance abuse or dependence (other than hallucinogens and sedatives), fair, poor, or very poor health, being female, and an educational attainment of college or higher. With respect to reasons for unmet need, cost was most often cited, followed by perceived stigma, structural barriers, and minimisation. Characteristics associated with increased odds of indicating cost as a reason for unmet need include: being uninsured or aged 26-35. Minimisation and low perceived effectiveness are mentioned by high-income persons as reasons for unmet need. College-educated persons and women had higher odds of citing structural barriers as a reason for unmet need. CONCLUSIONS: The correlates and causes of unmet need highlight the intersectionality of individual health needs with implications on addressing inequities in mental health policy and practice.

Private health insurance in Germany and Chile: two stories of co-existence, segmentation and conflict.

BACKGROUND: In Germany and Chile, substitutive private health insurance has been shaped by its co-existence with statutory social health insurance. Despite differences in the way choice is available to users in the health insurance regimes of Chile and Germany, the way in which each country has managed choice between private health insurance and statutory social health insurance provides a unique opportunity to comparatively assess the consequences of such an arrangement that has been previously underexamined. METHODS: We conducted a Most Similar Systems Design comparative policy analysis of the co-occurring private health insurance and statutory social health insurance systems in Germany and Chile. We describe and review the origins and development of the German and Chilean health care insurance systems with an emphasis on the substitutive co-existence between private health insurance and statutory social health insurance. We provide a critique of the market performance of the private health insurance regime in each country followed by a comparative assessment of the impact of private health insurance on financial protection, equity, and risk segmentation. RESULTS: Segmentation of insurance markets in both Germany and Chile has had significant consequences for equity, fairness, and financial protection. Due to market failures in health insurance and differences in the regulatory frameworks governing public and private insurers, the choice of public or private coverage has produced strong incentives for private insurers to select for risks, compromising equity in health care funding, heightening the financial risk borne by public insurers and lowering incentives for private insurers to operate efficiently. CONCLUSIONS: The degree of conflict arising from the substitutive parallel private health insurance system and the statutory social health insurance system varies between Germany and Chile, though policy goals remain similar. Recent reforms in both countries have attempted to improve the financial protection of the privately insured through regulation; nevertheless, concerns about risk segmentation remain largely unresolved.

A comprehensive meta-analysis on evidence of Mediterranean diet and cardiovascular disease: Are individual components equal?

Many studies have reported that higher adherence to Mediterranean diet may decrease cardiovascular disease (CVD) incidence and mortality. We performed a meta-analysis to explore the association in prospective studies and randomized control trials (RCTs) between Mediterranean diet adherence and CVD incidence and mortality. The PubMed database was searched up to June 2014. A total of 17 studies were extracted and 11 qualified for the quantitative analysis. Individuals in the highest quantile of adherence to the diet had lower incidence [relative risk (RR): 0.76, 95% confidence intervals (CI): 0.68, 0.83] and mortality (RR: 0.76, 95% CI: 0.68, 0.83) from CVD compared to those least adherent. A significant reduction of risk was found also for coronary heart disease (CHD) (RR: 0.72, 95% CI: 0.60, 0.86), myocardial infarction (MI) (RR: 0.67; 95% CI: 0.54, 0.83), and stroke (RR: 0.76; 95% CI: 0.60, 0.96) incidence. Pooled analyses of individual components of the diet revealed that the protective effects of the diet appear to be most attributable to olive oil, fruits, vegetables, and legumes. An average reduced risk of 40% for the aforementioned outcomes has been retrieved when pooling results of RCTs. A Mediterranean dietary pattern is associated with lower risks of CVD incidence and mortality, including CHD and MI. The relative effects of specific food groups should be further investigated.

Patellofemoral Contact Pressures After Patellar Distalization: A Biomechanical Study.

PURPOSE: To measure the patellofemoral contact pressure in early flexion after a tibial tubercle distalization osteotomy. METHODS: Ten matched-pair fresh-frozen cadaveric knees were studied. The average Blackburne-Peel ratio of the native knees was 0.91. The knees were placed on a testing rig, with a fixed femur and tibia mobile through 90° of flexion. Individual quadriceps heads and the iliotibial band were separated and loaded with 205 N in anatomic directions using a weighted pulley system. A straight tubercle distalization osteotomy of 1 cm was performed and fixed with screws, with and without a lateral release. Patellofemoral contact pressures were measured at 0°, 10°, 20°, 30°, 45°, 60°, and 90° of flexion using pressure-sensitive films on the medial trochlea and lateral trochlea. Contact force, area, and pressure were measured in the following states: (1) in the native knee, (2) after distalization, and (3) after distalization with lateral release. RESULTS: The average Blackburne-Peel ratio after distalization was 0.64. Tibial tubercle distalization resulted in a 6-fold increase in mean contact pressure at 0° (0.15 MPa vs 0.90 MPa, P < .001) and a 55% increase at 10° of flexion (0.70 MPa vs 1.09 MPa, P = .02). Mean contact pressure was similar from 20° to 90° of flexion (P > .1). After distalization, the total contact area was significantly higher at 0° of flexion (17.7 mm2 vs 58.4 mm2, P = .02). Lateral release after distalization did not significantly change contact pressure (P > .21). CONCLUSIONS: Our results suggest that patella baja, as a result of excessive patellar distalization, can cause increased patellofemoral contact pressures during early flexion at 0° and 10°. No changes were seen in contact pressure from 20° to 90°. CLINICAL RELEVANCE: Care should be taken to prevent excessive distalization of the patella to avoid patella baja and increased patellofemoral contact pressures during early flexion.

Hepatic ADC map as an adjunct to conventional abdominal MRI to evaluate hepatic fibrotic and clinical cirrhotic severity in biliary atresia patients.

OBJECTIVES: Hepatic apparent diffusion coefficient (ADC) values and ADC-related indices were correlated with the Mayo risk score for primary biliary cirrhosis (MRSPBC) and METAVIR scores of liver specimens to determine the clinical and pathological significance of diffusion-weighted magnetic resonance imaging (DWMRI). METHODS: Thirty-two patients with biliary atresia (BA; mean age 461 days, range 11-4616 days) received magnetic resonance examinations from March 2009 to August 2013. A free-breathing DWMRI sequence was performed with the single-shot echo-planar imaging technique with b = 0 and 500 s/mm(2) in all 32 BA patients and 24 controls. We used the ordinal logistic regression test and Spearman rank correlation test to analyse the relationships between the MRSPBC and METAVIR fibrosis scores and right liver-to-psoas ADC ratios (LTPARs). RESULTS: BA patients had significantly lower LTPARs in both hepatic lobes than controls (p < 0.01). Right LTPARs, showing moderate intraobserver agreement (intraclass correlation coefficient = 0.736) and interobserver reliability (intraclass correlation coefficient = 0.659), were negatively correlated with MRSPBC and METAVIR fibrosis scores (R(2) = 0.398, p = 0.024 and R(2) = 0.628, p < 0.001, respectively). CONCLUSION: Right LTPARs may be used for long-term follow-up of cirrhosis severity in BA patients. KEY POINTS: • Hepatic ADC values by DWI correlates well with clinical/pathologic fibrosis scores • Periodic, non-invasive, quantitative imaging follow-up of patients with biliary cirrhosis is feasible • Information on cirrhosis severity could help decide on management options in children with BA • ADC values may be useful in this regard.

The autophagic response to polystyrene nanoparticles is mediated by transcription factor EB and depends on surface charge.

BACKGROUND: A number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates bulk degradation of cytoplasmic material by the lysosomes. Depending on the specific physico-chemical properties of the nanomaterial, however, nanoparticle-induced autophagy may have different effects on cell physiology, ranging from enhanced autophagic degradation to blockage of autophagic flux. To investigate the molecular mechanisms underlying the impact of nanoparticle charge on the nature of the autophagic response, we tested polystyrene nanoparticles (50 nm) with neutral, anionic, and cationic surface charges. RESULTS: We found all polystyrene nanoparticles investigated in this study to activate autophagy. We showed that internalization of polystyrene nanoparticles results in activation of the transcription factor EB, a master regulator of autophagy and lysosome biogenesis. Autophagic clearance, however, was observed to depend specifically on the charge of the nanoparticles. Particularly, we found that the autophagic response to polystyrene nanoparticles presenting a neutral or anionic surface involves enhanced clearance of autophagic cargo. Cell exposure to polystyrene nanoparticles presenting a cationic surface, on the other hand, results in transcriptional upregulation of the pathway, but also causes lysosomal dysfunction, ultimately resulting in blockage of autophagic flux. CONCLUSIONS: This study furthers our understanding of the molecular mechanisms that regulate the autophagic response to nanoparticles, thus contributing essential design criteria for engineering benign nanomaterials.

Trends in the utilization of computed tomography and cardiac catheterization among children with congenital heart disease.

BACKGROUND/PURPOSE: Pediatric cardiac computed tomography (CT) is a noninvasive imaging modality used to clearly demonstrate the anatomical detail of congenital heart diseases. We investigated the impact of cardiac CT on the utilization of cardiac catheterization among children with congenital heart disease. METHODS: The study sample consisted of 2648 cardiac CT and 3814 cardiac catheterization from 1999 to 2009 for congenital heart diseases. Diagnoses were categorized into 11 disease groups. The numbers of examination, according to the different modalities, were compared using temporal trend analyses. The estimated effective radiation doses (mSv) of CT and catheterization were calculated and compared. RESULTS: The number of CT scans and interventional catheterizations had a slight annual increase of 1.2% and 2.7%, respectively, whereas that of diagnostic catheterization decreased by 6.2% per year. Disease groups fell into two categories according to utilization trend differences between CT and diagnostic catheterization. The increased use of CT reduces the need for diagnostic catheterization in patients with atrioventricular connection disorder, coronary arterial disorder, great vessel disorder, septal disorder, tetralogy of Fallot, and ventriculoarterial connection disorder. Clinicians choose either catheterization or CT, or both examinations, depending on clinical conditions, in patients with semilunar valvular disorder, heterotaxy, myocardial disorder, pericardial disorder, and pulmonary vein disorder. The radiation dose of CT was lower than that of diagnostic cardiac catheterization in all age groups. CONCLUSION: The use of noninvasive CT in children with selected heart conditions might reduce the use of diagnostic cardiac catheterization. This may release time and facilities within the catheterization laboratory to meet the increasing demand for cardiac interventions.

Reliability of patient self-assessment of shoulder range of motion and strength after shoulder arthroplasty.

BACKGROUND: Patient-derived self-assessment potentially minimizes loss of valuable outcomes data, conserves medical resources, and benefits patients by saving valuable time out of work and travel expenses. The purpose of this study was to determine the physician-patient correlation of a patient-derived outcomes questionnaire that assesses range of motion (ROM) and strength after shoulder arthroplasty. METHODS: One hundred twenty consecutive patients completed a home-based questionnaire before their 1-year postoperative visit after shoulder arthroplasty. The questionnaire contained demographic information such as age, gender, type of surgery, education level, and income. Diagram-based questions, in which patients were asked to identify the image representing their own active shoulder ROM in various planes, were included. Patients were asked to perform a strength examination using premeasured zip-lock bags filled with water that correspond to predetermined weights up to 2.72 kg. The κ statistics were used to assess the degree of agreement between the patient's self-assessment and the clinician's measures. RESULTS: The κ statistics indicated moderate clinician-patient agreement (0.5-0.59) on items related to ROM and substantial to almost perfect agreement (0.62-0.92) on items related to strength (forward flexion and abduction). A majority of patients (>88%) correctly estimated their ROM within 1 grade of the clinician's measurement. Patients tended to err toward overestimating their ROM. CONCLUSIONS: This patient-derived questionnaire provides a moderate to high level of agreement with clinician assessment. This assessment questionnaire may be an important tool in facilitating both clinical and research follow-up of patient outcomes after shoulder arthroplasty.

Reasoning with large language models for medical question answering.

OBJECTIVES: To investigate approaches of reasoning with large language models (LLMs) and to propose a new prompting approach, ensemble reasoning, to improve medical question answering performance with refined reasoning and reduced inconsistency. MATERIALS AND METHODS: We used multiple choice questions from the USMLE Sample Exam question files on 2 closed-source commercial and 1 open-source clinical LLM to evaluate our proposed approach ensemble reasoning. RESULTS: On GPT-3.5 turbo and Med42-70B, our proposed ensemble reasoning approach outperformed zero-shot chain-of-thought with self-consistency on Steps 1, 2, and 3 questions (+3.44%, +4.00%, and +2.54%) and (2.3%, 5.00%, and 4.15%), respectively. With GPT-4 turbo, there were mixed results with ensemble reasoning again outperforming zero-shot chain-of-thought with self-consistency on Step 1 questions (+1.15%). In all cases, the results demonstrated improved consistency of responses with our approach. A qualitative analysis of the reasoning from the model demonstrated that the ensemble reasoning approach produces correct and helpful reasoning. CONCLUSION: The proposed iterative ensemble reasoning has the potential to improve the performance of LLMs in medical question answering tasks, particularly with the less powerful LLMs like GPT-3.5 turbo and Med42-70B, which may suggest that this is a promising approach for LLMs with lower capabilities. Additionally, the findings show that our approach helps to refine the reasoning generated by the LLM and thereby improve consistency even with the more powerful GPT-4 turbo. We also identify the potential and need for human-artificial intelligence teaming to improve the reasoning beyond the limits of the model.

ChatGPT's Role in Improving Education Among Patients Seeking Emergency Medical Treatment.

Providing appropriate patient education during a medical encounter remains an important area for improvement across healthcare settings. Personalized resources can offer an impactful way to improve patient understanding and satisfaction during or after a healthcare visit. ChatGPT is a novel chatbot-computer program designed to simulate conversation with humans- that has the potential to assist with care-related questions, clarify discharge instructions, help triage medical problem urgency, and could potentially be used to improve patient-clinician communication. However, due to its training methodology, ChatGPT has inherent limitations, including technical restrictions, risk of misinformation, lack of input standardization, and privacy concerns. Medicolegal liability also remains an open question for physicians interacting with this technology. Nonetheless, careful utilization of ChatGPT in clinical medicine has the potential to supplement patient education in important ways.

Risk of Revision and Reoperation After Quadriceps Tendon Autograft ACL Reconstruction Compared With Patellar Tendon and Hamstring Autografts in a US Cohort of 21,973 Patients.

BACKGROUND: The use of quadriceps tendon (QT) autografts has increased in the past 10 years. However, there remains a dearth of large studies examining the effects of graft selection on anterior cruciate ligament reconstruction (ACLR) that includes QT grafts. PURPOSE: To evaluate the risk of subsequent surgical outcomes, including revision and reoperation, for a large cohort of patients with primary ACLR according to autograft selection. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Data from a US health care system ACLR registry were used to conduct a cohort study. Primary isolated autograft ACLRs were identified (2012-2021). The exposure of interest was autograft type: QT, bone-patellar tendon-bone (BPTB), and hamstring tendon (HT). Multivariable Cox regression models were used to evaluate the risk of aseptic revision (defined as a subsequent surgery where removal and replacement of the original graft for noninfectious reasons was required) and risk of aseptic reoperation (defined as any subsequent surgery for noninfectious reasons where the graft was left intact) according to autograft selection. RESULTS: The study sample comprised 21,973 ACLRs performed by 290 surgeons at 53 hospitals. QT, BPTB, and HT autografts were used in 1103 (5.0%), 9519 (43.3%), and 11,351 (51.7%) ACLRs, respectively. In adjusted models, no significant differences were observed in revision risk (hazard ratio [HR], 1.06; 95% CI, 0.60-1.89; P = .837) or reoperation risk (HR, 1.00; 95% CI, 0.70-1.43; P = .993) within 4 years of follow-up when comparing QT ACLR with BPTB ACLR. Additionally, no differences in 4-year revision (HR, 0.62; 95% CI, 0.34-1.12; P = .111) or reoperation (HR, 1.24; 95% CI, 0.85-1.80; P = .262) risks were observed when comparing QT ACLR with HT ACLR. HT ACLRs were noted to have a higher risk of revision (HR, 1.52; 95% CI, 1.25-1.84; P < .001) compared with BPTB ACLRs but a lower risk of reoperation (HR, 0.86; 95% CI, 0.75-0.98; P = .024). CONCLUSION: In this large multicenter study using data from an ACLR registry, the authors found no difference in the risk of revision or reoperation when QT was compared with BPTB or HT autograft with the numbers available, but they did find a 1.5 times higher risk of revision when HT autograft was compared with BPTB autograft. Surgeons may use this information when choosing the appropriate graft for ACLR in their patients.

Sexualized drug use and chemsex: A bibliometric and content analysis of published literature.

Sexualized drug use (SDU) describes drug-facilitated sexual enhancement, and chemsex is an SDU subculture involving the use of specific drugs by men who have sex with men (MSM). This study aimed to identify research trends, foci, and themes within the SDU and chemsex-specific literature. The Web of Science Core Collection was searched with a list of SDU synonyms. All SDU-related articles were analyzed using the R package, bibliometrix. Full text review identified chemsex-specific records, and text was extracted verbatim for content analysis in Leximancer. The search returned 1,866 unique records. A total of 521 addressed SDU, and 301 papers specifically addressed chemsex. The small but growing SDU literature primarily addressed consensual encounters between MSM, and drug-facilitated assault experienced by women, in Western settings. Little attention was given to transgender communities or consensual SDU in cisgender heterosexual individuals. The literature primarily viewed SDU through a public health lens, specifically focusing on the risk conferred to sexual health.The SDU and chemsex-specific literature are potentially limited in scope and may inadequately capture the geographical, demographic, and cultural diversity of these phenomena. Future research should address the myriad social and health implications of SDU and chemsex participation across all relevant communities and settings.

Quantified Striatal Dopaminergic Denervation as Predictor for Motor Outcomes in Parkinson's Disease.

Background: A hallmark of Parkinson's disease (PD) is progressive loss of dopamine terminals in the basal ganglia, with clinical symptoms including motor and non-motor manifestations such as bradykinesia, rigidity, and cognitive impairment. Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can be used to assess dopaminergic denervation by detecting loss of striatal dopamine transporters (DaT). Objective: We examined DaT binding scores' (DaTbs) association with motor outcomes in PD and explored its usefulness as a predictor of disease progression. Faster dopaminergic denervation in the basal ganglia was hypothesized to have stronger correlation and predictive value for poor motor outcomes. Methods: Data was analyzed from the Parkinson's Progression Markers Initiative. DaTbs in the putamen and caudate nucleus were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores for walking and balance difficulties, gait difficulties, and presence of dyskinesias. A predictive model using baseline speed of drop in DaT binding score was performed for each motor outcome. Results: All motor outcomes had mild, significantly negative correlation with DaTbs in the putamen and caudate nucleus, with similar degree of correlation per region. Speed of drop was predictive of only substantial gait difficulties when evaluated in the putamen but not the caudate. Conclusions: These findings suggest that analyzing speed of drop in DaTbs, which occurs early in the motor phase of the disease, may be helpful for predicting clinical outcomes in PD. Longer observation of this cohort may provide further data to investigate DaTbs as a prognostic marker in PD.

Sexual Orientation and Gender Identity Reporting in Highly Cited Current Alcohol Research.

Purpose: This study aimed to measure the frequency of high-quality and transparent sexual orientation and gender identity (SOGI) data collection and reporting in highly cited current alcohol use research, using the extant literature to identify community-informed priorities for the measurement of these variables. Methods: A single search to identify alcohol use literature was conducted on PubMed with results restricted to primary research articles published between 2015 and 2022. The 200 most highly cited studies from each year were identified and their titles and abstracts reviewed against inclusion criteria after deduplication. After full-text review, study characteristics and data indicating quality of SOGI reporting were extracted. The fidelity of the results was verified with a random sample before analyses. Results: The final sample comprised 580 records. Few studies reported gender identity (n = 194; 33.4%) and, of these, 7.2% reported the associated gender identity measure. A two-stage approach to measure gender was adopted in 3 studies, one study used an open-ended question with a free-text response option, and 13 studies recorded nonbinary gender identities (reported by 0.9% of the whole sample). Nineteen (3.3%) studies reported sexual orientation and more than half of these provided the sexual orientation measure. Eight of the 20 studies that reported sexual orientation and/or gender identity measures were classified as sexual and gender minority specialist research. Conclusions: Culturally competent SOGI reporting is lacking in highly cited current alcohol research. SOGI measures should be disclosed in future research and should provide free-text response options.

Investigating social deprivation and comorbid mental health diagnosis as predictors of treatment access among patients with an opioid use disorder using substance use services: a prospective cohort study.

BACKGROUND: Opioid use is a major public health concern across the globe. Opioid use and subsequent access to care is often shaped by co-occurring issues faced by people using opioids, such as deprivation, mental ill-health, and other forms of substance use. We investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London. METHODS: We conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed negative binominal regression and Cox proportional survival analyses to assess associations between exposures and outcomes. RESULTS: Comorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.91 (1.74-9.14) for non-opioid substance use comorbidity, 8.92 (1.81-64.4) for a single comorbid mental health diagnosis, and 15.9 (5.89-47.5) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services within this sample. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services. CONCLUSION: Comorbid substance and mental health difficulties amongst people with an opioid use disorder led to earlier and more frequent contact with crisis/inpatient mental health services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their wider needs (such as social, financial and other non-medical concerns) will ensure they are supported in their treatment journeys.