Normal, dust-obscured galaxies in the epoch of reionization.

Over the past decades, rest-frame ultraviolet (UV) observations have provided large samples of UV luminous galaxies at redshift (z) greater than 6 (refs. 1-3), during the so-called epoch of reionization. While a few of these UV-identified galaxies revealed substantial dust reservoirs4-7, very heavily dust-obscured sources at these early times have remained elusive. They are limited to a rare population of extreme starburst galaxies8-12 and companions of rare quasars13,14. These studies conclude that the contribution of dust-obscured galaxies to the cosmic star formation rate density at z > 6 is sub-dominant. Recent ALMA and Spitzer observations have identified a more abundant, less extreme population of obscured galaxies at z = 3-6 (refs. 15,16). However, this population has not been confirmed in the reionization epoch so far. Here, we report the discovery of two dust-obscured star-forming galaxies at z = 6.6813 ± 0.0005 and z = 7.3521 ± 0.0005. These objects are not detected in existing rest-frame UV data and were discovered only through their far-infrared [C II] lines and dust continuum emission as companions to typical UV-luminous galaxies at the same redshift. The two galaxies exhibit lower infrared luminosities and star-formation rates than extreme starbursts, in line with typical star-forming galaxies at z ≈ 7. This population of heavily dust-obscured galaxies appears to contribute 10-25% to the z > 6 cosmic star formation rate density.

Smoking at football clubs with and without smoke-free policies in the Netherlands: an observational study.

OBJECTIVES: Research shows that smoking persists in sports clubs with smoke-free policies (SFPs). It is unknown to what extent smoking occurs at such clubs and how much that may differ from clubs without SFPs. This study aimed to determine whether and to what extent smoking differs at Dutch football clubs with and without SFPs. STUDY DESIGN: This cross-sectional study used a purposive sampling method to compare smoking indicators at 117 Dutch football clubs, with 49 clubs (41.8%) having an SFP. METHODS: Using a standardised checklist, three smoking indicators were observed (number of people smoking, smoking facilities, and cigarette butts) and combined in a total smoking score (scale 0-9). Multi-level linear regression analysis was used to analyse the association between club SFP, local tobacco control policies (TCPs), and smoking indicators. RESULTS: Significantly fewer smoking facilities were present at clubs with an SFP (-2.35, 95% confidence interval [CI]: -3.61; -1.09), but no significant associations were found between SFP and the number of people smoking and cigarette butts. The total smoking score was 1.74 points lower for clubs with an SFP (95% CI: -2.53; -0.96) and 1.85 points lower for clubs in municipalities with strong local TCPs (95% CI: -2.98; -0.72). Strong local TCPs were associated with significantly fewer people smoking at clubs (-1.79, 95% CI: -3.41; -0.17). CONCLUSIONS: SFPs at sports clubs succeed in limiting the number of smoking facilities but do not show differences in terms of smoking rates or smoking-related litter when compared to clubs without SFPs. Our results highlight the need for enhancing implementation of comprehensive SFPs, including clear guidelines for compliance and enforcement.

The association of adolescents' smoking with the physical activity levels of their friends.

BACKGROUND: Smoking is inversely related to people's Physical Activity Level (PAL). As the behavior of friends may affect the choices and behavior of adolescents, having friends with a high PAL may potentially protect against adolescent smoking. This study aims to assess whether adolescents' smoking is associated with the PAL of their friends. METHODS: SILNE-R survey data of 11.918 adolescents from 55 different schools in 7 European cities was used to determine weekly smoking, individual PAL, PAL of friends, school PAL, and smoking of friends. Multilevel, multivariable logistic regression analysis were used to assess the association between the PAL of friends and weekly smoking. Several socio-demographic variables were included as covariates in the analysis. RESULTS: Our results indicated that 10.8% of the respondents was smoking weekly. Weekly smoking was most common among adolescents whose friends had a PAL of 0-42.0 min per day (14.5%). Respondents were significantly more likely to be smoking weekly if their friends were on average 0-42 min vs. 80-180 min physically active (OR 1.27 [95% CI 1.04-1.55]). This association existed independently of the individual PAL of respondents. Stratification for smoking of friends yielded equal results, although the association appeared to be somewhat stronger for those with smoking friends (OR 1.38 [95% CI 1.06-1.82]). CONCLUSION: Adolescents are less likely to smoke weekly if they associate with friends who spend >80 min per day on physical activity. Initiatives aimed at the prevention of smoking among adolescents may benefit from organizing group-based physical activity programs.

The impact of smoke-free policies on smoking at outdoor sports clubs: a qualitative study.

OBJECTIVES: Smoking may still occur at sports clubs with an outdoor smoke-free policy (SFP). This study aims to map the occurrence of smoking at various sports clubs in the Netherlands and to understand why smoking occurs at some clubs but not at others. STUDY DESIGN: This was a qualitative design in the form of semistructured interviews. METHODS: Semistructured interviews (n = 34) were held online with smoking and non-smoking members of 17 Dutch outdoor sports clubs (in field hockey, korfball, football, and tennis) with an outdoor SFP. Data were analyzed using content analysis. RESULTS: We identified four situations where smoking still occurred: (1) directly at the entrance, (2) at some distance from the entrance, (3) in particular places on the premises, and (4) in various places or on occasions when alcohol is consumed. Smoking directly at the entrance was most often perceived as a bothersome situation that was difficult to avoid. The occurrence of these situations differed per sports club depending on the scope of the SFP (the comprehensiveness of the SFP and the presence or absence of a smoking area) and factors influencing policy compliance (physical characteristics of the sports club's premises, the presence or absence of children, and several enforcement difficulties). CONCLUSION: In some sports clubs, smoking remained common on the premises despite an outdoor SFP. Exposure to second-hand smoke might be reduced by formulating a comprehensive SFP, improving policy compliance also in situations where children are absent, and organizing the enforcement of the policy.

Evaluation of a nationwide Dutch guideline to detect Lynch syndrome in patients with endometrial cancer.

OBJECTIVE: In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, supplemented with MLH1 methylation analysis if indicated. Test results are evaluated by the treating gynaecologist, who refers eligible patients to a clinical geneticist. We evaluated the implementation of this guideline. METHODS: From the nation-wide pathology database we selected all women diagnosed with EC < 70 years of age, treated from 1.6.2016-1.6.2017 in 14 hospitals. We collected data on the results of LSS and follow up of cases with suspected LS. RESULTS: In 183 out of 204 tumours (90%) LSS was performed. In 41 cases (22%) MMR protein expression was lost, in 25 cases due to hypermethylation of the MLH1 promotor. One patient was known with a pathogenic MLH1 variant. The option of genetic counselling was discussed with 12 of the 15 remaining patients, of whom three declined. After counselling by the genetic counsellor nine patients underwent germline testing. In two no pathogenic germline variant was detected, two were diagnosed with a pathogenic PMS2 variant, and five with a pathogenic MSH6 variant, in concordance with the IHC profiles. CONCLUSION: Coverage of LSS was high (90%), though referral for genetic counselling could be improved. Gynaecologists ought to be aware of the benefits and possible drawbacks of knowing mutational status, and require training in discussing this with their patients.

A critical appraisal of pharmacogenetic inference.

In essence, pharmacogenetic research is aimed at discovering variants of importance to gene-treatment interaction. However, epidemiological studies are rarely set up with this goal in mind. It is therefore of great importance that researchers clearly communicate which assumptions they have had to make, and which inherent limitations apply to the interpretation of their results. This review discusses considerations of, and the underlying assumptions for, utilizing different response phenotypes and study designs popular in pharmacogenetic research to infer gene-treatment interaction effects, with a special focus on those dealing with of clinical effects of drug treatment.

High-sensitivity C-reactive protein, low-grade systemic inflammation and type 2 diabetes mellitus: A two-sample Mendelian randomization study.

BACKGROUND AND AIMS: The role of inflammation in type 2 diabetes mellitus (T2D) remains unclear. We investigated the associations of high sensitivity C-reactive protein (hsCRP) concentration with T2D and glycemic traits using two-sample Mendelian Randomization. METHODS AND RESULTS: We used publically available summary-statistics data from genome-wide association studies on T2D (DIAGRAM: 12 171 cases; 56 862 controls) and glycemic traits (MAGIC: 46 186 participants without diabetes mellitus). We combined the effects of the genetic instrumental variables through inverse-variance weighting (IVW), and MR-Egger regression and weighted-median estimation as sensitivity analyses which take into account potential violations (e.g., directional pleiotropy) of the assumptions of instrumental variable analyses. Analyses were conducted using 15 known hsCRP genetic instruments among which 6 instruments are hsCRP specific and not involved in inflammatory processes beyond hsCRP concentration regulation. Though we found no association between the combined effect of the genetic instrumental variables for hsCRP and T2D with IVW (odds ratio per 1 ln [hsCRP in mg/L]: 1.15; 95% confidence interval: 0.93, 1.42), we found associations for T2D with MR-Egger regression and weighted-median estimation (odds ratio with 95% confidence interval per 1 ln [hsCRP in mg/L], MR-Egger regression: 1.29; 1.08, 1.49; weighted-median estimator: 1.21; 1.02, 1.39). We found no association with T2D for the combination of hsCRP-specific genetic instruments nor did we found associations with glycemic traits in any of the analyses. CONCLUSION: Evidence was provided for a potential causal association between hsCRP and T2D, but only after considering directional pleiotropy. However, hsCRP was not causally associated with glycemic traits.

Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study.

BACKGROUND: A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. METHODS: Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. RESULTS: Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. CONCLUSION: The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies.

PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive or actually non-adherent? Therefore, the aim of this study was to describe, within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), characteristics of both non-responders and high responders of statin treatment in order to possibly discriminate non-responders from non-adherers. METHODS: Baseline characteristics of non-responders to statin therapy (≤10 % LDL-C reduction) were compared with those of high responders (>40 % LDL-C reduction) through a linear regression analysis. In addition, pharmacogenetic candidate gene analysis was performed to show the effect of excluding non-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p < 0.001), had a higher alcohol consumption (p < 0.001), had lower LDL cholesterol levels (p < 0.001), had a lower prevalence of hypertension (p < 0.001), and had lower cognitive function (p = 0.035) compared to subjects who highly responded to pravastatin treatment. Moreover, excluding non-responders from pharmacogenetic studies yielded more robust results, as standard errors decreased. CONCLUSION: Our results suggest that non-responders to statin therapy are more likely to actually be non-adherers, since they have more characteristics that are viewed as indicators of high self-perceived health and low disease awareness, possibly making the subjects less adherent to study medication. We suggest that in pharmacogenetic research, extreme non-responders should be excluded to overcome the problem that non-adherence is investigated instead of non-responsiveness.

Keratocystic Odontogenic Tumour of the Mandible: a case report of decompression with a customised removable tube and review of literature.

Keratocystic odontogenic tumour (KOT or KCOT) is defined by the WHO to be 'a benign uni- or multicystic, intraosseous tumour of odontogenic origin'. In 2005, the World Health Organization renamed the lesion; previously known as an odontogenic keratocyst (OKC) as the KCOT. WHO recommends the term KCOT as it reflects its neoplastic nature. In this case report, a 21-year-old female with a histologically proven large parakeratinised KCOT of the right mandible underwent treatment that involved a 14-month period of decompression, followed by enucleation (with Carnoys application) of the residual cyst. During the period of decompression, a custom made removable mandibular chrome-cobalt appliance was used to hold the decompression tube in the oral cavity.

Using genetic variation for establishing causality of cardiovascular risk factors: overcoming confounding and reverse causality.

Cardiovascular disease (CVD) remains the leading cause of death in developed countries, despite the decline of CVD mortality over the last two decades. From observational, predictive research, efforts have been made to find causal risk factors for CVD. However, in recent years, some of these findings have been shown to be mistaken. Possible explanations for the discrepant findings are confounding and reverse causation. Genetic epidemiology has tried to address these problems through the use of Mendelian randomisation. In this paper, we discuss the promise and limitations of using genetic variation for establishing causality of cardiovascular risk factors.

Sex versus gender associations with brain structure.

In contrast to sex (a biological distinction), little is known about the associations between gender (a societal construct) and brain structure in the general population. In response to this knowledge gap, we examined the associations of sex vs. gender with FreeSurfer-generated cortical thickness and proportion-adjusted subcortical brain volume regions-of-interest (ROIs) in healthy adults (n = 88) screened for general medical conditions, mental illness, substance abuse, and intracranial pathologies. Gender role endorsement was assessed using the well-established and validated Bem Sex Role Inventory. For our main objectives, we calculated a continuum score as a composite measure of gender. For our secondary objectives, we examined sex-specific associations of the masculine vs. feminine gender role endorsement domains with brain structural outcomes. We found that female sex, independent of continuum scores, was associated with larger proportion-adjusted volumes for the basal ganglia, hippocampus, and ventral diencephalon. Higher continuum scores, independent of sex, were associated with thicker cortical thickness for the left and right superior frontal cortex, caudal and rostral middle frontal cortex, and right pars orbitalis. Female sex and higher continuum scores were independently associated with larger corpus callosum volumes. Post-hoc testing showed sex-specific associations between higher femininity scores and thicker prefrontal cortical thickness for the ROIs in females, but not in males. In conclusion, sex and gender showed semi-independent associations with brain structure in a general population sample. Our research supports the disaggregation of sex and gender to provide a more nuanced perspective on brain structural differences between men and women.

Relapse in schizophrenia: The role of factors other than non-adherence to treatment.

AIM: Relapse rates are very high in schizophrenia. However, little is known about the predictors of the time to relapse other than treatment non-adherence. We investigated possible risk factors for the time to relapse in patients with first-episode schizophrenia (n = 107) who received assured treatment by way of long-acting injectable antipsychotic over 24 months and who underwent regular clinical, cognitive, and metabolic assessments. METHODS: Using Cox regression analyses we assessed selected premorbid and baseline potential predictors of time to relapse. Relapse was defined using operationally defined relapse criteria. RESULTS: In the primary analysis only neurological soft signs total score retained significance, with higher scores predicting shorter time to relapse (HR = 1.05, 95% CI = 1.01-1.10, p = .029). In a more detailed secondary analysis poorer social relationships predicted shorter time to relapse (HR = 0.85, 95% CI = 0.76-0.95, p = .003). CONCLUSION: Our predominantly negative findings suggest that many of the previously implicated risk factors for the time to relapse are mediated by non-adherence rather than having a direct effect on relapse-proneness. Neurological soft signs, and perhaps quality of life in social relationships appear to play a role and merit further investigation.

Gaucher's Disease in an Adult Male: A Case Report of a Rare Mutation.

Gaucher's disease is a rare autosomal recessive inborn error of metabolism. As the presentation of this disease is similar to more common diseases like malaria, portal hypertension, hematological disorders, and kala-azar, this rare disease may not be thought of as a differential diagnosis, and a high index of suspicion is required to avoid diagnostic delay. We report a case of type 1 Gaucher's disease in an adult male born out of a consanguineous marriage. He was from a region where the prevalence of infectious diseases and sickle cell anemia is high. He presented with abdominal distension, hepatosplenomegaly, and pancytopenia. Bone marrow biopsy showed the presence of Gaucher cells. Glucocerebrosidase levels showed decreased enzyme activity. The genetic study revealed a very rare mutation that has not been reported in the 1000 Genomes database till now. Retrospectively, the most important clue was his birth out of a consanguineous marriage of his parents.

Melodious tuning of microbial dynamics in biofloc, cage, and pond culturing system: a study on Pangasius pangasius fish gut microbiome.

Aquaculture, a rapidly expanding sector, meets the global surging demand for aquatic food. Pangasius, a highly valued freshwater species, has seen a significant increase in demand due to its adaptability and potential for high yields, making it a promising candidate for aquaculture in India. This study investigates the gut microbiome composition of Pangasius pangasius fish cultured in three different systems (biofloc, cage, and pond). Metagenomic DNA extraction and 16S rRNA gene-targeted sequencing were performed. Outcomes revealed distinct microbial compositions across culture types, with significant differences in species richness and diversity, specifically in the biofloc system, compared to cages and ponds. Taxonomic analysis identified prevalent phyla such as Firmicutes and Fusobacteriota, with varying abundances among culture systems. The genus-level analysis highlighted dominant genera such as Cetobacterium and WWE3. Functional profiling indicated differences in enzymatic activity and metabolic pathways, emphasizing each culture sample type's unique microbial community structures. Notably, the microbiota from BF samples exhibited significant differences and unique metabolic pathways compared to the microbiota from C and P samples, which showed greater similarity and shared several common metabolic pathways. These findings highlight substantial differences in microbial diversity across the culturing systems, reflecting the microbiota's ability to adapt to specific environments and their potential role in promoting fish growth within those environments. Overall, this study provides insights into the gut microbiome diversity and functionality in Pangasius pangasius across different aquaculture environments, contributing to a better understanding of host-microbe interactions and aquaculture management strategies.

The need for smoking cessation counselling and nicotine withdrawal therapy for hospitalised patients: A smoking point prevalence study at Groote Schuur Hospital, Cape Town, South Africa.

Background: South Africa has high tobacco-attributable mortality and a smoking prevalence of 32.5% in males and 25.6% in females. There are limited data on smoking prevalence and desire to quit in hospitalised patients, who have limited access to smoking cessation services. Objectives: To determine smoking prevalence and the extent of nicotine withdrawal symptoms, using a hospital-wide inpatient survey. Methods: A 1-day point prevalence survey was conducted at Groote Schuur Hospital, Cape Town. All wards except the haematology isolation, active labour and psychiatry lock-up wards were evaluated. Smoking status, withdrawal symptoms and desire to quit were established. Results: Smoking status was confirmed in 85.8% of inpatients (n=501/584), of whom 31.9% (n=160) were current smokers; 43.5% (n=101/232) of male and 21.9% (n=59/269) of female inpatients were smokers. Documentation and confirmation of smoking status was highest in the maternity wards (100%) and lowest in the surgical wards (79.6%) and intensive care units (70.0%). Smoking prevalence ranged from 47.6% in male surgical patients to 15.2% in maternity patients. Of the smokers, 54.5% reported being motivated to quit, with a median (interquartile range) Fagerström test for nicotine dependence score of 4 (2 - 6), and 31.4% reported moderate to severe cravings to smoke, highest in the surgical wards. Conclusion: Smoking prevalence was higher in hospitalised patients than in the local general population. Many inpatients were not interested in quitting; however, a third had significant nicotine withdrawal symptoms. All inpatients who are active smokers should be identified and given universal brief smoking cessation advice. Patients with severe withdrawal symptoms should be allowed to smoke outside, and nicotine withdrawal pharmacotherapy should be provided to those who are bedbound or express a desire to stop smoking during the current admission. Study synopsis: What the study adds. A single data point prevalence study of active smokers at Groote Schuur Hospital, Cape Town, was conducted. The prevalence of smoking was higher in the hospitalised patients than in the general community, but not all smokers were identified by the clinicians. Although symptoms of nicotine withdrawal were severe in some patients, motivation to quit smoking was not related to the degree of withdrawal being experienced. Many patients were not motivated to quit smoking.Implications of the findings. Better identification of inpatient smokers is required, and all should be given smoking cessation advice. Withdrawal symptoms can be severe in some patients, and those who are not interested in stopping smoking should allowed to smoke outside or be provided with nicotine withdrawal pharmacotherapy while in hospital. Those who are willing to quit should be supported as well as possible, including provision of nicotine replacement therapy or varenicline, and followed up after discharge as best practice.

High-flow nasal oxygen in resource-constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic respiratory failure: Comparing outcomes of the first v. third waves at a tertiary centre in South Africa.

Background: High-flow nasal oxygen (HFNO) is an accepted treatment for severe COVID-19-related acute hypoxaemic respiratory failure (AHRF). Objectives: To determine whether treatment outcomes at Groote Schuur Hospital, Cape Town, South Africa, during the third COVID-19 wave would be affected by increased institutional experience and capacity for HNFO and more restrictive admission criteria for respiratory high-care wards and intensive care units. Methods: We included consecutive patients with COVID-19-related AHRF treated with HFNO during the first and third COVID-19 waves. The primary endpoint was comparison of HFNO failure (composite of the need for intubation or death while on HFNO) between waves. Results: A total of 744 patients were included: 343 in the first COVID-19 wave and 401 in the third. Patients treated with HFNO in the first wave were older (median (interquartile range) age 53 (46 - 61) years v. 47 (40 - 56) years; p<0.001), and had higher prevalences of diabetes (46.9% v. 36.9%; p=0.006), hypertension (51.0% v. 35.2%; p<0.001), obesity (33.5% v. 26.2%; p=0.029) and HIV infection (12.5% v. 5.5%; p<0.001). The partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2 /FiO2 ) ratio at HFNO initiation and the ratio of oxygen saturation/FiO2 to respiratory rate within 6 hours (ROX-6 score) after HFNO commencement were lower in the first wave compared with the third (median 57.9 (47.3 - 74.3) mmHg v. 64.3 (51.2 - 79.0) mmHg; p=0.005 and 3.19 (2.37 - 3.77) v. 3.43 (2.93 - 4.00); p<0.001, respectively). The likelihood of HFNO failure (57.1% v. 59.6%; p=0.498) and mortality (46.9% v. 52.1%; p=0.159) did not differ significantly between the first and third waves. Conclusion: Despite differences in patient characteristics, circulating viral variant and institutional experience with HFNO, treatment outcomes were very similar in the first and third COVID-19 waves. We conclude that once AHRF is established in COVID-19 pneumonia, the comorbidity profile and HFNO provider experience do not appear to affect outcome. Study synopsis: What the study adds. This study adds to the body of evidence demonstrating the utility of high-flow nasal oxygen (HFNO) in avoiding invasive mechanical ventilation (IMV) in patients with severe COVID-19 hypoxaemic respiratory failure, and shows that this utility remained consistent across different waves of the COVID-19 pandemic.Implications of the study. In resource-constrained settings, HFNO is a feasible non-invasive alternative to IMV and can be employed with favourable and consistent outcomes outside traditional critical care wards. It also confirms that the degree of gas exchange abnormality, and not pre-existing patient-related factors, circulating wave variant or provider experience, is the main predictor of HFNO failure.

Sex, gender, and outcome in first-episode psychosis: The role of premorbid functioning.

We examined the associations of sex (biological distinction) and gender (societal distinction) with psychopathology, depressive symptoms and social and occupational functioning over 24 months. We found that lower masculinity scores were associated with worse psychopathology outcomes, independent of sex and other neurodevelopmental factors. These effects were mediated by poor premorbid adjustment, which also mediated the relationship between childhood trauma and masculinity scores as predictors of disorganized symptom outcomes. Our findings highlight the importance of considering gender as a separate construct and the need for further research to understand the clinical implications of sex and gender differences in schizophrenia.

Asthma in the intensive care unit: A review of patient characteristics and outcomes.

Background: Most asthma-related deaths occur in low- and middle-income countries, and South Africa (SA) is ranked fifth in global asthma mortality. Little is known about the characteristics and outcome of asthma patients requiring intensive care unit (ICU) admission in SA. Objectives: To identify and characterise patients with acute severe asthma admitted to the respiratory ICU at Groote Schuur Hospital, Cape Town, SA, in order to evaluate outcomes and identify predictors of poor outcomes in those admitted. Methods: We performed a retrospective descriptive study of patients with severe asthma admitted to the respiratory ICU at Groote Schuur Hospital between 1 January 2014 and 31 December 2019. Results: One hundred and three patients (110 admission episodes) were identified with an acute asthma exacerbation requiring ICU admission; all were mechanically ventilated. There was a female preponderance (53.6%; n=59/110), with a median (range) age overall of 33 (13 - 84) years. Of all admissions, 40 (36.4%) were current tobacco smokers and 16 (14.5%) patients with a history of substance abuse. Two thirds (60.0%; n=66/110) of the patients were using an inhaled corticosteroid (ICS). No predictors of mortality were evident in multivariate modelling, although those who died were older, and had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores and longer duration of admission. Only 59 of the surviving 96 individual patients (61.5%) attended a specialist pulmonology clinic after discharge. Conclusion: Among patients admitted to the respiratory ICU at Groote Schuur Hospital for asthma exacerbations, there was a high prevalence of smokers and poor coverage with inhaled ICSs. Although mortality was low compared with general ICU mortality, more needs to be done to prevent acute severe asthma exacerbations. Study synopsis: What the study adds. Intensive care unit (ICU) admission represents the most severe form of exacerbation of asthma. South Africa (SA) has a very high rate of asthma deaths, and this study demonstrates that admission to an ICU with a very severe asthma exacerbation frequently results in a good outcome. However, many of the patients admitted to the ICU were not adequately treated with background asthma medications prior to their admission. Implications of the findings. Death from asthma should be avoidable, and admission to an ICU is not associated with high mortality. Patients are therefore likely to be dying at home or out of hospital. Better education and access to medication and early access to health services rather than improved in-hospital care would potentially alter SA's high asthma mortality.