Sex-Specific Effects of Birth Weight on Longitudinal Behavioral Outcomes: A Mendelian Randomization Approach Using Polygenic Scores.

Background: It is unclear whether sex differences in behavior arising from birth weight (BW) are genuine because of the cross-sectional nature and potential confounding in previous studies. We aimed to test whether sex differences associated with BW phenotype were reproducible using a Mendelian randomization approach, i.e., association between polygenic score (PGS) for BW and behavior outcomes across childhood and adolescence. Methods: Using data from the Raine Study, we had 1484 genotyped participants with a total of 6446 Child Behavior Checklist assessments from ages 5 to 17 years. We used BW-PGSs in linear mixed-effect models to predict parentally assessed attention, aggression, and social problems scales; we also derived estimates and significance for a sex-by-genotype interaction. We used a Bonferroni-corrected significance threshold and tested robustness of the results with teacher assessments of behavior and a second PGS. Results: We found a sex-by-genotype interaction with lower BW-PGSs associated with increased aggression in males compared with females. These findings were consistent across various analyses, including teacher assessments. Surprisingly, a lower BW-PGS showed protective effects in females, while a lower BW phenotype had detrimental effects in males with evidence of a genotype-phenotype mismatch increasing aggression problems in males only. Conclusions: This study underscores the genuine nature of behavioral sex differences arising from low BW and highlights the sex-dependent and diverging effects of environmental and genetic BW determinants.

Previous studies have suggested a link between low birth weight and poor behavioral outcomes in children and adolescents, but it is unclear if these effects differ between males and females. We demonstrated that genes influencing birth weight had different effects on aggressive behavior in males and females with effects throughout childhood and adolescence; furthermore, our study suggests that birth weight environment and birth weight genes have different effects on behavior. In males, a mismatch between the genetically determined birth weight and the measured birth weight resulted in more aggressive behavior.

Prediction models for identifying medication overuse or medication overuse headache in migraine patients: a systematic review.

BACKGROUND: Migraine is a debilitating neurological disorder that presents significant management challenges, resulting in underdiagnosis and inappropriate treatments, leaving patients at risk of medication overuse (MO). MO contributes to disease progression and the development of medication overuse headache (MOH). Predicting which migraine patients are at risk of MO/MOH is crucial for effective management. Thus, this systematic review aims to review and critique available prediction models for MO/MOH in migraine patients. METHODS: A systematic search was conducted using Embase, Scopus, Medline/PubMed, ACM Digital Library, and IEEE databases from inception to April 22, 2024. The risk of bias was assessed using the prediction model risk of bias assessment tool. RESULTS: Out of 1,579 articles, six studies with nine models met the inclusion criteria. Three studies developed new prediction models, while the remaining validated existing scores. Most studies utilized cross-sectional and prospective data collection in specific headache settings and migraine types. The models included up to 53 predictors, with sample sizes from 17 to 1,419 participants. Traditional statistical models (logistic regression and least absolute shrinkage and selection operator regression) were used in two studies, while one utilized a machine learning (ML) technique (support vector machines). Receiver operating characteristic analysis was employed to validate existing scores. The area under the receiver operating characteristic (AUROC) for the ML model (0.83) outperformed the traditional statistical model (0.62) in internal validation. The AUROCs ranged from 0.84 to 0.85 for the validation of existing scores. Common predictors included age and gender; genetic data and questionnaire evaluations were also included. All studies demonstrated a high risk of bias in model construction and high concerns regarding applicability to participants. CONCLUSION: This review identified promising results for MO/MOH prediction models in migraine patients, although the field remains limited. Future research should incorporate important risk factors, assess discrimination and calibration, and perform external validation. Further studies with robust designs, appropriate settings, high-quality and quantity data, and rigorous methodologies are necessary to advance this field.

The Effect of Sleep Duration and Excessive Daytime Sleepiness on All-Cause Dementia: A Longitudinal Analysis from the Hunter Community Study.

OBJECTIVES: It has been proposed that abnormal sleep duration and excessive daytime sleepiness might be risk factors for dementia. This study assessed the interaction between sleep duration and excessive daytime sleepiness, and the effect of sleep duration in the presence or absence of excessive daytime sleepiness on dementia risk in community-dwelling older adults. DESIGN: A longitudinal study. SETTING AND PARTICIPANTS: Data from 2187 community-dwelling participants with mean age 70 years from the Hunter Community Study were included in this study. METHODS: Participants were classified as participants with long sleep duration (slept >8 hours per night), recommended sleep duration (7-8 hours) as per the National Sleep Foundation, or short sleep duration (slept <7 hours per night). The Berlin Questionnaire was used to identify excessive daytime sleepiness. Dementia was defined as per International Classification of Diseases, 10th Revision codes. To calculate all-cause dementia risk, the Fine-Gray sub-distribution hazard model was computed with death as a competing risk. RESULTS: Over a mean follow-up of 6 years, 64 participants developed dementia and 154 deaths were identified. The average onset of dementia was 5.4 years. Long sleep duration was associated with increased dementia risk only in the presence of excessive daytime sleepiness (adjusted hazard ratio, 2.86; 95% confidence interval 1.03-7.91). A statistically significant interaction was found between excessive daytime sleepiness and sleep duration for all-cause dementia. CONCLUSIONS AND IMPLICATIONS: Long sleep duration with excessive daytime sleepiness was associated with increased risk of all-cause dementia. This suggests the importance of promoting awareness of healthy sleep and the possible role of nurturing good quantity and quality sleep in reducing the risk of dementia.

Efficacy of 100% autologous platelet-rich plasma and 100% autologous serum in dry eye disease: a randomised controlled trial.

OBJECTIVE: The 0bjective is to compare treatment effects between undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) in patients with moderate-to-severe dry eye disease (DED). METHODS AND ANALYSIS: A single-centre, randomised, double-masked, non-inferiority clinical trial was conducted. 96 adult DED patients with an Ocular Surface Disease Index (OSDI) Score of ≥23 and/or Oxford staining grade of ≥2 were randomised to receive either 100% APRP (n=48) or 100% AS (n=48) for 4 weeks. Primary outcomes included OSDI Score and ocular surface staining measured by Oxford grading scale at 4 weeks. Secondary outcomes included fluorescein tear break-up time, Schirmer's test, meibum quality and expressibility, and adverse events. The 95% CI for the mean difference in OSDI scores between groups was estimated to assess non-inferiority of the OSDI score at a prespecified margin of 4.18 points. RESULTS: At week 4, there was no significant difference in decreased OSDI scores between groups, with the mean difference (100% APRP-100% AS) of 1.41 (95% CI -1.26, 4.08, p=0.299). The upper limit was less than the prespecified margin, indicating non-inferiority of 100% APRP vs 100% AS. The probabilities of achieving an Oxford grade 0-1 after treatment were not significantly different between groups, with an OR of 0.61 (95% CI 0.25, 1.52, p=0.288). No significant differences in secondary outcomes were observed between groups. CONCLUSION: In the short-term, 100% APRP was not inferior to 100% AS in reducing dry eye symptoms and ocular surface staining in moderate-to-severe DED. TRIAL REGISTRATION NUMBER: NCT04683796.

A systematic review and quality assessment of economic evaluations of kidney replacement therapies in end-stage kidney disease.

End-stage kidney disease (ESKD) is fatal without treatment by kidney replacement therapies (KRTs). However, access to these treatment modalities can be problematic given the high costs. This systematic review (SR) aims to provide an updated economic evaluation of pairwise comparisons of KRTs and the implications for the proportion of patients with access to the KRT modalities, i.e., kidney transplantation (KT), hemodialysis (HD), and peritoneal dialysis (PD). This SR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020. We searched studies in PubMed, Embase, Scopus, and Cost Effectiveness Analysis (CEA) registry, from inception to March 2023. Thirteen studies were included with pairwise comparisons among three KRTs, with varying proportions of patients for each modality. Seven studies were from high-income countries, including five from Europe. Summary findings are presented on a cost-effectiveness plane and incremental net benefit (INB). KT was the most cost-effective intervention across the pairwise comparisons. KT and PD were both more cost-effective alternatives to HD. HD was more costly and less effective than PD in all studies except one. Concurrent efforts to increase both KT and PD represented the best scenario to improve treatment options for ESKD patients.

Increasing participation in resistance training using outdoor gyms: A study protocol for the ecofit type III hybrid effectiveness implementation trial.

Background: In this paper we outline the protocol for an implementation-effectiveness trial of ecofit, a multi-component mHealth intervention aimed at increasing participation in resistance and aerobic physical activity using the outdoor built environment (i.e., outdoor gyms) and social support. We have previously demonstrated the efficacy and effectiveness of the ecofit program in insufficiently active people with (or at risk of) type 2 diabetes and community-dwelling adults, respectively. The objective of this trial is to compare the effects of two implementation support models (i.e., 'Low' versus 'Moderate') on the reach (primary outcome), uptake, dose received, impact and fidelity of the ecofit program. Research design and methods: This hybrid type III implementation-effectiveness study will be evaluated using a two-arm randomized controlled trial, including 16 outdoor gym locations in two large regional municipalities in New South Wales, Australia. Outdoor gym locations will be pair-matched, based on an established socio-economic status consensus-based index (high versus low), and randomized to the 'Low' (i.e., ecofit app only) or 'Moderate' (i.e., ecofit app, face-to-face workout sessions and QR codes) implementation support group. The primary outcome of 'reach' will be measured using a modified version of the 'System for Observing Play and Recreation in Communities', capturing outdoor gym use amongst community members. Conclusion: This implementation-effectiveness trial will evaluate the effects of different levels of implementation support on participation in resistance-focused physical activity using mHealth and outdoor gyms across the broader community. This may guide widespread dissemination for councils (municipalities) nation-wide wanting to promote outdoor gym usage. Trial registry: This trial was preregistered with the Australian and New Zealand Clinical Trial Registry (ACTRN12624000261516).

Effectiveness of NSW health get healthy telephone coaching in adults screened from general practices.

BACKGROUND: The effectiveness of the NSW Health "Get Healthy Information and Coaching Service®"(Get Healthy) to facilitate weight loss on a population scale has been documented, but this was based on self-reported measures. Our study aims to test the effectiveness of the Get Healthy Service on objectively measured weight, BMI, waist circumference, and changes in other health behaviours, including nutrition, physical activity and alcohol intake. METHODS: Men and women aged 40-70 years (n = 154) with pre-diabetes (5.7% < HbA1c < 6.5%) were referred from GP Practices to the Get Healthy Service, NSW Health. A subset (n = 98) participated in the "Zinc In Preventing the Progression of pre-Diabetes" (ZIPPeD) trial (ACTRN12618001120268). RESULTS: The self-reported outcomes showed a statistically significant improvement from baseline to 12 months in weight (mean 2.7 kg loss, p < 0.001), BMI (mean 1 unit reduction, p < 0.001), and waist circumference (mean 4.3 cm reduction, p < 0.001). However, in the objectively measured outcomes from ZIPPeD, the differences were more modest, with point estimates of 0.8 kg mean weight loss (p = 0.1), 0.4 unit reduction in BMI (p = 0.03), and 1.8 cm reduction in waist circumference (p = 0.04). Bland-Altman plots indicated that discrepancies were due to a small number of participants who dramatically underestimated their weight or BMI. There were minimal changes in nutrition, physical activity, and alcohol. CONCLUSIONS: The potential benefits of Get Healthy should be interpreted with caution as we have shown significant differences between self-reported and objectively measured values. More valid and objective evidence is needed to determine the program's effectiveness and cost-effectiveness.

Spillover effects from a type 2 diabetes integrated model of care in 22,706 Australians: an open cohort stepped wedge trial.

BACKGROUND: Many Australian adults are not receiving timely or effective diabetes management to prevent or delay the onset of diabetes related complications. Integrated care, a worldwide trend in healthcare reform, aims to reduce the fragmented delivery of health services and improve outcomes. This study aimed to test whether a specialist-led integrated model of care provided to a small subset of patients in general practices leads to spillover clinical improvements in all patients of the practice with type 2 diabetes. METHODS: Seventy-two general practice sites (clusters) in New South Wales, Australia received the Diabetes Alliance intervention, creating a non-randomised open cohort stepped wedge trial. The intervention comprised of case conferencing, delivered directly to a small proportion of adults with type 2 diabetes (n = 1,072) of the general practice sites; as well as practice feedback, education and training. Spillover clinical improvements were assessed on all adults with type 2 diabetes within the general practice sites (n = 22,706), using practice level data recorded in the MedicineInsight electronic database, compared before and after the intervention. Outcome measures included frequency of diabetes screening tests in line with the Annual Cycle of Care, and clinical results for weight, blood pressure, HbA1c, lipids, and kidney function. RESULTS: Compared to before Diabetes Alliance, the odds of all practice patients receiving screening tests at or above the recommended intervals were significantly higher for all recommended tests after Diabetes Alliance (odds ratio range 1.41-4.45, p < 0.0001). Significant improvements in clinical outcomes were observed for weight (absolute mean difference: -1.38 kg), blood pressure (systolic - 1.12 mmHg, diastolic - 1.18 mmHg), HbA1c (-0.03% at the mean), total cholesterol (-0.11 mmol/L), and triglycerides (-0.02 mmol/L) (p < 0.05). There were small but significant declines in kidney function. CONCLUSIONS: Integrated care delivered to a small subset of patients with type 2 diabetes across a large geographic region has spillover benefits that improve the process measures and clinical outcomes for all practice patients with type 2 diabetes. TRIAL REGISTRATION: ACTRN12622001438741; 10th November 2022, retrospectively registered: https://www.anzctr.org.au/ACTRN12622001438741.aspx .

Manual Chest PRESSURE During Direct Current Cardioversion for Atrial Fibrillation: A Randomized Control Trial (PRESSURE-AF).

BACKGROUND: Direct current cardioversion is frequently used to return patients with atrial fibrillation (AF) to sinus rhythm. Chest pressure during cardioversion may improve the efficacy of cardioversion through decreasing transthoracic impedance and increasing cardiac energy delivery. OBJECTIVES: This study aimed to assess the efficacy and safety of upfront chest pressure during direct current cardioversion for AF with anterior-posterior pad positioning. METHODS: This was a multicenter, investigator-initiated, double-blinded, randomized clinical trial. Recruitment occurred from 2021 to 2023. Follow-up was until hospital discharge. Recruitment occurred across 3 centers in New South Wales, Australia. Inclusion criteria were age ≥18 years, referred for cardioversion for AF, and anticoagulation for 3 weeks or transesophageal echocardiography excluding left atrial appendage thrombus. Exclusion criteria were other arrhythmias requiring cardioversion, such as atrial flutter and atrial tachycardia. The intervention arm received chest pressure during cardioversion from the first shock. The primary efficacy outcome was total joules required per patient encounter. Secondary efficacy outcomes included first shock success, transthoracic impedance, cardioversion success, and sinus rhythm at 30 minutes post cardioversion. RESULTS: A total of 311 patients were randomized, 153 to control and 158 to intervention. There was no difference in total joules applied per encounter in the control arm vs intervention arm (355.0 ± 301 J vs 413.8 ± 347 J; P = 0.19). There was no difference in first shock success, total shocks provided, average impedance, and cardioversion success. CONCLUSIONS: This study does not support the routine application of chest pressure for direct current cardioversion in atrial fibrillation (PRESSURE-AF [Investigating the Efficacy of Chest Pressure for Direct Current Cardioversion in Atrial Fibrillation: A Randomized Controlled Trial]; ACTRN12620001028998).

A Large-Scale Genome-Wide Gene-Sleep Interaction Study in 732,564 Participants Identifies Lipid Loci Explaining Sleep-Associated Lipid Disturbances.

We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify novel genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. We collected data from 55 cohorts with a combined sample size of 732,564 participants (87% European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20% of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for the one-degree of freedom tests of interaction and two-degree of freedom joint tests of the main and interaction effect. In the cross-population meta-analyses, the one-degree of freedom variant-sleep interaction test identified 10 loci (P int <5.0e-9) not previously observed for lipids. Of interest, the ASPH locus (TG, LTST) is a target for aspartic and succinic acid metabolism previously shown to improve sleep and cardiovascular risk. The two-degree of freedom analyses identified an additional 7 loci that showed evidence for variant-sleep interaction (P joint <5.0e-9 in combination with P int <6.6e-6). Of these, the SLC8A1 locus (TG, STST) has been considered a potential treatment target for reduction of ischemic damage after acute myocardial infarction. Collectively, the 17 (9 with STST; 8 with LTST) loci identified in this large-scale initiative provides evidence into the biomolecular mechanisms underpinning sleep-duration-associated changes in lipid levels. The identified druggable targets may contribute to the development of novel therapies for dyslipidemia in people with sleep disturbances.

Fasting vs no fasting prior to catheterisation laboratory procedures: the SCOFF trial.

BACKGROUND AND AIMS: Current guidelines recommend 6 hours of solid food and 2 hours of clear liquid fasting for patients undergoing cardiac procedures with conscious sedation. There are no data to support this practice, and previous single centre studies support the safety of removing fasting requirements. The objective of this study was to determine the non-inferiority of a no fasting strategy to fasting prior to cardiac catheterisation procedures which require conscious sedation. METHODS: This is a multicentre, investigator-initiated, non-inferiority randomised trial conduced in Australia with a prospective open label blinded endpoint design. Patients referred for coronary angiography, percutaneous coronary intervention or cardiac implantable electronic device (CIED) related procedures were enrolled. Patients were randomised 1:1 to fasting as normal (6 hours solid food and 2 hours clear liquid) or no fasting requirements (encouraged to have regular meals but not mandated to do so). Recruitment occurred from 2022 to 2023. The primary outcome was a composite of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia assessed with a Bayesian approach. Secondary outcomes included patient satisfaction score, new ventilation requirement (non-invasive and invasive), new intensive care unit admission, 30-day readmission, 30-day mortality, 30-day pneumonia. RESULTS: 716 patients were randomised with 358 in each group. Those in the fasting arm had significantly longer solid food fasting (13.2 versus 3.0 hours, Bayes factor >100 indicating extreme evidence of difference) and clear liquid fasting times (7.0 versus 2.4 hours, Bayes factor >100). The primary composite outcome occurred in 19.1% of patients in the fasting arm and 12.0% of patients in the no fasting arm. The estimate of the mean posterior difference in proportions in the primary composite outcome was -5.2% (95% CI -9.6 to -0.9, ) favouring no fasting. This result confirms non-inferiority (posterior probability >99.5%) and superiority (posterior probability 99.1%) of no fasting for the primary composite outcome. The no fasting arm had improved patient satisfaction scores with a posterior mean difference of 4.02 points (95% CI 3.36 to 4.67, Bayes factor >100). Secondary outcome events were similar. CONCLUSIONS: In patients undergoing cardiac catheterisation and CIED related procedures, no fasting was non-inferior and superior to fasting for the primary composite outcome of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia. Patient satisfaction scores were significantly better with no fasting. This supports removing fasting requirements for patients undergoing cardiac catheterisation laboratory procedures that require conscious sedation.

A Qualitative Study Supporting Optimal Nutrition in Advanced Liver Disease-Unlocking the Potential for Improvement.

Malnutrition rates in Advanced Liver Disease (ALD) are significantly higher than those in well-compensated liver disease. In addition to its physiological impact, malnutrition is detrimental for quality of life and social, emotional, and psychological well-being. Studies within oncology and renal supportive care have identified the influence of non-physiological factors on malnutrition risk. Integrating similar factors into malnutrition screening for ALD could improve identification of at-risk patients to optimize treatment planning. This qualitative study aimed to understand the holistic factors influencing nutritional status in the ALD population. Semi-structured interviews with 21 patients, carers, and clinicians explored the experiences of malnutrition in ALD. Thematic analysis revealed five key themes: (i) appropriateness of healthcare delivery; (ii) health- and food-related factors; (iii) high symptom burden, (iv) social support impacting well-being, and (v) physical and structural supports. Current screening methods do not adequately capture all potential drivers of malnutrition in the ALD population. Adopting a more supportive approach including both physiological and non-physiological factors in ALD malnutrition screening may promote more timely and comprehensive nutritional interventions that address the complex and holistic needs of patients living with ALD.

The Effect of Temporal Persistence of Loneliness on Dementia: A Longitudinal Analysis From the Hunter Community Study.

OBJECTIVES: Loneliness is common and becoming a public health concern. Although there is the clear evidence of the variable effect of temporal differences in loneliness (transient/situational and persistent/chronic) on health, their effect on dementia risk is unclear. This study aims to assess the effect of transient/situational and persistent/chronic loneliness on dementia risk. METHOD: Participants aged 55 years and older from the Hunter Community Study were recruited. Loneliness was measured using a single item measure. Dementia was defined as per International Classification of Disease-10 (ICD 10) codes. The Fine-Gray subdistribution hazard model was performed to calculate dementia risk. RESULTS: Of 1968 total participants with mean age of 66 years, (3%) 57 developed dementia and (7%) 135 died over the mean follow up of 10 years. Both persistent/chronic and transient/situational loneliness significantly increased the risk of all cause dementia in adjusted models (HR 2.74, 95% CI 1.11-6.88, p 0.03 and HR 2.35, 95% CI 1.21-4.55, p 0.01 respectively) with mean time to event of 9.7 years. Feeling lonely below the age of 70 years elevated the risk of dementia in later life (HR 4.01, 95% CI 1.40-11.50, p 0.01). CONCLUSIONS: Loneliness (both persistent/chronic and transient/situational) was associated with increased risk of all cause dementia, especially if loneliness was experienced before the age of 70 years. These results suggest that promoting coping strategies for loneliness especially in persons 70 years and younger may play a role in preventing dementia.

Racial and socioeconomic disparities in the treatment of unruptured intracranial aneurysms: A county hospital experience.

BACKGROUND: With increasing prevalence of unruptured intracranial aneurysms (UIAs), there is a need to provide appropriate management. Several studies have suggested that minorities in the United States have limited access to non-invasive imaging leading to increased presentation of aneurysmal subarachnoid hemorrhages (aSAHs). Given our medical institution's commitment to ensuring racial equality within our health care system, we chose to analyze our practice to assess the utilization of care provided by our neuroendovascular team. We hypothesized that given our diverse neuroendovascular care team along with our dedication to equity in healthcare, that we would find no difference in care provided to minority patients versus white patients who presented with UIAs. METHODS: We conducted a retrospective electronic medical record-based review of all patients with UIAs (n = 140) between September 2010 and June 2022 treated at a county hospital. Data regarding age at the time of treatment, gender, race, insurance type and aneurysm location were obtained. RESULTS: Of the 140 patients that underwent treatment, 54 % of patients were from the Black/Hispanic group and 46 % were from the white/non-Hispanic group. Commercial/private insurance was more common among White/NonHispanic patients (57.7 % vs 51.4 %) whereas Medicaid or uninsured status was more common among Black/Hispanic patients (25.7 % vs 15.4 %), although these differences were not statistically significant. CONCLUSION: Building a diverse neuroendovascular physician team with intentionality to equity in healthcare, and providing appropriate funding and resources to facilities used by marginalized populations, such as safety-net institutions, can mitigate minority patients' limited access to intracranial aneurysmal care.

The effect of anxiety on all-cause dementia: A longitudinal analysis from the Hunter Community Study.

BACKGROUND: Anxiety is common, however, the effect of chronicity of anxiety on dementia has not been explored. This study aims to assess the longitudinal relationship between chronic versus resolved versus new onset anxiety, and all-cause dementia risk. METHODS: A total of 2132 participants with mean age 76 years from the Hunter Community Study were recruited. Anxiety was measured using Kessler Psychological Distress Scale (K10). Dementia was defined as per International Classification of Disease-10 codes. The Fine-Gray subdistribution hazard model was computed to assess dementia risk, while adjusting for the competing risk of death. RESULTS: Chronic anxiety and new onset anxiety at follow-up were associated with all-cause dementia risk (HR 2.80, 95% CI 1.35-5.72 and HR 3.20, 95% CI 1.40-7.45 respectively) with an average time to dementia diagnosis of 10 years (SD = 1.7) whereas resolved anxiety was not. In subgroup analyses, these results were driven particularly by chronic and new anxiety among participants below the age of 70 years (HR 4.58, 95% CI 01.12-18.81 and HR 7.21, 95%CI 1.86-28.02 respectively). Sensitivity analyses imputing missing data and addressing reverse causation gave very similar results. CONCLUSION: Chronic and new anxiety were associated with increased risk of all-cause dementia, and this association was significant in those 70 years and younger. However, the resolved anxiety at follow-up reduced the risk, similar to that of the non-exposed group. These results suggest that timely management of anxiety may be a viable strategy in reducing the risk of dementia.

Outcomes associated with postoperative cognitive dysfunction: a systematic review and meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) manifests as a subtle decline in cognition, potentially leading to unfavourable postoperative outcomes. We explored the impact of POCD on physical function, length of hospital stay (LOS), dementia and mortality outcomes. METHODS: PubMed and Scopus were searched until May 2023. All studies of major surgical patients that assessed POCD and outcomes of interest were included. POCD effects were stratified by surgery type (cardiac and noncardiac) and time of POCD assessment (<30 and ≥30 days postsurgery). RESULTS: Of 2316 studies, 20 met the inclusion criteria. POCD was not associated with functional decline postsurgery. Patients who experienced POCD postcardiac surgery had an increased relative risk (RR) of death of 2.04 [(95% CI: 1.18, 3.50); I2 = 0.00%]. Sensitivity analyses showed associations with intermediate-term mortality among noncardiac surgical patients, with an RR of 1.84 [(95% CI: 1.26, 2.71); I2 = 0.00%]. Patients who developed POCD <30 days postcardiac and noncardiac surgeries experienced longer LOS than those who did not [mean difference (MD) = 1.37 days (95% CI: 0.35, 2.39); I2 = 92.38% and MD = 1.94 days (95% CI: 0.48, 3.40); I2 = 83.29%, respectively]. Postoperative delirium (POD) may contribute to the heterogeneity observed, but limited data were reported within the studies included. CONCLUSIONS: Patients undergoing cardiac and noncardiac surgeries who developed POCD <30 days postsurgery had poorer outcomes and an increased risk of premature death. Early recognition of perioperative neurocognitive disorders in at-risk patients may enable early intervention. However, POD may confound our findings, with further studies necessary to disentangle the effects of POD from POCD on clinical outcomes.

Individual treatment effects of sodium-glucose co-transporter-2 inhibitors on the risk of chronic kidney disease in patients with type 2 diabetes: A counterfactual prediction model based on real-world data.

AIM: To estimate individual treatment effects (ITEs) of sodium-glucose co-transporter-2 inhibitors (SGLT2is) on lowering the risk of developing chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and to identify those most probable to benefit from treatment. METHODS: This study followed a T2D cohort from Ramathibodi Hospital, Thailand, from 2015 to 2022. A counterfactual model was constructed to predict factual and counterfactual risks of CKD if patients did/did not receive SGLT2is. ITEs were estimated by subtracting the factual risk from the counterfactual risk of CKD. RESULTS: There were 1619 and 15 879 patients included in the SGLT2i and non-SGLT2i groups, respectively. The estimated ITEs varied from -1.19% to -17.51% with a median of -4.49%, that is, 50% of patients had a 4.49% or greater lower CKD risk if they received an SGLT2i. Patients who gained the greatest benefit from SGLT2is were more probable to be male, aged at least 60 years, with a history of diabetes duration of at least 3 months, hypertension, peripheral arterial disease, diabetic retinopathy and low high-density lipoprotein cholesterol. CONCLUSIONS: Our prediction model provides individualized information that helps target T2D patients who may benefit more from SGLT2is. This could help clinical decision making and implementation of personalized medicine in clinical practice, especially in resource-limited settings.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

Sex-specific effects of birth weight on longitudinal behavioural outcomes in children and adolescents: findings from the raine study.

Previous cross-sectional studies suggest that birth weight (BW) is associated with aggression-, social- and attention problems differently in boys and girls. We sought to test if these differences could be confirmed in a longitudinal study. The 1989 Raine Study provided prospectively collected data on perinatal variables and repeated child behaviour checklist assessments from ages 5 to 17. Linear mixed effects models provided crude and adjusted relationships between BW and childhood behaviour at a conservative significance threshold using prenatal maternal covariables in adjusted models. Sensitivity analyses included an age10 teacher assessment. Data on behaviour, BW and sex, was available in 2269 participants. Male sex was associated with increased aggression problems at lower BW compared to females in the crude model (Interaction B: -0.436, 98.3%CI: [-0.844, -0.0253]), but not the adjusted model (Interaction B: -0.310, 98.3%CI: [-0.742, 0.140]). Male sex was associated with increased attention problems at lower BW compared to females in both the crude model (Interaction B: -0.334, 98.3%CI: [-0.530, -0.137]) and the adjusted model (Interaction B: -0.274, 98.3%CI: [-0.507, -0.0432]). Male sex was associated with increased social problems at lower BW compared to females in both the crude model (Interaction B: -0.164, 98.3%CI: [-0.283, -0.0441]) and the adjusted model (Interaction B: -0.148, 98.3%CI: [-0.285, -0.00734]). Using repeated measures from ages 5-17 we were able to show a crude and adjusted male vulnerability to lower BW in the development of attention problems and social problems. We did not find a BW x sex interaction for the development of aggressive behaviour.