Prevalence and determinants of low back pain among residents in Abha City, Saudi Arabia.

Background: Healthcare work is a major risk for having musculoskeletal disorders (MSDs), including low back pain (LBP). This study aimed to estimate the prevalence of LBP and define its associated risk factors among resident physicians. Material and Methods: A descriptive cross-sectional survey was conducted among all resident physicians of all specialties in Abha city during the period from July 2020 to September 2020. Data were collected using an online pre-structured data collection tool. The Nordic Musculoskeletal Questionnaire (NMQ) (back pain section) was applied to assess the effect of LBP on the residents' ability to perform job duties effectively. Results: A total of 312 resident physicians responded. Their age ranged between 25 and 41 years. Males represented 57.7% of them. The prevalence of LBP was 64.7%. The most common reported aggravating factors for LBP were working in uncomfortable posture (73.3%), standing for long periods (64.4%), and long sitting sessions (51.5%). Regarding the pain-relieving factors, sleeping ranked first (60.4%), followed by taking analgesics (48.5%) and maintaining a good posture (35.6%). Multivariate logistic regression analysis revealed that obese subjects were at higher risk than underweight subjects to develop LBP (adjusted odds ratio (AOR) =6.18, 95% confidence interval (CI): 1.26-30.34, P = 0.025). Compared to resident physicians without family history of back pain, those with such history were at almost 4-fold higher risk of developing LBP (AOR = 3.90, 95% CI: 2.33-6.52, P < 0.001). Conclusion: LBP is a very prevalent problem among resident physicians, particularly obese subjects and those with family history of back pain. LBP adversely impacts the work performance of the affected physicians.

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

Retracted Publications in Otolaryngology-Head and Neck Surgery: What Mistakes Are Being Made?

Objectives: Retraction of publications is critical to maintaining scientific integrity, yet there is a lack of research on its occurrence in Otolaryngology. This study investigates characteristics, trends, and reasons for retraction of publications in otolaryngology journals. Study Design: Bibliometric analysis. Setting: PubMed, Scopus, Web of Science. Methods: A PubMed search for publications retracted during 1990 to 2022 from the top 60 journals with the subject "Otorhinolaryngology" using Scopus' CiteScore was performed. Publications were excluded if they were not in English, had missing information or did not have available abstracts or full-text. Publication and retraction dates, journal, country of origin, citation counts, journal impact factor (JIF), topic, and reason for retraction were recorded. Pearson correlation coefficients were calculated to identify potential associations in the data. Results: Fifty-three publications were included. The 2020s had the highest number of retractions per year (4.33), with publications being retracted on average, 35 months after initial publication. The most common retracted topic and country of origin were head and neck (26.4%) and China (17.0%), respectively. Most publications were retracted because of plagiarism or duplicate publication (52.8%). Mean citation count was 6.92 ± 8.32 and mean JIF was 2.80 ± 1.35. Citation count was positively associated with months until retraction (r = .432, P = .001). There was no significant correlation between months to retraction and JIF (r = .022, P = .878). Conclusion: The most cited reasons for retraction were plagiarism and duplicate publication. An understanding of the reasons for retraction can better position journals to enforce more meticulous review standards and reduce such publications from being published. Level of Evidence: Level 4.

Plasma metabolomics changes comparing daytime to overnight infusions of home parenteral nutrition in adult patients with short bowel syndrome: Secondary analysis of a clinical trial.

BACKGROUND: Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight. METHODS: This secondary analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were examined from plasma samples. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis. RESULTS: Nine patients (mean age, 52.6 years; 78% female; mean BMI 20.7 kg/m2) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at Punadj < 0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA; 22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified changes in pathways related to the biosynthesis of unsaturated fatty acids, d-arginine, and d-ornithine metabolism, and linoleic acid metabolism (Punadj<0.05). CONCLUSION: Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.

Screening and Treatment of Posttraumatic Stress Disorder in Wildfire Evacuees: A Cost-Utility Analysis.

Background. Global climate change is resulting in dramatic increases in wildfires. Individuals exposed to wildfires experience a high burden of posttraumatic stress disorder (PTSD), and the cost-effectiveness of the treatment options to address PTSD from wildfires has not been studied. The objective of this study was to conduct a cost-utility analysis comparing screening followed by treatment with paroxetine or trauma-focused cognitive behavioral therapy (TF-CBT) versus no screening in Canadian adult wildfire evacuees. Methods. Using a Markov model, quality-adjusted life-years (QALYs) and costs were evaluated over a 5-y time horizon using health care and societal perspectives. All costs and utilities in the model were discounted at 1.5%. Probabilistic and deterministic sensitivity analyses examined the uncertainty in the incremental net monetary benefit (INMB) under a willingness-to-pay threshold of $50,000. Results. From a societal perspective, no screening (NMB = $177,641) was dominated by screening followed by treatment with paroxetine (NMB = $180,733) and TF-CBT (NMB = $181,787), with TF-CBT having the highest likelihood of being cost-effective at a willingness-to-pay threshold of $50,000 per QALY (probability = 0.649). The initial prevalence of PTSD, probability of acceptance of treatment, and costs of productivity had the largest impact on the INMB of both paroxetine or TF-CBT versus no screening. Neither intervention was cost-effective at a willingness-to-pay threshold of $50,000 per QALY from a health care perspective. Interpretation. Screening followed by treatment with paroxetine or TF-CBT compared with no screening was found to be cost-saving while providing additional QALYs in wildfire evacuees. Governments should consider funding screening programs for PTSD followed by treatment with TF-CBT for wildfire evacuees. Highlights: Two prior studies examined the cost-effectiveness of screening followed by treatment for PTSD among individuals exposed to other disaster-type events (i.e., terrorist attack and Hurricane Sandy) and found screening followed by treatment (i.e., cognitive behavioral therapy [CBT]) to be highly cost-effective.Among wildfire evacuees, screening followed by treatment with paroxetine or trauma-focused (TF)-CBT provides additional quality-adjusted life-years (QALYs) and is cost-saving from a societal perspective. TF-CBT was the treatment option found most likely to be cost-effective.Neither treatment option was cost-effective at a willingness-to-pay threshold of $50,000 per QALY from a health care perspective.Screening programs for PTSD should be considered for wildfire evacuees, and individuals diagnosed with PTSD could be prescribed either TF-CBT or paroxetine depending on their preference and resources availability.

Sleep and home parenteral nutrition in adults: A narrative review.

Infusions of home parenteral nutrition (HPN) are often cycled at night coinciding with sleep episodes. Adult consumers of HPN are known to experience poor sleep attributed to frequent awakenings and long durations of wakefulness after falling asleep. Consequently, most consumers do not meet recommendations for sleep duration and quality or daytime napping. The primary underlying pathophysiology resulting in sleep problems is nocturia; however, other factors also exist, including disruptions caused by medical equipment (ie, pump alarms), comorbid conditions, dysglycemia, and medication use. Early guidance on sleep is imperative because of the central role of sleep in physical health and wellbeing, including mitigating complications, such as infection risk, gastrointestinal problems, pain sensitivity, and fatigue. Clinicians should routinely inquire about the sleep of their patients and address factors known to perturb sleep. Nonpharmacologic opportunities to mitigate sleep problems include education on healthy sleep practices (ie, sleep hygiene); changes in infusion schedules, volumes, rates, and equipment; and, possibly, behavioral interventions, which have yet to be examined in this population. Addressing comorbid conditions, such as mood disorders, and nutrition deficiencies may also help. Pharmacologic interventions and technological advancement in HPN delivery are also needed. Research on sleep in this population is considered a priority, yet it remains limited at this time.

Using routinely collected clinical data for circadian medicine: A review of opportunities and challenges.

A wealth of data is available from electronic health records (EHR) that are collected as part of routine clinical care in hospitals worldwide. These rich, longitudinal data offer an attractive object of study for the field of circadian medicine, which aims to translate knowledge of circadian rhythms to improve patient health. This narrative review aims to discuss opportunities for EHR in studies of circadian medicine, highlight the methodological challenges, and provide recommendations for using these data to advance the field. In the existing literature, we find that data collected in real-world clinical settings have the potential to shed light on key questions in circadian medicine, including how 24-hour rhythms in clinical features are associated with-or even predictive of-health outcomes, whether the effect of medication or other clinical activities depend on time of day, and how circadian rhythms in physiology may influence clinical reference ranges or sampling protocols. However, optimal use of EHR to advance circadian medicine requires careful consideration of the limitations and sources of bias that are inherent to these data sources. In particular, time of day influences almost every interaction between a patient and the healthcare system, creating operational 24-hour patterns in the data that have little or nothing to do with biology. Addressing these challenges could help to expand the evidence base for the use of EHR in the field of circadian medicine.

Corridor and real-time 6-minute walk tests in healthy young adults: A randomized cross-over study.

Objective: Cardiopulmonary endurance is important for comfortably participating in activities of daily living. Exercise tests, such as the 6-minute walk test (6MWT), are commonly used to evaluate cardiopulmonary endurance. We investigated the effects of the Gait Real-Time Analysis Interactive Lab (GRAIL)- and corridor-based 6MWTs on functional performance. Methods: Thirty healthy men were randomly divided into two groups. Group A participants performed a corridor-based 6MWT, followed by a washout period (1 h). Subsequently, they performed the GRAIL-based 6MWT. Group B participants performed the tests in the reverse order of that performed by Group A participants. Results: The corridor-based 6MWT resulted in significantly higher 6MW distance and 6MW speed than the GRAIL-based 6MWT. No significant differences were observed between the two groups in any of the following secondary outcomes: systolic blood pressure, diastolic blood pressure, oxygen saturation, heart rate, dyspnea, and overall fatigue. A strong positive correlation was observed between the 6MW distance and 6MW speed. Conclusion: The corridor- and GRAIL-based 6MWT should not be used interchangeably.

Diagnostic Accuracy of Integrating Ultrasound and Shear Wave Elastography in Assessing Carpal Tunnel Syndrome Severity: a Prospective Observational Study.

Purpose: Carpal tunnel syndrome (CTS) is a common condition characterized by compression of the median nerve (MN) within the carpal tunnel. Accurate diagnosis and assessment of CTS severity are crucial for appropriate management decisions. This study aimed to investigate the combined diagnostic utility of B-mode ultrasound (US) and shear wave elastography (SWE) for assessing the severity of CTS in comparison to electrodiagnostic tests (EDT). Materials and Methods: This prospective observational study was conducted over 9-month periods at a tertiary care hospital. A total of 48 patients (36 females, 12 males; mean age 44 ± 10.9 years; age range 28-57 years) with clinically suspected CTS were enrolled. All patients underwent EDT, US, and SWE. Based on the EDT results, CTS cases were categorized into four groups: mild, moderate, severe, and negative. The cross-sectional area (CSA) and elasticity (E) of the MN were measured at the tunnel inlet (CSAu and Eu) and pronator quadratus region (CSAo and Eo). The differences (CSAu-CSAo and Eu-Eo) were calculated. The primary outcomes were the diagnostic performance of CSAu, CSAu-CSAo, Eu, and Eu-Eo in differentiating moderate/severe from mild/negative CTS compared to EDT findings. Secondary outcomes included a correlation of US/SWE parameters with EDT grades and between each other. ANOVA, correlation, regression, and receiver operating characteristic (ROC) curve analyses were performed. Results: CSAu and CSAu-CSAo increased progressively with worsening CTS severity. E measurements were significantly higher in moderate-to-severe CTS compared to mild or negative cases. The combined metric of CSAu-CSAo at a 5 mm threshold exhibited enhanced performance, with a higher sensitivity (83.3%), specificity (100%), and area under the curve (AUC) (0.98), surpassing the results of CSAu when used independently. Similarly, the SWE measurements indicated that Eu-Eo at a 56.1kPa cutoff achieved an AUC of 0.95, with a sensitivity of 93.3% and specificity of 94.4%, outperforming the metrics for Eu when used alone, which had an AUC of 0.93, with identical sensitivity and specificity values (93.3% and 94.4%, respectively). Conclusion: The integration of ultrasound, shear wave elastography, and electrodiagnostic tests provides a comprehensive approach to evaluate anatomical and neurological changes and guide management decisions for CTS.

Healthy Sleep Practices for Consumers of Home Total Parenteral Nutrition: A Mixed-Methods Community-Based Participatory Study.

Background: Consumers of overnight home parenteral nutrition (HPN) often experience sleep disruption; however, existing healthy sleep recommendations are widely inapplicable to consumers. Objectives: The aim of this mixed-methods, community-based participatory research study was to develop tailored recommendations on healthy sleep practices for HPN consumers. Methods: The multipart study involved the following: 1) an initial draft of sleep recommendations based on the evaluation of existing general sleep hygiene guidelines by an expert panel of clinicians and consumers with lived experience; 2) semi-structured focus groups with consumers and clinicians; 3) pre- and post-knowledge tests completed by consumers, and 4) final approval of the recommendations by the expert panel. Results: The literature synthesis resulted in 51 recommendations evaluated for relevance for HPN consumers. Focus groups with 20 HPN consumers and clinicians contributed additional recommendations based on lived experience. Ultimately, the final resource included recommendations spanning 4 sections: getting ready for bed, preparing the bedroom for sleep, daytime behaviors, and overall strategies for better sleep. Of the 36 recommendations, 58% were derived from existing general sleep hygiene guidelines, and the remaining 42% addressed sleep challenges experienced uniquely by consumers, including nocturnal polyuria, noise/light from medical equipment, and infusion schedules. Knowledge tests completed by 10 additional consumers indicated a modest increase in sleep health knowledge. Conclusions: The curated healthy sleep resource tailored for HPN consumers was facilitated by a multidisciplinary expert panel, a strategic collaboration with members of the HPN community and their clinicians, and in partnership with patient advocacy and support organizations. The wide distribution of these resources may improve the overall well-being of HPN consumers.

Home parenteral nutrition, sleep patterns, and depressive symptoms: Secondary analysis of cross-sectional data.

BACKGROUND: Patients receiving home parenteral nutrition (HPN) are known to experience psychological distress and have profoundly disrupted sleep. The aim of this analysis was to examine the relationship between sleep patterns with depressive symptoms and HPN characteristics. METHODS: The study was a secondary analysis of cross-sectional data examining sleep patterns using subjective and objective measures. Sleep was assessed by surveys and 7-day actigraphy. The Patient Health Questionnaire-8 was used to evaluate depressive symptoms. Participants provided information on HPN. Spearman correlations were calculated between sleep measures with depressive symptoms and HPN characteristics. Correlations were further examined in multivariable linear regression models. RESULTS: Thirty-two adults (age = 53 years; 75% female; 94% White) were included. Lower sleep quality (r = 0.54-0.60; P < 0.001) and later sleep timing (r = -0.35; P = 0.049) were correlated with higher depressive symptoms. Sleep patterns were also correlated with several HPN characteristics (r = -0.47 to 0.51). In linear regression models, rate of infusion was associated with sleep duration (ß = -0.004 [0.002] h; P = 0.046) in which each 100 mL/h was associated with 24-min shorter duration. Higher total energy was associated with lower sleep quality (ß = 0.0004 [0.0002] log-unit; P = 0.042), and higher volume was associated with longer sleep onset latency (ß = 0.0006 [0.0003] log-min; P = 0.049). CONCLUSIONS: We provide evidence supporting the link between poor and later sleep with higher depressive symptoms and identify potentially modifiable infusion characteristics (notably, slower rate of infusion and lower total energy and volume) that, on further verification, may support sleep among those receiving HPN.

Underdiagnosis of Borderline oxacillin-resistant Staphylococcus aureus (BORSA) - Case series.

Borderline oxacillin-resistant Staphylococcus aureus (BORSA) are mecA-negative strains with oxacillin minimum inhibitor concentration (MIC) close to the resistance breakpoint of ≥ 4µg/mL. Instead of producing penicillin-binding protein with low affinity to methicillin (oxacillin) mediated by mecA gene as in methicillin-resistant S. aureus (MRSA), BORSA strains are characterised by the hyperproduction of ß-lactamase enzymes, thus able to break down methicillin. Common laboratory methods to detect MRSA such as cefoxitin disk diffusion alone may fail to detect methicillin resistance due to BORSA. We report five cases of BORSA blood-stream infections in a university teaching hospital. All isolates were found to be susceptible to cefoxitin using disk diffusion, resistant to oxacillin using automated MIC method, and did not harbour mecA gene. All patients were suscessfully treated with anti-MRSA antibiotics, and removal of primary sources were done if identified. A more cost-effective method for screening and diagnosis of BORSA is needed in addition to cefoxitin disk diffusion test, in order to monitor the spread, and to enable routine detection and treatment of this pathogen.

Penile erection and cardiovascular function: effects and pathophysiology.

Penile erection (PE) is a hemodynamic event that results from a neuroendocrine process, and it is influenced by the cardiovascular status of the patient. However, it may also modulate an individual's cardiovascular events. The present study provides the mechanisms involved in the association of PE and cardiovascular function. Erection upsurges the cardiac rate, blood pressure, and oxygen uptake. Sex-enhancing strategies, such as phosphodiesterase inhibitors, alprostadil, and testosterone also promote vasodilatation and cardiac performance, thus preventing myocardial infarction. More so, drugs that are used in the treatment of hypertensive heart diseases (such as angiotensin system inhibitors and ß-blockers) facilitate vasodilatation and PE. These associations have been linked with nitric oxide- and testosterone-dependent enhancing effects on the vascular endothelium. In addition, impaired cardiovascular function may negatively impact PE; therefore, impaired PE may be a pointer to cardiovascular pathology. Hence, evaluation of the cardiovascular status of an individual with erectile dysfunction (ED) is essential. Also, employing strategies that are used in maintaining optimal cardiac function may be useful in the management of ED.

The economic and resource burden of e-scooter-related orthopaedic injuries: A district general hospital's experience.

PURPOSE: Electric scooters (e-scooters) are an increasingly popular method of transportation worldwide. However, there are concerns regarding their safety, specifically with regards to orthopaedic injuries. We aimed to investigate the overall burden and financial impact on orthopaedic services as a result of e-scooter-related orthopaedic injuries. METHODS: We retrospectively identified all e-scooter-related injuries requiring orthopaedic admission or surgical intervention in a large District General Hospital in England over a 16-month period between September 2020 and December 2021. Injuries sustained, surgical management, inpatient stay and resources used were calculated. RESULTS: Seventy-nine patients presented with orthopaedic injuries as a result of e-scooter transportation with a mean age of 30.1 years (SD 11.6), of which 62 were males and 17 were females. A total of 86 individual orthopaedic injuries were sustained, with fractures being the most common type of injury. Of these, 23 patients required 28 individual surgical procedures. The combined theatre and recovery time of these procedures was 5500 min, while isolated operating time was 2088 min. The total cost of theatre running time for these patients was estimated at £77,000. A total of 17 patients required hospital admission under Trauma and Orthopaedics, which accounted for total combined stay of 99 days with a mean length of stay of 5.8 days. CONCLUSION: While there are potential environmental benefits to e-scooters, we demonstrate the risks of injury associated with their use and the associated increased burden to the healthcare system through additional emergency attendances, frequent outpatient clinic appointments, surgical procedures, and hospital inpatient admissions.

The Saudi initiative for asthma - 2024 update: Guidelines for the diagnosis and management of asthma in adults and children.

The Saudi Initiative for Asthma 2024 (SINA-2024) is the sixth version of asthma guidelines for the diagnosis and management of asthma for adults and children that was developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up-to-date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA Panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5-12 years, and children aged <5 years. SINA guidelines have focused more on personalized approaches reflecting a better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. The medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient-doctor partnership in the management that also includes a self-management plan.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, and together may provide a more complete picture of sleep health, while also illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p<8.3e-9), along with 341 previously reported loci (p<5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2=0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections to behavioral, psychological, and cardiometabolic traits.

Associations of a multidimensional polygenic sleep health score and a sleep lifestyle index on health outcomes and their interaction in a clinical biobank.

Sleep is a complex behavior regulated by genetic and environmental factors, and is known to influence health outcomes. However, the effect of multidimensional sleep encompassing several sleep dimensions on diseases has yet to be fully elucidated. Using the Mass General Brigham Biobank, we aimed to examine the association of multidimensional sleep with health outcomes and investigate whether sleep behaviors modulate genetic predisposition to unfavorable sleep on mental health outcomes. First, we generated a Polygenic Sleep Health Score using previously identified single nucleotide polymorphisms for sleep health and constructed a Sleep Lifestyle Index using data from self-reported sleep questions and electronic health records; second, we performed phenome-wide association analyses between these indexes and clinical phenotypes; and third, we analyzed the interaction between the indexes on prevalent mental health outcomes. Fifteen thousand eight hundred and eighty-four participants were included in the analysis (mean age 54.4; 58.6% female). The Polygenic Sleep Health Score was associated with the Sleep Lifestyle Index (ß=0.050, 95%CI=0.032, 0.068) and with 114 disease outcomes spanning 12 disease groups, including obesity, sleep, and substance use disease outcomes (p<3.3×10-5). The Sleep Lifestyle Index was associated with 458 disease outcomes spanning 17 groups, including sleep, mood, and anxiety disease outcomes (p<5.1×10-5). No interactions were found between the indexes on prevalent mental health outcomes. These findings suggest that favorable sleep behaviors and genetic predisposition to healthy sleep may independently be protective of disease outcomes. This work provides novel insights into the role of multidimensional sleep on population health and highlights the need to develop prevention strategies focused on healthy sleep habits.

Impact of polygenic score for BMI on weight loss effectiveness and genome-wide association analysis.

BACKGROUND: While environmental factors play an important role in weight loss effectiveness, genetics may also influence its success. We examined whether a genome-wide polygenic score for BMI was associated with weight loss effectiveness and aimed to identify common genetic variants associated with weight loss. METHODS: Participants in the ONTIME study (n = 1210) followed a uniform, multimodal behavioral weight-loss intervention. We first tested associations between a genome-wide polygenic score for higher BMI and weight loss effectiveness (total weight loss, rate of weight loss, and attrition). We then conducted a genome-wide association study (GWAS) for weight loss in the ONTIME study and performed the largest weight loss meta-analysis with earlier studies (n = 3056). Lastly, we ran exploratory GWAS in the ONTIME study for other weight loss outcomes and related factors. RESULTS: We found that each standard deviation increment in the polygenic score was associated with a decrease in the rate of weight loss (Beta (95% CI) = -0.04 kg per week (-0.06, -0.01); P = 3.7 × 10-03) and with higher attrition after adjusting by treatment duration. No associations reached genome-wide significance in meta-analysis with previous GWAS studies for weight loss. However, associations in the ONTIME study showed effects consistent with published studies for rs545936 (MIR486/NKX6.3/ANK1), a previously noted weight loss locus. In the meta-analysis, each copy of the minor A allele was associated with 0.12 (0.03) kg/m2 higher BMI at week five of treatment (P = 3.9 × 10-06). In the ONTIME study, we also identified two genome-wide significant (P < 5×10-08) loci for the rate of weight loss near genes implicated in lipolysis, body weight, and metabolic regulation: rs146905606 near NFIP1/SPRY4/FGF1; and rs151313458 near LSAMP. CONCLUSION: Our findings are expected to help in developing personalized weight loss approaches based on genetics. CLINICAL TRIAL REGISTRATION: Obesity, Nutrigenetics, Timing, and Mediterranean (ONTIME; clinicaltrials.gov: NCT02829619) study.