High Risk Research Articles (Page 1)

BACKGROUND:Complex regional pain syndrome (CRPS) is a debilitating and painful condition accompanied by sensory, autonomic, trophic, and/or motor abnormalities. Although CRPS is rare in the general population, the prevalence among individuals at higher risk, particularly posttraumatic and postsurgical patients, remains unknown. This study aims to provide a benchmark that quantifies CRPS prevalence in high-risk groups, and offers insights on potential predictors of developing CRPS.METHODS:We conducted a systematic review and meta-analysis to identify studies reporting prevalence of CRPS after an inciting event (eg, fracture, surgery), specifically 12-month and 24-month prevalence (primary outcomes), as well as 3-month and 6-month prevalence (secondary outcomes). Estimates from individual studies were transformed using double-arcsine transformation, and the resulting estimates with 95% confidence interval (CI) were pooled in a meta-analysis using a random-effects model.RESULTS:We included 214 articles with data from 2491,378 participants worldwide (35 countries), of which 16,873 had CRPS. The pooled 12-month and 24-month global prevalence was 3.04% (95% CI, 2.64–3.48) and 6.46% (95% CI, 5.46–7.53), respectively. Subgroup analysis and meta-regression were performed to understand the impact of population-dependent (mechanism of injury, type of CRPS), contextual-dependent (socioeconomic status), and methodological-dependent (study design, publication year) factors. The 12-month prevalence was higher in countries with a high human development index (HDI) compared to those with a medium or very high HDI, was higher in participants with a traumatic inciting injury only versus those with surgical injury only or traumatic/surgical injury, and was higher in prospective versus retrospective studies. Meta-regression analysis showed that publication year was a significant moderator, with more recent articles reporting lower 12-month prevalence.CONCLUSIONS:This study provides a benchmark of the global prevalence of CRPS, which anesthesiologists and pain specialists can use to prioritize early diagnosis and identify those at the highest risk for CRPS.

Intracranial atherosclerosis disease (ICAD) accounts for 30% of ischemic strokes, has the highest stroke recurrence rate, and is associated with accelerated cognitive decline. This study investigates associations between diet patterns and the risk of ICAD. Participants in a longitudinal clinical neuropathologic cohort study, with complete dietary, medical history, and neuropathology data, were included. Diet scores were computed (median interval to death = 5.9 [3.0-8.7] years). History of hypertension (HTN) and myocardial infarction (MI) were self-reported. Large vessel ICAD was evaluated at the circle of Willis, and severity of ICAD was assessed based on number of atherosclerotic plaques, extent of vessel involvement, and degree of vessel occlusion to create a 4-level grading system (0-3). All regression models were adjusted for age, sex, education, caloric intake, and APOE4. Of the 676 participants (mean age at death = 91.1 years, SD = 6.1, 71% women), 361 (53%) had mild, 142 (21%) had moderate, and 28 (4%) had severe ICAD. There was no direct relationship between diet and ICAD. The association between ICAD and MI (OR 1.38, 95% CI 0.95-2.00) was not significant. HTN (OR 1.598, 95% CI 1.15-2.18) was positively associated with ICAD. The association of diet with ICAD differed by history of MI (Mediterranean-DASH intervention for neurodegenerative delay [MIND] [p = 0.007], MedDiet [p = 0.006]). The association between ICAD and the MIND diet also differed by whether HTN was reported (β = -0.212, SE = 0.111, p = 0.055) as did the relationship between ICAD and the MedDiet (β = -0.077, SE = 0.035, p = 0.029). In stratified analysis, among individuals with preexisting MI (N = 130), those with a better diet had lower odds of ICAD (MedDiet: OR 0.88, 95% CI 0.81-0.96; MIND: OR 0.69, 95% CI 0.53-0.90). A direct relationship between diet and ICAD was not seen. Stratified analysis suggested that healthy diet may be of value for individuals with HTN or MI: In these high-risk individuals, a healthy dietary pattern is associated with lower odds of severe large vessel ICAD. In vivo studies of dietary habits and brain health, specifically in those at high vascular risk, are needed.

Deep brain stimulation (DBS) is considered off-label and investigational in pediatric populations with some exceptions. There are limited data on the relative rates of complications after DBS across different indications and targets in children. This study aimed to evaluate the safety of DBS surgery for children with movement disorders (MDs; dystonia, chorea, or tic disorders), drug-resistant epilepsy (DRE), or neurodevelopmental disorders, namely, self-injurious behavior (SIB). Data were collected both prospectively and retrospectively from children implanted with DBS through the North American multicenter Child and Youth CompreHensIve Longitudinal Database for Deep Brain Stimulation and included demographic, clinical, operative, and postoperative variables. Complications included infection, noninfectious surgical site findings (dehiscence or seroma), hardware-related issues (disconnection or impedance change), intracranial injury, or other complications. The primary outcome was major complications, defined as any adverse event causing permanent neurologic injury or requiring surgical intervention. The secondary outcome was minor complications, defined as nonmajor complications. Generalized linear models were used to assess for any significant associations with complications. A total of 130 children and youth (mean age 12.2 ± 4.2; range 3-18) years and weighing 12.5-126.6 kg underwent DBS. The most common indication was MD (77, 59.2%), followed by DRE (47, 36.2%) and SIB (6, 4.6%). Major complications occurred in 11.5%, with a greater likelihood in MD (n = 12, 15.6%) compared with DRE (n = 2, 4.3%; odds ratio [OR] 3.55, 95% CI 2.66-4.73, p < 0.001) and significantly associated with lower weight at surgery (p < 0.001) and urgent intervention (p = 0.028). These included infection (6.2%), hardware malfunction (3.1%), and wound dehiscence (0.8%). Minor complications were also higher with MD compared with DRE (OR 1.83, 95% CI 1.16-2.89, p = 0.010) occurring in 22 participants (16.9%; 14 MD, 7 DRE, 1 SIB), including infection (6.2%), high impedance (1.5%), unrelated hydrocephalus (0.8%), perioperative worsening of symptoms (3.8%), incidental tract hemorrhage (2.3%), and noninfectious peri-electrode cystic changes (0.8%). DBS-associated complications were low across multiple pediatric indications and targets, with MD associated with higher risk of major complications. Limitations include a focus on surgical postoperative complications and not stimulation-related adverse outcomes. These findings demonstrate the safety profile of DBS in children in a large cohort.

Concomitant use of tramadol and antidepressants with potent inhibition of the cytochrome P450 2D6 (CYP2D6) enzyme is postulated to increase risk of seizures in older adults; yet, such an association has not been empirically tested in populations. We aimed to examine the association of concomitant tramadol and CYP2D6-inhibiting vs CYP2D6-neutral antidepressant use and the risk of seizures among older nursing home (NH) residents. This population-based cohort study was conducted using a 100% Medicare NH sample from January 2010 to December 2021. We included long-term residents aged 65 years or older who initiated antidepressants on existing tramadol use (tramadol-antidepressant users) or initiated tramadol on existing antidepressant use (antidepressant-tramadol users). Patients were followed up until the end of 1 year, NH discharge, death, or study end. The key exposure was concomitant use of tramadol with CYP2D6-inhibiting vs CYP2D6-neutral antidepressants. The key outcome was incident rates of medical encounters with a diagnosis of seizure and analyzed using negative binomial or Poisson regression models adjusted for baseline covariates (e.g., pain status and depressive, physical, and cognitive function) through the inverse probability of treatment weighting. We identified 11,162 concomitant tramadol-antidepressant users (mean [SD] age, 86.2 [8.5] years; 9,077 [81.3%] female) and 58,994 concomitant antidepressant-tramadol users (mean [SD] age, 85.3 [8.4] years; 47,053 [79.8%] female). The incidence rate of seizures was 16.10 and 20.17 per 100 patient-years, respectively, for the tramadol-antidepressant and antidepressant-tramadol group. In both subgroups, co-use of tramadol with CYP2D6-inhibiting (vs with CYP2D6-neutral) antidepressants was associated with higher adjusted incidence rate ratios of seizures (1.09 [95% CI 1.02-1.18] and 1.06 [95% CI 1.03-1.10]). Findings were corroborated by a negative control exposure analysis in which co-use of hydrocodone with CYPD2D6-inhibiting (vs CYP2D6-neutral) antidepressants was not associated with risk of seizures. Concomitant use of tramadol with CYP2D6-inhibiting vs CYP2D6-neutral antidepressants was associated with increased risk of seizures. Findings are only generalizable to long-term NH populations and are subject to residual confounding. Clinicians should be mindful of seizure risk in older patients who use tramadol concomitantly with antidepressants, particularly CYP2D6-inhibiting antidepressants. This study provides Class II evidence that the combination of tramadol and CYP2D6-inhibiting antidepressants is associated with a higher risk of seizures compared with the combination of tramadol and CYP2D6-neutral antidepressants.

ABSTRACT Objectives Examine different sources of social support/network depending on depressive symptoms among older adults. Methods Data were obtained from two waves of the Age, Gene/Environment Susceptibility – Reykjavik Study (AGES-Reykjavik): Wave I (2002–2006, N = 5.764) and Wave II (2007–2011, N = 3.316). Seven questions (meet with friends/children feeling close to family/friends telephone children/friends living alone were used as: single question (social support)/social network score (SNS). The Geriatric Depression Scale (GDS) screened for depressive symptoms, recoded as: low score (GDS score < 6) and high score (GDS score ≥6). Longitudinal linear regression assessed associations between social questions and GDS score at follow-up among low and high depressive symptoms. Results Among low depressive symptoms (mean age 77) decrease in depressive symptoms was found for those meeting with children (β: −0.439, p = .007); friends (β: −0.288, p = .002); feeling close to family (β: −0.232, p ≤ .001) and friends (β: −0.217, p = .009). Among high depressive symptoms (mean age 78) decrease in depressive symptoms was when telephoning children (β: −4.679, p = .002); meeting with children (β: −2.725, p = .018). Conclusions In older community-dwelling adults regular social support decreases depressive symptoms with most meaningful support arriving from children and friends. Clinical implications Incorporating social network assessments into routine geriatric evaluations could help identify individuals at higher risk of developing or sustaining depressive symptoms.

Abstract Background Plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are promising blood-based biomarkers of neuroaxonal injury and astrocytic activation, relevant in neurodegeneration. We investigated their pre-diagnostic profiles across common neurodegenerative diseases, including Parkinson’s disease (PD), atypical parkinsonian disorders (APD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). Methods Forty-eight thousand five hundred and twenty-four UK Biobank participants with baseline plasma proteomic data for NfL and GFAP were included. Incident diagnoses of PD, APD, AD, and ALS were identified through ICD-10—coded health records, after careful inclusion/exclusion procedures. Baseline plasma NfL and GFAP concentrations were standardized as z -scores adjusted for relevant covariates. The hazard ratio (HR) for incident neurodegenerative diseases was estimated using Cox regression models adjusted for demographic, clinical, socioeconomic and genetic factors. Results The final sample included 1196 cases (505 PD, 26 APD, 476 AD, 189 ALS) and 44,107 control subjects. In Cox regression models, NfL was associated with higher risk of incident ALS (HR 1.69; 95% CI, 1.58–1.80, p &lt; 0.001), APD (HR 1.51; 95% CI, 1.22–1.87, p &lt; 0.001), AD (HR 1.31; 95% CI, 1.22–1.41, p &lt; 0.001), and PD (HR 1.14; 95% CI, 1.05–1.23, p &lt; 0.001). GFAP was independently associated with incident AD only (HR 1.72; 95% CI, 1.63–1.82, p &lt; 0.001). Conclusion Plasma NfL and GFAP showed distinct pre-diagnostic profiles. NfL was associated with incident diagnosis of several neurodegenerative diseases, while GFAP was specific to AD, reinforcing its role in dementia. These results may help optimize the identification of target populations at risk of neurodegenerative diseases for future neuroprotective treatments.

Cannabis use is prevalent in Australia; however, limited research has explored the proportion of high-risk, disordered cannabis use within nationally representative samples. This study aimed to address this gap by measuring the proportion of individuals meeting criteria for high-risk cannabis use and identifying its correlates in a representative Australian dataset. Observational study using data from the 2022-2023 Australian National Drug Strategy Household Survey on respondents self-reporting cannabis use in the past three months (n = 1504). Cannabis use risk was assessed using the World Health Organization's ASSIST-Lite (WHO-ASSIST-Lite). Multinomial logistic regression examined associations between risk and cannabis use patterns, psychological distress and sociodemographic characteristics. Most respondents had low or no risk of cannabis-related problems [71.6%, 95% confidence interval (CI)_= 68.6-74.6%], with 22.2% (95% CI = 19.4-25.0%) at moderate risk and 6.2% (95% CI = 4.6-7.8%) at high risk. Daily consumption of cannabis was strongly associated with an increased risk of high-risk use [relative risk ratio (RRR) = 5.70, 95% CI = 3.25-9.98, P < 0.001] compared with weekly use. Early initiation, particularly before age 15, was also associated with greater probability of high-risk use (RRR = 2.52, 95% CI = 1.25-5.08, P = 0.009), as was initiation between ages 15-17 (RRR = 2.25, 95% CI = 1.19-4.25, P = 0.013), compared with initiation at age 18 or older. Respondents who reported psychological distress had an increased risk of high-risk cannabis use (RRR = 3.19, 95% CI = 1.66-6.11, P < 0.001). A substantial proportion of Australians who consume cannabis appear to meet criteria for high-risk use. Daily use, early age of initiation and high psychological distress may be key risk factors.

Obstructive sleep apnea (OSA) is linked to cognitive decline in the general older population and lower cognition in Parkinson's disease (PD) patients in clinical cohorts. This study evaluates the association between high OSA risk and cognitive function in PD individuals from a population-based cohort. Participants with PD were identified in Canadian Longitudinal Study on Aging (CLSA) comprehensive cohort at baseline or at 3-year follow-up. High OSA risk was determined using the STOP (≥ 2). Cognitive measures included the Rey Auditory Verbal Learning Test, Animal Fluency Test, Mental Alternation Test (MAT), Controlled Oral Word Association Test (COWAT), Stroop Test, Prospective Memory Test, and Choice Reaction Time task. Linear regression assessed relationships between OSA risk and cognitive measures, adjusted for age, sex, BMI, income, and education. Sex-stratified analyses were also performed. We identified 89 PD individuals at CLSA baseline and 61 more at the 3-yr follow-up. Among them, 55 had a high OSA risk (mean age 70.9 (SD 8.8) years, 72.7% male) and 95 did not (mean age 69.5 (9.2) years, 63.2% male). High OSA risk was associated with lower MAT (ß= -3.51; 95%CI:-6.14,-0.28; p = 0.02) and COWAT (ß= -5.19;95%CI: 9.78,-0.59; p = 0.03) scores in adjusted analyses. Significant associations were observed only in females in sex-stratified analyses. High OSA risk is linked to poorer executive function test results in PD participants from the CLSA cohort. The association occurring only in females suggests OSA may differentially impact cognitive health based on sex.

Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear. To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia. This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac risk undergoing major vascular or general surgery operations. Participants were enrolled from February 2018 to March 2023 across 16 Veterans Affairs Medical Centers in the US. Seven hundred fourteen participants with postoperative hemoglobin less than 10 g/dL were randomized to a liberal strategy (transfusion trigger at hemoglobin level <10 g/dL) and 714 to a restrictive strategy (transfusion trigger at hemoglobin <7 g/dL). The primary end point was a composite of all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke within 90 days after randomization. Secondary end points included a composite of cardiac complications other than myocardial infarction (arrhythmias, heart failure, and nonfatal cardiac arrest). Of the 1424 analyzed veterans (mean age, 69.9 [SD, 7.9] years; 1393 male [97.8%]; 268 Black [18.8%]; 48 Hispanic [4.1%]; 1071 White [75.2%]), 1297 (91.1%) underwent vascular surgical procedures. The mean hemoglobin difference between transfusion strategies was 2.0 g/dL on day 5 after randomization. The primary outcome rate in the liberal group was 9.1% (61 of 670) compared with 10.1% (71 of 700) in the restrictive group (relative risk, 0.90; 95% CI, 0.65-1.24). The secondary end point of cardiac complications without myocardial infarction, which was 1 of 5 secondary end points, occurred in 5.9% (38 of 647) of patients in the liberal group and 9.9% (67 of 678) of patients in the restrictive group (relative risk, 0.59; 99% CI, 0.36-0.98). After major vascular or general surgery operations among patients at high risk of a cardiac event, a liberal transfusion strategy did not reduce 90-day death or major ischemic outcome rates compared with a restrictive strategy. ClinicalTrials.gov Identifier: NCT03229941.

Abstract Background People with HIV (PWH) have a higher incidence of heart failure (HF) and acute myocardial infarction (AMI) than people without HIV (PWoH). While hospital readmission is a common quality-of-care indicator, readmission risk for HF or AMI by HIV status is not well defined. Methods We included adults hospitalized for HF or AMI from the 2016-2022 Nationwide Readmissions Database. The outcome was 30-day all-cause unplanned readmission. We examined trends in readmission risk between 2016 and 2022, and subgroup-specific readmission risk in 2022, by HIV status. Crude and age-and sex-adjusted risk ratios (aRR) were calculated using marginal estimates from mixed-effects logistic regressions. Results From 2016 to 2022, 30-day readmission risk significantly declined among PWH hospitalized for HF(39.5%-to-33.0%), PWoH hospitalized for HF(22.9%-to-21.6%), and PWH hospitalized for AMI(19.3%-to-16.8%). In 2022, we included 1,062,309 weighted index hospitalizations for HF and 470,369 for AMI. PWH had significantly higher readmission risk than PWoH for both HF (aRR=1.46;95%CI=1.39-1.53) and AMI (aRR=1.59;95%CI=1.39-1.80). For HF, the most common readmission diagnosis for both PWH and PWoH was hypertensive heart and stage 1-4 chronic kidney disease with heart failure. For AMI, recurrent unspecified AMI was the most common readmission diagnosis in both groups. In age- and sex-stratified analyses, PWH consistently had higher readmission risk than PWoH for both HF and AMI, with the largest disparities in younger males and older females. Conclusions PWH had a significantly higher 30-day readmission risk after HF and AMI hospitalization. Targeted interventions, such as early follow-up and multidisciplinary care, are needed to reduce readmission risks.

ABSTRACT The effects of pesticide exposure on human health are a significant concern in the global agricultural sector. However, developed risk matrix of occupational exposure and pesticide screening have rarely been studied. This study aimed to investigate the sensitivity, specificity and accuracy of a developed occupational risk assessment matrix. Data were collected from both an interview questionnaire and serum cholinesterase testing by using cholinesterase reactive paper. The participants were 421 pesticide sprayers in northeastern Thailand. The risk matrix (4x4) was developed by multiplying the likelihood of pesticide exposure by the severity level of adverse symptoms. The risk score was classified into acceptable and unacceptable levels of risk. The sensitivity, specificity and accuracy of the risk matrix were assessed by using a standard 2 × 2table. Most of the sprayers were male (69%) and their ages ranged between 19 and 76 years old (mean = 53; SD = 10). Abnormal cholinesterase test results indicated an unsafe level of risk for 48% of sprayers (95% CI: 44% −53%). The risk matrix showed that the largest proportion of sprayers (42.52%, 95%CI: 38% −47%) were classified as moderate risk, followed by those at a low-to-very high risk (57%, 95% CI: 53% −62%). The risk matrix findings showed a sensitivity of 73.17% (95% CI: 69% −77%) and a specificity of 64% (95% CI: 59% −68%) for risk screening. The positive predictive value was 99% (95% CI: 98% −100%), the negative predictive value was 6% (95% CI: 4% −8%) and the accuracy was 73% (95% CI: 69% −77%). Conclusion: These pesticide sprayers represent a high-risk group, highlighting the need for effective guidance in conducting risk assessment programs for pesticide exposure. Therefore, this developed risk matrix is also valuable for health screening among pesticide applicators.

Aspirin has been fundamental in secondary prevention of cardiovascular disease (CVD) due to its antithrombotic effect. Its use in primary prevention, that is, preventing first-time cardiovascular events in persons without known CVD, has been controversial. Early trials, which were done in the late 20th century, showed moderate myocardial infarction reductions with aspirin, but they also showed an increased risk of bleeding. Over the past 10 years, several large randomized controlled trials (including Aspirin to Reduce Risk of Initial Vascular Events, A Study of Cardiovascular Events in Diabetes, and Aspirin in Reducing Events in the Elderly) have revisited this problem in diverse populations, which yielded mixed results that generally question the net benefit of routine aspirin use in low- to moderate-risk individuals. These findings brought some major guideline updates. Recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines restrict aspirin to a few groups who are at a higher risk and advise against the routine use of aspirin in the rest of the population, while European Society of Cardiology guidelines generally discourage aspirin usage in primary prevention; its use is limited to specific, very high-risk settings. This article provides us with an overall summary of the evidence for aspirin primary prevention of CVD, taking into account prominent trials, the balance between benefits (eg, reduction in myocardial infarction) and harms (eg, bleeding), evolving clinical guidelines, and practical considerations of risk stratification and patient selection. Our work tried to highlight the manner in which aspirin's use in primary prevention in current practice is narrowly focused and should be individualized by careful consideration of risk-benefit and shared decision-making.

In May 2024 with a subsequent update in June 2025, the Swedish Medical Products Agency's expert group revised guidelines on the management and treatment of respiratory syncytial virus (RSV) infection. This is an abridged version and commentary on the full recommendation including specific recommendations for the RSV-season 2025/2026. Key points are: (i) RSV is a seasonal, highly contagious infection. Almost all children are infected by age two, usually with mild illness; (ii) Some infants, children with underlying conditions, and frail elderly are at risk for developing severe disease requiring hospital care; (iii) Preventive measures-such as hand hygiene and avoiding contact with people with colds-are essential to protect infants and the elderly; (iv) Prophylactic treatment with monoclonal antibodies reduces the risk of infants developing severe RSV disease and requiring hospital care. The long-acting drug nirsevimab is preferred over the shorter-acting palivizumab; (v) Universal prophylaxis in infants reduce disease burden for both families and society; (vi) If supply is limited, children at highest risk should be prioritised for prophylaxis; (vii) Maternal vaccination during pregnancy lowers the risk of severe RSV in newborns, decreasing hospital admissions. The protective effect is considered to be equivalent to that of monoclonal antibodies. Recommendations and funding decision for maternal vaccination is under investigation during the autumn of 2025; (viii) In the elderly, vaccination is the most effective pharmacological prevention; (ix) There is no effective antiviral treatment for established RSV disease; management is symptomatic and supportive. Hospitalised children should not be subjected to measures with no proven effect, preferable minimal interventions, with treatment focused on ensuring adequate nutrition; (x) The Swedish recommendations state that during the RSV season 2025/2026, nirsevimab should be administered to prevent RSV infection in all infants aged 0-3 months during the RSV season and to infants under 12 months with increased risk of severe RSV and certain high risk children under 24 months.

Invasive non-typhoidal Salmonella (iNTS) disease is a global health concern, particularly for sub-Saharan Africa. Despite high case fatality risks, there is no vaccine available against the disease. An obstacle to vaccine development is a lack of data on the economic burden of iNTS disease in many parts of the world. The main aim of the current study is to estimate the economic burden of iNTS disease in 123 countries. Several multivariate regression models were parameterised with the data obtained from an existing systematic literature review on the economic burden of iNTS disease and all forms of NTS disease. Various model diagnostics were performed to validate the statistical significance of each model outcome, and the most suitable model was selected to predict costs in countries where no data points were available. A generalised linear model with gamma distribution with log link was chosen based on model diagnostics. While the average economic burden per iNTS disease episode ranged from US$341 in Africa to US$2194 in Europe, the total economic burden of iNTS disease was the highest in Africa due to the high burden of the disease in the region. The current study indicates that the economic burden of iNTS disease is substantial. Given the scarcity of field-based iNTS disease economic burden estimates, cost extrapolation through an econometric framework can be helpful for understanding the associated cost implications in a resource-limited setting and for informing the cost-effectiveness of public health interventions including future vaccination strategies.

Postoperative Transfusion in Patients at High Cardiac Risk: Evidence, Uncertainty, and Nuance.

Abstract Background Blood pressure (BP) present a diurnal pattern with a nocturnal decrease and an increase in early morning. Evidence suggests that an exaggerated morning BP surge is associated with higher cardiovascular risk. This is the first study evaluating the association between dialysis timing and morning BP surge in hemodialysis. Methods 113 patients dialyzed on the morning shift were age- and sex-matched in a 1:1 ratio with 113 patients dialyzed on the midday/evening shifts. All patients underwent 48-h ambulatory BP monitoring. Morning BP surge at the first and second days of the recording was calculated using three definitions: pre-awakening, sleep-trough and rising morning BP surge. Results The two groups were similar in terms of age, BMI and comorbidities. Morning shift patients presented higher mean sleep-through SBP/DBP surges (SBP: 18.71 ± 13.11 vs 14.22 ± 10.25mmHg, p = 0.005; DBP: 12.05 ± 8.04 vs 9.46 ± 8.53mmHg, p = 0.020) and higher mean pre-awakening SBP/DBP surges (SBP: 12.05 ± 8.04 vs 9.46 ± 8.53mmHg, p = 0.020; DBP: 10.16 ± 9.56 vs 6.53 ± 10.78mmHg, p = 0.008). No between-groups differences were observed in mean rising SBP surge. During the 1st 24-h period, morning shift patients showed higher pre-awakening SBP/DBP surges (SBP: 9.85 ± 11.15 vs 6.22 ± 11.77mmHg, p = 0.018) and, during the 2nd 24-h period, higher sleep-through SBP/DBP surges (SBP: 20.02 ± 18.17 vs 12.79 ± 12.91mmHg, p = 0.001; DBP: 12.49 ± 10.76 vs 9.64 ± 10.53, p = 0.046). Dipping patterns did not differ between groups. Conclusions Patients dialyzed on the morning shift exhibited significantly higher morning BP surge compared to the other two shifts. Future studies should confirm these observations and examine the need for individualizing the choice of dialysis shift for patients with specific circadian BP profiles.

Bone mineral density (BMD) is a key indicator of bone health, particularly in older populations, where lower BMD is linked to increased risk of osteoporosis and fractures. Metabolic factors like serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) have emerged as possible determinants of bone health. The uric acid to HDL cholesterol ratio (UHR) may offer a new perspective on these metabolic influences. This study explores the association between UHR and femoral neck BMD, with a focus on non-linear relationships and subgroup variations by body mass index (BMI), age, and sex. The study used data from 2178 participants from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). UHR was calculated as the ratio of serum UA to HDL-C. BMD measurements were obtained using dual-energy X-ray absorptiometry (DXA) at the femoral neck. A two-piecewise linear regression model was applied to examine the non-linear relationship between UHR and BMD. Stratified analyses were conducted by BMI, gender, and age groups. A significant inflection point was found at UHR 19. Below this threshold, UHR was positively associated with femoral neck BMD (β = 0.0054, p = 0.013), while above the threshold, the association was negative but not statistically significant (β = -0.0016, p = 0.478). Stratified analysis revealed that the relationship between UHR and BMD remained significant among Mexican Americans even after adjusting for covariates (β = 0.0145, p = 0.012). This study identifies a non-linear association between UHR and femoral neck BMD, with a key inflection point at UHR 19. These findings suggest that UHR could be a useful biomarker for bone health, especially in populations with higher metabolic risks. Further longitudinal studies are necessary to establish causality and explore potential interventions targeting UHR to improve bone health.

Obstructivesleep apnea (OSA) presents with diverse clinical manifestations,complicating its diagnosis and management. Cluster-based phenotypinghas emerged as a promising approach to improve diagnostic precision and guide individualized therapy; however, such data are lacking in Saudi Arabia. To address this gap, we used clinical OSA clusters from a previous clustering analysis to determine their prevalence in the Saudi population. We reviewed the records of 650 adult patients with OSA from a single sleep laboratory in Saudi Arabia. Participants were classified into sleepy, insomniac, or minimal symptomatic clusters based on their chief complaint. Demographics, anthropometrics, medical history, Epworth Sleepiness Scale (ESS), and polysomnography measurements were compared between groups. The sleepy, insomnia, and minimally symptomatic clusters comprised 41%, 30%, and 29% of the cohort, respectively. The minimally symptomatic group was significantly younger than the sleepy and insomniac groups (47±15 vs. 50±16 vs. 52±15 years, respectively; p=0.01). The insomniac group had a lower BMI than the sleepy and minimally symptomatic groups (34±9 vs. 37±9 vs. 39±11 kg/m2, respectively; p<0.001). The sleepy group had higher ESS than the insomniac and minimally symptomatic groups (14±5 vs. 8±6 and 10±6, respectively; p<0.001). The proportion of patients with a high risk of OSA was greater in the sleepy group than in the insomniac and minimally symptomatic groups (75%, 62%, and 67%, respectively; p=0.03). The clinical clusters from international cohorts of sleepiness, insomnia, and minimal symptoms were applicable in patient with OSA in the Saudi population.

Antenatal corticosteroids (ACS) can improve the outcomes of preterm infants and have been widely adopted as the standard practice in managing pregnancies at high risk of preterm delivery between 22+0 and 33+6 weeks. Due to their significant benefit for the majority of pregnant women, several guidelines also state that maternal diabetes is not a contraindication for the use of ACS. However, no such evidence has been obtained from diabetic pregnancies. The Chinese Neonatal Network (CHNN), a national multicenter cohort study, recruited 31,915 very preterm infants (VPIs) from 79 NICUs. The outcomes were mortality and morbidity in hospital. Logistic regression models were employed to calculate the odds ratios (ORs) and its 95% confidence intervals (CIs) to estimate the associations between ACS and these outcomes. Stratification and sensitivity analyses were conducted to test the robustness of the results in different population. A total of 4337 VPIs born to diabetic mothers enrolled in the present study: 3605 VPIs were exposed to ACS and 732 were not. ACS was associated with a lower risk in the combined outcome (death or any severe morbidity) (adjusted OR [aOR] 0.66, 95% CI 0.54-0.79), in-hospital death (aOR 0.55, 95% CI 0.41-0.73), severe bronchopulmonary dysplasia (BPD, aOR 0.69, 95% CI 0.55-0.85), low Apgar score (aOR 0.76, 95% CI 0.61-0.96), respiratory distress syndrome (RDS, aOR 0.79, 95% CI 0.66-0.94), or the need for invasive ventilation (aOR 0.62, 95% CI 0.52-0.73). However, a significantly higher risk of maternal chorioamnionitis (aOR 2.09, 95% CI 1.61-2.72) was observed in the ACS group. Similar results were observed in stratification and sensitivity analyses. Conclusions:In VPIs of diabetic mothers, ACS exposure was associated with lower mortality and reduced risks of BPD, low Apgar score, RDS, and invasive ventilation, but with higher odds of maternal chorioamnionitis. What is Known: • Antenatal corticosteroids (ACS) are standard care for reducing neonatal morbidity and mortality in pregnancies at high risk of preterm birth between 22+0 and 33+6 weeks. • However, recommendations for ACS use in pregnant women with diabetes at risk of preterm delivery remain inconsistent due to limited evidence. What is New: • This large, national multicenter cohort study provides the first specific evidence that ACS administration in diabetic pregnancies is associated with significantly lower risks of neonatal mortality, bronchopulmonary dysplasia, respiratory distress syndrome, and the need for invasive ventilation. • Our findings support the benefit of ACS in this understudied population, demonstrating a favorable risk-benefit profile.

To compare the diagnostic utility of umbilical cord blood culture (UCBC) versus neonatal blood culture (NBC) in the evaluation and management of early-onset neonatal sepsis (EONS) in late preterm and term infants and to determine the contamination rate of UCBC. A retrospective analysis was conducted on late preterm and term neonates born between December 2020 and January 2025, who underwent EONS evaluation with UCBCs and NBCs. The study assessed detection rates of true-positive cultures, contamination rates (false positives), and incidence of culture-negative sepsis. A total of 336 infants had UCBCs performed, with 223 undergoing concomitant NBCs. Positive culture rates were similar: 4 UCBCs (1.2%) and 3 NBCs (1.3%) were positive. UCBC had two contaminants (0.6%) while NBC had one (0.45%). One infant had both cultures positive for E. coli. No infants required prolonged antibiotics for culture-negative sepsis. The contamination rate of UCBC was extremely low in the cohort of infants at high risk for EONS. Our protocol and collection technique may serve as a model for others aiming to reduce contamination rates. While NBC can be positive despite a negative UCBC, and vice versa, obtaining both UCBC and NBC can improve the sensitivity of EONS diagnosis and help minimize prolonged antibiotic use in cases of culture-negative sepsis. UCBC demonstrated a low contamination rate and comparable diagnostic yield to NBC. UCBC may be considered a reliable alternative or adjunct to NBC in the evaluation and management of EONS.