Category: Nevin Manimala

JAMA Netw Open. 2025 Dec 1;8(12):e2548060. doi: 10.1001/jamanetworkopen.2025.48060.

ABSTRACT

IMPORTANCE: The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial.

OBJECTIVE: To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded.

EXPOSURE: Administration of etomidate or ketamine as the induction agent for RSI.

MAIN OUTCOMES AND MEASURES: The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups.

RESULTS: Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes.

CONCLUSIONS AND RELEVANCE: In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

PMID:41396604 | DOI:10.1001/jamanetworkopen.2025.48060

JAMA Netw Open. 2025 Dec 1;8(12):e2548869. doi: 10.1001/jamanetworkopen.2025.48869.

ABSTRACT

IMPORTANCE: The potential utility of real-time digital therapeutics that identify impending behavioral outbursts to proactively apply evidence-based interventions for managing children with disruptive behavior disorder has not been tested.

OBJECTIVES: To evaluate feasibility and adherence of a digitally augmented, real-time, proactive behavioral intervention (smartwatch) for children with disruptive behaviors.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted between March 1, 2022, and December 31, 2023, at Mayo Clinic in Rochester, Minnesota. The study enrolled children aged 3 to 7 years with externalizing behavior problems rated above the clinically significant range (I score ≥120; T score ≥60) on the Eyberg Child Behavior Inventory (ECBI).

INTERVENTIONS: Twelve weekly sessions of parent-child interaction therapy (PCIT) (treatment as usual [TAU] arm) vs artificial intelligence (AI)-enhanced PCIT augmented with real-time behavioral outburst alerts (PCIT-AI arm).

MAIN OUTCOMES AND MEASURES: The primary outcome was achieving the a priori feasibility benchmark set at greater than 70% for both completion of PCIT sessions and daily smartwatch wear. Parental reaction time to behavior prompts was measured in seconds. Secondary outcomes were percentage changes in ECBI and Pediatric Sleep Questionnaire scores. Behavioral outburst duration was examined based on parental logs of start and end times of observed tantrums using a smartphone application.

RESULT: This study enrolled 50 children (median [IQR] age, 5.0 [4.0-6.0] years; 34 [68%] male and 16 [32%] female; 28 randomized to the PCIT-AI arm and 22 to the PCIT-TAU arm). Of these children, 37 (74%; 21 in the PCIT-AI arm and 16 in the PCIT-TAU arm) completed PCIT, with children wearing the watch a median (IQR) 75.7% (67.8%-82.9%) of the time, thus achieving the feasibility benchmark (primary outcome). Median (IQR) response time to behavior prompts in the PCIT-AI arm was 3.65 (2.07-7.08) seconds. Assessing between-group differences, there was no statistically significantly greater numerical improvement in ECBI-intensity percentage change (13.86%; 95% CI, -1.41% to 29.14%), ECBI-problem percentage change subscale scores (38.59%; 95% CI, -1.22% to 78.40%), or absolute change in Pediatric Sleep Questionnaire scores (-0.16; 95% CI, -1.85 to 1.53) with the PCIT-AI arm than with the PCIT-TAU arm. Children in the PCIT-AI arm had significantly shorter mean (SD) tantrum durations (10.4 [20.8] minutes vs 22.1 [30.0] minutes; P < .001) and lower odds of tantrums lasting for 15 minutes or more (odds ratio, 3.66; 95% CI, 2.72-4.95).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, both recruitment and technology feasibility benchmarks were achieved. The findings inform the design of fully powered efficacy study of wearable, digitally augmented PCIT for children with disruptive behaviors.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05077722.

PMID:41396603 | DOI:10.1001/jamanetworkopen.2025.48869

JAMA Netw Open. 2025 Dec 1;8(12):e2549730. doi: 10.1001/jamanetworkopen.2025.49730.

ABSTRACT

IMPORTANCE: There is clear evidence that deleterious germline variants in CHEK2 increase risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers.

OBJECTIVE: To quantify the prevalence of as well as cancer risk and survival associated with CHEK2 germline pathogenic and likely pathogenic variants using genomic ascertainment.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study used 2 electronic health record-linked and exome-sequenced biobanks: UK Biobank (n = 469 765) and Geisinger MyCode (adults only; n = 167 050). Variants were classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Cases were defined as individuals with heterozygous CHEK2, harboring pathogenic or likely pathogenic variants; controls as individuals with a benign or likely benign CHEK2 variation or wildtype CHEK2. Cancer registry (MyCode since approximately 1943; UK Biobank since approximately 1970) and demographic data were retrieved; to adjust for relatedness, association analysis was performed with SAIGE-GENE+ with Bonferroni correction.

MAIN OUTCOMES AND MEASURES: Prevalence of as well as cancer risk and survival in adults with CHEK2 germline variants.

RESULTS: Of 469 765 individuals in the UK Biobank, there were 3232 case participants (mean [SD] age, 70.8 [8.0] years; 3139 [97.1%] White; 1744 [54.0%] women); of 167 050 individuals with MyCode, there were 3153 case participants (mean [SD] age, 60.5 [17.8] years; 3123 [98.8%] White; 1935 [61.5%] women). In case participants in both MyCode and UKBB, there was a significant excess risk of all cancers (odds ratio [OR], 1.33 [95% CI, 1.18-1.49]; OR, 1.41 [95% CI, 1.26-1.59], respectively), breast (OR, 1.54 [95% CI, 1.18-2.00]; OR, 1.84 [95% CI, 1.49-2.27], respectively), prostate (OR, 1.62 [95% CI, 1.27-2.07]; OR, 1.78 [95% CI, 1.48-2.16], respectively), kidney (OR, 1.58 [95% CI, 1.03-2.41]; OR, 1.84 [95% CI, 1.22-2.77], respectively), and bladder (OR, 1.50 [95% CI, 1.01-2.23]; OR, 1.64 [95% CI, 1.17-2.31], respectively) cancers as well as lymphoid leukemia (OR, 2.08 [95% CI, 1.17-3.69]; OR, 2.21 [95% CI, 1.19-4.08], respectively). Compared with control participants, time to cancer in case participants was significantly shorter in both cohorts; no significant difference was observed between the age-dependent penetrance of truncating and missense variants for cancer in either cohort. Overall survival was significantly decreased in case participants in UK Biobank; however, the primary consequence was seen after 75 years. There was no statistical difference in survival in MyCode. There were no differences in survival between case participants with cancer and control participants with cancer.

CONCLUSIONS AND RELEVANCE: In this case-control study of genomic ascertainment of individuals with heterozygous CHEK2 pathogenic or likely pathogenic variants in 2 population-scale cohorts, there was a significant excess risk of breast, prostate, kidney, bladder, and lymphoid leukemia cancer. The conferred excess mortality and cancer risk was low (ORs <2). This has clinical implications for individuals ascertained this way (vs with a family history of cancer).

PMID:41396600 | DOI:10.1001/jamanetworkopen.2025.49730

Eur J Public Health. 2025 Dec 15:ckaf239. doi: 10.1093/eurpub/ckaf239. Online ahead of print.

ABSTRACT

BACKGROUND: Physician shortages threaten healthcare system sustainability across Europe. Retaining physicians is critical to maintaining service capacity and quality. Despite its importance, physician retention remains a pressing issue in Europe, including in Portugal, where the Portuguese National Health Service (NHS) continues to face significant retention challenges.

METHODS: We conducted a quantitative, observational, cross-sectional study to identify determinants of physician retention in Portugal. A validated survey was developed using a Nominal Group Technique and Delphi Panel with stakeholders. The questionnaire measured job satisfaction with Likert scales. A stratified sampling strategy ensured representation across Portugal’s five mainland health regions, yielding 1398 physicians. Data were collected via self-administered electronic questionnaires. Analyses included descriptive statistics, ANOVA, t-tests, and linear regression to assess predictors of retention.

RESULTS: Physicians with longer seniority reported higher intention to remain, with those over 10 years showing the strongest intention (mean = 3.72; SD = 1.05; p < .001). Fixed schedules were linked to higher intended retention than shift work (mean = 3.42 vs. 3.18; p = .015). Job satisfaction was the strongest predictor (β = .267; p < .001), followed by age (β = .222; p < .001), satisfaction with work characteristics (β = .125; p = .002), and career development (β = .097; p = .011). Satisfaction with human resources and work-life balance was not significant.

CONCLUSIONS: Physician retention is shaped by seniority, schedule stability, work environment, and career development. Policies fostering supportive environments, predictable schedules, and professional growth are needed to sustain the workforce, to European systems.

PMID:41396586 | DOI:10.1093/eurpub/ckaf239

J Palliat Care. 2025 Dec 15:8258597251406805. doi: 10.1177/08258597251406805. Online ahead of print.

ABSTRACT

ObjectiveCaregivers have a key role in the palliative care process. However, they need to cope with the challenges brought about by caregiving. Psychological resilience is an important concept for caregivers in coping with challenges. This study examined the relationship between psychological resilience and care burden among caregivers in palliative care settings.MethodsThis cross-sectional study was conducted with 120 caregivers in the palliative care clinic between December 2023 and May 2024 in Turkey. Data were collected using a personal information form, the Resilience Scale for Adults (RSA), and the Zarit Caregiver Burden Scale (ZCBS). Data were analyzed using descriptive statistics, Pearson’s correlation coefficient, and simple and multiple linear regression analyses.ResultsThe mean total RSA score was 123.93 ± 14.00, which was above average. The mean total ZCBS score was 40.08 ± 11.79, and 47.5% of the caregivers had moderate levels of care burden. A negative statistically significant correlation was found between mean RSA and ZCBS scores (P < .01). Psychological resilience alone was a significant predictor of care burden (R² = 0.096, P < .001). Psychological resilience, income status, and family/work/social roles and responsibilities were all statistically significant predictors of care burden (R² = 0.285, P = .000).ConclusionsThe results of this study revealed that psychological resilience is important in the care burden perceived by caregivers in palliative care settings. Therefore, it is important for health professionals to incorporate interventions aimed at enhancing caregivers’ psychological resilience into their programs.

PMID:41396583 | DOI:10.1177/08258597251406805

Intensive Care Med. 2025 Dec 15. doi: 10.1007/s00134-025-08248-7. Online ahead of print.

NO ABSTRACT

PMID:41396555 | DOI:10.1007/s00134-025-08248-7

J Back Musculoskelet Rehabil. 2025 Dec 15:10538127251406955. doi: 10.1177/10538127251406955. Online ahead of print.

ABSTRACT

BackgroundIndividuals with low back pain (LBP) exhibit altered diaphragm function and poor psychological health. Chronic maladaptation of diaphragm activity has been linked to impaired emotional and physical well-being; however, no study has directly examined whether self-reported disability contributes to diaphragm function in LBP.ObjectiveTo compare ultrasonographic measures of diaphragm function in the standing position between young male participants with and without LBP and examine the associations between patient-oriented measures of physical function and psychological status and diaphragm function in those with LBP.MethodsA cross-sectional comparative study was conducted involving 22 young males with LBP and 17 healthy controls. Six validated questionnaires assessed physical and psychological status. Ultrasonography quantified bilateral diaphragmatic contractility and right hemidiaphragm excursion in the standing position.ResultsParticipants with LBP exhibited significantly lower contractility in both hemidiaphragms than controls (p < 0.05). The strongest predictor of right hemidiaphragm contractility was the mental component summary of the Short Form-36 (R² = 0.356, p = 0.003). The combination of social life dysfunction and pain-related disorder domains in the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire explained 25.0% of the variance in left hemidiaphragm contractility (R² = 0.250, p = 0.065). While the regression model of the left hemidiaphragm contractility approached statistical significance (p = 0.065), it did not meet our criterion alpha (0.05).ConclusionReduced diaphragm contractility in standing posture may be associated with poorer psychological health in young males with LBP. These findings suggest diaphragm dysfunction as a potential contributor to the multidimensional burden of LBP. Larger, prospective studies including females are warranted to clarify these associations.

PMID:41396527 | DOI:10.1177/10538127251406955

World J Urol. 2025 Dec 15;44(1):43. doi: 10.1007/s00345-025-06135-w.

ABSTRACT

PURPOSE: Individuals with neurogenic lower urinary tract dysfunction after spinal cord injury should undergo regular scintigraphy to assess renal function. However, renal scintigraphy entails radiation exposure and is not widely available. Consequently, reliable alternative diagnostic parameters are needed. We have, thus, investigated whether renal sonography and cystatin-C measurements are consistent with renal scintigraphy results in this population.

METHODS: Adult individuals with chronic spinal cord injury (duration ≥ 5 years) underwent renal sonography and cystatin-C measurement during routine consultation, followed by renal scintigraphy within six weeks. The correlation between renal sonographic parameters (arterial resistive index, renal parenchymal thickness, and kidney dimensions), serum cystatin-C, and scintigraphy clearance values was assessed using Pearson and Spearman’s rank correlation coefficients. Furthermore, the classification accuracy (for scintigraphy clearance ≤ 150 ml/min) of variables with statistically significant correlation coefficients was investigated.

RESULTS: Data of 8 women and 42 men (54 ± 14 years old; duration spinal cord injury 24.4 ± 14.6 years) were analyzed. There was a fair correlation between scintigraphy clearance and cystatin-C levels (r = -0.37, p = 0.013) as well as left renal resistive index (r = -0.44, p = 0.002). However, there were no correlations between scintigraphy clearance and renal parenchymal thickness (p > 0.45) as well as kidney dimensions (p > 0.13). Cystatin-C and left renal resistive index showed good classification performance (area under curve = 0.74/0.84, p < 0.00001).

CONCLUSION: Individuals with reduced renal function can be identified reliably using cystatin-C serum concentration and renal arterial resistance. These parameters may serve as additional diagnostic parameters to assess renal function and to determine whether scintigraphy examination is required.

CLINICAL TRIAL REGISTRATION: NCT04241666.

PMID:41396487 | DOI:10.1007/s00345-025-06135-w

Childs Nerv Syst. 2025 Dec 15;41(1):417. doi: 10.1007/s00381-025-07061-3.

ABSTRACT

INTRODUCTION: Co-existence of Dandy Walker malformation (DWM) and occipital encephalocele (OE) is extremely unique, and only a limited number of cases have been documented in literature. Their rarity poses distinct diagnostic and therapeutic challenges across the prenatal-postnatal continuum.

OBJECTIVES: To describe the correlation of these two diverse congenital disorders, and to perform a systematic review of the existing literature.

METHODOLOGY: Retrospective review of prospectively maintained database identified 5/128 DWM + OE patients (3.9%) managed between 2012 and 2024. Several parameters were noted and appropriate analysis was performed. Systematic literature review following PRISMA guidelines identified 79 cases for pooled comparison.

RESULTS: Mean age was 5.6 ± 2.41 months; male-to-female ratio 4:1. Four were first-order children, requiring NICU admission with all having delayed milestones. Two had significant microcephaly while one had macrocephaly. Giant sized OE was seen in four cases. On follow-up, two cases (40%) subsequently developed age-appropriate milestones. Systematic review confirmed significant statistical correlation between patients who underwent only repair vs patient who were shunted ± repair; the cases that were shunted fared better (p-value0.03).

CONCLUSION: VP/CP shunt is essential in surgical management leading to better prognosis as compared to repair alone. Giant size of OE/OM and associated anomalies may also dictate long-term outcomes. We affirmed that the pathophysiology resulting in hydrocephalus and OE/OM in DWM to be co-dependent. Our experience adds to this limited pool of data and our analysis of the largest studied number of cases in literature to date provides comprehensive insights into the clinical implications of this association.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41396485 | DOI:10.1007/s00381-025-07061-3

World J Urol. 2025 Dec 15;44(1):41. doi: 10.1007/s00345-025-06137-8.

ABSTRACT

PURPOSE: Thiazide (THZ) and thiazide-like (TL) diuretics are routinely prescribed and considered to be the gold-standard prophylaxis for kidney stones (KS) recurrence in current guidelines despite having limited evidence. Thus, we aimed to investigate the efficacy and safety of different doses of THZ and TL diuretics in preventing KS recurrence.

METHODS: We searched for randomised controlled trials in PubMed, Web of Science, Embase, CENTRAL, and clinical trials registries from their inception through January 2025. The clinical or radiological KS recurrence was the primary endpoint, while the occurrence of adverse effects at any time was the secondary endpoint. We estimated odds ratio (OR) in a frequentist random-effects network meta-analysis with P < 0.05. This study was prospectively registered (CRD42025650062).

RESULTS: Nine trials (n = 999) were included. Chlorthalidone 50 mg/d (OR: 0.18, 95% confidence interval [CI] 0.04-0.88), hydrochlorothiazide 50 mg/d (OR: 0.52, CI 0.29-0.93), and trichlormethiazide 4 mg/d (OR: 0.26, CI 0.10-0.68) were different from placebo in terms of KS recurrence. There was no evidence of dose-dependent effect when comparing hydrochlorothiazide 50 mg/d to 12.5 mg/d (OR: 0.58, CI 0.25-1.34) or 25 mg/d (OR: 0.65, CI 0.28-1.48), nor comparing chlorthalidone 50 mg/d to 25 mg/d (OR: 0.80, CI 0.12-5.20). Only trichlormethiazide 4 mg/d (OR: 49.96, CI 1.78-1 402.80) provoked more adverse effects than placebo.

CONCLUSION: Although some therapies were statistically different from placebo, the current evidence does not support their use in preventing KS recurrence due to several limitations, indicating that THZ and/or TL diuretics should not be routinely prescribed. Further well-designed trials are urgently needed to address head-to-head comparisons and provide high-quality evidence.

PMID:41396435 | DOI:10.1007/s00345-025-06137-8