Category: Nevin Manimala

Diabetol Metab Syndr. 2025 Aug 27;17(1):360. doi: 10.1186/s13098-025-01928-w.

ABSTRACT

BACKGROUND: Type 1 diabetes (T1D) and autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), are characterized by immune-mediated damage. Prior observational studies have reported associations between these conditions, but definitive causal relationships remain elusive. This study leverages genetic data to clarify the nature of these associations.

METHODS: We conducted a bidirectional Mendelian randomization (MR) analysis using summary-level data from large-scale genome-wide association studies. The inverse variance weighted was the primary method, supplemented by diverse sensitivity analyses (MR-Egger, weighted median, weighted mode, cML-MA, BWMR, MR-PRESSO, and CAUSE) to rigorously assess causality and address potential pleiotropy. We assessed genetic correlation using linkage disequilibrium score regression and performed colocalization to evaluate shared causal variants.

RESULTS: Our findings revealed a causal effect of genetically predicted T1D on an increased risk of AIH (OR = 1.32, 95% CI: 1.16-1.50, P = 2.72 × 10⁻⁵), robustly supported by sensitivity analyses and replicated in an independent cohort. Evidence for a potential bidirectional causal relationship emerged between T1D and PBC, where genetically predicted T1D increased PBC risk (OR = 1.10; 95% CI: 1.02-1.20; P = 0.014), and genetically predicted PBC also increased T1D risk (OR = 1.13; 95% CI: 1.09-1.17; P = 3.45 × 10⁻¹¹), albeit with potential pleiotropy. No evidence for a genetic causal relationship was observed between T1D and PSC (IVW, P = 0.695). Significant genetic correlations were present between T1D and all AILDs, but colocalization did not support shared causal variants.

CONCLUSIONS: This study provides genetic evidence for a causal effect of T1D on AIH and a likely bidirectional relationship between T1D and PBC. These findings refine our understanding of their comorbidity, suggesting the need for heightened clinical surveillance and warranting further mechanistic investigation to elucidate the biological pathways.

PMID:40866980 | DOI:10.1186/s13098-025-01928-w

Trials. 2025 Aug 27;26(1):314. doi: 10.1186/s13063-025-09041-z.

ABSTRACT

BACKGROUND: Patients with persistent pain and comorbid insomnia often experience a dual burden with significant day- and nighttime impairments. This comorbidity is associated with health problems like depression and a self-perpetuating vicious circle in which pain and insomnia symptoms mutually reinforce each other. Cognitive behavioural therapy for insomnia (CBT-i) has demonstrated efficacy in facilitating the behavioural and psychological changes necessary to improve sleep. However, its applicability to patients with the insomnia-pain comorbidity condition is underexplored. We will expand the knowledge base of CBT-i to this patient group by examining the effects on core insomnia symptoms, including sleep onset, the frequency and duration of nightly and early morning awakenings, sleep efficiency and daytime impairments at post-test and follow-up. Secondary outcomes include reductions in pain intensity and interference, depression and fatigue; improved pain acceptance and quality of life; and more adaptive sleep-related beliefs. This study also explores mediators of the expected effects, patient experiences of the feasibility and acceptability of the intervention and how these experiences relate to individual differences in treatment benefits.

METHODS: The study includes hospital patients with a chronic pain condition according to the criteria from the International Association for the Study of Pain and a DSM-5 diagnosis of insomnia. The study will recruit 106 patients based on a power analysis that accounts for 20% dropout, and block-randomise them to a group-based CBT-i intervention or treatment as usual (TAU). The latter consists of consultations and potential pain- and sleep medication. The participant timeline includes a baseline registration, seven sessions of the CBT-i within a 10-week period, a post-test and two follow-up measurements at 4 and 12 months, respectively. The statistical analyses will be intention-to-treat and include random factors to adjust for data dependencies. Patients’ experiences of feasibility and acceptability will be analysed using a reflexive thematic approach.

DISCUSSION: This study addresses a knowledge gap by evaluating the effectiveness of CBT-i adapted for patients with insomnia and non-malignant, persistent pain. Given positive findings, the study may support clinical recommendations by providing empirical evidence for implementing psychological sleep interventions for somatic hospital patients having comorbid sleep issues.

TRIAL REGISTRATION: Clinical Trials.gov ID NCT06351839. Registered 08 April 2024.

PMID:40866978 | DOI:10.1186/s13063-025-09041-z

Trials. 2025 Aug 27;26(1):317. doi: 10.1186/s13063-025-09035-x.

ABSTRACT

BACKGROUND: Opioid use and misuse during pregnancy rose from 1.5 to 6.5 per 1000 deliveries between 1999 and 2014 and continues as a significant public health concern. A fivefold increase in neonatal opioid withdrawal syndrome (NOWS) has accompanied the increase in opioid use. The Eating, Sleeping, Consoling care approach (ESC) has been shown to improve outcomes for infants with NOWS and is quickly becoming the standard of care for infants affected by opioid use disorder. Quality improvement initiatives following the implementation of ESC provide some evidence to suggest that symptom-based (i.e., as needed, PRN, just in time) dosing of opioid medications for infants with significant withdrawal may be an effective alternative to using a traditional scheduled opioid taper approach. These initiatives have shown reduced length of hospital stay and decreased postnatal opioid exposure when compared to scheduled opioid dosing for infants with NOWS who receive pharmacologic treatment. It is unknown if the findings from these quality improvement initiatives are generalizable, and little is known about the safety of this approach in a diverse population. The purpose of this manuscript is to describe the design and rationale for an ongoing study to evaluate the effect of symptom-based opioid dosing compared to traditional scheduled opioid taper on short-term outcomes for infants with NOWS.

METHODS/DESIGN: In this ongoing multi-center two-period cluster crossover randomized controlled trial, 24 sites within the USA were randomized at the site level into one of two sequences. Prior to randomization, sites were stratified by care approach used (ESC vs. usual care) and these strata were independently randomized. All study sites will provide care based on their random allocation. Data will be collected under waiver of consent for in-hospital and short-term outcomes for eligible infants. A minimum of 480 infants will be enrolled. We hypothesize that use of symptom-based dosing will safely reduce the length of time until infants with NOWS and at risk for pharmacological treatment are medically ready for discharge when compared to infants treated with a scheduled opioid taper.

DISCUSSION: This trial is uniquely and efficiently designed to establish the efficacy, safety, and generalizability of the symptom-based dosing approach to opioid treatment for NOWS.

TRIAL REGISTRATION: NCT05980260 ; registered July 27, 2023.

PMID:40866977 | DOI:10.1186/s13063-025-09035-x

Int J Health Geogr. 2025 Aug 27;24(1):23. doi: 10.1186/s12942-025-00400-2.

ABSTRACT

BACKGROUND: The optimal placement of ambulances is critical for ensuring timely emergency medical responses, especially in regions with high accident frequencies. In Rwanda, where road accidents are a leading cause of injury and death, the strategic positioning of ambulances can significantly reduce response times and improve survival rates. The national records of Rwanda reveal a rising trend in the number of road accidents and deaths. In 2020, there were 4203 road traffic crashes throughout Rwanda with 687 deaths, data from 2021 demonstrated 8639 road traffic crashes with 655 deaths. Then in 2022 national statistics indicated 10,334 crushes with 729 deaths. The study used emergency response and road accident data collected by Rwanda Biomedical Centre in two fiscal years 2021-2022 and 2022-2023 consolidated with the administrative boundary of Rwandan sectors (shapefiles).

METHODS: The main objective was to optimize ambulance locations based on road accident data using machine learning algorithms. The methodology of this study used the random forest model to predict emergency response time and k-means clustering combined with linear programming to identify optimal hotspots for ambulance locations in Rwanda.

RESULTS: Random forest yields an accuracy of 94.3%, and positively classified emergency response time as 926 fast and 908 slow. K-means clustering combined with an optimization technique has grouped accident locations into two clusters and identified 58 optimal hotspots (stations) for ambulance locations in different regions of Rwanda with an average distance of 1092.773 m of ambulance station to the nearest accident location.

CONCLUSION: Machine learning may identify hidden information that standard statistical approaches cannot, the developed model for random forest and k-means clustering combined with linear programming reveals a strong performance for optimizing ambulance location using road accident data.

PMID:40866972 | DOI:10.1186/s12942-025-00400-2

Infect Agent Cancer. 2025 Aug 27;20(1):59. doi: 10.1186/s13027-025-00690-y.

ABSTRACT

BACKGROUND: Women treated with cervical loop electrosurgical excision procedure require follow-up to detect residual or recurrent HSIL+, defined as high-grade squamous intraepithelial lesions, adenocarcinoma in situ or cervical cancer. Currently, co-testing with cytology and human papillomavirus (HPV) analysis is usually recommended. This study investigates whether HPV testing alone is comparable to co-testing in detecting HSIL + up to three years after treatment. Recurrence rates of HSIL + are also presented, with follow-up extending up to 18 years.

METHODS: This retrospective cohort study included all 3,540 women treated with a cervical excision in Uppsala County between 1 January 2005 and 31 December 2019. Women with cancer identified in the cone biopsy were excluded. The main outcome was HSIL + detected within three years of follow-up. Sensitivity, specificity and negative predictive value were calculated for the 1,938 women who had a co-testing result as part of their test of cure. Thus, the analysis for the main outcome could finally be performed on 1,938 out of the total number of 3,540 women. Additionally, long-term data on recurrence and time to HSIL+, along with a separate analysis of results prior to cervical cancer diagnosis, were collected for the whole cohort of 3,399 women.

RESULTS: The sensitivity and negative predictive value for detecting HSIL + were 69% and 97% for HPV alone, and 74% and 98% for co-testing, respectively. These differences were not statistically significant. Specificity was higher for HPV alone than for co-testing. The negative predictive value of HPV testing for excluding cervical cancer (n = 5) within three years was 100%. Recurrence rate of HSIL + in the three-year follow up was 8%, and the total recurrence rate of HSIL + with a mean follow-up of nine years was 10%. Mean time to recurrence was 28 months. None of 19 cervical cancer cases identified in the long-term follow-up had a co-testing result showing negative HPV but positive cytology.

CONCLUSIONS: HPV testing alone, as a single test, is comparable to co-testing in detecting HSIL + up to three years after treatment independently of margin status, and demonstrates a higher specificity. Cytology plays a very limited role in the test of cure analysis and could therefore be omitted.

PMID:40866961 | DOI:10.1186/s13027-025-00690-y

Radiat Oncol. 2025 Aug 27;20(1):134. doi: 10.1186/s13014-025-02713-9.

ABSTRACT

BACKGROUND: Radiotherapy (RT) is a standard curative treatment for prostate cancer (PCa) and there is growing evidence of the high efficacy of moderate and ultra-hypofractionated RT. Reducing treatment duration to one week or less is a major advance, but very few studies have explored single-fraction therapy. This study evaluates the feasibility, safety, and efficacy of single-fraction stereotactic body RT (SBRT) while delivering the entire procedure in one day, with a potentially high benefit in terms of patient comfort and therapy cost and logistics.

METHODS: This prospective, non-randomized monocentric trial uses Robotic Radiosurgery (CyberKnife v.7 system) to deliver a single 24 Gy fraction to the prostate (± seminal vesicles) with a “urethral sparing HDR-like” technique, and target tracking. The first phase will enroll 13 PCa patients following Simon’s optimal design. Treatment is to be stopped if ≥ 2 patients develop ≥ G3 toxicity (CTCAE v5.0) within a month from RT end; otherwise, 52 more patients will be added, totaling 65. To account for minimal drop-out, 5 extra patients will be enrolled, reaching 70. All procedures are performed in a single day, including fiducial implantation, imaging acquisition, contouring, planning, dosimetry quality control, and treatment. Apart from treatment feasibility in terms of one-month acute toxicity, secondary endpoints include late toxicity, biochemical and clinical control.

DISCUSSION: Few others have investigated the 24 Gy single-fraction schedule using different delivery modalities (not including tracking), which has proved to be non-inferior to 5 fraction SBRT. Our approach aims to maintain (and possibly improve) the previously reported acute, subacute and late toxicity as well as disease control, adding evidence in favor of single-fraction delivery. Another significant goal of the study is the demonstration that all the complex treatment procedures can be safely delivered in a single day. This would be especially appealing for patients far from radiotherapy centers and those with work commitments not allowing daily hospital visits. The study of response to RT can also provide useful information about PCa radiobiology. Planned additional analyses may help in better assessing the clinical value of PSMA PET/CT in the selection of high-risk patients with true limited disease, and in identifying radiomic features associated to outcome.

TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov (NCT05936736).

PMID:40866948 | DOI:10.1186/s13014-025-02713-9

BMC Public Health. 2025 Aug 27;25(1):2955. doi: 10.1186/s12889-025-24358-9.

ABSTRACT

BACKGROUND: Persistent low fertility in China poses critical socioeconomic challenges. Family functioning has been implicated in reproductive decisionmaking, yet its heterogeneity remain underexplored, particularly among young adults. This study employs Latent Profile Analysis (LPA) to identify high and lowfunctioning family profiles among Chinese university students and their parents, and to quantify their associations with marriageandchildbearing attitudes and explicit fertility intentions.

METHODS: In a crosssectional survey of 484 student-parent pairs from two northwest Chinese universities, we administered a 68item questionnaire incorporating the 30item Chinese Family Assessment Device and standardized measures of fertility intentions and marriageandchildbearing views. LPA classified families into two profiles. Multinomial logistic regression (Models 1-3) tested the effect of family functioning on students’ ideal number of children (“0,” “1,” “≥ 2,” vs. “indifferent”), sequentially adjusting for student and parental sociodemographic covariates.

RESULTS: LPA yielded two profiles: lowfunctining (57.0%) and highfunctoning (43.0%) families. In Model 1, lowfunctioning membership increased the odds of intending 0 children (R = 2.90, 95% CI 1.53-5.49, p < 0.01), 1 child (OR = 2.65, 1.51-4.63, p < 0.01), and ≥ 2 children (OR = 3.54, 2.28-5.49, p < 0.001) versus remaining indifferent. Adjusting for student factors (Model 2) attenuated the zerochild effect (p = 0.21) but retained significant associations for 1 child (OR = 2.22, 1.20-4.12, p < 0.05) and ≥ 2 children (OR = 3.08, 1.77-5.35, p < 0.001). In the fully adjusted model (Model 3), lowfunctioning status remained a predictor only of ≥ 2 children (OR = 2.57, 1.40-4.73, p < 0.01). Older parental age independently predicted zerochild intentions (OR = 1.20, 1.08-1.33, p < 0.001), while parental occupation moderated highintention outcomes.

CONCLUSIONS: Low family functioning exerts a robust influence on both low and high fertility intentions, although its effect on zerochild plans is largely explained by student and parental characteristics. By uncovering multidimensional familyfunctioning profiles and their differential impacts, this study advances theoretical models of intergenerational value transmission and informs targeted familyeducation and policy interventions aimed at mitigating China’s lowfertility trajectory.

PMID:40866946 | DOI:10.1186/s12889-025-24358-9

World J Surg Oncol. 2025 Aug 27;23(1):322. doi: 10.1186/s12957-025-03959-z.

ABSTRACT

BACKGROUND: Achieving optimal surgical margins is critical in breast-conserving surgery (BCS) to reduce local recurrence (LR) and the need for re-excision. This meta-analysis evaluated the impact of intraoperative margin optimization strategies on key surgical and oncologic outcomes in patients who underwent BCS.

METHODS: A systematic review and meta-analysis were conducted according to the PRISMA guidelines, including six randomized controlled trials (RCTs). The outcomes assessed included the re-excision rate (primary outcome), positive margin rate, local recurrence (LR), and overall survival (OS). The risk of bias was evaluated using the ROB 2 tool, and the certainty of evidence was assessed using GRADE. The study protocol was prospectively registered in the PROSPERO database ( CRD420251000564 ).

RESULTS: Intraoperative margin optimization significantly reduced re-excision rates (OR 0.54, 95% CI 0.32-0.90), corresponding to 169 fewer re-excisions per 1,000 patients. Positive margin rates were also significantly lower (OR 0.40, 95% CI 0.22-0.73), translating to 139 fewer positive margins per 1,000 patients. No statistically significant differences were observed for LR (OR 0.72, 95% CI, 0.16-3.19) or OS (OR 0.87, 95% CI, 0.73-1.03).

CONCLUSION: Intraoperative margin optimization effectively reduces positive margins and re-excisions in BCS without adversely affecting LR or OS. The incorporation of these strategies should be considered a standard practice to enhance surgical quality and patient outcomes.

PMID:40866944 | DOI:10.1186/s12957-025-03959-z

BMC Med Educ. 2025 Aug 27;25(1):1206. doi: 10.1186/s12909-025-07791-7.

ABSTRACT

BACKGROUND: Tooth avulsion is a severe type of dental trauma requiring immediate response and management. Timely treatment according to International Association of Dental Traumatology (IADT) protocols is important in achieving an optimal outcome. This study aimed to assess the knowledge, perception, and clinical practices of dental professionals located in Sanaa, Yemen, in regard to the management of avulsed teeth.

METHODS: A cross-sectional survey was conducted using a validated questionnaire with 25 closed-ended items that assessed demographics, generalized knowledge of traumatic dental injuries (TDIs), and clinical management of avulsed teeth. Data were analyzed using descriptive statistics and chi-square tests to determine whether differences are statistically significant (α = 0.05).

RESULTS: A total of 202 individuals completed the shared questionnaire. The majority (87.62%) of the participants recognized that a knocked-out tooth should be reinserted, 40.10% knew about the ideal transport medium for an avulsed tooth, and 63.86% acknowledged the critical time period for successful replantation. Statistically significant differences were noted between the correct and incorrect responses of knowledge items (all p < 0.05), except items related to splinting type and the prognosis of an avulsed tooth. The overall percentage of correct responses to all questions was 69.19%.

CONCLUSION: The knowledge of dentists in relation to the clinical management of dental avulsions was moderate but inadequate, and certain aspects of the proper management protocol for avulsed teeth could still be improved. Thus, improvement is needed regarding the effective handling of avulsed tooth cases.

PMID:40866936 | DOI:10.1186/s12909-025-07791-7

BMC Med. 2025 Aug 27;23(1):500. doi: 10.1186/s12916-025-04354-x.

ABSTRACT

BACKGROUND: Patients with diabetes mellitus (DM) have a significantly increased risk of developing heart failure (HF), which exacerbates adverse cardiovascular outcomes. Limited data are available on the prognostic value of cardiac MRI in DM. We aimed to evaluate the association between MRI-derived strain analysis and adverse outcomes in DM patients at different heart failure (HF) stages.

METHODS: In this prospective study, DM participants with preserved ejection fraction (EF) underwent MRI examination between January 2019 and December 2021 were evaluated. Feature tracking strain parameters were measured using cine MRI. The primary outcome was a composite outcome including HF hospitalization or cardiovascular death. Cox proportional regression was used to assess the association between risk factors and outcomes.

RESULTS: A total of 581 DM participants (mean age, 56 years ± 13; 401 men) including 390 asymptomatic patients (stage A/B HF) and 191 heart failure with preserved EF were evaluated. After a median follow-up of 34.3 months, 74 DM patients reached the primary outcome; 13(2.2%) had cardiovascular mortality and 61(10.5%) had heart failure hospitalization. Kaplan-Meier survival curves showed that patients with global longitudinal strain (GLS) greater than or equal to -13.76% and patients with global early diastolic longitudinal strain rate (eGLSR) less than or equal to 0.51/s were more likely to experience the primary outcome (log-rank P < 0.001). In multivariable analysis, eGLSR was independently associated with an increased risk of the primary endpoint(per SD, adjusted HR: 2.038; 95% CI: 1.384-3.002; P < 0.001), but GLS was not. When risk stratification was based on GLS and eGLSR, Kaplan-Meier survival curves showed that patients with abnormal eGLSR had a significantly higher risk of adverse outcomes, regardless of GLS status. In addition, eGLSR provided incremental predictive power over clinical and imaging variables, achieving the largest C-statistic of 0.744. Of note, the association between eGLSR and outcomes was consistent in stage A/B HF patients and patients with HFpEF. Subgroup analysis showed non-ischemic LGE assessed by MRI was also independently associated with outcomes in patients with DM.

CONCLUSIONS: In DM patients with preserved ejection fraction, left ventricular eGLSR measured by cardiac MRI was an independent predictor of adverse outcomes and offered incremental prognostic value over conventional clinical and imaging indices.

PMID:40866930 | DOI:10.1186/s12916-025-04354-x