Nevin Manimala

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

Brain Behav. 2025 Aug;15(8):e70730. doi: 10.1002/brb3.70730.

ABSTRACT

OBJECTIVE: This study aims to investigate the alterations in structural and functional connectivity networks (SCN and FCN) in children with hypothalamic syndrome (HS) following craniopharyngioma resection and to explore the relationship between these network changes and clinical manifestations.

MATERIALS AND METHODS: We performed graph theory analysis on SCN and FCN derived from 36 patients with HS and 36 age- and sex-matched healthy controls (HC), with an age range of 6 to 13 years. We evaluated characteristics, nodal properties, and the coupling between SCN and FCN across 90 brain nodes. Partial correlation analyses examined relationships between graph theory properties and clinical scales, including the Wechsler Intelligence Scale for Children (WISC), the Wechsler Memory Scale (WMS), and the Attention Deficit Hyperactivity Disorder (ADHD) scale.

RESULTS: The SCN in the HS group exhibited abnormal global properties, including increased characteristic path length (Lp), decreased global efficiency (Eg), and local efficiency (ELOC), alongside notable reductions in nodal properties, such as degree centrality (Dc) and nodal efficiency (Ne) across multiple nodes. The FCN in the HS group also displayed abnormal global attributes, with elevated Lp and reduced Eg, alongside decreased Dc at the median cingulate and paracingulate gyri (DCG.L) node. However, no statistically significant differences were found in structural-functional connectivity (SC-FC) coupling between groups. Correlation analysis revealed significant links between WISC, WMS, and ADHD scales and various graph-theoretic properties in the HS group.

CONCLUSION: In patients with HS following craniopharyngioma resection, alterations in SCN and FCN characteristics have been observed. These neural changes are associated with cognitive developmental impairments related to HS, providing neuroimaging evidence elucidating the mechanisms underlying cognitive deficits in HS patients.

PMID:40864521 | DOI:10.1002/brb3.70730

Clin Orthop Relat Res. 2025 Aug 21. doi: 10.1097/CORR.0000000000003662. Online ahead of print.

ABSTRACT

BACKGROUND: Lower extremity splints are commonly used for the treatment of foot and ankle injuries and carry the risk of posterior heel pressure injury. Assessing heel contact pressures in a splint may guide clinicians toward specific splint designs that are associated with lower contact pressures.

QUESTIONS/PURPOSES: This biomechanical study tested multiple splint characteristics to answer: (1) Which combination of heel position, padding thickness, and padding type (brand) minimizes posterior heel contact pressure? (2) Are there factors while making a splint that are associated with higher contact pressures?

METHODS: Twenty legs in 10 volunteer participants (mean ± SD age 30 ± 14 years) without current foot or ankle injury were recruited for this biomechanical study. Three of 10 volunteers were female. A pressure transducer was used over the posterior heel to measure contact pressure in a short leg splint. To answer our first research question about the effects of different splint characteristics, we measured contact pressures with 0, 2, 4, 6, 8, and 10 layers of two undercast padding brands, with both resting the heel down and floating the heel freely by placing the leg on a pillow to keep the splinted heel free of contact. Pressures were compared with a threshold of 32 mm Hg, the pressure of dermal arteriolar capillary collapse. To answer our second research question about factors associated with higher contact pressures, we recorded measurements of abnormal pressure spikes and observed the effect of improperly bunched or folded padding behind the heel.

RESULTS: Mean contact pressure remained above 32 mm Hg when resting the heel down, independent of padding thickness or brand. Floating the heel, by resting the leg on a pillow, with 6, 8, and 10 layers of thicker undercast padding or 8 and 10 layers of thinner padding reduced pressure below the threshold of 32 mm Hg. The mean contact pressure between 8 and 10 layers of padding was not different (10 layers reduced contact pressure by 4 mm Hg more than 8 layers [95% confidence interval -3 to 11]; p = 0.22). Improperly bunched undercast padding behind the heel increased mean contact pressure roughly threefold compared with evenly applied padding (median 270% increase [range 187% to 575%]).

CONCLUSION: In this study, the best splint configuration consisted of 8 or 10 evenly applied layers of thicker undercast padding when floating the heel. Lower extremity positioning with the heel floating freely appears to be an important modifiable factor to reduce heel dermal pressures. We contend that attention to these details of splint application might reduce the likelihood of pressure ulcers in patients, but future clinical studies of patients with various injuries or other indications for splinting are warranted.

CLINICAL RELEVANCE: These findings may be relevant to orthopaedic surgeons, emergency department and primary care providers, as well as cast technicians, all of whom play a role in mitigating the mechanical factors that contribute to iatrogenic posterior heel pressure ulcers in patients with foot and ankle injuries.

PMID:40864515 | DOI:10.1097/CORR.0000000000003662

JMIR Public Health Surveill. 2025 Aug 27;11:e77195. doi: 10.2196/77195.

ABSTRACT

BACKGROUND: Ethiopia is faced with poor measles-containing vaccine second dose (MCV2) coverage, leading to recurrent outbreaks.

OBJECTIVE: This meta-analysis and systematic review aimed at combining evidence of MCV2 uptake in Ethiopia and its determinants to inform interventions for increased vaccination uptake and control of public health challenges.

METHODS: This review examined observational quantitative research on measles second dose vaccination among children in Ethiopia using databases such as PubMed Central, Cochrane Library, Web of Science, Scopus, MEDLINE, and Embase. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Heterogeneity was evaluated using I² statistics and the Cochran Q test, and the analysis used a random-effects model. Publication bias was assessed through funnel plots, the Egger test, and nonparametric trim-and-fill tests.

RESULTS: The overall MCV2 uptake among children aged <5 years in Ethiopia was only 34.4% (95% CI 18.8%-49.9%). Significant determinants of MCV2 uptake included high level of maternal education (adjusted odds ratio [AOR] 3.31, 95% CI 1.32-5.30), attendance to antenatal care follow-ups (AOR 2.02, 95% CI 1.12-2.92), use of postnatal care services (AOR 3.03, 95% CI 1.77-4.28), reduced waiting times at vaccination sites (AOR 2.56, 95% CI 1.98-3.13), good awareness of measles vaccination (AOR 2.17, 95% CI 1.59-2.74), and positive perceptions of the vaccine (AOR 3.58, 95% CI 1.97-6.30).

CONCLUSIONS: This study found that the uptake of MCV2 among children aged <5 years in Ethiopia was 34%, which is far below the global and national goal of 95%. Key factors contributing to low coverage include mothers’ educational levels, use of antenatal and postnatal care services, waiting times at vaccination sites, and mothers’ awareness of the measles vaccine. Improving community-based education programs, increasing access to antenatal and postnatal care services, reducing waiting times, and raising awareness about immunization all contribute to increasing vaccine uptake.

TRIAL REGISTRATION: PROSPERO CRD42024619031; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024619031.

PMID:40864500 | DOI:10.2196/77195

JMIR Res Protoc. 2025 Aug 27;14:e71955. doi: 10.2196/71955.

ABSTRACT

BACKGROUND: Falls and cognitive impairment are major sources of disability in Parkinson disease (PD). The ability to accurately identify individuals with PD at high risk for falls and cognitive impairment would provide an opportunity for intervention and potentially improve long-term outcomes. In a previous study, Assessing Telehealth Outcomes in Multiyear Extensions of Parkinson Disease Trials (AT-HOME PD), we remotely characterized participants with early PD who had participated in 1 of 2 PD clinical trials over 2 years of follow-up. These participants with advancing disease provide a unique opportunity to examine whether the capture of objective in-home measures via digital tools and bothersome symptoms via direct participant report improves the prediction of disease milestones.

OBJECTIVE: Assessing Telehealth Outcomes in Multiyear Extensions of Parkinson Disease Trials-2 (AT-HOME PD2) aims to examine whether digital tools and remote participant reporting can improve the prediction of falls and cognitive impairment, quantify changes in physical activity over time, and explore the relationship between physical activity and clinical progression over time.

METHODS: This is a decentralized observational study of up to 200 individuals with PD, with clinical and digital phenotyping for up to 3 years of follow-up. Participants are those who took part in the STEADY-PD III (NCT02168842), Study of Urate Elevation in Parkinson’s Disease, Phase 3 (SURE-PD3; NCT02642393), AT-HOME PD (NCT03538262), or PD GENEration (NCT04057794) studies. All participants complete 2 video visits per year, wear 2 wrist-worn sensors (Fitbit Charge 5 and ActiGraph CentrePoint Insight Watch) for 1 week each month, complete smartphone-based motor tasks (using the mPower 2.0 app) for 10 days each quarter, and complete online surveys (within the companion Fox Insight study) each quarter. Falls are assessed via a weekly automated telephone call. A cognitive diagnosis is determined by a consensus committee that considers scores on a global cognitive measure, detailed neuropsychological tests, a cognitive-related disability measure, and clinical information. Prediction models will be constructed, and prediction accuracy will be compared across the models.

RESULTS: Recruitment for the study was initiated in September 2023. Enrollment is ongoing, with 142 participants enrolled as of January 2025. Within the cohort, the average age is 69.2 (SD 8.7) years; 85 (59.9%) participants are male, 137 (96.5%) are White, and 2 (1.4%) are Hispanic or Latino; and the average disease duration is 8.9 (SD 1.3) years.

CONCLUSIONS: AT-HOME PD2 is remotely clinically and digitally phenotyping participants with midstage PD to predict falls and cognitive impairment and to provide insights into long-term progression.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/71955.

PMID:40864497 | DOI:10.2196/71955