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Nevin Manimala Statistics

Content Validation of a Medication Adherence Risk Score (MARS) for Mortality Risk Prediction: A Delphi Consensus

Clin Pharmacol Ther. 2026 Apr 3. doi: 10.1002/cpt.70274. Online ahead of print.

ABSTRACT

The Medication Adherence Risk Score (MARS) is an objective adherence-based score, derived from transactional dispensary data. This study provides expert consensus to validate the use of the MARS as a predictor of mortality risk. A systematic review and assessment of South African health legislation and professional guidelines informed the development of consensus statements regarding the relevance, validity, predictive power, and implementation feasibility of the MARS. A two-round modified Delphi approach using a 5-point Likert scale was employed. Consensus was reached if at least 80% of respondents selected “agree” or “strongly agree.” Nonconsensus statements were revised based on qualitative feedback and subsequently reevaluated in a second round. Thirteen clinical, actuarial, and academic experts were successfully recruited. Consensus was achieved for 20 of the 28 statements in Round 1. Five of 18 (27.8%; risk score components), 1 of 3 (33.3%, validity/predictive power), and 2 of 7 statements (26.5%, real-world implementation) did not initially reach consensus. Nonconsensus statements were revised to provide clarity, after which consensus was achieved for all statements by the end of Round 2. Expert consensus supports the inclusion, exclusion, and weighting of MARS risk factors. The panel agreed that the score offers predictive value for mortality outcomes, and that real-world application for enhancing risk stratification and reducing healthcare costs is feasible. Future statistical analysis is necessary to demonstrate its relationship with mortality risk. Developing practical implementation strategies will facilitate incorporation into clinical practice and public health interventions.

PMID:41933437 | DOI:10.1002/cpt.70274

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Impact of the COVID-19 pandemic on the incidence of Clostridioides difficile infection based on hospital surveillance data: a systematic review and meta-analysis

Antimicrob Resist Infect Control. 2026 Apr 3. doi: 10.1186/s13756-026-01737-4. Online ahead of print.

ABSTRACT

BACKGROUND: Clostridioides difficile infection (CDI) remains a substantial burden on healthcare systems worldwide. The COVID-19 pandemic has had profound and multifaceted effects on healthcare delivery and infection control practices, potentially influencing the epidemiology of CDI.

OBJECTIVE: To assess whether the coronavirus disease 2019 (COVID-19) pandemic has influenced the incidence of CDI and to explore potential contributing factors.

METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Seven databases were searched for relevant literature published from December 2019 to October 2025. Study quality was assessed via the Newcastle‒Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) critical appraisal tools. Random- or fixed-effects models were selected according to heterogeneity. Publication bias was evaluated via funnel plots and Egger’s test, and sensitivity analyses were conducted. The primary outcome was the incidence rate of CDI, expressed as cases per 10,000 patient-days. Incidence rate ratios (IRR) were calculated to compare the incidence of CDI between the prepandemic and pandemic periods.

RESULTS: Sixteen studies were included. The pooled CDI incidence rate was 4.42 (95% CI: 3.37-5.46) per 10,000 patient-days in the prepandemic period and 3.80 (95% CI: 2.63-4.96) per 10,000 patient-days during the pandemic. The pooled incidence rate ratio was 0.80 (95% CI: 0.67-0.97), indicating a significant reduction in the incidence of CDI. This decline was associated with changes in medical practices (e.g., the suspension of nonurgent and high-risk procedures), antimicrobial stewardship practices, and strengthened infection control measures (e.g., enhanced hand hygiene and environmental disinfection) during the pandemic.

CONCLUSION: Compared with the prepandemic period, the incidence of CDI decreased significantly during the COVID-19 pandemic. This finding suggests that strengthened infection prevention measures, improved antimicrobial stewardship, and adaptations in healthcare delivery may have contributed to reduced CDI transmission. Reinforcing these evidence-based foundational strategies may help mitigate ‌the risk of CDI and other healthcare-associated infections during future public health emergencies.

PMID:41933426 | DOI:10.1186/s13756-026-01737-4

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Primary versus rerupture of the anterior cruciate ligament: rupture site patterns and graft elongation-a systematic review and meta-analysis

Knee Surg Relat Res. 2026 Apr 3;38(1):15. doi: 10.1186/s43019-026-00313-9.

ABSTRACT

BACKGROUND: While the rupture pattern of the native anterior cruciate ligament (ACL) has been well characterized-most frequently occurring in the proximal third of the ligament-there is limited consensus on whether reconstructed ACLs fail in a similar fashion. The purpose of this meta-analysis is to compare rupture localization patterns between first ruptures and reruptures.

MATERIALS AND METHODS: MEDLINE (PubMed), Embase, and the Cochrane Library databases were searched to identify studies analyzing rupture locations after both first rupture and rerupture. The main extracted outcome was the anatomical site of ACL rupture, categorized as proximal, mid-substance, distal, or elongation. A random-effects meta-analysis was performed to calculate pooled proportions and odds ratios (ORs), with between-study heterogeneity assessed using the I2 statistic.

RESULTS: The pooled meta-analysis revealed no significant differences (p > 0.05) in the distribution of proximal, mid-substance, or distal rupture locations between the first rupture and rerupture groups. However, graft elongation was significantly more frequent in reruptures (p < 0.05). Using first rupture as the reference, the odds of elongation were 1.63-fold higher in the rerupture group (OR 1.63, 95% CI 1.46-1.83; p < 0.001).

CONCLUSIONS: This meta-analysis found no statistically significant differences in rupture-site localization between first ruptures and reruptures, indicating that reconstructed ACLs tend to fail in anatomical patterns resembling those of the native ligament. However, the markedly higher incidence of graft elongation observed in the rerupture cohort suggests a distinct mode of failure. These findings highlight graft elongation as a specific mechanism that may be influenced by surgical or biological factors, warranting further investigation.

LEVEL OF EVIDENCE: Systematic review and meta-analysis of Level 4 studies.

STUDY REGISTRATION: PROSPERO Registry CRD420251073835.

PMID:41933414 | DOI:10.1186/s43019-026-00313-9

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Coverage validation survey of preventive chemotherapy for schistosomiasis in interruption of transmission districts of Ethiopia, 2025

Infect Dis Poverty. 2026 Apr 3;15(1):39. doi: 10.1186/s40249-026-01439-4.

ABSTRACT

BACKGROUND: Ethiopia bears a substantial burden of neglected tropical diseases, including schistosomiasis, which remains a major public health problem in endemic areas. Preventive chemotherapy is the main strategy for controlling and eliminating schistosomiasis. This study aimed to assess the reach of the mass drug administration program and validate the reported praziquantel coverage in interruption-of-transmission districts of Ethiopia.

METHODS: A community-based cross-sectional survey was conducted from 1 to 30 August 2025 in eight purposively selected districts across three Ethiopian regions targeted for schistosomiasis interventions. Using a three-stage sampling method, data were collected using WHO-standard tools via KoboToolbox. The data were analyzed using descriptive statistics, including frequencies and percentages, in SPSS version 26 to estimate program reach and survey coverage.

RESULT: The average programs reach (participants who offered praziquantel) was 84.2%, while surveyed coverage (participants who reported swallowing the drug) was 83.0% (95% CI: 82.7-83.3%). West Badewacho district achieved the highest survey coverage, 95.4%, while Hammer and Bena Tsemay districts achieved 92.1% and 92.4%, respectively. The lowest coverage was recorded in Menit Goldya (66.2%), Mizan (72.0%), and South Bench (72.4%). Treatment uptake among those offered praziquantel was 98.5%.

CONCLUSIONS: The survey showed that praziquantel treatment coverage was below the 95% target and the national reported average, with notable variation across districts. Surveyed coverage was largely influenced by whether the treatment was offered; districts with lower program reach consistently had lower treatment coverage. Improving the delivery and offering of praziquantel at the community level is therefore essential to increase treatment uptake.

PMID:41933407 | DOI:10.1186/s40249-026-01439-4

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Accelerating tuberculosis diagnosis in Mozambican prisons using digital chest X-rays with computer-aided detection: a longitudinal, comprehensive health intervention

BMC Glob Public Health. 2026 Apr 3;4(1):31. doi: 10.1186/s44263-026-00256-z.

ABSTRACT

BACKGROUND: Mozambique has a high burden of tuberculosis (TB) and in 2021, an estimated 18,000 persons with TB nationwide were not diagnosed. Estimates suggest that globally 47% of TB disease in prisons is undiagnosed. We implemented an integrated-care model health intervention to enhance the diagnosis and treatment of TB disease, provide TB preventive treatment (TPT), and identify and treat other undiagnosed health conditions in three prisons in Maputo, Mozambique.

METHODS: From July 11, 2023, through the second quarter of 2024, we systematically screened for TB using digital chest X-rays with computer-aided detection (DCXR-CAD). This was combined with symptom screening in a parallel algorithm. We conducted clinical assessments for other health conditions and delivered TPT. Graphs visually compare TB case notification trends with two control prisons, which continued the usual standard of care, symptom screening for TB. An interrupted time series (ITS) analysis was used to evaluate TB case notification counts before and after the intervention in the intervention prisons.

RESULTS: Of 7912 individuals screened, 264 new diagnoses of TB disease were notified, a TB screening yield of 3.34% and a number needed to screen of 30, and 1346 persons were initiated on TPT. Other conditions diagnosed and treated include HIV (28), malnutrition (830), and skin conditions (462). TB case notifications were higher in the intervention prisons during the intervention than in the preceding period in the same prisons. Comparing case notifications during the intervention with an equivalent period prior to the intervention showed an increase of about 52% in intervention prisons but a decrease in control prisons by the same magnitude. The ITS analysis found the effect of the intervention on TB case notification counts statistically significant in two of the intervention prisons: (incidence rate ratio [IRR] 3.96, 95% confidence interval [CI] 1.51-10.40; p = 0.005) and (IRR 6.17, 95% CI 2.17-17.55; p < 0.001).

CONCLUSIONS: Strengthening local infrastructure and implementing DCXR-CAD for screening likely contributed to a higher TB yield in the intervention prisons. Screening and diagnosing TB, delivering TB disease treatment and prevention, and addressing other health conditions simultaneously in this vulnerable population were feasible and important.

PMID:41933406 | DOI:10.1186/s44263-026-00256-z

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Nevin Manimala Statistics

Performance benchmarking of deep learning models for real-time median nerve segmentation and cross-sectional area measurement in ultrasound imaging

Med Phys. 2026 Apr;53(4):e70414. doi: 10.1002/mp.70414.

ABSTRACT

BACKGROUND: Median nerve, a major peripheral nerve, connects the hand to the central nervous system, facilitating upper limb motor function and sensation by transmitting sensory data from the palm and fingers. Damage to this nerve can result in motor and sensory deficits, with carpal tunnel syndrome (CTS) causing compression, leading to tingling and numbness in the thumb, index, middle, and lateral ring fingers.

PURPOSE: This study aimed to develop an accurate deep-learning-based segmentation method for measuring the cross-sectional area (CSA) of the median nerve to facilitate the diagnosis of nerve entrapment syndromes and aid in surgical planning, with a focus on CTS.

METHODS: This study introduces MNSeg-Net, a novel lightweight multiscale feature fusion network with 2.46M parameters for median nerve segmentation in ultrasound (US) frames, specifically designed to enable a fully automated, end-to-end clinical setup supporting real-time segmentation and CSA computation. The dataset comprised 100 subjects and 30 000 ultrasound frames, which were split into training (80%), validation (10%), and testing (10%) subsets with subject-wise separation to avoid data leakage. MNSeg-Net was benchmarked against state-of-the-art segmentation models, including UNet and its variants (UNet++ and U2Net). The performance was assessed using metrics such as the Dice similarity coefficient (DSC) and CSA difference. The statistical significance of performance differences was evaluated using paired t-tests, effect size (Cohen’s d), and one-way ANOVA with Tukey’s HSD correction for multiple comparisons at a p $p$ -value threshold of 0.05, while statistical equivalence between models within predefined margins was formally assessed using the two one-sided test (TOST) procedure. Following quantitative validation, the model was deployed in a real-time clinical setup utilizing an Av.io HD Epiphan frame grabber to stream ultrasound images from the ultrasound machine to a GPU-equipped system. A secondary display running parallel to the original ultrasound screen visualized the segmented median nerve and computed the CSA values in real time.

RESULTS: MNSeg-Net achieved high segmentation performance, with average DSC scores of 94.7% at the wrist and 83.4% from the wrist to the elbow, and the lowest Hausdorff distance, matching the performance of the best-performing 44-million-parameter heavy U2Net model. Compared to U2Net, MNSeg-Net showed no statistically significant difference in DSC performance ( p = 9.11 × 10 1 $p = 9.11 times 10^{-1}$ ; Cohen’s d = 0.003 $d = -0.003$ ; mean difference = -0.001), with formal equivalence testing confirming equivalence across all tested margins ( ± 0.01 , ± 0.03 , ± 0.05 $pm 0.01, pm 0.03, pm 0.05$ ). For CSA estimation, MNSeg-Net also showed no statistically significant difference from clinician-annotated values ( p = 1.14 × 10 1 $p = 1.14 times 10^{-1}$ ; Cohen’s d = 0.041 $d = -0.041$ ; mean difference = -0.081), and equivalence was established at the ± 0.5 $pm 0.5$ margin, confirming a strong alignment with expert clinical assessments. MNSeg-Net demonstrated real-time performance by processing up to 43 frames per second on a single GPU, successfully segmenting the median nerve and computing CSA from ultrasound frames.

CONCLUSION: The developed MNSeg-Net-based clinical system represents an important step toward real-time median nerve assessment, enabling a fully automated solution for CTS diagnosis. By combining a lightweight architecture, real-time processing capability, and successful clinical deployment, it represents a substantial advancement in the CTS detection and management.

PMID:41933401 | DOI:10.1002/mp.70414

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Plasma EBV DNA dynamics during chemotherapy as a prognostic biomarker in AIDS-related non-Hodgkin lymphoma

Infect Agent Cancer. 2026 Apr 3. doi: 10.1186/s13027-026-00758-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the associations of plasma EBV-DNA and tumor EBV status with clinical outcomes in patients with AIDS-related non-Hodgkin lymphoma (ARL).

METHODS: We retrospectively analyzed ARL patients diagnosed at Shanghai Public Health Clinical Center between 2013 and 2021. Tumor EBV status was determined by EBV-encoded RNA (EBER) in situ hybridization, and plasma EBV-DNA was quantified using real-time PCR. Survival outcomes were evaluated using Kaplan-Meier analysis and Cox regression. Longitudinal EBV-DNA patterns during chemotherapy were classified into four groups: persistently negative, persistently positive, clearance, and conversion.

RESULTS: Among 183 ARL patients, 99 underwent tumor EBER testing with 45.5% (45/99) positivity. Survival analysis was performed in 85 ARL patients who received treatment. The 2-year overall survival (OS) did not differ by EBER status (positive: 63.2% vs. negative: 52.5%; HR 0.86, 95% CI 0.41-1.80; p = 0.695). Baseline plasma EBV-DNA was quantified in 52 patients, with 47 (90.4%) undergoing ≥ 4 tests during chemotherapy cycles. Baseline plasma EBV-DNA levels were not predictive of prognosis. However, detectable EBV-DNA during chemotherapy was associated with significantly inferior OS (p = 0.048) and remained an independent prognostic factor after adjustment. Longitudinal analysis showed no statistically significant survival differences among four EBV-DNA patterns (p = 0.074), but patients with persistently positive or conversion patterns exhibited poorer outcomes, while persistently negative or clearance patterns were associated with more favorable prognosis. Pairwise analysis confirmed significantly better survival in persistently negative compared with persistently positive patients (p = 0.016).

CONCLUSION: Dynamic monitoring of plasma EBV-DNA during chemotherapy provides important prognostic information in ARL. Persistent or newly detectable EBV-DNA identifies patients at higher risk of poor outcomes, supporting the clinical utility of longitudinal EBV-DNA assessment for risk stratification and treatment guidance.

PMID:41933387 | DOI:10.1186/s13027-026-00758-3

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Vector competence of Belgian Anopheles plumbeus mosquitoes for West Nile virus under different temperature conditions

Parasit Vectors. 2026 Apr 3. doi: 10.1186/s13071-026-07346-9. Online ahead of print.

ABSTRACT

BACKGROUND: Belgium will likely be confronted with the introduction of West Nile virus (WNV) in the near future, as its presence in neighboring countries has been documented, and the high abundance of Culex pipiens, the main vector of this virus, has been documented in Belgium as well. Other mosquito species, such as Anopheles plumbeus, could also play a role in disease transmission. Anopheles plumbeus is a tree hole-breeding species whose habitat is expanding to urban sites, thus increasing its contact with humans. Only limited data are available on the vector competence of this species for arboviruses, let alone WNV. Such knowledge is important with respect to risk assessments and a preparedness plan in case a WNV introduction in Belgium takes place.

METHODS: A vector competence study with field-collected Belgian Anopheles plumbeus mosquitoes for WNV (lineage 1) was performed under different temperature conditions: a constant 25 °C, 25/20 °C, and 25/15 °C day/night temperature gradient.

RESULTS: At 14 days post-blood-feeding, the different temperature conditions did not impact the infection rate, ranging between 24% and 29%, nor the viral load in the gut, indicating a similar level of viral replication. Interestingly, statistically significant differences in virus dissemination from the gut to secondary tissues were observed between the different conditions. At a constant temperature of 25 °C, WNV was detected via quantitative reverse transcription polymerase chain reaction (RT-qPCR) in the saliva of one mosquito, resulting in a transmission efficiency of 1.6%. In contrast, no WNV was detected in the saliva under gradient conditions. WNV could not be isolated from the RT-qPCR positive saliva sample.

CONCLUSIONS: Since no proof could be found of infectious WNV being present in the saliva of Anopheles plumbeus under any temperature condition, this species cannot be considered a competent vector on the basis of our results. As also only a low viral RNA load was detected by RT-qPCR in one saliva sample at the 25 °C condition, we conclude that Anopheles plumbeus will probably play no role in WNV transmission in Belgium, especially under temperature conditions that more closely reflect the current Belgian climate (25/15 °C) or what could occur in the future (25/20 °C) during the vector season.

PMID:41933367 | DOI:10.1186/s13071-026-07346-9

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Pharmacokinetics and homeostatic impact of golden bile powder: evidence from surrogate analyte-based UPLC-MS/MS in rats

Chin Med. 2026 Apr 3;21(1):109. doi: 10.1186/s13020-026-01371-7.

ABSTRACT

BACKGROUND: Golden bile powder (GBP), an artificial bear bile powder, is used for liver protection and contains taurine-conjugated bile acids (BAs) with broad pharmacological activities. However, its pharmacokinetics and effects on endogenous BA homeostasis are unclear.

METHODS: Sprague-Dawley rats received oral administration of GBP (54 mg/kg/day) combined with three deuterated taurine-conjugated BAs at fixed ratios for 7 days to facilitate separate analysis of changes in exogenous and endogenous BAs following administration. Single deuterated taurine-conjugated BA groups were also included. Blood samples were collected over a 24 h time window on days 1 and 7. We developed and validated a surrogate analyte-based UPLC-MS/MS method to quantify six BAs in rat plasma, eliminating endogenous interference. Pharmacokinetic parameters were obtained by non-compartmental analysis, and gender differences and accumulation effects were assessed using appropriate statistical comparisons.

RESULTS: The UPLC-MS/MS method demonstrated good linearity (r > 0.999), accuracy (89.1%-115%), precision (RSD < 15%), and stability (within ± 15%). Pharmacokinetic studies showed taurine-conjugated BAs in GBP had long half-lives (8.43-12.7 h) and gender-specific accumulation, with females displaying higher systemic exposure. For example, the AUC0-24 h of TCA was approximately 16-fold higher in females than in males. Repeated GBP administration (54 mg/kg/day for 7 days) reshaped systemic BA composition, increasing both exogenous and endogenous BA concentrations, with the latter displaying more pronounced elevations-approximately fivefold higher than the exogenous BA AUC increase. Sex differences were evident, as female rats exhibited enhanced conversion of conjugated BAs to free forms. The BA shifts observed may be related to known enterohepatic circulation and gut microbiota-mediated BA transformation pathways.

CONCLUSIONS: This work establishes an analytical framework for evaluating endogenous and exogenous BA dynamics, contributing to future mechanistic and translational studies involving GBP and its potential applications.

PMID:41933363 | DOI:10.1186/s13020-026-01371-7

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Using genomic epidemiology and geographic activity spaces to investigate tuberculosis outbreaks in Botswana

Int J Health Geogr. 2026 Apr 3. doi: 10.1186/s12942-026-00467-5. Online ahead of print.

NO ABSTRACT

PMID:41933361 | DOI:10.1186/s12942-026-00467-5