Category: Nevin Manimala

Trials. 2025 Sep 24;26(1):352. doi: 10.1186/s13063-025-09050-y.

ABSTRACT

BACKGROUND: The optimal duration of antibiotic treatment must strike a delicate balance: it must be long enough to achieve desirable efficacy yet short enough to prevent the development of toxicities, adverse events, and mitigate other arduous aspects related to patient burden. Historically, the approach used to determine duration of antibiotic treatment has been inefficient, severely impacting the refinement of therapeutics for tuberculosis (TB) where treatment duration, and its complications, can be extensive. Many of the challenges in duration-ranging have parallels and proposed solutions in the field of dose-ranging where the literature is substantially more established and where the traditions of qualitative, pairwise comparison studies have been replaced with model-based approaches. Such methods are more efficient and allow for interpolation between the doses observed.

METHODS: This work examines the utility of cutting-edge dose-finding methods (such as MCP-Mod) for duration-ranging of TB treatments. We compare the operating characteristics of the adapted model-based duration-ranging methodologies against standard qualitative methods for the purposes of estimating optimal duration and describing the duration-response relationship, using a simulation study motivated by a Multi-Arm Multi-Stage Response Over Continuous Intervention (MAMS-ROCI) clinical trial design. We explore three specific targets: (1) power to detect a duration-response relationship, (2) ability to accurately reproduce the duration-response curve, and (3) ability to estimate the optimal duration within an acceptable margin of error.

RESULTS: We find that model-based methods outperform standard qualitative comparisons on every target examined, particularly when the sample size is constrained to that of a typical Phase II trial.

CONCLUSIONS: We conclude that the success of the next era in TB therapeutics duration evaluation trials, and antibiotics duration-ranging more broadly, will meaningfully rely on the ability to simultaneously pair innovative model-based statistical methods with re-imagined study designs such as MAMS-ROCI.

PMID:40993799 | DOI:10.1186/s13063-025-09050-y

Cardiooncology. 2025 Sep 24;11(1):82. doi: 10.1186/s40959-025-00347-0.

ABSTRACT

BACKGROUND: Fruquintinib is a highly selective tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, which play a critical role in angiogenesis and tumor growth. As a novel anti-angiogenic agent, Fruquintinib has demonstrated promising efficacy in the treatment of various advanced malignancies, including metastatic colorectal cancer. However, concerns about its cardiovascular safety have emerged, given that VEGFR inhibition is often associated with cardiovascular adverse events.

METHODOLOGY: We conducted a systematic search through PubMed, Scopus, Embase, and Web of Science to identify randomized controlled trials and cohort studies that assessed the safety of Fruquintinib compared with placebo in patients with metastatic colorectal and other cancers. The evaluated outcomes included hypertension, coronary artery disease, cerebrovascular accidents, peripheral artery disease, heart failure, thromboembolism, arrhythmias, aortic dissection, and superior vena cava syndrome. Two independent reviewers screened the titles/abstracts based on predefined inclusion and exclusion criteria, followed by a full-text review of potentially relevant studies. Any disagreements between the reviewers were resolved through consultation with a third reviewer to ensure the accuracy and consistency of the study selection.

RESULTS: Fifteen reports were included in our study. Out of 3832 patients taking Fruquintinib monotherapy, a total of 997 developed hypertension with a pooled estimate incidence of 0.329 (95% CI: 0.248, 0.410; P < 0.001). In comparison to placebo, Fruquintinib was associated with significantly higher odds of developing hypertension (OR: 6.856; 95% CI: 5.071, 9.268; P < 0.001). Compared to Regorafenib, Fruquintinib demonstrated an OR of 1.549 (95% CI: 0.804, 2.983; P = 0.191) for the development of hypertension. Additionally, patients taking Fruquintinib had a pooled estimate incidence of 0.041 (95% CI: 0.021, 0.060, P < 0.001) for thromboembolism development with an OR of 2.092 (95% CI: 0.813, 5.385; P = 0.126) compared to placebo. Other reported cardiovascular side effects included sinus tachycardia, superior vena cava syndrome, peripheral edema, heart failure, myocardial enzymes elevation, and vascular access complications.

CONCLUSION: Our study found that Fruquintinib is associated with significant cardiovascular risks, with hypertension being the most common adverse event, while thromboembolism did not reach statistical significance. Therefore, close monitoring for treatment-related cardiovascular events should be considered in these patients.

PMID:40993794 | DOI:10.1186/s40959-025-00347-0

Parasit Vectors. 2025 Sep 24;18(1):378. doi: 10.1186/s13071-025-06938-1.

ABSTRACT

BACKGROUND: African animal trypanosomosis (AAT) and human African trypanosomosis (HAT) are transmitted and spread primarily by tsetse flies (Glossina spp.) in sub-Saharan Africa. The animal disease poses significant challenges to agropastoral systems, including in Kenya, where 38 out of 47 counties are infested with eight species of Glossina. Climate change and human activities can also aggravate these infestations, putting rural-scale farmers who rely on agropastoral systems at a greater risk. Geographical gaps in existing entomological datasets limit a comprehensive understanding of tsetse fly distribution across the country, especially amid rapid landscape dynamics.

METHODS: This study aimed to predict the spatial distribution of tsetse flies habitat in Kenya using recent entomological data (i.e., tsetse fly occurrence records), satellite-derived environmental variables, landscape structure, demographic indicators, and species-distribution modeling techniques. We applied four machine learning (ML) algorithms-random forest (RF), support vector machines (SVM), maximum entropy (MaxEnt), and generalized linear models (GLM)-to predict tsetse flies habitat suitability. Additionally, we developed ensemble models that combine the predictive power of the four algorithms. Predictions were made at the genus level (Glossina spp.) and the species level for one priority species (Glossina pallidipes).

RESULTS: The models performed well with true skill statistic (TSS) and area under the curve (AUC) metric measures of 0.67 and 0.88 for Glossina spp. and 0.85 and 0.96 for G. pallidipes, respectively. The predictions indicated an estimated potential suitable area of about 26% of Kenya for Glossina spp. and 9% for G. pallidipes. Tsetse fly habitat suitability was positively correlated with increased sheep density, normalized difference vegetation index, and soil moisture. However, suitability declined when the maximum land surface temperature (LST) exceeded 40 °C and elevation increased above 400 m.

CONCLUSIONS: These findings can help improve the targeting and, hence, the cost-effectiveness of surveillance and ultimately support an evidence-based progressive control of tsetse flies infestation in Kenya.

PMID:40993789 | DOI:10.1186/s13071-025-06938-1

Cancer Imaging. 2025 Sep 24;25(1):110. doi: 10.1186/s40644-025-00914-9.

ABSTRACT

BACKGROUND: In the era of therapeutic de-escalation, the opportunity to move from systematic axillary lymph node dissection (ALND) to sentinel lymph node biopsy in axillary node-positive breast cancer patients after neoadjuvant systemic therapy (NST) is currently considered. The purpose of this study was to identify FDG-PET parameters associated with axillary pathological complete response (pRAx) in the most proliferative tumor subtypes, eg Triple Negative (TN) and HER2-amplified.

METHODS: Patients with newly-diagnosed TN or HER2-amplified breast cancer, with pathologically-proven axillary node metastasis, no distant metastasis and indication of NST were prospectively included from September 2017 to December 2021. Sequential FDG-PET/CT scans were performed at baseline and after one cycle of NST. Metabolic parameters at baseline and their changes (Delta in %) of axillary nodes were assessed: SUVmax, SUVratio (SUVmax/SUVmax liver), SUVpeak, SUVmean, TLG and MTV. Logistic regressions with ROC curves were used to determine parameters associated with pRAx.

RESULTS: Sixty-one patients (24 TN, 19 ER-negative/HER2-amplified and 18 ER-positive/HER2-amplified) were recruited. Median value of Axillary SUVmax at baseline were 7.9, 7.0 and 5.2 and Delta Axillary SUVmax were -62%,-60% and -47% in these 3 subgroups, respectively. In univariate model, in the whole population, Delta Axillary SUVmax showed the greatest AUC for prediction of pRAx of 0.72 (95%CI: 0.59-0.85), whereas AUC of Axillary SUVmax at baseline was not statistically significant (AUC = 0.6 (95%CI: 0.46-0.74)). Specificity, sensitivity, PPV and NPV of Delta Axillary SUVmax were 96%, 49%, 94% and 58% respectively for predicting pRAx with a threshold of -68.7%. Odd Ratio associated with Delta Axillary SUVmax < -68.7% compared to ≥ -68.7% was 24.0 (95%CI: 2.9-194). In multivariate model, adjusted on tumor subtypes, Delta Axillary SUVmax was still significantly associated with pRAx (OR = 20.7 (95%IC: 2.5-172). AUCs adjusted on the tumor subtype were not significantly modified compared to univariate model (p = 0.45 compared to unadjusted AUC) suggesting that thresholds were not significantly different in each tumor subtype.

CONCLUSIONS: Delta Axillary SUVmax seems to be the most relevant metabolic parameter to predict an axillary pathological complete response and early metabolic response could be a valuable tool for selecting patients eligible for axillary surgical de-escalation after NST, regardless tumor subtypes.

PMID:40993786 | DOI:10.1186/s40644-025-00914-9

BMC Sports Sci Med Rehabil. 2025 Sep 24;17(1):269. doi: 10.1186/s13102-025-01285-1.

ABSTRACT

BACKGROUND: Physical preparation in basketball is essential but often limited by training time and prior focus on tactical and technical skills. While postural stability is known to assist injury prevention and performance, its specific impact on game-related performance remains unclear. With the development of motion analysis systems, the numerical values of external and internal loads measured during matches have become measurable. This study aimed to examine the relationship between postural stability and game-related performance and introduce a method for visualizing key competencies.

METHOD: Twenty-three U16 female basketball players (age = 15.22 ± 0.82 years, mass = 66.3 ± 8.85 kg, high = 174.0 ± 8.2 cm) participated from the Hungarian first league. Postural stability was assessed via plank test and one minute dynamic standing balance tests, while game-related performance was monitored through match-derived internal and external load values measured by WIMU PRO™ System, alongside statistical data derived from the official box scores. After the postural stability measurements, we monitored an official basketball match, which was conducted according to official International Basketball Association (FIBA) rules. For clear and comprehensive presentation, we combined the game-related performance indicators using Principal Component Analysis (PCA).

RESULTS: A moderate correlation (0.5 < r < 0.8, p < 0.05) was found between the game-related performance and postural stability variables. However, plank test indicators showed no significant correlations with game-related performance variables, except for bad throws (r = 0.56, p = 0.037), the postural error (PE), a variable reflecting compensatory movement during fatigue in the plank test, correlated with balance indicators (r = 0.63, p = 0.014). Mediolateral balance control correlated with explosive game-related performace metrics, including maximum acceleration (r = -0.65, p = 0.01), deceleration (r = 0.56, p = 0.035), and steals (r = -0.52, p = 0.05). PCA proved effective in creating game competency scores, enabling a graphical representation of game-related performance.

CONCLUSION: Findings suggest that trunk endurance alone was not directly related to game-related performance, while dynamic balance metrics showed moderate correlations. The PE values provide deeper insights into the balance-trunk stability relation. The dynamic balance test could support player monitoring, and the PCA based method facilitates player profiling.

PMID:40993779 | DOI:10.1186/s13102-025-01285-1

Trials. 2025 Sep 24;26(1):345. doi: 10.1186/s13063-025-09079-z.

ABSTRACT

OBJECTIVE: The study attempted to explore the postoperative pain control of ultrasound-guided iliac fascia and trigeminus block anesthesia among patients undergoing free flap reconstruction for head-and-neck tumors.

METHODS: This research implemented a prospective, double-blinded, randomized, and placebo-controlled clinical trial. Patients between 18 and 85 years who had accepted a radical head-and-neck tumor resection while simultaneously undergoing the vascularized anterolateral femoral free flap reconstruction for the surgical coloboma were recruited. The subjects were randomly divided into nerve block and blank groups. Faciocervical pain while speaking was the primary outcome variable. It was measured using the visual analog scale (VAS) during the perioperative period up to postoperative 7 days. Descriptive statistics and logistic regression analysis were performed. The data were analyzed using the Mann-Whitney U test, linear mixed-effects model, chi-square test, and Fisher’s exact test. The statistically significant level was set at P < 0.05.

RESULTS: The sample comprised 145 subjects with a mean age of 58.4 (SD = 12.7), 102 (70.3%) males. There were 71 (49.0%) and 74 (51.0%) participants in the nerve block and blank groups. Nerve block anesthesia reduced postoperative pain, depicted by VASS (0.99 ± 1.72 P < 0.0001). The out-of-bed mobilization started before within the nerve block group (47.45 ± 19.68 P = 0.017). The high expression of IL-6 could decrease the efficacy of this protocol (P = 0.0176).

CONCLUSION: Ultrasound-guided iliac fascia combined with trigeminus block anesthesia is an effective method for pain management in patients who underwent head-and-neck tumor surgery in conjunction with the simultaneous repair using the vascularized anterolateral femoral free flap.

TRIAL REGISTRATION: The Institutional Ethics Review Board approved the study and retrospectively registered it with the Chinese Clinical Trial Registry at January 10, 2024 (ChiCTR2400079720).

PMID:40993773 | DOI:10.1186/s13063-025-09079-z

Diabetol Metab Syndr. 2025 Sep 24;17(1):370. doi: 10.1186/s13098-025-01931-1.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent metabolic condition lacking sensitive and accessible biomarkers for early detection and risk stratification.

OBJECTIVE: To investigate the association between serum alpha-1-acid glycoprotein (AGP) levels and MAFLD prevalence among young and middle-aged women, and to evaluate the dose-response relationship and diagnostic performance of AGP.

METHODS: Data were obtained from 2,003 female participants aged 20-49 years in the NHANES 2017-2020 cycles. Weighted multivariable logistic regression models assessed the association between AGP and MAFLD, with adjustments for demographic, metabolic, and inflammatory covariates. Restricted cubic spline (RCS) regression evaluated nonlinear trends, and ROC analysis assessed predictive accuracy.

RESULTS: Higher AGP levels were significantly associated with increased MAFLD risk. In the fully adjusted model, the highest AGP tertile had an odds ratio of 2.63 (95% CI: 1.65-4.19) compared to the lowest. RCS analysis showed a nonlinear, biphasic relationship with an inflection point around 0.9 g/L. ROC analysis indicated moderate discriminatory ability (AUC = 0.734), with AGP outperforming traditional liver enzymes. Subgroup analyses confirmed consistency across metabolic risk strata.

CONCLUSION: AGP is independently and nonlinearly associated with MAFLD and may serve as a non-invasive biomarker for early identification of at-risk individuals. These findings support the potential clinical utility of AGP in MAFLD screening and risk assessment.

PMID:40993765 | DOI:10.1186/s13098-025-01931-1

Parasit Vectors. 2025 Sep 24;18(1):375. doi: 10.1186/s13071-025-06844-6.

ABSTRACT

BACKGROUND: Taenia solium cysticercosis is a zoonotic parasitic disease with significant public health implications, particularly in endemic regions of low- and middle-income countries. In pigs, cyst burden varies widely, with most harboring fewer than 10 cysts and only a small fraction carrying high cyst loads. Age has been identified as a key factor influencing infection susceptibility. However, inconsistencies in previous studies have hindered clear characterization of infection patterns and immunity. In this study, we conducted controlled experiments involving the infection of pigs with T. solium eggs to evaluate the relationship between pig age and susceptibility to infection.

METHODS: A total of 52 pigs from northern Peru, aged 4 to 22 weeks, were experimentally infected with T. solium eggs to examine age-related differences in cyst burden. Pigs were housed individually under controlled conditions and fed commercial pig diets. Infections were administered using an esophageal catheter, delivering 20,000 T. solium eggs in gelatin capsules. Six age groups were studied using a standardized egg pool to ensure consistency across infection rounds. After 10 weeks, necropsies were performed to count cysts in all muscles, the brain, and other organs. Weekly serological tests monitored seroconversion. Statistical models were used to analyze cyst counts and assess the effects of age and other predictors.

RESULTS: The number of live, degenerated, and total cysts was overdispersed, making a negative binomial model the most suitable choice to represent the data and their dependence on age at infection. Younger pigs showed low median live cyst count, similar to older pigs, while median cyst burden increased in pigs infected at intermediate ages, around natural weaning age. The negative binomial regression showed that age and a covariate inversely related to age at infection were significantly associated with cyst count at necropsy. Other covariates such as egg pool viability and sex did not significantly affect model performance. Serological tests confirmed seroconversion in all pigs.

CONCLUSIONS: Our results show that younger pigs display partial protection against the development of cysticerci compared to those infected at the natural weaning age (around 9 to 12 weeks of age). Additionally, infection susceptibility then decreases with age in a way that is consistent with previous literature.

PMID:40993763 | DOI:10.1186/s13071-025-06844-6

BMC Public Health. 2025 Sep 24;25(1):3065. doi: 10.1186/s12889-025-24272-0.

ABSTRACT

Diabetic kidney disease (DKD) is a severe and prevalent complication of diabetes. Social contexts have been increasingly recognized as critical factors in the escalation and ongoing management of chronic diseases, including DKD. This study aimed to evaluate the connection between social risk profile (SRP) and DKD in United States. METHODS: Data were sourced from the National Health and Nutrition Examination Survey (1999-2018). DKD was defined as the coexistence of diabetes and chronic kidney disease (CKD). SRP scores, based on the number of positive measures, were categorized into four quartiles: low (0-2), lower-middle (3-4), upper-middle (5-6), and high (7-8). The associations of SRP with the prevalence and mortality of DKD were assessed. RESULTS: A total of 6,464 participants were included in the study, among them, 2,668 had DKD, and 1,153 died during a mean follow-up of 143 months. SRP scores were associated with the prevalence and mortality of DKD. Compared with high SRP scores, low SRP levels were related with a higher risk of DKD (OR, 1.86; 95% CI, 1.54 to 2.26, P < 0.0001). Higher SRP scores were associated with lower risks of mortality, including all-cause (HR, 0.84; 95% CI, 0.81-0.88; P < 0.0001), cardiovascular disease (HR, 0.85; 95% CI, 0.80-0.91; P < 0.0001), and diabetes-related mortality (HR, 0.86; 95% CI, 0.76-0.96; P = 0.009). CONCLUSION: Lower SRP scores showed a connection to higher DKD prevalence and worse outcomes, highlighting the potential importance of social risk screening and targeted interventions.

PMID:40993757 | DOI:10.1186/s12889-025-24272-0

Trials. 2025 Sep 24;26(1):348. doi: 10.1186/s13063-025-09068-2.

ABSTRACT

BACKGROUND: The Estimands framework, introduced in the Addendum to ICH E9, provides a structured method to define treatment effects in clinical trials. The main novelty of the framework is the discussion of intercurrent events as part of the treatment effect definition. It is widely believed that the application of the framework to non-inferiority and equivalence trials deserves specific consideration.

METHODS: To examine the current practices of using the estimand framework in non-inferiority and equivalence trials, we reviewed the scientific advice provided by the European Medicines Agency to drug developers in 2022. This review aimed to determine how often the estimands framework is used by drug developers and/or recommended by EMA and to describe what intercurrent events and handling strategies are being proposed by drug developers and recommended by EMA.

RESULTS: The use of the framework varied substantially by clinical development phases. While it was used for phase 3 trials in 47% (25/53) by developers, it was used in 5% (1/19) of the phase 1 trials. For 39% (11/28) of the trials where developers did not use the estimands framework in phase 3, there was no regulatory recommendation to adopt the framework in the response. The most discussed intercurrent event in our sample was ‘treatment discontinuation’ (n = 47), for which developers most often proposed either a treatment policy strategy (17/47, 36%) or a hypothetical strategy (11/47, 23%). In contrast, EMA most often recommended the use of two co-primary estimands with two different strategies (22/47, 47%).

CONCLUSIONS: Generally, the proposed and recommended strategies depend on the clinical setting and the respective intercurrent event. Developers almost always proposed a single primary estimand, whereas EMA often recommended two co-primary estimands differing in the strategies used to handle some or all the intercurrent events. Further interaction between academia, industry and regulators is necessary to progress the implementation process of the estimands framework for non-inferiority and equivalence trials.

PMID:40993752 | DOI:10.1186/s13063-025-09068-2