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Nevin Manimala Statistics

Clinical outcomes and cost-utility analysis of GKRS plus TKIs versus TKIs in patients with EGFR-mutant lung adenocarcinoma and brain metastases: a Markov decision model

J Neurosurg. 2025 Jan 10:1-10. doi: 10.3171/2024.7.JNS24310. Online ahead of print.

ABSTRACT

OBJECTIVE: This study focuses on epidermal growth factor receptor-mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition.

METHODS: Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW). In the incremental cost-utility ratio (ICUR) model, a healthcare provider perspective, a 1-month cycle length, a 5-year time horizon, and a discount rate of 2% per year for both effectiveness and costs were adopted. Probabilistic and one-way sensitivity analyses were also conducted to demonstrate the robustness of the findings. Statistical analysis was performed using IBM SPSS version 23.0, and cost-effectiveness analysis was conducted using TreeAge Pro software.

RESULTS: After applying IPTW, the GKRS+TKI group included 205 patients, and the TKI group consisted of 102 patients, with no statistically significant differences in whole confounders. The GKRS+TKI group demonstrated significantly prolonged median progression-free survival (37.5 months vs 10.6 months, p < 0.001) and median overall survival (55.1 months vs 30.8 months, p < 0.001) compared with the TKI group. The GKRS plus TKI strategy achieved an ICUR of $30,532.25 per quality-adjusted life year relative to the TKIs at the willingness-to-pay threshold of US$33,059 (Taiwan’s per capita gross domestic product).

CONCLUSIONS: The use of GKRS plus TKIs not only reduces disease recurrence and improves prognosis but also demonstrates a higher level of cost-effectiveness. These findings offer valuable guidelines for clinicians and inform healthcare authorities in optimizing resource allocation for improved medical care.

PMID:39793022 | DOI:10.3171/2024.7.JNS24310

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Nevin Manimala Statistics

Methodology for the Positive Voices 2022 Survey of People With HIV Accessing Care in England, Wales, and Scotland: Cross-Sectional Questionnaire Study

JMIR Res Protoc. 2025 Jan 10;14:e58531. doi: 10.2196/58531.

ABSTRACT

BACKGROUND: Due to advances in treatment, HIV is now a chronic condition with near-normal life expectancy. However, people with HIV continue to have a higher burden of mental and physical health conditions and are impacted by wider socioeconomic issues. Positive Voices is a nationally representative series of surveys of people with HIV in the United Kingdom. It monitors the physical, mental, and social health, well-being, and needs of this population so that they can be addressed.

OBJECTIVE: This paper aimed to describe the methodology, recruitment strategies, and key sociodemographic features of participants recruited for the second national round of Positive Voices (PV2022).

METHODS: PV2022 was a national, cross-sectional questionnaire study that included people attending HIV care at 101 of the 178 clinics in the United Kingdom between April 2022 and March 2023. Data from the HIV and AIDS reporting system (HARS), a national surveillance database of people with HIV and attending care that is held at the UK Health Security Agency (UKHSA), was used as a sampling frame. The information collected in PV2022 included demographic and socioeconomic factors, HIV diagnoses and treatment, mental and physical health, health service use and satisfaction, social care and support, met and unmet needs, stigma and discrimination, quality of life, lifestyle factors, and additional challenges experienced due to the COVID-19 pandemic. Data linkage to HARS enabled the extraction of clinical information on antiretroviral therapy (ART), HIV viral load, and CD4 lymphocyte counts. Probabilistic sampling was used to provide a randomly selected, representative sample of people attending HIV care who could be invited to complete a paper or online questionnaire ‘on the web’ to online. At the start of 2023, the study was underrecruiting, mainly due to the mpox outbreak, and a separate sequential recruitment strategy was initiated in 14 of the largest and most demographically diverse clinics to increase participant numbers.

RESULTS: Of the 4622 participants who completed the questionnaire, 3692 were recruited through probabilistic recruitment and 930 through sequential recruitment. The overall response rate (measured as the number of people who completed a questionnaire of those who either accepted or declined) was 50%. Survey respondents represented approximately 1 in 20 people diagnosed with HIV in England, Wales, and Scotland. The median age of participants was 52 years, 3428 of participants were male, 2991 were of White ethnicity, and 1121 were of Black ethnicity.

CONCLUSIONS: PV2022 is currently the largest survey of people with HIV in the United Kingdom (as of September 2024). The PV2022 findings will be used to explore the health and well-being of the HIV population and examine associations with demographic, socioeconomic, lifestyle, and other HIV-related factors.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/58531.

PMID:39793018 | DOI:10.2196/58531

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Incidence of idiopathic syrinx in pediatric patients diagnosed with VACTERL association

J Neurosurg Pediatr. 2025 Jan 10:1-6. doi: 10.3171/2024.10.PEDS24242. Online ahead of print.

ABSTRACT

OBJECTIVE: While the association of a syrinx with a tethered spinal cord in the context of VACTERL (vertebral defects [V], imperforate anus or anal atresia [A], cardiac malformations [C], tracheoesophageal defects [T] with or without esophageal atresia [E], renal anomalies [R], and limb defects [L]) association is known, the incidence of idiopathic syrinxes among these patients has not previously been reported. The authors aimed to characterize the incidence of syrinxes and the pattern of congenital anomalies in pediatric patients with VACTERL association, with a specific focus on the presence of idiopathic syrinxes in this population.

METHODS: An institutional database was retrospectively queried for all pediatric patients with VACTERL association. Patients were assessed for the presence of a syrinx. Those with no accompanying lesion to which the syrinx could be ascribed were designated idiopathic. Descriptive statistics and qualitative analyses characterized the clinical presentation and outcomes of this population.

RESULTS: The authors retrospectively identified 186 patients between 1993 and 2023 with VACTERL association. Of these 186 patients, 141 (75.8%) had a tethered spinal cord and 44 (23.7%) had a syrinx. Most syrinxes could be ascribed to the presence of a tethered spinal cord and/or Chiari malformation; however, 4 (9.1%) of the 44 appeared idiopathic, suggesting the incidence of idiopathic syrinxes in this patient population may be as high as 2.2% (4/186). Most patients remained asymptomatic aside from a single patient who presented with mild gait dysfunction that resolved over time. All syrinxes were managed conservatively, and all but one decreased or remained stable in size on follow-up imaging.

CONCLUSIONS: Although limited, current estimates suggest the general incidence of an idiopathic syrinx is between 5.6 and 8.4 per 100,000 people; these findings in a pediatric cohort with VACTERL association suggest an incidence of 2200 per 100,000 (i.e., 2.2%). Thus, an idiopathic syrinx may be 200-400 times as prevalent in the pediatric VACTERL population.

PMID:39793014 | DOI:10.3171/2024.10.PEDS24242

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A comprehensive multicenter analysis of clinical, molecular, and imaging characteristics and outcomes of H3 K27-altered diffuse midline glioma in adults

J Neurosurg. 2025 Jan 10:1-12. doi: 10.3171/2024.8.JNS241180. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective was to comprehensively investigate the clinical, molecular, and imaging characteristics and outcomes of H3 K27-altered diffuse midline glioma (DMG) in adults.

METHODS: Retrospective chart and imaging reviews were performed in 111 adult patients with H3 K27-altered DMG from two tertiary institutions. Clinical, molecular, imaging, and survival characteristics were analyzed. Characteristics were compared between adult and 365 pediatric patients from a previous multicenter meta-analysis dataset. Cox analyses were performed to determine predictors of overall survival (OS) in adult patients.

RESULTS: The median (range) age of adult patients was 40 (18-75) years, and 64 males and 47 females were included. Adults had a higher male proportion (57.7% vs 45.3%, p = 0.023), lower proportion of histological grade 4 (41.4% vs 74.0%, p < 0.001), and different tumor locations (p < 0.001) compared with pediatric patients; adults commonly showed a thalamus location (41.5%) followed by the spinal cord (27.0%), whereas pediatric patients predominantly showed a pons location (64.9%). The OS of adults was longer than that of pediatric patients (30.3 vs 12.0 months, p < 0.001, log-rank test). Older age at diagnosis (HR 0.96, p = 0.001), histologically lower grade (HR 0.25, p = 0.003), and gross-total resection of nonenhancing tumor (HR 0.15, p = 0.003) were independent favorable prognostic factors.

CONCLUSIONS: Adult patients with H3 K27-altered DMG showed distinct clinical, histological, and imaging characteristics compared to pediatric counterparts, with a significantly better prognosis. The authors’ results suggest that aggressive surgery should be pursued when deemed feasible for better survival outcomes.

PMID:39793011 | DOI:10.3171/2024.8.JNS241180

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Unveiling Sociocultural Barriers to Breast Cancer Awareness Among the South Asian Population: Case Study of Bangladesh and West Bengal, India

JMIR Hum Factors. 2025 Jan 10;12:e53969. doi: 10.2196/53969.

ABSTRACT

BACKGROUND: Bangladesh and West Bengal, India, are 2 densely populated South Asian neighboring regions with many socioeconomic and cultural similarities. In dealing with breast cancer (BC)-related issues, statistics show that people from these regions are having similar problems and fates. According to the Global Cancer Statistics 2020 and 2012 reports, for BC (particularly female BC), the age-standardized incidence rate is approximately 22 to 25 per 100,000 people, and the age-standardized mortality rate is approximately 11 to 13 per 100,000 for these areas. In Bangladesh, approximately 90% of patients are at stages III or IV, compared with 60% in India. For the broader South Asian population, this figure is 16%, while it is 11% in the United States and the United Kingdom. These statistics highlight the need for an urgent investigation into the reasons behind these regions’ late diagnoses and treatment.

OBJECTIVE: Early detection is essential for managing BC and reducing its impact on individuals. However, raising awareness in diverse societies is challenging due to differing cultural norms and socioeconomic conditions. We aimed to interview residents to identify barriers to BC awareness in specific regions.

METHODS: We conducted semistructured interviews with 17 participants from West Bengal and Bangladesh through Zoom (Zoom Video Communications). These were later transcribed and translated into English for qualitative data analysis. All our participants were older than 18 years, primarily identified as female, and most were married.

RESULTS: We have identified 20 significant barriers to effective BC care across 5 levels-individual, family, local society, health care system, and country or region. Key obstacles include neglect of early symptoms, reluctance to communicate, societal stigma, financial fears, uncertainty about treatment costs, inadequate mental health support, and lack of comprehensive health insurance. To address these issues, we recommend context-specific solutions such as integrating BC education into middle and high-school curricula, providing updates through media channels like talk shows and podcasts, promoting family health budgeting, enhancing communication at cultural events and religious gatherings, offering installment payment plans from health care providers, encouraging regular self-examination, and organizing statewide awareness campaigns. In addition, social media can be a powerful tool for raising mass awareness while respecting cultural and socioeconomic norms.

CONCLUSIONS: Fighting BC or any fatal disease is challenging and requires support from various dimensions. However, studies show that raising mass awareness is crucial for the early detection of BC. By adopting a sensitive and well-informed approach, we aim to improve the early detection of BC and help reduce its impact on South Asian communities.

PMID:39793010 | DOI:10.2196/53969

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Nevin Manimala Statistics

Barriers to Research for Academic Otologists/Neurotologists in the United States

Otol Neurotol. 2025 Feb 1;46(2):229-236. doi: 10.1097/MAO.0000000000004396. Epub 2024 Dec 11.

ABSTRACT

OBJECTIVE: The physician-scientist workforce is shrinking in the United States. Academic otologists/neurotologists face a diverse set of barriers to successful careers. We aimed to characterize the factors affecting contemporary otology/neurotology surgeon-scientists.

STUDY DESIGN: An electronic survey was distributed to faculty members of the American Neurotology Society and the American Otological Society in 2021. The survey queried demographics, practice setting, compensation, and barriers to conducting research for respondents in academic practice.

RESULTS: One hundred fifty-seven otologists/neurotologists responded to the survey, corresponding to an overall response rate of 25%. Of the respondents, 94 were in academic practice. The median protected research time was 0.5 days/wk, whereas the mode was zero. Across academic rank, salary compensation was lower for academic surgeons with active research funding and for female academic surgeons as compared with their male counterparts. Grant-funded female academic surgeons had significantly worse compensation compared with rank-matched male surgeons with similar protected time. No grant-funded female earned more than the 30th percentile for their rank. Identified barriers to research were pressure to maintain clinical productivity, insufficient protected time, and personal/family demands. Respondents highlighted several areas for improvement: compensation for research activity, administrative support, and improved grant funding mechanisms for clinician-scientists.

CONCLUSIONS: Otology/neurotology surgeon-scientists face barriers to research, including limited protected time, poor administrative support, increasingly competitive funding environments, and misaligned compensation models. New initiatives by the National Institute on Deafness and other Communication Disorders aim to increase the surgeon-scientist workforce, but their success may depend upon removing identified barriers at the level of academic institutions.

PMID:39792984 | DOI:10.1097/MAO.0000000000004396

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Angiotensin-Receptor Blockers Prevent Vestibular Schwannoma-Associated Hearing Loss

Otol Neurotol. 2025 Feb 1;46(2):183-189. doi: 10.1097/MAO.0000000000004376.

ABSTRACT

BACKGROUND INTRODUCTION: Vestibular schwannoma (VS) tumors typically present with sensorineural hearing loss (SNHL). Losartan has recently demonstrated prevention of tumor-associated SNHL in a mouse model of VS through suppression of inflammatory and pro-fibrotic factors, and the current study investigates this association in humans.

METHODS: This is a retrospective study of patients with unilateral VS and hypertension followed with sequential audiometry at a tertiary referral hospital from January 1994 to June 2023. Patients were stratified into subgroups by anti-hypertensive medication class. SNHL progression was assessed using Kaplan-Meier analysis to account for variable follow-up times.

RESULTS: Two hundred thirty-six patients were identified with diagnosis of both VS and hypertension, and with sequential audiometry. Of these, 186 were taking anti-hypertensive therapy at the time of initial VS diagnosis, and 23 were taking losartan or another angiotensin receptor blocker (ARB). Patients taking an ARB were both more likely to have normal baseline hearing and no progressive hearing loss with 36.5 total patient-years of follow-up. Patients taking other anti-hypertensives all showed expected declines in hearing consistent with natural history of VS tumors.

DISCUSSION CONCLUSION: This study represents the first statistically significant association between ARB intake and hearing preservation in a real-world VS patient population. Significant confounding factors, such as concomitant hypertension in these patients, could still cloud the full effect of ARB medications’ interaction with SNHL progression. Given that ARBs are well tolerated and safe, the results advocate for a prospective clinical trial to validate this effect.

PMID:39792982 | DOI:10.1097/MAO.0000000000004376

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Pöschl Reformations Created from High-Resolution Noncontrast Enhanced CT Head Exams Can Be Used to Detect and Classify Superior Semicircular Canal Abnormalities

Otol Neurotol. 2025 Feb 1;46(2):176-182. doi: 10.1097/MAO.0000000000004395. Epub 2024 Dec 18.

ABSTRACT

OBJECTIVE: To compare the diagnostic capability of Pöschl reformations created from temporal bone CT (TBCT) and high-resolution noncontrast CT head exams (HR-NECTH) to detect and classify superior semicircular canal (SSC) abnormalities.

STUDY DESIGN: Retrospective case review.

SETTING: Tertiary referral center.

PATIENTS: Individuals with normal and abnormal SSC who received TBCT and HR-NECTH.

INTERVENTIONS: Pöschl reformations of each patient’s temporal bones (TB) were created using TBCT and HR-NECTH. Screenshots displaying the SSC were randomized into an interpretation test sent to neuroradiologists who interpreted the SSC as normal/abnormal and classified abnormalities as thinning (SST)/dehiscence (SSD).

MAIN OUTCOME MEASURE: Analysis of responses to interpretation test, interrater reliability, and sensitivity, specificity, and positive/negative predictive values of Pöschl reformations from TBCT and HR-NECTH.

RESULTS: Fourteen patients were enrolled, 28 TB were reviewed. Sixteen TB demonstrated SST/SDD and 12 were normal as per gold standard TBCT. Interpretation test displaying screenshots of the SSC, in a randomized, blinded fashion, was completed by four neuroradiologists. Analysis of TBCT and HR-NECTH Pöschl reformation interpretations yielded no statistically significant difference in proportion of true/false-positive/negative responses (χ2 = 3.37, p = 0.83), similar and substantial interrater reliability (k = 0.78 vs. 0.73, respectively), and similar sensitivity, specificity, and positive/negative predictive values (0.86, 1, 1, 0.84 vs. 0.78, 0.96, 0.96, 0.77, respectively). Neuroradiologists also correctly classified SST/SSD on TBCT and HR-NECTH Pöschl reformations at a rate of 70.9% vs. 78.0%, respectively.

CONCLUSION: Pöschl reformations created from HR-NECTH demonstrated similar diagnostic capability as those created from TBCT to detect and classify SSC abnormalities.

PMID:39792981 | DOI:10.1097/MAO.0000000000004395

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Use of Hearing Aids Embedded with Inertial Sensors and Artificial Intelligence to Identify Patients at Risk for Falling

Otol Neurotol. 2025 Feb 1;46(2):121-127. doi: 10.1097/MAO.0000000000004386. Epub 2024 Dec 17.

ABSTRACT

OBJECTIVE: To compare fall risk scores of hearing aids embedded with inertial measurement units (IMU-HAs) and powered by artificial intelligence (AI) algorithms with scores by trained observers.

STUDY DESIGN: Prospective, double-blinded, observational study of fall risk scores between trained observers and those of IMU-HAs.

SETTING: Tertiary referral center.

PATIENTS: Two hundred fifty participants aged 55-100 years who were at risk for falls.

INTERVENTIONS: Fall risk was categorized using the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test battery consisting of the 4-Stage Balance, Timed Up and Go (TUG), and 30-Second Chair Stand tests. Performance was scored using bilateral IMU-HAs and compared to scores by clinicians blinded to the hearing aid measures.

MAIN OUTCOME MEASURES: Fall risk categorizations based on 4-Stage Balance, Timed Up and Go (TUG), and 30-Second Chair Stand tests obtained from IMU-HAs and clinicians.

RESULTS: Interrater reliability was excellent across all clinicians. The 4-Stage Balance and TUG showed no statistically significant differences between clinician and HAs. However, the IMU-HAs failed to record a response in 12% of TUG trials. For the 30-Second Chair Stand test, there was a significant difference of nearly one stand count, which would have altered fall risk classification in 21% of participants.

CONCLUSIONS: These results suggest that fall risk as determined by the STEADI tests was in most instances similar for IMU-HAs and trained observers; however, differences were observed in certain situations, suggesting improvements are needed in the algorithm to maximize accurate fall risk categorization.

PMID:39792975 | DOI:10.1097/MAO.0000000000004386

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A robust transfer learning approach for high-dimensional linear regression to support integration of multi-source gene expression data

PLoS Comput Biol. 2025 Jan 10;21(1):e1012739. doi: 10.1371/journal.pcbi.1012739. Online ahead of print.

ABSTRACT

Transfer learning aims to integrate useful information from multi-source datasets to improve the learning performance of target data. This can be effectively applied in genomics when we learn the gene associations in a target tissue, and data from other tissues can be integrated. However, heavy-tail distribution and outliers are common in genomics data, which poses challenges to the effectiveness of current transfer learning approaches. In this paper, we study the transfer learning problem under high-dimensional linear models with t-distributed error (Trans-PtLR), which aims to improve the estimation and prediction of target data by borrowing information from useful source data and offering robustness to accommodate complex data with heavy tails and outliers. In the oracle case with known transferable source datasets, a transfer learning algorithm based on penalized maximum likelihood and expectation-maximization algorithm is established. To avoid including non-informative sources, we propose to select the transferable sources based on cross-validation. Extensive simulation experiments as well as an application demonstrate that Trans-PtLR demonstrates robustness and better performance of estimation and prediction when heavy-tail and outliers exist compared to transfer learning for linear regression model with normal error distribution. Data integration, Variable selection, T distribution, Expectation maximization algorithm, Genotype-Tissue Expression, Cross validation.

PMID:39792955 | DOI:10.1371/journal.pcbi.1012739