Category: Statistics

BMC Public Health. 2024 Oct 21;24(1):2913. doi: 10.1186/s12889-024-20343-w.

ABSTRACT

BACKGROUND: Smear-positive TB patients greatly contribute to community-level transmission of this disease. Locating hotspots would make it easier to prioritize and target control interventions. This study aimed to assess the spatial distribution of smear-positive index TB cases and their secondary cases and the predictors of clustering of smear-positive TB cases.

METHODS: This study was conducted in the Silti Zone of Central Ethiopia from 2020 to 2022. The data of smear-positive index TB patients were collected from the unit TB registries of healthcare facilities. Contacts of all index TB patients were screened in the community and tested to identify secondary TB patients. We performed spatial analysis, including Moran’s I statistic, the Getis-Ord Gi* statistic and geographically weighted regression (GWR), to assess the global distribution, local clustering and predictors of clustering of smear-positive TB patients, respectively. Additionally, we used inverse distance weighting (IDW) interpolation to predict the distribution of smear-positive TB cases and develop a continuous raster map for places with no data.

RESULTS: Spatial autocorrelation analysis revealed that the distribution of smear-positive TB patients exhibited significant clustering (Moran’s I = 0.70029; p value < 0.000). The Getis-Ord Gi* output indicated the presence of statistically significant hotspots as well as cold spots in the study area. Significant hotspots were found in 11 Kebeles of the Silti, Dalocha and Misrak Silti districts. Significant coldspots were also found in five kebeles of the Silti and Misrak districts. GWR analysis revealed that no education, primary education, family size and thatched roof houses were significant predictors of the spatial clustering of smear-positive TB cases. We also found that the majority of the secondary TB cases were found in hotspots identified through spatial analysis.

CONCLUSION: The study revealed a heterogenous distribution of smear positive TB in the study area and it could act as a model that can be replicated in other regions. The identified hotspots of TB could be targeted through location-based interventions such as systematic active screening in the form of outreach programs to improve the performance of TB prevention and control, including reducing the transmission of TB. Educational status, family size and housing type were some of the factors that significantly influenced the spatial distribution of smear-positive TB in the study area. The distribution of secondary TB cases found through household contact screening coincided with the identified hotspots, indicating greater transmission of the disease in these places.

PMID:39434061 | DOI:10.1186/s12889-024-20343-w

Mol Med. 2024 Oct 21;30(1):182. doi: 10.1186/s10020-024-00958-w.

ABSTRACT

BACKGROUND: Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease’s progression characteristics holds significant practical importance.

METHODS: Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer’s protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe²⁺) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company.

RESULTS: In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe²⁺ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects.

CONCLUSIONS: This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe²⁺ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis.

PMID:39434056 | DOI:10.1186/s10020-024-00958-w

BMC Public Health. 2024 Oct 21;24(1):2905. doi: 10.1186/s12889-024-20297-z.

ABSTRACT

Continuous surveillance and risk assessment of inactivated Coronavirus Disease 2019 (COVID-19)) vaccines provide an understanding of their safety profiles, guide vaccination strategy and public health policy. This study aims to analyze the characteristics and prevalence of officially reported serious adverse events following immunization (AEFIs) with inactivated COVID-19 vaccines by System Organ Class (SOC), age, and sex.To achieve this aim, a retrospective observational study was conducted between February 14th, 2021, and June 30th, 2022. Reported AEFIs were evaluated for data completeness. Causality assessment adhered to the World Health Organization guidelines.Findings revealed that the AEFIs occurrence did not significantly differ between vaccines used (ChAdOx1 vs. BNT162b2), sex, or SOC. The most prevalent AEFIs were vascular disorders (37%), followed by cardiac (25%) and nervous system disorders (14%). The adverse events were predominantly reported post-vaccination with the BNT162b2 vaccine, mainly after the first dose. The mean age was highest for miscellaneous disorders (70 ± 21.7 years) and the lowest for nervous system (46 ± 22 years) and immune system disorders (45 ± 19 years). Age differences were statistically different for vascular disorders (p = 0.003) and immune system disorders (p = 0.012).In conclusion, ongoing surveillance and risk assessment of the vaccine’s safety profile is crucial for detecting potential safety signals. Active surveillance of the reported serious AEFIs is highly needed to support evidence-based vaccination strategies and maintain public confidence in immunization programs.

PMID:39434043 | DOI:10.1186/s12889-024-20297-z

BMC Cancer. 2024 Oct 21;24(1):1300. doi: 10.1186/s12885-024-13049-0.

ABSTRACT

PURPOSE: Despite suffering from the same disease, each patient exhibits a distinct microbiological profile and variable reactivity to prescribed treatments. Most doctors typically use a standardized treatment approach for all patients suffering from a specific disease. Consequently, the challenge lies in the effectiveness of this standardized treatment and in adapting it to each individual patient. Personalized medicine is an emerging field in which doctors use diagnostic tests to identify the most effective medical treatments for each patient. Prognosis, disease monitoring, and treatment planning rely on manual, error-prone methods. Artificial intelligence (AI) uses predictive techniques capable of automating prognostic and monitoring processes, thus reducing the error rate associated with conventional methods.

METHODS: This paper conducts an analysis of current literature, encompassing the period from January 2015 to 2023, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

RESULTS: In assessing 25 pertinent studies concerning predicting neoadjuvant treatment (NAT) response in breast cancer (BC) patients, the studies explored various imaging modalities (Magnetic Resonance Imaging, Ultrasound, etc.), evaluating results based on accuracy, sensitivity, and area under the curve. Additionally, the technologies employed, such as machine learning (ML), deep learning (DL), statistics, and hybrid models, were scrutinized. The presentation of datasets used for predicting complete pathological response (PCR) was also considered.

CONCLUSION: This paper seeks to unveil crucial insights into the application of AI techniques in personalized oncology, particularly in the monitoring and prediction of responses to NAT for BC patients. Finally, the authors suggest avenues for future research into AI-based monitoring systems.

PMID:39434042 | DOI:10.1186/s12885-024-13049-0

J Med Internet Res. 2024 Oct 21;26:e51710. doi: 10.2196/51710.

ABSTRACT

BACKGROUND: Suicide is the leading cause of death among children and adolescents in Japan. Internet search volume may be useful in detecting suicide risk. However, few studies have shown an association between suicides attempted by children and adolescents and their internet search volume.

OBJECTIVE: This study aimed to examine the relationship between the number of suicides and the volume of school-related internet searches to identify the search terms that could serve as the leading indicators of suicide prevention among children and adolescents.

METHODS: We used data on weekly suicides attempted by elementary, middle, and high school students in Japan from 2016 to 2020, provided by the National Police Agency. Internet search volume was weekly data for 20 school-related terms obtained from Google Trends. Granger causality and cross-correlation analysis were performed to estimate the temporal back-and-forth and lag between suicide deaths and search volume for the related terms.

RESULTS: The search queries “I do not want to go to school” and “study” showed Granger causality with suicide incidences. The cross-correlation analysis showed significant positive correlations in the range of -2 to 2 for “I do not want to go to school” (highest value at time lag 0, r=0.28), and -1 to 2 for “study” (highest value at time lag -1, r=0.18), indicating that the search volume increased as the number of suicides increased. Furthermore, during the COVID-19 pandemic period (January-December 2020), the search trend for “I do not want to go to school,” unlike “study,” was highly associated with suicide frequency.

CONCLUSIONS: Monitoring the volume of internet searches for “I do not want to go to school” could be useful for the early detection of suicide risk among children and adolescents and for optimizing web-based helpline displays.

PMID:39432900 | DOI:10.2196/51710

JMIR Med Educ. 2024 Oct 21;10:e48518. doi: 10.2196/48518.

ABSTRACT

BACKGROUND: As part of the residency application process in the United States, many medical specialties now offer applicants the opportunity to send program signals that indicate high interest to a limited number of residency programs. To determine which residency programs to apply to, and which programs to send signals to, applicants need accurate information to determine which programs align with their future training goals. Most applicants use a program’s website to review program characteristics and criteria, so describing the current state of residency program websites can inform programs of best practices.

OBJECTIVE: This study aims to characterize information available on obstetrics and gynecology residency program websites and to determine whether there are differences in information available between different types of residency programs.

METHODS: This was a cross-sectional observational study of all US obstetrics and gynecology residency program website content. The authorship group identified factors that would be useful for residency applicants around program demographics and learner trajectories; application criteria including standardized testing metrics, residency statistics, and benefits; and diversity, equity, and inclusion mission statements and values. Two authors examined all available websites from November 2011 through March 2022. Data analysis consisted of descriptive statistics and one-way ANOVA, with P<.05 considered significant.

RESULTS: Among 290 programs, 283 (97.6%) had websites; 238 (82.1%) listed medical schools of current residents; 158 (54.5%) described residency alumni trajectories; 107 (36.9%) included guidance related to the preferred United States Medical Licensing Examination Step 1 scores; 53 (18.3%) included guidance related to the Comprehensive Osteopathic Medical Licensing Examination Level 1 scores; 185 (63.8%) included international applicant guidance; 132 (45.5%) included a program-specific mission statement; 84 (29%) included a diversity, equity, and inclusion statement; and 167 (57.6%) included program-specific media or links to program social media on their websites. University-based programs were more likely to include a variety of information compared to community-based university-affiliated and community-based programs, including medical schools of current residents (113/123, 91.9%, university-based; 85/111, 76.6%, community-based university-affiliated; 40/56, 71.4%, community-based; P<.001); alumni trajectories (90/123, 73.2%, university-based; 51/111, 45.9%, community-based university-affiliated; 17/56, 30.4%, community-based; P<.001); the United States Medical Licensing Examination Step 1 score guidance (58/123, 47.2%, university-based; 36/111, 32.4%, community-based university-affiliated; 13/56, 23.2%, community-based; P=.004); and diversity, equity, and inclusion statements (57/123, 46.3%, university-based; 19/111, 17.1%, community-based university-affiliated; 8/56, 14.3%, community-based; P<.001).

CONCLUSIONS: There are opportunities to improve the quantity and quality of data on residency websites. From this work, we propose best practices for what information should be included on residency websites that will enable applicants to make informed decisions.

PMID:39432889 | DOI:10.2196/48518

JCO Precis Oncol. 2024 Oct;8:e2400275. doi: 10.1200/PO.24.00275. Epub 2024 Oct 21.

ABSTRACT

PURPOSE: We introduce a novel algorithmic approach to design phase I trials for oncology drug combinations.

METHODS: Our proposed Toxicity Adaptive Lists Design (TALE) is straightforward to implement, requiring the prespecification of a small number of parameters that define rules governing dose escalation, de-escalation, or reassessment of previously explored dose levels. These rules effectively regulate dose exploration and control the number of toxicities. A key feature of TALE is the possibility of simultaneous assignment of multiple-dose combinations that are deemed safe by previously accrued data.

RESULTS: A numerical study shows that TALE shares comparable operative characteristics, in terms of identification of the maximum tolerated dose (MTD), to alternative approaches such as the Bayesian optimal interval design, the COPULA, the product of independent beta probabilities escalation, and the continual reassessment method for partial ordering designs while reducing the risk of overdosing patients.

CONCLUSION: The proposed TALE design provides a favorable balance between maintaining patient safety and accurately identifying the MTD. To facilitate the use of TALE, we provide a user-friendly R Shiny application and an R package for computing relevant operating characteristics, such as the risk of assigning highly toxic dose combinations.

PMID:39432880 | DOI:10.1200/PO.24.00275

JCO Oncol Pract. 2024 Oct 21:OP2400472. doi: 10.1200/OP-24-00472. Online ahead of print.

ABSTRACT

PURPOSE: Abiraterone use for prostate cancer can cause mineralocorticoid excess syndrome (MES; eg, hypertension and hypokalemia). Prednisone mitigates these effects; however, the optimal dose level is unclear. This study examines MES effects from abiraterone with 5 mg of prednisone once daily versus 5 mg twice daily.

METHODS: Data for 1,410 abiraterone-treated patients from 2011 to 2022 were identified from a large academic/community hospital system. Three hundred and fifty-three patients were excluded for missing medication data and use of an alternative steroid; 1,057 patients remained (5 mg once daily, n = 550, 5 mg twice daily, n = 507). Prednisone dose was treated as a time-varying covariate. Hypokalemia and hypertension incidence over 24 weeks after abiraterone initiation was analyzed via Cox proportional hazard models using Common Terminology Criteria for Adverse Events (v5.0) grading via direct clinical measurements and International Classification of Diseases (ICD)-10 code outcomes.

RESULTS: Patients receiving 5 mg of prednisone twice daily had a statistically significant decrease in cumulative hazard for experiencing at least one MES event (hypertension and/or hypokalemia) via direct clinical measurement (hazard ratio [HR], 0.79 [CI, 0.68 to 0.91]; P = .002) and by ICD-10 code (HR, 0.65 [CI, 0.54 to 0.79]; P < .001) analysis. This finding was durable with individual end point analysis of hypertension and hypokalemia. There were no changes to BMI or hyperglycemia (>140 mg/dL) between the cohorts.

CONCLUSION: This retrospective analysis shows a decrease in risk for the development of at least one episode of hypertension or hypokalemia with abiraterone using 5 mg twice-daily prednisone in the study population. Assessments of metabolic impacts (BMI, hyperglycemia) did not show differences with prednisone dosing. These findings may merit consideration when determining an optimal prednisone dosing regimen.

PMID:39432865 | DOI:10.1200/OP-24-00472

Anesthesiology. 2024 Oct 21. doi: 10.1097/ALN.0000000000005267. Online ahead of print.

ABSTRACT

BACKGROUND: Diaphragm dysfunction is common in intensive care unit and associated with weaning failure and mortality. Diagnosis gold standard is the transdiaphragmatic or tracheal pressure induced by magnetic phrenic nerve stimulation. However, the equipment is not commonly available and requires specific technical skills. We aimed to evaluate ultrasound guided transcutaneous phrenic nerve stimulation for daily bedside assessment of diaphragm function by targeted electrical phrenic nerve stimulation.

METHODS: In this randomized cross-over study we compared a new method of ultrasound guided transcutaneous electrical phrenic nerve stimulation (SONOTEPS method) using a peripheral nerve stimulator, with the magnetic phrenic nerve stimulation. Intensive care unit adult patients under mechanical ventilation with a Richmond-Agitation-Sedation-Scale score of -4 or -5 were included. Each patient received the two methods of stimulation, in a randomized order. The primary outcome was the tracheal pressure (Ptrach) induced by stimulation.

RESULTS: We analyzed 232 measures of Ptrach from 116 patients of whom 77 presented a diaphragm dysfunction (Ptrach < 11 cmH2O) and 50 a severe diaphragm dysfunction (Ptrach < 8 cmH2O). The Passing-Bablok regression showed no significant differences (intercept A of -0.03 [CI95:-0.83-0.52] and slope B of 0.98 [CI95:0.90-1.05]) between SONOTEPS method and magnetic stimulation which were positively correlated (R²=0.639). The mean bias was -1.08 (CI95 5.02, -7.18) cmH2O. The receiver operating curves showed an excellent performance for the diagnosis of diaphragm dysfunction and severe diaphragm dysfunction with respectively an area under curve of 0.90 (CI95 0.83-0.97) and 0.88 (CI95 0.82-0.95). This performance was not significantly affected by the body mass index or the presence of a neck catheter.

CONCLUSIONS: The SONOTEPS method is a simple and accurate tool for bedside assessment of diaphragm function with ultrasound guided transcutaneous phrenic nerve stimulation in sedated patients with no or minimal spontaneous respiratory activity.

PMID:39432817 | DOI:10.1097/ALN.0000000000005267

Pain. 2024 Oct 16. doi: 10.1097/j.pain.0000000000003424. Online ahead of print.

ABSTRACT

The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted – chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average-however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.

PMID:39432808 | DOI:10.1097/j.pain.0000000000003424