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Cellular Oncology (Dordrecht) Jun 2024Gynecomastia denotes the benign proliferation of glandular breast tissue and stands as a recognized risk factor for male breast cancer. Nonetheless, the underlying...
BACKGROUND
Gynecomastia denotes the benign proliferation of glandular breast tissue and stands as a recognized risk factor for male breast cancer. Nonetheless, the underlying carcinogenic mechanisms orchestrating the progression from gynecomastia to cancer remain poorly understood.
METHODS
This study employed single-cell RNA sequencing (scRNA-seq) to meticulously dissect the cellular landscape of gynecomastia and unravel potential associations with male breast cancer at a single-cell resolution. Pseudotime and evolutionary analyses were executed to delineate the distinct features characterizing gynecomastia and male breast cancer. The TCGA database, along with cell-cell communication analysis and immunohistochemistry staining, was harnessed to validate differential gene expression, specifically focusing on CD13.
RESULT
From the copy number variation profiles and evolutionary tree, we inferred shared mutation characteristics (18p and 18q) underpinning both conditions. The developmental trajectory unveiled an intriguing overlap between gynecomastia and malignant epithelial cells. Moreover, the differential gene CD13 emerged as a common denominator in both gynecomastia and male breast cancer when compared with normal mammary tissue. Cell-cell interaction analysis and communication dynamics within the tumor microenvironment spotlighted distinctions between CD13 and CD13 subsets, with the former exhibiting elevated expression of FGFR1-FGF7.
CONCLUSIONS
Our investigation provides novel insights into the evolutionary progression from gynecomastia to male breast cancer, shedding light on the pivotal role of CD13 in driving this transition. The identification of CD13 as a potential therapeutic target suggests the feasibility of CD13-targeted interventions, specifically tailored for male breast cancer treatment.
PubMed: 38888848
DOI: 10.1007/s13402-024-00964-4 -
Journal of Thoracic Disease May 2024Lung cancer is the most common cancer killer worldwide. Nearly 80 percent of lung cancers are diagnosed at advanced stages. Lack of access to medical care and...
BACKGROUND
Lung cancer is the most common cancer killer worldwide. Nearly 80 percent of lung cancers are diagnosed at advanced stages. Lack of access to medical care and undwerutilized lung cancer screening are key reasons for advanced diagnoses. We sought to understand the regional differences in presentation of lung cancer across Michigan. Utilizing a comprehensive cancer registry over 33 years, our goal was to examine associations between sociodemographic patient factors and diagnoses at advanced stages.
METHODS
The Michigan Cancer Registry was queried from 1985 to 2018 to include all new diagnoses of non-small cell lung cancer (NSCLC) using International Classification of Diseases for Oncology (ICD-O) version 3 codes. NSCLC was categorized as early, regional and distant disease. Advanced disease was considered to be any disease that was regional or distant. NSCLC rates were calculated and mapped at the zip code level using the 2010 population as the denominator and spatial empirical Bayes methodology. Regional hospital service areas were constructed using travel time to treatment from the patient's zip code centroid. Logistic regression models were estimated to investigate the significance of rural urban and travel time on level of disease at presentation. Kaplan-Meier and multivariate survival analysis was performed to evaluate the association between distance from the nearest medical center and length of survival controlling for known risk factors for lung cancer.
RESULTS
From 1985 to 2018, there were 141,977 patients in Michigan diagnosed with NSCLC. In 1985, men were 2.2 times more likely than women to be diagnosed but by 2018 women and men developed disease at equal rates. Mean age was 67.8 years. Among all patients with known stage of disease, 72.5% of patients were diagnosed with advanced disease. Regional and distant NSCLC rates were both higher in the northern parts of the state. Longer drive times in rural regions also significantly increased the likelihood of advanced NSCLC diagnoses, in particular regional lung cancer. Patients with longer drive times also experienced overall worse survival after controlling for other factors.
CONCLUSIONS
Regional disparities exist in Michigan for diagnoses of NSCLC at advanced stages. Factors such as lack of screening in urban regions and distances to treating institutions in rural areas likely contribute to the increased likelihood of advanced NSCLC. Future interventions should target the specific needs of residents to detect disease at earlier stages and improve overall outcomes.
PubMed: 38883653
DOI: 10.21037/jtd-24-205 -
JAMA Health Forum Jun 2024Millions of economically disadvantaged children depend on Medicaid for dental care, with states differing in whether they deliver these benefits using fee-for-service or...
IMPORTANCE
Millions of economically disadvantaged children depend on Medicaid for dental care, with states differing in whether they deliver these benefits using fee-for-service or capitated managed care payment models. However, there is limited research examining the association between managed care and the accessibility of dental services.
OBJECTIVE
To estimate the association between the adoption of managed care for dental services in Florida's Medicaid program and nontraumatic dental emergency department visits and associated charges.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used an event-study difference-in-differences design, leveraging Florida Medicaid's staggered adoption of managed care to examine its association with pediatric nontraumatic dental emergency department visits and associated charges. This study included all Florida emergency department visits from 2010 to 2014 in which the patient was 17 years or younger, the patient was a Florida resident, Medicaid paid for the visit, and a primary or secondary International Classification of Diseases, Ninth Revision, code was used to classify a nontraumatic dental condition. Analyses were conducted between May 2023 and April 2024.
EXPOSURE
The county of residence transitioning Medicaid dental services from fee-for-service to a fully capitated managed care program managed by a dental plan.
MAIN OUTCOMES AND MEASURES
The rate of nontraumatic dental emergency department visits per 100 000 pediatric Medicaid enrollees and the associated mean charges per visit. Nontraumatic dental emergency department visits are a well-documented proxy for access to dental care. Data on emergency department visit counts came from the Florida Agency for Health Care Administration. Medicaid population denominators were derived from the American Community Survey's 5-year estimates.
RESULTS
Among the 34 414 pediatric nontraumatic dental emergency department visits that met inclusion criteria across Florida's 67 counties, the mean (SD) age of patients was 8.11 (5.28) years, and 50.8% of patients were male. Of these, 10 087 visits occurred in control counties and 24 327 in treatment counties. Control counties generally had lower rates of NTDC ED visits per 100 000 enrollees compared with treatment counties (123.5 vs 132.7). Over the first 2.5 years of implementation, the adoption of managed care was associated with an 11.3% (95% CI, 4.0%-18.4%; P = .002) increase in nontraumatic dental emergency department visits compared with pre-implementation levels. There was no evidence that the average charge per visit changed.
CONCLUSIONS AND RELEVANCE
In this cohort study, Florida Medicaid's adoption of managed care for pediatric dental services was associated with increased emergency department visits for children, which could be associated with decreased access to dental care.
Topics: Humans; Medicaid; Emergency Service, Hospital; United States; Florida; Child; Managed Care Programs; Male; Female; Adolescent; Child, Preschool; Health Services Accessibility; Cohort Studies; Infant; Dental Care for Children; Emergency Room Visits
PubMed: 38874960
DOI: 10.1001/jamahealthforum.2024.1472 -
Statistical Methods in Medical Research Jun 2024Estimation of the 100 percent lethal dose () is of great interest to pharmacologists for assessing the toxicity of certain compounds. However, most existing literature...
Estimation of the 100 percent lethal dose () is of great interest to pharmacologists for assessing the toxicity of certain compounds. However, most existing literature focuses on the interval estimation of and little attention has been paid to its point estimation. Currently, the most commonly used method for estimating the is the maximum likelihood estimator (MLE), which can be represented as a ratio estimator, with the denominator being the slope estimated from the logistic regression model. However, the MLE can be seriously biased when the sample size is small, a common nature in such studies, or when the dose-response curve is relatively flat (i.e. the slope approaches zero). In this study, we address these issues by developing a novel penalised maximum likelihood estimator (PMLE) that can prevent the denominator of the ratio from being close to zero. Similar to the MLE, the PMLE is computationally simple and thus can be conveniently used in practice. Moreover, with a suitable penalty parameter, we show that the PMLE can (a) reduce the bias to the second order with respect to the sample size and (b) avoid extreme estimates. Through simulation studies and real data applications, we show that the PMLE generally outperforms the existing methods in terms of bias and root mean square error.
PubMed: 38865137
DOI: 10.1177/09622802241259174 -
Journal of Psychopharmacology (Oxford,... Jun 2024By manipulating inclusion criteria, one can prove whatever point one wishes in meta-analysis. This critique examines a recent meta-analysis claiming lithium...
By manipulating inclusion criteria, one can prove whatever point one wishes in meta-analysis. This critique examines a recent meta-analysis claiming lithium ineffectiveness for suicidality, based on three biased features: inclusion of many large studies specifically designed to exclude suicidality, producing zero suicide outcomes in all groups ( = 1856), thereby artificially decreasing statistical significance; arbitrary exclusion of all trials prior to the year 2000, thereby excluding two randomized clinical trials which demonstrated benefit for lithium; and underreporting of placebo suicide events in a recent randomized trial. It thereby created a smaller effect size (two suicides with lithium versus five with placebo = RR = 0.42), though still beneficial for lithium, and a larger denominator of no events (total for included studies = 2578), leading to the claim of statistical non-significance (95% confidence intervals (CIs) 0.1-4.5). The same literature can be analyzed including the two excluded older studies, and including the two placebo deaths in the recent trial, producing a larger effect size (two suicides with lithium versus nine with placebo, RR = 0.25). Furthermore, uninformative studies with no events could be excluded (total for included studies = 1203), as is standard practice in meta-analysis, producing statistically significant results (95% CIs 0.05, 0.83). This more complete, more accurate, and less biased meta-analysis is provided in this article.In short, including all studies with non-zero suicide outcomes, there is clear benefit for lithium. The recent meta-analysis is a classic example of pseudoscience, using scientific technique superficially to confirm, rather than refute, one's own opinions.
PubMed: 38863399
DOI: 10.1177/02698811241257833 -
European Journal of Neurology Jun 2024Hereditary spastic paraplegias (HSPs) comprise a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness. Botulinum toxin has...
BACKGROUND AND PURPOSE
Hereditary spastic paraplegias (HSPs) comprise a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness. Botulinum toxin has been approved for lower limb spasticity following stroke and cerebral palsy, but its effects in HSPs remain underexplored. We aimed to characterize the effects of botulinum toxin on clinical, gait, and patient-reported outcomes in HSP patients and explore the potential of mobile digital gait analysis to monitor treatment effects and predict treatment response.
METHODS
We conducted a prospective, observational, multicenter study involving ambulatory HSP patients treated with botulinum toxin tailored to individual goals. Comparing data at baseline, after 1 month, and after 3 months, treatment response was assessed using clinical parameters, goal attainment scaling, and mobile digital gait analysis. Machine learning algorithms were used for predicting individual goal attainment based on baseline parameters.
RESULTS
A total of 56 patients were enrolled. Despite the heterogeneity of treatment goals and targeted muscles, botulinum toxin led to a significant improvement in specific clinical parameters and an improvement in specific gait characteristics, peaking at the 1-month and declining by the 3-month follow-up. Significant correlations were identified between gait parameters and clinical scores. With a mean balanced accuracy of 66%, machine learning algorithms identified important denominators to predict treatment response.
CONCLUSIONS
Our study provides evidence supporting the beneficial effects of botulinum toxin in HSP when applied according to individual treatment goals. The use of mobile digital gait analysis and machine learning represents a novel approach for monitoring treatment effects and predicting treatment response.
PubMed: 38859620
DOI: 10.1111/ene.16367 -
Journal of Pharmacological and... Jun 2024Determination of a drug's potency in blocking the hERG channel is an established safety pharmacology study. Best practice guidelines have been published for reliable...
Supporting an integrated QTc risk assessment using the hERG margin distributions for three positive control agents derived from multiple laboratories and on multiple occasions.
BACKGROUND
Determination of a drug's potency in blocking the hERG channel is an established safety pharmacology study. Best practice guidelines have been published for reliable assessment of hERG potency. In addition, a set of plasma concentration and plasma protein binding fraction data were provided as denominators for margin calculations. The aims of the current analysis were five-fold: provide data allowing creation of consistent denominators for the hERG margin distributions of the key reference agents, explore the variation in hERG margins within and across laboratories, provide a hERG margin to 10 ms QTc prolongation based on several newer studies, provide information to use these analyses for reference purposes, and provide recommended hERG margin 'cut-off' values.
METHODS
The analyses used 12 hERG IC 'best practice' data sets (for the 3 reference agents). A group of 5 data sets came from a single laboratory. The other 7 data sets were collected by 6 different laboratories.
RESULTS
The denominator exposure distributions were consistent with the ICH E14/S7B Training Materials. The inter-occasion and inter-laboratory variability in hERG IC values were comparable. Inter-drug differences were most important in determining the pooled margin variability. The combined data provided a robust hERG margin reference based on best practice guidelines and consistent exposure denominators. The sensitivity of hERG margin thresholds were consistent with the sensitivity described over the course of the last two decades.
CONCLUSION
The current data provide further insight into the sensitivity of the 30-fold hERG margin 'cut-off' used for two decades. Using similar hERG assessments and these analyses, a future researcher can use a hERG margin threshold to support a negative QTc integrated risk assessment.
PubMed: 38852689
DOI: 10.1016/j.vascn.2024.107524 -
JMIR Medical Informatics Jun 2024Increasing and substantial reliance on Electronic health records (EHR) and data types (i.e., diagnosis (Dx), medication (Rx), laboratory (Lx)) demands assessment of its...
BACKGROUND
Increasing and substantial reliance on Electronic health records (EHR) and data types (i.e., diagnosis (Dx), medication (Rx), laboratory (Lx)) demands assessment of its data quality (DQ) as a fundamental approach; especially since there is need to identify appropriate denominator population with chronic conditions, such as Type-2 Diabetes (T2D), using commonly available computable phenotype definitions (phenotype).
OBJECTIVE
To bridge this gap, our study aims to assess how issues of EHR DQ, and variations and robustness (or lack thereof) in phenotypes may have potential impact in identifying denominator population.
METHODS
Approximately 208k patients with T2D were included in our study using retrospective EHR data of Johns Hopkins Medical Institution (JHMI) during 2017-2019. Our assessment included 4 published phenotypes, and 1 definition from a panel of experts at Hopkins. We conducted descriptive analyses of demographics (i.e., age, sex, race, ethnicity), healthcare utilization (inpatient and emergency room visits), and average Charlson Comorbidity score of each phenotype. We then used different methods to induce/simulate DQ issues of completeness, accuracy and timeliness separately across each phenotype. For induced data incompleteness, our model randomly dropped Dx, Rx, and Lx codes independently at increments of 10%; for induced data inaccuracy, our model randomly replaced a Dx or Rx code with another code of the same data type and induced 2% incremental change from -100% to +10% in Lx result values; and lastly, for timeliness, data was modeled for induced incremental shift of date records by 30 days up to a year.
RESULTS
Less than a quarter (23%) of population overlapped across all phenotypes using EHR. The population identified by each phenotype varied across all combination of data types. Induced incompleteness identified fewer patients with each increment, for e.g., at 100% diagnostic incompleteness, Chronic Conditions Data Warehouse (CCW) phenotype identified zero patients as its phenotypic characteristics included only Dx codes. Induced inaccuracy and timeliness similarly demonstrated variations in performance of each phenotype and therefore, resulting in fewer patients being identified with each incremental change.
CONCLUSIONS
We utilized EHR data with Dx, Rx, and Lx data types from a large tertiary hospital system to understand the T2D phenotypic differences and performance. We learned how issues of DQ, using induced DQ methods, may impact identification of the denominator populations upon which clinical (e.g., clinical research and trials, population health evaluations) and financial/operational decisions are made. The novel results from our study may inform in shaping a common T2D computable phenotype definition that can be applicable to clinical informatics, managing chronic conditions, and additional healthcare industry-wide efforts.
PubMed: 38850555
DOI: 10.2196/56734 -
Bundesgesundheitsblatt,... Jun 2024There are significant regional differences in antibiotic prescribing behaviour. The reasons for this are still largely unknown. Beneath demographic and morbidity-related...
BACKGROUND
There are significant regional differences in antibiotic prescribing behaviour. The reasons for this are still largely unknown. Beneath demographic and morbidity-related factors, doctor-specific or "cultural" factors may also play a role. A differentiated analysis including diagnostic data is needed to put these data into context.
METHODS
A data analysis with secondary data available via the Westphalia-Lippe Association of Statutory Health Insurance Physicians (KVWL) was conducted on infection diagnoses and antibiotic prescriptions of outpatient paediatricians in the KV district of Bielefeld from 2015 to 2018. In addition, algorithmized 1:1 connections between diagnoses and prescriptions were performed.
RESULTS
For 262,969 "medication patients" (AMP), 28,248 antibiotic prescriptions and 90,044 infection diagnoses were evaluated, from which 11,131 1:1 connections could be generated. Concerning the prescribing behaviour of individual paediatric GP offices, after adjusting for the denominator AMP and despite a comparable age and gender structure, there were some significant differences. This affected both the frequency of prescriptions and the qualitative composition of the substance groups prescribed.
DISCUSSION
The differences in antibiotic prescribing behaviour, even at GP office level, cannot be adequately explained by the demographic composition or different morbidities of the respective clientele. Individual attitudes and local prescribing cultures are likely to play a relevant role. To address these offers an important approach for antibiotic stewardship (ABS). In addition to the area of outpatient paediatrics presented here, the methodology described can also be used as a model for more detailed analysis in other outpatient speciality groups.
PubMed: 38837054
DOI: 10.1007/s00103-024-03891-9 -
Journal of Managed Care & Specialty... Jun 2024Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased... (Comparative Study)
Comparative Study
Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.
BACKGROUND
Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder.
OBJECTIVE
To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder.
METHODS
South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests.
RESULTS
A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; < 0.0001), and higher persistence (82% vs 64%; < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, = 0.90; 3.68 vs 2.96 emergency department visits, = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort ( < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; < 0.0001).
CONCLUSIONS
Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.
Topics: Humans; Antipsychotic Agents; Medicaid; Schizophrenia; Male; Female; Adult; Medication Adherence; United States; Middle Aged; South Carolina; Administration, Oral; Young Adult; Delayed-Action Preparations; Patient Acceptance of Health Care; Adolescent; Retrospective Studies; Aged; Injections; Health Care Costs; Psychotic Disorders
PubMed: 38824623
DOI: 10.18553/jmcp.2024.30.6.549