Tag: pubmed

Medicina (B Aires). 2023;83(6):890-899.

ABSTRACT

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is an epileptic syndrome with onset in childhood and adolescence with myoclonus, absences, and generalized tonic-clonic seizures. Reflex stimuli such as sensitivity to light or photosensitivity, eyelid opening and closing, and praxis induction produce epileptiform discharges and seizures. These reflex triggers are not all systematically studied.

OBJECTIVE: Examine reflex features in patients with JME.

METHODS: One hundred adolescents and adults with JME who received different anti-seizure treatments were evaluated consecutively. A standard electroencephalogram was performed with an intermittent light stimulation (SLI) protocol and another for the evaluation of praxias through neurocognitive activity (CNA). The statistical analysis was descriptive and of correlation with a p > 0.05.

RESULTS: Current age was 28±11 (14-67). The seizure began at 15 years ±3 (Range 8-25 years). They presented myoclonus and generalized tonic-clonic seizures in 58%. 50% received valproic acid and 31% continued with seizures. Epileptiform discharges at rest 20%; hyperventilation 30%; eyelid opening and closing 12%; photoparoxysmal response in SLI 40%; CNA 23%. Higher percentage of discharges and delay in performing CNA in those who presented seizures. Valproic acid compared to other drugs did not demonstrate superiority in seizure control.

CONCLUSIONS: These findings confirm the importance of studying reflex traits for diagnosis, follow-up, and therapeutic control.

PMID:38117708

Cancer Biol Ther. 2024 Dec 31;25(1):2287120. doi: 10.1080/15384047.2023.2287120. Epub 2023 Dec 20.

ABSTRACT

This study was designed to evaluate the diagnostic efficacy of relevant parameters of ¹⁸F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in predicting the pathological grade of primary prostate cancer. Briefly, a prospective analysis was performed on 53 patients diagnosed with prostate cancer by systematic puncture biopsy, followed by ¹⁸F-PSMA-1007 PET/CT examination prior to treatment within 10 d. The patients were grouped in accordance with the Gleason grading system revised by the International Association of Urology Pathology (ISUP). They were divided into high-grade group (ISUP 4-5 group) and low-grade group (ISUP 1-3 group). The differences in maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), intraprostatic PSMA-derived tumor volume (iPSMA-TV), and intraprostatic total lesion PSMA (iTL-PSMA) between the high- and low-grade group were statistically significant (p < .001). No significant difference was found for mean standardized uptake value (SUVmean) between the high- and low-grade groups (Z = -1.131, p = .258). Besides, binary multivariate logistic regression analysis showed that only iPSMA-TV and iTL-PSMA were independent predictors of the pathological grading, for which the odds ratios were 18.821 [95% confidence interval (CI): 2.040-173.614, p = .010] and 0.758 (95% CI: 0.613-0.938, p = .011), respectively. The area under the ROC of this regression model was 0.983 (95% CI: 0.958-1.00, p < .001). Only iTL-PSMA was a significant parameter for distinguishing ISUP-4 and ISUP-5 groups (Z = -2.043, p = .041). In a nutshell, ¹⁸F-PSMA-1007 PET/CT has good application value in predicting the histopathological grade of primary prostate cancer. Three-dimensional volume metabolism parameters iPSMA-TV and iTL-PSMA were found to be independent predictors for pathological grade.

PMID:38117551 | DOI:10.1080/15384047.2023.2287120

Cancer Res. 2023 Dec 20. doi: 10.1158/0008-5472.CAN-23-0900. Online ahead of print.

ABSTRACT

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers [odds ratio (OR) = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18×10-16], which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor HLTF. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis.

PMID:38117513 | DOI:10.1158/0008-5472.CAN-23-0900

JAMA Netw Open. 2023 Dec 1;6(12):e2347195. doi: 10.1001/jamanetworkopen.2023.47195.

ABSTRACT

IMPORTANCE: Home-delivered meals promote food security and independence among homebound older adults. However, it is unclear which of the 2 predominant modes of meal delivery, daily-delivered vs mailed (or drop-shipped) frozen meals, promotes community living for homebound older adults with dementia.

OBJECTIVE: To assess the risk of nursing home admission within 6 months between homebound individuals receiving daily-delivered vs drop-shipped frozen meals.

DESIGN, SETTING, AND PARTICIPANTS: This pilot, multisite, 2-arm, pragmatic clinical trial included older adults with self-reported dementia on waiting lists for meals at 3 Meals on Wheels (MOW) programs in Texas and Florida between April 7 and October 8, 2021, to assess time to nursing home placement.

INTERVENTIONS: Participants were randomized to receive either meals delivered by an MOW driver or frozen meals that were mailed to participants’ homes every 2 weeks. Participants received their assigned intervention for up to 6 months.

MAIN OUTCOMES AND MEASURES: The primary study outcome was days from randomization to a Minimum Data Set nursing home admission assessment within 6 months. Feasibility of conducting this type of study was examined by tracking enrollment, examining baseline characteristics, monitoring participants’ intervention fidelity, measuring the proportion of participants linked with Centers for Medicare & Medicaid Services (CMS) data, and analyzing the primary study outcome.

RESULTS: Among 325 eligible participants who were randomized, 243 enrolled in the study (mean [SD] age, 81 [8.0] years; 152 (62.6%) were female): 128 to the daily-delivered meals group and 115 to the drop-shipped frozen meals group; 119 participants (49.0%) lived alone. Among the total participants enrolled, 227 (93.4%) were linked deterministically to their CMS data; probabilistic methods were used to link the remaining 16 participants (6.6%). At 6 months from randomization, 160 participants (65.8%) were still receiving meals, and 25 (10.1%; 95% CI, 6.3%-14.0%) were admitted to a nursing home. After adjusting for sex, race and ethnicity, age, program, and living arrangement and the use of death as a censoring event, the adjusted log hazard ratio of nursing home placement between daily-delivered and drop-shipped frozen meals was -0.67 (95% CI, -1.52 to 0.19).

CONCLUSIONS AND RELEVANCE: This pilot randomized clinical trial demonstrated the feasibility of enrolling participants with self-reported dementia on waiting lists at MOW programs, linking their data, and evaluating outcomes. While this pilot study was not powered to detect meaningful, statistically significant differences in nursing home placement, its feasibility and initial results warrant exploration in a follow-on, adequately powered trial.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04850781.

PMID:38117500 | DOI:10.1001/jamanetworkopen.2023.47195

JAMA Netw Open. 2023 Dec 1;6(12):e2348439. doi: 10.1001/jamanetworkopen.2023.48439.

ABSTRACT

IMPORTANCE: Psychiatric conditions in parents are associated with many psychiatric and nonpsychiatric outcomes in offspring. However, it remains unknown whether this intergenerational transmission is attributable to broader psychopathology comorbidity or to specific conditions.

OBJECTIVE: To estimate associations between general and specific psychopathology factors in parents and a wide range of register-based outcomes in their offspring.

DESIGN, SETTING, AND PARTICIPANTS: This Swedish national register-based cohort study included 2 947 703 individuals born between 1970 and 2000 and followed up with participants through December 31, 2013. Statistical analysis was performed from October 2022 to October 2023.

EXPOSURES: Hierarchical factor model consisting of 1 general and 3 specific psychopathology factors fit to 9 parental psychiatric diagnoses and violent criminal court convictions.

MAIN OUTCOMES AND MEASURES: A total of 31 outcomes were measured in offspring and sorted into 6 broad clusters: psychotic-like outcomes, neurodevelopmental outcomes, internalizing outcomes, externalizing outcomes, behavior and accidents, and psychosocial outcomes.

RESULTS: Of 2 947 703 individuals, 1 518 252 (51.5%) were male, and the mean (SD) age at the end of follow-up was 28.7 (8.9) years. The general psychopathology factor in parents was significantly associated with all 31 offspring outcomes (range: odds ratio [OR] for accidents, 1.08 [95% CI, 1.07-1.08] to OR for social welfare recipiency, 1.40 [95% CI, 1.39-1.40]), which means that children whose parents scored 1 SD above the mean on the general psychopathology factor had an 8% to 40% higher odds of different studied outcomes. The specific psychotic factor in parents was primarily associated with all 5 psychotic-like outcomes (range: OR for prescription of antiepileptics, 1.05 [95% CI, 1.04-1.06] to OR for schizophrenia, 1.25 [95% CI, 1.23-1.28]) and the specific internalizing factor in parents was primarily associated with all 6 internalizing outcomes (range: OR for prescription of anxiolytics, 1.10 [95% CI, 1.09-1.10] to OR for depression, 1.13 [95% CI, 1.12-1.13]) and all 6 neurodevelopmental outcomes (range: OR for intellectual disability, 1.02 [95% CI, 1.01-1.03] to OR for autism spectrum disorder, 1.10 [95% CI, 1.09-1.11]) in offspring. The specific externalizing factor in parents was associated with all 6 externalizing outcomes (range: OR for violent crimes, 1.21 [95% CI, 1.19-1.23] to OR for oppositional defiant disorder, 1.32 [95% CI, 1.32-1.33]) and all 6 internalizing outcomes (range: OR for obsessive-compulsive disorder, 1.01 [95% CI, 1.00-1.02] to OR for posttraumatic stress disorder, 1.13 [95% CI, 1.12-1.13]) in offspring.

CONCLUSIONS AND RELEVANCE: This cohort study of the Swedish population suggests that the intergenerational transmission of psychiatric conditions across different types of spectra may largely be attributable to a parental general psychopathology factor, whereas specific factors appeared to be primarily responsible for within-spectrum associations between parents and their offspring. Professionals who work with children (eg, child psychologists, psychiatrists, teachers, and social workers) might benefit from taking the total number of parental psychiatric conditions into account, regardless of type, when forecasting child mental health and social functions.

PMID:38117496 | DOI:10.1001/jamanetworkopen.2023.48439

JAMA Netw Open. 2023 Dec 1;6(12):e2348557. doi: 10.1001/jamanetworkopen.2023.48557.

ABSTRACT

IMPORTANCE: There is interest in reducing long-term benzodiazepine prescribing given harms associated with use, but the cumulative risks or benefits of discontinuation are unknown.

OBJECTIVE: To identify the association of benzodiazepine discontinuation with mortality and other adverse events among patients prescribed stable long-term benzodiazepine therapy, stratified by baseline opioid exposure.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study with a trial emulation approach included data from a US commercial insurance database between January 1, 2013, and December 31, 2017. Eligible participants were adults with stable long-term benzodiazepine prescription treatment. Data were analyzed between December 2022 and November 2023.

EXPOSURE: Benzodiazepine discontinuation, defined as no benzodiazepine prescription coverage for 31 consecutive days identified during a 6-month grace period after baseline.

MAIN OUTCOME AND MEASURES: Mortality during 12 months of follow-up; secondary outcomes included nonfatal overdose, suicide attempt or self-inflicted injury, suicidal ideation, and emergency department use, identified in medical claims. Inverse probability weighting was used to adjust for baseline confounders that potentially affected treatment assignment and censoring due to death or disenrollment. Primary analysis used an intention-to-treat approach; a secondary per-protocol analysis estimated associations after accounting for nonadherence. Analyses were stratified by opioid use.

RESULTS: The study included 213 011 (136 609 female [64.1%]; mean [SD] age, 62.2 [14.9] years; 2953 Asian [1.4%], 18 926 Black [8.9%], 22 734 Hispanic [10.7%], and 168 398 White [60.2%]) and 140 565 (91 811 female [65.3%]; mean [SD] age, 61.1 [13.2] years; 1319 Asian [0.9%], 15 945 Black [11.3%], 11 989 Hispanic [8.5%], and 111 312 White [79.2%]) patients with stable long-term benzodiazepine use without and with opioid exposure, respectively. Among the nonopioid exposed, the adjusted cumulative incidence of death after 1 year was 5.5% (95% CI, 5.4%-5.8%) for discontinuers, an absolute risk difference of 2.1 percentage points (95% CI, 1.9-2.3 percentage points) higher than for nondiscontinuers. The mortality risk was 1.6 (95% CI, 1.6-1.7) times that of nondiscontinuers. Among those with opioid exposure, the adjusted cumulative incidence of death was 6.3% (95% CI, 6.0%-6.6%) for discontinuers, an absolute risk difference of 2.4 percentage points (95% CI, 2.2-2.7 percentage points) higher than for nondiscontinuers and a mortality risk 1.6 (95% CI, 1.5-1.7) times that of nondiscontinuers. Cumulative incidence of secondary outcomes was also higher among discontinuers.

CONCLUSIONS AND RELEVANCE: This study identifies small absolute increases in risk of harms among patients with stable long-term prescription benzodiazepine treatment who appear to discontinue relative to continuing treatment, including those with and without recent prescription opioid exposure. Policy broadly promoting benzodiazepine discontinuation may have unintended risks.

PMID:38117495 | DOI:10.1001/jamanetworkopen.2023.48557

JAMA Netw Open. 2023 Dec 1;6(12):e2348814. doi: 10.1001/jamanetworkopen.2023.48814.

ABSTRACT

IMPORTANCE: PIK3CA mutations may be associated with outcomes of patients with ERBB2/HER2-positive early breast cancer (EBC).

OBJECTIVES: To assess if PIK3CA mutations among patients with ERBB2/HER2-positive EBC are associated with treatment response and outcome, and if these associations vary by hormone receptor (HR) status or intrinsic molecular subtype (IMS).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study derived data on 184 patients from the phase 3 neoadjuvant Cancer and Leukemia Group B (CALGB) 40601 trial that enrolled patients with ERBB2/HER2-positive EBC in North America between January 1, 2008, and December 31, 2012. Participants received neoadjuvant paclitaxel with trastuzumab, lapatinib, or both. Statistical analysis was performed from March 23, 2022, to March 9, 2023.

EXPOSURES: Gene expression profiling by RNA sequencing with Prediction Analysis of Microarray 50-determined IMS and PIK3CA mutations from whole-exome sequencing were obtained from pretreatment biopsies from 184 of 305 trial participants.

MAIN OUTCOMES AND MEASURES: The primary end point was pathologic complete response (pCR) and the secondary end point of event-free survival (EFS). The association of PIK3CA mutations with pCR and EFS by HR status and IMS was estimated using logistic and Cox proportional hazards regression models.

RESULTS: All 184 participants were women, with a median age of 49 years (range 24-75 years). A total of 121 participants (66%) had clinical stage II tumors; 32 (17%) had PIK3CA mutations, most frequently H1047R (38% [12 of 32]) and E545K (22% [7 of 32]). PIK3CA mutations were present in 20 of 102 cases of HR-positive EBC (20%) and 12 of 82 cases HR-negative EBC (15%) and varied by IMS (luminal B, 9 of 25 [36%]; luminal A, 2 of 21 [10%]; and ERBB2/HER2-enriched tumors, 19 of 102 [19%]). Pathologic complete response rates were lower in PIK3CA mutated than PIK3CA wild type in the overall population (34% [11 of 32] vs 49% [74 of 152]; P = .14) and were significantly different among those receiving trastuzumab (30% [7 of 23] vs 54% [63 of 117]; P = .045). At a median follow-up of 9 years, PIK3CA mutations were significantly associated with worse EFS in the overall cohort (hazard ratio, 2.58 [95% CI, 1.24-5.35]; P = .01), which persisted in a multivariable model including pCR, HR status, stage, and IMS (hazard ratio, 2.52 [95% CI, 1.16-5.47]; P = .02). The negative association of PIK3CA mutation was significant in HR-positive (hazard ratio, 3.60 [95% CI, 1.45-8.96]; P = .006) and luminal subtypes (hazard ratio, 4.84 [95% CI, 1.08-21.70]; P = .04), but not in nonluminal and HR-negative tumors.

CONCLUSIONS AND RELEVANCE: In ERBB2/HER2-positive EBC, PIK3CA mutations were associated with lower pCR rates and independently associated with worse long-term EFS. These findings appear to be associated with PIK3CA mutations in HR-positive and luminal EBC.

PMID:38117494 | DOI:10.1001/jamanetworkopen.2023.48814

Gen Thorac Cardiovasc Surg. 2023 Dec 20. doi: 10.1007/s11748-023-01995-8. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to statistically analyze the factors that influence cardiovascular surgery recruitment.

METHODS: Fifth- and sixth-year medical students and first-year residents who participated in cardiovascular surgery-related events at our university over a 10-year period from April 2013 to August 2022 were included. The primary endpoint was admission to the department of cardiovascular surgery. Gender, participation in sixth-year elective clinical training, participation in national academic conferences, participation in cardiovascular surgery summer school, and the cost of participation in these events (airfares and lodging) were included as analytic factors.

RESULTS: Fifty-three participants attended cardiovascular surgery events during the study period. The sample included 48 males (84%) and 9 females (16%), and 3 fifth-year medical students (5%), 45 sixth-year students (79%), and 9 students in their first year of clinical training (16%). Eighteen (32%) of the participants eventually joined the department. Gender, participation in national academic conferences, cardiovascular surgery summer school, and cost of participation were not significantly related to the decision to join the department, but participation in elective clinical training was significantly positively related to the decision to join the department for sixth-year students (p < 0.01).

CONCLUSIONS: We statistically analyzed the factors involved in the recruitment of students and initial clinical residents to the department of cardiovascular surgery. The results showed that participation in elective clinical training was significantly positively associated with the decision to join the department, suggesting that efforts to encourage participation in elective clinical training are important.

PMID:38117430 | DOI:10.1007/s11748-023-01995-8

Neurol Sci. 2023 Dec 20. doi: 10.1007/s10072-023-07235-4. Online ahead of print.

ABSTRACT

The purpose of this study was to systematically evaluate the efficacy of repetitive transcranial magnetic stimulation in children with cerebral palsy and to compare the differences in efficacy of different treatment parameters. Computer searches of PubMed, Embase, Cochrane Library, Scopus, Web of Science, China Knowledge Network, Wanfang Data Knowledge Service Platform, Vipshop and China Biomedical Literature Database were conducted to collect randomized controlled trials (RCTs) of TMS to improve function in children with cerebral palsy. The search period was from the establishment of the database to April 2023. Two researchers independently screened the literature and extracted data information, and the risk of bias was assessed for the included studies using the Cochrane Systematic Evaluation Manual 5.1.0. Statistical analysis was performed using RevMan 5.4 and Stata software. A total of 18 studies containing 1675 patients with cerebral palsy were included, and r-TMS did not differ significantly from other treatments in improving language function [MD = 2.80, 95% CI (-1.51, 7.11), Z = 1.27, P = 0.20] after treatment. The results of the reticulated meta-analysis showed the best probability ranking of the effect of three different frequencies of r-TMS on motor function scores in children with cerebral palsy: combined LF-rTMS + HF-rTMS (49.8%) > LF-rTMS (45.6%) > HF-rTMS (4.6%) > conventional rehabilitation (0%). Publication bias showed no significant asymmetry in the inverted funnel plot, but the possibility of publication bias could not be excluded. The results of this study showed that r-TMS was not statistically significant in improving language function in children with cerebral palsy compared to conventional treatment. r-TMS was almost unanimously significantly effective in motor function in children with cerebral palsy according to current literature data, and the combined high- and low-frequency transcranial magnetic therapy was better than low-frequency transcranial magnetic therapy.

PMID:38117402 | DOI:10.1007/s10072-023-07235-4

Patient. 2023 Dec 20. doi: 10.1007/s40271-023-00666-3. Online ahead of print.

ABSTRACT

INTRODUCTION: The health of a community depends on the health of its individuals; therefore, individual health behaviour can implicitly affect the health of the entire community. This is particularly evident in the case of infectious diseases. Because the level of prosociality in a community might determine the effectiveness of health programmes, prosocial behaviour may be a crucial disease-control resource. This study aimed to extend the literature on prosociality and investigate the role of altruism in antibiotic decision making.

METHODS: A discrete choice experiment was conducted to assess the influence of altruism on the general public’s preferences regarding antibiotic treatment options. The survey was completed by 378 Swedes. Latent class analysis models were used to estimate antibiotic treatment characteristics and preference heterogeneity. A three-class model resulted in the best model fit, and altruism significantly impacted preference heterogeneity.

RESULTS: Our findings suggest that people with higher altruism levels had more pronounced preferences for treatment options with lower contributions to antibiotic resistance and a lower likelihood of treatment failure. Furthermore, altruism was statistically significantly associated with sex, education, and health literacy.

CONCLUSIONS: Antibiotic awareness, trust in healthcare systems, and non-discriminatory priority setting appear to be structural elements conducive to judicious and prosocial antibiotic behaviour. This study suggests that prosocial messages could help to decrease the demand for antibiotic treatments.

PMID:38117400 | DOI:10.1007/s40271-023-00666-3