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Nevin Manimala Statistics

Intergenerational Transmission of Psychiatric Conditions and Psychiatric, Behavioral, and Psychosocial Outcomes in Offspring

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

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Benzodiazepine Discontinuation and Mortality Among Patients Receiving Long-Term Benzodiazepine Therapy

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

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Association of PIK3CA Mutation With Pathologic Complete Response and Outcome by Hormone Receptor Status and Intrinsic Subtype in Early-Stage ERBB2/HER2-Positive Breast Cancer

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

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Multivariate analysis of the factors affecting medical students’ decision to join the cardiovascular surgery department

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

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Therapeutic effects of repetitive transcranial magnetic stimulation in patients with cerebral palsy: a systematic review and network meta-analysis

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

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Prosocial Behaviour and Antibiotic Resistance: Evidence from a Discrete Choice Experiment

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

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Oncogene-induced senescence in meningiomas-an immunohistochemical study

J Neurooncol. 2023 Dec 20. doi: 10.1007/s11060-023-04532-y. Online ahead of print.

ABSTRACT

PURPOSE: Meningiomas are tumours originating from meningothelial cells, the majority belonging to grade 1 according to the World Health Organization classification of the tumours of the Central Nervous System. Factors contributing to the progression to the higher grades (grades 2 and 3) have not been elucidated yet. Senescence has been proposed as a potential mechanism constraining the malignant transformation of tumours. Senescence-associated beta-galactosidase (SA-β-GAL) and inhibitors of cyclin-dependent kinases p16 and p21 have been suggested as senescence markers.

METHODS: We analysed 318 meningiomas of total 343 (178 grade 1, 133 grade 2 and 7 grade 3). Tissue microarrays were constructed and stained immunohistochemically, using antibodies for SA-β-GAL, p16 and p21.

RESULTS: The positive correlation of the tumour grade with the expression of p16 (p = 0.016) and SA-β-GAL (p = 0.002) was observed. The expression of p16 and SA-β-GAL was significantly higher in meningiomas grade 2 compared to meningiomas grade 1 (p = 0.006 and p = 0.004, respectively). SA-β-GAL positivity positively correlated with p16 and p21 in the whole cohort. In grade 2 meningiomas, a positive correlation was only between SA-β-GAL and p16. Correlations of senescence markers in meningiomas grade 2 were not present.

CONCLUSION: Our findings suggest the senescence activation in meningiomas grade 2 as a potential mechanism for the restraining of tumour growth and give hope for applying of promising senolytic therapy.

PMID:38117375 | DOI:10.1007/s11060-023-04532-y

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Metals in species of the Cambeva (Teleostei: Trichomycteridae) genus of the Iguaçu River basin (Brazil)

Environ Monit Assess. 2023 Dec 20;196(1):68. doi: 10.1007/s10661-023-12195-5.

ABSTRACT

The population growth is connected to the demand for resources and waste disposal in water. Metals are among several pollutants affecting aquatic ecosystems, posing risks to biota when in high concentrations. Metals can present a great danger to the aquatic ecosystem because they are not degradable and can bioaccumulate. Many rivers are already considered highly polluted. Among them is the Iguaçu River, located in southern Brazil, which is recognized for the Iguaçu Falls and its rate of endemism. One species of the Cambeva genus is among the endemic species found in the Iguaçu River and is threatened with extinction due to anthropization. Thus, we aimed to evaluate and compare the concentrations of copper, zinc, iron, lead, manganese, and cadmium in Cambeva stawiarski and Cambeva sp. 1 in four different streams of the Iguaçu River (Brazil). We collected 20 fish in two municipalities along the Iguaçu River tributaries. The results showed a statistical difference in the metal concentrations in different species and locations, mainly manganese, iron, and copper, observed in both species and municipalities and cadmium, which showed a statistical difference only for C. sp1. Fish from agricultural regions generally had the highest concentrations of metals, some above the permitted limits. Cadmium was found at high concentrations, generating great ecological concern since it is one of the most toxic metals, even in small quantities. The lack of limits in Brazilian legislation makes it challenging to predict the long-term effects of iron.

PMID:38117368 | DOI:10.1007/s10661-023-12195-5

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Impact of diastolic pulmonary gradient and pulmonary vascular remodeling on survival after left ventricular assist device implantation and heart transplantation

Egypt Heart J. 2023 Dec 20;75(1):102. doi: 10.1186/s43044-023-00428-4.

ABSTRACT

BACKGROUND: The left ventricular assist devices (LVADs) are increasingly used for advanced heart failure as a bridge to heart transplantation or as a destination therapy. The aim of this study was to investigate the changes of diastolic pulmonary gradient (DPG), pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) after LVAD implantation and their impact on survival after LVAD and heart transplantation.

RESULTS: A total of 73 patients who underwent LVAD (HeartMate III) implantation between 2016 and 2022 were retrospectively studied. According to pre-LVAD catheterization, 49 (67.1%) patients had DPG < 7 mmHg and 24 (32.9%) patients had DPG ≥ 7 mmHg. The patients with a pre-VAD DPG ≥ 7 mmHg had higher frequencies of right ventricular (RV) failure (p < 0.001), RVAD insertion (p < 0.001), need for renal replacement therapy (p = 0.002), total mortality (p = 0.036) and on-VAD mortality (p = 0.04) with a longer ICU stay (p = 0.001) compared to the patients with DPG < 7 mmHg. During the follow-up period of 38 (12-60) months, 24 (32.9%) patients died. Pre-LVAD DPG ≥ 7 mmHg (adjusted HR 1.83, 95% CI 1.21-6.341, p = 0.039) and post-LVAD DPG ≥ 7 mmHg (adjusted HR 3.824, 95% CI 1.482-14.648, p = 0.002) were associated with increased risks of mortality. Neither pre-LVAD TPG ≥ 12 (p = 0.505) nor post-LVAD TPG ≥ 12 mmHg (p = 0.122) was associated with an increased risk of death. Pre-LVAD PVR ≥ 3 WU had a statistically insignificant risk of mortality (HR 2.35, 95% CI 0.803-6.848, p = 0.119) while post-LVAD PVR ≥ 3 WU had an increased risk of death (adjusted HR 2.37, 95% CI 1.241-7.254, p = 0.038). For post-transplantation mortality, post-LVAD DPG ≥ 7 mmHg (p = 0.55), post-LVAD TPG ≥ 12 mmHg (p = 0.85) and PVR ≥ 3 WU (p = 0.54) did not have statistically increased risks. The logistic multivariable regression showed that post-LVAD PVR ≥ 3 WU (p = 0.013), post-LVAD DPG ≥ 7 mmHg (p = 0.026) and RVF (p = 0.018) were the predictors of mortality after LVAD implantation. Pre-LVAD DPG ≥ 7 mmHg (p < 0.001) and pre-LVAD PVR ≥ 3 WU (p = 0.036) were the predictors of RVF after LVAD implantation.

CONCLUSIONS: Persistently high DPG was associated with right ventricular failure and mortality after LVAD implantation rather than after heart transplantation. DPG is a better predictor of pulmonary vascular remodeling compared to TPG and PVR. Further larger prospective studies are required in this field due to the growing numbers of patients with advanced heart failure, as possible candidates for LVAD implantation, and limitations of heart transplantation.

PMID:38117355 | DOI:10.1186/s43044-023-00428-4

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Association between occupational noise and obesity: a retrospective cohort study in China

Int Arch Occup Environ Health. 2023 Dec 20. doi: 10.1007/s00420-023-02032-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the relationship between occupational noise, and obesity and body mass index (BMI) changes.

METHODS: Baseline data were collected from participants (n = 1264) who were followed for 6 years in a retrospective study. The noise exposure level (LAeq,8h) was determined by equivalent continuous weighted sound pressure levels using the fixed-point surveillance method for noise monitoring. The cumulative noise exposure (CNE) level was determined using the equal energy formula, which is based on exposure history and level.

RESULTS: The incidence of obesity at low (RR = 2.364, 95% CI 1.123-4.739]), medium (RR = 3.921, 95% CI 1.946-7.347]), high (RR = 5.242, 95% CI 2.642-9.208]), and severe noise levels (RR = 9.322, 95% CI 5.341-14.428]) was higher risk than the LAeq,8h control level. The risk of obesity among participants exposed to low (RR = 2.957, 95% CI 1.441-6.068]) and high cumulative noise levels (RR = 7.226, 95% CI 3.623-14.415]) was greater than the CNE control level. For every 1 dB(A) increase in LAeq,8h, the BMI increased by 0.063 kg/m2 (95% CI 0.055-0.071], SE = 0.004). For every 1 dB(A) increase in the CNE, the BMI increased by 0.102 kg/m2 (95% CI 0.090-0.113], SE = 0.006).

CONCLUSIONS: Occupational noise is related to the incidence of obesity. The occupational noise level and occupational noise cumulative level were shown to be positively correlated with an increase in BMI.

PMID:38117351 | DOI:10.1007/s00420-023-02032-0