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Altered Hippocampal Activation in Seizure-Prone CACNA2D2 Knock-out Mice

eNeuro. 2024 May 15;11(5):ENEURO.0486-23.2024. doi: 10.1523/ENEURO.0486-23.2024. Print 2024 May.

ABSTRACT

The voltage-gated calcium channel subunit α2δ-2 controls calcium-dependent signaling in neurons, and loss of this subunit causes epilepsy in both mice and humans. To determine whether mice without α2δ-2 demonstrate hippocampal activation or histopathological changes associated with seizure activity, we measured expression of the activity-dependent gene c-fos and various histopathological correlates of temporal lobe epilepsy (TLE) in hippocampal tissue from wild-type (WT) and α2δ-2 knock-out (CACNA2D2 KO) mice using immunohistochemical staining and confocal microscopy. Both genotypes demonstrated similarly sparse c-fos and ΔFosB expressions within the hippocampal dentate granule cell layer (GCL) at baseline, consistent with no difference in basal activity of granule cells between genotypes. Surprisingly, when mice were assayed 1 h after handling-associated convulsions, KO mice had fewer c-fos-positive cells but dramatically increased ΔFosB expression in the dentate gyrus compared with WT mice. After administration of a subthreshold pentylenetetrazol dose, however, KO mice dentate had significantly more c-fos expression compared with WT mice. Other histopathological markers of TLE in these mice, including markers of neurogenesis, glial activation, and mossy fiber sprouting, were similar between WT and KO mice, apart from a small but statistically significant increase in hilar mossy cell density, opposite to what is typically found in mice with TLE. This suggests that the differences in seizure-associated dentate gyrus function in the absence of α2δ-2 protein are likely due to altered functional properties of the network without associated structural changes in the hippocampus at the typical age of seizure onset.

PMID:38749701 | DOI:10.1523/ENEURO.0486-23.2024

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Practice of breast self-examination and associated factors among women of reproductive age in the North Shoa Zone, Oromia, Ethiopia, 2022: a convergent mixed-methods study

BMJ Open. 2024 May 15;14(5):e073951. doi: 10.1136/bmjopen-2023-073951.

ABSTRACT

OBJECTIVE: To assess practice of breast self-examination (BSE) and associated factors among women of reproductive age in the North Shoa Zone, Oromia, Ethiopia.

DESIGN: Community-based cross-sectional study with a convergent mixed-methods approach.

SETTING: The study was conducted in the North Shoa Zone of Oromia, Central Ethiopia, between 1 May 2022 and 30 June 2022.

PARTICIPANTS: 1076 women of reproductive age were selected using simple random sampling technique for the quantitative study. For the qualitative part, a total of 46 women were approached purposively to elicit rich ideas and insight into the issue. The quantitative data were collected using an interviewer-administered questionnaire, and focus group discussions were used for the qualitative part. Quantitative data were analysed using SPSS V.26. An adjusted OR with a 95% CI was employed. Thematic analysis approach was applied for the qualitative data analysis.

OUTCOME MEASURES: Participants were interviewed to respond whether they practised BSE.

RESULTS: Overall, 192 (18.2%; 15.7%-20.5%) of the participants had ever performed BSE. Having a family history of breast cancer (BC) (adjusted OR (AOR)=6.9, 95% CI 4.6 to 10.3), being knowledgeable on BSE (AOR=3, 95% CI 1.9 to 4.3), having high perceived susceptibility (AOR=1.7, 95% CI 1.2 to 2.5), having high self-efficacy (AOR=1.5, 95% CI 1.1 to 2.3) and having a high perceived benefit to BSE (AOR=1.5, 95% CI 1.1 to 2.3) were significantly associated with increased odds of BSE practice.Four main themes emerged from the qualitative analysis: BC and BSE-related knowledge, perceived benefits of treatment, barriers to BSE practice and enablers of BSE practice.

CONCLUSION: The practice of BSE in this area was considerably low. The North Shoa Zonal Health Office and other stakeholders should disseminate instructional materials that cover the techniques and benefits of regularly performing BSE. Healthcare professionals should engage in the community to address the obstacles women face in practising BSE.

PMID:38749697 | DOI:10.1136/bmjopen-2023-073951

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Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013-2016

BMJ Open. 2024 May 15;14(5):e073527. doi: 10.1136/bmjopen-2023-073527.

ABSTRACT

OBJECTIVE: To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).

DESIGN: Cross-sectional analysis.

SETTING: US National Health and Nutrition Examination Survey, 2013-2016.

OUTCOME MEASURES: Serum sex hormone measures included total testosterone (TT) and oestradiol (E2), sex hormone-binding globulin (SHBG), the ratio of TT and E2 and free androgen index (FAI). Isotope dilution-liquid chromatography tandem mass spectrometry was used to measure serum TT and E2. SHBG was measured using immunoassay. The ratio of TT and E2 and FAI were calculated. SHS exposure was defined as serum cotinine concentration of 0.05-10 ng/mL.

PARTICIPANTS: A total of 622 female participants aged ≥20 years were included in the analysis.

RESULTS: For never smokers, a doubling of serum cotinine concentration was associated with a 2.85% (95% CI 0.29% to 5.47%) increase in TT concentration and a 6.29% (95% CI 0.68% to 12.23%) increase in E2 in fully adjusted models. The never smokers in the highest quartile (Q4) of serum cotinine level exhibited a 10.30% (95% CI 0.78% to 20.72%) increase in TT concentration and a 27.75% (95% CI 5.17% to 55.17%) increase in E2 compared with those in the lowest quartile (Q1). For former smokers, SHBG was reduced by 4.36% (95% CI -8.47% to -0.07%, p for trend=0.049) when the serum cotinine level was doubled, and the SHBG of those in Q4 was reduced by 17.58% (95% CI -31.33% to -1.07%, p for trend=0.018) compared with those in Q1.

CONCLUSION: SHS was associated with serum sex hormone concentrations among female adults. In never smokers, SHS was associated with increased levels of TT and E2. In former smokers, SHS was associated with decreased SHBG levels.

PMID:38749695 | DOI:10.1136/bmjopen-2023-073527

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Predicting the association of different levels of physical activity on postoperative pulmonary complications using the international physical activity questionnaire in patients undergoing thoracoscopic lung surgery under general anaesthesia: protocol for a prospective cohort study

BMJ Open. 2024 May 15;14(5):e077183. doi: 10.1136/bmjopen-2023-077183.

ABSTRACT

INTRODUCTION: Postoperative pulmonary complications (PPCs) occur frequently in patients undergoing lung surgery under general anaesthesia and are strongly associated with longer postoperative hospital stays and increased mortality. The existing literature has shown that a higher level of preoperative physical activity (PA) plays a positive role in the low incidence of postoperative complications and the quality of life in patients undergoing lung surgery. However, the association between preoperative PA levels and the incidence of PPCs has rarely been studied, particularly in thoracoscopic lung surgery. This study aims to evaluate PA levels in patients undergoing thoracoscopic lung surgery using the International Physical Activity Questionnaire and to investigate the association between PA levels and the incidence of PPCs.

METHODS AND ANALYSIS: A total of 204 participants aged 18-80 years undergoing thoracoscopic lung surgery (thoracoscopic wedge resection, thoracoscopic segmentectomy and thoracoscopic lobectomy) will be included in the study. The primary outcome is the incidence of PPCs within the first 5 postoperative days. The secondary outcomes include the number of PPCs, the incidence of PPCs 1 month postoperatively, the arterial blood levels of inflammatory markers, the incidence of postoperative adverse events within the first 5 postoperative days, extubation time, unplanned admission to the intensive care unit, postoperative length of stay and mortality 1 month postoperatively.

ETHICS AND DISSEMINATION: The study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Shandong First Medical University on 31 March 2022 (YXLL-KY-2022(014)) and is registered at ClinicalTrials.gov. We plan to disseminate the data and findings of this study in international and peer-reviewed journals.

TRIAL REGISTRATION NUMBER: The trial has been prospectively registered at the clinicaltrials.gov registry (NCT05401253).

PMID:38749692 | DOI:10.1136/bmjopen-2023-077183

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Residents’ willingness towards first-contact with primary health care under uncertainty in healthcare: a cross-sectional study in rural China

BMJ Open. 2024 May 15;14(5):e077618. doi: 10.1136/bmjopen-2023-077618.

ABSTRACT

OBJECTIVE: To estimate Chinese rural residents’ willingness degree of initially contacting primary healthcare (PHC) under uncertainty in healthcare and to explore its influencing factors.

SETTING: This study collected primary data from rural residents in Dangyang, Hubei Province in China.

PARTICIPANTS: The study investigated 782 residents and 701 finished the survey. The response rate was 89.64%. A further 27 residents failed the internal consistency test, so the effective sample size was 674.

DESIGN: In this cross-sectional study, residents’ willingness was reflected by the threshold of disease severity for PHC (TDSP), the individual maximal disease scope for considering PHC based on residents’ decision-making framework. TDSP was measured through scenario tests. Univariate analysis and unordered multiple logistic regression were used to explore the influencing factors of three-level TDSP: low, general, and high.

RESULTS: Only 28.2% of respondents had high TDSP and high willingness towards PHC. Compared with general TDSP, respondents who were younger than 40 (OR 7.344, 95% CI 2.463 to 21.894), rich (OR 1.913, 95% CI 1.083 to 3.379), highly risk-averse (OR 1.958, 95% CI 1.016 to 3.774), had substitute medical decision-maker (OR value of parent/child was 2.738, 95% CI 1.386 to 5.411) and had no visits to PHC in the last 6 months (OR 2.098, 95% CI 1.316 to 3.346) tended to have low TDSP and low willingness towards PHC. Compared with general TDSP, no factors were found to significantly influence respondents’ high TDSP.

CONCLUSIONS: TDSP can be a good indicator of residents’ willingness. TDSP results demonstrate rural residents’ generally low willingness towards first-contact with PHC that some residents refuse to consider PHC even for mild diseases. This study provides practical significance for elaborating the underutilisation of PHC from resident decision-making and offers advice to policymakers and researchers for future modifications.

PMID:38749685 | DOI:10.1136/bmjopen-2023-077618

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Analysis of the immunological response to antiviral therapy in patients with different subtypes of HIV/AIDS: a retrospective cohort study

BMJ Open. 2024 May 15;14(5):e072597. doi: 10.1136/bmjopen-2023-072597.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population.

DESIGN: A retrospective cohort study was performed, and PLWHA residing in Huzhou, China, between 2018 and 2020, were enrolled.

SETTING AND PARTICIPANTS: Data from 625 patients, who were newly diagnosed with HIV/AIDS in the AIDS Prevention and Control Information System in Huzhou between 2018 and 2020, were reviewed.

ANALYSIS AND OUTCOME MEASURES: Data regarding demographic characteristics and laboratory investigation results were collected. Immune system recovery was used to assess the effectiveness of ART, and an increased percentage of CD4+ T lymphocyte counts >30% after receiving ART for >1 year was determined as immunopositive. A multiple logistic regression model was used to comprehensively quantify the association between PLWHA immunological response status and virus subtype. In addition, the joint association between different subtypes and treatment regimens on immunological response status was investigated.

RESULTS: Among 326 enrolled PLWHA with circulating recombinant forms (CRFs) CRF01_AE, CRF07_BC and other HIV/AIDS subtypes, the percentages of immunopositivity were 74.0%, 65.6% and 69.6%, respectively. According to multivariate logistic regression models, there was no difference in the immunological response between patients with CRF01_AE, CRF07_BC and other subtypes of HIV/AIDS who underwent ART (CRF07_BC: adjusted OR (aOR) (95% CI) = 0.8 (0.4 to 1.4); other subtypes: aOR (95% CI) = 1.2 (0.6 to 2.3)). There was no evidence of an obvious joint association between HIV subtypes and ART regimens on immunological response.

CONCLUSIONS: Standardised ART was beneficial to all PLWHA, regardless of HIV subtypes, although it was more effective, to some extent, in PLWHA with CRF01_AE.

PMID:38749684 | DOI:10.1136/bmjopen-2023-072597

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The outcome and related risk factors of unvaccinated patients with end-stage kidney disease during the Omicron pandemic: a multicentre retrospective study

BMJ Open. 2024 May 15;14(5):e084649. doi: 10.1136/bmjopen-2024-084649.

ABSTRACT

OBJECTIVES: The study aims to identify the outcome and the related factors of unvaccinated patients with end-stage kidney disease during the Omicron pandemic.

DESIGN: A multicentre retrospective study of patients with end-stage kidney disease undergone maintenance haemodialysis (HD) in China.

SETTING: 6 HD centres in China.

PARTICIPANTS: A total of 654 HD patients who tested positive for SARS-CoV-2 were ultimately included in the study.

OUTCOME MEASURES: The primary outcomes of interest were adverse outcomes, including hospitalisation due to COVID-19 and all-cause mortality.

RESULTS: The average age of the patients was 57 years, with 33.6% of them being over 65 years. Among the patients, 57.5% were male. During the follow-up period, 158 patients (24.2%) experienced adverse outcomes, and 93 patients (14.2%) died. The majority of patients (88/158) developed adverse outcomes within 30 days, and most deaths (77/93) occurred within 1 month. An advanced multivariable Cox regression analysis identified that adverse outcomes were associated with various factors while all-cause mortality was related to advanced age, male gender, high levels of C reactive protein (CRP) and low levels of prealbumin. The Kaplan-Meier curves demonstrated significantly higher all-cause mortality rates in the older, male, high CRP and low prealbumin subgroups.

CONCLUSIONS: Among unvaccinated HD patients with confirmed Omicron infections, various factors were found to be linked to adverse outcomes. Notably, age, sex, CRP and prealbumin had a substantial impact on the risk of all-cause mortality.

PMID:38749679 | DOI:10.1136/bmjopen-2024-084649

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Examining the hospital costs of children born into relative deprivation in England

J Epidemiol Community Health. 2024 May 15:jech-2023-221175. doi: 10.1136/jech-2023-221175. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the association between being born into relative deprivation and hospital costs during childhood.

DESIGN: Retrospective cohort study.

METHODS: We created a birth cohort using Hospital Episode Statistics for children born in NHS hospitals in 2003/2004. The Index of Multiple Deprivation (IMD) rank at birth was missing from 75% of the baby records, so we linked mother and baby records to obtain the IMD decile from the mother’s record. We aggregated and costed each child’s hospital inpatient admissions, and outpatient and emergency department (ED) attendances up to 15 years of age. We used 2019/2020 NHS tariffs to assign costs. We constructed an additional cohort, all children born in 2013/2014, to explore any changes over time, comparing the utilisation and costs up to 5 years of age.

RESULTS: Our main cohort comprised 567 347 babies born in 2003/2004, of which we could include 91%. Up to the age of 15 years, children born into the most deprived areas used more hospital services than those born in the least deprived, reflected in higher costs of inpatient, outpatient and ED care. The highest costs and greatest differences are in the year following birth. Comparing this with the later cohort (up to age 5 years), the average cost per child increased across all deprivation deciles, but differences between the most and least deprived deciles appeared to narrow slightly.

CONCLUSIONS: Healthcare utilisation and costs are consistently higher for children who are born into the most deprived areas compared with the least.

PMID:38749646 | DOI:10.1136/jech-2023-221175

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Case Volumes and Outcomes Among Early-Career Interventional Cardiologists in the United States

J Am Coll Cardiol. 2024 May 21;83(20):1990-1998. doi: 10.1016/j.jacc.2024.03.395.

ABSTRACT

BACKGROUND: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States.

OBJECTIVES: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022.

METHODS: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated.

RESULTS: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status.

CONCLUSIONS: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists.

PMID:38749617 | DOI:10.1016/j.jacc.2024.03.395

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Efficacy of Intrawound Vancomycin in Prevention of Periprosthetic Joint Infection After Primary Total Knee Arthroplasty: A Prospective Double-Blinded Randomized Control Trial

J Arthroplasty. 2024 Jun;39(6):1569-1576. doi: 10.1016/j.arth.2024.01.003. Epub 2024 Apr 10.

ABSTRACT

BACKGROUND: Periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a devastating complication. Intrawound vancomycin powder has been shown to reduce infection rates in spine surgery, but its role in arthroplasty remains controversial. This prospective randomized control trial aimed to evaluate the efficacy of intrawound vancomycin in preventing PJI after primary TKA.

METHODS: A total of 1,022 patients were randomized to the study group (n = 507, who received 2 grams intrawound vancomycin powder before arthrotomy closure) or to the control group (n = 515, no local vancomycin) with a minimum follow-up of 12-months. The primary outcome was the incidence of PJI or surgical site infection (SSI). Secondary outcomes included associated minor complications such as stitch abscess, persistent wound drainage, and delayed stitch removal. Other parameters evaluated include reoperation rates and incidences of nephrotoxicity.

RESULTS: The overall infection rate in 1,022 patients was 0.66%. There was no significant difference in PJI rate in the study group (N = 1; 0.2%) versus the control group (N = 3; 0.58%), P = .264. Reoperation rates in the study group (N = 4; 0.78%) and control (N = 5; 0.97%), and SSI rates in the study (N = 1; 0.2%) and control groups (N = 2; 0.38%) were comparable. The Vancomycin cohort, however, demonstrated a significantly higher number of minor wound complications (n = 67; 13.2%) compared to the control group (n = 39; 7.56%, P < .05). Subgroup analysis showed diabetics in the study group to also have a higher incidence of minor wound complications (24 [14.1%] versus 10 [6.2%]; P < 05]. Multivariate analyses found that vancomycin use (odds ratio = 1.64) and smoking (odds ratio = 1.85) were associated with an increased risk of developing minor wound complications. No cases of nephrotoxicity were reported.

CONCLUSIONS: Intrawound vancomycin powder does not appear to reduce PJI/SSI rate in primary total knee arthroplasties, including high-risk groups. Although safe from a renal perspective, intrawound vancomycin was associated with an increase in postoperative aseptic wound complications. Intrawound vancomycin may not be effective in reducing the rate of PJI in primary TKA.

PMID:38749600 | DOI:10.1016/j.arth.2024.01.003