Endothelial TRPV4 channel mediates the vasodilation induced by Tanshinone IIA.

Tanshinone IIA (TSA), the main lipo-soluble component from the dried rhizome of Salvia miltiorrhiza, has been shown to induce vasodilation. However, the underlying mechanisms remains unclear. This study aimed to investigate the effect of TSA on the vasodilation of small resistant arteries ex vivo. Vascular myography revealed that endothelial denudation reduced significantly the vasodilatory effect of TSA. Blocking transient receptor potential vanilloid 4 (TRPV4) channels prevented TSA-induced vasodilation. Whole-cell patch-clamp analysis revealed that the current passing through TRPV4 channels increased after TSA treatment in endothelial cells (ECs). This was attributed to reduced TRPV4 protein degradation along with its increased expression. The TRPV4 inhibitor HC-067047 lowed nitric oxide (NO) production and TSA-induced expression of endothelial nitric oxide synthase (eNOS). Moreover, it increased the production of cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG). The present results indicate that TSA induces endothelium-dependent vasodilation, which is mediated by the TRPV4-NO-PKG signaling pathway. These findings highlight the potential of TSA, a compound known in traditional Chinese medicine as Danshen (Salvia miltiorrhiza), for future cardiovascular therapeutic strategies.

Online medical consultation in China: Demand-side analysis of obese patients' preferences and willingness-to-pay for online obesity consultations.

Objective: With obesity a major health concern and call on healthcare resources in China, we explored the preferences and willingness to pay (WTP) for obesity OMC, including the influencing factors behind WTP and preferences. Method: We recruited 400 obese participants to undertake a discrete choice experiment (DCE) and the contingent value method (CVM) survey. We used CVM to measure obese participants' WTP for one-click services (OCS) and used DCE to estimate obesity participants' preferences and WTP for OMC with different attributes. Results: Obese participants were willing to pay more than RMB80 on average for OCS, and more than 50% of participants had a WTP over RMB50 and 5% had a WTP over RMB300, reflecting the strong willingness of Chinese obese patients to pay for OMC. Educational background, income, ethnicity, previous OMC experience and accessibility to offline hospitals with different levels impacted WTP. The relative importance score of attributes in descending order was cost, doctors' hospital level, doctors' level, online waiting time, consultation time and consultation form. Obese patients preferred lower cost, doctors from higher-level hospitals, doctors with higher expertise levels, shorter waiting time and consultation duration, and telephone consultation were preferred. 30-min waiting time, 15-min consultation duration and telephone consultation were the most economically efficient set we found. Conclusion: To maximize health resources, provincial tertiary and municipal hospitals face different paths to developing obesity OMC platforms. We encouraged young doctors to use OMC. OMC regulators should implement consumer protection policies to optimize OMC pricing and address potential 'unfair' pricing.

Protocol for a longitudinal study examining the trajectory of COVID-19, post-COVID, multidimensional disadvantage and health-related quality of life in India: the IndiQol Project.

INTRODUCTION: The COVID-19 pandemic has raised concerns about the persistence of symptoms after infection, commonly referred to as 'post-COVID' or 'long-COVID'. While countries in high-resource countries have highlighted the increased risk of disadvantaged communities, there is limited understanding of how COVID-19 and post-COVID conditions affect marginalised populations in low-income and middle-income countries. We study the longitudinal patterns of COVID-19, post-COVID symptoms and their impact on the health-related quality of life through the IndiQol Project. METHODS AND ANALYSIS: The IndiQol Project conducts household surveys across India to collect data on the incidence of COVID-19 and multidimensional well-being using a longitudinal design. We select a representative sample across six states surveyed over four waves. A two-stage sampling design was used to randomly select primary sampling units in rural and urban areas of each State. Using power analysis, we select an initial sample of 3000 household and survey all adult household members in each wave. The survey data will be analysed using limited dependent variable models and matching techniques to provide insights into the impact of COVID-19 pandemic and post-COVID on health and well-being of individuals in India. ETHICS AND DISSEMINATION: Ethics approval for the IndiQol Project was obtained from the Macquarie University Human Research Ethics Committee in Sydney, Australia and Institutional Review Board of Morsel in India. The project results will be published in peer-reviewed journals. Data collected from the IndiQol project will be deposited with the EuroQol group and will be available to use by eligible researchers on approval of request.

A web-based video messaging intervention for suicide prevention in men: study protocol for a five-armed randomised controlled trial.

BACKGROUND: More than 50% of people who die by suicide have not been in contact with formal mental health services. The rate of people who fly 'under the radar' of mental health services is higher among men than women, indicating a need to improve engagement strategies targeted towards men who experience suicidal thoughts and/or behaviours. In Australia, a range of mental health support services exist, designed specifically for men, yet, a substantial proportion of men do not use these services. The aim of this study is to evaluate whether a brief online video-based messaging intervention is an effective approach for encouraging men with suicidal thoughts and/or behaviours to engage with existing support services. METHODS: Informed by a literature review, surveys, and consultation with men with a lived experience of suicidal thoughts and/or behaviours, we designed five video-based messages that will be used in this five-arm randomised controlled trial. A total of 380 (76 per arm) men aged 18 years or older with suicidal thoughts who are not currently accessing formal mental health services will be recruited online and randomly assigned to watch one of the five web-based video messages. After viewing the video, men will be presented with information about four existing Australian support services, along with links to these services. The primary outcome will be help-seeking, operationalised as a click on any one of the four support service links, immediately after viewing the video. Secondary outcomes include immediate self-reported help-seeking intentions in addition to self-reported use of the support services during a 1-week follow-up period. We will also use the Discrete Choice Experiment methodology to determine what aspects of support services (e.g. low cost, short appointment wait times) are most valued by this group of men. DISCUSSION: This study is the first to evaluate the effectiveness of a brief web-based video messaging intervention for promoting engagement with existing support services among men with suicidal thoughts who are not currently receiving formal help. If found to be effective, this would represent a scalable, cost-effective approach to promote help-seeking for this at-risk population. Limitations and strengths of this study design are discussed.

How should regulatory schemes be optimized to enhance deterrence against medical insurance fraud by enrollees? Evidence from a discrete choice experiment in China.

Medical insurance fraud (MIF) poses a substantial global financial challenge, necessitating effective regulatory strategies, especially in China, where such measures are in a critical developmental phase. This study investigates the effectiveness of various regulatory components in deterring MIF among enrollees and explores preference heterogeneity among individuals with different characteristics, utilizing a discrete choice experiment survey. Grounded in deterrence theory, our conceptual framework incorporates five attributes: intensity of economic penalties, restrictions on medical insurance benefits, deterioration of social reputation, and certainty and celerity of penalties. Employing a D-efficiency design, 24 choice sets were generated and blocked into three versions. A multistage stratified sampling method was adopted to collect data from the basic medical insurance enrollees in Shanghai. The survey was conducted from September to October 2022. The sample representativeness was further improved via the entropy balancing approach. Data from the final sample of 1034 respondents were analyzed using mixed logit models (MIXLs), incorporating interactions with individual characteristics to assess preference heterogeneity. Results reveal that escalating economic penalties, suspending insurance benefits, listing individuals as unfaithful parties, ensuring penalty certainty, and expediting enforcement significantly enhance the deterrent effect. We observed preference heterogeneity across different demographics, including age, gender, education, health status, and employment status. The study underscores the pivotal role of economic penalties in deterring MIF, while also acknowledging the significance of non-economic measures such as enforcement efficiency and social sanctions. These findings offer valuable insights for policymakers to tailor and strengthen regulatory schemes against MIF, contributing to the advancement of more effective and precise healthcare policies.

Health Care Needs and Costs for Children Exposed to Prenatal Substance Use to Adulthood.

Importance: Children exposed to substance use during pregnancy have increased health needs but whether these are influenced by engagement in out-of-home care is uncertain. Objective: To evaluate the association between substance use during pregnancy, out-of-home care and hospitalization utilization, and costs from birth up to age 20 years. Design, Setting, and Participants: This was a retrospective cohort study using individual-linked population birth, hospital, and out-of-home care information of all liveborn infants from New South Wales, Australia, between 2001 and 2020 using longitudinal population-based linkage records from administrative databases. Substance use during pregnancy included newborns with neonatal abstinence syndrome (n = 5946) and intrauterine exposure to drugs of addiction (n = 1260) and other substances (eg, tobacco, alcohol, and illicit drugs or misused prescription drugs; n = 202 098). Children not exposed to substance use during pregnancy were those without known exposure to substance use during pregnancy (n = 1 611 351). Data were analyzed from July 2001 to December 2021. Main Outcomes: Main outcomes were hospital readmission, length of stay, and cost burden associated with substance use during pregnancy from birth up to age 20 years. Outcomes were investigated using 2-part and Poisson regression models adjusted for sociodemographic characteristics. Mediation analysis was used to evaluate whether the association of substance use during pregnancy with risk of readmission was mediated through engagement with out-of-home care. Results: Of the 1 820 655 live births, 935 807 (51.4%) were male. The mean (SD) age of mothers was 30.8 (5.5) years. Compared with children who were not exposed to substance use during pregnancy, those who were exposed incurred significantly higher birth hospital costs (adjusted mean difference, A$1585 per child [US$1 = A$1.51]; 95% CI, 1585-1586). If discharged alive, more children with exposure to substance use during pregnancy had at least 1 readmission (90 433/209 304 [43.4%] vs 616 425/1 611 351[38.3%]; adjusted relative risk [RR], 1.06; 95% CI, 1.06-1.07), most commonly for respiratory conditions (RR, 1.11; 95% CI, 1.09-1.12) and mental health/behavioral disorders (RR, 1.36; 95% CI, 1.33-1.41). Excess hospital costs associated with substance use during pregnancy were A$129.0 million in 2019 to 2020. Mediation analyses showed that any out-of-home care contact mediated the association between substance use during pregnancy and risk of inpatient readmission and lower health care cost (decreased by A$25.4 million). For children with neonatal abstinence syndrome, any out-of-home care contact mediated readmission risk by approximately 30%, from adjusted RR, 1.28; 95% CI, 1.19-1.35, to RR, 1.01; 95% CI, 0.98-1.02. Conclusion and Relevance: Children who were exposed to substance use during pregnancy incurred more hospital costs than children who were not exposed up to 20 years of age, but this was reduced in association with any contact with out-of-home care. This provides insights into possible strategies for reducing health and financial burdens associated with exposure to substance use during pregnancy for children.

Taraxasterol protects against acetaminophen-induced hepatotoxicity by reducing liver inflammatory response and ameliorating oxidative stress in mice.

Acute liver failure is mainly caused by the overdose of acetaminophen (APAP) globally. The traditional Chinese medicinal (TCM) herb, Taraxacum, contains Taraxasterol (TAX) as one of the active components. It is a pentacyclic-triterpene compound isolated from this herb. Present work aimed to investigate the in vitro and in vivo protection effect of TAX in APAP-induced acute liver injury, and determine the potential regulatory mechamisms. The liver injury caused by APAP is attenuated by TAX, as shown by the alleviated pathological changes of mice liver and the reduced serological indexes. TAX evidently controlled the oxidative stress and liver inflammation in mice liver. In vitro studies found that TAX reversed the decrease in LO2 cell viability induced by APAP, and protected LO2 cells from APAP-induced injury. In addition, TAX reduced the secretion of inflammatory factors in RAW264.7 macrophages as induced via APAP. Besides, TAX inhibited oxidative stress in LO2 cells induced by APAP in vitro. Noteworthy, TAX enhanced protein and mRNA expressions of Nrf2 in vivo, and knockdown of Nrf2 by using adeno-associated virus (AAV)-Nrf2-KO attenuated inhibitory impact of TAX in acute liver injury induced by APAP. Also, AAV-NRF2-KO weakened the inhibitory impact of TAX against APAP-triggered liver inflammation and oxidative stress of mice liver. Moreover, TAX activated the Nrf2 signaling in APAP-induced LO2 cells, as shown by the increased nuclear Nrf2 expression together with downstream HO-1 expression in vitro. Inhibition of Nrf2 by using ML-385, anNrf2inhibitor, weakened the inhibitory effect of TAX against APAP-induced oxidative stress and cell injury in LO2 cells. Moreover, inhibition of Nrf2 attenuated anti-inflammatory effect of TAX for APAP-induced RAW264.7 cells. Collectively, TAX could protect against APAP-triggered hepatotoxicitythrough suppression of liver oxidative stress and inflammatory response in mice.

A qualitative exploration of the over-the-counter availability of oral contraceptive pills in Australia.

INTRODUCTION: The prevention of unintended pregnancy is a public health issue affecting women worldwide. In Australia, women are required to get a prescription to obtain the oral contraceptive pill (OCP), which may limit access and be a barrier to its initiation and continuing use. Changing the availability of the OCP from prescription-only to over-the-counter (OTC) is one solution, however, to ensure success policymakers need to understand women's preferences. Telehealth services also might serve as an alternative to obtain prescriptions and increase accessibility to OCPs. This study aims to explore the preferences for OTC OCPs among Australian women, and whether the expansion of telehealth impacted women's preferences. METHODS: A mixed methods approach was used to explore women's preferences regarding access to the OCP. Focus group discussions (FGDs) were conducted to organically identify the preferences followed by an empirical ranking exercise. Three FGDs in two phases were conducted, pre and post-expansion of telehealth in Australia due to the COVID-19 pandemic. Convenience sampling was employed. The technique of constant comparison was used for thematic analysis where transcripts were analysed iteratively, and codes were allowed to emerge during the process to give the best chance for the attributes to develop from the data. RESULTS: Thematic analysis revealed that women perceived OTC availability of OCPs as a mechanism to increase the accessibility of contraception by reducing cost, travel time, waiting time, and increasing opening hours. They also believed that it would increase adherence to OCPs. However, some potential safety concerns and logistical issues were raised, including pharmacist training, access to patient's medical history, the ability to discuss other health issues or undertake opportunistic health screening, adherence to checklists, and privacy in the pharmacy environment. Following the expansion of telehealth, accessibility issues such as opening hours, travel time, and location of the facility were considered less important. CONCLUSIONS: The participants expressed their support for reclassifying OCPs to OTC, particularly for repeat prescriptions, as it would save valuable resources and time. However, some safety and logistical issues were raised. Women indicated they would balance these concerns with the benefits when deciding to use OTC OCPs. This could be explored using a discrete choice experiment. The expansion of telehealth was perceived to reduce barriers to accessing OCPs. The findings are likely to be informative for policymakers deciding whether to reclassify OCPs to OTC, and the concerns of women that need addressing to ensure the success of any policy change.

Impact of CYP2A6 Gene Polymorphism on the Efficacy and Safety of S-1 Therapy in Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: The relationship of CYP2A6 polymorphisms with S-1 therapy outcomes in gastric cancer is unclear. This review aimed to assess the association between CYP2A6 gene polymorphisms (CYP2A6*4, *7, *9, *10) and S-1 therapy outcomes in gastric cancer, aiming to identify predictive markers for S-1 efficacy and adverse reactions. METHODS: We searched seven databases, using random or fixed-effect models to calculate hazard ratio (HR) and 95% confidence interval (CI) based on study heterogeneity. RESULTS: A total of 1,143 articles were retrieved from multiple online databases as of March 28, 2023. After screening, seven articles containing seven investigations were included in the meta-analysis. Our results revealed a significant association between the CYP2A6 polymorphism site and the overall survival (OS) of variant/variant group (V/V) patients compared to wild-type/wild-type (W/W) or wild-type/variant (W/V) patients (HR = 2.73, 95% CI: 1.45-5.14, p = 0.002). S-1 was more beneficial for W/W or W/V patients than V/V patients in terms of progression-free survival (PFS) (HR = 3.15, 95% CI: 1.47-6.75, p = 0.003). There was no association between CYP2A6 polymorphism and hematological adverse reactions (OR = 0.52, 95% CI: 0.23-1.15, p = 0.104). CONCLUSION: CYP2A6 polymorphisms correlate with S-1 efficacy (OS and PFS) in gastric cancer, suggesting their potential as predictive markers. However, the generalizability of findings is limited by the small number of studies from Eastern countries and variations in chemotherapy regimens and detection methods. Further, large-scale studies are needed to confirm these associations.

Preparation and characterization of pectin-alginate-based microbeads reinforced by nano montmorillonite filler for probiotics encapsulation: Improving viability and colonic colonization.

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.

Learning Middle-Latitude Cyclone Formation up in the Air: Student Learning Experience, Outcomes, and Perceptions in a CAVE-Enabled Meteorology Class.

Cave Automatic Virtual Environment (CAVE) is a virtual reality (VR) environment that has not been fully studied due to its high cost and complexity in system integration. Previous CAVE-related studies mainly focused on comparing its effectiveness with other learning media, such as textbooks, desktop VR, or head-mounted display (HMD) VR. In this study, through the utilization of CAVE in a meteorology class, we concentrated on CAVE itself, measured how CAVE impacted learners' learning outcomes before and after using CAVE in an actual ongoing undergraduate-level class, and investigated how learners perceived their learning experiences. Quantitative data were collected to examine the students' knowledge acquisition and learning experience. We also triangulated the quantitative results with qualitative data from the interviews regarding learners' perceptions of the CAVE-enabled class and their knowledge mastery. The results indicated that their learning outcomes increased through learning with CAVE and that their perceptions of immersion, presence, and engagement significantly correlated with each other. The interview results showed a great fondness of and satisfaction with the learning experience, group collaboration, and effectiveness of the CAVE-enabled class from the learners. We also learned that the learners' learning experiences in CAVE could be further improved if we provided them with more learner-environment interaction, offered them a better sense of immersion, and reduced cybersickness. Implications of these findings are discussed.

Patient preferences and willingness to pay for central venous access devices in breast cancer: A multicenter discrete choice experiment.

BACKGROUND: Despite being a significant management decision in clinical or nursing practice, there is limited understanding of the preferences regarding risks, benefits, costs, and other attributes of patients with breast cancer when selecting peripherally inserted central catheters or totally implanted ports. The objective of this study is to investigate the preferences of patients with breast cancer who require chemotherapy when selecting an optimal central venous access device. METHODS: Data on patients' preferences for central venous access devices were collected using a face-to-face discrete choice experiment from the oncology departments of three public hospitals in China representing the eastern (Zhejiang province), central (Henan province), and western (Sichuan province) regions. The study used six attributes to describe the preferences of breast cancer patients for central venous access devices, including out-of-pocket cost, limitations in activities of daily living, catheter maintenance frequency, risk of catheter-related thrombosis, risk of catheter-related infection, and size of incision. Data were analyzed using a conditional logit model and mixed logit model. The marginal willingness to pay (mWTP) was calculated by assessing the ratio of the preference for other attributes to the preference for out-of-pocket cost. RESULTS: A total of 573 respondents completed the survey. The discrete choice experiment results showed that respondents strongly preferred a central venous access device with a catheter maintenance frequency of one time a month (vs four times a month, ß = 1.188, p < 0.001), the lower risk of catheter-related thrombosis (2 % vs 10 %, ß = 1.068; p < 0.001) and lower risk of catheter-related infection (2 % vs 8 % risk: ß = 0.824; p < 0.001). Respondents were willing to pay CNY ¥11,968.1 (US$1776.5) for a central venous access device with a catheter maintenance frequency of one time a month rather than four times a month, ¥10,753.6 (US$1596.2) for a central venous access device with 2 % thrombosis risk over one with 10 %, and ¥8302.0 (US$1232.3) for a central venous access device with 2 % infection risk over one with 8 %. Respondents with longer travel time to the hospital, younger than 50 years old, and with urban employee basic medical insurance were willing to pay more for an improvement in the attributes. CONCLUSIONS: These findings suggest that patients with breast cancer were mainly concerned with the out-of-pocket cost, catheter maintenance frequency, risk of catheter-related thrombosis and risk of catheter-related infection when choosing a central venous access device for the delivery of chemotherapy. In clinical or nursing practice, when making central venous access device recommendation for young patients and those who live far from hospitals, totally implanted ports may be a preferable choice.

Diagnostic value of Procalcitonin, C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with Bacteraemia in the intensive care unit.

BACKGROUND: To explore the diagnostic value of procalcitonin (PCT), C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with bacteremia in the intensive care unit (ICU). METHODS: This case-control study included 359 patients with suspected bacteremia were divided into a bacteremia group (n = 152) and a control group (n = 207) from September 2018 to April 2023. Patient data were collected using a laboratory information system (LIS). ROC curves for PCT, CLR, CRP, and NLR in predicting patients with bacteremia. RESULTS: For PCT, CLR, CRP and NLR to predict patients with bacteremia in the ICU, the AUCs were 0.991(95%CI: 0.974-0.998), 0.960(95%CI: 0.935-0.978), 0.955(95%CI: 0.928-0.974), and 0.898(95%CI:0.862-0.927), respectively; the optimal thresholds were 0.248 ng/mL, 47.52 mg/109, 48.32 mg/L, and 6.51, respectively; the sensitivities were 95.4(95%CI: 90.7-98.1), 88.2(95%CI: 81.9-92.8), 87.5(95%CI: 81.2-92.3), and 86.8(95%CI:80.4-91.8), respectively; and the specificities were 95.7(95%CI: 91.9-98.0), 90.8(95%CI: 86.0-94.4), 90.3(95%CI: 85.5-94.0), and 85.0(95%CI:79.4-89.6), respectively. The sensitivities of PCT, CLR, CRP and NLR for predicting bacteremia due to E. coli infection are as high as over 90%, the specificity of PCT is 100, and the sensitivity of NLR is 100. The sensitivity of CRP for predicting bacteremia due to non-Enterobacer infection is 100. CONCLUSIONS: Compared with those in the control group, PCT, CLR, CRP and NLR were significantly greater in the bacteremia group. The PCT, CLR, CRP, and NLR can all predict the occurrence of bacteremia. The PCT had the highest sensitivity and specificity in predicting bacteremia in ICU patients.

Cerebral circulation time on DSA after thrombectomy associated with hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: To investigate the association between cerebral circulation time (CCT) on digital subtraction angiography immediately after thrombectomy and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). METHODS: Retrospectively enrolled consecutive AIS patients presented with large vessel occlusion who received thrombectomy and achieved successful recanalization between January 2019 and June 2021. The time interval from the beginning of the siphon segment of internal carotid artery visualization until the end of the arterial phase during cerebral angiography was calculated as CCT. The independent association of CCT with HT was evaluated using logistic regression analyses. The receiver operating characteristic curve was analyzed to evaluate the association between CCT and HT. RESULTS: Two hundred and twenty-four patients were included, of whom 86 (38.4%) suffered HT. Compared with patients without HT, patients with HT were of advanced age, less commonly male, had more diabetes mellitus, had higher baseline National Institutes of Health Stroke Scale score, lower Alberta Stroke Program Early Computed Tomographic Score, and shorter CCT (P < 0.05). Multivariable logistic regression suggested that CCT was independently associated with HT (adjusted odds ratio, 0.170; 95% confidence interval, 0.004-0.450; P < 0.001). According to the receiver operating characteristic curve, the optimal cut-off value for the strong correlation between CCT and HT was 1.72 s, which had 76.6% sensitivity, 81.6% specificity, and the area under the curve was 0.846. CONCLUSION: Shorter post-thrombectomy CCT was independently associated with HT.

Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers.

BACKGROUND: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. METHODS: A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle-Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. RESULTS: A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. CONCLUSIONS: Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.