Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Patient Experiences with a Multidisciplinary Fibroid Program.

STUDY OBJECTIVE: Although medical, interventional, and surgical treatment options for fibroids have expanded over the last decade, many patients are not thoroughly counseled about all available therapies. Patients desire a more comprehensive approach with shared decision-making tailored to their health goals. The aim of this study is to assess patient knowledge regarding treatment options before and after consultation with a multidisciplinary fibroid center. DESIGN: Prospective Survey Study SETTING: Academic medical center in New York, NY. PATIENTS AND PARTICIPANTS: Patients who presented for initial consultation with a multidisciplinary fibroid program from July 2021 through January 2022. INTERVENTIONS: Patients were offered same-day office consultation with a minimally invasive gynecologic surgeon (MIGS) followed by a telemedicine visit with an interventional radiologist (IR) within three weeks of appointment request. Collaborative discussions were held between providers regarding patient care. Patients were asked to complete the survey following both appointments. Data was collected regarding demographics, prior evaluation of fibroids, knowledge about treatment options, and overall experience. RESULTS: A total of 102 patients completed the survey (response rate 77%). A majority (55.9%) had known about their fibroids for at least two years. Most patients sought out the fibroid program for a 2nd (28.4%), 3rd (22.5%) or 4th (7.8%) opinion. Notably, 35.3% of patients who had previously been seen by an obstetrician-gynecologist (OB/GYN) were not offered any treatment. Of those who had been offered treatment, 24.5% were counseled on medical management with oral contraceptives, 28.4% on surgical options and 5.9% on uterine artery embolization. Nearly all patients (86.3%) endorsed that they would not have sought two separate consultations had it not been for the program. Patients were overall well-informed after their experience, with 95.1% reporting they were more knowledgeable about their options and none reporting the two separate consults created more confusion for them. CONCLUSION: Many patients with symptomatic fibroids seeking secondary opinions have not been adequately counseled on fibroid management options. A collaborative approach to fibroid management better educates patients, provides an opportunity to be thoroughly counseled by the specialists performing either surgical or interventional procedures, and increases patient knowledge about fibroid treatment options.

Women and Cardiovascular Health: Unraveling Gender-Specific Factors, Risks, and Therapeutic Approaches in Contemporary Medicine.

Background and objective Cardiovascular diseases (CVDs) constitute a significant global health challenge, causing millions of deaths annually and straining healthcare systems worldwide. This study aimed to investigate and elucidate gender-specific factors, risks, and therapeutic approaches related to cardiovascular health in women within the context of contemporary medicine. Methodology We conducted a prospective observational study spanning one year (November 2022 to October 2023) at the Peshawar Medical Complex Hospital, to meticulously explore the field of women's cardiovascular health. With a diverse cohort of 435 women (age range: 18-55 years), representing various socioeconomic backgrounds and geographic locations, our study aimed to elicit comprehensive insights. Through structured interviews covering reproductive history, lifestyle, and psychosocial aspects, coupled with clinical assessments, we gathered multifaceted data. Statistical analysis was done using SPSS Statistics version 23.0 (IBM Corp., Armonk, NY). By employing descriptive and t-tests for quantitative analysis and by thematically analyzing qualitative insights, our approach ultimately sought to provide a nuanced understanding of gender-specific factors impacting women's cardiovascular health. Results The study, involving 435 women, revealed various prevalent cardiovascular risk factors. Notable findings include a high incidence of a family history of CVD (n=213, 48.96%, p=0.013), hypertension (n=207, 47.58%), hypercholesterolemia (n=114, 26.21%), elevated triglycerides (n=162, 37.24%), and diabetes (n=64, 14.71%). Physical inactivity was also significantly more common (53.56%, p=0.004) compared to those engaging in regular activity. Women-specific risk factors comprised miscarriage (n=191, 43.91%). Therapeutic preferences varied, with a majority opting for lifestyle modifications (n=263, 60.39%) and pharmacological interventions (n=331, 76.33%). Conclusions This study provides a comprehensive understanding of prevalent cardiovascular risk factors, distinctive women-specific contributors, and diverse therapeutic preferences, highlighting the importance of personalized and targeted interventions to optimize women's cardiovascular health outcomes in contemporary medicine.

Efficacy and safety of fezolinetant for vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vasomotor symptoms (VMS), such as hot flashes and night sweats, are highly prevalent and burdensome for women experiencing menopausal transition. Fezolinetant, a selective neurokinin 3 receptor (NK3R) antagonist, is a potential therapeutic option for mitigating VMS. OBJECTIVES: Our aim is to assess the efficacy and evaluate the safety profile of fezolinetant compared with placebo in post-menopausal women suffering from VMS, by pooling all the relevant data and reflecting the most current evidence. SEARCH STRATEGY/SELECTION CRITERIA: An extensive literature search was performed in the PubMed, Medline and Cochrane Library databases from inception until June 2023 to identify relevant trials. DATA COLLECTION AND ANALYSIS: Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous outcomes. Risk ratios (RRs) were calculated for dichotomous outcomes. All statistical analyses were performed using R Statistical Software. MAIN RESULTS: A total of six randomized controlled trials were added. For the frequency of daily VMS, the combined pooled result favored the fezolinetant group over placebo (MD -2.38, 95% CI -2.64 to -2.12; P < 0.001, I2 = 0%). For the severity of daily VMS, fezolinetant was again found to be superior to the placebo group (MD -0.40, 95% CI -0.51 to -0.29; P < 0.001, I2 = 70%). Fezolinetant (120 mg) consistently demonstrated a significant reduction in the severity of daily moderate/severe VMS compared with other doses at both 4 and 12 weeks. Patient-reported outcomes (PROs) of Greene Climacteric Scale (GCS), PROMIS the Sleep Disturbance Short Form 8b and Menopause-Specific Quality of Life (MENQoL) scores indicated significant improvement with fezolinetant. No significant difference in efficacy of fezolinetant at 4 and 12 weeks were observed in any outcome. As for safety, no significant differences in the treatment emergent adverse events at 12 weeks were found between fezolinetant and placebo. CONCLUSIONS: Our study significantly favors fezolinetant over placebo regarding the primary efficacy outcomes of daily moderate to severe VMS frequency and severity, including PROs, while both the groups are comparable in terms of treatment emergent adverse events. Further studies are needed to confirm these findings.

Integration and usability of a digital cancer risk stratification tool to optimize identification of patients at risk for hereditary cancers: A pilot study.

BACKGROUND: Patients with a personal or family history of cancer may have elevated risk of developing future cancers, which often remains unrecognized due to lapses in screening. This pilot study assessed the usability and clinical outcomes of a cancer risk stratification tool in a gynecologic oncology clinic. METHODS: New gynecologic oncology patients were prompted to complete a commercially developed personal and family history-based risk stratification tool to assess eligibility for genetic testing using National Comprehensive Cancer Network criteria and estimated lifetime breast cancer risk using the Tyrer-Cuzick model. After use of the risk stratification tool, usability was assessed via completion rate and the System Usability Scale, and health literacy was assessed using the BRIEF Health Literacy Screening Tool. RESULTS: 130 patients were prompted to complete the risk stratification tool; 93 (72%) completed the tool. Race and ethnicity and insurance type were not associated with tool completion. The median System Usability Scale score was 83 out of 100 (interquartile range, 60-95). Health literacy positively correlated with perceived usability. Public insurance and race or ethnicity other than non-Hispanic White was associated with lower perceived usability. Sixty (65%) patients met eligibility criteria for genetic testing, and 21 (38% of 56 eligible patients) were candidates for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of ≥20%. CONCLUSIONS: A majority of patients completed the digital cancer risk stratification tool. Older age, lower health literacy, public insurance, and race or ethnicity other than non-Hispanic White were associated with lower perceived tool usability.

Personalized survivorship care: Routine breast cancer risk assessment in the gynecologic oncology clinic.

INTRODUCTION: Gynecologic and breast cancers share several risk factors. Breast cancer risk assessment tools can identify those at elevated risk and allow for enhanced breast surveillance and chemoprevention, however such tools are underutilized. We aim to evaluate the use of routine breast cancer risk assessment in a gynecologic oncology clinic. METHODS: A patient-facing web-based tool was used to collect personal and family history and run four validated breast cancer risk assessment models (Tyrer-Cuzick (TC), Gail, BRCAPRO, and Claus) in a gynecologic oncology clinic. We evaluated completion of the tools and identification of patients at elevated risk for breast cancer using the four validated models. RESULTS: A total of 99 patients were included in this analysis. The BRCAPRO model had the highest completion rate (84.8%), followed by the TC model (74.7%), Gail model (74.7%), and the Claus model (52.1%). The TC model identified 21.6% of patients completing the model as having ≥20% lifetime risk of breast cancer, compared to 6.8% by the Gail model, and 0% for both the BRCAPRO and Claus models. The Gail model identified 52.5% of patients as having ≥1.67% 5-year risk of breast cancer. Among patients identified as high-risk for breast cancer and eligible for screening, 9/9 (100%) were referred to a high-risk breast clinic. CONCLUSION: Among patients that completed the TC breast cancer risk assessment in a gynecologic oncology clinic, approximately 1 in 5 were identified to be at significantly elevated lifetime risk for breast cancer. The gynecologic oncologist's office might offer a convenient and feasible setting to incorporate this risk assessment into routine patient care, as gynecologic oncologists often have long-term patient relationships and participate in survivorship care.

Free-Flowing Polymer-Bonded Powder Composition of Hexahydro-1,3,5-trinitro-1,3,5-triazine Using Solvent-Slurry Coating.

A number of coating techniques have been used to improve the processability of high explosives. These techniques are typically used for developing compositions, such as boosters and fillers. The most typically used technique is the "solvent-slurry coating". Several compositions of polymer-bonded explosives have been industrialized using this technique. The NUPC-6 polymer-bonded powder composition of hexahydro-1,3,5-trinitro-1,3,5-triazine is optimized using the solvent-slurry coating. It involved multiple processes, i.e., preparing a slurry of high explosives in an aqueous phase, dissolving the modified polymer binder in an organic solvent, maintaining both the solvent and slurry at controlled temperatures, introducing polymer binder solution and ingredients in the slurry, distilling the solvent, mixing contents homogeneously, filtering the polymer-coated hexahydro-1,3,5-trinitro-1,3,5-triazine composition, and drying in a vacuum oven. The phlegmatizing and hydrophobic agents enhance flowability and hydrophobicity. The mass flow rate, bulk density, tapped density, compressibility index, and Hausner ratio are determined to evaluate its flowability during filling operations. The results show that the composition is flowable using a filling funnel, with a 150 mm upper diameter, 25 mm flow diameter, and 136 mm total funnel height. The raw polymer binder was modified using diisooctylsebacate and SAE-10 oil. The additives in the composition enhance its flowability, and it might be used in underwater applications.

Performance of T2-based PCA mix control chart with KDE control limit for monitoring variable and attribute characteristics.

In this work, the mixed multivariate T2 control chart's detailed performance evaluation based on PCA mix is explored. The control limit of the proposed control chart is calculated using the kernel density approach. Through simulation studies, the proposed chart's performance is assessed in terms of its capacity to identify outliers and process shifts. When 30% more outliers are included in the data, the proposed chart provides a consistent accuracy rate for identifying mixed outliers. For the balanced percentage of attribute qualities, misdetection happens because of the high false alarm rate. For unbalanced attribute qualities and excessive proportions, the masking effect is the key issue. The proposed chart shows the improved performance for the shift in identifying the shift in the process.

Thermal and hydraulic performance of ZnO/EG based nanofluids in mini tubes of different diameters: An experimental investigation.

The present experimental study investigates the thermal and hydraulic performance of Ethylene Glycol (EG)-based ZnO nanofluids (NFs) in circular minichannel test sections, each of 330 mm in length and 1.0-2.0 mm inner diameters. The experiments were conducted under steady-state constant heat flux and laminar flow conditions. The stable ZnO/EG-based NFs were synthesized using a standard two-step method in varying nanoparticles (NPs) loadings (0.012-0.048 wt%). The morphological characteristics, crystal structure, and specific surface area (SSA) showed that the NPs were sized in nm, possessing excellent crystal structure and enhanced surface area. Thermal conductivity (TC) and viscosity (VC) of the NFs were examined in the 20-60 °C temperature range. Both TC and VC possessed an increasing trend with the rise in concentration of the NPs. However, with the temperature rise, TC increased while the VC decreased and vice versa. The highest enhancements in TC and VC were 14.38 % and 15.22 %, respectively, at 40 °C and 0.048 wt% of NPs loading. The highest enrichment recorded in the local and average heat transfer coefficient (HTC) were 14.80 % and 13.48% in a minichannel with 1.0 mm inner diameter, respectively. It was directly proportional to the NPs loading and volume flow rate of the NFs. The friction factor was also directly proportional to the test section's inner cross-sectional area, while the pressure gradient showed an inverse behavior. An inverse relationship was recorded for the volume flow rate of the NFs and vice versa. Maximum friction factor and the pressure drop for all three minichannel test sections were recorded as 34.58 % and 32.16 %, respectively. The well-known Shah correlation predicted the local and average HTC within ±15.0 %, while the friction factor and the pressure gradient were well predicted by the Darcy correlation within the ±10.0 % range.

Serum Leptin levels in newly diagnosed Epileptic Patients.

Objectives: To compare leptin levels in newly-diagnosed treatment-naive epileptic patients and healthy controls. METHODS: This case-control study was conducted from January 10 to September 15, 2022, at the Dow University of Health Sciences, Karachi, and comprised newly-diagnosed epileptic patients age 12-35years who had no comorbidity. The subjects were enrolled from the Neurology out-patient department of Civil Hospital, Karachi. Healthy individuals matched for age, gender and body mass index were also enrolled as controls. Blood samples were collected between 8am and 10am for the evaluation of serum leptin levels using enzyme-linked immunosorbent assay. Data was analysed using SPSS 26. RESULTS: Of the 100 subjects, 64(64%) were males and 36(36%) were females. There were 50(50%) cases with mean age 19.34±5.65 years, and 50(50%) controls with mean age 19.76±5.67 (p=0.614). 100% of 50 individuals in control group did not have any family history of epilepsy,while 18% of cases (9) reported a positive family history. Mean leptin level in cases was 31.03±19.37 compared to 5.25±4.03 in the controls (p<0.05). CONCLUSIONS: Serum leptin levels were elevated in newly-diagnosed epileptic patients compared to healthy controls.

Innovations in Aortic Valve Replacement: A Comprehensive Overview of the Intuity Rapid Deployment Valve.

Rapid deployment/sutureless (RDS) valves have recently emerged as an innovative surgical solution, providing an alternative to traditional methods of surgical aortic valve replacement (SAVR) by eliminating the need for suture placement and tying. This innovation leads to a reduction in aortic crossclamp and cardiopulmonary bypass times, enhancing the efficiency of the procedure. Among the 2 available RDS valves, the Edwards Intuity valve in particular has been demonstrated to be a particularly promising substitute in the field of SAVR. The Intuity valve distinguishes itself from other RDS and conventional valves by yielding superior outcomes, such as a significant reduction in mortality, increase in the longevity of the valve, and a marked decrease in both mean and peak transvalvular pressure gradients. These benefits collectively contribute to its appeal as a favorable new solution. However, further investigation is needed to conclusively determine the long-term outcomes and safety of RDS valves. Nevertheless, the utilization of the Intuity valve presents an exciting solution to the existing limitations of conventional and minimally invasive SAVR, especially for patients afflicted with severe aortic stenosis.

Protein lysine acetylation does not contribute to the high rates of fatty acid oxidation seen in the post-ischemic heart.

High rates of cardiac fatty acid oxidation during reperfusion of ischemic hearts contribute to contractile dysfunction. This study aimed to investigate whether lysine acetylation affects fatty acid oxidation rates and recovery in post-ischemic hearts. Isolated working hearts from Sprague Dawley rats were perfused with 1.2 mM palmitate and 5 mM glucose and subjected to 30 min of ischemia and 40 min of reperfusion. Cardiac function, fatty acid oxidation, glucose oxidation, and glycolysis rates were compared between pre- and post-ischemic hearts. The acetylation status of enzymes involved in cardiac energy metabolism was assessed in both groups. Reperfusion after ischemia resulted in only a 41% recovery of cardiac work. Fatty acid oxidation and glycolysis rates increased while glucose oxidation rates decreased. The contribution of fatty acid oxidation to ATP production and TCA cycle activity increased from 90 to 93% and from 94.9 to 98.3%, respectively, in post-ischemic hearts. However, the overall acetylation status and acetylation levels of metabolic enzymes did not change in response to ischemia and reperfusion. These findings suggest that acetylation may not contribute to the high rates of fatty acid oxidation and reduced glucose oxidation observed in post-ischemic hearts perfused with high levels of palmitate substrate.

Quercetin modulates expression of serum exosomal long noncoding RNA NEAT1 to regulate the miR-129-5p/BDNF axis and attenuate cognitive impairment in diabetic mice.

AIMS: Cognitive impairment poses a considerable health challenge in the context of type 2 diabetes mellitus (T2DM), emphasizing the need for effective interventions. This study delves into the therapeutic efficacy of quercetin, a natural flavonoid, in mitigating cognitive impairment induced by T2DM in murine models. MATERIALS AND METHODS: Serum exosome samples were obtained from both T2DM-related and healthy mice for transcriptome sequencing, enabling the identification of differentially expressed mRNAs and long noncoding RNAs (lncRNAs). Subsequent experiments were conducted to ascertain the binding affinity between mmu-miR-129-5p, NEAT1 and BDNF. The structural characteristics and dimensions of isolated exosomes were scrutinized, and the expression levels of exosome-associated proteins were quantified. Primary mouse hippocampal neurons were cultured for in vitro validation, assessing the expression of pertinent genes as well as neuronal vitality, proliferation, and apoptosis capabilities. For in vivo validation, a T2DM mouse model was established, and quercetin treatment was administered. Changes in various parameters, cognitive ability, and the expression of insulin-related proteins, along with pivotal signaling pathways, were monitored. KEY FINDINGS: Analysis of serum exosomes from T2DM mice revealed dysregulation of NEAT1, mmu-miR-129-5p, and BDNF. In vitro investigations demonstrated that NEAT1 upregulated BDNF expression by inhibiting mmu-miR-129-5p. Overexpression of mmu-miR-129-5p or silencing NEAT1 resulted in the downregulation of insulin-related protein expression, enhanced apoptosis, and suppressed neuronal proliferation. In vivo studies validated that quercetin treatment significantly ameliorated T2DM-related cognitive impairment in mice. SIGNIFICANCE: These findings suggest that quercetin holds promise in inhibiting hippocampal neuron apoptosis and improving T2DM-related cognitive impairment by modulating the NEAT1/miR-129-5p/BDNF pathway within serum exosomes.