Reduced Breast and Ovarian Cancer Through Targeted Genetic Testing: Estimates Using the NEEMO Microsimulation Model.

The effectiveness and cost-effectiveness of genetic testing for hereditary breast and ovarian cancer largely rely on the identification and clinical management of individuals with a pathogenic variant prior to developing cancer. Simulation modelling is commonly utilised to evaluate genetic testing strategies due to its ability to synthesise collections of data and extrapolate over long time periods and large populations. Existing genetic testing simulation models use simplifying assumptions for predictive genetic testing and risk management uptake, which could impact the reliability of their estimates.

Using polygenic risk modification to improve breast cancer prevention: study protocol for the PRiMo multicentre randomised controlled trial.

Introduction: Established personal and familial risk factors contribute collectively to a woman's risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to investigate these risks but recent information on the role of common genomic variants, in the form of a Polygenic Risk Score (PRS), has provided the potential to further personalise breast and ovarian cancer risk assessment. Data from cohort studies support the potential of an integrated risk assessment to improve targeted risk management but experience of this approach in clinical practice is limited.

Personalising genetic counselling (POETIC) trial: Protocol for a hybrid type II effectiveness-implementation randomised clinical trial of a patient screening tool to improve patient empowerment after cancer genetic counselling.

Background: Genetic counselling aims to identify, and address, patient needs while facilitating informed decision-making about genetic testing and promoting empowerment and adaptation to genetic information. Increasing demand for cancer genetic testing and genetic counsellor workforce capacity limitations may impact the quality of genetic counselling provided. The use of a validated genetic-specific screening tool, the Genetic Psychosocial Risk Instrument (GPRI), may facilitate patient-centred genetic counselling.

Cost-effectiveness of long-term clinical management of BRCA pathogenic variant carriers.

Purpose: Women who inherit a BRCA1 or BRCA2 pathogenic variant are at high risk of developing breast and ovarian cancer. Evidence for the effectiveness and cost-effectiveness of long-term management in clinical practice is lacking. The purpose of this study was to evaluate the real-world cost-effectiveness of BRCA carrier management within a structured clinical program.

A Microsimulation Model for Evaluating the Effectiveness of Cancer Risk Management for BRCA Pathogenic Variant Carriers: miBRovaCAre.

Objectives: To develop a validated model for evaluating the real-world effectiveness of long-term clinical management strategies for women with germline BRCA1 or BRCA2 pathogenic variants.

Methods: A microsimulation model was developed that included a BRCA-specific natural history for breast and ovarian cancer, a clinical framework for carrier follow-up, and cancer risk management strategies (breast screening, risk-reducing mastectomy, and bilateral salpingo-oophorectomy). Adherence rates and outcomes for breast screening and risk-reducing surgery were obtained from BRCA carriers seen through a familial cancer service in Melbourne, Australia.

Evaluation of telephone genetic counselling to facilitate germline BRCA1/2 testing in women with high-grade serous ovarian cancer.

Systemic healthcare issues and geographical challenges restrict women's access to BRCA1/2 testing to inform the use of tailored treatments for high-grade serous ovarian cancer. Consequently, BRCA1/2 testing in this population is low and improved testing pathways are urgently needed. This study aimed to determine the acceptability and feasibility of telephone genetic counselling (TGC) to facilitate treatment-focused BRCA1/2 testing in Australia for women with high-grade serous ovarian cancer.

Correction: Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis.

In the original version of this Article, the affiliation details for Lei Zhang were given as Monash University. While working on the Article Dr. Zhang was also affiliated with the Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China.

Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis.

Purpose: To consider the impact and cost-effectiveness of offering preventive population genomic screening to all young adults in a single-payer health-care system.

Methods: We modeled screening of 2,688,192 individuals, all adults aged 18-25 years in Australia, for pathogenic variants in BRCA1/BRCA2/MLH1/MSH2 genes, and carrier screening for cystic fibrosis (CF), spinal muscular atrophy (SMA), and fragile X syndrome (FXS), at 71% testing uptake using per-test costs ranging from AUD$200 to $1200 (~USD$140 to $850). Investment costs included genetic counseling, surveillance, and interventions (reimbursed only) for at-risk individuals/couples.

Changing landscape of hereditary breast and ovarian cancer germline genetic testing in Australia.

Federal funding for germline genetic testing in hereditary breast and ovarian cancer (HBOC) was recently introduced. Germline testing for HBOC under Medicare Benefits Schedule items 73296/73297 can be requested by any specialist, whereas the previous state- and territory-funded testing was limited to those operating within a familial cancer service. The impact of this decentralisation of HBOC testing on health and economic outcomes is uncertain, primarily as it has potential to significantly disrupt the clinical framework that generated the evidence used to justify clinical implementation of the Medicare Benefits Schedules.

Cost-effectiveness and comparative effectiveness of cancer risk management strategies in BRCA1/2 mutation carriers: a systematic review.

Purpose: To review the evidence for the effectiveness and cost-effectiveness of cancer risk management interventions for BRCA carriers.

Methods: Comparative effectiveness and cost-effectiveness analyses were identified by searching scientific and health economic databases. Eligible studies modeled the impact of a cancer risk management intervention in BRCA carriers on life expectancy (LE), cancer incidence, or quality-adjusted life years (QALYs), with or without costs.

Consumer attitudes towards the establishment of a national Australian familial cancer research database by the Inherited Cancer Connect (ICCon) Partnership.

Clinical genetics units hold large amounts of information which could be utilised to benefit patients and their families. In Australia, a national research database, the Inherited Cancer Connect (ICCon) database, is being established that comprises clinical genetic data held for all carriers of mutations in cancer predisposition genes. Consumer input was sought to establish the acceptability of the inclusion of clinical genetic data into a research database.

Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

Aim: To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.

Methods: Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density.

Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation.

Background: Tumour-derived extracellular vesicles (EVs) play a role in tumour progression; however, the spectrum of molecular mechanisms regulating EV secretion and cargo selection remain to be fully elucidated. We have reported that cavin-1 expression in prostate cancer PC3 cells reduced the abundance of a subset of EV proteins, concomitant with reduced xenograft tumour growth and metastasis.

Methods: We examined the functional outcomes and mechanisms of cavin-1 expression on PC3-derived EVs (PC3-EVs).

[Effect of veroshpiron on hormone level in patients with Parkinson's disease].

Blood hormones and urinary excretion of corticosteroids were measured in 39 parkinsonian patients receiving chemotherapy with adjuvant 3-week course of verospiron (50-100 mg/day). The latter promoted normalization of endocrine and clinical statuses in the majority of the patients. It is suggested that the response may be obtained via neuropeptide systems of the brain.

[The characteristics of catecholamine excretion in parkinsonism patients in effective treatment and therapeutic resistance].

Catecholamines excretion has been analyzed in 36 patients suffering from parkinsonism and in 30 normal subjects. Curable patients demonstrated the same proportion of epinephrine and norepinephrine/DOPA excretion as normal subjects did. In resistant to treatment subjects and in unlikely curable the above coefficients were significantly larger.

[Fahr's syndrome].

A rare syndrome is described. Combined investigation, including CT, yielded in a patient a typical clinical picture of nonatherosclerotic brain vessel calcification, especially within basal ganglia, parkinsonism, psychoemotional disorders, motor paroxysms. The syndrome etiology is discussed.

[Correlation of clinico-physiologic indices and the serotonin content of the blood of patients with parkinsonism].

On withdrawal of L-DOPA-containing drugs the blood serotonin content decreased in parkinsonism patients irrespective of form and etiology of the disease. L-DOPA-containing drugs caused the blood serotonin levels to rise. Substantial correlations of the blood serotonin levels and clinico-physiologic indices were found mostly in postencephalitic parkinsonism.

[Dynamics of various electrophysiologic indices in patients with mild acute closed craniocerebral injuries during complex treatment using reflexotherapy].

An analysis of 117 cases of acute closed craniocerebral trauma (CCCT) of a mild degree, the time-course of the EEG, EchoEG and REG findings in the process of treatment has shown that mild CCCT was expressed clinically in CSF hypertension, as well as vegetovascular and asthenoneurotic syndromes. The detection at the early stages of the injury of the leading clinical syndrome contributes to the conduction of purposeful therapeutic measures. A positive time-course of some electrophysiological parameters indicates the normalization of vegetovascular dysfunctions under the impact of acupuncture, which permits the use of this method in the multiple modality treatment of CCCT in the acute period.

[Electromyographic characteristics of the neuromuscular disorders in botulism].

The total bioelectrical activity of the muscles of the upper extremities as well as the neuromuscular transmission were examined in 30 patients with botulism at various stages of the disease. A picture of low-amplitude interference electromyogram was revealed. The results of stimulation electromyography pointed to a peculiar disorder of the neuromuscular transmission associated with a defect in the mediator release.