A patient decision aid for risk-reducing surgery in premenopausal BRCA1/2 mutation carriers: Development process and pilot testing

Background: BRCA1/2 mutation carriers’ choice between risk-reducing salpingo-oophorectomy (RRSO) and salpingectomy with delayed oophorectomy is very complex. Aim was to develop a patient decision aid that combines evidence with patient preferences to facilitate decision making. Design: Systematic development of a patient decision aid in an iterative process of prototype development, alpha testing by patients and clinicians and revisions using International Patient Decision Aid Standards (IPDAS) quality criteria. Information was based on the available literature and current guidelines. A multidisciplinary steering group supervised the process. Setting and participants: Pre-menopausal BRCA1/2 mutation carriers choosing between RRSO and salpingectomy with delayed oophorectomy in Family Cancer Clinics in the Netherlands. Main outcome measures: IPDAS quality criteria, relevance, usability, clarity. Results: The patient decision aid underwent four rounds of alpha testing and revisions. Finally, two paper decision aids were developed: one for BRCA1 and one for BRCA2. They both contained a general introduction, three chapters and a step-by-step plan containing a personal value clarification worksheet. During alpha testing, risk communication and information about premature menopause and hormone therapy were the most revised items. The patient decision aids fulfil 37 of 43 (86%) IPDAS criteria for content and development process. Discussion and conclusions: Both BRCA1/2 mutation carriers and professionals are willing to use or offer the developed patient decision aids for risk-reducing surgery. The patient decision aids have been found clear, balanced and comprehensible. Future testing among patients facing the decision should point out its effectiveness in improving decision making

Salpingectomy with delayed oophorectomy in BRCA1/2 mutation carriers

Contains fulltext : 173261.pdf (publisher's version ) (Open Access)Radboud University, 22 juni 2017Promotores : Massuger, L.F.A.G., Hoogerbrugge-van der Linden, N. Co-promotores : Hullu, J.A. de, Hermens, R.P.M.G

How medical choices influence quality of life of women carrying a BRCA mutation

Germline mutations in BRCA1 and BRCA2 genes were discovered twenty years ago. Female BRCA mutation carriers have an increased risk of breast and ovarian cancer at a relatively young age. Several choices have to be made with respect to cancer risk management, and consequences of these choices may affect quality of life. A review of the literature was performed to evaluate quality of life in unaffected BRCA mutation carriers and the influence of these medical choices. Overall, general quality of life appears not to be permanently affected in BRCA mutation carriers or by their choices. Risk-reducing salpingo-oophorectomy and its subsequent premature menopause affect (menopause specific) quality of life most. Hormone replacement therapy does not fully alleviate climacteric symptoms and therefore, there is a strong need for alternative strategies to reduce ovarian cancer risk and/or for improvements in postoperative care. Future research should focus on these needs

Robot-mediated ACtive REhabilitation (ACRE2) for the hemiplegic upper limb after a stroke: A pilot study

Although scientific evidence shows that therapy improves movement recovery following a stroke, the duration of the reimbursed therapy available to patients is decreasing. To compensate for the reduction in personal therapy self-training procedures using robotic arms have been developed for hemiplegic patients. In this Dutch pilot study, the experiences of stroke patients and their therapists with the second prototype of a robotic arm device for ACtive REhabilitation (ACRE2) are evaluated. Positive results for patients and therapists are reported and the development of a system that can be used at home (ACRE3) is recommended. © 2007 IOS Press. All rights reserved

Further insights into the role of tumour characteristics in survival of young women with epithelial ovarian cancer

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Risk-reducing salpingectomy with delayed oophorectomy in BRCA1/2 mutation carriers: Patients' and professionals' perspectives

OBJECTIVE: To identify influencing factors of BRCA1/2 mutation carriers and their professionals for risk-reducing salpingectomy (RRS) with delayed oophorectomy (RRO) as a substitute for risk-reducing salpingo-oophorectomy (RRSO) and for study participation on this concept. METHODS: A qualitative study was performed by four focus group interviews with 39 BRCA1/2 mutation carriers and semi-structured in-depth interviews with 23 professionals in the field of hereditary cancer. We used a theoretical framework of determinants of innovation within healthcare organizations to classify influencing factors (barriers and facilitators). RESULTS: Among BRCA1/2 mutation carriers, main barriers for RRS with delayed RRO were seriousness of ovarian cancer, family history, and previous breast cancer. Among professionals, delay of risk-reducing effect of oophorectomy on breast cancer risk and a second operation were recognized as main barriers. Both BRCA1/2 mutation carriers and professionals found uncertainty about the effect of RRS with delayed RRO and ease of the decision to undergo RRSO important barriers. The main facilitator mentioned by both was longer maintenance of ovarian function thereby delaying negative effects of early surgical menopause. For study participation, BRCA1/2 mutation carriers mentioned a randomized study design as the main barrier, whereas professionals identified two facilitators, namely willingness of BRCA1/2 mutation carriers for study participation and uniform counseling. Furthermore, most BRCA1/2 mutation carriers and professionals were willing to consider participation in a future non-randomized study. CONCLUSIONS: We identified several barriers and facilitators for RRS with delayed RRO, and for study participation which can be addressed to optimize the design and implementation of a non-randomized study

A three-goal model for patients with multimorbidity: A qualitative approach

Contains fulltext : 190875.pdf (publisher's version ) (Open Access)BACKGROUND: To meet the challenge of multimorbidity in decision making, a switch from a disease-oriented to a goal-oriented approach could be beneficial for patients and clinicians. More insight about the concept and the implementation of this approach in clinical practice is needed. OBJECTIVE: This study aimed to develop conceptual descriptions of goal-oriented care by examining the perspectives of general practitioners (GPs) and clinical geriatricians (CGs), and how the concept relates to collaborative communication and shared decision making with elderly patients with multimorbidity. METHOD: Qualitative interviews with GPs and CGs were conducted and analyzed using thematic analysis. RESULTS: Clinicians distinguished disease- or symptom-specific goals, functional goals and a new type of goals, which we labelled as fundamental goals. "Fundamental goals" are goals specifying patient's priorities in life, related to their values and core relationships. These fundamental goals can be considered implicitly or explicitly in decision making or can be ignored. Reasons to explicate goals are the potential mismatch between medical standards and patient preferences and the need to know individual patient values in case of multimorbidity, including the management in acute situations. CONCLUSION: Based on the perspectives of clinicians, we expanded the concept of goal-oriented care by identifying a three-level goal hierarchy. This model could facilitate collaborative goal-setting for patients with multiple long-term conditions in clinical practice. Future research is needed to refine and validate this model and to provide specific guidance for medical training and practice

Cytokine production induced by non-encapsulated and encapsulated Porphyromonas gingivalis strains

OBJECTIVE: Although the exact reason is not known, encapsulated gram-negative Porphyromonas gingivalis strains are more virulent than non-encapsulated strains. Since difference in virulence properties may be due to difference in cytokine production following recognition of the bacteria or their products by the host inflammatory cells, we compared cytokine production following stimulation with bacteria or lipopolysaccharides (LPS) of a non-encapsulated and an encapsulated P. gingivalis strain (K(-) and K1). DESIGN: Tumour necrosis factor-alpha (TNF-alpha) production following stimulation of the cell-line Mono Mac 6 with bacteria or LPS of both P. gingivalis strains was determined using flow cytometry. Furthermore, we investigated the effects of the two P. gingivalis strains or their LPS on TNF-alpha and Interleukin (IL-1beta, IL-6, IL-12 and IL-10) production in whole blood using Luminex. In both experiments, Escherichia coli bacteria and LPS were used as a reference. RESULTS: Both P. gingivalis strains induced lower cytokine production than E. coli with the exception of IL-6. P. gingivalis K1 bacteria elicited a higher overall cytokine production than P. gingivalis K(-). In contrast, P. gingivalis K1 LPS stimulation induced a lower cytokine production than P. gingivalis K(-) LPS. CONCLUSIONS: Our findings suggest that the encapsulated P. gingivalis K1 bacteria induce higher cytokine production than the non-encapsulated P. gingivalis K(-). This was not due to its LPS. The stronger induction of cytokines may contribute to the higher virulence of P. gingivalis K1

Identification of the structural basis of thermal lability of a virus provides a rationale for improved vaccines

Virus stability and dynamics play critical roles during infection. Some viruses, including foot-and-mouth disease virus (FMDV), are surprisingly prone to thermal dissociation outside the cell. The structural bases and functional implications of this distinctive trait were essentially unknown. This study (1) uncovers the structural determinants of FMDV thermolability, (2) investigates the relationship between virus thermolability and infectivity, and (3) provides a structure-based rationale for engineering thermostable virus particles to develop improved vaccines and nanocontainers. The results reveal that negatively charged residues close to protein-protein interfaces exert electrostatic repulsions between capsid subunits and mediate the sensitivity of the virion to thermal dissociation, even at neutral pH. Based on these results, a series of fully infectious virions of increased thermostability were engineered by individually removing different carboxylates involved in intersubunit repulsions. The implications for virus biology and the design of thermostable vaccines are discussed

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis.

BACKGROUND: Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations. OBJECTIVE AND RATIONALE: We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers. SEARCH METHODS: A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods. OUTCOMES: Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36-1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90-1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52-0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38-0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26-0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53-1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low. WIDER IMPLICATIONS: The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients' preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time