Hereditary ovarian cancer risk reduction: a retrospective evaluation of patient perspectives and service provision at a regional hereditary gynaecologic cancer clinic 2006-2016.

BACKGROUND: Germline pathogenic variants in BRCA1/2 have been established in hereditary breast and ovarian cancer (HBOC) syndrome and result in significantly elevated lifetime risk of ovarian cancer. Risk reduction interventions are presently the only effective means of improving survival and specialized counselling clinics have been established as an effective means of aiding this population in navigating complex decisions surrounding these interventions. This study sought to evaluate patient perceptions of a specialized counselling clinic for patients with HBOC Syndrome and referral patterns to this clinic. METHODS: We completed a retrospective review of 200 patients with HBOC in Nova Scotia, Canada seen through Maritime Medical Genetics Services between 2006 and 2016. Data were collected on referral pattern to the Hereditary Gynaecologic Risk Reduction Clinic (HGRRC), demographics, health history, and uptake of risk-reducing interventions. Participants were invited to complete a questionnaire about their experience. RESULTS: 156/200(78%) women were referred to HGRCC and 135/156 (85.9%) of those referred attended their appointment. 124/200 (62%) were over age 40 at the time of testing. The mean time from referral to HGRCC appointment was 134.68 days (SD 85.78). 85/135 (63%) underwent risk-reducing bilateral salpingo-oophorectomy following their HGRCC appointment. The questionnaire was completed by 94/188 (50.3%) women. Most participants found information received from genetics clinics (81/94; 91%) and genetic counsellors (87/94; 95%) most helpful in making choices around risk-reduction strategies. 83/94 (88%) participants felt they had sufficient information to make an informed decision. CONCLUSION: The majority of women with HBOC in Nova Scotia during the study period were referred to and counselled through HGRRC. Genetic counselling was found most valuable in risk-reduction decision making, which highlights the importance of a multidisciplinary team. Patients viewed this clinic as an effective care model to support informed choice about risk-reducing intervention.

Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model.

Women with pathogenic variants in BRCA1/2 have a significantly increased lifetime risk of breast and ovarian cancers. The availability of genetic testing to identify BRCA1/2 carriers is imperative to disease prevention and treatment. We evaluated the effectiveness of a new collaborative care model in Nova Scotia, involving the integration of genetic counselors into tumor board rounds, reduction in time allotted for initial genetic counseling appointments from 60 to 45 min, and a standardized dictation template, to increase referral rate for genetic counseling. We also assessed the study cohorts' preferences on timing for genetic testing. A retrospective chart review was performed on all women diagnosed with epithelial ovarian cancer (EOC) from 2012 to 2017 (N = 386). Pertinent clinical outcomes were categorized and wait times to different nodes of the clinical pathway assessed. A questionnaire was sent to this same cohort of women to identify preference for the timing of genetic testing (n = 103). The chi-square and Wilcoxon's rank-sum tests were used to compare demographic and clinical variables pre- and post-care model implementation. We identified a 48.2% (95% CI: 39.4-56.7, p < .001) increase in referral for genetic counseling following implementation of the new care model. Median time from diagnosis to referral decreased by 74.0 days (p < .001) and median time from referral to first appointment by 54.0 days (p < .001). 56.3% of women desired referral at the time of diagnosis. This care model for women newly diagnosed with EOC in Nova Scotia was successful in increasing referral rates for genetic counseling. Majority of women pursued genetic testing following and favored that referral for genetic counseling be made at the time of diagnosis, highlighting the importance for timely access.

Effect of Bisphosphonates on Bone Health in Adult Renal Transplant Patients: Beyond the First Year Posttransplant-A Systematic Review and Meta-Analysis.

BACKGROUND: Bone mineral density (BMD) decreases postrenal transplantation. Evidence demonstrating the effects of bisphosphonates on BMD and fracture risk beyond 1-year posttransplant is sparse in existing literature, but remains essential to enhance clinical outcomes in this population. OBJECTIVE: Our study aimed to systematically review and meta-analyze the current literature on the use of any bisphosphonate in the adult renal transplant population beyond the first year of renal transplant to determine its effect on BMD and fracture incidence. DESIGN: We conducted a systematic review and meta-analysis of primary research literature that included full-text, English-language, original randomized clinical trials (RCTs) and observational studies. SETTING: Patient data were primarily captured in an outpatient setting across various studies. PATIENTS: Our population of interest was patients older than 18 years who received deceased/living donor kidney transplantation and any bisphosphonate with a follow-up greater than 12 months posttransplantation. MEASUREMENTS: The primary outcome was change in BMD from baseline. Secondary outcomes were the incidence of fractures and effects of other confounders on bone health. METHODS: We included RCTs and observational studies that satisfied our inclusion criteria. Each study was analyzed for risk of bias and data were extrapolated to analyze for overall statistical significance accounting for heterogeneity of studies. RESULTS: Sixteen studies (N = 1762) were analyzed. The follow-up ranged from 12 to 98 months. There was a nonsignificant improvement in BMD with bisphosphonate treatment persisting into the second and third years posttransplant at the lumbar spine. The calculated standardized mean BMD difference was -0.29 (-0.75 to 0.17), P = .22. Only 5 studies reported a total of 43 new fractures. Prednisone (P < .01), low body weight (P < .001), low body mass index (P < .01), and male gender (P < .05) correlated with reduced lumbar and femoral BMD. LIMITATIONS: Limitations of this review include the use of BMD as a surrogate outcome, the bias of the included studies, and the incomplete reporting data in numerous analyzed studies. CONCLUSIONS: We demonstrate no statistically significant benefit of bisphosphonate treatment on BMD beyond the first year postrenal transplantation. Despite heterogeneity of treatment, a differential nonsignificant improvement in lumbar spine BMD was consistent and may be clinically relevant. TRIAL REGISTRATION: PROSPERO CRD42019125593.

CONTEXTE: La densité minérale osseuse (DMO) décroit à la suite d'une greffe rénale. Les données probantes faisant état des effets des bisphosphonates sur la DMO et le risque de fracture au-delà d'un an post-greffe sont rares dans la littérature, mais demeurent essentielles pour améliorer les résultats cliniques pour cette population. OBJECTIF: L'étude actuelle visait à réaliser une revue systématique et une méta-analyse de la littérature faisant état de l'usage des bisphosphonates dans une population de greffés rénaux adultes, au-delà de la première année post-greffe, afin de connaître les effets de cette médication sur la DMO et sur l'incidence de fractures. TYPE D'ÉTUDE: Une revue systématique et une méta-analyse de la littérature ont été réalisées à partir d'articles rédigés en anglais, présentant les résultats d'essais cliniques et d'études observationnelles. CADRE: Dans les différentes études, les données provenaient principalement de patients suivis sur une base externe. SUJETS: Notre population d'intérêt était constituée de patients adultes ayant subi une greffe rénale provenant d'un donneur décédé ou vivant, ayant reçu un traitement par un bisphosphonate et ayant été suivis pendant plus de douze mois post-transplantation. MESURES: L'issue principale était une variation de la DMO par rapport à la valeur initiale. L'incidence de fractures et les effets des autres facteurs de confusion sur la santé osseuse constituaient les issues secondaires. MÉTHODOLOGIE: Ont été inclus les essais cliniques et les études observationnelles qui répondaient à nos critères d'inclusion. Chaque étude a fait l'objet d'une analyse des risques de biais et les données ont été extrapolées pour analyser la signification statistique de l'ensemble en tenant compte de l'hétérogénéité des études. RÉSULTATS: Seize études (n=1762) ont été analysées. La période de suivi variait de 12 à 98 mois. Une amélioration non significative de la DMO du rachis lombaire ayant persisté dans la deuxième et la troisième année post-greffe a été observée à la suite d'un traitement par un bisphosphonate. La moyenne normalisée calculée des variations de la DMO s'établissait à -0,29 (-0,75 à 0,17; p=0,22). Seules cinq études ont rapporté de nouvelles fractures, pour un total de 43 fractures. La prise de prednisone (p<0,01), un faible poids (p<0, 001), un faible IMC (p<0,01) et le fait d'être un homme (p<0,05) ont corrélé avec une DMO lombaire ou fémorale réduite. LIMITES: Le recours à la DMO comme issue intermédiaire, les biais contenus dans les études incluses et le fait que plusieurs des études analysées comportaient des données incomplètes constituent les limites de l'étude. CONCLUSION: Nous n'avons pu démontrer un avantage statistiquement significatif sur la DMO à poursuivre un traitement par les bisphosphonates au-delà de la première année suivant une greffe rénale. Malgré l'hétérogénéité du traitement, une amélioration non significative de la DMO lombaire a été observée et pourrait s'avérer pertinente sur le plan clinique.

Combined Autoimmune Cytopenias Presenting in Childhood.

BACKGROUND: Pediatric patients with chronic and/or refractory autoimmune multi-lineage cytopenias present challenges in both diagnosis and management. Increasing availability of diagnostic testing has revealed an underlying immune dysfunction in patients previously diagnosed with Evans Syndrome. However, the data are sparse and the majority of patients are adults. PROCEDURE: We performed a retrospective chart review to document the natural history of 23 pediatric patients with autoimmune multi-lineage cytopenias followed at three tertiary care pediatric hematology clinics. RESULTS: Investigations revealed seven patients (30.4%) with an autoimmune lymphoproliferative-like syndrome and six patients (26.1%) with other primary immunodeficiencies. Only one (4.3%) patient was suspected to have systemic lupus erythematosus and six patients (26.1%) had other types of autoimmunity. Treatment consisted of immunosuppressive therapy, intravenous gammaglobulin, and splenectomy. Supportive care included granulocyte-colony stimulating factor, and blood product transfusions. Two patients (8.7%) died. Complete remission was achieved in 3 patients (13.0%); of the remaining, 14 patients (60.9%) had chronic immune thrombocytopenic purpura, 10 patients (43.5%) chronic autoimmune neutropenia, and 4 patients (17.4%) chronic autoimmune hemolytic anemia with a median follow up of 5 years (2 months-12 years). CONCLUSIONS: These data suggest that pediatric patients presenting with autoimmune multi-lineage cytopenias should undergo investigation for underlying immune dysregulation, including autoimmune lymphoproliferative syndrome, other primary immunodeficiencies and autoimmune disorders. The development of an international registry for such patients is imperative to improve the understanding of their complex natural history.

The value of usability testing for Internet-based adolescent self-management interventions: "Managing Hemophilia Online".

BACKGROUND: As adolescents with hemophilia approach adulthood, they are expected to assume responsibility for their disease management. A bilingual (English and French) Internet-based self-management program, "Teens Taking Charge: Managing Hemophilia Online," was developed to support adolescents with hemophilia in this transition. This study explored the usability of the website and resulted in refinement of the prototype. METHODS: A purposive sample (n=18; age 13-18; mean age 15.5 years) was recruited from two tertiary care centers to assess the usability of the program in English and French. Qualitative observations using a "think aloud" usability testing method and semi-structured interviews were conducted in four iterative cycles, with changes to the prototype made as necessary following each cycle. This study was approved by research ethics boards at each site. RESULTS: Teens responded positively to the content and appearance of the website and felt that it was easy to navigate and understand. The multimedia components (videos, animations, quizzes) were felt to enrich the experience. Changes to the presentation of content and the website user-interface were made after the first, second and third cycles of testing in English. Cycle four did not result in any further changes. CONCLUSIONS: Overall, teens found the website to be easy to use. Usability testing identified end-user concerns that informed improvements to the program. Usability testing is a crucial step in the development of Internet-based self-management programs to ensure information is delivered in a manner that is accessible and understood by users.