Attitudes, Knowledge, and Risk Perceptions of Patients who Received Elective Genomic Testing as a Clinical Service.

BACKGROUND: Elective genomic testing (EGT) is increasingly available clinically. Limited real world evidence exists about attitudes and knowledge of EGT recipients. METHODS: After web-based education, patients who enrolled in an EGT program at a rural nonprofit healthcare system completed a survey that assessed attitudes, knowledge, and risk perceptions. RESULTS: From August 2020 to April 2022, 5,920 patients completed the survey and received testing. Patients most frequently cited interest in learning their personal disease risks as their primary motivation. Patients most often expected results to guide medication management (74.0%), prevent future disease (70.4%), and provide information about risks to offspring (65.4%). Patients were "very concerned" most frequently about the privacy of genetic information (19.8%) and how well testing predicted disease risks (18.0%). On average, patients answered 6.7 of 11 knowledge items correctly (61.3%). They more often rated their risks for colon and breast cancers as lower rather than higher than the average person, but more often rated their risk for a heart attack as higher rather than lower than the average person (all p<0.001). CONCLUSION: Patients pursued EGT because of the utility expectations, but often misunderstood the test's capabilities.

Benefits, harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model.

PURPOSE: Population newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain. METHODS: We developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns. Those identified with pathogenic/likely pathogenic variants associated with increased risk of HCM underwent surveillance and recommended treatment, whereas in usual care, individuals with family histories of HCM underwent surveillance. RESULTS: In a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 years by 44 (95% uncertainty interval [UI] = 10-103) however increase the numbers of children undergoing surveillance by 8127 (95% UI = 6308-9664). Compared with usual care, newborn genetic screening costs $267,000 per life year saved (95% UI, $106,000 to $919,000 per life year saved). CONCLUSION: Newborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance. This study shows how modeling can provide insights into the tradeoffs between benefits and costs that will need to be considered as newborn genetic screening is more widely adopted.

Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Community Health Study/Study of Latinos.

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.

Improved provider preparedness through an 8-part genetics and genomic education program.

PURPOSE: Large-scale genetics education appropriate for general practice providers is a growing priority. We describe the content and impact of a mandatory system-wide program implemented at Sanford Health. METHODS: The Imagenetics Initiative at Sanford Health developed a 2-year genetics education program with quarterly web-based modules that were mandatory for all physicians and advanced practice providers. Scores of 0 to 5 were calculated for each module on the basis of the number of objectives that the participants reported as fulfilled. In addition, the participants completed surveys before starting and after finishing the education program, which included a 7-item measure scored 7 to 28 on the perceived preparedness to practice genetics. RESULTS: Between 2252 and 2822 Sanford Health employees completed each of the 8 quarterly education modules. The ratings were highest for the module about using genomics to improve patient management (mean score = 4.3) and lowest for the module about different types of genetic tests and specialists. The mean perceived preparedness scores increased from 15.7 at pre-education to 19.1 at post-education (P < .001). CONCLUSION: Web-based genetics education was highly effective in increasing health care providers' confidence about using genetics. Both comfort with personal knowledge and confidence regarding access to the system's genomic medicine experts increased significantly. The results demonstrate how scalable approaches can improve provider preparedness.

Reducing the expression of the Numb adaptor protein in neurons increases the searching behavior of Drosophila larvae.

Drosophila larval crawling is easily-observable and relatively stereotyped. Crawling consists of linear locomotion interrupted by periods when the larvae pause, swing their heads, and change direction (a 'search'). Here we identify Numb, a peripheral membrane adaptor protein, as an important regulator of searching behavior. When Numb RNAi transgenes were expressed in all neurons, searching frequency increased while linear movement appeared normal. Numb's role in suppressing searching behavior was verified by rescuing this phenotype with a Numb homologue from mice. Such behavioral specificity suggests that further analysis of searching might help identify additional, evolutionarily-conserved interactors of the Numb protein.

Primary care providers' responses to unsolicited Lynch syndrome secondary findings of varying clinical significance.

PURPOSE: How primary care providers (PCPs) respond to genomic secondary findings (SFs) of varying clinical significance (pathogenic, uncertain significance [VUS], or benign) is unknown. METHODS: We randomized 148 American Academy of Family Physicians members to review three reports with varying significance for Lynch syndrome. Participants provided open-ended responses about the follow-up they would address and organized the SF reports and five other topics in the order they would prioritize responding to them (1 = highest priority, 6 = lowest priority). RESULTS: PCPs suggested referrals more often for pathogenic variants or VUS than benign variants (72% vs. 16%, p < 0.001). PCPs were also more likely to address further workup, like a colonoscopy or esophagogastroduodenoscopy, in response to pathogenic variants or VUS than benign variants (43% vs. 4%, p < 0.001). The likelihoods of addressing referrals or further workup were similar when PCPs reviewed pathogenic variants and VUS (both p > 0.46). SF reports were prioritized highest for pathogenic variants (2.7 for pathogenic variants, 3.6 for VUS, 4.3 for benign variants, all p ≤ 0.014). CONCLUSION: Results suggest that while PCPs appreciated the differences in clinical significance, disclosure of VUS as SFs would substantially increase downstream health-care utilization.

Precision Population Medicine in Primary Care: The Sanford Chip Experience.

Genetic testing has the potential to revolutionize primary care, but few health systems have developed the infrastructure to support precision population medicine applications or attempted to evaluate its impact on patient and provider outcomes. In 2018, Sanford Health, the nation's largest rural nonprofit health care system, began offering genetic testing to its primary care patients. To date, more than 11,000 patients have participated in the Sanford Chip Program, over 90% of whom have been identified with at least one informative pharmacogenomic variant, and about 1.5% of whom have been identified with a medically actionable predisposition for disease. This manuscript describes the rationale for offering the Sanford Chip, the programs and infrastructure implemented to support it, and evolving plans for research to evaluate its real-world impact.

Chronic disease management interventions for people with chronic kidney disease in primary care: a systematic review and meta-analysis.

Background: Primary care providers manage the majority of patients with chronic kidney disease (CKD), although the most effective chronic disease management (CDM) strategies for these patients are unknown. We assessed the efficacy of CDM interventions used by primary care providers managing patients with CKD. Methods: The Medline, Embase and Cochrane Central databases were systematically searched (inception to November 2014) for randomized controlled trials (RCTs) assessing education-based and computer-assisted CDM interventions targeting primary care providers managing patients with CKD in the community. The efficacy of CDM interventions was assessed using quality indicators [use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), proteinuria measurement and achievement of blood pressure (BP) targets] and clinical outcomes (change in BP and glomerular filtration rate). Two independent reviewers evaluated studies for inclusion, quality and extracted data. Random effects models were used to estimate pooled odds ratios (ORs) and weighted mean differences for outcomes of interest. Results: Five studies (188 clinics; 494 physicians; 42 852 patients with CKD) were included. Two studies compared computer-assisted intervention strategies with usual care, two studies compared education-based intervention strategies with computer-assisted intervention strategies and one study compared both these intervention strategies with usual care. Compared with usual care, computer-assisted CDM interventions did not increase the likelihood of ACEI/ARB use among patients with CKD {pooled OR 1.00 [95% confidence interval (CI) 0.83-1.21]; I2 = 0.0%}. Similarly, education-related CDM interventions did not increase the likelihood of ACEI/ARB use compared with computer-assisted CDM interventions [pooled OR 1.12 (95% CI 0.77-1.64); I2 = 0.0%]. Inconsistencies in reporting methods limited further pooling of data. Conclusions: To date, there have been very few randomized trials testing CDM interventions targeting primary care providers with the goal of improving care of people with CKD. Those conducted to date have shown minimal impact, suggesting that other strategies, or multifaceted interventions, may be required to enhance care for patients with CKD in the community.

The association between individual counselling and health behaviour change: the See Kidney Disease (SeeKD) targeted screening programme for chronic kidney disease.

BACKGROUND: Health behaviour change is an important component of management for patients with chronic kidney disease (CKD); however, the optimal method to promote health behaviour change for self-management of CKD is unknown. The See Kidney Disease (SeeKD) targeted screening programme screened Canadians at risk for CKD and promoted health behaviour change through individual counselling and goal setting. OBJECTIVES: The objectives of this study are to determine the effectiveness of individual counselling sessions for eliciting behaviour change and to describe participant characteristics associated with behaviour change. DESIGN: This is a cross-sectional, descriptive study. SETTING: The study setting is the National SeeKD targeted screening programme. PATIENTS: The participants are all 'at risk' patients who were screened for CKD and returned a follow-up health behaviour survey (n = 1129). MEASUREMENTS: Health behaviour change was defined as a self-reported change in lifestyle, including dietary changes or medication adherence. METHODS: An individual counselling session was provided to participants by allied healthcare professionals to promote health behaviour change. A survey was mailed to all participants at risk of CKD within 2-4 weeks following the screening event to determine if behaviour changes had been initiated. Descriptive statistics were used to describe respondent characteristics and self-reported behaviour change following screening events. Results were stratified by estimated glomerular filtration rate (eGFR) (< 60 and ≥ 60 mL/min/1.73 m(2)). Log binomial regression analysis was used to determine the predictors of behaviour change. RESULTS: Of the 1129 respondents, the majority (89.8 %) reported making a health behaviour change after the screening event. Respondents who were overweight (body mass index [BMI] 25-29.9 kg/m(2)) or obese (BMI ≥ 30.0 kg/m(2)) were more likely to report a behaviour change (prevalence rate ratio (PRR) 0.66, 95 % confidence interval (CI) 0.44-0.99 and PRR 0.49, 95 % CI 0.30-0.80, respectively). Further, participants with a prior intent to change their behaviour were more likely to make a behaviour change (PRR 0.58, 95 % CI 0.35-0.96). Results did not vary by eGFR category. LIMITATIONS: We are unable to determine the effectiveness of the behaviour change intervention given the lack of a control group. Potential response bias and social desirability bias must also be considered when interpreting the study findings. CONCLUSIONS: Individual counselling and goal setting provided at screening events may stimulate behaviour change amongst individuals at risk for CKD. However, further research is required to determine if this behaviour change is sustained and the impact on CKD progression and outcomes.

MISE EN CONTEXTE: Les changements dans les habitudes de vie sont une composante majeure dans la prise en charge des patients atteints d'insuffisance rénale chronique (IRC). Malgré cela, la méthode pour promouvoir efficacement ces changements auprès de cette clientèle particulière n'est pas connue. Le programme de dépistage précoce et ciblé See Kidney Disease (SeeKD) a permis d'identifier les Canadiens à risque de développer une IRC. Ce programme a aussi servi à promouvoir l'adoption de changements d'habitudes bénéfiques pour la santé, par le biais de consultations individuelles et par l'établissement d'objectifs. OBJECTIFS DE L'ÉTUDE: Cette étude avait pour objectif de mesurer l'efficacité de séances de consultation individuelle offertes aux patients en vue de susciter des changements comportementaux. L'étude visait également à établir les caractéristiques des patients associées à ces changements de comportement. CADRE DE L'ÉTUDE: Il s'agit d'une étude transversale descriptive qui s'est tenue dans le cadre du programme national de dépistage ciblé SeeKD. PARTICIPANTS: La cohorte était constituée de tous les patients identifiés « à risque de développer une IRC ¼ par le programme SeeKD, et ayant retourné le questionnaire de suivi au sujet des changements dans leurs habitudes de vie, soit un total de 1129 participants. MESURES: Une séance de consultation individuelle ayant pour but de promouvoir l'intégration de nouvelles d'habitudes de vie a été offerte aux participants par les professionnels de la santé à la suite de l'activité de dépistage. Entre deux et quatre semaines plus tard, les participants ont également reçu un questionnaire par la poste à l'aide duquel on a pu vérifier s'ils avaient entamé les changements de comportement proposés. Des statistiques descriptives ont été utilisées pour établir les caractéristiques des répondants ainsi que les changements de comportement que ces derniers ont rapporté avoir adoptés à la suite de l'activité de dépistage. Les résultats ont été stratifiés en deux groupes selon les valeurs de DFGe des participants (< 60 mL/min/1.73 m2 et ≥ 60 mL/min/1.73 m2). L'analyse par régression logistique binomiale a été utilisée pour identifier les indicateurs de changement de comportement chez les patients. RÉSULTATS: La grande majorité (89,8 %) des 1129 participants ont rapporté avoir adopté de nouveaux comportements en matière de santé après avoir été déclarés à risque de développer une IRC. Les répondants souffrant d'embonpoint (indice de masse corporelle [IMC] entre 25 et 29,9 kg/m2) ou obèses (IMC ≥ 30,0 kg/m2) se sont avérés plus ouverts à l'idée d'adopter de nouveaux comportements en regard de leur santé (rapport du taux de prévalence [RTP] : 0,66 ; intervalle de confiance à 95 % [I.C. à 95 %] : entre 0,44 et 0,99 et RTP : 0,49 ; I.C. à 95 % : entre 0,30 et 0,80 respectivement). Par ailleurs, les répondants qui avaient déjà l'intention d'adopter de nouveaux comportements avant même d'être dépistés ont été les plus enclins à le faire (RTP : 0,58 ; I.C. à 95 % : entre 0,35 et 0,96). Aucune variation significative de ces résultats n'a été observée selon le DFGe. LIMITES DE L'ÉTUDE: Nous n'avons pu déterminer avec précision l'efficacité des changements de comportement adoptés en raison de l'absence d'un groupe contrôle. De plus, un biais dû aux réponses des participants ou par désirabilité sociale est à considérer dans l'interprétation des résultats. CONCLUSIONS: L'établissement d'objectifs ainsi que le counselling individuel fourni à la suite de l'activité de dépistage pourraient stimuler l'adoption de nouvelles habitudes de vie chez les patients à risque de développer une IRC. Toutefois, des recherches supplémentaires sont requises afin de déterminer si ces changements de comportement sont maintenus par les patients et s'ils ont une réelle influence sur le pronostic de la maladie.

The See Kidney Disease Targeted Screening Program for CKD.

BACKGROUND AND OBJECTIVES: The effectiveness of targeted screening for identification of CKD is largely unknown. The See Kidney Disease (SeeKD) targeted screening project aimed to determine the prevalence of unrecognized CKD in Canada. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The SeeKD project was conducted across Canada using a convenience sample approach and events to identify adults with risk factors for CKD (i.e., diabetes, hypertension, vascular disease, family history of kidney problems, etc.). Participants with at least one risk factor received a point-of-care creatinine measurement to identify unrecognized CKD (CKD-Epidemiology Collaboration eGFR <60 ml/min per 1.73 m(2)). Baseline information included clinical characteristics, sociodemographics, and health knowledge. Semistructured telephone interviews were conducted with each Kidney Foundation of Canada branch (regionalized locations) after the screening events to characterize local screening strategies, which were subsequently categorized as individual-targeted (specifically targeting individuals at risk of CKD) and community-targeted (event in a community location in proximity to a high-risk population). We calculated the prevalence of unrecognized CKD overall, and by screening strategy. RESULTS: Between January 2011 and February 2014, 6329 Canadians participated in SeeKD screening events. Participants were predominantly female (65.3%), middle-aged (mean, 58.5 years), and the majority (88.9%) self-reported at least one risk factor for CKD. Of participants with at least one risk factor, 92.3% (n=5194) were screened, of whom 18.8% (95% confidence interval [95% CI], 17.8 to 19.9) had unrecognized CKD; the majority (13.8%) had stage 3a CKD (eGFR=45-60 ml/min per 1.73 m(2)). The prevalence of unrecognized CKD was higher for branches with individual versus community-targeted events (21.9% [95% CI, 20.5 to 23.4] versus 14.7% [95% CI, 13.2 to 16.2]). CONCLUSIONS: Targeted screening identified a high proportion of individuals with risk factors for CKD and a high prevalence of unrecognized CKD. Future research will evaluate the ability of targeted screening to promote self-management behaviors addressing priorities for people with CKD.

The Steroids In the Maintenance of remission of Proliferative Lupus nephritis (SIMPL) pilot trial.

BACKGROUND: Patients with proliferative lupus nephritis are at risk of frequent relapses. Whether low- dose prednisone prevents relapses is uncertain. OBJECTIVES: We undertook a pilot RCT to determine the feasibility of a larger trial. DESIGN: Pilot randomized controlled trial. SETTING: Single center Canadian outpatient nephrology clinic. PATIENTS: Participants with systemic lupus erythematosus (SLE) and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible. MEASUREMENTS: Feasibility: proportion of eligible patients randomized and adherence to tapering regimen. Clinical: occurrence of renal or major non-renal flare of SLE. METHODS: We conducted a blinded, two-parallel-group randomized controlled trial of prednisone 7.5 mg/day (continuation) compared to a matching placebo (withdrawal). RESULTS: Of nineteen eligible patients screened, 15 (79%) were recruited and randomized; 8 to prednisone continuation and seven to withdrawal. All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target. Over 36 months, the primary outcome occurred in four (50%) patients in the continuation group (three renal and one major non-renal flare), compared with one patient (14%) in the withdrawal group (one renal flare). Three participants (38%) in the continuation group had minor flares, while no patients in the withdrawal group did. LIMITATIONS: This pilot RCT was small and not designed to assess the efficacy or safety of maintenance with low-dose prednisone. CONCLUSIONS: The high proportion of eligible patients recruited, and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31327267.

CONTEXTE: Les patients atteints de néphropathie lupique proliférative sont sujets à de nombreuses rechutes. Il est incertain que l'administration de faibles doses de prednisone aide à prévenir ses rechutes. OBJECTIFS: Nous avons entrepris un essai randomisé contrôlé (ERC) (étude pilote) afin de déterminer la faisabilité d'une étude plus vaste. TYPE D'ÉTUDE: Essai randomisé contrôlé (étude pilote). CONTEXTE: La clinique externe de néphrologie d'un centre canadien. PATIENTS: Les personnes atteintes de lupus érythémateux disséminé (LED), avec antécédents de néphropathie lupique de stades III et IV, en rémission (minimalement partielle) et toujours en traitement de maintien sous prednisone étaient admissibles à l'étude. MESURES: Faisabilité : Assignation aléatoire à partir de l'échantillon des patients admissibles et observance de la posologie dégressive. Clinique : apparition d'une poussée lupique rénale ou d'une poussée lupique grave non rénale. MÉTHODE: Nous avons mené un essai clinique aléatoire, en parallèle et à double insu, d'un groupe sous 7,5 mg de prednisone (traitement continu) et d'un groupe sous placebo (sevrage). RÉSULTATS: Du bassin des dix-neuf patients triés, 15 d'entre eux (79%) ont été sélectionnés. Le choix du traitement a été attribué de façon aléatoire : 8 patients pour le traitement de maintien sous prednisone et 7 patients pour le sevrage. Tous les participants ont observé le protocole de posologie dégressive qui leur était attribué et dont le but était le sevrage ou le maintien avec de faibles doses de prednisone. Sur une période de 36 mois, le premier indicateur des résultats est apparu chez quatre patients (50%) du groupe sous prednisone à faible dose (trois poussées rénales et une poussée grave non rénale), comparativement à un patient (14%) du groupe sous sevrage (une poussée rénale). Trois des participants (38%) du groupe sous prednisone à faible dose ont eu des poussées lupiques mineures; aucune poussée lupique mineure n'est apparue dans le groupe sous placebo. LIMITES DE L'ÉTUDE: Cet essai randomisé contrôlé pilote a été effectué sur un petit groupe; il n'a pas été conçu pour évaluer l'efficacité ou la sûreté d'un entretien sous prednisone à faible dose. CONCLUSION: Le succès combiné du large échantillon de départ de patients admissibles et l'observance du protocole de posologie dégressive laisse suggérer qu'une étude plus vaste comparant le traitement de maintien à la prednisone et le sevrage est faisable.