Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.

AIM: Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing. METHODS: Three electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-genetic informed prescribing, reported drug specific adverse drug events and clinical effectiveness outcomes. Two reviewers independently screened titles and abstracts, extracted data and assessed study quality. Meta-analyses of specific outcomes were conducted where data allowed. RESULTS: Fifteen studies, involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria. Eight studies had statistically significant results for their primary outcome in favour of genotype-guided prescribing. Nine studies evaluated genotype-guided warfarin dosing. Analysis of percentage of time in therapeutic international normalized ratio range (1952 individuals) showed a statistically significant benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95% CI 1.34, 12.0, I(2) = 80%). There was a statistically significant reduction in numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33, 0.99; I(2) = 60%). It was not possible to meta-analyze genotype-guided dosing for other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a statistically significant benefit for their primary outcome, odds ratio 0.03 (95% CI 0.00, 0.62, P < 0.001) for abacavir. CONCLUSIONS: There is evidence of improved clinical effectiveness associated with genotype-guided warfarin dosing.

Content verification of the EORTC QLQ-C30/EORTC QLQ-BR23 with the International Classification of Functioning, Disability and Health.

PURPOSE: The aims of this study were to estimate the extent to which the content of the EORTC QLQ-C30 and EORTC QLQ-BR23 goes beyond functioning and include global feeling of well-being. METHODS: Respectively, 21 and 13 healthcare professionals agreed to link the EORTC QLQ-C30 and EORTC QLQ-BR23 to the ICF. Mappers were asked to independently identify appropriate codes for the corresponding items of the EORTC QLQ-C30 and EORTC QLQ-BR23 following standardized linking rules and methodology. A Delphi technique was used in order to reach consensus. The threshold of agreement was 70 %. Rounds were stopped when the threshold was obtained or when it was clear that no consensus would be reached. RESULTS: A total of 25 items out of 30 were endorsed for the EORTC QLQ-C30: 8 items were endorsed at the 4-digit level, 15 items at the 3-digit level, and 2 items reach the consensus that the items were not cover within the ICF. Only 2 items out of 23 did not reach consensus in the EORTC QLQ-BR23. Of the 21 items endorsed, 3 items were endorsed at the 5-digit level, 10 items at the 4-digit level, and 8 at the 3-digit level. CONCLUSION: This study demonstrates that the content of the EORTC QLQ-C30 goes beyond functioning and includes global feeling of well-being and that the content of the EORTC QLQ-BR23 is related to functioning. Furthermore, linking items to the ICF framework could be an additional method to validate the content of health-related questionnaires.

Pedometer-facilitated walking intervention shows promising effectiveness for reducing cancer fatigue: a pilot randomized trial.

OBJECTIVE: Mechanisms for cancer related fatigue suggest that exercise but "not too much and not too little" could be effective. This study aimed to investigate feasibility and estimate the potential effects of a walking exercise program in people with advanced cancer and fatigue. DESIGN: A pilot randomized trial. SETTING: McGill University Health Centre (MUHC), Montreal, Canada. SUBJECTS: People with advanced cancer undergoing interdisciplinary assessment and rehabilitation with a fatigue level of 4 to 10 on a visual analogue scale. INTERVENTIONS: An 8-week fatigue-adapted, walking intervention, facilitated using a pedometer (STEPS), and offered at the same time as or after rehabilitation. MEASURES: Measures of fatigue, physical function and well-being were administered at entry, and 8, 16 and 24 weeks. Generalized estimating equations (GEE) estimated the odds of response for people receiving the STEPS program in comparison to the odds of response in the controls (odds ratio, OR). RESULTS: Twenty-six persons were randomized to three groups: during rehabilitation, after rehabilitation, and usual care. For the fatigue measures the OR for STEPS offered at any time using an intention-to-treat approach was 3.68 (95%CI: 1.05-12.88); for the physical function measures, the OR was 1.40 (95%CI: 0.41- 4.79) and 2.36 (95%CI: 0.66-8.51) for the well-being measures. CONCLUSION: Fifty percent of eligible people were able to participate. This small trial suggests that a personalized exercise program reduces fatigue and that 100 people are needed in a full strength trial.

Screening for lifestyle and mental health risk factors in the waiting room: feasibility study of the Case-finding Health Assessment Tool.

OBJECTIVE: To assess the feasibility and acceptability of administering the validated Case-finding Health Assessment Tool (CHAT) in Canadian family practice waiting rooms to identify risk factors for depression, anxiety, anger control,smoking, drinking, other drug use, gambling, exposure to abuse, and physical inactivity. DESIGN: Cross-sectional survey. SETTING: One urban academic family practice and one inner-city community health centre in British Columbia. PARTICIPANTS: Convenience sample of consecutive adult patients (19 years of age or older) and their attending family physicians. MAIN OUTCOME MEASURES: Rates of completion; positive responses to and wanting help with identified lifestyle and mental health risk factors; rates of objections to any questions; and positive and negative comments about the CHAT by participating physicians and patients. RESULTS: A total of 265 eligible adults presented in the waiting rooms over 5 full days and 3 half-days, 176 (66%) of whom enrolled in the study; 161(91%) completed the CHAT, and 107 (66%) completed acceptability feedback forms. The prevalence of risk factors among patients in the academic and inner-city practice samples was different, with 20% and 63%, respectively,recording positive responses to both depression screening questions,34% and 60% positive for anxiety, 11% and 71% currently smoking, 6%and 22% feeling they needed to cut down on alcohol, 1% and 48% having used recreational drugs in the past year, and 11% and 65% with problems controlling anger. While many requested help with reducing risk factors,such as smoking (20%) and mental health symptoms (25% to 27%), a total of 35% (57 of 161) wanted help with an identified issue that day. Patients and physicians found the CHAT acceptable, with no patients objecting to any question except the alcohol question (2 objected). Most comments were positive. CONCLUSION: The CHAT allowed efficient identification of 9 risk factors, as well as identification of those wanting help. It could be used to screen all or targeted adult Canadian primary care patients in waiting rooms.

Program evaluation of a model to integrate internationally educated health professionals into clinical practice.

BACKGROUND: The demand for health professionals continues to increase, partially due to the aging population and the high proportion of practitioners nearing retirement. The University of British Columbia (UBC) has developed a program to address this demand, by providing support for internationally trained Physiotherapists in their preparation for taking the National Physiotherapy competency examinations.The aim was to create a program comprised of the educational tools and infrastructure to support internationally educated physiotherapists (IEPs) in their preparation for entry to practice in Canada and, to improve their pass rate on the national competency examination. METHODS: The program was developed using a logic model and evaluated using program evaluation methodology. Program tools and resources included educational modules and curricular packages which were developed and refined based on feedback from clinical experts, IEPs and clinical physical therapy mentors. An examination bank was created and used to include test-enhanced education. Clinical mentors were recruited and trained to provide clinical and cultural support for participants. RESULTS: The IEP program has recruited 124 IEPs, with 69 now integrated into the Canadian physiotherapy workforce, and more IEPs continuing to apply to the program. International graduates who participated in the program had an improved pass rate on the national Physiotherapy Competency Examination (PCE); participation in the program resulted in them having a 28% (95% CI, 2% to 59%) greater possibility of passing the written section than their counterparts who did not take the program. In 2010, 81% of all IEP candidates who completed the UBC program passed the written component, and 82% passed the clinical component. CONCLUSION: The program has proven to be successful and sustainable. This program model could be replicated to support the successful integration of other international health professionals into the workforce.

Evaluation of buccal swabs for pharmacogenetics.

OBJECTIVE: A simple, non-invasive sample collection method is key for the integration of pharmacogenetics into clinical practice. The aim of this study was to gain samples for pharmacogenetic testing and evaluate the variation between dry-flocked and sponge-tipped buccal swabs in yield and quality of DNA isolated. RESULTS: Thirty-one participants collected samples using dry-flocked swabs and sponge-tipped swabs. Samples were assessed for DNA yield, quality and genotyping performance on a qPCR OpenArray platform of 28 pharmacogenetic SNPs and a CYP2D6 TaqMan copy number variant. DNA from sponge-tipped swabs had a significantly greater yield compared to DNA collected with dry-flocked swabs (p = 4.4 × 10-7). Moreover, highest genotyping call rates across all assays and highest CNV confidence scores were observed in DNA samples collected from sponge-tipped swabs (97% vs. 54% dry-flocked swabs; 0.99 vs. 0.88 dry-flocked swabs, respectively). Sample collection using sponge-tipped swabs provides a DNA source of sufficient quantity and quality for pharmacogenetic variant detection using qPCR.

Introducing pharmacogenetic testing with clinical decision support into primary care: a feasibility study.

BACKGROUND: Inappropriate prescribing increases patient illness and death owing to adverse drug events. The inclusion of genetic information into primary care medication practices is one solution. Our aim was to assess the ability to obtain and genotype saliva samples and to determine the levels of use of a decision support tool that creates medication options adjusted for patient characteristics, drug-drug interactions and pharmacogenetics. METHODS: We conducted a cohort study in 6 primary care settings (5 family practices and 1 pharmacy), enrolling 191 adults with at least 1 of 10 common diseases. Saliva samples were obtained in the physician's office or pharmacy and sent to our laboratory, where DNA was extracted and genotyped and reports were generated. The reports were sent directly to the family physician/pharmacist and linked to an evidence-based prescribing decision support system. The primary outcome was ability to obtain and genotype samples. The secondary outcomes were yield and purity of DNA samples, ability to link results to decision support software and use of the decision support software. RESULTS: Genotyping resulted in linking of 189 patients (99%) with pharmacogenetic reports to the decision support program. A total of 96.8% of samples had at least 1 actionable genotype for medications included in the decision support system. The medication support system was used by the physicians and pharmacists 236 times over 3 months. INTERPRETATION: Physicians and pharmacists can collect saliva samples of sufficient quantity and quality for DNA extraction, purification and genotyping. A clinical decision support system with integrated data from pharmacogenetic tests may enable personalized prescribing within primary care. Trial registration: ClinicalTrials.gov, NCT02383290.

Preventing diabetes in primary care: a feasibility cluster randomized trial.

OBJECTIVE: To determine the feasibility of implementing a large-scale primary care-based diabetes prevention trial. METHODS: A feasibility cluster randomized controlled trial was conducted in British Columbia, Canada, amongst adults with prediabetes using the Facilitated Lifestyle Intervention Prescription (FLIP) vs. usual care. FLIP included lifestyle advice, a pedometer, and telephone support from a lifestyle facilitator for 6 months. Indicators of feasibility included recruitment rates of family practices, participants and facilitators, as well as feasibility and retention rates in the FLIP program and study protocols. RESULTS: Six family practices participated; 59 patients were enrolled between October 2012 and March 2013. The trial protocol was acceptable to practices and participants and had a 95% participant retention rate over the 6 months (56/59). Adherence to the intervention was high (97%), with 34 of 35 patients continuing to receive telephone calls from the facilitator for 6 months. The mean cost of the intervention was C$144 per person. Compared with control, intervention participants significantly reduced weight by 3.2 kg (95% CI, 1.7 to 4.6); body mass index by 1.2 (95% CI, 0.7 to 1.7) and waist circumference by 3 cm (95% CI, 0.3 to 5.7). CONCLUSIONS: It is feasible to implement FLIP and to conduct a trial to assess effectiveness. A larger trial with longer follow up to assess progression to diabetes is warranted.

Assessing Physical Therapy Students' Performance during Clinical Practice.

PURPOSE: To assess the feasibility and acceptability of using the Assessment of Physiotherapy Practice (APP) instrument to assess physiotherapy students' clinical competencies. METHODS: A convenience sample of clinical educators (CEs) and students from the University of British Columbia (UBC) in Vancouver, Canada, completed the instrument currently in use, the Physical Therapist Clinical Performance Instrument (PT-CPI), and the APP. A cross-sectional survey of CEs and physiotherapy students was conducted from 2011 to 2012; the survey included questions worded to elicit opinions about the two instruments when used in the clinical environment with students at different stages of training. Questions addressed various aspects of the instruments, including ease of use, provision of feedback, and completion time. RESULTS: Data were analyzed from 63 CEs from a variety of settings; sufficient data were recorded on 71 student PT-CPI and APP forms. A grading comparison between the PT-CPI and the APP demonstrated equivalence of entry-to-practice standard. Mean completion time was 80 (SD 53) minutes for the PT-CPI and 23 (13) minutes for the APP; mean time difference was 57 (95% CI, 39-75). Students would prefer (82%) that the APP be used to provide feedback and assess their performance on clinical placements. CONCLUSIONS: It is feasible and acceptable to use the APP to assess physiotherapy students' clinical competencies at the University of British Columbia.

Objectif : Évaluer la faisabilité d'utiliser les instruments d'évaluation de la pratique de la physiothérapie (EPP) et leur accessibilité afin d'évaluer les compétences cliniques des étudiants en physiothérapie. Méthodes : Un échantillon de commodité constitué de formateurs cliniciens (FC) et d'étudiants de l'Université de la Colombie-Britannique (UCB) à Vancouver, au Canada, a rempli l'instrument utilisé actuellement, soit l'Instrument d'évaluation du rendement clinique des physiothérapeutes (ERC-PT) et l'EPP. On a réalisé, de 2011 à 2012, un sondage transversal auprès de formateurs cliniciens et d'étudiants en physiothérapie qui comportait des questions visant à réunir des opinions sur les deux instruments utilisés dans l'environnement clinique avec des étudiants à différents stades de la formation. Les questions portaient sur divers aspects des instruments, y compris la facilité d'utilisation, la formulation de commentaires et le temps nécessaire pour y répondre. Résultats : On a analysé des données provenant de 63 formateurs cliniciens de toutes sortes de contextes et 71 formulaires d'ERC-PT et d'EPP d'étudiants contenaient suffisamment de données. Une comparaison des cotes entre l'instrument ERC-PT et l'EPP a démontré une équivalence des normes au niveau débutant. Il a fallu en moyenne 80 (ET 53) minutes pour remplir l'ERC-PT et 23 (13) minutes pour répondre à l'EPP. La différence moyenne s'est établie à 57 (IC à 95%, 39 à 75). Les étudiants préféreraient (82%) qu'on utilise l'EPP pour formuler des commentaires et évaluer leur rendement au cours des stages cliniques. Conclusions : Il est possible et acceptable d'utiliser l'EPP pour évaluer les compétences cliniques des étudiants en physiothérapie à l'Université de la Colombie-Britannique.

Impact of lymphoedema on arm function and health-related quality of life in women following breast cancer surgery.

OBJECTIVE: To estimate the extent to which the impairments associated with lymphoedema (volume increase, local oedema and sensory alteration) are linked to arm dysfunction and sub-optimal health-related quality of life. PATIENTS AND METHODS: A cross-sectional study, embedded within a pilot for an epidemiologic study, was undertaken involving women who had undergone surgery for unilateral stage I or II breast cancer. Two questionnaires (a lymphoedema screening questionnaire and the Disabilities of Arm, Shoulder and Hand questionnaire) were mailed and 72 of 204 responders reported having one or more symptoms of lymphoedema (prevalence 35%). A total of 50 women with symptoms attended for further testing. RESULTS: Women with self-reported symptoms of lymphoedema had a significantly higher score on the Disabilities of Arm, Shoulder and Hand questionnaire (mean difference 23.4, 95% confidence interval 19.3-27.5), indicating activity limitation and participation restriction. Pain was the only impairment directly correlated with activity limitation, participation restriction and sub-optimal health-related quality of life. CONCLUSION: These findings have implications for treatment, and the outcome measures used for the assessment of lymph?oedema. Treatments focusing on decreasing arm volume without addressing issues of pain may not result in improvements in activity, participation, or health-related quality of life.