Reexamining the surfaces of bone in boys and girls during adolescent growth: A 12-Year mixed longitudinal pQCT Study

We revisit Stanley Garn's theory related to sex differences in endocortical and periosteal apposition during adolescence using a 12-year mixed longitudinal study design. We used peripheral quantitative computed tomography to examine bone parameters in 230 participants (110 boys, 120 girls; aged 11.0 years at baseline). We assessed total (Tt.Ar, mm2), cortical (Ct.Ar, mm2), and medullary canal area (Me.Ar, mm2), Ct.Ar/Tt.Ar, cortical bone mineral density (Ct.BMD, mg/cm3), and polar strength-strain index (SSIp, mm3) at the tibial midshaft (50% site). We used annual measures of height and chronological age to identify age at peak height velocity (APHV) for each participant. We compared annual accrual rates of bone parameters between boys and girls, aligned on APHV using a linear mixed effects model. At APHV, boys demonstrated greater Tt.Ar (ratio = 1.27; 95% confidence interval [CI] 1.21, 1.32), Ct.Ar (1.24 [1.18, 1.30]), Me.Ar (1.31 [1.22, 1.40]), and SSIp (1.36 [1.28, 1.45]) and less Ct.Ar/Tt.Ar (0.98 [0.96, 1.00]) and Ct.BMD (0.97 [0.96, 0.97]) compared with girls. Boys and girls demonstrated periosteal bone formation and net bone loss at the endocortical surface. Compared with girls, boys demonstrated greater annual accrual rates pre-APHV for Tt.Ar (1.18 [1.02, 1.34]) and Me.Ar (1.34 [1.11, 1.57]), lower annual accrual rates pre-APHV for Ct.Ar/Tt.Ar (0.56 [0.29, 0.83]) and Ct.BMD (–0.07 [–0.17, 0.04]), and similar annual accrual rates pre-APHV for Ct.Ar (1.10 [0.94, 1.26]) and SSIp (1.14 [0.98, 1.30]). Post-APHV, boys demonstrated similar annual accrual rates for Ct.Ar/Tt.Ar (1.01 [0.71, 1.31]) and greater annual accrual rates for all other bone parameters compared with girls (ratio = 1.23 to 2.63; 95% CI 1.11 to 3.45). Our findings support those of Garn and others of accelerated periosteal apposition during adolescence, more evident in boys than girls. However, our findings challenge the notion of greater endocortical apposition in girls, suggesting instead that girls experience diminished endocortical resorption compared with boy

Constructing treatment episodes from concomitant medication logs: a prospective observational study

ObjectivesTo describe an approach using concomitant medication log records for the construction of treatment episodes. Concomitant medication log records are routinely collected in clinical studies. Unlike prescription and dispensing records, concomitant medication logs collect utilisation data. Logs can provide information about drug safety and drug repurposing.DesignA prospective multicentre, multicohort observational study.SettingTwenty-one clinical sites in the USA, Europe, Israel and Australia.Participants415 subjects from the de novo cohort of the Parkinson’s Progression Markers Initiative.MethodsWe construct treatment episodes of concomitant medication use. The proposed approach treats temporal gaps as a stoppage of medication and temporal overlaps as simultaneous use or changes in dose. Log records with no temporal gaps were combined into a single treatment episode.Results5723 concomitant medication log records were used to construct 3655 treatment episodes for 65 medications. There were 405 temporal gaps representing a stoppage of medication; 985 temporal overlaps representing simultaneous regimens of the same medication and 2696 temporal overlaps representing a change in dose regimen. The median episode duration was 37 months (IQ interval: 11–73 months).ConclusionsThe proposed approach for constructing treatment episodes offers a method of estimating duration and dose of treatment from concomitant medication log records. The accompanying recommendations guide log data collection to improve their quality for drug safety and drug repurposing

Prophylactic Surgery in the BRCA+ Patient: Do Women Develop Breast Cancer While Waiting?

Breast cancer susceptibility gene (BRCA) mutation carriers have an increased risk of breast cancer. Mitigation of this risk can be achieved via surveillance or prophylactic mastectomy with or without breast reconstruction. Those that choose surgery expect to reduce their chance of developing cancer. The purpose of this study was to determine the incidence of patients developing breast cancer prior to surgery and to identify modifiable contributing factors within the patient journey. This is a historical cohort study of all BRCA mutation carriers identified through the British Columbia Cancer Hereditary Cancer Program between 2000 and 2012. Patients were divided into two groups: surveillance (S) and prophylactic mastectomy with immediate breast reconstruction (PM/IBR). The incidence of cancer, time to PM/IBR and patient journeys were analyzed. A total of 333 women were identified. The time to surgery from mutation disclosure was a median of 31 (5.3, 75.7) months. During this period, 6% of patients developed breast cancer compared with a 14% incidence of breast cancer in patients choosing surveillance. The majority of time to surgery was attributed to the period between mutation disclosure and the decision to proceed with surgery. Strategies to facilitate decision-making as well as wait list prioritization and dedicated operative time should be targeted to this population to decrease the number of women developing an interval cancer prior to surgery.Medicine, Faculty ofMedical Oncology, Division ofSurgery, Department ofReviewedFacultyResearche

A systematic, concept-based method of developing the exposure measure for drug safety and effectiveness studies.

PURPOSE In drug safety and effectiveness studies based on secondary data, the choice of an appropriate exposure measure for a given outcome can be challenging. Different measures of exposure can yield different estimates of treatment effect and safety. There is a knowledge gap with respect to developing and refining measures of drug exposure, to ensure that the exposure measure addresses the study question and is suitable for statistical analysis. METHODS We present a transparent, step-by-step approach to the development of drug exposure measures involving secondary data. This approach would be of interest to students and investigators with initial training in pharmacoepidemiology. We illustrate the approach using a study about Parkinson's disease. RESULTS We described the exposure specifications according to the study question. Next, we refined the exposure measure by linking it to knowledge about four major concepts in drug safety and effectiveness studies: drug use patterns, duration, timing, and dose. We then used this knowledge to guide the ultimate choice of exposure measure: time-varying, cumulative 6-month exposure to tamsulosin (a drug used to treat prostate hyperplasia). CONCLUSIONS The proposed approach links exposure specifications to four major concepts in drug safety and effectiveness studies. Formulating subject-matter knowledge about these major concepts provides an avenue to develop the rationale and specifications for the exposure measure

Naloxone interventions in opioid overdoses: a systematic review protocol

Background: North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Methods: To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies. Discussion: Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs.Medicine, Faculty ofOther UBCNon UBCEmergency Medicine, Department ofPopulation and Public Health (SPPH), School ofReviewedFacult

Empowering pharmacists in asthma management through interactive SMS (EmPhAsIS): study protocol for a randomized controlled trial

Background: Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and periods of symptom remission experienced by patients. Pharmacists are suited to impact medication adherence given their training, skills, and frequent contact with patients. The Empowering pharmacists in asthma management through interactive SMS (EmPhAsIS) trial involves an intervention leveraging mobile health (mHealth) technology to support community pharmacy practice with the hypothesis of improved medication adherence in asthma. Methods/Design This study is a pragmatic pharmacy-based, cluster, randomized controlled trial with 12 months of intervention delivery and follow-up. Pharmacies (the clusters) will be randomized at a 1:1 ratio to provide intervention or usual care. The EmPhAsIS intervention consists of patient asthma education, short message service (SMS)-based monthly assessment of adherence, and follow-up of non-adherent individuals by community pharmacists. There are no inclusion or exclusion criteria for pharmacies. Patients are eligible if they: are 14 years of age or older, fill a prescription for inhaled corticosteroid (either monotherapy or in a combination inhaler with long-acting beta-agonists), have been diagnosed with asthma, possess a mobile phone with SMS capabilities, and have no communication difficulties such as inability to communicate in English, or significant impairment in vision, hearing, or speech. The primary outcome is adherence to inhaled corticosteroids ascertained by the medication possession ratio, the ratio of the days of medication supplied to days in a given time interval. This study will also evaluate secondary outcomes including: asthma control, asthma-related quality of life, asthma-related hospital admissions, and use of reliever medications during the follow-up period. A nested economic evaluation using a probabilistic decision-analytic model will be used to perform a cost-effectiveness analysis from the societal perspective of the intervention compared with usual care over a 10-year time horizon. Discussion Considering the prevalence of asthma, the extent of the non-adherence problem in this disease, and the availability of effective treatments, there is a tremendous potential to reduce the burden of asthma through improving adherence. This is the first study of an intervention based on mobile communication technology involving community pharmacists in asthma management. Trial registration ClinicalTrials.gov identifier: NCT02170883 ; date of registration: 19 June 2014.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofNon UBCReviewedFacult

Incontinence and Nocturia in Older Adults After Hip Fracture: Analysis of a Secondary Outcome for a Parallel Group, Randomized Controlled Trial

Objective: To test the effect of a follow-up clinic on urinary incontinence (UI) and nocturia among older adults with hip fracture. Method: Fifty-three older adults (≥65 years) 3 to 12 months following hip fracture were enrolled and randomized to receive usual care plus the intervention (B4), or usual care (UC) only. The B4 group received management by health professionals, with need-based referrals. UI, nocturia, and quality of life were measured with questionnaires at baseline, 6 months, and 12 months. Results: There were 48 participants included in this analysis, and at baseline, 44% of study participants self-reported UI. At final assessment, six out of 24 B4 participants and 12 out of 24 UC participants reported UI. Four out of five study participants reported nocturia at baseline; this did not decrease during the study. Discussion : Following hip fracture, many older adults report UI and most report nocturia. Health professionals should be aware of the high occurrence of urinary symptoms among older adults post hip fracture

Post-discharge management following hip fracture - get you back to B4: A parallel group, randomized controlled trial study protocol

Abstract Background Fall-related hip fractures result in significant personal and societal consequences; importantly, up to half of older adults with hip fracture never regain their previous level of mobility. Strategies of follow-up care for older adults after fracture have improved investigation for osteoporosis; but managing bone health alone is not enough. Prevention of fractures requires management of both bone health and falls risk factors (including the contributing role of cognition, balance and continence) to improve outcomes. Methods/Design This is a parallel group, pragmatic randomized controlled trial to test the effectiveness of a post-fracture clinic compared with usual care on mobility for older adults following their hospitalization for hip fracture. Participants randomized to the intervention will attend a fracture follow-up clinic where a geriatrician and physiotherapist will assess and manage their mobility and other health issues. Depending on needs identified at the clinical assessment, participants may receive individualized and group-based outpatient physiotherapy, and a home exercise program. Our primary objective is to assess the effectiveness of a novel post-discharge fracture management strategy on the mobility of older adults after hip fracture. We will enrol 130 older adults (65 years+) who have sustained a hip fracture in the previous three months, and were admitted to hospital from home and are expected to be discharged home. We will exclude older adults who prior to the fracture were: unable to walk 10 meters; diagnosed with dementia and/or significant comorbidities that would preclude their participation in the clinical service. Eligible participants will be randomly assigned to the Intervention or Usual Care groups by remote allocation. Treatment allocation will be concealed; investigators, measurement team and primary data analysts will be blinded to group allocation. Our primary outcome is mobility, operationalized as the Short Physical Performance Battery at 12 months. Secondary outcomes include frailty, rehospitalizations, falls risk factors, quality of life, as well as physical activity and sedentary behaviour. We will conduct an economic evaluation to determine health related costs in the first year, and a process evaluation to ascertain the acceptance of the program by older adults, as well as clinicians and staff within the clinic. Trial registration number ClinicalTrials.gov: NCT01254942</p