Perceived Health Status and Capability after Hip Fracture: Secondary Outcomes from an Randomized Controlled Trial.

INTRODUCTION: Hip fractures can have a significant impact on the lives of older people and their families. We conducted a pragmatic randomized controlled trial of post-discharge comprehensive geriatric care (CGC) for community-dwelling older adults after a surgically repaired hip fracture. The objective of this study was to conduct a secondary analysis to compare changes in health status and perceived capability from baseline to 12 months after randomization with: the EuroQol 5-Dimension (EQ-5D-5L) (1) utility score and (2) visual analog scale (VAS); and (3) well-being as measured by participants' perceptions of their ability (or capability) toward completing life activities using the ICEpop Capability Measure for Older People (ICECAP-O). METHODS: We tested the effect of usual care (control) versus usual care and an outpatient CGC clinic (intervention) on mobility after hip fracture in community-dwelling older adults (65 years+). In this secondary analysis, we report the following outcomes: EQ-5D-5L utility score and VAS collected monthly via telephone and ICECAP-O collected in person three times at baseline, 6 months, and 12 months. Data were analyzed using area under the curve and regression adjusted for baseline values for utility scores and capability, and constrained longitudinal data analysis for VAS. RESULTS: We enrolled 53 older adults, including 34 women and 19 men, with mean (SD) age of 80 (8) years. There were no statistical or clinically meaningful differences between groups (control group - intervention group values) for all variables: utility score = -0.028 (95% CI: -0.071, 0.014; p = 0.18); VAS: -0.03 (95% CI: -0.39 to 0.33; p = 0.86); and capability = -0.021 (95% CI: -0.090, 0.046; p = 0.54). CONCLUSIONS: There were no differences in outcomes between groups over 12 months, but values remained constant, contrary to a potential decline for this age group, especially after a major life event like a hip fracture.

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.

Feasibility of Concussion Rehabilitation Approaches Tailored to Psychological Coping Styles: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the feasibility of a clinical trial involving participants with concussion randomized to treatments designed to address fear avoidance or endurance coping, which are risk factors for disability. A secondary objective was to evaluate whether each treatment could affect selective change on targeted coping outcomes. DESIGN: Randomized controlled trial. SETTING: Outpatient concussion clinics. PARTICIPANTS: Adults (N=73, mean age=42.5y) who had persistent postconcussion symptoms and high avoidance or endurance behavior were enrolled at a mean of 12.9 weeks post injury. Ten participants did not complete treatment. INTERVENTIONS: Participants were randomized to an interdisciplinary rehabilitation program delivered via videoconferencing and tailored to avoidance coping (graded exposure therapy [GET]) or endurance coping (operant condition-based pacing strategies plus mindfulness training [Pacing+]). MAIN OUTCOME MEASURES: Feasibility outcomes included screening efficiency, accrual, credibility, treatment fidelity, adherence, and retention. Avoidance was measured with the Fear Avoidance Behavior after Traumatic Brain Injury Questionnaire and endurance behavior with the Behavioral Response to Illness Questionnaire. RESULTS: Screening efficiency, or the proportion of clinic patients who were assessed for eligibility, was 44.5% (275 of 618). A total of 65.8% (73 of 111) of eligible patients were randomized (37 to GET, 36 to Pacing+), meeting accrual targets; 91.7% (55 of 60) of participants perceived treatment as credible. Therapists covered a mean of 96.8% of essential prescribed elements, indicating excellent fidelity. The majority (71.2%; 47 of 66) of participants consistently attended treatment sessions and completed between-session homework. Retention was strong, with 65 of 73 (89%) randomized participants completing the outcome assessment. GET was associated with greater posttreatment reductions in avoidance behavior compared with Pacing+ (Cohen's drepeated measures, 0.81), whereas the treatment approach-specific effect of Pacing+ on endurance behavior was less pronounced (Cohen's drepeated measures, 0.39). CONCLUSIONS: These findings support a future efficacy-focused clinical trial. GET has the potential to selectively reduce fear avoidance behavior after concussion, and, via this mechanism, to prevent or reduce disability.

Comprehensive Geriatric Care to Improve Mobility after Hip Fracture: An RCT.

BACKGROUND: Comprehensive geriatric care (CGC) for older adults during hospitalization for hip fracture can improve mobility, but it is unclear whether CGC delivered after a return to community living improves mobility compared with usual post-discharge care. OBJECTIVE: To determine if an outpatient clinic-based CGC regime in the first year after hip fracture improved mobility performance at 12 months. METHODS: A two-arm, 1:1 parallel group, pragmatic, single-blind, single-center, randomized controlled trial at 3 hospitals in Vancouver, BC, Canada. Participants were community-dwelling adults, aged ≥65 years, with a hip fracture in the previous 3-12 months, who had no dementia and walked ≥10 m before the fracture occurred. Target enrollment was 130 participants. Clinic-based CGC was delivered by a geriatrician, physiotherapist, and occupational therapist. Primary outcome was the Short Physical Performance Battery (SPPB; 0-12) at 12 months. RESULTS: We randomized 53/313 eligible participants with a mean (SD) age of 79.7 (7.9) years to intervention (n = 26) and usual care (UC, n = 27), and 49/53 (92%) completed the study. Mean 12-month (SD) SPPB scores in the intervention and UC groups were 9.08 (3.03) and 8.24 (2.44). The between-group difference was 0.9 (95% CI -0.3 to 2.0, p = 0.13). Adverse events were similar in the 2 groups. CONCLUSION: The small sample size of less than half our recruitment target precludes definitive conclusions about the effect of our intervention. However, our results are consistent with similar studies on this population and intervention.

The Burden of Brain Hypoxia and Optimal Mean Arterial Pressure in Patients With Hypoxic Ischemic Brain Injury After Cardiac Arrest.

OBJECTIVES: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation. DESIGN: Prospective interventional study. SETTING: Quaternary ICU. PATIENTS: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest. INTERVENTIONS: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software. MEASUREMENTS AND MAIN RESULTS: Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure. CONCLUSIONS: Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest.

Gas density alters expiratory time constants before and after experimental lung injury.

NEW FINDINGS: What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τE either before or after injury? What is the main finding and its importance? The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures. Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τE). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride (SF6). Values for τE decreased with injury and were more variable after injury than before (P < 0.001). Values for τE increased throughout expiration both before and after injury, and the rate of increase in τE was lessened by SF6 (P < 0.001 when compared with N2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF6 in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both N2 and He mixtures. Importantly, SF6 mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with N2 and He mixtures.

A randomized feasibility trial of clonidine to reduce perioperative cardiac risk in patients on chronic beta-blockade: the EPIC study.

PURPOSE: Clonidine may help prevent cardiac complications in patients undergoing non-cardiac surgery and receiving chronic beta-blocker therapy. We conducted a multicentre pilot randomized trial to estimate recruitment rates for a full-scale trial and to assess the safety and tolerability of combining clonidine with chronic beta-blockade. METHODS: Patients who were at elevated perioperative cardiac risk, receiving chronic beta-blockade, and scheduled for major non-cardiac surgery were recruited in a blinded (participants, clinicians, outcome assessors) placebo-controlled randomized trial at three Canadian hospitals. Participants were randomized to clonidine (0.2 mg oral tablet one hour before surgery, plus 0.2 mg·day(-1) transdermal patch placed one hour before surgery and removed four days after surgery or hospital discharge, whichever came first) or matching placebo. Feasibility was evaluated based on recruitment rates, with each centre being required to recruit 50 participants within 12-18 months. Additionally, we reviewed study drug withdrawals and safety outcomes, including clinically significant hypotension or bradycardia. RESULTS: Eighty-two of the 168 participants were randomized to receive clonidine and 86 to receive placebo. The average time to recruit 50 participants at each centre was 14.3 months. Six patients (7%) withdrew from clonidine, while four (5%) withdrew from placebo. Based on qualitative review, there were no major safety concerns related to clonidine. There was a moderate overall rate of cardiac morbidity, with 18 participants (11%) suffering postoperative myocardial infarction. CONCLUSION: This pilot randomized trial confirmed the feasibility, safety, and tolerability of a full-scale trial of oral and transdermal clonidine for reducing the risk of cardiac complications during non-cardiac surgery. This trial was registered at www.clinicaltrials.gov: NCT00335582.

Physical activity correlates with arterial stiffness in community-dwelling individuals with stroke.

BACKGROUND: Physical inactivity contributes to atherosclerotic processes, which manifest as increased arterial stiffness. Arterial stiffness is associated with myocardial demand and coronary perfusion and is a risk factor for stroke and other adverse cardiac outcomes. Poststroke mobility limitations often lead to physical inactivity and sedentary behaviors. This exploratory study aimed to identify functional correlates, reflective of daily physical activity levels, with arterial stiffness in community-dwelling individuals >1 year poststroke. METHODS: Carotid-femoral pulse wave velocity (cfPWV) was measured in 35 participants (65% men; mean ± SD age 66.9 ± 6.9 years; median time poststroke 3.7 years). Multivariable regression analyses examined the relationships between cfPWV and factors associated with daily physical activity: aerobic capacity (VO2 peak), gait speed, and balance ability (Berg Balance Scale). Age and the use of antihypertensive medications, known to be associated with pulse wave velocity, were also included in the model. RESULTS: Mean cfPWV was 11.2 ± 2.4 m/s. VO2 peak and age were correlated with cfPWV (r = -0.45 [P = .006] and r = 0.46 [P = .004], respectively). In the multivariable regression analyses, age and the use of antihypertensive medication accounted for 20.4% of the variance of cfPWV, and the addition of VO2 peak explained an additional 4.5% of the variance (R2 = 0.249). CONCLUSIONS: We found that arterial stiffness is elevated in community-dwelling, ambulatory individuals with stroke relative to healthy people. Multivariable regression analysis suggests that aerobic capacity (VO2 peak) may contribute to the variance of cfPWV after accounting for the effects of age and medication use. Whether intense risk modification and augmented physical activity will improve arterial stiffness in this population remains to be determined.

External Validation of the Post-Concussion Symptoms Rule for Predicting Mild Traumatic Brain Injury Outcome.

Persistent symptoms are common after a mild traumatic brain injury (mTBI). The Post-Concussion Symptoms (PoCS) Rule is a newly developed clinical decision rule for the prediction of persistent post-concussion symptoms (PPCS) 3 months after an mTBI. The PoCS Rule includes assessment of demographic and clinical characteristics and headache presence in the emergency department (ED), and follow-up assessment of symptoms at 7 days post-injury using two thresholds (lower/higher) for symptom scoring. We examined the PoCS Rule in an independent sample. We analyzed a clinical trial that recruited participants with mTBI from EDs in Greater Vancouver, Canada. The primary analysis used data from 236 participants, who were randomized to a usual care control group, and completed the Rivermead Postconcussion Symptoms Questionnaire at 3 months. The primary outcome was PPCS, as defined by the PoCS authors. We assessed the overall performance of the PoCS rule (area under the receiver operating characteristic curve [AUC]), sensitivity, and specificity. More than 40% of participants (median age 38 years, 59% female) reported PPCS at 3 months. Most participants (88%) were categorized as being at medium risk based on the ED assessment, and a majority were considered as being at high risk according to the final PoCS Rule (81% using a lower threshold and 72% using a higher threshold). The PoCS Rule showed a sensitivity of 93% (95% confidence interval [CI], 88-98; lower threshold) and 85% (95% CI, 78-92; higher threshold), and a specificity of 28% (95% CI, 21-36) and 37% (95% CI, 29-46), respectively. The overall performance was modest (AUC 0.61, 95% CI 0.59, 0.65). In conclusion, the PoCS Rule was sensitive for PPCS, but had a low specificity in our sample. Follow-up assessment of symptoms can improve risk stratification after mTBI.

Optical coherence tomography-based correlation between choroidal thickness and drusen load in dry age-related macular degeneration.

PURPOSE: Spectral domain optical coherence tomography can be used to measure both choroidal thickness and drusen load. The authors conducted an exploratory study using spectral domain optical coherence tomography to determine if a correlation between choroidal thickness and drusen load exists in patients with dry age-related macular degeneration. METHODS: Forty-four patients with dry age-related macular degeneration were recruited. The drusen area and volume were determined using the automated software algorithm of the spectral domain optical coherence tomography device, and choroidal thickness was measured using enhanced depth imaging. Correlations were determined using multivariable and univariable analyses. RESULTS: The authors found an inverse correlation between choroidal thickness and drusen load (r = -0.35, P = 0.04). Drusen load was also correlated with visual acuity (r = 0.32, P = 0.04). A correlation between choroidal thickness and visual acuity was suggested (r = -0.22, P = 0.21). CONCLUSION: Spectral domain optical coherence tomography can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. The measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for patients with dry age-related macular degeneration.

Blood flow index using near-infrared spectroscopy and indocyanine green as a minimally invasive tool to assess respiratory muscle blood flow in humans.

Near-infrared spectroscopy (NIRS) in combination with indocyanine green (ICG) dye has recently been used to measure respiratory muscle blood flow (RMBF) in humans. This method is based on the Fick principle and is determined by measuring ICG in the respiratory muscles using transcutaneous NIRS in relation to the [ICG] in arterial blood as measured using photodensitometry. This method is invasive since it requires arterial cannulation, repeated blood withdrawals, and reinfusions. A less invasive alternative is to calculate a relative measure of blood flow known as the blood flow index (BFI), which is based solely on the NIRS ICG curve, thus negating the need for arterial cannulation. Accordingly, the purpose of this study was to determine whether BFI can be used to measure RMBF at rest and during voluntary isocapnic hyperpnea at 25, 40, 55, and 70% of maximal voluntary ventilation in seven healthy humans. BFI was calculated as the change in maximal [ICG] divided by the rise time of the NIRS-derived ICG curve. Intercostal and sternocleidomastoid muscle BFI were correlated with simultaneously measured work of breathing and electromyography (EMG) data from the same muscles. BFI showed strong relationships with the work of breathing and EMG for both respiratory muscles. The coefficients of determination (R(2)) comparing BFI vs. the work of breathing for the intercostal and sternocleidomastoid muscles were 0.887 (P < 0.001) and 0.863 (P < 0.001), respectively, whereas the R(2) for BFI vs. EMG for the intercostal and sternocleidomastoid muscles were 0.879 (P < 0.001) and 0.930 (P < 0.001), respectively. These data suggest that the BFI closely reflects RMBF in conscious humans across a wide range of ventilations and provides a less invasive and less technically demanding alternative to measuring RMBF.

Canadian Optically-guided approach for Oral Lesions Surgical (COOLS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Oral cancer is a major health problem worldwide. The 5-year survival rate ranges from 30-60%, and has remained unchanged in the past few decades. This is mainly due to late diagnosis and high recurrence of the disease. Of the patients who receive treatment, up to one third suffer from a recurrence or a second primary tumor. It is apparent that one major cause of disease recurrence is clinically unrecognized field changes which extend beyond the visible tumor boundary. We have previously developed an approach using fluorescence visualization (FV) technology to improve the recognition of the field at risk surrounding a visible oral cancer that needs to be removed and preliminary results have shown a significant reduction in recurrence rates. METHOD/DESIGN: This paper describes the study design of a randomized, multi-centre, double blind, controlled surgical trial, the COOLS trial. Nine institutions across Canada will recruit a total of 400 patients with oral severe dysplasia or carcinoma in situ (N = 160) and invasive squamous cell carcinoma (N = 240). Patients will be stratified by participating institution and histology grade and randomized equally into FV-guided surgery (experimental arm) or white light-guided surgery (control arm). The primary endpoint is a composite of recurrence at or 1 cm within the previous surgery site with 1) the same or higher grade histology compared to the initial diagnosis (i.e., the diagnosis used for randomization); or 2) further treatment due to the presence of severe dysplasia or higher degree of change at follow-up. This is the first randomized, multi-centre trial to validate the effectiveness of the FV-guided surgery. DISCUSSION: In this paper we described the strategies, novelty, and challenges of this unique trial involving a surgical approach guided by the FV technology. The success of the trial requires training, coordination, and quality assurance across multiple sites within Canada. The COOLS trial, an example of translational research, may result in reduced recurrence rates following surgical treatment of early-stage oral cancer with significant impacts on survival, morbidity, patients' quality of life and the cost to the health care system. TRIAL REGISTRATION: Clinicaltrials.gov NCT01039298.

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

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.

Avoidance and endurance coping after mild traumatic brain injury are associated with disability outcomes.

Objective: Fear-avoidance and endurance behavior are well-established maladaptive coping styles in several chronic health conditions. There is also emerging evidence that both fear-avoidance and endurance coping are associated with poor outcome from mild traumatic brain injury (mTBI). The current study sought to characterize the early trajectories of avoidance and endurance behavior and confirm their association with disability outcomes. Method: Adults with mTBI (N = 88) completed measures of avoidance, endurance, and postconcussive symptoms at clinic intake (M = 40.2 days since injury). Avoidance and endurance measures were readministered 1 month later (N = 79), and a measure of perceived functional disability (World Health Organization Disability Assessment Schedule 2.0) was completed 3 months after clinic intake (N = 69). Results: Avoidance and endurance coping were weakly positively correlated with each other at intake (r = .28) and at 1 month postintake (r = .28). Change scores on these two measures over time were not significantly correlated (r = .04). Avoidance coping tended to decrease over time (95% CI [0.6, 2.5]; p = .002), whereas changes in endurance coping were variable. In generalized linear modeling, higher avoidance and endurance at clinic intake and increasing (or less rapidly decreasing) levels of these coping styles over 1 month was associated with greater perceived disability ratings at 3 months, even after controlling for postconcussion symptom severity at intake. Conclusion: These findings suggest that avoidance and endurance behavior are distinct coping styles with unique trajectories during the subacute recovery period. The results also support the need for psychologically informed early interventions that target specific profiles of maladaptive coping to mitigate risk for poor outcomes post-mTBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Using ActionADE to create information continuity to reduce re-exposures to harmful medications: study protocol for a randomized controlled trial.

BACKGROUND: Repeat exposures to culprit medications are a common cause of preventable adverse drug events. Health information technologies have the potential to reduce repeat adverse drug events by improving information continuity. However, they rarely interoperate to ensure providers can view adverse drug events documented in other systems. We designed ActionADE to enable rapid documentation of adverse drug events and communication of standardized information across health sectors by integrating with legacy systems. We will leverage ActionADE's implementation to conduct two parallel, randomized trials: patients with adverse drug reactions in the main trial and those diagnosed with non-adherence in a secondary trial. Primary objective of the main trial is to evaluate the effects of providing information continuity about adverse drug reactions on culprit medication re-dispensations over 12 months. Primary objective of the secondary trial is to evaluate the effect of providing information continuity on adherence over 12 months. METHODS: We will conduct two parallel group, triple-blind randomized controlled trials in participating hospitals in British Columbia, Canada. We will enroll adults presenting to hospital with an adverse drug event to prescribed outpatient medication. Clinicians will document the adverse drug event in ActionADE. The software will use an algorithm to determine patient eligibility and allocate eligible patients to experimental or control. In the experimental arm, ActionADE will transmit information to PharmaNet, where adverse drug event information will be displayed in community pharmacies when re-dispensations are attempted. In the control arm, ActionADE will retain information in the local record. We will enroll 3600 adults with an adverse drug reaction into the main trial. The main trial's primary outcome is re-dispensation of a culprit or same-class medication within 12 months; the secondary trial's primary outcome will be adherence to culprit medication. Secondary outcomes include health services utilization and mortality. DISCUSSION: These studies have the potential to guide policy decisions and investments needed to drive health information technology integrations to prevent repeat adverse drug events. We present an example of how a health information technology implementation can be leveraged to conduct pragmatic randomized controlled trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04568668 , NCT04574648 . Registered on 1 October 2020.

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.

Screening for Obstructive Sleep Apnea in an Atrial Fibrillation Population: What's the Best Test?

BACKGROUND: Among individuals with nonvalvular atrial fibrillation (AF), the prevalence of obstructive sleep apnea (OSA) can be as high as 85%. Continuous positive airway pressure treatment for moderate or severe OSA might improve AF outcomes and quality of life, so early identification of OSA might be of value. However, screening questionnaires for OSA are suboptimal because they are weighted toward tiredness and loud snoring, which might be absent in AF patients. NoSAS (Neck, Obesity, Snoring, Age, Sex) is a new OSA questionnaire that excludes these parameters. Acoustic pharyngometry (AP) is a potential novel screening technique that measures pharyngeal cross-sectional area, which is reduced in patients with OSA. METHODS: We prospectively compared the accuracy of the NoSAS, the STOP-BANG questionnaire (Snoring, Tiredness, Observed apnea, blood Pressure, Body mass index, Age, Neck circumference and Gender), and AP with home sleep apnea testing (HSAT) in consecutive patients with nonvalvular AF. RESULTS: Of 188 participants, 86% had OSA and 49% had moderate or severe OSA. Mean Epworth Sleepiness Scale scores were low; 5.9 (SD, 3.9), indicating that most participants were not sleepy. Receiver operating characteristic curves for comparisons of screening tests with HSAT showed suboptimal accuracy. For moderate plus severe and severe only groups respectively, the area under the curve was 0.50 (95% confidence interval [CI], 0.42-0.58) and 0.42 (95% CI, 0.34-0.52) for AP, 0.65 (95% CI, 0.58-0.73) and 0.63 (95% CI, 0.52-0.74) for the STOP-BANG questionnaire, and 0.68 (95% CI, 0.60-0.75) and 0.69 (95% CI, 0.59-0.80) for the NoSAS. CONCLUSIONS: AP and NoSAS are not sufficiently accurate for screening AF patients for OSA. Because of the high rates of OSA in this cohort, the potential benefits of OSA treatment, and the suboptimal accuracy of current screening questionnaires, cardiologists should consider HSAT for AF patients.

CONTEXTE: Chez les sujets présentant une fibrillation auriculaire (FA) non valvulaire, la prévalence de l'apnée obstructive du sommeil (AOS) peut atteindre 85 %. En cas d'AOS modérée ou sévère, un traitement par ventilation spontanée en pression positive continue peut améliorer les résultats liés à la FA et la qualité de vie du patient; un diagnostic précoce d'AOS pourrait donc être utile. Les questionnaires de dépistage de l'AOS ne sont toutefois pas optimaux parce qu'ils accordent une grande importance à la fatigue et aux ronflements sonores, des symptômes qui ne se manifestent pas nécessairement en cas de FA. Le questionnaire NoSAS (de l'anglais Neck, Obesity, Snoring, Age, Sex) est un nouvel outil d'évaluation de l'AOS qui ne tient pas compte de ces paramètres. La pharyngométrie acoustique (PA) pourrait aussi constituer une nouvelle technique de dépistage; elle mesure l'aire de section transversale du pharynx, qui est réduite chez les patients souffrant d'AOS. MÉTHODOLOGIE: Nous avons comparé de façon prospective la précision du score au questionnaire NoSAS, du score au questionnaire STOP-BANG (de l'anglais Snoring, Tiredness, Observed apnea, blood Pressure, Body mass index, Age, Neck circumference and Gender) et des résultats de la PA à celle du test d'apnée du sommeil à domicile (TASD) chez des patients consécutifs présentant une FA non valvulaire. RÉSULTATS: Sur les 188 participants, 86 % présentaient une AOS et 49 % souffraient d'AOS modérée ou sévère. Le score moyen sur l'échelle de somnolence d'Epworth était faible et se situait à 5,9 (écart-type : 3,9), ce qui indique que la plupart des participants ne ressentaient pas de somnolence. La comparaison entre les questionnaires de dépistage et le TASD effectuée au moyen des courbes caractéristiques de la performance des tests a révélé une précision sous-optimale. Dans les groupes souffrant d'AOS modérée ou sévère et d'AOS sévère seulement, les aires sous la courbe étaient respectivement de 0,50 (intervalle de confiance [IC] à 95 % : de 0,42 à 0,58) et de 0,42 (IC à 95 % : de 0,34 à 0,52) pour la PA, de 0,65 (IC à 95 % : de 0,58 à 0,73) et de 0,63 (IC à 95 % : de 0,52 à 0,74) pour le questionnaire STOP-BANG, et de 0,68 (IC à 95 % : de 0,60 à 0,75) et de 0,69 (IC à 95 % : de 0,59 à 0,80) pour le questionnaire NoSAS. CONCLUSIONS: La PA et le questionnaire NoSAS ne sont pas suffisamment précis pour dépister l'AOS chez les patients présentant une FA. Compte tenu de la forte prévalence de l'AOS dans cette cohorte, des bienfaits potentiels d'un traitement de l'AOS et de la précision sous-optimale des questionnaires de dépistage actuels, il conviendrait d'envisager un TASD chez les patients présentant une FA.

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

OBJECTIVES: To 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. DESIGN: A prospective multicentre, multicohort observational study. SETTING: Twenty-one clinical sites in the USA, Europe, Israel and Australia. PARTICIPANTS: 415 subjects from the de novo cohort of the Parkinson's Progression Markers Initiative. METHODS: We 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. RESULTS: 5723 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). CONCLUSIONS: The 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.

Naloxone dosing in the era of ultra-potent opioid overdoses: a systematic review.

OBJECTIVES: Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses. METHODS: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old. RESULTS: A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions. CONCLUSIONS: Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.

Near-Infrared Spectroscopy to Assess Cerebral Autoregulation and Optimal Mean Arterial Pressure in Patients With Hypoxic-Ischemic Brain Injury: A Prospective Multicenter Feasibility Study.

We provide preliminary multicenter data to suggest that recruitment and collection of physiologic data necessary to quantify cerebral autoregulation and individualized blood pressure targets are feasible in postcardiac arrest patients. We evaluated the feasibility of a multicenter protocol to enroll patients across centers, as well as collect continuous recording (≥ 80% of monitoring time) of regional cerebral oxygenation and mean arterial pressure, which is required to quantify cerebral autoregulation, using the cerebral oximetry index, and individualized optimal mean arterial pressure thresholds. Additionally, we conducted an exploratory analysis to assess if an increased percentage of monitoring time where mean arterial pressure was greater than or equal to 5 mm Hg below optimal mean arterial pressure, percentage of monitoring time with dysfunctional cerebral autoregulation (i.e., cerebral oximetry index ≥ 0.3), and time to return of spontaneous circulation were associated with an unfavorable neurologic outcome (i.e., 6-mo Cerebral Performance Category score ≥ 3). DESIGN SETTING AND PATIENTS: A prospective multicenter cohort study was conducted in ICUs in three teaching hospitals across Canada. Patients (≥ 16 yr old) were included if their cardiac arrest occurred within the previous 36 hours, they had greater than or equal to 20 consecutive minutes of spontaneous circulation following resuscitation, and they had a post-resuscitation Glasgow Coma Scale of less than or equal to 8. MEASUREMENTS AND MAIN RESULTS: Recruitment rates were calculated across sites, and patients underwent continuous regional cerebral oxygenation monitoring using near-infrared spectroscopy, as well as invasive blood pressure monitoring. Exploratory multivariable logistic regression was performed. Although it was feasible to recruit patients across multiple centers, there was variability in the recruitment rates. Physiologic data were captured in 86.2% of the total monitoring time and the median monitoring time was 47.5 hours (interquartile interval, 29.4-65.0 hr) across 59 patients. Specifically, 88% of mean arterial pressure and 96% of bilateral frontal regional cerebral oxygenation data were acquired, and 90% of cerebral oximetry index and 70% of optimal mean arterial pressure values were quantified. However, there was substantial variation in the amount of data captured among individuals. Time to return of spontaneous circulation was associated with an increased odds of an unfavorable neurologic outcome. CONCLUSIONS AND RELEVANCE: We demonstrated feasibility to recruit and collect high frequency physiologic data in patients after cardiac arrest. Future investigations will need to systematically document the reasons for data attrition, as well as how these methodological complications were resolved. Due to underpowered analyses and the inability to control for potential confounds, further studies are needed to explore the association between cerebral autoregulatory capacity and individualized mean arterial pressure thresholds with neurologic outcomes.