Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study.

BACKGROUND: The relations of alcohol consumption and gene expression remain to be elucidated. MATERIALS AND METHODS: We examined cross-sectional associations between alcohol consumption and whole blood derived gene expression levels and between alcohol-associated genes and obesity, hypertension, and diabetes in 5531 Framingham Heart Study (FHS) participants. RESULTS: We identified 25 alcohol-associated genes. We further showed cross-sectional associations of 16 alcohol-associated genes with obesity, nine genes with hypertension, and eight genes with diabetes at P < 0.002. For example, we observed decreased expression of PROK2 (ß = -0.0018; 95%CI: -0.0021, -0.0007; P = 6.5e - 5) and PAX5 (ß = -0.0014; 95%CI: -0.0021, -0.0007; P = 6.5e - 5) per 1 g/day increase in alcohol consumption. Consistent with our previous observation on the inverse association of alcohol consumption with obesity and positive association of alcohol consumption with hypertension, we found that PROK2 was positively associated with obesity (OR = 1.42; 95%CI: 1.17, 1.72; P = 4.5e - 4) and PAX5 was negatively associated with hypertension (OR = 0.73; 95%CI: 0.59, 0.89; P = 1.6e - 3). We also observed that alcohol consumption was positively associated with expression of ABCA13 (ß = 0.0012; 95%CI: 0.0007, 0.0017; P = 1.3e - 6) and ABCA13 was positively associated with diabetes (OR = 2.57; 95%CI: 1.73, 3.84; P = 3.5e - 06); this finding, however, was inconsistent with our observation of an inverse association between alcohol consumption and diabetes. CONCLUSIONS: We showed strong cross-sectional associations between alcohol consumption and expression levels of 25 genes in FHS participants. Nonetheless, complex relationships exist between alcohol-associated genes and CVD risk factors.

What do primary care providers want to know when caring for patients living with frailty? An analysis of eConsult communications between primary care providers and specialists.

BACKGROUND: Frailty is a complex condition that primary care providers (PCPs) are managing in increasing numbers, yet there is no clear guidance or training for frailty care. OBJECTIVES: The present study examined eConsult questions PCPs asked specialists about patients with frailty, the specialists' responses, and the impact of eConsult on the care of these patients. DESIGN: Cross-sectional observational study. SETTING: ChamplainBASE™ eConsult located in Eastern Ontario, Canada. PARTICIPANTS: Sixty one eConsult cases closed by PCPs in 2019 that use the terms "frail" or "frailty" to describe patients 65 years of age or older. MEASUREMENTS: The Taxonomy of Generic Clinical Questions (TGCQ) was used to classify PCP questions and the International Classification for Primary Care 3 (ICPC-3) was used to classify the clinical content of each eConsult. The impact of eConsult on patient care was measured by PCP responses to a mandatory survey. RESULTS: PCPs most frequently directed their questions to cardiology (n = 7; 11%), gastroenterology (n = 7; 11%), and endocrinology (n = 6; 10%). Specialist answers most often pertained to medications (n = 63, 46%), recommendations for clinical investigation (n = 24, 17%), and diagnoses (n = 22, 16%). Specialist responses resulted in PCPs avoiding referral in 57% (n = 35) of cases whereas referrals were still required in 15% (n = 9) of cases. Specialists responded to eConsults in a median 1.11 days (IQR = 0.3-4.7), and 95% (n = 58) of cases received a response within 7 days. Specialists recorded a median of 15 min to respond (IQR = 10-20), with a median cost of $50.00 CAD (IQR = 33.33 - 66.66) per eConsult. CONCLUSIONS: Through the analysis of questions and responses submitted to eConsult, this study provides novel information on PCP knowledge gaps and approaches to care for patients living with frailty. Furthermore, these analyses provide evidence that eConsult is a feasible and valuable tool for improving care for patients with frailty in primary care settings.

A systematic review of perioperative clinical practice guidelines for care of older adults living with frailty.

BACKGROUND: Perioperative frailty is prevalent and requires complex management, which could be guided by clinical practice guidelines (CPGs). The objective of this systematic review was to identify and synthesise CPGs that provide perioperative recommendations specific to older adults living with frailty. METHODS: After protocol registration, we performed a systematic review of CPGs. MEDLINE, Embase, CINAHL, and 14 grey literature databases were searched (January 1, 2000 until December 22, 2021). We included all CPGs that contained at least one frailty-specific recommendation related to any phase of the perioperative period. We compiled all relevant recommendations, extracted underlying strength of evidence, and categorised them by perioperative phase of care. Within each phase, recommendations were synthesised inductively into themes. Quality of CPGs was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: From 4707 citations, 13 guidelines were included; 8/13 were focused on the perioperative care of older surgical patients in general. Among 110 recommendations extracted, 37 themes were generated, with the majority pertaining to preoperative care. Four themes were supported by strong evidence: performing preoperative frailty assessments, using multidimensional frailty instruments, reducing urinary catheter use, and following multidisciplinary care and communication throughout the perioperative period. Per AGREE II, most guidelines (8/13; 62%) were recommended for use with modifications. CONCLUSIONS: Despite increasing numbers of patients living with frailty, few guidelines exist that address frailty-specific perioperative care. Given the lack of strong evidence-based recommendations, particularly outside the preoperative period, high-quality primary research is required to underpin future guidelines and better inform the care of older surgical patients with frailty. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022320149.

Barriers and facilitators to participation in exercise prehabilitation before cancer surgery for older adults with frailty: a qualitative study.

BACKGROUND: Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. METHODS: This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. RESULTS: Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. CONCLUSIONS: Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions.

Afatinib treatment in a large real-world cohort of nonsmall cell lung cancer patients with common and uncommon epidermal growth factor receptor mutation.

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) afatinib improves survival in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. We analysed the outcome between EGFR mutation subtypes in a large afatinib-treated cohort in which 516 EGFR-mutated NSCLC patients receiving afatinib as front-line treatment. EGFR uncommon mutations include exon 20 insertion, de novo T790M of high or low allele frequency (dT790MHAF /dT790MLAF ), non-T790M compound mutation and others, where EGFR exon 20 insertion and dT790MHAF were defined as type-I and the rest as type-II uncommon mutation. Four hundred and sixty-one (89.3%) and 55 (10.7%) patients were common and uncommon mutation, respectively. Exon 20 insertion and dT790MHAF patients demonstrated a significantly shortened progression-free survival (PFS) (2.6 and 4.1 months) compared to EGFR common mutation, dT790MLAF and other uncommon mutation patients (15.1, 27.0 and 18.4 months; P = 3 × 10-8 ). Type-I uncommon mutation was an independent predictor of PFS (HR 4.46 [95% CI, 2.60-7.64]; P < .001) and OS (HR 2.56 [95% CI, 1.37-4.75]; P = .003). EGFR L858R patients demonstrated a significantly higher CNS progression (cause-specific HR, 3.16; 95% CI 1.24-8.08; P = .016), and type-I uncommon mutation patients exhibited a significantly higher systemic progression (cause-specific HR, 4.95; 95% CI 2.30-10.60; P = 4.3 × 10-5 ). Tendencies of higher CNS and lower systemic progression were observed in type-II uncommon mutation patients. A PFS ≥ 12 months (OR 2.38 [95% CI, 1.18-4.89]; P = .016) and uncommon EGFR mutation (OR 0.08 [95% CI, 0.01-0.48]; P = .021) were independent predictors of secondary T790M. Afatinib-treated NSCLC patients presented an EGFR genotype-specific pattern of disease progression and outcome.

Home-based prehabilitation with exercise to improve postoperative recovery for older adults with frailty having cancer surgery: the PREHAB randomised clinical trial.

BACKGROUND: Frailty is a state of vulnerability as a result of decreased reserves. Prehabilitation may increase reserve and improve postoperative outcomes. Our objective was to determine if home-based prehabilitation improves postoperative functional recovery in older adults with frailty having cancer surgery. METHODS: This double blind randomised trial enrolled people ≥60 yr having elective cancer surgery and ≥3 weeks from enrolment to surgery as eligible. Participation in a remotely supported, home-based exercise prehabilitation program plus nutritional guidance was compared with standard care plus written advice on age-appropriate activity and nutrition. The primary outcome was 6-min walk test (6MWT) distance at the first postoperative clinic visit. Secondary outcomes included physical performance, quality of life, disability, length of stay, non-home discharge, and 30-day readmission. RESULTS: Of 543 patients assessed, 254 were eligible and 204 (80%) were randomised (102 per arm); 182 (94 intervention and 88 control) had surgery and were analysed. Mean age was 74 yr and 57% were female. Mean duration of participation was 5 weeks, mean adherence was 61% (range 0%-100%). We found no significant difference in 6MWT at follow-up (+14 m, 95% confidence interval -26-55 m, P=0.486), or for secondary outcomes. Analyses using a prespecified adherence definition of ≥80% supported improvements in 6MWT distance, complication count, and disability. CONCLUSIONS: A home-based prehabilitation program did not significantly improve postoperative recovery or other outcomes in older adults with frailty having cancer surgery. Program adherence may be a key mediator of prehabilitation efficacy. CLINICAL TRIAL REGISTRATION: NCT02934230.

Development and evaluation of an evidence-based, theory-grounded online Clinical Frailty Scale tutorial.

INTRODUCTION: Frailty is a robust predictor of adverse outcomes in older people. Practice guidelines recommend routine screening for frailty; however, this does not occur regularly. The Clinical Frailty Scale (CFS) is a validated, feasible instrument that can be used in a variety of clinical settings and is associated with many adverse outcomes. Our objective was to develop and evaluate an online training module to guide frailty assessment using the CFS. METHODS: A multidisciplinary team of clinical experts developed an evidence-based, theory-grounded online training module for users who wished to perform frailty assessment using the CFS. The module was prospectively evaluated for user satisfaction, effectiveness and feasibility using a standardised questionnaire. Qualitative feedback was analysed with thematic analysis. RESULTS: Version 1 of the CFS module was used 627 times from 21 October 2019 to 24 March 2020. Satisfaction, effectiveness and feasibility of the module were positively rated (≥4/5 on a 5-point Likert scale n = 582 [93%], n = 507, [81%], n = 575, [91%], respectively). Qualitative feedback highlighted ease of use, likelihood of users to share the module with others and opportunities to increase multimedia content. CONCLUSION: An online tutorial, designed using evidence and theory to guide frailty assessment using the CFS, was positively rated by users. The module's content and structure was rated effective and feasible, and users were satisfied with, and likely to share, the module. Research evaluating the module's impact on the accuracy of frailty assessment is required.

Comparison of Clinical Characteristics and Outcomes of Hospitalized Patients Infected with the D614G Strain or Alpha Variant of COVID-19 in Taiwan: A Multi-Center Cohort Study.

Objective: Direct comparison of the clinical traits of coronavirus disease 2019 (COVID-19) in strain D614G, which originated from Wuhan, China, and the Alpha variant, which contains 17 mutations, infected patients could help physicians distinguish between strains and make clinical decisions accordingly. This study sought to compare the clinical characteristics and outcomes of the D614G strain and Alpha variant of SARS-COV-2 and identify the predictors for viral RNA clearance and in-hospital mortality in patients with COVID-19. Methods: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were determined. Results: Among the 239 enrolled patients, 11.2% (27/239) were infected with strain D614G and 88.7% (212/239) were infected with the Alpha variant. There were no significant differences in disease progression, rate of respiratory failure, subsequent development of acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, duration of stay in the intensive care unit or hospital, discharge rate, mortality rate, or viral RNA clearance time between the two groups. Multivariate Cox regression revealed that antibiotic therapy reduced the risk of delayed viral RNA clearance (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.13-0.55), while autoimmune disease increased the risk of delayed viral RNA clearance (HR, 3.98; 95% CI, 1.21-13.04). Elderly patients (age > 65 years) and patients with a history of cerebrovascular accident (CVA) were at increased risk of in-hospital mortality (HR, 5.14; 95% CI, 1.06-24.72 and HR, 3.62; 95% CI, 1.25-10.42, respectively). Conclusions: There were no significant differences between the D614G strain and Alpha variant of COVID-19 in terms of clinical characteristics and outcomes. However, factors affecting viral RNA clearance and the risk of in-hospital mortality were identified. These results could help to inform the future prioritization of resource allocation and identify patients in need of intense monitoring.

Identifying barriers and facilitators to routine preoperative frailty assessment: a qualitative interview study.

PURPOSE: Preoperative frailty assessment is recommended by multiple practice guidelines and may improve outcomes, but it is not routinely performed. The barriers and facilitators of routine preoperative frailty assessment have not been formally assessed. Our objective was to perform a theory-guided evaluation of barriers and facilitators to preoperative frailty assessment. METHODS: This was a research ethics board-approved qualitative study involving physicians who perform preoperative assessment (consultant and resident anesthesiologists and consultant surgeons). Semistructured interviews were conducted by a trained research assistant informed by the Theoretical Domains Framework to identify barriers and facilitators to frailty assessment. Interview transcripts were independently coded by two research assistants to identify specific beliefs relevant to each theoretical domain. RESULTS: We interviewed 28 clinicians (nine consultant anesthesiologists, nine consultant surgeons, and ten anesthesiology residents). Six domains (Knowledge [100%], Social Influences [96%], Social Professional Role and Identity [96%], Beliefs about Capabilities [93%], Goals [93%], and Intentions [93%]) were identified by > 90% of respondents. The most common barriers identified were prioritization of other aspects of assessment (e.g., cardio/respiratory) and a lack of awareness of evidence and guidelines supporting frailty assessment. The most common facilitators were a high degree of familiarity with frailty, recognition of the importance of frailty assessment, and strong intentions to perform frailty assessment. CONCLUSION: Barriers and facilitators to preoperative frailty assessment are multidimensional, but generally consistent across different types of perioperative physicians. Knowledge of barriers and facilitators can guide development of evidence-based strategies to increase frailty assessment.

RéSUMé: OBJECTIF: L'évaluation préopératoire de la fragilité est recommandée par plusieurs lignes directrices de pratique et pourrait améliorer les devenirs, mais elle n'est pas systématiquement réalisée. Les obstacles et les facilitateurs de l'évaluation de routine de la fragilité préopératoire n'ont pas été officiellement évalués. Notre objectif était de mener une évaluation théorique des obstacles et des facilitateurs de l'évaluation préopératoire de la fragilité. MéTHODE: Il s'agissait d'une étude qualitative approuvée par le comité d'éthique de la recherche impliquant des médecins menant des évaluations préopératoires (anesthésiologistes, résidents en anesthésiologie et chirurgiens). Des entrevues semi-structurées ont été réalisées par un assistant de recherche formé en se fondant sur le Cadre des domaines théoriques afin d'identifier les obstacles et les facilitateurs à l'évaluation de la fragilité. Les transcriptions des entrevues ont été codées de manière indépendante par deux assistants de recherche afin d'identifier les croyances spécifiques pertinentes à chaque domaine théorique. RéSULTATS: Nous avons interrogé 28 cliniciens (neuf anesthésiologistes, neuf chirurgiens et dix résidents en anesthésiologie). Six domaines (Connaissances [100 %], Influences sociales [96 %], Rôle et identité socio-professionnels [96 %], Croyances concernant les capacités [93 %], Objectifs [93 %] et Intentions [93 %]) ont été identifiés par > 90 % des répondants. Les obstacles les plus fréquemment cités étaient la priorisation accordée à d'autres aspects de l'évaluation (p. ex., cardio/respiratoire) et le manque de connaissances des données probantes et des lignes directrices à l'appui de l'évaluation de la fragilité. Les facilitateurs les plus courants étaient un degré élevé de familiarité avec la fragilité, la reconnaissance de l'importance de l'évaluation de la fragilité et de fortes intentions de réaliser une évaluation de la fragilité. CONCLUSION: Les obstacles et les facilitateurs de l'évaluation préopératoire de la fragilité sont multidimensionnels, mais généralement uniformes parmi les différents types de médecins périopératoires. La connaissance des obstacles et des facilitateurs peut guider l'élaboration de stratégies fondées sur des données probantes pour augmenter l'évaluation de la fragilité.

Increased Distraction Magnitude Leads to Greater Reduction in the Apnea-Hypopnea Index in Infants With Robin Sequence.

PURPOSE: Upper airway obstruction seen in Robin Sequence (RS) is commonly treated with mandibular distraction osteogenesis (MDO). The purpose of this study is to evaluate the impact of distraction distance on sleep study outcomes in patients with obstructive sleep apnea (OSA) secondary to RS. METHODS: A retrospective cohort study was conducted for patients with isolated RS who underwent MDO at Children's Hospital Los Angeles between January 2006-September 2021. The predictor variable was distraction distance (maximal distraction using a 30 mm device vs sub-maximal distraction), and the primary outcome variable was OSA scores. Relationships between covariates, including demographic characteristics, preoperative sleep variables, and postoperative OSA outcomes using polysomnography, were also analyzed. Descriptive statistics and tests of statistical significance were performed using the Statistical Package for Social Sciences (SPSS) (version 28.0), including Student's t-test, proportions testing, multiple linear regression, and correlation analysis. RESULTS: Seventy-one patients met inclusion criteria (39.4% female, 60.6% male). Average age at MDO was 3.0 ± 10.2 months. Fifty-six patients were distracted maximally with a 30 mm distractor, while the remaining 15 patients experienced shorter distraction due to distractor limitations (25 mm distractor), persistent infection or family request. Looking at absolute values of postoperative sleep study variables, there were no significant differences between patients who were maximally and sub-maximally distracted across apnea-hypopnea index (AHI), highest carbon dioxide, lowest oxygen saturation, and oxygen requirement. However, both cohorts demonstrated significant improvements in lowest oxygen saturation, AHI, highest carbon dioxide level, and highest oxygen requirement compared to their pre-distraction levels. Compared with patients distracted <30 mm, maximal distraction had a significantly greater improvement in AHI when controlling for preoperative sleep study variables (P = .047). CONCLUSION: Patients with isolated RS who have more severe OSA experienced greater improvements in AHI, oxygen requirement, and oxygen saturation after MDO. Two-thirds of patients no longer had oxygen requirements after MDO. Our results suggest that MDO is helpful in treating patients with RS regardless of distraction distance. However, our study provides evidence that increasing the distraction distance may further improve AHI, which is particularly beneficial to patients with a significant preoperative AHI.

A retrospective study of alectinib versus ceritinib in patients with advanced non-small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed.

BACKGROUND: Crizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion. Failure of crizotinib treatment frequently involves drug intolerance or resistance. Comparison of using second-generation ALK inhibitors in this setting remains lacking. METHODS: Sixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy. RESULTS: Forty-three (66.2%) and 22 (33.8%) patients received alectinib and ceritinib, respectively. Comparing alectinib to ceritinib treatment: the 12-month progression-free survival (PFS) rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); the hazard ratio (HR) for disease progression or death, 0.61 (95% CI, 0.31-1.17; p = 0.135). Multivariate Cox regression showed ECOG PS (0-1 vs. 2-3 HR 0.09 [95% CI, 0.02-0.33]; p < 0.001) and cause of crizotinib treatment failure (resistance vs. intolerance HR 2.75 [95% CI, 1.26-5.99]; p = 0.011) were the independent predictors for the PFS of second-generation ALK inhibitors. Treatment of alectinib, compared to ceritinib, was associated with a lower incidence of CNS progression (cause-specific HR, 0.10; 95% CI 0.01-0.78; p = 0.029) and a higher efficacy in patients whose cause of crizotinib treatment failure was intolerance (HR 0.29 [95% CI, 0.08-1.06]; p = 0.050). The most commonly noted adverse events were elevated AST/ALT in 10 (23.3%) patients treated with alectinib and diarrhea in 8 (36.4%) patients treated with ceritinib. CONCLUSION: Second-generation ALK inhibitors in crizotinib-treated patients showed a satifactory efficacy. Alectinib treatment demonstrated a CNS protection activity and a higher PFS in selected patients failing crizotinib treatment.

Peripheral Nerve Blocks and Potentially Attributable Adverse Events in Older People with Hip Fracture: A Retrospective Population-based Cohort Study.

BACKGROUND: Peripheral nerve blocks are being used with increasing frequency for management of hip fracture-related pain. Despite converging evidence that nerve blocks may be beneficial, safety data are lacking. This study hypothesized that peripheral nerve block receipt would not be associated with adverse events potentially attributable to nerve blocks, as well as overall patient safety incidents while in hospital. METHODS: This was a preregistered, retrospective population-based cohort study using linked administrative data. This study identified all hip fracture admissions in people 50 yr of age or older and identified all nerve blocks (although we were unable to ascertain the specific anatomic location or type of block), potentially attributable adverse events (composite of seizures, fall-related injuries, cardiac arrest, nerve injury), and any patient safety events using validated codes. The study also estimated the unadjusted and adjusted association of nerve blocks with adverse events; adjusted absolute risk differences were also calculated. RESULTS: In total, 91,563 hip fracture patients from 2009 to 2017 were identified; 15,631 (17.1%) received a nerve block, and 5,321 (5.8%; 95% CI, 5.7 to 6.0%) patients experienced a potentially nerve block-attributable adverse event: 866 (5.5%) in patients with a block and 4,455 (5.9%) without a block. Before and after adjustment, nerve blocks were not associated with potentially attributable adverse events (adjusted odds ratio, 1.05; 95% CI, 0.97 to 1.15; and adjusted risk difference, 0.3%, 95% CI, -0.1 to 0.8). CONCLUSIONS: The data suggest that nerve blocks in hip fracture patients are not associated with higher rates of potentially nerve block-attributable adverse events, although these findings may be influenced by limitations in routinely collected administrative data.

Detection of adverse drug events in e-prescribing and administrative health data: a validation study.

BACKGROUND: Administrative health data are increasingly used to detect adverse drug events (ADEs). However, the few studies evaluating diagnostic codes for ADE detection demonstrated low sensitivity, likely due to narrow code sets, physician under-recognition of ADEs, and underreporting in administrative data. The objective of this study was to determine if combining an expanded ICD code set in administrative data with e-prescribing data improves ADE detection. METHODS: We conducted a prospective cohort study among patients newly prescribed antidepressant or antihypertensive medication in primary care and followed for 2 months. Gold standard ADEs were defined as patient-reported symptoms adjudicated as medication-related by a clinical expert. Potential ADEs in administrative data were defined as physician, ED, or hospital visits during follow-up for known adverse effects of the study medication, as identified by ICD codes. Potential ADEs in e-prescribing data were defined as study drug discontinuations or dose changes made during follow-up for safety or effectiveness reasons. RESULTS: Of 688 study participants, 445 (64.7%) were female and mean age was 64.2 (SD 13.9). The study drug for 386 (56.1%) patients was an antihypertensive, and for 302 (43.9%) an antidepressant. Using the gold standard definition, 114 (16.6%) patients experienced an ADE, with 40 (10.4%) among antihypertensive users and 74 (24.5%) among antidepressant users. The sensitivity of the expanded ICD code set was 7.0%, of e-prescribing data 9.7%, and of the two combined 14.0%. Specificities were high (86.0-95.0%). The sensitivity of the combined approach increased to 25.8% when analysis was restricted to the 27% of patients who indicated having reported symptoms to a physician. CONCLUSION: Combining an expanded diagnostic code set with e-prescribing data improves ADE detection. As few patients report symptoms to their physician, higher detection rates may be achieved by collecting patient-reported outcomes via emerging digital technologies such as patient portals and mHealth applications.

Intoxication is a Significant Risk Factor for Severe Craniomaxillofacial Injuries in Standing Electric Scooter Accidents.

PURPOSE: Standing electric scooters are a relatively new mode of transportation that are becoming increasingly popular in large metropolitan areas. The purpose of this study was to characterize injury patterns and identify risk factors for craniomaxillofacial injuries in standing electric scooter accidents. METHODS: This retrospective cohort study used a Clinical Data Warehouse search engine to identify patients who sustained standing electric scooter accidents from 2017 to 2019 using the International Classification of Diseases 10th revision codes. Predictors including patient demographics, presence of intoxication, helmet use, mechanism of injury, and other noncraniomaxillofacial injuries sustained at the time of standing electric scooter injury were identified. Patients were grouped as per the presence or absence of craniomaxillofacial injuries so that risk factors could be identified for craniomaxillofacial injuries in standing electric scooter accidents. Logistic regression analysis was performed to identify potential risk factors and association for craniomaxillofacial injuries. RESULTS: The sample was composed of 165 patients with a mean age of 30.3 years and 73.9% were men. Of them, 38 (23.0%) sustained craniomaxillofacial trauma. They were ten times more likely to have been intoxicated than those who did not have craniomaxillofacial injuries (4.7 vs 52.6%). Concomitant injuries of the extremities and the craniomaxillofacial region were rare indicating that in many cases the arms and legs were not outstretched to "break the fall." The high numbers of mandibular fractures to the condylar, subcondylar, and symphyseal regions (23.8, 33.3, and 28.6%, respectively), Le Fort fractures (18.4%), and frontal sinus fractures (15.8%) indicate that falls in the anterior-posterior direction occur with the main point of impact occurring at the chin, midface, and forehead. CONCLUSIONS: Intoxication may inhibit or depress protective reflexes that leave the face and head vulnerable during standing electric scooter accidents.

Passing The Scalpel: A Student Initiative in Identifying and Addressing Unmet Needs in Dental Education.

PURPOSE: Becoming an oral-maxillofacial surgeon is often challenging for young trainees. The purpose of this manuscript is to explore how a student-led group, which emphasizes networking, mentorship, and academic opportunities, may impact one's journey to becoming an oral-maxillofacial surgeon. PATIENTS AND METHODS: This was a cross-sectional descriptive study where a 5-question Likert-type survey was administered to students who matriculated into residency and participated in a student-led group called Passing The Scalpel (PTS). This survey evaluated the value of PTS in providing exposure, career decision-making, networking/mentorship, and camaraderie. The results were analyzed, and statistical outcomes were evaluated. RESULTS: There was an 80.5% response rate (n = 29). Question 1 regarding first exposure to oral-maxillofacial surgery had a mean score of 2.55 (standard deviation [SD] = 1.35; χ2 = 15.39; P < .05). Question 2 regarding choosing oral-maxillofacial surgery as a career had a mean score of 3.66 (SD = 1.11; χ2 = 10.84; P < .05). Question 3 regarding offering mentorship and networking had a mean score of 4.14 (SD = 0.92; χ2 = 27.81; P < .05). Question 4 regarding increasing applicant camaraderie had a mean score of 4.21 (SD = 0.77; χ2 = 36.71; P < .05). Question 5 regarding the importance of PTS within a dental curriculum had a score of 4.48 (SD = 0.68; χ2 = 41.89; P < .05). CONCLUSION: PTS is an effective student-led initiative that emphasizes early exposure, networking, and mentorship opportunities and encourages students in choosing oral-maxillofacial surgery as a specialty. PTS demonstrates that student-led initiatives can fulfill unmet needs in the dental curriculum.

Frailty as a Predictor of Death or New Disability After Surgery: A Prospective Cohort Study.

OBJECTIVE: To compare the accuracy of the modified Fried Index (mFI) and the Clinical Frailty Scale (CFS) to predict death or patient-reported new disability 90 days after major elective surgery. BACKGROUND: The association of frailty with patient-reported outcomes, and comparisons between preoperative frailty instruments are poorly described. METHODS: This was a prospective multicenter cohort study. We determined frailty status in individuals ≥65 years having elective noncardiac surgery using the mFI and CFS. Outcomes included death or patient-reported new disability (primary); safety incidents, length of stay (LOS), and institutional discharge (secondary); ease of use, usefulness, benefit, clinical importance, and feasibility (tertiary). We measured the adjusted association of frailty with outcomes using regression analysis and compared true positive and false positive rates (TPR/FPR). RESULTS: Of 702 participants, 645 had complete follow up. The CFS identified 297 (42.3%) with frailty, the mFI 257 (36.6%); 72 (11.1%) died or experienced a new disability. Frailty was significantly associated with the primary outcome (CFS adjusted odds ratio, OR, 2.51, 95% confidence interval, CI, 1.50-4.21; mFI adjusted-OR 2.60, 95% CI 1.57-4.31). TPR and FPR were not significantly different between instruments. Frailty was the only significant predictor of death or new disability in a multivariable analysis. Need for institutional discharge, costs and LOS were significantly increased in individuals with frailty. The CFS was easier to use, required less time and had less missing data. CONCLUSIONS: Older people with frailty are significantly more likely to die or experience a new patient-reported disability after surgery. Clinicians performing frailty assessments before surgery should consider the CFS over the mFI as accuracy was similar, but ease of use and feasibility were higher.

Frailty and long-term postoperative disability trajectories: a prospective multicentre cohort study.

BACKGROUND: Frailty is associated with early postoperative outcomes. How frailty influences long-term postoperative recovery is poorly described. Our objective was to evaluate the association of frailty with postoperative disability trajectories in the year after surgery. METHODS: Prespecified 1-yr follow-up of a prospective multicentre cohort study. Patients ≥65 yr were assessed for frailty before major elective noncardiac surgery (Clinical Frailty Scale [CFS] and Fried Phenotype [FP]). The primary outcome was patient-reported disability score (using the WHO Disability Assessment Schedule 2.0) at baseline, 30, 90, and 365 days after surgery. Repeated measures linear regression estimated the association of preoperative frailty with changes in disability scores over time, adjusted for procedure. Group-based trajectory modelling was used to identify subgroup trajectories of people with frailty. RESULTS: One-year follow-up was complete for 687/702 (97.9%) participants. Frailty was associated with a significant difference in disability trajectory (P<0.0001). Compared with baseline, people with frailty experienced a decrease in disability score at 365 days (CFS frailty: -7.3 points, 95% confidence interval [CI] -10.2 to -4.5); (FP frailty: -5.4 points, 95% CI -8.5 to -2.3); people without frailty had no significant change in their disability score from baseline (no CFS frailty: +0.8 points, 95% CI -1.7 to 3.2; no FP frailty: +1.1 points, 95% CI -3.5 to 1.3). More than one-third of people with frailty experienced an early increase in disability before achieving a net decrease in disability. CONCLUSIONS: Decision-making and care planning should integrate the possible trade-offs between early adverse outcomes with longer-term benefit when frailty is present in older surgical patients.

Prospective Comparison of Preoperative Predictive Performance Between 3 Leading Frailty Instruments.

BACKGROUND: Guidelines recommend routine preoperative frailty assessment for older people. However, the degree to which frailty instruments improve predictive accuracy when added to traditional risk factors is poorly described. Our objective was to measure the accuracy gained in predicting outcomes important to older patients when adding the Clinical Frailty Scale (CFS), Fried Phenotype (FP), or Frailty Index (FI) to traditional risk factors. METHODS: This was an analysis of a multicenter prospective cohort of elective noncardiac surgery patients ≥65 years of age. Each frailty instrument was prospectively collected. The added predictive performance of each frailty instrument beyond the baseline model (age, sex, American Society of Anesthesiologists' score, procedural risk) was estimated using likelihood ratio test, discrimination, calibration, explained variance, and reclassification. Outcomes analyzed included death or new disability, prolonged length of stay (LoS, >75th percentile), and adverse discharge (death or non-home discharge). RESULTS: We included 645 participants (mean age, 74 [standard deviation, 6]); 72 (11.2%) participants died or experienced a new disability, 164 (25.4%) had prolonged LoS, and 60 (9.2%) had adverse discharge. Compared to the baseline model predicting death or new disability (area under the curve [AUC], 0.67; R, 0.08, good calibration), prolonged LoS (AUC, 0.73; R, 0.18, good calibration), and adverse discharge (AUC, 0.78; R, 0.16, poor calibration), the CFS improved fit per the likelihood ratio test (P < .02 for death or new disability, <.001 for LoS, <.001 for discharge), discrimination (AUC = 0.71 for death or new disability, 0.76 for LoS, 0.82 for discharge), calibration (good for death or new disability, LoS, and discharge), explained variance (R = 0.11 for death or new disability, 0.22 for LoS, 0.25 for discharge), and reclassification (appropriate directional reclassification) for all outcomes. The FP improved discrimination and R for all outcomes, but to a lesser degree than the CFS. The FI improved discrimination for death or new disability and R for all outcomes, but to a lesser degree than the CFS and the FP. These results were consistent in internal validation. CONCLUSIONS: Frailty instruments provide meaningful increases in accuracy when predicting postoperative outcomes for older people. Compared to the FP and FI, the CFS appears to improve all measures of predictive performance to the greatest extent and across outcomes. Combined with previous research demonstrating that the CFS is easy to use and requires less time than the FP, clinicians should consider its use in preoperative practice.

Derivation and Validation of a Generalizable Preoperative Frailty Index Using Population-based Health Administrative Data.

OBJECTIVE: To develop and validate a preoperative frailty index (pFI) for use in population-based health administrative (HA) data. SUMMARY BACKGROUND DATA: Frailty is a robust predictor of adverse postoperative outcomes. Population-level frailty measures used in surgical studies have significant methodological limitations. Frailty indices (FIs) are a well-defined approach to measuring frailty with well-described methods for development and evaluation. An appropriate preoperative FI in HA data has not been derived or evaluated. METHODS: Retrospective cohort study using linked HA data in Canada. We identified people >65 years (2002-2015) who had major elective or emergency surgery. Standardized methods were used to construct a 30-variable pFI. Unadjusted and multilevel, multivariable adjusted models were used to measure the association of the pFI with 1-year mortality and institutional discharge. Elective patients were the derivation cohort, emergency patients were the validation cohort. Prespecified sensitivity analyses were performed. RESULTS: We identified 415,704 elective, and 95,581 emergency patients. The elective 1-year mortality rate was 4.7%. Thirty percent of population-level deaths occurred in people with frailty. Every 0.1-unit increase in the pFI was associated with a 2.20-fold increase in the adjusted odds of mortality (95% CI 2.15-2.26; c-statistic 0.81), and a 1.70-fold increase in institutional discharge (95% CI 1.59-1.80; c-statistic 0.71). pFI performance was similar in emergency patients, and was robust to changes in index composition. CONCLUSIONS: A preoperative FI derived from HA data is a robust method to measure frailty in elective and emergency patients. Generalizable FIs should be considered a standard approach to population-level study of surgical frailty.

Recent Approaches to Improve Medication Adherence in Patients with Coronary Heart Disease: Progress Towards a Learning Healthcare System.

PURPOSE OF REVIEW: Non-adherence to medications for the secondary prevention of myocardial infarction (MI) is a major contributor to morbidity and mortality in these patients. This review describes recent advances in promoting adherence to therapies for coronary artery disease (CAD). RECENT FINDINGS: Two large randomized controlled trials to "incentivize" adherence were somewhat disappointing; neither financial incentives nor "peer pressure" successfully increased rates of adherence in the post-MI population. Patient education and provider engagement appear to be critical aspects of improving adherence to CAD therapies, where the provider is a physician, pharmacist, or nurse and follow-up is performed in person or by telephone. Fixed-dose combinations of CAD medications, formulated as a so-called "polypill," have shown some early efficacy in increasing adherence. Technological advances that automate monitoring and/or encouragement of adherence are promising but seem universally dependent on patient engagement. For example, medication reminders via text message perform better if patients are required to respond. Multifaceted interventions, in which these and other interventions are combined together, appear to be most effective. There are several available types of proven interventions through which providers, and the health system at large, can advance patient adherence to CAD therapies. No single intervention to promote adherence will be successful in all patients. Further study of multifaceted interventions and the interactions between different interventions will be important to advancing the field. The goal is a learning healthcare system in which a network of interventions responds and adapts to patients' needs over time.