A phylogenetic method linking nucleotide substitution rates to rates of continuous trait evolution.

Genomes contain conserved non-coding sequences that perform important biological functions, such as gene regulation. We present a phylogenetic method, PhyloAcc-C, that associates nucleotide substitution rates with changes in a continuous trait of interest. The method takes as input a multiple sequence alignment of conserved elements, continuous trait data observed in extant species, and a background phylogeny and substitution process. Gibbs sampling is used to assign rate categories (background, conserved, accelerated) to lineages and explore whether the assigned rate categories are associated with increases or decreases in the rate of trait evolution. We test our method using simulations and then illustrate its application using mammalian body size and lifespan data previously analyzed with respect to protein coding genes. Like other studies, we find processes such as tumor suppression, telomere maintenance, and p53 regulation to be related to changes in longevity and body size. In addition, we also find that skeletal genes, and developmental processes, such as sprouting angiogenesis, are relevant.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Distinct antinociceptive and conditioned behavioral effects are produced by individual cannabinoids and a cannabis-derived mixture.

Cannabinoids have been proposed as therapeutics for pain mitigation. Therefore, the antihyperalgesic effects of a proprietary cannabis-derived mixture, Non-Euphoric Phytocannabinoid Elixir #14 (NEPE14), were examined in a persistent Complete Freund's Adjuvant (CFA)-induced model of inflammatory pain. The acute antinociceptive and operant behavioral effects of NEPE14 were then compared with single cannabinoid preparations of Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-THC, the synthetic cannabinoid (-)-CP 55,940 (CP), and cannabidiol (CBD). The THC isomers and CP were also administered with cannabinoid-type-1 receptor (CB1R) antagonist, AM251, and NEPE14 was administered in combination with THC or CP. To induce inflammation, CFA or saline was administered into the paw of male and female Wistar rats. After injections, mechanical hypersensitivity was assessed with Von Frey filaments, and thermal hyperalgesia with a thermal probe. Nine Sprague Dawley rats were also trained to respond under a fixed-ratio 30 schedule for food reinforcers during a 60-min session. Response rates were recorded during the session and warm-water tail-withdrawal latency post session. In CFA-administered rats, mechanical and thermal paw-withdrawal thresholds significantly decreased compared to vehicle, indicating hyperalgesia. Both i.p. (6.6-20.7 ml/kg) and o.m. (30-300 µL) NEPE14 significantly reduced the mechanical and thermal hyperalgesia. In contrast, neither NEPE14 (3.7-20.7 mL/kg i.p., 100-1000 µL o.m.) nor CBD (10-100 mg/kg) significantly decreased response rates or increased tail-withdrawal latency. Acute Δ9-THC, Δ8-THC (1-5.6 mg/kg), and CP (0.032-0.18 mg/kg) significantly and dose-dependently decreased overall response rate and increased tail-withdrawal latency compared to vehicle. AM251 significantly antagonized the rate-decreasing effects of THC, and CP, as well as the antinociceptive effects of CP. Combinations of NEPE14 with Δ9-THC or CP were not significantly different from these cannabinoids alone. In summary, while NEPE14 significantly reduced CFA-induced hyperalgesia, it was more similar to CBD than Δ9-THC, Δ8-THC, and CP for significantly reducing thermal nociception and disrupting conditioned behavior.

Ancient duplication, coevolution, and selection at the MHC class IIA and IIB genes of birds.

Introduction: The Major Histocompatibility Complex (MHC) of vertebrates is a dynamically evolving multigene family primarily responsible for recognizing non-self peptide antigens and triggering a pathogen-specific adaptive immune response. In birds, the MHC was previously thought to evolve via concerted evolution with high degree of gene homogenization and the rapid loss of orthology. However, the discovery of two ancient avian MHC-IIB gene lineages (DAB1 and DAB2) originating before the radiation of extant birds indicated that despite the action of concerted evolution, orthology may be detectable for long evolutionary periods. Methods: Here, we take advantage of rapidly accumulating digital genomic resources to search for the signal of an ancient duplication at the avian MHC-IIA genes, as well as to compare phylogenetic distribution and selection between MHC-IIA and IIB gene lineages. Results: The analysis of MHC sequences from over 230 species representing ca. 70 bird families revealed the presence of two ancient MHC-IIA gene lineages (DAA1 and DAA2) and showed that their phylogenetic distribution matches exactly the distribution of DAB1 and DAB2 lineages, suggesting tight coevolution. The early post-duplication divergence of DAA1 and DAA2 was driven by positive selection fixing radical amino acid differences within the membrane-proximal domain and, most probably, being functionally related to the interactions between α2 and ß2 chains of the MHC-II heterodimer. We detected no evidence for an overall (gene-wide) relaxation or intensification of selection at either DAA1/DAB1 or DAA2/DAB2, but codon-specific differences in selection signature were found at the peptide-binding sites between the two gene lineages, perhaps implying specialization to different pathogen regimes. Discussion: Our results suggest that specific pairing of MHC-II α and ß chains may have an adaptive significance, a conclusion that advances knowledge on the macroevolution of the avian MHC-II and opens exciting novel directions for future research.

HR+/HER2- Advanced Breast Cancer Treatment in the First-Line Setting: Expert Review.

The approval of CDK4/6 inhibitors has dramatically improved care for the treatment of HR+/HER2- advanced breast cancer, but navigating the rapidly-expanding treatment evidence base is challenging. In this narrative review, we provide best-practice recommendations for the first-line treatment of HR+/HER2- advanced breast cancer in Canada based on relevant literature, clinical guidelines, and our own clinical experience. Due to statistically significant improvements in overall survival and progression-free survival, ribociclib + aromatase inhibitor is our preferred first-line treatment for de novo advanced disease or relapse ≥12 months after completion of adjuvant endocrine therapy and ribociclib or abemaciclib + fulvestrant is our preferred first-line treatment for patients experiencing early relapse. Abemaciclib or palbociclib may be used when alternatives to ribociclib are needed, and endocrine therapy can be used alone in the case of contraindication to CDK4/6 inhibitors or limited life expectancy. Considerations for special populations-including frail and fit elderly patients, as well as those with visceral disease, brain metastases, and oligometastatic disease-are also explored. For monitoring, we recommend an approach across CDK4/6 inhibitors. For mutational testing, we recommend routinely performing ER/PR/HER2 testing to confirm the subtype of advanced disease at the time of progression and to consider ESR1 and PIK3CA testing for select patients. Where possible, engage a multidisciplinary care team to apply evidence in a patient-centric manner.

Clinical Pharmacy Services in Ambulatory Oncology: An Environmental Scan of the Canadian Practice Landscape.

Background: Canadian clinical pharmacy key performance indicators (cpKPIs) have been developed for inpatient hospital practice but are not established for ambulatory oncology. This study represents the first step in developing cpKPIs for ambulatory oncology. Objectives: To describe the current landscape of pharmacy services in ambulatory oncology in Canada and to identify perspectives related to the development and implementation of cpKPIs in this practice setting. Methods: In this national cross-sectional study, a web-based questionnaire was distributed to pharmacists working in ambulatory oncology settings. Potential participants who self-identified as pharmacists practising in an ambulatory oncology setting were eligible. Survey questions focused on participants' demographic characteristics, oncology pharmacy services provided, metrics captured, and pharmacists' perceptions of cpKPIs. All data were analyzed using descriptive statistics. Results: A total of 44 responses were received, with most respondents practising in community hospitals in British Columbia, Ontario, and Atlantic Canada. The services most commonly provided were chemotherapy order verification, laboratory monitoring, identification and resolution of drug therapy problems, and counselling on anticancer medications. Twenty-six of the 44 respondents (59%) indicated that performance metrics or patient outcomes were tracked at their respective institutions, with none being universally captured. Overall, 43 (98%) of the respondents favoured the development of cpKPIs for ambulatory oncology practice. Conclusions: Despite growing patient care needs in ambulatory oncology, there is significant heterogeneity in the scope of pharmacy services offered and the outcomes used to qualify their impact within this setting across Canada. This study demonstrates a clear need for national consensus cpKPIs to inform pharmacy resource utilization and patient-centred quality improvement initiatives.

Contexte: Des indicateurs clés de performance de la pharmacie clinique canadienne (cpKPI) ont été élaborés pour la pratique hospitalière en milieu hospitalier, mais n'ont pas été définis pour l'oncologie ambulatoire. Cette étude constitue la première étape de l'élaboration de cpKPI pour l'oncologie ambulatoire. Objectifs: Décrire le paysage actuel des services pharmaceutiques en oncologie ambulatoire au Canada et cerner les perspectives liées au développement et à la réalisation de cpKPI dans ce contexte de pratique. Méthodes: Dans cette étude transversale nationale, un questionnaire en ligne a été distribué aux pharmaciens qui travaillent en oncologie ambulatoire. Les participants potentiels qui se sont identifiés comme des pharmaciens exerçant dans ce contexte étaient autorisés à participer. Les questions de l'étude portaient sur les caractéristiques démographiques des participants, les services de pharmacie offerts en oncologie, les paramètres saisis et les perceptions des pharmaciens à l'égard des cpKPI. Toutes les données ont été analysées à l'aide de statistiques descriptives. Résultats: Au total, 44 réponses ont été reçues, la plupart des répondants exerçant dans des hôpitaux communautaires de la Colombie-Britannique, de l'Ontario et du Canada atlantique. Les services les plus couramment fournis étaient : la vérification des ordonnances de chimiothérapie, la surveillance en laboratoire, l'identification et la résolution des problèmes de pharmacothérapie et les conseils portant sur les médicaments anticancéreux. Vingt-six des 44 répondants (59 %) ont indiqué que les indicateurs de performance ou les résultats pour les patients faisaient l'objet d'un suivi dans leurs établissements respectifs, bien qu'aucun ne soit universellement saisi. Dans l'ensemble, 43 répondants (98 %) étaient favorables à l'élaboration de cpKPI pour la pratique de l'oncologie ambulatoire. Conclusions: Malgré les besoins croissants des patients en oncologie ambulatoire, la portée des services pharmaceutiques offerts et les résultats utilisés pour qualifier leur effet dans ce contexte au Canada sont fortement hétérogènes. Cette étude démontre un besoin évident de consensus portant sur les cpKPI à l'échelle nationale pour éclairer l'utilisation des ressources pharmaceutiques et les initiatives d'amélioration de la qualité centrées sur le patient.

The Safety and Biological Activity of OTT166, a Novel Topical Selective Integrin Inhibitor for the Treatment of Diabetic Eye Disease: A Phase 1b Study.

BACKGROUND AND OBJECTIVES: To evaluate the safety, tolerability, and biological activity of a topical selective integrin inhibitor (OTT166) eyedrop administered BID for diabetic retinopathy (DR) and diabetic macular edema (DME). STUDY DESIGN/MATERIALS AND METHODS: A prospective, multicenter, randomized, double-masked Phase 1b study. Subjects with nonproliferative DR and DME with central subfield thickness (CST) &gt; 325 microns were randomized to OTT166 eyedrops (2.5% or 5%) BID for 28 days. Subjects were followed for an additional 28 days after treatment cessation. RESULTS: Forty-four subjects were enrolled. No drug-related serious adverse events (SAEs) and two drug-related adverse events (AEs) were reported. OTT166 was well-tolerated with no evidence of ocular toxicity. Best-corrected visual acuity (BCVA) remained stable. Mean central retinal thickness (CRT) overall was variable: +12.8/+1.8 microns at Day 28 (end of treatment) and -50.3/+5.5 microns at Day 56 (end of study) for the 2.5% and 5% groups, respectively. Median CRT overall demonstrated consistent reduction by end of study: -39.0/-16.5 microns for the 2.5% and 5% groups, respectively. Median responses were greater in the treatment-naïve group (-41.5/-26.0 microns for the 2.5% and 5% groups, respectively). Thirty-seven percent of 'responder' subjects exhibited a mean reduction in CRT of 46.6 microns on optical coherence tomography (OCT) at end of treatment (Day 28) which persisted to end of the study (Day 56) - mean reduction of 67.4 microns, suggesting a durable effect. CONCLUSION: OTT166 eyedrops were safe, well-tolerated, and demonstrated biological activity in 37% of responders. These results warrant further evaluation of OTT166 eyedrops. <b>[<i>Ophthalmic Surg Lasers Imaging Retina</i> 2022;53:553-560.]</b>.

Evolution of the DAN gene family in vertebrates.

The DAN gene family (DAN, Differential screening-selected gene Aberrant in Neuroblastoma) is a group of genes that is expressed during development and plays fundamental roles in limb bud formation and digitation, kidney formation and morphogenesis and left-right axis specification. During adulthood the expression of these genes are associated with diseases, including cancer. Although most of the attention to this group of genes has been dedicated to understanding its role in physiology and development, its evolutionary history remains poorly understood. Thus, the goal of this study is to investigate the evolutionary history of the DAN gene family in vertebrates, with the objective of complementing the already abundant physiological information with an evolutionary context. Our results recovered the monophyly of all DAN gene family members and divide them into five main groups. In addition to the well-known DAN genes, our phylogenetic results revealed the presence of two new DAN gene lineages; one is only retained in cephalochordates, whereas the other one (GREM3) was only identified in cartilaginous fish, holostean fish, and coelacanth. According to the phyletic distribution of the genes, the ancestor of gnathostomes possessed a repertoire of eight DAN genes, and during the radiation of the group GREM1, GREM2, SOST, SOSTDC1, and NBL1 were retained in all major groups, whereas, GREM3, CER1, and DAND5 were differentially lost.

Early origin of sweet perception in the songbird radiation.

Early events in the evolutionary history of a clade can shape the sensory systems of descendant lineages. Although the avian ancestor may not have had a sweet receptor, the widespread incidence of nectar-feeding birds suggests multiple acquisitions of sugar detection. In this study, we identify a single early sensory shift of the umami receptor (the T1R1-T1R3 heterodimer) that conferred sweet-sensing abilities in songbirds, a large evolutionary radiation containing nearly half of all living birds. We demonstrate sugar responses across species with diverse diets, uncover critical sites underlying carbohydrate detection, and identify the molecular basis of sensory convergence between songbirds and nectar-specialist hummingbirds. This early shift shaped the sensory biology of an entire radiation, emphasizing the role of contingency and providing an example of the genetic basis of convergence in avian evolution.

Pilot Study of the Adaptation of an Alcohol, Tobacco, and Illicit Drug Use Intervention for Vulnerable Urban Young Adults.

Objectives: There is limited information about the applicability and effectiveness of tobacco and illicit drug use interventions in urban and racial/ethnic minority youth, a population with great need for prevention of alcohol and drug use. We pilot-tested the feasibility of a behavioral intervention to reduce alcohol, tobacco, and illicit drug use among urban young adults in New Orleans, Louisiana. Study Design: The 12-week intervention pilot project was developed to be implemented at a community-based social service organization that provides educational, juvenile justice-related case management, and mentoring services to youth with substance use and incarceration histories. Methods: One-hour intervention sessions included interactive discussions and lesson reviews guided by a health educator and peer facilitators. Recruitment was done by case managers. Thirty African American young adults aged 16-21 years participated between January 2016 and July 2017. Results: We were able to adapt the 14-session intervention to a 12-session, weekly curriculum that was well-received by the target population. Average rating for each session was 9.5 ± 0.3 (scale 0-10). Youth were willing to engage in the program, but retention was low. Rates of alcohol and drug use were significantly higher within our pilot population than national estimates. We found no significant decreases in self-reported alcohol, tobacco, or illicit drug use after participation in the intervention. Conclusion: Results emphasize the need to devote additional educational resources to intervention and retention factors for vulnerable youth. Individuals often experiment with drugs during adolescence; thus, this period represents a prime opportunity for education and intervention.

The Global Museum: natural history collections and the future of evolutionary science and public education.

Natural history museums are unique spaces for interdisciplinary research and educational innovation. Through extensive exhibits and public programming and by hosting rich communities of amateurs, students, and researchers at all stages of their careers, they can provide a place-based window to focus on integration of science and discovery, as well as a locus for community engagement. At the same time, like a synthesis radio telescope, when joined together through emerging digital resources, the global community of museums (the 'Global Museum') is more than the sum of its parts, allowing insights and answers to diverse biological, environmental, and societal questions at the global scale, across eons of time, and spanning vast diversity across the Tree of Life. We argue that, whereas natural history collections and museums began with a focus on describing the diversity and peculiarities of species on Earth, they are now increasingly leveraged in new ways that significantly expand their impact and relevance. These new directions include the possibility to ask new, often interdisciplinary questions in basic and applied science, such as in biomimetic design, and by contributing to solutions to climate change, global health and food security challenges. As institutions, they have long been incubators for cutting-edge research in biology while simultaneously providing core infrastructure for research on present and future societal needs. Here we explore how the intersection between pressing issues in environmental and human health and rapid technological innovation have reinforced the relevance of museum collections. We do this by providing examples as food for thought for both the broader academic community and museum scientists on the evolving role of museums. We also identify challenges to the realization of the full potential of natural history collections and the Global Museum to science and society and discuss the critical need to grow these collections. We then focus on mapping and modelling of museum data (including place-based approaches and discovery), and explore the main projects, platforms and databases enabling this growth. Finally, we aim to improve relevant protocols for the long-term storage of specimens and tissues, ensuring proper connection with tomorrow's technologies and hence further increasing the relevance of natural history museums.

Steroid Injection and Open Trigger Finger Release Outcomes: A Retrospective Review of 999 Digits.

Background: Open surgical release of the A1 pulley is the definitive treatment for the common hand condition of trigger finger, or inflammatory stenosing tenosynovitis. Anecdotal evidence among hand surgeons has questioned whether or not recent steroid injection may be related to complications following open trigger finger release, particularly wound infection, but no studies have primarily studied this connection to date. We aimed to determine whether recent steroid injection was associated with postoperative surgical infections. Methods: We performed a retrospective chart review of 780 adult patients who had undergone open trigger finger release of 999 digits by 6 fellowship-trained hand surgeons at three affiliated hospital settings from January 1, 2014, to January 1, 2016. Data on timing of steroid injections relative to surgery, number of steroid injections, concomitant conditions, use of antibiotics, and postoperative complications including infections were gathered. Results: Steroid injection timing relative to subsequent operative intervention correlated with postoperative surgical site infection in trigger finger release. Older age and decreasing days between steroid injection and surgery correlated with infection rates. Other factors found to be associated with infection rates included smoking, use of preoperative antibiotics, and use of lidocaine with epinephrine. The other factors examined did not correlate with infection rates. Conclusions: Steroid injection, smoking, increasing age, lesser number of days between steroid injection and surgery, and use of lidocaine with epinephrine are risk factors for postoperative trigger surgical infections. We recommend careful preoperative counseling regarding higher wound healing risks for smokers, avoidance of steroid injections immediately prior to an operative date, and scheduling operative dates that tend to be greater than 80 days from the date of last steroid injection. We also recommend avoidance of epinephrine in the local anesthetic solution, as this may minimize surgical site infection risks.

Outcomes of Unstable Scaphoid Nonunion With Segmental Defect Treated With Plate Fixation and Autogenous Cancellous Graft.

PURPOSE: Treatment of scaphoid nonunion with a segmental defect presents a challenging clinical problem. Various techniques have been proposed, often involving structural grafting with vascularized and nonvascularized bone. The authors hypothesize that satisfactory clinical and radiographic outcomes are possible with a relatively simplified technique of volar plate fixation with autogenous, purely cancellous graft. METHODS: The authors performed a retrospective review of 34 patients with scaphoid nonunions with segmental defects, treated with plate fixation and purely cancellous bone grafting. Cases with avascular necrosis were excluded. Surgical management included a volar incision, reduction, bone grafting from the ipsilateral distal radius and/or olecranon, and application of a volar locking plate. Postoperative outcome measures included time to union based on computed tomography, return to work and sports, patient-reported pain and disability scores, grip strength, and range of motion. RESULTS: Thirty-four patients with an average age of 31 years (range, 16-55 years) were treated with volar plate fixation and cancellous grafting, an average of 34 months after initial injury. Twenty-six patients (76%) were treated for nonunion at the scaphoid waist, 7 (21%) at the proximal pole, and 1 (3%) at the distal pole. Mean final follow-up was 18.7 months (range, 12-34 months). When union was defined by computed tomography evidence of healing, 2 (6%) scaphoids healed by 6 weeks after surgery, 28 (82%) healed by 12 weeks, and 100% healed by 18 weeks. Mean Disabilities of the Arm, Shoulder, and Hand score improved from 27.1 ± 7.3 before surgery to 11.8 ± 5.8 after surgery. Grip strength, corrected for hand dominance, improved from 77.5% of the nonsurgical side before surgery to 90.5% after surgery. All employed patients returned to work, although 3 (9%) did not return to full capacity. CONCLUSIONS: The combination of scaphoid plate fixation and pure cancellous bone grafting for scaphoid nonunion with segmental defects yields reliable union rates and good patient outcomes. Autogenous cancellous grafting may be an alternative to more technically demanding or morbid grafting procedures for the treatment of scaphoid nonunion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Plate Fixation With Cancellous Graft for Scaphoid Nonunion With Avascular Necrosis.

PURPOSE: Currently, there is no consensus on the optimal treatment for scaphoid nonunion with avascular necrosis (AVN). Various techniques, often involving vascularized corticocancellous bone grafting, have been proposed. The authors hypothesized that similar outcomes might be possible with volar plate fixation augmented with autogenous pure cancellous graft. METHODS: The authors performed a retrospective chart review of 13 cases of scaphoid nonunions with AVN in 12 patients treated with plate fixation and pure cancellous bone grafting. Surgical management included a volar incision, reduction, impaction of cancellous bone graft from the ipsilateral olecranon and/or distal radius, and application of a volar locking plate. Postoperative outcome measures included time to union based on computed tomography, patient-reported pain and disability scores, grip strength, range of motion, and return to work and sports. RESULTS: The average patient was 32 years old (range, 17-50 years) and treated an average of 18 months after initial injury (range, 6-49 months). Two of 12 patients (15.7%) were female, 3 of 12 patients (25%) were smokers, and 5 of 12 patients (41.7%) had failed union with previous screw fixation. Twelve scaphoids (92.3%) were treated for AVN associated with a proximal pole fracture, and 1 (7.7%) for AVN proximal to a scaphoid waist fracture. Mean follow-up was 19.5 months (range, 12-29 months). Union was achieved in all patients. Two scaphoids (15%) achieved union by 12 weeks, 7 scaphoids (54%) by 18 weeks, 2 scaphoids (15%) by 24 weeks, and 2 scaphoids (15%) by 30 weeks (range, 8.9-28 weeks). Mean Disabilities of the Arm, Shoulder, and Hand score improved from 30.6 ± 6.2 before surgery to 17.2 ± 6.5 after surgery. All 11 employed patients returned to work, although 3 (27.2%) did not return to full capacity. CONCLUSIONS: Scaphoid plate fixation and pure nonvascularized cancellous bone grafting for scaphoid nonunion with AVN yields excellent union rates and good patient-reported and functional outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Patient monitoring programs in oncology pharmacy practice: A survey of oncology pharmacists in Atlantic Canada.

BACKGROUND: There has been a dramatic increase in new drug approvals in oncology, consisting of both small molecule inhibitors and monoclonal antibodies. However, Health Canada approval for many of the new agents was based on single randomized trials consisting of only a few hundred patients. As more patients get treated with these newer agents, there is the potential for new and discrete toxicities. Pharmacists are in an ideal position to identify, monitor, manage, and even preempt future events, given their close proximity to the patient. However, the extent of pharmacists' involvement in formal patient programs is unknown. To address this knowledge gap, a survey of oncology pharmacists practicing in Atlantic Canada was conducted. METHODS: A structured mailing strategy was adopted as recommended by Dillman (1978). Standardized data collection forms were electronically mailed to 60 oncology pharmacists. Survey items consisted of respondent demographic information, practice setting, the existence of a formal patient monitoring program managed, and if patients are contacted by telephone following the completion of their anticancer cycle. RESULTS: Overall, 31 completed surveys were received, for an overall response rate of 50%. Respondents had a median age of 42 and a median of 18 years' (range 1 to 25) professional experience as a pharmacist. Only 18 of the 31 (58%) respondents indicated that there was a formal monitoring and call back program managed by pharmacy available at their institution. For those without such programs, the main reasons were due to staffing issues and lack of adequately trained clinical personnel. Overall, 100% of respondents would favor the development of a formal monitoring program in hospitals with a high volume of anticancer drug prescribing. CONCLUSIONS: Even though the number of new anticancer drugs being introduced into clinical pharmacy practice is increasing, formal patient monitoring and patient call back programs are not universal in Atlantic Canada hospitals.

A Biomechanical Comparison of Screw and Plate Fixations for Scaphoid Fractures.

Background Headless screw fixation is the current gold standard of surgical repair for scaphoid fractures. However, maintaining reduction of certain types of scaphoid fractures is challenging with a compression screw. Plate fixation may offer superior fixation in some scaphoid fractures, particularly those with comminution, nonunion, segmental bony defects, and osteopenic or osteoporotic bone. Purpose This study questions whether method of fixation is a determinant in load to failure in segmental scaphoid fractures, and whether any fixation provides a greater mechanical advantage in simulated normal versus osteoporotic bone. Materials and Methods Polyurethane models were fashioned to simulate scaphoids with 3-mm segmental defects. Defects were bridged by one of three constructs: a locking plate, a nonlocking plate, or a headless compression screw. Three models for each fixation construct were tested for both simulated normal and osteoporotic bone density. Load to failure was recorded as the load at which the 3-mm segmental defect was closed. Results Gap closure occurred in all trials. In simulated normal bone, there were no statistically significant differences in load to failure between fixation methods. In simulated osteoporotic bone, the locking plate had a 28% greater load to failure as compared with screw fixation. Conclusion While biomechanical testing shows that plate and screw fixations are equivalent in normal density bone for fixation of a segmental scaphoid defect, locking plates are superior to screw fixation in simulated osteoporotic bone models. Clinical Relevance Plate fixation may provide superior fixation for complex scaphoid fractures, particularly in osteopenic bone.

The Olecranon Osteotomy-Facilitated Elbow Release (OFER).

BACKGROUND: Elbow contractures can cause functional limitation, and treatment can be challenging. The purpose of this article is to describe a novel technique that releases posttraumatic elbow contractures through an olecranon osteotomy and report the outcomes. METHODS: Thirty-five patients with refractory posttraumatic elbow contracture who underwent an olecranon osteotomy-facilitated elbow release (OFER) procedure were included in the study. The average patient age was 39.5 years (range, 18 to 63 years), and the mean duration of follow-up was 37.2 months (range, 24 to 72 months). Preoperative and postoperative data included age, sex, cause of contracture, previous surgical procedures, active elbow range of motion, Disabilities of the Arm, Shoulder and Hand (DASH) scores, visual analog scale pain scores, and radiographs. Intraoperative tourniquet time and complications were recorded. RESULTS: The mean preoperative elbow motion arc was 33° (51° to 84° of flexion). Postoperatively, the motion arc improved significantly (p < 0.001) to 110° (16° to 126° of flexion). The mean visual analog pain scale score improved from 6.3 preoperatively to 1.4 at the time of follow-up (p < 0.001). The mean DASH score improved from 57.5 preoperatively to 10.9 postoperatively (p < 0.001). The maximal improvement in the motion arc occurred at a mean of 8.7 weeks. There was 1 postoperative ulnar neurapraxia that resolved spontaneously. The intraoperative tourniquet time averaged 27 minutes (range, 18 to 45 minutes). The average time until radiographic evidence of union of the olecranon osteotomy site was 6.6 weeks (range, 5.7 to 7.7 weeks). CONCLUSIONS: The OFER is a safe and effective means of treating posttraumatic elbow contractures, and is an alternative to traditional open or arthroscopic techniques. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Gene flow during glacial habitat shifts facilitates character displacement in a Neotropical flycatcher radiation.

BACKGROUND: Pleistocene climatic fluctuations are known to be an engine of biotic diversification at higher latitudes, but their impact on highly diverse tropical areas such as the Andes remains less well-documented. Specifically, while periods of global cooling may have led to fragmentation and differentiation at colder latitudes, they may - at the same time - have led to connectivity among insular patches of montane tropical habitat with unknown consequences on diversification. In the present study we utilized ~5.5 kb of DNA sequence data from eight nuclear loci and one mitochondrial gene alongside diagnostic morphological and bioacoustic markers to test the effects of Pleistocene climatic fluctuations on diversification in a complex of Andean tyrant-flycatchers of the genus Elaenia. RESULTS: Population genetic and phylogenetic approaches coupled with coalescent simulations demonstrated disparate levels of gene flow between the taxon chilensis and two parapatric Elaenia taxa predominantly during the last glacial period but not thereafter, possibly on account of downward shifts of montane forest habitat linking the populations of adjacent ridges. Additionally, morphological and bioacoustic analyses revealed a distinct pattern of character displacement in coloration and vocal traits between the two sympatric taxa albiceps and pallatangae, which were characterized by a lack of gene flow. CONCLUSION: Our study demonstrates that global periods of cooling are likely to have facilitated gene flow among Andean montane Elaenia flycatchers that are more isolated from one another during warm interglacial periods such as the present era. We also identify a hitherto overlooked case of plumage and vocal character displacement, underpinning the complexities of gene flow patterns caused by Pleistocene climate change across the Andes.

Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary.

The timing of the diversification of placental mammals relative to the Cretaceous-Paleogene (KPg) boundary mass extinction remains highly controversial. In particular, there have been seemingly irreconcilable differences in the dating of the early placental radiation not only between fossil-based and molecular datasets but also among molecular datasets. To help resolve this discrepancy, we performed genome-scale analyses using 4,388 loci from 90 taxa, including representatives of all extant placental orders and transcriptome data from flying lemurs (Dermoptera) and pangolins (Pholidota). Depending on the gene partitioning scheme, molecular clock model, and genic deviation from molecular clock assumptions, extensive sensitivity analyses recovered widely varying diversification scenarios for placental mammals from a given gene set, ranging from a deep Cretaceous origin and diversification to a scenario spanning the KPg boundary, suggesting that the use of suboptimal molecular clock markers and methodologies is a major cause of controversies regarding placental diversification timing. We demonstrate that reconciliation between molecular and paleontological estimates of placental divergence times can be achieved using the appropriate clock model and gene partitioning scheme while accounting for the degree to which individual genes violate molecular clock assumptions. A birth-death-shift analysis suggests that placental mammals underwent a continuous radiation across the KPg boundary without apparent interruption by the mass extinction, paralleling a genus-level radiation of multituberculates and ecomorphological diversification of both multituberculates and therians. These findings suggest that the KPg catastrophe evidently played a limited role in placental diversification, which, instead, was likely a delayed response to the slightly earlier radiation of angiosperms.

Comparison of Postoperative Complications Associated With Anesthetic Choice for Surgery of the Hand.

PURPOSE: There is a recent trend toward performing most hand surgery procedures under local and/or regional anesthesia without sedation. However, little evidence exists regarding the postoperative complications associated with local/regional anesthesia without sedation, especially compared with local/regional anesthesia with sedation or general anesthesia. METHODS: Patients who underwent hand procedures as part of the American College of Surgeons National Surgical Quality Improvement Program were identified. Thirty-day postoperative complications were compared among patients who received local/regional anesthesia without sedation, local/regional anesthesia with sedation, and general anesthesia with adjustment for patient and procedural factors. RESULTS: We identified 27,041 patients as having undergone hand surgery from 2005 to 2013. A total of 4,614 underwent local/regional anesthesia without sedation (17.1%), 3,527 underwent local/regional anesthesia with sedation (13.0%), and 18,900 underwent general anesthesia (69.9%). Overall, both local/regional anesthesia with and without sedation were associated with fewer postoperative complications compared with general anesthesia. In patients aged over 65 years, there was an additional benefit of avoiding all forms of sedation; these data showed that treatment with local/regional anesthesia without sedation decreased the odds of sustaining a postoperative complication compared with sedation and general anesthesia. CONCLUSIONS: Although the overall risk of postoperative complications remains small in hand surgery, these data suggest that avoiding general anesthesia may decrease the overall risk of sustaining postoperative complications. In addition, for patients aged over 65 years, avoiding any form of sedation may decrease the risk of postoperative complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.