Are older adults considered in asthma and chronic obstructive pulmonary disease mobile health research? A scoping review.

BACKGROUND: The use of mobile health (mHealth) for asthma and chronic obstructive pulmonary disease (COPD) is rapidly growing and may help address the complex respiratory care needs of our ageing population. However, little is currently known about how airways mHealth is developed and used among older adults (≥65 years). OBJECTIVE: To identify if and how older adults with asthma and COPD have been incorporated across the mHealth research cycle. METHODS: We searched Ovid MEDLINE, EMBASE, CINAHL and the Cochrane Central Registry of Controlled Trials for studies pertaining to the development or evaluation of asthma and COPD mHealth for adults published after 2010. Study, participant and mHealth details, including any considerations of older age, were extracted, synthesised and charted. RESULTS: A total of 334 studies of 191 mHealth tools were identified. Adults ≥65 years old were included in 33.3% of asthma mHealth studies and 85.3% of COPD studies. Discussions of older age focused on barriers to technology use. Methodologic and/or analytic considerations of older age were mostly absent throughout the research cycle. Among the 28 instances quantitative age-related analyses were detailed, 12 described positive mHealth use and satisfaction outcomes in older adults versus negative or equivocal outcomes. CONCLUSION: We identified an overall lack of consideration for older age throughout the airways mHealth research cycle, even among COPD mHealth studies that predominantly included older adults. We also found a contrast between the perceptions of how older age might negatively influence mHealth use and available quantitative evaluations. Future airways mHealth research must better integrate the needs and concerns of older adults.

Outcomes of critically ill older adults with COVID-19: a multicentre retrospective cohort study.

PURPOSE: Older adults with COVID-19 have a high prevalence of complications and mortality during hospitalization. Given the large proportion of older adults requiring admission to an intensive care unit (ICU), we aimed to describe the management and outcomes of older adults with COVID-19 requiring ICU care and identify predictors of hospital mortality. METHODS: We included consecutive patients ≥ 65 yr of age who were admitted between 11 March 2020 and 30 June 2021 to one of five Toronto (ON, Canada) ICUs with a primary diagnosis of SARS-CoV-2 infection in a retrospective cohort study. Patient characteristics, ICU treatment, and outcomes were recorded. We used multivariable logistic regression to identify predictors of in-hospital mortality. RESULTS: Of the 273 patients, the median [interquartile range] age was 74 [69-80] yr, 104 (38.1%) were female, and 164 (60.1%) required invasive mechanical ventilation. One hundred and forty-two patients (52.0%) survived their hospital stay. Compared with survivors, nonsurvivors were older (74 [70-82] yr vs 73 [68-78] yr; P = 0.03), and a smaller proportion was female (39/131, 29.8% vs 65/142, 45.8%; P = 0.01). Patients had long hospital (19 [11-35] days) and ICU (9 [5-22] days) stays, with no significant differences in ICU length of stay or duration of invasive mechanical ventilation between the two groups. Higher APACHE II score, increasing age, and the need for organ support were independently associated with higher in-hospital mortality while female sex was associated with lower mortality. CONCLUSIONS: Older critically ill COVID-19 patients had long ICU and hospital stays, and approximately half died in hospital. Further research is needed to identify individuals who will benefit most from an ICU admission and to evaluate posthospitalization outcomes.

RéSUMé: OBJECTIF: Les personnes âgées atteintes de la COVID-19 ont une prévalence élevée de complications et de mortalité pendant l'hospitalisation. Compte tenu de la forte proportion de personnes âgées nécessitant une admission dans une unité de soins intensifs (USI), nous avons cherché à décrire la prise en charge et les devenirs des personnes âgées atteintes de COVID-19 nécessitant des soins intensifs et à identifier les prédicteurs de mortalité hospitalière. MéTHODE: Nous avons inclus des patient·es consécutif·ves âgé·es de ≥ 65 ans admis·es entre le 11 mars 2020 et le 30 juin 2021 dans l'une des cinq unités de soins intensifs de Toronto (ON, Canada) avec un diagnostic primaire d'infection par le SRAS-CoV-2 dans une étude de cohorte rétrospective. Les caractéristiques des patient·es, le traitement en USI et les devenirs ont été enregistrés. Nous avons utilisé une régression logistique multivariable pour identifier les prédicteurs de mortalité hospitalière. RéSULTATS: Parmi les 273 patient·es, l'âge médian [écart interquartile] était de 74 [69-80] ans, 104 (38,1 %) étaient des femmes et 164 (60,1 %) ont nécessité une ventilation mécanique invasive. Cent quarante-deux personnes (52,0 %) ont survécu à leur séjour à l'hôpital. Comparativement aux personnes survivantes, les personnes qui n'ont pas survécu étaient plus âgées (74 [70-82] ans vs 73 [68­78] ans; P = 0,03), et une plus faible proportion était de sexe féminin (39/131, 29,8 % vs 65/142, 45,8 %; P = 0,01). Les séjours des patient·es à l'hôpital (19 [11-35] jours) et à l'USI (9 [5-22] jours) étaient longs, sans différence significative dans la durée du séjour en USI ou la durée de la ventilation mécanique invasive entre les deux groupes. Un score APACHE II plus élevé, un âge plus avancé et le besoin de mesures de soutien d'organes étaient indépendamment associés à une mortalité plus élevée à l'hôpital, tandis que le sexe féminin était associé à une mortalité plus faible. CONCLUSION : Les personnes plus âgées gravement malades atteintes de la COVID-19 ont eu de longs séjours en soins intensifs et à l'hôpital, et environ la moitié sont décédées à l'hôpital. D'autres recherches sont nécessaires pour identifier les personnes qui bénéficieraient le plus d'une admission à l'USI et pour évaluer les devenirs post-hospitalisation.

Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations.

The voltage-gated Hv1 proton channel is a ubiquitous membrane protein that has roles in a variety of cellular processes, including proton extrusion, pH regulation, production of reactive oxygen species, proliferation of cancer cells, and increased brain damage during ischemic stroke. A crystal structure of an Hv1 construct in a putative closed state has been reported, and structural models for the channel open state have been proposed, but a complete characterization of the Hv1 conformational dynamics under an applied membrane potential has been elusive. We report structural models of the Hv1 voltage-sensing domain (VSD), both in a hyperpolarized state and a depolarized state resulting from voltage-dependent conformational changes during a 10-µs-timescale atomistic molecular dynamics simulation in an explicit membrane environment. In response to a depolarizing membrane potential, the S4 helix undergoes an outward displacement, leading to changes in the VSD internal salt-bridge network, resulting in a reshaping of the permeation pathway and a significant increase in hydrogen bond connectivity throughout the channel. The total gating charge displacement associated with this transition is consistent with experimental estimates. Molecular docking calculations confirm the proposed mechanism for the inhibitory action of 2-guanidinobenzimidazole (2GBI) derived from electrophysiological measurements and mutagenesis. The depolarized structural model is also consistent with the formation of a metal bridge between residues located in the core of the VSD. Taken together, our results suggest that these structural models are representative of the closed and open states of the Hv1 channel.

Impact of an orthogeriatric collaborative care model for older adults with hip fracture in a community hospital setting.

Background: Studies have shown that the incidence of postoperative delirium, the hospital length of stay and time to surgery are reduced when older adults with a hip fracture are cared for by a multidisciplinary team providing comprehensive geriatric assessments. Most of these studies have been conducted in academic centres. We sought to determine if implementation of an orthogeriatric collaborative care model would improve key quality of care metrics in a community hospital setting. Methods: This retrospective pre- and postintervention single-site study was conducted in a community hospital in Ontario, Canada. We included consecutive patients aged 65 years or older who were admitted for a hip fracture between June 2015 and June 2017. In the intervention period, a new postoperative order set included a referral to a geriatrician for comprehensive geriatric assessment, with direct implementation of recommendations. Primary outcomes were the incidence of postoperative delirium and length of stay. Secondary outcomes included Health Quality Ontario's quality standards for hip fracture. Results: A total of 212 consecutive patients (95 in the preintervention group and 117 in the postintervention group) were included in the study. The incidence of postoperative delirium (26.3% v. 26.5%, p = 0.98) and length of stay (interquartile range 4-10 v. 5-10 d, p = 0.32) were similar in the preintervention and postintervention groups. There were improvements (p < 0.001) in the rates of asssessment of mental status, falls and bone health; identification of delirium prevention strategies; prescription of vitamin D or calcium or both; and recommendations for antiresorptive therapy. Despite systemic implementation of the orthogeriatric model, only 74.4% of patients in the postintervention group were seen by a geriatric medicine consultant. Conclusion: Although the implementation of an orthogeriatric collaborative care model for older adults with a hip fracture did not reduce the incidence of postoperative delirium or length of stay, there were improvements in the rates at which several other key quality standards for hip fracture care were met. Earlier proactive, comprehensive geriatric assessment in a community hospital setting will be the target for further quality improvement initiatives.

Contexte: Des études ont montré que l'incidence du délire postopératoire, la durée du séjour à l'hôpital et le temps d'attente avant la chirurgie sont réduits lorsque les personnes âgées présentant une fracture de la hanche reçoivent les soins d'une équipe multidisciplinaire qui réalise une évaluation gériatrique complète. La plupart de ces études ont été effectuées dans des centres universitaires. Nous souhaitions donc déterminer si l'intégration d'un modèle de soins orthogériatriques collaboratif améliorerait les principaux indicateurs de la qualité des soins dans les hôpitaux communautaires. Méthodes: Cette étude rétrospective comparant 2 groupes de patients avant et après la mise en oeuvre d'une intervention a été menée dans un seul hôpital communautaire en Ontario, au Canada. Nous avons inclus les patients consécutifs de 65 ans et plus admis pour une fracture de la hanche entre juin 2015 et juin 2017. Pendant la période d'intervention, un nouvel ensemble d'ordonnances postopératoires a été ajouté. Il comprenait l'aiguillage vers un gériatre pour une évaluation gériatrique complète et l'application directe des recommandations. Les principales issues à l'étude étaient l'incidence du délire postopératoire et la durée de l'hospitalisation. Les issues secondaires comprenaient le respect des normes de qualité relatives à la fracture de la hanche de Qualité des services de santé Ontario. Résultats: Au total, 212 patients consécutifs (95 dans le groupe préintervention et 117 dans le groupe postintervention) ont été inclus dans l'étude. L'incidence du délire postopératoire (26,3 % c. 26,5 %, p = 0,98) et la durée de l'hospitalisation (écart interquartile 4­10 jours c. 5­10 jours, p = 0,32) étaient similaires dans les 2 groupes. Il y a eu des améliorations (p < 0,001) dans le taux d'évaluation de l'état mental, des chutes et de la santé des os; dans l'intégration de stratégies de prévention du délire; dans la prescription de vitamine D ou de calcium, ou des deux; et dans les recommandations de traitement antirésorptif. Malgré l'adoption du modèle orthogériatrique dans l'ensemble du centre, seulement 74,4 % des patients du groupe postintervention ont eu une consultation en gériatrie. Conclusion: Bien que la mise en œuvre d'un modèle de soins orthogériatriques collaboratif chez les personnes âgées présentant une fracture de la hanche n'ait pas réduit l'incidence du délire postopératoire ou la durée de l'hospitalisation, il y a eu une amélioration du respect de plusieurs normes de qualité importantes relatives à ce type de fracture. L'évaluation gériatrique complète réalisée tôt, de manière proactive, dans les hôpitaux communautaires sera la cible d'initiatives d'amélioration de la qualité à venir.

Molecular Mechanism of Aggregation of the Cataract-Related γD-Crystallin W42R Variant from Multiscale Atomistic Simulations.

The mechanisms leading to aggregation of the crystallin proteins of the eye lens remain largely unknown. We use atomistic multiscale molecular simulations to model the solution-state conformational dynamics of γD-crystallin and its cataract-related W42R variant at both infinite dilution and physiologically relevant concentrations. We find that the W42R variant assumes a distinct conformation in solution that leaves the Greek key domains of the native fold largely unaltered but lacks the hydrophobic interdomain interface that is key to the stability of wild-type γD-crystallin. At physiologically relevant concentrations, exposed hydrophobic regions in this alternative conformation become primary sites for enhanced interprotein interactions leading to large-scale aggregation.

Increased hydrophobic surface exposure in the cataract-related G18V variant of human γS-crystallin.

BACKGROUND: The objective of this study was to determine whether the cataract-related G18V variant of human γS-crystallin has increased exposure of hydrophobic residues that could explain its aggregation propensity and/or recognition by αB-crystallin. METHODS: We used an ANS fluorescence assay and NMR chemical shift perturbation to experimentally probe exposed hydrophobic surfaces. These results were compared to flexible docking simulations of ANS molecules to the proteins, starting with the solution-state NMR structures of γS-WT and γS-G18V. RESULTS: γS-G18V exhibits increased ANS fluorescence, suggesting increased exposed hydrophobic surface area. The specific residues involved in ANS binding were mapped by NMR chemical shift perturbation assays, revealing ANS binding sites in γS-G18V that are not present in γS-WT. Molecular docking predicts three binding sites that are specific to γS-G18V corresponding to the exposure of a hydrophobic cavity located at the interdomain interface, as well as two hydrophobic patches near a disordered loop containing solvent-exposed cysteines, all but one of which is buried in γS-WT. CONCLUSIONS: Although both proteins display non-specific binding, more residues are involved in ANS binding to γS-G18V, and the affected residues are localized in the N-terminal domain and the nearby interdomain interface, proximal to the mutation site. GENERAL SIGNIFICANCE: Characterization of changes in exposed hydrophobic surface area between wild-type and variant proteins can help elucidate the mechanisms of aggregation propensity and chaperone recognition, presented here in the context of cataract formation. Experimental data and simulations provide complementary views of the interactions between proteins and the small molecule probes commonly used to study aggregation. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Spontaneous Regression of a Congenital Melanocytic Nevus by Sclerosis.

Congenital melanocytic nevi (CMNs) naturally evolve throughout life, growing proportionately with the child, darkening, and exhibiting textural or surface changes (e.g., papillomatous, verrucous, cerebriform), hypertrichosis, and, later in life, lightening of pigmentation. We report the case of a 5-year-old child with complete resolution of a medium-sized CMN involving the distal left leg and foot via sclerosis and in the absence of any halo phenomenon. Spontaneous regression of CMN via sclerosis is rare, and it is thought that an immunologic mechanism different from the mechanism that the halo phenomenon induces mediates this regression. We reviewed the literature on this phenomenon and discuss how it might lead to regression of the nevus.

Adapting care provision in family practice during the COVID-19 pandemic: a qualitative study exploring the impact of primary care reforms in four Canadian regions.

BACKGROUND: Over the past two decades, Canadian provinces and territories have introduced a series of primary care reforms in an attempt to improve access to and quality of primary care services, resulting in diverse organizational structures and practice models. We examine the impact of these reforms on family physicians' (FPs) ability to adapt their roles during the COVID-19 pandemic, including the provision of routine primary care. METHODS: As part of a larger case study, we conducted semi-structured qualitative interviews with FPs in four Canadian regions: British Columbia, Newfoundland and Labrador, Nova Scotia, and Ontario. During the interviews, participants were asked about their personal and practice characteristics, the pandemic-related roles they performed over different stages of the pandemic, the facilitators and barriers they experienced in performing these roles, and potential roles FPs could have filled. Interviews were transcribed and a thematic analysis approach was applied to identify recurring themes in the data. RESULTS: Sixty-eight FPs completed an interview across the four regions. Participants described five areas of primary care reform that impacted their ability to operate and provide care during the pandemic: funding models, electronic medical records (EMRs), integration with regional entities, interdisciplinary teams, and practice size. FPs in alternate funding models experienced fewer financial constraints than those in fee-for-service practices. EMR access enhanced FPs' ability to deliver virtual care, integration with regional entities improved access to personal protective equipment and technological support, and team-based models facilitated the implementation of infection prevention and control protocols. Lastly, larger group practices had capacity to ensure adequate staffing and cover additional costs, allowing FPs more time to devote to patient care. CONCLUSIONS: Recent primary care system reforms implemented in Canada enhanced FPs' ability to adapt to the uncertain and evolving environment of providing primary care during the pandemic. Our study highlights the importance of ongoing primary care reforms to enhance pandemic preparedness and advocates for further expansion of these reforms.

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF).

Background: Thiamine supplementation may improve cardiac function in older adults with heart failure (HF). Our objectives were to determine the following: (i) the feasibility of conducting a large trial of thiamine supplementation in HF; and (ii) the effects of thiamine on clinical outcomes. Methods: We conducted a double-blinded randomized placebo-controlled 2-period crossover feasibility study from June 2018 to April 2021. Adults aged ≥ 60 years with symptomatic HF and reduced ejection fraction (≤ 45%) were included. Participants were randomized to thiamine mononitrate 500 mg, or placebo, for 90 days and were switched to the opposite treatment for 90 days after a 6-week washout period. The primary feasibility outcome was recruitment of 24 participants in 11 months. Results: We screened 330 patients over 21 months to recruit 24 patients. Participants' mean age was 73.4 years. The targets for refusal rate, retention rate, and adherence rate were met. Nonsignificant improvements occurred in left ventricular ejection fraction and N-terminal pro-brain natriuretic peptide (NT-proBNP) level with thiamine. A total of 13 serious adverse events occurred in 7 patients; none were related to the study drug. Conclusions: Although we did not reach our recruitment target, we found high-dose thiamine supplementation to be well tolerated, with potential improvements in biomarker outcomes. A larger trial of thiamine supplementation is warranted.

Introduction: La supplémentation en thiamine peut améliorer la fonction cardiaque chez les personnes âgées atteintes d'insuffisance cardiaque (IC). Nos objectifs visaient à déterminer : (i) la faisabilité d'un essai de grande envergure sur la supplémentation en thiamine lors d'IC ; (ii) les effets de la thiamine sur les résultats cliniques. Méthodes: Nous avons réalisé une étude de faisabilité croisée à double insu et à répartition aléatoire contre placebo sur deux périodes de juin 2018 à avril 2021. Nous avons retenu les adultes de ≥ 60 ans qui avaient une IC symptomatique et une fraction d'éjection réduite (≤ 45 %). Nous avons réparti les participants de façon aléatoire pour recevoir 500 mg de mononitrate de thiamine ou le placebo durant 90 jours, et avons inversé le traitement durant 90 jours après une période de lavage de 6 semaines. Le principal critère de faisabilité était le recrutement de 24 participants en 11 mois. Résultats: Nous avons recruté 24 patients sur les 330 patients sélectionnés durant 21 mois. L'âge moyen des participants était de 73,4 ans. Les cibles des taux de refus, des taux de rétention et des taux d'adhésion ont été atteintes. Avec la thiamine, nous avons observé des améliorations non significatives de la fraction d'éjection ventriculaire gauche et de la concentration de propeptide natriurétique de type B N-terminal (NT-proBNP). Parmi les 13 événements indésirables sérieux qu'ont subis sept patients, aucun n'a été associé au médicament étudié. Conclusions: Bien que nous n'ayons pas atteint notre cible de recrutement, nous avons observé que la supplémentation en thiamine à dose élevée était bien tolérée et qu'il y avait des améliorations potentielles des résultats des biomarqueurs. Un essai de plus grande envergure sur la supplémentation en thiamine est justifié.

Recommendations from long-term care reports, commissions, and inquiries in Canada.

Background: Multiple long-term care (LTC) reports have issued similar recommendations for improvement across Canadian LTC homes. Our primary objective was to identify the most common recommendations made over the past 10 years. Our secondary objective was to estimate the total cost of studying LTC issues repeatedly from 1998 to 2020. Methods: The qualitative and cost analyses were conducted in Canada from July to October 2020. Using a list of reports, inquiries and commissions from The Royal Society of Canada Working Group on Long-Term Care, we coded recurrent recommendations in LTC reports. We contacted the sponsoring organizations for a cost estimate, including direct and indirect costs. All costs were adjusted to 2020 Canadian dollar values. Results: Of the 80 Canadian LTC reports spanning the years of 1998 to 2020, 24 (30%) were based on a national level and 56 (70%) were focused on provinces or municipalities. Report length ranged from 4 to 1491 pages and the median number of contributors was 14 (interquartile range, IQR, 5-26) per report. The most common recommendation was to increase funding to LTC to improve staffing, direct care and capacity (67% of reports). A median of 8 (IQR 3.25-18) recommendations were made per report. The total cost for all 80 reports was estimated to be $23,626,442.78. Conclusions: Problems in Canadian LTC homes and their solutions have been known for decades. Despite this, governments and non-governmental agencies continue to produce more reports at a monetary and societal cost to Canadians.

Deprescribing fall-risk increasing drugs (FRIDs) for the prevention of falls and fall-related complications: a systematic review and meta-analysis.

OBJECTIVES: Prevention of falls and fall-related injuries is a priority due to the substantial health and financial burden of falls on patients and healthcare systems. Deprescribing medications known as 'fall-risk increasing drugs' (FRIDs) is a common strategy to prevent falls. We conducted a systematic review to determine its efficacy for the prevention of falls and fall-related complications. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL and grey literature from inception to 1 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of FRID withdrawal compared with usual care evaluating the rate of falls, incidence of falls, fall-related injuries, fall-related fractures, fall-related hospitalisations or adverse effects related to the intervention in adults aged ≥65 years. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed citation screening, data abstraction, risk of bias assessment and certainty of evidence grading. Random-effects models were used for meta-analyses. RESULTS: Five trials involving 1305 participants met eligibility criteria. Deprescribing FRIDs did not change the rate of falls (rate ratio (RaR) 0.98, 95% CI 0.63 to 1.51), the incidence of falls (risk difference 0.01, 95% CI -0.06 to 0.09; relative risk 1.04, 95% CI 0.86 to 1.26) or rate of fall-related injuries (RaR 0.89, 95% CI 0.57 to 1.39) over a follow-up period of 6-12 months. No trials evaluated the impact of deprescribing FRIDs on fall-related fractures or hospitalisations. CONCLUSION: There is a paucity of robust high-quality evidence to support or refute that a FRID deprescribing strategy alone is effective at preventing falls or fall-related injury in older adults. Although there may be other reasons to deprescribe FRIDs, our systematic review found that it may result in little to no difference in the rate or risk of falls as a sole falls reduction strategy. PROSPERO REGISTRATION NUMBER: CRD42016040203.

Cost-effectiveness of antithrombotic agents for atrial fibrillation in older adults at risk for falls: a mathematical modelling study.

BACKGROUND: Antithrombotic drugs decrease stroke risk in patients with atrial fibrillation, but they increase bleeding risk, particularly in older adults at high risk for falls. We aimed to determine the most cost-effective antithrombotic therapy in older adults with atrial fibrillation who are at high risk for falls. METHODS: We conducted a mathematical modelling study from July 2019 to March 2020 based on the Ontario, Canada, health care system. We derived the base-case age, sex and fall risk distribution from a published cohort of older adults at risk for falls, and the bleeding and stroke risk parameters from an atrial fibrillation trial population. Using a probabilistic microsimulation Markov decision model, we calculated quality-adjusted life years (QALYs), total cost and incremental cost-effectiveness ratios (ICERs) for each of acetylsalicylic acid (ASA), warfarin, apixaban, dabigatran, rivaroxaban and edoxaban. Cost data were adjusted for inflation to 2018 values. The analysis used the Ontario public payer perspective with a lifetime horizon. RESULTS: In our model, the most cost-effective antithrombotic therapy for atrial fibrillation in older patients at risk for falls was apixaban, with an ICER of $8517 per QALY gained (5.86 QALYs at $92 056) over ASA. It was a dominant strategy over warfarin and the other antithrombotic agents. There was moderate uncertainty in cost-effectiveness ranking, with apixaban as the preferred choice in 66% of model iterations (given willingness to pay of $50 000 per QALY gained); edoxaban, 30 mg, was preferred in 31% of iterations. Sensitivity analysis across ranges of age, bleeding risk and fall risk still favoured apixaban over the other medications. INTERPRETATION: From a public payer perspective, apixaban is the most cost-effective antithrombotic agent in older adults at high risk for falls. Health care funders should implement strategies to encourage use of the most cost-effective medication in this population.

The Predictive Value of the Clinical Frailty Scale on Discharge Destination and Complications in Older Hip Fracture Patients.

OBJECTIVES: To determine whether the Clinical Frailty Scale (CFS), a validated frailty tool, was associated with discharge destination. Secondary objectives were to determine whether the CFS was associated with in-hospital complications and length of stay. DESIGN: This is a 5-year retrospective cohort study. SETTING: The study took place at an academic Level 1 trauma center. PATIENTS/PARTICIPANTS: All patients 65 years of age and older admitted with an isolated hip fracture were included (N = 423). INTERVENTION: Preadmission CFS was determined as part of routine clinical care prospectively and abstracted from the chart. MAIN OUTCOME MEASUREMENTS: We collected demographic and process data associated with adverse outcomes (age, sex, time to surgery, and mode of anesthesia) and used multivariable logistic regression to determine the association between CFS with discharge destination, in-hospital complications, and length of stay. RESULTS: Preadmission frailty was independently associated with adverse discharge destination (adjusted odds ratio 23.0; 95% confidence interval, 3.0-173.5) and in-hospital complications (adjusted odds ratio 4.8; 95% confidence interval, 2.1-10.8) in greater magnitude than traditional risk factors such as age, male sex, time to surgery, and mode of anesthesia. There was a dose-response relationship between increasing frailty and length of stay (P < 0.001). CONCLUSIONS: Preadmission frailty as quantified by the CFS is associated with discharge destination, in-hospital complications, and length of stay. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Role of Conformational Flexibility in Monte Carlo Simulations of Many-Protein Systems.

Efficient computational modeling of biological systems characterized by high concentrations of macromolecules often relies on rigid-body Brownian Dynamics or Monte Carlo (MC) simulations. However, the accuracy of rigid-body models is limited by the fixed conformation of the simulated biomolecules. Multi-conformation Monte Carlo (mcMC) simulations of protein solutions incorporate conformational flexibility via a conformational swap trial move within a predetermined library of discrete protein structures, thereby alleviating artifacts arising from the use of a single protein conformation. Here, we investigate the impact of the number of distinct protein structures in the conformational library and the extent of conformational sampling used in its generation on structural observables computed from simulations of hen egg white lysozyme (HEWL), human γD-Crystallin, and bovine γB-Crystallin solutions. We find that the importance of specific protocols for the construction of the protein structure library is strongly dependent on the nature of the simulated system.

Distribution of in situ forces in the anterior cruciate ligament in response to rotatory loads.

The anterior cruciate ligament (ACL) can be anatomically divided into anteromedial (AM) and posterolateral (PL) bundles. Current ACL reconstruction techniques focus primarily on reproducing the AM bundle, but are insufficient in response to rotatory loads. The objective of this study was to determine the distribution of in situ force between the two bundles when the knee is subjected to anterior tibial and rotatory loads. Ten cadaveric knees (50+/-10 years) were tested using a robotic/universal force-moment sensor (UFS) testing system. Two external loading conditions were applied: a 134 N anterior tibial load at full knee extension and 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion and a combined rotatory load of 10 Nm valgus and 5 Nm internal tibial torque at 15 degrees and 30 degrees of flexion. The resulting 6 degrees of freedom kinematics of the knee and the in situ forces in the ACL and its two bundles were determined. Under an anterior tibial load, the in situ force in the PL bundle was the highest at full extension (67+/-30 N) and decreased with increasing flexion. The in situ force in the AM bundle was lower than in the PL bundle at full extension, but increased with increasing flexion, reaching a maximum (90+/-17 N) at 60 degrees of flexion and then decreasing at 90 degrees. Under a combined rotatory load, the in situ force of the PL bundle was higher at 15 degrees (21+/-11 N) and lower at 30 degrees of flexion (14+/-6 N). The in situ force in the AM bundle was similar at 15 degrees and 30 degrees of knee flexion (30+/-15 vs. 35+/-16 N, respectively). Comparing these two external loading conditions demonstrated the importance of the PL bundle, especially when the knee is near full extension. These findings provide a better understanding of the function of the two bundles of the ACL and could serve as a basis for future considerations of surgical reconstruction in the replacement of the ACL.

Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue.

The ability to determine trabecular bone tissue elastic and failure properties has biological and clinical importance. To date, trabecular tissue yield strains remain unknown due to experimental difficulties, and elastic moduli studies have reported controversial results. We hypothesized that the elastic and tensile and compressive yield properties of trabecular tissue are similar to those of cortical tissue. Effective tissue modulus and yield strains were calibrated for cadaveric human femoral neck specimens taken from 11 donors, using a combination of apparent-level mechanical testing and specimen-specific, high-resolution, nonlinear finite element modeling. The trabecular tissue properties were then compared to measured elastic modulus and tensile yield strain of human femoral diaphyseal cortical bone specimens obtained from a similar cohort of 34 donors. Cortical tissue properties were obtained by statistically eliminating the effects of vascular porosity. Results indicated that mean elastic modulus was 10% lower (p<0.05) for the trabecular tissue (18.0+/-2.8 GPa) than for the cortical tissue (19.9+/-1.8 GPa), and the 0.2% offset tensile yield strain was 15% lower for the trabecular tissue (0.62+/-0.04% vs. 0.73+/-0.05%, p<0.001). The tensile-compressive yield strength asymmetry for the trabecular tissue, 0.62 on average, was similar to values reported in the literature for cortical bone. We conclude that while the elastic modulus and yield strains for trabecular tissue are just slightly lower than those of cortical tissue, because of the cumulative effect of these differences, tissue strength is about 25% greater for cortical bone.

Biomechanical analysis of an anatomic anterior cruciate ligament reconstruction.

BACKGROUND: The focus of most anterior cruciate ligament reconstructions has been on replacing the anteromedial bundle and not the posterolateral bundle. HYPOTHESIS: Anatomic two-bundle reconstruction restores knee kinematics more closely to normal than does single-bundle reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Ten cadaveric knees were subjected to external loading conditions: 1) a 134-N anterior tibial load and 2) a combined rotatory load of 5-N x m internal tibial torque and 10-N x m valgus torque. Resulting knee kinematics and in situ force in the anterior cruciate ligament or replacement graft were determined by using a robotic/universal force-moment sensor testing system for 1) intact, 2) anterior cruciate ligament deficient, 3) single-bundle reconstructed, and 4) anatomically reconstructed knees. RESULTS: Anterior tibial translation for the anatomic reconstruction was significantly closer to that of the intact knee than was the single-bundle reconstruction. The in situ force normalized to the intact anterior cruciate ligament for the anatomic reconstruction was 97% +/- 9%, whereas the single-bundle reconstruction was only 89% +/- 13%. With a combined rotatory load, the normalized in situ force for the single-bundle and anatomic reconstructions at 30 degrees of flexion was 66% +/- 40%and 91% +/- 35%, respectively. CONCLUSIONS: Anatomic reconstruction may produce a better biomechanical outcome, especially during rotatory loads. CLINICAL RELEVANCE: Results may lead to the use of a two-bundle technique.

Peripheral neuropathy for dermatologists: what if not diabetic neuropathy?

BACKGROUND: Patients with cutaneous manifestations associated with peripheral neuropathy often present to the dermatologist's office. OBJECTIVE/METHODS: This article outlines a practical approach for obtaining the history, performing a screening physical examination, and ordering initial diagnostic testing to diagnose the cause of nondiabetic neuropathy. When to refer for neurologic consultation and principles of management of neuropathic pain and neuropathy-related ulcers are also discussed. RESULTS: Cutaneous manifestations of peripheral neuropathy may be secondary to a medical condition predisposing the patient to neuropathy or a manifestation of neuropathy itself. In the latter category, skin affected by neuropathy may show characteristics of xerosis, anhidrosis, rubor, edema, callus, ulceration, muscle wasting, and foot deformity. Most often these findings occur in association with diabetic neuropathy; however, many other infectious, inflammatory, metabolic, paraneoplastic, hereditary, and medication- or toxin-related causes should be considered. The treatment of cutaneous manifestations of neuropathy includes pressure downloading, control of edema, and optimal ulcer and neuropathic pain management. CONCLUSION: It is important for dermatologists to have a basic approach to neuropathy in patients with related skin disease. Referral to Neurology is warranted when basic workup for reversible causes is negative or for any severe, rapidly progressive symptoms.