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The development of effective antivirals is of great importance due to the threat associated with the rapid spread of viral infections. The accumulation of data in scientific publications and in databases of biologically active compounds provides an opportunity to extract specific information about interactions between chemicals and their viral and host targets. This information can be used for elucidation of knowledge about potential antiviral activity of chemical compounds, their side effects and toxicities. Our study aims to extract knowledge about virus-host interactions and potential antiviral agents based on the mining of massive amounts of scientific publications. With a set of previously developed algorithms, we have extracted comprehensive information on virus-host interactions and chemical compounds that interact with both viral and host targets. We collected data on the interactions of several viruses, including hepatitis B and C viruses, SARS-CoV-2, influenza A and B, and herpes simplex viruses, with (1) the host (human body), (2) potential antiviral agents, and, also extracted information on the interactions between potential antiviral agents and host proteins. Based on the data analysis performed, we created a freely available knowledge base on the interaction of chemical compounds with viral proteins and their host targets, allowing the exploration of both well-studied and recently discovered novel virus-host-chemical-compound interactions.

Background: Prior research has shown that patients with stable ischemic heart disease who undergo delayed coronary artery bypass graft (CABG) surgery face higher mortality rates than those who receive CABG within the time recommended by physicians. However, this research did not account for percutaneous coronary intervention (PCI), a widely available alternative to delayed CABG in many settings. We sought to establish whether there was a difference in mortality between timely PCI and delayed CABG., Methods: We identified 25,520 patients 60 years or older who underwent first-time non-emergency revascularization for angiographically-proven, stable left main or multi-vessel ischemic heart disease in British Columbia between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted mortality after index revascularization or last staged PCI for patients undergoing delayed CABG compared to timely PCI., Findings: After adjustment with inverse probability of treatment weights, at three years, patients who underwent delayed CABG had a statistically significant lower mortality compared with patients who received timely PCI (4.3% delayed CABG, 13.5% timely PCI; risk ratio 0.32, 95% CI 0.24-0.40)., Interpretation: Patients who undergo CABG with delay have a lower risk of death than patients who undergo PCI within appropriate time. Our results suggest that patients who wish to receive CABG as their revascularization treatment will receive a mortality benefit over PCI as an alternative strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hardiman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: In patients with stable ischemic heart disease, there is no evidence for the effect of revascularization treatment timing on the need for repeat procedures. We aimed to determine if repeat revascularizations differed among patients who received coronary artery bypass graft surgery after the time recommended by physicians compared with those who had timely percutaneous coronary intervention., Methods: We identified 25,520 British Columbia residents 60 years or older who underwent first-time nonemergency revascularization for angiographically proven, stable left main or multivessel ischemic heart disease between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted cumulative incidence functions for repeat revascularization, in the presence of death as a competing risk, after index revascularization or last staged percutaneous coronary intervention for patients undergoing delayed coronary artery bypass grafting compared with timely percutaneous coronary intervention., Results: After adjustment with inverse probability of treatment weights, at 3 years, patients who underwent delayed coronary artery bypass grafting had a statistically significant lower cumulative incidence of a repeat revascularization compared with patients who received timely percutaneous coronary intervention (4.84% delayed coronary artery bypass grafting, 12.32% timely percutaneous coronary intervention; subdistribution hazard ratio, 0.16, 95% CI, 0.04-0.65)., Conclusions: Patients who undergo delayed coronary artery bypass grafting have a lower cumulative incidence of repeat revascularization than patients who undergo timely percutaneous coronary intervention. Patients who want to wait to receive coronary artery bypass grafting will see the benefit of lower repeat revascularization over percutaneous coronary intervention unaffected by a delay in treatment., Competing Interests: The authors reported no conflicts of interest. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Background: Biosensor technologies have been proposed as a solution to provide recognition and facilitate earlier responses to unwitnessed out-of-hospital cardiac arrest (OHCA) cases. We sought to estimate the effect of recognition on survival and modelled the potential incremental impact of increased recognition of unwitnessed cases on survival to hospital discharge, to demonstrate the potential benefit of biosensor technologies., Methods: We included cases from the British Columbia Cardiac Arrest Registry (2019-2020), which includes Emergency Medical Services (EMS)-assessed OHCAs. We excluded cases that would not have benefitted from early recognition (EMS-witnessed, terminal illness, or do-not-resuscitate). Using a mediation analysis, we estimated the relative benefits on survival of a witness recognizing vs. intervening in an OHCA; and estimated the expected additional number of survivors resulting from increasing recognition alone using a bootstrap logistic regression framework., Results: Of 13,655 EMS-assessed cases, 11,412 were included (6314 EMS-treated, 5098 EMS-untreated). Survival to hospital discharge was 191/8879 (2.2%) in unwitnessed cases and 429/2533 (17%) in bystander-witnessed cases. Of the total effect attributable to a bystander witness, recognition accounted for 84% (95% CI: 72, 86) of the benefit. If all previously unwitnessed cases had been bystander witnessed, we would expect 1198 additional survivors. If these cases had been recognized, but no interventions performed, we would expect 912 additional survivors., Conclusion: Unwitnessed OHCA account for the majority of OHCAs, yet survival is dismal. Methods to improve recognition, such as with biosensor technologies, may lead to substantial improvements in overall survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: to investigate physiotherapists' perspectives of effective community provision following hip fracture., Methods: qualitative semi-structured interviews were conducted with 17 community physiotherapists across England. Thematic analysis drawing on the Theoretical Domains Framework identified barriers and facilitators to implementation of effective provision. Interviews were complemented by process mapping community provision in one London borough, to identify points of care where suggested interventions are in place and/or could be implemented., Results: four themes were identified: ineffective coordination of care systems, ineffective patient stratification, insufficient staff recruitment and retention approaches and inhibitory fear avoidance behaviours. To enhance care coordination, participants suggested improving access to social services and occupational therapists, maximising multidisciplinary communication through online notation, extended physiotherapy roles, orthopaedic-specific roles and seven-day working. Participants advised the importance of stratifying patients on receipt of referrals, at assessment and into appropriately matched interventions. To mitigate insufficient staff recruitment and retention, participants proposed return-to-practice streams, apprenticeship schemes, university engagement, combined acute-community rotations and improving job description advertisements. To reduce effects of fear avoidance behaviour on rehabilitation, participants proposed the use of patient-specific goals, patient and carer education, staff education in psychological strategies or community psychologist access. Process mapping of one London borough identified points of care where suggested interventions to overcome barriers were in place and/or could be implemented., Conclusion: physiotherapists propose that effective provision of community physiotherapy following hip fracture could be improved by refining care coordination, utilising stratification techniques, employing enhanced recruitment and retainment strategies and addressing fear avoidance behaviours., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To examine the association between physiotherapy access after hip fracture and discharge home, readmission, survival, and mobility recovery., Methods: A 2017 Physiotherapy Hip Fracture Sprint Audit was linked to hospital records for 5383 patients. Logistic regression was used to estimate the association between physiotherapy access in the first postoperative week and discharge home, 30-day readmission post-discharge, 30-day survival and 120-days mobility recovery post-admission adjusted for age, sex, American Society of Anesthesiology grade, Hospital Frailty Risk Score and prefracture mobility/residence., Results: Overall, 73% were female and 40% had high frailty risk. Patients who received ≥2 hours of physiotherapy (versus less) had 3% (95% Confidence Interval: 0-6%), 4% (2-6%), and 6% (1-11%) higher adjusted probabilities of discharge home, survival, and outdoor mobility recovery, and 3% (0-6%) lower adjusted probability of readmission. Recipients of exercise (versus mobilisation alone) had 6% (1-12%), 3% (0-7%), and 11% (3-18%) higher adjusted probabilities of discharge home, survival, and outdoor mobility recovery, and 6% (2-10%) lower adjusted probability of readmission. Recipients of 6-7 days physiotherapy (versus 0-2 days) had 8% (5-11%) higher adjusted probability of survival. For patients with dementia, improved probability of survival, discharge home, readmission and indoor mobility recovery were observed with greater physiotherapy access., Conclusion: Greater access to physiotherapy was associated with a higher probability of positive outcomes. For every 100 patients, greater access could equate to an additional eight patients surviving to 30-days and six avoiding 30-day readmission. The findings suggest a potential benefit in terms of home discharge and outdoor mobility recovery. CONTRIBUTION OF THE PAPER., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The advantage of coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI), established in trials, may not be generalizable to populations in which the method of treatment determines the time to treatment. We sought to describe the methodology of a population-based observational study for assessing how changes in time to treatment may affect the comparative effectiveness of these 2 methods of coronary revascularization., Methods: We propose a framework of causal mediation analysis to compare the outcomes of choosing CABG over PCI, if patients selected for either method waited the same amount of time had they undergone a PCI. We will include patients who underwent a first-time, nonurgent isolated CABG or single-session PCI for multivessel or left main coronary artery disease from January 2001 to December 2016, in British Columbia. We will use absolute risk difference as a measure of the total effect of choosing CABG over PCI and partition it into the direct effect of the treatment choice and the effect mediated by the treatment-specific timing., Interpretation: Understanding how time to treatment mediates the relation between method of revascularization and outcomes will have implications for treatment selection, resource allocation and planning benchmarks. Findings on the benefits and risks of performing PCI or CABG within a certain time will guide multidisciplinary teams in determining the appropriate revascularization method for individual patients., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Additional physiotherapy in the first postoperative week was associated with fewer days to discharge after hip fracture surgery. A 7-day physiotherapy service in the first postoperative week should be considered as a new key performance indicator in evaluating the quality of care for patients admitted with a hip fracture., Introduction: To examine the association between physiotherapy in the first week after hip fracture surgery and discharge from acute hospital., Methods: We linked data from the UK Physiotherapy Hip Fracture Sprint Audit to hospital records for 5395 patients with hip fracture in May and June 2017. We estimated the association between the number of days patients received physiotherapy in the first postoperative week; its overall duration (< 2 h, ≥ 2 h; 30-min increment) and type (mobilisation alone, mobilisation and exercise) and the cumulative probability of discharge from acute hospital over 30 days, using proportional odds regression adjusted for confounders and the competing risk of death., Results: The crude and adjusted odds ratios of discharge were 1.24 (95% CI 1.19-1.30) and 1.26 (95% CI 1.19-1.33) for an additional day of physiotherapy, 1.34 (95% CI 1.18-1.52) and 1.33 (95% CI 1.12-1.57) for ≥ 2 versus < 2 h physiotherapy, and 1.11 (95% CI 1.08-1.15) and 1.10 (95% CI 1.05-1.15) for an additional 30-min of physiotherapy. Physiotherapy type was not associated with discharge., Conclusion: We report an association between physiotherapy and discharge after hip fracture. An average UK hospital admitting 375 patients annually may save 456 bed-days if current provision increased so all patients with hip fracture received physiotherapy on 6-7 days in the first postoperative week. A 7-day physiotherapy service totalling at least 2 h in the first postoperative week may be considered a key performance indicator of acute care quality after hip fracture., (© 2021. The Author(s).)

Objectives: Previous research reports numerous factors of post-operative mortality in patients undergoing isolated coronary artery bypass graft surgery. However, this evidence has not been mapped to the conceptual framework of care improvement. Without such mapping, interventions designed to improve care quality remain unfounded., Methods: We identified reported factors of in-hospital mortality post isolated coronary artery bypass graft surgery in adults over the age of 19, published in English between January 1, 2000 and December 31, 2019, indexed in PubMed, CINAHL, and EMBASE. We grouped factors and their underlying mechanism for association with in-hospital mortality according to the augmented Donabedian framework for quality of care., Results: We selected 52 factors reported in 83 articles and mapped them by case-mix, structure, process, and intermediary outcomes. The most reported factors were related to case-mix (characteristics of patients, their disease, and their preoperative health status) (37 articles, 27 factors). Factors related to care processes (27 articles, 12 factors) and structures (11 articles, 6 factors) were reported less frequently; most proposed mechanisms for their mortality effects., Conclusions: Few papers reported on factors of in-hospital mortality related to structures and processes of care, where intervention for care quality improvement is possible. Therefore, there is limited evidence to support quality improvement efforts that will reduce variation in mortality after coronary artery bypass graft surgery., (© 2022. The Author(s).)

Objective: to explore physiotherapists' perceptions of mechanisms to explain observed variation in early postoperative practice after hip fracture surgery demonstrated in a national audit., Methods: a qualitative semi-structured interview study of 21 physiotherapists working on orthopaedic wards at seven hospitals with different durations of physiotherapy during a recent audit. Thematic analysis of interviews drawing on Normalisation Process Theory to aid interpretation of findings., Results: four themes were identified: achieving protocolised and personalised care; patient and carer engagement; multidisciplinary team engagement across the care continuum and strategies for service improvement. Most expressed variation from protocol was legitimate when driven by what is deemed clinically appropriate for a given patient. This tailored approach was deemed essential to optimise patient and carer engagement. Participants reported inconsistent degrees of engagement from the multidisciplinary team attributing this to competing workload priorities, interpreting 'postoperative physiotherapy' as a single professional activity rather than a care delivery approach, plus lack of integration between hospital and community care. All participants recognised changes needed at both structural and process levels to improve their services., Conclusion: physiotherapists highlighted an inherent conflict between their intention to deliver protocolised care and allowing for an individual patient-tailored approach. This conflict has implications for how audit results should be interpreted, how future clinical guidelines are written and how physiotherapists are trained. Physiotherapists also described additional factors explaining variation in practice, which may be addressed through increased engagement of the multidisciplinary team and resources for additional staffing and advanced clinical roles., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Computationally predicting the interaction of proteins and ligands presents three main directions: the search of new target proteins for ligands, the search of new ligands for targets, and predicting the interaction of new proteins and new ligands. We proposed an approach providing the fuzzy classification of protein sequences based on the ligand structural features to analyze the latter most complicated case. We tested our approach on five protein groups, which represented promised targets for drug-like ligands and differed in functional peculiarities. The training sets were built with the original procedure overcoming the data ambiguity. Our study showed the effective prediction of new targets for ligands with an average accuracy of 0.96. The prediction of new ligands for targets displayed the average accuracy 0.95; accuracy estimates were close to our previous results, comparable in accuracy to those of other methods or exceeded them. Using the fuzzy coefficients reflecting the target-to-ligand specificity, we provided predicting interactions for new proteins and new ligands; the obtained accuracy values from 0.89 to 0.99 were acceptable for such a sophisticated task. The protein kinase family case demonstrated the ability to account for subtle features of proteins and ligands required for the specificity of protein-ligand interaction.

Background: Competing demands for operative resources may affect time to hip fracture surgery. We sought to determine the time to hip fracture surgery by variation in demand in Canadian hospitals., Methods: We obtained discharge abstracts of 151,952 patients aged 65 years or older who underwent surgery for a hip fracture between January, 2004 and December, 2012 in nine Canadian provinces. We compared median time to surgery (in days) when demand could be met within a two-day benchmark and when demand required more days, i.e. clearance time, to provide surgery, overall and stratified by presence of medical reasons for delay., Results: For persons admitted when demand corresponded to a 2-day clearance time, 68% of patients underwent surgery within the 2-day benchmark. When demand corresponded to a clearance time of one week, 51% of patients underwent surgery within 2 days. Compared to demand that could be served within the two-day benchmark, adjusted median time to surgery was 5.1% (95% confidence interval [CI] 4.1-6.1), 12.2% (95% CI 10.3-14.2), and 22.0% (95% CI 17.7-26.2) longer, when demand required 4, 6, and 7 or more days to clear the backlog, respectively. After adjustment, delays in median time to surgery were similar for those with and without medical reasons for delay., Conclusion: Increases in demand for operative resources were associated with dose-response increases in the time needed for half of hip fracture patients to undergo surgery. Such delays may be mitigated through better anticipation of day-to-day supply and demand and increased response capability.

The alternative splicing is a mechanism increasing the number of expressed proteins and a variety of these functions. We uncovered the protein domains most frequently lacked or occurred in the splice variants. Proteins presented by several isoforms participate in such processes as transcription regulation, immune response, etc. Our results displayed the association of alternative splicing with branched regulatory pathways. By considering the published data on the protein proteins encoded by the 18th human chromosome, we noted that alternative products display the differences in several functional features, such as phosphorylation, subcellular location, ligand specificity, protein-protein interactions, etc. The investigation of alternative variants referred to the protein kinase domain was performed by comparing the alternative sequences with 3D structures. It was shown that large enough insertions/deletions could be compatible with the kinase fold if they match between the conserved secondary structures. Using the 3D data on human proteins, we showed that conformational flexibility could accommodate fold alterations in splice variants. The investigations of structural and functional differences in splice isoforms are required to understand how to distinguish the isoforms expressed as functioning proteins from the non-realized transcripts. These studies allow filling the gap between genomic and proteomic data., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The affinity of different drug-like ligands to multiple protein targets reflects general chemical-biological interactions. Computational methods estimating such interactions analyze the available information about the structure of the targets, ligands, or both. Prediction of protein-ligand interactions based on pairwise sequence alignment provides reasonable accuracy if the ligands' specificity well coincides with the phylogenic taxonomy of the proteins. Methods using multiple alignment require an accurate match of functionally significant residues. Such conditions may not be met in the case of diverged protein families. To overcome these limitations, we propose an approach based on the analysis of local sequence similarity within the set of analyzed proteins. The positional scores, calculated by sequence fragment comparisons, are used as input data for the Bayesian classifier. Our approach provides a prediction accuracy comparable or exceeding those of other methods. It was demonstrated on the popular Gold Standard test sets, presenting different sequence heterogeneity and varying from the group, including different protein families to the more specific groups. A reasonable prediction accuracy was also found for protein kinases, displaying weak relationships between sequence phylogeny and inhibitor specificity. Thus, our method can be applied to the broad area of protein-ligand interactions., Competing Interests: The authors declare no conflict of interest.

Little is known about post-acute care following hip fracture surgery. We investigated discharge destinations from surgical hospitals for nine Canadian provinces. We identified significant heterogeneity in discharge patterns across provinces suggesting different post-acute recovery pathways. Further work is required to determine the impact on patient outcomes and health system costs., Introduction: To examine discharge destinations by provinces in Canada, adjusting for patient, injury, and care characteristics., Methods: We analyzed population-based hospital discharge abstracts from a national administrative database for community-dwelling patients who underwent hip fracture surgery between 2004 and 2012 in Canada. Discharge destination was categorized as rehabilitation, home, acute care, and continuing care. Multinomial logistic regression modeling compared proportions of discharge to rehabilitation, acute care, and continuing care versus home between each province and Ontario. Adjusted risk differences and risk ratios were estimated., Results: Of 111,952 previously community-dwelling patients aged 65 years or older, 22.5% were discharged to rehabilitation, 31.6% to home, 27.0% to acute care, and 18.2% to continuing care, with significant variation across provinces (p < 0.001). The proportion of discharge to rehabilitation ranged from 2.4% in British Columbia to 41.0% in Ontario while the proportion discharged home ranged from 20.3% in Prince Edward Island to 52.2% in British Columbia. The proportion of discharge to acute care ranged from 15.2% in Ontario to 58.8% in Saskatchewan while the proportion discharged to continuing care ranged from 9.3% in Manitoba and Prince Edward Island to 22.9% in New Brunswick. Adjusting for hospital type changed the direction of the provincial effect on discharge to continuing care in two provinces, but statistical significance remained consistent with the primary analysis., Conclusions: Discharge destination from the surgical hospital after hip fracture is highly variable across nine Canadian provinces. Further work is required to determine the impact of this heterogeneity on patient outcomes and health system costs.

Introduction: To examine prognostic factors that influence complications after hip fracture surgery. To summarize proposed underlying mechanisms for their influence., Methods: We reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Scoping Review extension. We searched MEDLINE, Embase, CINAHL, AgeLine, Cochrane Library, and reference lists of retrieved studies for studies of prognostic factor/s of postoperative in-hospital medical complication/s among patients 50 years and older treated surgically for non-pathological closed hip fracture, published in English on January 2008-January 2018. We excluded studies of surgery type or in-hospital medications. Screening was duplicated by two independent reviewers. One reviewer completed the extraction with accuracy checks by the second reviewer. We summarized the extent, nature, and proposed underlying mechanisms for the prognostic factors of complications narratively and in a dependency graph., Results: We identified 44 prognostic factors of in-hospital complications after hip fracture surgery from 56 studies. Of these, we identified 7 patient factors-dehydration, anemia, hypotension, heart rate variability, pressure risk, nutrition, and indwelling catheter use; and 7 process factors-time to surgery, anesthetic type, transfusion strategy, orthopedic versus geriatric/co-managed care, multidisciplinary care pathway, and potentially modifiable during index hospitalization. We identified underlying mechanisms for 15 of 44 factors. The reported association between 12 prognostic factors and complications was inconsistent across studies., Conclusions: Most factors were reported by one study with no proposed underlying mechanism for their influence. Where reported by more than one study, there was inconsistency in reported associations and the conceptualization of complications differed, limiting comparison across studies. It is therefore not possible to be certain whether intervening on these factors would reduce the rate of complications after hip fracture surgery.

Objective: We describe steps to operationalise a published conceptual framework for a contiguous hospitalisation episode using acute care hospital discharge abstracts. We then quantified the degree of bias induced by a first abstract episode, which does not account for hospital transfers., Design: Retrospective observational study., Setting: All acute care hospitals in nine Canadian provinces., Participants: We retrieved acute hospitalisation discharge abstracts for 189 448 patients aged 65 years and older admitted to acute care with hip fracture between 2003 and 2013., Primary and Secondary Outcome Measures: The percentage of patients treated surgically, delayed to surgery (defined as two or more days after admission) and dying, between contiguous hospitalisation episodes and the first abstract episodes of care., Results: Using contiguous hospitalisation episodes, 91.6% underwent surgery, 35.7% were delayed two or more days after admission and 6.7% died postoperatively, whereas, using the first abstract only, these percentages were 83.7%, 32.5% and 6.5%, respectively., Conclusion: We demonstrate that not accounting for hospital transfers when evaluating the association between surgical timing and death underestimates reporting of the percentage of patients treated surgically and delayed to surgery by 9%, and the percentage who die after surgery by 3%. Researchers must be aware of this potential and avoidable bias as, depending on the purpose of the study, erroneous inferences may be drawn., Competing Interests: Competing interests: The authors declare that (1) Boris Sobolev, Pierre Guy and the Collaborative have received grants from the Canadian Institutes of Health Research related to this work. (2) Pierre Guy also receives funding from the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the British Columbia Specialists Services Committee for work around hip fracture care not related to this manuscript. He has also received fees from the BC Specialists Services Committee (for a provincial quality improvement project on redesign of hip fracture care) and from Stryker Orthopedics (as a product development consultant). He is a board member and shareholder in Traumis Surgical Systems Inc. and a board member for the Canadian Orthopedic Foundation. He also serves on the speakers’ bureaus of AO Trauma North America and Stryker Canada. (3) Suzanne Morin reports research grants from Amgen Canada, and from Merck, personal fees from Amgen Canada outside the submitted work., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery., Design: systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections., Results: from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level-anaemia and cognition. We assigned Parkinson's disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome., Conclusion: we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.

Background: The appropriate timing of hip fracture surgery remains a matter of debate. We sought to estimate the effect of changes in timing policy and the proportion of deaths attributable to surgical delay., Methods: We obtained discharge abstracts from the Canadian Institute for Health Information for hip fracture surgery in Canada (excluding Quebec) between 2004 and 2012. We estimated the expected population-average risks of inpatient death within 30 days if patients were surgically treated on day of admission, inpatient day 2, day 3 or after day 3. We weighted observations with the inverse propensity score of surgical timing according to confounders selected from a causal diagram., Results: Of 139 119 medically stable patients with hip fracture who were aged 65 years or older, 32 120 (23.1%) underwent surgery on admission day, 60 505 (43.5%) on inpatient day 2, 29 236 (21.0%) on day 3 and 17 258 (12.4%) after day 3. Cumulative 30-day in-hospital mortality was 4.9% among patients who were surgically treated on admission day, increasing to 6.9% for surgery done after day 3. We projected an additional 10.9 (95% confidence interval [CI] 6.8 to 15.1) deaths per 1000 surgeries if all surgeries were done after inpatient day 3 instead of admission day. The attributable proportion of deaths for delays beyond inpatient day 2 was 16.5% (95% CI 12.0% to 21.0%)., Interpretation: Surgery on admission day or the following day was estimated to reduce postoperative mortality among medically stable patients with hip fracture. Hospitals should expedite operating room access for patients whose surgery has already been delayed for nonmedical reasons., Competing Interests: Competing interests: Boris Sobolev, Pierre Guy and the Collaborative report receiving grants from the Canadian Institutes of Health Research related to this work. Pierre Guy reports receiving grants from the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the British Columbia Specialists Services Committee for work regarding hip fracture care, outside the submitted work. He has also received fees from the BC Specialists Services Committee (for a provincial quality improvement project on redesign of hip fracture care) and from Stryker Orthopaedics (as a product development consultant), outside the submitted work. He is a board member and shareholder in Traumis Surgical Systems Inc. and a board member for the Canadian Orthopaedic Foundation. He also serves on the speakers’ bureaus of AOTrauma North America and Stryker Canada. Suzanne Morin reports research grants from Amgen Canada, outside the submitted work. Jason Kim and Lisa Kuramoto report receiving grants from the Canadian Institutes of Health Research, during the conduct of the study. No other competing interests were declared., (© 2018 Joule Inc. or its licensors.)

Identifying amino acid positions that determine the specific interaction of proteins with small molecule ligands, is required for search of pharmaceutical targets, drug design, and solution of other biotechnology problems. We studied applicability of an original method SPrOS (specificity projection on sequence) developed to recognize functionally significant positions in amino acid sequences. The method allows residues specific to functional subgroups to be determined within the protein family based on their local surroundings in amino acid sequences. The efficiency of the method has been estimated on the protein kinase family. The residues associated with the protein specificity to inhibitors have been predicted. The results have been verified using 3D structures of protein-ligand complexes. Three small molecule inhibitors have been tested. Residues predicted with SPrOS either in contacted the inhibitor or influenced the conformation of the ligand-binding area. Excluding close homologues from the studied set makes it possible to decrease the number of difficult to interpret positions. The expediency of this procedure was determined by the relationship between an inhibitory spectrum and phylogenic partition. Thus, the method efficiency has been confirmed by matching the prediction results with the protein 3D structures.

The extent of Canadian provincial variation in hip fracture surgical timing is unclear. Provinces performed a similar proportion of surgeries within three inpatient days after adjustment. Time to surgery varied by timing of admission across provinces. This may reflect different approaches to providing access to hip fracture surgery., Introduction: The aim of this study was to compare whether time to surgery after hip fracture varies across Canadian provinces for surgically fit patients and their subgroups defined by timing of admission., Methods: We retrieved hospitalization records for 140,235 patients 65 years and older, treated surgically for hip fracture between 2004 and 2012 in Canada (excluding Quebec). We studied the proportion of surgeries on admission day and within 3 inpatient days, and times required for 33%, 66%, and 90% of surgeries across provinces and by subgroups defined by timing of admission. Differences were adjusted for patient, injury, and care characteristics., Results: Overall, provinces performed similar proportions of surgeries within the recommended three inpatient days, with all provinces requiring one additional day to perform the recommended 90% of surgeries. Prince Edward Island performed 7.0% more surgeries on admission day than Ontario irrespective of timing of admission (difference = 7.0; 95% CI 4.0, 9.9). The proportion of surgeries on admission day was 6.3% lower in Manitoba (difference = - 6.3; 95% CI - 12.1, - 0.6), and 7.7% lower in Saskatchewan (difference = - 7.7; 95% CI - 12.7, - 2.8) compared to Ontario. These differences persisted for late weekday and weekend admissions. The time required for 33%, 66%, and 90% of surgeries ranged from 1 to 2, 2-3, and 3-4 days, respectively, across provinces by timing of admission., Conclusions: Provinces performed similarly with respect to recommended time for hip fracture surgery. The proportion of surgeries on admission day, and time required to complete 33% and 66% of surgeries, varied across provinces and by timing of admission. This may reflect different provincial approaches to providing access to hip fracture surgery.

In hip fracture care, it is disputed whether mortality worsens when surgery is delayed. This knowledge gap matters when hospital managers seek to justify resource allocation for prioritizing access to one procedure over another. Uncertainty over the surgical timing-death association leads to either surgical prioritization without benefit or the underuse of expedited surgery when it could save lives. The discrepancy in previous findings results in part from differences between patients who happened to undergo surgery at different times. Such differences may produce the statistical association between surgical timing and death in the absence of a causal relationship. Previous observational studies attempted to adjust for structure, process, and patient factors that contribute to death, but not for relationships between structure and process factors, or between patient and process factors. In this article, we (1) summarize what is known about the factors that influence, directly or indirectly, both the timing of surgery and the occurrence of death; (2) construct a dependency graph of relationships among these factors based explicitly on the existing literature; (3) consider factors with a potential to induce covariation of time to surgery and the occurrence of death, directly or through the network of relationships, thereby explaining a putative surgical timing-death association; and (4) show how age, sex, dependent living, fracture type, hospital type, surgery type, and calendar period can influence both time to surgery and occurrence of death through chains of dependencies. We conclude by discussing how these results can inform the allocation of surgical capacity to prevent the avoidable adverse consequences of delaying hip fracture surgery.

Purpose: Failure to account for medically necessary delays may lead to an underestimation of early surgery benefits. This study investigated the feasibility of using administrative data to identify the National Institute for Health and Care Excellence (NICE) 124 guideline list of conditions that appropriately delay hip fracture surgery., Methods: We assembled a list of diagnosis and procedure codes to reflect the NICE 124 conditions. The list was reviewed and updated by an advanced clinical coder. The list was refined by five clinical experts. We then screened Canadian Institute for Health Information discharge abstracts for 153 918 patients surgically treated for a non-pathological first hip fracture between 1 January 2004 and 31 December 2012 for diagnosis codes present on admission and procedure codes that antedated hip fracture surgery. We classified abstracts as having medical reasons for delaying surgery based on the presence of these codes., Results: In total, 10 237 (6.7%; 95% CI 6.5% to 6.8%) patients had diagnostic and procedure codes indicating medical reasons for delay. The most common reasons for medical delay were exacerbation of a chronic chest condition (35.9%) and acute chest infection (23.2%). The proportion of patients with reasons for medical delays increased with time from admission to surgery: 3.9% (95% CI 3.6% to 4.1%) for same day surgery; 4.7% (95% CI 4.5% to 4.8%) for surgery 1 day after admission; 7.1% (95% CI 6.9% to 7.4%) for surgery 2 days after admission; and 15.5% (95% CI 15.1% to 16.0%) for surgery more than 2 days after admission. The trend was seen for admissions on weekday working hours, weekday after hours and on weekends., Conclusion: Administrative data can be considered to identify conditions that appropriately delay hip fracture surgery. Accounting for medically necessary delays can improve estimates of the effectiveness of early surgery., Competing Interests: Competing interests: The authors declare the following. (1) BS, PG and the Collaborative have received grants from the Canadian Institutes of Health Research related to this work. (2) PG also receives funding from the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the British Columbia Specialists Services Committee for work around hip fracture care not related to this manuscript. He has also received fees from the BC Specialists Services Committee (for a provincial quality improvement project on redesign of hip fracture care) and from Stryker Orthopedics (as a product development consultant). He is a board member and shareholder in Traumis Surgical Systems Inc. and a board member for the Canadian Orthopedic Foundation. He also serves on the speakers’ bureaus of AO Trauma North America and Stryker Canada. (3) SM reports research grants from Amgen Canada and from Merck, personal fees from Amgen Canada outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Recognition of the phosphorylation sites in proteins is required for reconstruction of regulatory processes in living systems. This task is complicated because the phosphorylation motifs in amino acid sequences are considerably degenerated. To improve the prediction efficacy researchers often use additional descriptors, which should reflect physicochemical features of site-surrounding regions. We have evaluated the reasonability of this approach by applying molecular descriptors (MNA) for structural presentation of the peptide segments. Comparative testing was performed using the prognostic method PASS and two input data types: sets of the MNA descriptors represented peptides as chemical structures and amino acid sequences written using a one-letter code. Training sets were classified in accordance with the established types of the enzymes (protein kinases), modifying corresponding phosphorylation sites. The accuracy estimates obtained by prognosis validation for various classes of substrates were significantly different with both the letters and molecular descriptors. In case of the letter description, the prognosis accuracy demonstrated less dependence on the length of peptides in the training set, while in the case of structural descriptors the accuracy level was determined by the peptide size and descriptor characteristics (MNA levels). The maximal prognosis accuracy related to various kinase families was achieved at different sizes of molecular fragments covered by the MNA descriptors of corresponding levels. This obviously reflected structural differences in surroundings of phosphorylation sites modified by various protein kinases. The use of molecular descriptors provided the prognostic results comparable with the results obtained using traditional letter representation. The prognosis accuracy demonstrated less dependence on the method describing site-surrounding peptides at higher accuracy rates. Applying the MNA descriptors it is possible to achieve better accuracy in the cases when the letter description cannot provide acceptable accuracy.

Objectives: It is disputed whether the time a patient waits for surgery after hip fracture increases the risk of in-hospital death. This uncertainty matters as access to surgery following hip fracture may be underprioritised due to a lack of definitive evidence. Uncertainty in the available evidence may be due to differences in characteristics of patients, their injury and their care. We summarised the literature on patients and system factors associated with time to surgery, and collated proposed mechanisms for the associations., Methods: We used the framework developed by Arksey and O'Malley and Levac et al for synthesis of factors and mechanisms of time to surgery after hip fracture in adults aged >50 years, published in English, between 1 January 2000 and 28 February 2017, and indexed in MEDLINE, EMBASE, CINAHL or Ageline. Proposed mechanisms for reported associations were extracted from discussion sections., Results: We summarised evidence from 26 articles that reported on 24 patient and system factors of time to surgery post hip fracture. In total, 16 factors were reported by only one article. For 16 factors we found proposed mechanisms for their association with time to surgery which included surgical readiness, available resources, prioritisation and out-of-hours admission., Conclusions: We identified patient and system factors associated with time to surgery after hip fracture. This new knowledge will inform evaluation of the putative timing-death association. Future interventions should be designed to influence factors with modifiable mechanisms for delay., Competing Interests: Competing interests: PG has received grants from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the British Columbia Specialists Services Committee for work around hip fracture care not related to this manuscript. He has also received fees from the BC Specialists Services Committee (for a provincial quality improvement project on redesign of hip fracture care) and from Stryker Orthopedics (as a product development consultant). He is a board member and shareholder of Traumis Surgical Systems Inc. and a board member of the Canadian Orthopedic Foundation. He also serves on the speakers’ bureaus of AO Trauma North America and Stryker Canada. KJS, BS and YFVV declare they have no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Hospitalization data underestimate the occurrence of transient ischemic attack (TIA). As TIA is frequently diagnosed in primary care, methodologies for the accurate ascertainment of a TIA from physician claims data are required for surveillance and health systems planning in this population. The present study evaluated the diagnostic accuracy of multiple algorithms for TIA from a longitudinal population-based physician billing database., Methods: Population-based administrative data from the province of British Columbia were used to identify the base population (1992-2007; N=102,492). Using discharge records for hospital admissions for acute ischemic stroke with a recent (<90 days) TIA as the reference standard, we performed receiver-operating characteristic analyses to calculate sensitivity, specificity, positive and negative predictive values and overall accuracy, and to compare area under the curve for each physician billing algorithm. To evaluate the impact of different case definitions on population-based TIA burden, we also estimated the annual TIA occurrence associated with each algorithm., Results: Physician billing algorithms showed low to moderate sensitivity, with the algorithm for two consecutive physician visits within 90 days showing the highest sensitivity at 37.7% (CI 95%=37.4-38.1). All algorithms demonstrated high specificity and moderate to high overall accuracy, resulting in low positive predictive values (≤5%), low discriminability (0.53-0.57) and high false positive rates (1 - specificity). Population-based estimates of TIA occurrence were comparable to prior studies and declined over time., Conclusions: Physician billing data have insufficient sensitivity to identify TIAs but may be used in combination with hospital discharge data to improve the accuracy of estimating the population-based occurrence of TIAs.

Purpose: There is limited information in administrative databases on the occurrence of serious but treatable complications after hip fracture surgery. This study sought to determine the feasibility of identifying the occurrence of serious but treatable complications after hip fracture surgery from discharge abstracts by applying the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator 4 (PSI-4) case-finding tool., Methods: We obtained Canadian Institute for Health Information discharge abstracts for patients 65 years or older, who were surgically treated for non-pathological first hip fracture between 1 January 2004 and 31 December 2012 in Canada, except for Quebec. We applied specifications of AHRQ Patient Safety Indicators 04, Version 5.0 to identify complications from hip fracture discharge abstracts., Results: Out of 153 613 patients admitted with hip fracture, we identified 12 383 (8.1%) patients with at least one postsurgical complication. From patients with postsurgical complications, we identified 3066 (24.8%) patient admissions to intensive care unit. Overall, 7487 (4.9%) patients developed pneumonia, 1664 (1.1%) developed shock/myocardial infarction, 651 (0.4%) developed sepsis, 1862 (1.1%) developed deep venous thrombosis/pulmonary embolism and 1919 (1.3%) developed gastrointestinal haemorrhage/acute ulcer., Conclusions: We report that 8.1% of patients developed at least one inhospital complication after hip fracture surgery in Canada between 2004 and 2012. The AHRQ PSI-4 case-finding tool can be considered to identify these serious complications for evaluation of postsurgical care after hip fracture., Competing Interests: Competing interests: The authors declare that (1) BS, PG and the Collaborative have received grants from the Canadian Institutes of Health Research related to this work. (2) PG also receives funding from the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the British Columbia Specialists Services Committee for work around hip fracture care not related to this manuscript. He has also received fees from the BC Specialists Services Committee (for a provincial quality improvement project on redesign of hip fracture care) and from Stryker Orthopedics (as a product development consultant). He is a board member and shareholder in Traumis Surgical Systems Inc. and a board member for the Canadian Orthopedic Foundation. He also serves on the speakers’ bureaus of AO Trauma North America and Stryker Canada. (3)SNM reports research grants from Amgen Canada, and from Merck, personal fees from Amgen Canada outside the submitted work. (4) KJS is a postdoctoral fellow whose salary is paid by Canadian Institutes of Health Research funding related to this work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Second hip fractures account for up to 15% of all hip fractures. We sought to determine if the proportion of hip fracture surgeries for second hip fracture changed over time in terms of patient and fracture characteristics., Methods: We reviewed the records of patients older than 60 years hospitalized for hip fracture surgery between 1990 and 2005 in British Columbia. We studied the proportion of surgeries for second hip fracture among all hip fracture surgeries. Linear regression tested for trends across fiscal years for women and men., Results: We obtained 46 341 patient records. Second hip fracture accounted for 8.3% of hip fracture surgeries. For women the proportion of second hip fracture surgeries increased linearly from 4% to 13% with each age decade ( p = 0.001) and across fiscal years ( p = 0.002). In men the proportion of second hip fracture surgeries was 5% for each age decade between the ages of 60 and 90 years across fiscal years, increasing to 8% for men older than 90 years across fiscal years ( p = 0.20). These sex-specific trends were similar for both pertrochanteric and transcervical fracture types., Conclusion: Second hip fracture surgeries account for an increasing proportion of hip fracture surgeries and may require more health care resources to minimize poorer reported outcomes. Future research should determine whether more health care resources are required to manage these patients and optimize their outcomes.

Two hypotheses were offered for the effect of shorter hospital stays on mortality after hip fracture surgery: worsening the quality of care and shifting death occurrence to postacute settings.We tested whether the risk of hospital death after hip fracture surgery differed across years when postoperative stays shortened, and whether care factors moderated the association.Analysis of acute hospital discharge abstracts for subgroups defined by hospital type, bed capacity, surgical volume, and admission time.153,917 patients 65 years or older surgically treated for first hip fracture.Risk of hospital death.We found a decrease in the 30-day risk of hospital death from 7.0% (95%CI: 6.6-7.5) in 2004 to 5.4% (95%CI: 5.0-5.7) in 2012, with an adjusted odds ratio [OR] 0.71 (95%CI: 0.63-0.80). In subgroup analysis, only large community hospitals showed the reduction of ORs by calendar year. No trend was observed in teaching and medium community hospitals. By 2012, the risk of death in large higher volume community hospitals was 34% lower for weekend admissions, OR = 0.66 (95%CI: 0.46-0.95) and 39% lower for weekday admissions, OR = 0.61 (95%CI: 0.40-0.91), compared to 2004. In large lower volume community hospitals, the 2012 risk was 56% lower for weekend admissions, OR = 0.44 (95%CI: 0.26-0.75), compared to 2004.The risk of hospital death after hip fracture surgery decreased only in large community hospitals, despite universal shortening of hospital stays. This supports the concern of worsening the quality of hip fracture care due to shorter stays.

Background: Adverse drug events are a leading cause of emergency department visits and unplanned admissions, and prolong hospital stays. Medication review interventions aim to identify adverse drug events and optimize medication use. Previous evaluations of in-hospital medication reviews have focused on interventions at discharge, with an unclear effect on health outcomes. We assessed the effect of early in-hospital pharmacist-led medication review on the health outcomes of high-risk patients., Methods: We used a quasi-randomized design to evaluate a quality improvement project in three hospitals in British Columbia, Canada. We incorporated a clinical decision rule into emergency department triage pathways, allowing nurses to identify patients at high-risk for adverse drug events. After randomly selecting the first eligible patient for participation, clinical pharmacists systematically allocated subsequent high-risk patients to medication review or usual care. Medication review included obtaining a best possible medication history and reviewing the patient's medications for appropriateness and adverse drug events. The primary outcome was the number of days spent in-hospital over 30 days, and was ascertained using administrative data. We used median and inverse propensity score weighted logistic regression modeling to determine the effect of pharmacist-led medication review on downstream health services use., Results: Of 10,807 high-risk patients, 6,416 received early pharmacist-led medication review and 4,391 usual care. Their baseline characteristics were balanced. The median number of hospital days was reduced by 0.48 days (95% confidence intervals [CI] = 0.00 to 0.96; p = 0.058) in the medication review group compared to usual care, representing an 8% reduction in the median length of stay. Among patients under 80 years of age, the median number of hospital days was reduced by 0.60 days (95% CI = 0.06 to 1.17; p = 0.03), representing 11% reduction in the median length of stay. There was no significant effect on emergency department revisits, admissions, readmissions, or mortality., Limitations: We were limited by our inability to conduct a randomized controlled trial, but used quasi-random patient allocation methods and propensity score modeling to ensure balance between treatment groups, and administrative data to ensure blinded outcomes ascertainment. We were unable to account for alternate level of care days, and therefore, may have underestimated the treatment effect in frail elderly patients who are likely to remain in hospital while awaiting long-term care., Conclusions: Early pharmacist-led medication review was associated with reduced hospital-bed utilization compared to usual care among high-risk patients under 80 years of age, but not among those who were older. The results of our evaluation suggest that medication review by pharmacists in the emergency department may impact the length of hospital stay in select patient populations., Competing Interests: We have the following interests: Isabella Ghement is affiliated to Ghement Statistical Consulting Company Ltd. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: Where patients with hip fracture undergo treatment may influence their outcome. We compared the risk of in-hospital death after hip fracture by treatment setting in Canada., Methods: We examined all discharge abstracts from the Canadian Institute for Health Information with diagnosis codes for hip fracture involving patients 65 years and older who were admitted to hospital with a nonpathological first hip fracture between Jan. 1, 2004, and Dec. 31, 2012, in Canada (excluding Quebec). We compared the risk of in-hospital death, overall and after surgery, between teaching hospitals and community hospitals of various bed capacities, accounting for variation in length of stay., Results: Compared with the number of deaths per 1000 admissions at teaching hospitals, there were an additional 3 (95% confidence interval [CI] 1-6), 14 (95% CI 10-18) and 43 (95% CI 35-51) deaths per 1000 admissions at large, medium and small community hospitals, respectively. For the risk of in-hospital death overall, the adjusted odds ratios (ORs) were 1.05 (95% CI 0.99-1.11), 1.16 (95% CI 1.09-1.24) and 1.44 (95% CI 1.31-1.57) at large, medium and small community hospitals, respectively, compared with teaching hospitals. For the risk of postsurgical death in hospital, the adjusted ORs were 1.06 (95% CI 1.00-1.13), 1.13 (95% CI 1.04-1.23) and 1.18 (95% CI 0.87-1.60) at large, medium and small community hospitals, respectively., Interpretation: Compared with teaching hospitals, the risk of in-hospital death among patients with hip fracture was higher at medium and small community hospitals, and the risk of in-hospital death after surgery was higher at medium community hospitals. No differences were found between teaching and large community hospitals. Future research should examine the role of volume, demand and bed occupancy for observed differences., (© 2016 Canadian Medical Association or its licensors.)

Background: Several patient and health system factors were associated with the risk of death among patients with hip fracture. However, without knowledge of underlying mechanisms interventions to improve survival post hip fracture can only be designed on the basis of the found statistical associations., Methods: We used the framework developed by Arksey and O'Malley and Levac et al. for synthesis of factors and mechanisms of mortality post low energy hip fracture in adults over the age of 50 years, published in English, between September 1, 2009 and October 1, 2014 and indexed in MEDLINE. Proposed mechanisms for reported associations were extracted from the discussion sections., Results: We synthesized the evidence from 56 articles that reported on 35 patient and 9 system factors of mortality post hip fracture. For 21 factors we found proposed biological mechanisms for their association with mortality which included complications, comorbidity, cardiorespiratory function, immune function, bone remodeling and glycemic control., Conclusions: The majority of patient and system factors of mortality post hip fracture were reported by only one or two articles and with no proposed mechanisms for their effects on mortality. Where reported, underlying mechanisms are often based on a single article and should be confirmed with further study. Therefore, one cannot be certain whether intervening on such factors may produce expected results.

Episodes of care defined by the event of hip fracture surgery are widely used for the assessment of surgical wait times and outcomes. However, this approach does not consider nonoperative deaths, implying that survival time begins at the time of procedure. This approach makes treatment effect implicitly conditional on surviving to treatment. The purpose of this article is to describe a novel conceptual framework for constructing an episode of hip fracture care to fully evaluate the incidence of adverse events related to time after admission for hip fracture. This admission-based approach enables the assessment of the full harm of delay by including deaths while waiting for surgery, not just deaths after surgery. Some patients wait until their conditions are optimized for surgery, whereas others have to wait until surgical service becomes available. We provide definitions, linkage rules, and algorithms to capture all hip fracture patients and events other than surgery. Finally, we discuss data elements for stratifying patients according to administrative factors for delay to allow researchers and policymakers to determine who will benefit most from expedited access to surgery., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Unlabelled: Changes in bed management and access policy aimed to shorten Canadian hip fracture hospital stay. Secular trends in hip fracture total, preoperative, and postoperative stay are unknown. Hip fracture stay shortened from 2004 to 2012, mostly from shortening postoperative stay. This may reflect changes in bed management rather than access policy., Purpose: To compare the probability of discharge by time after patient admission to hospital with first-time hip fracture over a period of nine calendar years., Methods: We retrieved acute hospitalization records for 169,595 patients 65 years and older, who were admitted to an acute care hospital with hip fracture between 2004 and 2012 in Canada (outside of Quebec). The main outcome measure was cumulative incidence of discharge by inpatient day, accounting for competing events that end hospital stay., Results: The probability of surgical discharge within 30 days of admission increased from 57.2 % in 2004 to 67.3 % in 2012. The probability of undergoing surgery on day of admission or day after fluctuated around 58.5 % over the study period. For postoperative stay, the discharge probability increased from 6.8 to 12.2 % at day 4 after surgery and from 57.2 to 66.6 % at day 21 after surgery, between 2004 and 2012. The differences across years persisted after adjustment for characteristics of patients, fracture, comorbidity, treatment, type and timing of surgery, and access to care., Conclusions: Hospital stay following hip fracture shortened substantially between 2004 and 2012 in Canada, mostly due to shortening of postoperative stays. Shorter hospital stays may reflect changes in bed management protocols rather than in access policy.

Unlabelled: Hip fracture increases death risk. Ten percent of survivors have second hip fracture. It is not known if second hip fracture further increases death risk. Here, we report that second hip fracture increases death risk beyond that expected for an increase in age. Secondary prevention after hip fracture could save lives., Introduction: The purpose of this study is to determine if second hip fracture is associated with an increased death rate., Methods: We retrieved 42,435 hospitalization records of patients aged 60 years or older, who were discharged after admission for hip fracture surgery between 1990 and 2005 in British Columbia, Canada. The outcome variable was the time to death., Results: During follow-up, the average monthly death rate was 16.2 (95 % CI 16.0-16.4) per 1000 patient-months for those without second hip fracture and 21.1 (95 % CI 20.2-22.1) per 1000 patient-months for those with second hip fracture. The hazard of death was 55 % higher for patients with second hip fracture compared to those without second hip fracture (HR = 1.55, 95 % CI 1.47-1.63). The hazard of death was 58 % higher for men with second hip fracture than in men without second hip fracture (HR = 1.58, 95 % CI 1.42-1.75). The hazard of death was 54 % higher for women with second hip fracture compared to women without second hip fracture (HR = 1.54, 95 % CI 1.46-1.63). These sex-specific HRs were not statistically different (p = 0.70)., Conclusion: Our results are the first to show that second hip fracture increases the risk of death above that anticipated for an increase in age for both men and women. Effective secondary prevention strategies could not only reduce morbidity after hip fracture but could also save lives.

Aims: Adverse drug events are an important cause of emergency department visits, unplanned admissions and prolonged hospital stays. Our objective was to synthesize the evidence on the effect of early in-hospital pharmacist-led medication review on patient-oriented outcomes based on observed data., Methods: We systematically searched eight bibliographic reference databases, electronic grey literature, medical journals, conference proceedings, trial registries and bibliographies of relevant papers. We included studies that employed random or quasi-random methods to allocate subjects to pharmacist-led medication review or control. Medication review had to include, at a minimum, obtaining a best possible medication history and reviewing medications for appropriateness and adverse drug events. The intervention had to be initiated within 24 h of emergency department presentation or 72 h of admission. We extracted data in duplicate and pooled outcomes from clinically homogeneous studies of the same design using random effects meta-analysis., Results: We retrieved 4549 titles of which seven were included, reporting the outcomes of 3292 patients. We pooled data from studies of the same design, and found no significant differences in length of hospital admission (weighted mean difference [WMD] -0.04 days, 95% confidence interval [CI] -1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI 0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting reductions in readmissions could not be included in our pooled estimates due to differences in study design., Conclusions: Wide confidence intervals suggest that additional research is likely to influence the effect size estimates and clarify the effect of medication review on patient-oriented outcomes. This systematic review failed to identify an effect of pharmacist-led medication review on health outcomes., (© 2015 The British Pharmacological Society.)

Background: Secondary prevention often targets women who suffer from higher rates of second hip fracture than men, especially in the early years after first fracture. Yet, the occurrence of second hip fracture by certain times also depends on the death rate, which is higher in men than women. We compared the risk of sustaining second hip fracture by a certain time between women and men remaining alive at that time., Methods: We retrieved 38,383 hospitalization records of patients aged 60 years or older, who were discharged alive after admission for hip fracture surgery between 1990 and 2005 in British Columbia, Canada. The outcome variable was the time to a subsequent hip fracture., Results: During ten years of follow-up, 2,902 (8%) patients sustained a second hip fracture, and 21,428 (56%) died before sustaining a second hip fracture. The risk of second hip fracture in the surviving post-fracture patients was higher in women than in men: 2% vs 2%, 5% vs 4%, 9% vs 7%, 15% vs 13%, and 35% vs 30% at 1, 2, 3, 5, and 10 years after initial trauma, respectively, crude OR=1.25 (95% CI: 1.13-1.39). However, the risk did not differ between women and men after adjustment, OR=1.09 (95% CI: 0.98-1.21)., Conclusions: The risk of second hip fracture persists for at least ten years among hip fracture survivors, and therefore secondary prevention should continue beyond an early post-fracture period. Women and men have similar risks of second hip fracture and both should be considered for secondary prevention., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

In order to surpass the problem of genetic variability of hepatitis C virus envelope proteins during vaccine development, we used the so-called "reverse vaccinology"approach--"from genome to vaccine". Database of HCV protein sequences was designed, viral genome analysis was performed, and several highly conserved sites were revealed in HCV envelope proteins in the framework of this approach. These sites demonstrated low antigenic activity in full-size proteins and HCV virions: antibodies against these sites were not found in all hepatitis C patients. However, two sites, which contained a wide set of potential T-helper epitope motifs, were revealed among these highly conserved ones. We constructed and prepared by solid-phase peptide synthesis several artificial peptide constructs composed of two linker-connected highly conserved HCV envelope E2 protein sites; one of these sites contained a set of T-helper epitope motifs. Experiments on laboratory animals demonstrated that the developed peptide constructs manifested immunogenicity compared with one of protein molecules and were able to raise antibodies, which specifically bound HCV envelope proteins. We succeeded in obtaining antibodies reactive with HCV from hepatitis C patient plasma upon the immunization with some constructs. An original preparation of a peptide vaccine against hepatitis C is under development on the basis of these peptide constructs.

Background: Adverse drug events are unintended and harmful events related to medication use. They are a leading cause of visits to the emergency department, unplanned admissions to hospital and death. Adverse drug events can be misdiagnosed in the emergency department, resulting in treatment delays. Our objective was to describe a process to evaluate the effect of pharmacist-led medication review in high-risk patients in the emergency department on the number of days these patients subsequently spent in hospital within 30 days of their index visit., Methods: We describe the evaluation of a prospective multicentre quality improvement program. During the evaluation period, triage nurses will flag incoming patients to the emergency department at high risk for adverse drug events by applying a clinical decision rule consisting of 4 variables (comorbid conditions, antibiotic use within 7 days, medication changes within 28 days and age). Consecutive eligible patients will be enrolled in the study and systematically allocated to either a pharmacist-led medication review group or a control group. In the intervention group, pharmacists will collect best-possible medication histories, review the patient's medications for appropriateness and adverse drug events, and communicate the results of their medication review to patients, caregivers and physicians. In the control group, nurses will start medication reconciliation by collecting best-possible medication histories, and physicians will refer patients to onsite pharmacists for specific medication management questions as needed. Health outcomes will be assessed using anonymized data linkage to administrative health databases. The primary outcome will be the percent days spent in hospital over a 30-day period., Interpretation: This protocol describes the methods for evaluating the effect of pharmacist-led medication review in high-risk patients in the emergency department on use of health services, and highlights the methodological challenges that will be encountered. We plan to disseminate the results of this evaluation through articles published in peer-reviewed journals, presentations at scientific meetings and briefing notes to institutional, provincial and national stakeholders.

Many trauma survivors face challenges of impaired functioning, limited activities and reduced participation. Recovery from injury after acute care, therefore, becomes an important public health issue. This commentary discusses a framework for evaluating outcomes of acute care.

Background: Screening for acute stress is not part of routine trauma care owing in part to high variability of acute stress symptoms in identifying later onset of posttraumatic stress disorder (PTSD). The objective of this pilot study was to assess the sensitivity, specificity, and power to predict onset of PTSD symptoms at 1 and 4 months using a routine screening program in comparison to current ad hoc referral practice., Methods: Prospective cross-sectional observational study of a sample of hospitalized trauma patients over a four-month period from a level-I hospital in Canada. Baseline assessments of acute stress (ASD) and subsyndromal ASD (SASD) were measured using the Stanford Acute Stress Reaction Questionnaire (SASRQ). In-hospital psychiatric consultations were identified from patient discharge summaries. PTSD symptoms were measured using the PTSD Checklist-Specific (PCL-S). Post-discharge health status and health services utilization surveys were also collected., Results: Routine screening using the ASD (0.43) and SASD (0.64) diagnoses were more sensitive to PTSD symptoms at one month in comparison to ad hoc referral (0.14) and also at four months (0.17, 0.33 versus 0.17). Ad hoc referral had greater positive predictive power in identifying PTSD caseness at 1 month (0.50) in comparison to the ASD (0.46) and SASD (0.43) diagnoses and also at 4 months (0.67 versus 0.25 and 0.29)., Conclusions: Ad hoc psychiatric referral process for acute stress is a more conservative approach than employing routine screening for identifying persons who are at risk of psychological morbidity following injury. Despite known limitations of available measures, routine patient screening would increase identification of trauma survivors at risk of mental health sequelae and better position trauma centers to respond to the circumstances that affect mental health during recovery.

Background: Adverse drug events are a frequent cause of emergency department presentations. Administrative data could be used to identify patients presenting with adverse drug events for post-market surveillance, and to conduct research in patient safety and in drug safety and effectiveness. However, such data sources have not been evaluated for their completeness with regard to adverse drug event reporting. Our objective was to determine the proportion of adverse drug events to outpatient medications diagnosed at the point-of-care in emergency departments that were documented in administrative data., Methods: We linked the records of patients enrolled in a prospective observational cohort study on adverse drug events conducted in two Canadian tertiary care emergency departments to their administrative data. We compared the number of adverse drug events diagnosed and recorded at the point-of-care in the prospective study with the number of adverse drug events recorded in the administrative data., Results: Among 1574 emergency department visits, 221 were identified as adverse drug event-related in the prospective database. We found 15 adverse drug events documented in administrative records with ICD-10 codes clearly indicating an adverse drug event, indicating a sensitivity of 6.8% (95% CI 4.0-11.2%) of this code set. When the ICD-10 code categories were broadened to include codes indicating a very likely, likely or possible adverse event to a medication, 62 of 221 events were identifiable in administrative data, corresponding to a sensitivity of 28.1% (95% CI 22.3-34.6%)., Conclusions: Adverse drug events to outpatient medications were underreported in emergency department administrative data compared to the number of adverse drug events diagnosed and recorded at the point-of-care.

In this study, we assess the accuracy of fertility estimates that stem from the retrospective information that can be derived from an existing cross-sectional population. Swedish population registers contain information on the childbearing of all people ever registered as living in Sweden, and thus allow us to avoid problems of selectivity by the virtue of survival or nonemigration when estimating the fertility measures for previous calendar periods. We calculate two types of fertility rates for each year in 1961-1999: (i) rates that are based on the population that was living in Sweden at the end of 1999, and (ii) rates that also include information on people who had died or emigrated before the turn of the twentieth century. We find that the omission of information on individuals who had emigrated or died, as the situation would be in any demographic survey, most often have negligible effects on fertility measures. However, first-birth rates of immigrants gradually become more biased as we move back in time from 1999 so that they increasingly tend to over-estimate the true fertility of that population.

Unlabelled: We determined age-standardized first hip fracture rates in British Columbia between 1990 and 2004. We found sex and fracture type rates in keeping with previous reports and that fracture rates have decreased approximately 18% overall in both men and women., Introduction: To determine whether there have been changes in the age-, sex-, and subtype-specific first hip fracture rates in Canadian province of British Columbia (BC) between 1990 and 2004., Methods: Records of all persons aged 60 years and older hospitalized with hip fractures in BC between 1985 and 2004 were obtained from the Canadian Institute for Health Information Discharge Abstract Database. Only the first hip fracture records were included, and fractures likely due to causes other than trauma were excluded. Age- and sex-specific rates were calculated using population denominators from Statistics Canada and direct standardization was used. Age-standardized rates allowed for comparison across years with adjustment for age distribution., Results: There were 41,990 records of first hip fracture included, and 73% were in women. Trends in age-specific rates by fracture type were similar to previous reports. Between 1990 and 2004, there has been an age-adjusted 18% decrease in first hip fracture rates in women, and 19% decrease in first hip fracture rates in men. The decrease was statistically significant in femoral neck fractures in women, but not in men., Conclusions: There has been a decrease in age-adjusted hip fracture rates in BC between 1990 and 2004, which is in contrast to previous projections for hip fracture rates in Canada.

Unlabelled: A comprehensive review of literature was conducted to investigate variation in hip fracture incident rates around the world. The original crude incidence rates were standardized for age and sex for comparability. After standardization, the highest rates of hip fracture were found in Scandinavia and the lowest rates in Africa., Introduction: This study was conducted to investigate the geographic trends of the incidence of osteoporotic hip fractures through a comprehensive review of literature., Methods: Studies were identified for inclusion in the review by searching the MEDLINE database via PubMed and applying strict inclusion and exclusion criteria. Age-specific incidence rates were extracted from the articles, and in order to provide a common platform for analysis, we used directly age-standardized and age-sex-standardized rates (using the 2005 United Nations estimates of the world population as standard) to complete the analysis., Results: Forty-six full text articles spanning 33 countries/regions were included in the review. For ease of comparison, the results were analyzed by geographic regions: North America, Latin America, Scandinavia, Europe (excluding Scandinavia), Africa, Asia, and Australia. The highest hip fracture rates were found in Scandinavia and the lowest in Africa. We found comparable rates from countries in North America, Australia, and Europe outside of Scandinavia. The diverse makeup of the Asian continent also resulted in quite variable hip fracture rates: ranging from relatively high rates in Iran to low rates, comparable to those from Africa, in mainland China., Conclusions: Given the aging of populations globally, and in the industrialized countries specifically, hip fractures will become a progressively larger public health burden. The geographic trends observed in hip fracture incidence rates can provide important clues to etiology and prevention.

Study Objective: Our objectives are to describe the outcomes of patients presenting to the emergency department (ED) because of an adverse drug event and to compare them with outcomes of patients presenting for other reasons., Methods: This prospective observational study was conducted at Vancouver General Hospital, a 955-bed tertiary care hospital. We prospectively enrolled adults presenting to the ED between March and June 2006, using a systematic sampling algorithm. Pharmacists and physicians independently evaluated patients for adverse drug events. An independent committee reviewed and adjudicated cases in which assessments were discordant or uncertain. Data from the index visit were linked to vital statistics, administrative health services utilization, and cost of care data., Results: Of 1,000 patients, 122 (12.2%; 95% confidence interval [CI] 10.3% to 14.4%) presented to the ED because of an adverse drug event. Of these, 48 presented because of an adverse drug reaction (one type of adverse drug event defined as an unintended response that occurred despite use of an appropriate drug dosage). We found no difference in mortality among patients presenting with and without adverse drug reactions (14.6% versus 5.9%; hazard ratio 1.57; 95% CI 0.70 to 3.52). After adjustment, patients with adverse drug events had a higher risk of spending additional days in the hospital per month (6.3% versus 3.4%; odds ratio 1.52; 95% CI 1.43 to 1.62) and higher rate of outpatient health care encounters (1.73 versus 1.22; rate ratio 1.20; 95% CI 1.03 to 1.40). The adjusted median monthly cost of care was 1.90 times higher (Can $325 versus $96; 95% CI 1.18 to 3.08)., Conclusion: ED patients presenting with an adverse drug event incurred greater health services utilization and costs during a 6-month follow-up period compared with patients presenting for other reasons., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: The knowledge about proteins with specific interaction capacity to the protein partners is very important for the modeling of cell signaling networks. However, the experimentally-derived data are sufficiently not complete for the reconstruction of signaling pathways. This problem can be solved by the network enrichment with predicted protein interactions. The previously published in silico method PAAS was applied for prediction of interactions between protein kinases and their substrates., Results: We used the method for recognition of the protein classes defined by the interaction with the same protein partners. 1021 protein kinase substrates classified by 45 kinases were extracted from the Phospho.ELM database and used as a training set. The reasonable accuracy of prediction calculated by leave-one-out cross validation procedure was observed in the majority of kinase-specificity classes. The random multiple splitting of the studied set onto the test and training set had also led to satisfactory results. The kinase substrate specificity for 186 proteins extracted from TRANSPATH database was predicted by PAAS method. Several kinase-substrate interactions described in this database were correctly predicted. Using the previously developed ExPlain system for the reconstruction of signal transduction pathways, we showed that addition of the newly predicted interactions enabled us to find the possible path between signal trigger, TNF-alpha, and its target genes in the cell., Conclusions: It was shown that the predictions of protein kinase substrates by PAAS were suitable for the enrichment of signaling pathway networks and identification of the novel signaling pathways. The on-line version of PAAS for prediction of protein kinase substrates is freely available at http://www.ibmc.msk.ru/PAAS/.

Objectives: The purpose of the study was to develop a population-based simulation model of osteoarthritis (OA) in Canada that can be used to quantify the future health and economic burden of OA under a range of scenarios for changes in the OA risk factors and treatments. In this article we describe the overall structure of the model, sources of data, derivation of key input parameters for the epidemiological component of the model, and preliminary validation studies., Design: We used the Population Health Model (POHEM) platform to develop a stochastic continuous-time microsimulation model of physician-diagnosed OA. Incidence rates were calibrated to agree with administrative data for the province of British Columbia, Canada. The effect of obesity on OA incidence and the impact of OA on health-related quality of life (HRQL) were modeled using Canadian national surveys., Results: Incidence rates of OA in the model increase approximately linearly with age in both sexes between the ages of 50 and 80 and plateau in the very old. In those aged 50+, the rates are substantially higher in women. At baseline, the prevalence of OA is 11.5%, 13.6% in women and 9.3% in men. The OA hazard ratios for obesity are 2.0 in women and 1.7 in men. The effect of OA diagnosis on HRQL, as measured by the Health Utilities Index Mark 3 (HUI3), is to reduce it by 0.10 in women and 0.14 in men., Conclusions: We describe the development of the first population-based microsimulation model of OA. Strengths of this model include the use of large population databases to derive the key parameters and the application of modern microsimulation technology. Limitations of the model reflect the limitations of administrative and survey data and gaps in the epidemiological and HRQL literature., (Copyright 2009 Osteoarthritis Research Society International. All rights reserved.)