Cardiorenal effects of Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people underrepresented in trials: analysis of routinely collected data with emulation of a reference trial (ONTARGET).

Cardiovascular disease (CVD) is a leading cause of death globally. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), compared in the ONTARGET trial, each prevent CVD. However, trial results may not be generalisable and their effectiveness in underrepresented groups is unclear. Using trial emulation methods within routine-care data to validate findings, we explored generalisability of ONTARGET results. For people prescribed an ACEi/ARB in the UK Clinical Practice Research Datalink GOLD from 1/1/2001-31/7/2019, we applied trial criteria and propensity-score methods to create an ONTARGET trial-eligible cohort. Comparing ARB to ACEi, we estimated hazard ratios for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure), and secondary outcomes. As the pre-specified criteria were met confirming trial emulation, we then explored treatment heterogeneity among three trial-underrepresented subgroups: females, those aged ≥75 years and those with chronic kidney disease (CKD). In the trial-eligible population (n=137,155), results for the primary outcome demonstrated similar effects of ARB and ACEi, (HR 0.97 [95% CI: 0.93, 1.01]), meeting the pre-specified validation criteria. When extending this outcome to trial-underrepresented groups, similar treatment effects were observed by sex, age and CKD. This suggests that ONTARGET trial findings are generalisable to trial-underrepresented subgroups.

Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. METHODS: With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021. RESULTS: Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P = .45). CONCLUSIONS: The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform.

BACKGROUND: There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation. METHODS AND FINDINGS: With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants. CONCLUSIONS: In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England. METHODS: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region. FINDINGS: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories. INTERPRETATION: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination. FUNDING: Medical Research Council.

Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: a cohort study from OpenSAFELY.

BACKGROUND: While the vaccines against COVID-19 are highly effective, COVID-19 vaccine breakthrough is possible despite being fully vaccinated. With SARS-CoV-2 variants still circulating, describing the characteristics of individuals who have experienced COVID-19 vaccine breakthroughs could be hugely important in helping to determine who may be at greatest risk. METHODS: With the approval of NHS England, we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY-TPP database of fully vaccinated individuals, linked to secondary care and death registry data and described the characteristics of those experiencing COVID-19 vaccine breakthroughs. RESULTS: As of 1st November 2021, a total of 15,501,550 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: ​107-179). From within this population, a total of 579,780 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate (IR) was 98.06 (95% CI 97.93-98.19). There were 28,580 COVID-19-related hospital admissions, 1980 COVID-19-related critical care admissions and 6435 COVID-19-related deaths; corresponding IRs 4.77 (95% CI 4.74-4.80), 0.33 (95% CI 0.32-0.34) and 1.07 (95% CI 1.06-1.09), respectively. The highest rates of breakthrough COVID-19 were seen in those in care homes and in patients with chronic kidney disease, dialysis, transplant, haematological malignancy or who were immunocompromised. CONCLUSIONS: While the majority of COVID-19 vaccine breakthrough cases in England were mild, some differences in rates of breakthrough cases have been identified in several clinical groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the number of positive SARS-CoV-2 tests still occurring is concerning and as numbers of fully vaccinated (and boosted) individuals increases and as follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, to assess vaccine waning and rates of breakthrough COVID-19 between different variants, aimed at identifying individuals at higher risk, are needed.

Development and internal validation of a multivariable risk prediction model for severe rebound pain after foot and ankle surgery involving single-shot popliteal sciatic nerve block.

BACKGROUND: Rebound pain occurs after up to 50% of ambulatory surgeries involving regional anaesthesia. To assist with risk stratification, we developed a model to predict severe rebound pain after foot and ankle surgery involving single-shot popliteal sciatic nerve block. METHODS: After ethics approval, we performed a single-centre retrospective cohort study. Patients undergoing lower limb surgery with popliteal sciatic nerve block from January 2016 to November 2019 were included. Exclusion criteria were uncontrolled pain in the PACU, use of a perineural catheter, or loss to follow-up. We developed and internally validated a multivariable logistic regression model for severe rebound pain, defined as transition from well-controlled pain in the PACU (numerical rating scale [NRS] 3 or less) to severe pain (NRS ≥7) within 48 h. A priori predictors were age, sex, surgery type, planned admission, local anaesthetic type, dexamethasone use, and intraoperative anaesthesia type. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC), Nagelkerke's R2, scaled Brier score, and calibration slope. RESULTS: The cohort included 1365 patients (mean [standard deviation] age: 50 [16] yr). The primary outcome was abstracted in 1311 (96%) patients, with severe rebound pain in 652 (50%). Internal validation revealed poor model performance, with AUROC 0.632 (95% confidence interval [CI]: 0.602-0.661; bootstrap optimisation 0.021), Nagelkerke's R2 0.063, and scaled Brier score 0.047. Calibration slope was 0.832 (95% CI: 0.623-1.041). CONCLUSIONS: We show that a multivariable risk prediction model developed using routinely collected clinical data had poor predictive performance for severe rebound pain after foot and ankle surgery. Prospective studies involving other patient-related predictors are needed. CLINICAL TRIAL REGISTRATION: NCT05018104.

Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials.

Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.We performed a historical cohort study (2000-2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants, as follows. Control group 1: people with COPD not prescribed fluticasone propionate (FP)-salmeterol (SAL); control group 2: people with COPD prescribed SAL only. FP-SAL exposed groups were then selected from CPRD by propensity score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia.2652 FP-SAL exposed people were propensity score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SAL versus SAL (0.85, 95% CI 0.74-0.97 versus 0.88, 0.81-0.95) but not for FP-SAL versus no FP-SAL (1.30, 1.19-1.42 versus 0.75, 0.69-0.81). In addition, active comparator results were consistent with TORCH for mortality (hazard ratio 0.93, 0.65-1.32 versus 0.93, 0.77-1.13) and pneumonia (risk ratio 1.39, 1.04-1.87 versus 1.47, 1.25-1.73).We obtained very similar results to the TORCH trial for active comparator analyses, but were unable to reproduce placebo-controlled results. Application of these validated methods for active comparator analyses to groups excluded from randomised controlled trials provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts.

OBJECTIVES: To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. METHODS: We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. RESULTS: In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. CONCLUSIONS: We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

Proton pump inhibitors and risk of all-cause and cause-specific mortality: A cohort study.

AIM: To investigate the association between proton pump inhibitors (PPIs) and both all-cause and cause-specific mortality. METHODS: We conducted a cohort study using the UK Clinical Practice Research Datalink GOLD database. We compared 733 885 new users of PPIs to 124 410 new users of H2 receptor antagonists (H2Ras). In a secondary analysis we compared 689 602 PPI new users to 1 361 245 nonusers of acid suppression therapy matched on age, sex and calendar year. Hazard ratios for all-cause and cause-specific mortality were estimated using propensity score (PS) weighted Cox models. RESULTS: PPI prescription was associated with increased risk of all-cause mortality, with hazard ratios decreasing considerably by increasing adjustment (unadjusted hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.62-1.69; PS-weighted HR 1.38, 95% CI 1.33-1.44; high-dimensional PS-weighted HR 1.31, 95% CI 1.26-1.37). Short-term associations were observed with mortality from causes where a causal short-term association is unexpected (eg, lung cancer mortality: PS-weighted HR at 6 months 1.77, 95% CI 1.39-2.25). Adjusted hazard ratios were substantially higher when compared to nonusers (PS-weighted HR all-cause mortality 1.96, 95% CI 1.94-1.99) rather than H2RA users. CONCLUSIONS: PPI prescription was strongly associated with all-cause and cause-specific mortality. However, the change in hazard ratios (a) by increasing adjustment and (b) between comparator groups indicates that residual confounding is likely to explain the association between poor health outcomes and PPI use, and fully accounting for this using observational data may not be possible.

Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February.

The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.

The Impact of Concomitant LOW Back Pain (LBP) on Functional Outcomes in Total Ankle Arthroplasty (TAA).

Although numerous studies have demonstrated that concomitant low back pain (LBP) is associated with worse functional outcomes in patients undergoing total hip and knee arthroplasty, no study has analyzed its impact on patients undergoing total ankle arthroplasty (TAA). The aim of this study was to determine the prevalence of LBP in people undergoing TAA and analyze its impact on patient reported functional outcome measures (PROMs). A retrospective review was performed on data from the Vancouver End Stage Ankle Arthritis Database. In total, 87 patients undergoing TAA were studied, with patient demographics collected preoperatively, including the absence or presence of LBP. Postoperative follow-up was performed at 5 years, primarily analyzing disease-specific PROMs including the Ankle Osteoarthritis Score and Ankle Arthritis Score. The Short Form-36 was used as a secondary outcome measure to assess global function. Multivariable linear mixed-effects regression models were conducted to compare the PROM between patients with LBP with those without LBP. In total, 30 patients (35%) presented with concomitant LBP. There were no significant differences at baseline between the LBP group and no LBP group in terms of demographics or baseline primary disease-specific PROMs. At 5 years, the patients with LBP had significantly worse Ankle Arthritis Score (32 ± 23 vs 22 ± 17, p = .03), Ankle Osteoarthritis Score Total (34 ± 23 vs 22 ± 16, p = .01), and Short Form-36 physical (PCS) components summaries (33 ± 12 vs 44 ± 9, p = .001) compared to the no-LBP group. Both groups improved significantly from baseline across all outcome measures. Our study demonstrated that the prevalence of concomitant LBP in end stage ankle arthritis undergoing TAA is similar to that described in arthritic knees and hips. If present, it can be associated with worse functional outcomes in the intermediate term. However it is not a contraindication to surgery, with patients still experiencing significant improvements from baseline. Further studies are needed to evaluate if LBP influences complications, implant failure rates and survival.

Successful fifth metatarsal bulk autograft reconstruction of thermal necrosis post intramedullary fixation.

Reamed intramedullary (IM) screw fixation for proximal fifth metatarsal fractures is technically challenging with potentially devastating complications if basic principles are not followed. A case of an iatrogenic fourth-degree burn after elective reamed IM screw fixation of a proximal fifth metatarsal fracture in a high-level athlete is reported. The case was complicated by postoperative osteomyelitis with third-degree soft-tissue defect. This was successfully treated with staged autologous bone graft reconstruction, tendon reconstruction, and local bi-pedicle flap coverage. The patient returned to competitive-level sports, avoiding the need for fifth ray amputation. Critical points of the IM screw technique and definitive reconstruction are discussed. Bulk autograft reconstruction is a safe and effective alternative to ray amputation in segmental defects of the fifth metatarsal.Level of evidence V.

Heterotopic Ossification in Total Ankle Arthroplasty: Case Series and Systematic Review.

Heterotopic ossification after total ankle arthroplasty (TAA) is a known sequela and has been reported to contribute to reduced range of motion and poor functional outcomes. However, conflicting results have been reported in the literature. The present study documents the incidence of heterotopic ossification for a novel fourth-generation fixed-bearing 2-component prosthesis and reports a systematic review of the literature. We reviewed the incidence and functional outcome of consecutively enrolled patients who underwent primary Infinity TAA between 2013 and 2015 in a prospective observational study. Preoperative and postoperative radiographic and functional outcome data were collected. A systematic review was also conducted investigating all published studies between 1998 and 2018 reporting the incidence of heterotopic ossification after TAA. The incidence of heterotopic ossification was 70.5% in the 61 patients who underwent primary TAA in the case series. There was no association between heterotopic ossification and American Orthopaedic Foot and Ankle Society (AOFAS) score, foot function index (FFI), visual analogue scale (VAS), and ankle osteoarthritis scale (AOS). Sixteen studies on 1339 TAA implants were included. The overall incidence of heterotopic ossification after TAA was 66.0% at average 3.6 years (range 22.2% to 100%). Four studies (299 ankles) did not address functional outcomes. Eleven studies (960 ankles) reported no association between heterotopic ossification and functional outcomes. One study (80 ankles) reported a statistically significant difference in range of motion (7°) and AOFAS score (7 points). In conclusion, although the incidence of heterotopic ossification after TAA is considerable, there is insufficient literature to suggest that heterotopic ossification after TAA impacts range of motion or functional outcome.

Do preoperative patient-reported outcomes predict hospital length of stay for surgically-treated end-stage ankle osteoarthritis patients?

BACKGROUND: End-stage ankle arthritis is often debilitating, associated with diminished mobility, pain, and reduced health related quality of life. Direct hospital costs of AA and TAA differ, with hospital length of stay being a major contributor. The objective of this study is to test the association between four patient-reported outcome measures with hospital length of stay, potentially important for preoperative planning and care. METHODS: This study is based on a prospective cohort of patients scheduled for AA or TAA for end-stage ankle arthritis in the Vancouver Coastal Health authority, Canada. Participants completed a condition-specific instrument, the AOS, and three generic instruments, the PHQ-9, PEG and EQ-5D(3L) shortly after being scheduled for surgery. Multivariate mixed-effects Poisson regression models were used to measure the association between preoperative patient-reported outcome measures and length of stay. RESULTS: Among the 183 patients eligible to participate, the participation rate was 48.5%. There were 89 participants. Participants reported a high level of preoperative ankle impairment and pain. The adjusted results found no relationship between the AOS, EQ-5D(3L) VAS or PHQ-9 values and participants' LOS. Participants with at least one chronic health condition and lowest SES category had longer LOS. CONCLUSIONS: This study found no evidence of an association between four PROs collected prior to AA or TAA with hospital LOS. This finding suggests collecting these PROs preoperatively may not help with discharge planning.

Validating the Foot and Ankle Outcome score for measuring foot dysfunction among hallux valgus surgery patients using item response theory.

BACKGROUND: There is an absence of high quality research validating instruments that measure foot and ankle related quality of life among hallux valgus (bunion) patients' perspectives. The Foot and Ankle Outcome Scale is a patient-reported outcome instrument, that when administered to patients with symptomatic hallux valgus, provides a patient-centric perspective of their foot function. The aim of this study is to assess the psychometric properties of the instrument's five subscales among preoperative bunion surgery patients. METHODS: The Foot and Ankle Outcome Scale instrument measures Pain, Symptoms, Activities of Daily Living, Sport and Recreational Activities and Foot/Ankle Related Quality of Life. Preoperative data is collected from a sample of patients scheduled for surgical treatment of their condition in Vancouver, Canada. Classical and item response theory methods are used to report on reliability, validity and differential item functioning among subgroups. RESULTS: This study included 249 surveys, representing an overall response rate of 44.1% among 564 eligible patients. The instrument demonstrated high reliability for all subscales, though 18 items across subscales, exhibited poor discrimination between item levels. Four items score differently according to patients' sex and one item scored differently by age. CONCLUSIONS: The instrument measures five domains of health important to bunion patients. These findings suggest that the current instrument can be used with an understanding of its limitations, including redundant questions and sex-based differences. Future research should revise a number of items. The results highlight the importance of the psychometric analyses of instruments in specific patient populations.

Improving health information systems during an emergency: lessons and recommendations from an Ebola treatment centre in Sierra Leone.

BACKGROUND: The 2014-2016 West Africa Ebola epidemic highlighted the difficulty of collecting patient information during emergencies, especially in highly infectious environments. Health information systems (HISs) appropriate for such settings were lacking prior to this outbreak. Here we describe our development and implementation of paper and electronic HISs at the Sierra Leone Kerry Town Ebola treatment centre (ETC) from 2014 to 2015. We share our approach, experiences, and recommendations for future health emergencies. METHODS: We developed eight fact-finding questions about data-related needs, priorities, and restrictions at the ETC ("inputs") to inform eight structural decisions ("outputs") across six core HIS components. Semi-structured interviews about the "inputs" were then conducted with HIS stakeholders, chosen based on their teams' involvement in ETC HIS-related activities. Their responses were used to formulate the "output" results to guide the HIS design. We implemented the HIS using an Agile approach, monitored system usage, and developed a structured questionnaire on user experiences and opinions. RESULTS: Some key "input" responses were: 1) data needs for priorities (patient care, mandatory reporting); 2) challenges around infection control, limited equipment, and staff clinical/language proficiencies; 3) patient/clinical flows; and 4) weak points from staff turnover, infection control, and changing protocols. Key outputs included: 1) determining essential data, 2) data tool design decisions (e.g. large font sizes, checkboxes/buttons), 3) data communication methods (e.g. radio, "collective memory"), 4) error reduction methods (e.g. check digits, pre-written wristbands), and 5) data storage options (e.g. encrypted files, accessible folders). Implementation involved building data collection tools (e.g. 13 forms), preparing the systems (e.g. supplies), training staff, and maintenance (e.g. removing old forms). Most patients had basic (100%, n = 456/456), drug (96.9%, n = 442/456), and additional clinical/epidemiological (98.9%, n = 451/456) data stored. The questionnaire responses highlighted the importance of usability and simplicity in the HIS. CONCLUSIONS: HISs during emergencies are often ad-hoc and disjointed, but systematic design and implementation can lead to high-quality systems focused on efficiency and ease of use. Many of the processes used and lessons learned from our work are generalizable to other health emergencies. Improvements should be started now to have rapidly adaptable and deployable HISs ready for the next health emergency.

Nonanimal Hyaluronic Acid for the Treatment of Ankle Osteoarthritis: AProspective, Single-Arm Cohort Study.

Ankle osteoarthritis (OA) can cause disabling symptoms, and some patients prefer to be treated with minimally invasive procedures. Nonanimal hyaluronic acid (NASHA) is a cross-linked hyaluronic acid product that has a prolonged intra-articular residence time. The authors report the first study of NASHA for the treatment of ankle OA. Thirty-seven patients with Kellgren-Lawrence grade II or III ankle OA received an intra-articular injection of NASHA (1 mL). Outcomes included visual analogue scale (VAS) scores for pain and disability. At baseline, the mean VAS pain score was 50.1 ± 14.5mm. During the 26-week follow-up period, the least squares (LS) mean change from baseline in the ankle OA VAS pain score was -20.5mm (95% confidence interval [CI] -25.5 to -15.6 mm), an LS mean percentage reduction of 40.0% (95% CI 30.2% to 49.9%). The LS mean change from baseline in the VAS disability score during 26 weeks was -19.2mm (95% CI -24.8 to -13.6 mm), a percentage reduction of 34% (95% CI 22.3% to 45.7%). Five participants experienced a total of 7 adverse events considered to be related to study treatment (injection site pain, n = 3; injection site joint pain, n = 3; plantar fasciitis, n = 1). This study shows promise for viscosupplementation with NASHA in the treatment of ankle OA. A single injection was associated with clinically meaningful reductions in pain and disability during a 26-week period and, in general, was well tolerated.

Development of a Pediatric Ebola Predictive Score, Sierra Leone1.

We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014-March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%-90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required.

Symptom- and Laboratory-Based Ebola Risk Scores to Differentiate Likely Ebola Infections.

Rapidly identifying likely Ebola patients is difficult because of a broad case definition, overlap of symptoms with common illnesses, and lack of rapid diagnostics. However, rapid identification is critical for care and containment of contagion. We analyzed retrospective data from 252 Ebola-positive and 172 Ebola-negative patients at a Sierra Leone Ebola treatment center to develop easy-to-use risk scores, based on symptoms and laboratory tests (if available), to stratify triaged patients by their likelihood of having Ebola infection. Headache, diarrhea, difficulty breathing, nausea/vomiting, loss of appetite, and conjunctivitis comprised the symptom-based score. The laboratory-based score also included creatinine, creatine kinase, alanine aminotransferase, and total bilirubin. This risk score correctly identified 92% of Ebola-positive patients as high risk for infection; both scores correctly classified >70% of Ebola-negative patients as low or medium risk. Clinicians can use these risk scores to gauge the likelihood of triaged patients having Ebola while awaiting laboratory confirmation.

Quantification of the risk of liver injury associated with flucloxacillin: a UK population-based cohort study.

Background: Flucloxacillin is an established cause of liver injury. Despite this, there are a lack of published data on both the strength of association after adjusting for potential confounders, and the absolute incidence among different subgroups of patients. Objectives: To assess the relative and absolute risks of liver injury following exposure to flucloxacillin and identify subgroups at potentially increased risk. Methods: A cohort study between 1 January 2000 and 1 January 2012 using the UK Clinical Practice Research Datalink, including 1 046 699 people with a first prescription for flucloxacillin (861 962) or oxytetracycline (184 737). Absolute risks of experiencing both symptom-defined (jaundice) and laboratory-confirmed liver injury within 1-45 and 46-90 days of antibiotic initiation were estimated. Multivariable logistic regression was used to estimate 1-45 day relative effects. Results: There were 183 symptom-defined cases (160 prescribed flucloxacillin) and 108 laboratory-confirmed cases (102 flucloxacillin). The 1-45 day adjusted risk ratio for laboratory-confirmed injury was 5.22 (95% CI 1.64-16.62) comparing flucloxacillin with oxytetracycline use. The 1-45 day risk of laboratory-confirmed liver injury was 8.47 per 100 000 people prescribed flucloxacillin (95% CI 6.64-10.65). People who received consecutive flucloxacillin prescriptions had a 1-45 day risk of jaundice of 39.00 per 100 000 (95% CI 26.85-54.77), while those aged >70 receiving consecutive prescriptions had a risk of 110.57 per 100 000 (95% CI 70.86-164.48). Conclusions: The short-term risk of laboratory-confirmed liver injury was >5-fold higher after a flucloxacillin prescription than an oxytetracycline prescription. The risk of flucloxacillin-induced liver injury is particularly high within those aged >70 and those who receive multiple flucloxacillin prescriptions. The stratified risk estimates from this study could help guide clinical care.