Beyond high-risk: analysis of the outcomes of extreme-risk patients in the National Emergency Laparotomy Audit.

Patients who require emergency laparotomy are defined as high risk if their 30-day predicted risk of mortality is ≥ 5%. Despite a large difference in the characteristics of patients with a mortality risk score of between 5% and 50%, these outcomes are aggregated by the National Emergency Laparotomy Audit (NELA). Our aim was to describe the outcomes of the cohort of patients at extreme risk of death, which we defined as having a NELA-predicted 30-day mortality of ≥ 50%. All patients enrolled in the NELA database between December 2012 and 2020 were included. We compared patient characteristics; length of hospital stay; rates of unplanned return to the operating theatre; and 90-day survival in extreme-risk groups (predicted ≥ 50%) and high-risk patients (predicted 5-49%). Of 161,337 patients, 5193 (3.2%) had a predicted mortality of ≥ 50%. When patients were further subdivided, 2437 (47%) had predicted mortality of 50-59% (group 50-59); 1484 (29%) predicted mortality of 60-69% (group 60-69); 840 (16%) predicted mortality of 70-79% (group 70-79); and 423 (8%) predicted mortality of ≥ 80% (group 80+). Extreme-risk patients were significantly more likely to have been admitted electively than high-risk patients (p < 0.001). Length of stay increased from a median (IQR [range]) of 26 (16-43 [0-271]) days in group 50-59 to 35 (21-56 [0-368]) days in group 80+, compared with 17 (10-30 [0-1136]) days for high-risk patients. Rates of unplanned return to the operating theatre were higher in extreme-risk groups compared with high-risk patients (11% vs. 8%). The 90-day survival was 43% in group 50-59, 34% in group 60-69, 27% in group 70-79 and 17% in group 80+. These data underscore the need for a differentiated approach when discussing risk with patients at extreme risk of mortality following an emergency laparotomy. Clinicians should focus on patient priorities on quantity and quality of life during informed consent discussions before surgery. Future work should extend beyond the immediate postoperative period to encompass the longer-term outcomes (survival and function) of patients who have emergency laparotomies.

The management of adult appendicitis during the COVID-19 pandemic: an interim analysis of a UK cohort study.

BACKGROUND: Acute appendicitis (AA) is the most common general surgical emergency. Early laparoscopic appendicectomy is the gold-standard management. SARS-CoV-2 (COVID-19) brought concerns of increased perioperative mortality and spread of infection during aerosol generating procedures: as a consequence, conservative management was advised, and open appendicectomy recommended when surgery was unavoidable. This study describes the impact of the first weeks of the pandemic on the management of AA in the United Kingdom (UK). METHODS: Patients 18 years or older, diagnosed clinically and/or radiologically with AA were eligible for inclusion in this prospective, multicentre cohort study. Data was collected from 23rd March 2020 (beginning of the UK Government lockdown) to 1st May 2020 and included: patient demographics, COVID status; initial management (operative and conservative); length of stay; and 30-day complications. Analysis was performed on the first 500 cases with 30-day follow-up. RESULTS: The patient cohort consisted of 500 patients from 48 sites. The median age of this cohort was 35 [26-49.75] years and 233 (47%) of patients were female. Two hundred and seventy-one (54%) patients were initially treated conservatively; with only 26 (10%) cases progressing to an operation. Operative interventions were performed laparoscopically in 44% (93/211). Median length of hospital stay was significantly reduced in the conservatively managed group (2 [IQR 1-4] days vs. 3 [2-4], p < 0.001). At 30 days, complications were significantly higher in the operative group (p < 0.001), with no deaths in any group. Of the 159 (32%) patients tested for COVID-19 on admission, only 6 (4%) were positive. CONCLUSION: COVID-19 has changed the management of acute appendicitis in the UK, with non-operative management shown to be safe and effective in the short-term. Antibiotics should be considered as the first line during the pandemic and perhaps beyond.

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Association between preadmission frailty and care level at discharge in older adults undergoing emergency laparotomy.

BACKGROUND: Older adults undergoing emergency abdominal surgery have significantly poorer outcomes than younger adults. For those who survive, the level of care required on discharge from hospital is unknown and such information could guide decision-making. The ELF (Emergency Laparotomy and Frailty) study aimed to determine whether preoperative frailty in older adults was associated with increased dependence at the time of discharge. METHODS: The ELF study was a UK-wide multicentre prospective cohort study of older patients (65 years or more) undergoing emergency laparotomy during March and June 2017. The objective was to establish whether preoperative frailty was associated with increased care level at discharge compared with preoperative care level. The analysis used a multilevel logistic regression adjusted for preadmission frailty, patient age, sex and care level. RESULTS: A total of 934 patients were included from 49 hospitals. Mean(s.d.) age was 76·2(6·8) years, with 57·6 per cent women; 20·2 per cent were frail. Some 37·4 per cent of older adults had an increased care level at discharge. Increasing frailty was associated with increased discharge care level, with greater predictive power than age. The adjusted odds ratio for an increase in care level was 4·48 (95 per cent c.i. 2·03 to 9·91) for apparently vulnerable patients (Clinical Frailty Score (CFS) 4), 5·94 (2·54 to 13·90) for those mildly frail (CFS 5) and 7·88 (2·97 to 20·79) for those moderately or severely frail (CFS 6 or 7), compared with patients who were fit. CONCLUSION: Over 37 per cent of older adults undergoing emergency laparotomy required increased care at discharge. Frailty scoring was a significant predictor, and should be integrated into all acute surgical units to aid shared decision-making and discharge planning.

ANTECEDENTES: Los adultos mayores sometidos a cirugía abdominal de urgencia tienen resultados significativamente peores que los adultos jóvenes. Para aquellos pacientes que sobreviven, el nivel de atención que requieren tras el alta hospitalaria se desconoce y esta información podría servir de guía en la toma de decisiones. El estudio ELF (Emergency Laparotomy and Frailty) tenía como objetivo determinar si la fragilidad preoperatoria en adultos mayores se asociaba con un aumento de la dependencia en el momento del alta. MÉTODOS: El estudio ELF era un estudio multicéntrico extenso efectuado en el Reino Unido (n = 49) que incluyó una cohorte prospectiva de 934 pacientes mayores (> 65 años) sometidos a laparotomía de urgencia durante marzo-junio de 2017. El objetivo fue establecer si la fragilidad preoperatoria aumentaba el nivel de asistencia en el momento del alta en comparación con el nivel de asistencia preoperatorio. Para el análisis se utilizó una regresión logística multinivel ajustada a características previas al ingreso: fragilidad, edad del paciente, género, y nivel de asistencia. RESULTADOS: La edad media de los pacientes fue 76,2 años (DE = 6,83), con un 57% de mujeres, un 20,2% de pacientes frágiles y un 37,4% de adultos mayores que presentaron un aumento en el nivel de asistencia en el momento del alta. Un aumento de la fragilidad se asoció con un incremento en el nivel de asistencia en el momento del alta (y mayor poder predictivo que la edad). La razón de oportunidades (odds ratio, OR) ajustada por el aumento del nivel de asistencia fue 4,48 (i.c. del 95% 2,03-9,91) para pacientes aparentemente vulnerables (Clinical Frailty Scale, CFS 4); 5,94 (i.c. del 95% 2,54-13,90) para aquellos ligeramente frágiles (CFS 5); y 7,88 (i.c. del 95% 2,97-20,79) para aquellos con fragilidad moderada o grave (CFS 6 and 7) en comparación con pacientes en buenas condiciones. CONCLUSIÓN: Este es el primer estudio que documenta que más del 37% de adultos mayores sometidos a laparotomía de urgencia precisaron un aumento en el nivel de asistencia en el momento del alta. La evaluación de la fragilidad debería integrarse en todas las unidades quirúrgicas de agudos para ayudar a compartir la toma de decisiones y los planes de tratamiento.

Frailty predicts mortality in all emergency surgical admissions regardless of age. An observational study.

BACKGROUND: frail patients in any age group are more likely to die than those that are not frail. We aimed to evaluate the impact of frailty on clinical mortality, readmission rate and length of stay for emergency surgical patients of all ages. METHODS: a multi-centre prospective cohort study was conducted on adult admissions to acute surgical units. Every patient presenting as a surgical emergency to secondary care, regardless of whether they ultimately underwent a surgical procedure was included. The study was carried out during 2015 and 2016.Frailty was defined using the 7-point Clinical Frailty Scale. The primary outcome was mortality at Day 90. Secondary outcomes included: mortality at Day 30, length of stay and readmission within a Day 30 period. RESULTS: the cohort included 2,279 patients (median age 54 years [IQR 36-72]; 56% female). Frailty was documented in patients of all ages: 1% in the under 40's to 45% of those aged 80+. We found that each incremental step of worsening frailty was associated with an 80% increase in mortality at Day 90 (OR 1.80, 95% CI: 1.61-2.01) supporting a linear dose-response relationship. In addition, the most frail patients were increasingly likely to stay in hospital longer, be readmitted within 30 days, and die within 30 days. CONCLUSIONS: worsening frailty at any age is associated with significantly poorer patient outcomes, including mortality in unselected acute surgical admissions. Assessment of frailty should be integrated into emergency surgical practice to allow prognostication and implementation of strategies to improve outcomes.

Multicentre observational study of outcomes after drainage of acute perianal abscess.

INTRODUCTION: Management of perianal abscesses has remained largely unchanged for over 50 years. The evidence for postoperative wound packing is limited and may expose patients to painful procedures with no clinical benefit and at considerable increased cost. METHODS: Patients were recruited in 15 UK centres between December 2013 and October 2014. Outcome measures included number of dressing (pack) changes, healing, recurrence, return to work/normal function, postoperative fistula in ano and health utility scores (EQ-5D™). Pain was measured before, during and after dressing change on a visual analogue scale. RESULTS: Some 141 patients were recruited (median age 39 (range 18-86) years). The mean number of dressing changes in the first 3 weeks was 13 (range 0-21), equating to an annual cost to the National Health Service of €6 453 360 in England alone per annum. Some 43·8 per cent of wounds were healed by 8 weeks after surgery and 86 per cent of patients had returned to normal function. Some 7·6 per cent of abscesses had recurred and 26·7 per cent of patients developed a fistula in ano by 6 months following surgery. Patients reported a twofold to threefold increase in pain scores during and after dressing changes. CONCLUSION: Recurrent abscess is rare and fistula occurs in one-quarter of the patients. Packing is painful and costly.

Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.

BACKGROUND: Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. METHODS: In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130-149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306. FINDINGS: 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137-139) in the higher-target group and 127 mm Hg (95% CI 126-128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64-1·03, p=0·08), disabling or fatal stroke (0·81, 0·53-1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68-1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15-0·95, p=0·03). Treatment-related serious adverse events were infrequent. INTERPRETATION: Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial. FUNDING: National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS).

The influence of frailty on outcomes for older adults admitted to hospital with benign biliary disease: a single-centre, observational cohort study.

INTRODUCTION: The prevalence and complications of biliary disease increase with age. Frailty has been associated with adverse outcomes in the hospital setting. We describe the prevalence of frailty in older patients hospitalised with benign biliary disease and its association with duration of hospital stay, and 90-day and 1-year mortality. METHODS: We performed a retrospective cohort study of patients aged 75 years and over admitted with acute biliary disease between 17 September 2014 and 20 March 2017. Clinical Frailty Scale (CFS) score was recorded on admission. RESULTS: We included 200 patients with a median age of 82 (75-99) years, 60% were female; 154 (77%) were independent for personal activities of daily living (ADLs) and 99 (49.5%) for instrumental ADLs. Cholecystitis was the most common diagnosis (43%) followed by cholangitis (36%) and pancreatitis (21%). Ninety-nine patients were non frail (NF; CFS 1-4) and 101 were frail (F; CFS 5-9). Some 104 patients received medical treatment only. Surgery was more common in NF patients (11% vs F 2%), percutaneous drainage more frequently performed in F patients (15% vs NF 5%) and endoscopic cholangiopancreatography was similar in both groups (F 32% vs NF 31%). Frailty was associated with worse clinical outcomes in F vs NF: functional deconditioning (34% vs 11%), increased care level (19% vs 3%), length of stay (12 vs 7 days), 90-day mortality (8% vs 3%) and 1-year mortality (48% vs 24%). CONCLUSIONS: Half of patients in our cohort were frail and spent longer in hospital, were less likely to undergo surgery and were less likely to remain alive at 1 year after discharge.

Pasteurization of milk: the heat inactivation kinetics of milk-borne dairy pathogens under commercial-type conditions of turbulent flow.

This is the first study to report kinetic data on the survival of a range of significant milk-borne pathogens under commercial-type pasteurization conditions. The most heat-resistant strain of each of the milk-borne pathogens Staphylococcus aureus, Yersinia enterocolitica, pathogenic Escherichia coli, Cronobacter sakazakii (formerly known as Enterobacter sakazakii), Listeria monocytogenes, and Salmonella was selected to obtain the worst-case scenario in heat inactivation trials using a pilot-plant-scale pasteurizer. Initially, approximately 30 of each species were screened using a submerged coil unit. Then, UHT milk was inoculated with the most heat-resistant pathogens at ~10(7)/mL and heat treated in a pilot-plant-scale pasteurizer under commercial-type conditions of turbulent flow for 15s over a temperature range from 56 to 66°C and at 72°C. Survivors were enumerated on nonselective media chosen for the highest efficiency of plating of heat-damaged bacteria of each of the chosen strains. The mean log(10) reductions and temperatures of inactivation of the 6 pathogens during a 15-s treatment were Staph. aureus >6.7 at 66.5°C, Y. enterocolitica >6.8 at 62.5°C, pathogenic E. coli >6.8 at 65°C, C. sakazakii >6.7 at 67.5°C, L. monocytogenes >6.9 at 65.5°C, and Salmonella ser. Typhimurium >6.9 at 61.5°C. The kinetic data from these experiments will be used by the New Zealand Ministry of Agriculture and Forestry to populate the quantitative risk assessment model being developed to investigate the risks to New Zealand consumers from pasteurized, compared with nonpasteurized, milk and milk products.

The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers.

OBJECTIVE: To investigate if a lower dose of arginine in the form of an oral nutritional supplement can show similar benefit in the healing rate of pressure ulcers compared with the current evidence for 9g of arginine. METHOD: Twenty-three inpatients with category II, III or IV pressure ulcers were randomised to receive daily, for 3 weeks, the standard hospital diet plus 4.5 or 9g arginine in the form of a commercial supplement. Pressure ulcer size and severity was measured weekly (by PUSH tool; pressure ulcer scale for healing; 0= completely healed, 17= greatest severity). Nutritional status was determined by Subjective Global Assessment. RESULTS: There were no significant differences in patients' age, gender, BMI, haemoglobin levels, albumin levels and diagnosis of diabetes between treatment groups. There was a significant decrease in pressure ulcer severity over time (p < 0.001), with no evidence of a difference in healing rate between the two arginine dosages (p=0.991). Based on expected healing time, patients in both treatment groups were estimated to achieve an almost 2-fold improvement compared with the historical control group. Patients categorised as malnourished showed clinically significant impaired healing rates compared with well nourished patients (p=0.057), although this was unaffected by arginine dosage (p=0.727). CONCLUSION: Similar clinical benefits in healing of pressure ulcers can be achieved with a lower dosage of arginine, which can translate into improved concordance and significant cost-savings for both the health-care facilities and for patients.

Fine-tuned long-acting interleukin-2 superkine potentiates durable immune responses in mice and non-human primate.

BACKGROUND: Recombinant human interleukin-2 (rhIL-2, aldesleukin) is Food and Drug Administration approved for the treatment of metastatic melanoma and renal cell carcinoma and has achieved durable response in a subset of patients. However, its utility as an immunotherapeutic drug is limited by undesirable activation of immune suppressive regulatory T cells (Tregs) and a short half-life requiring frequent high dose administration, leading to unacceptable toxicities. We have engineered MDNA11, a long-acting IL-2 superkine, to overcome these limitations by (1) modifying receptor selectivity in favor of anti-cancer immune cells to increase therapeutic efficacy and (2) fusion to human albumin to extend the pharmacokinetic (PK) profile, circumventing the need for frequent dosing. METHODS: MDNA11 was evaluated using in vitro and in vivo studies including: binding analyses to measure receptor affinity, IL-2 pathway signaling, PK studies in mice, and efficacy studies in syngeneic tumor models as single agent and in combination with immune checkpoint inhibitors. Finally, the safety and pharmacodynamic profile of MDNA11 was assessed in non-human primate (NHP). RESULTS: Binding studies with MDNA11 demonstrated increased affinity for IL-2Rß (CD122) and no binding to IL-2Rα (CD25). As a result, MDNA11 exhibits reduced/limited Treg stimulation while triggering an enhanced activation of natural killer and naïve CD8 T cells compared with rhIL-2. When administered to animals with pre-established tumors, MDNA11 controlled tumor growth in a monotherapy setting and in combination with anti-PD1 or anti-CTLA4 to induce durable tumor clearance with a once weekly dosing regimen. In a NHP model, MDNA11 was well tolerated while triggering durable and potent immune responses including expansion of lymphocytes without significant effect on Tregs and eosinophils, the latter been linked to an increased risk of vascular leak syndrome. CONCLUSION: MDNA11 is a next generation long-acting IL-2 immunotherapeutic with a highly favorable pharmacodynamic profile that translates to a strong therapeutic efficacy in preclinical tumor models and a strong and durable immune response in NHP.

Characterizing a New Fluorescent Protein for a Low Limit of Detection Sensing in the Cell-Free System.

Cell-free protein synthesis-based biosensors have been developed as highly accurate, low-cost biosensors. However, since most biomarkers exist at low concentrations in various types of biopsies, the biosensor's dynamic range must be increased in the system to achieve low limits of detection necessary while deciphering from higher background signals. Many attempts to increase the dynamic range have relied on amplifying the input signal from the analyte, which can lead to complications of false positives. In this study, we aimed to increase the protein synthesis capability of the cell-free protein synthesis system and the output signal of the reporter protein to achieve a lower limit of detection. We utilized a new fluorescent protein, mNeonGreen, which produces a higher output than those commonly used in cell-free biosensors. Optimizations of DNA sequence and the subsequent cell-free protein synthesis reaction conditions allowed characterizing protein expression variability by given DNA template types, reaction environment, and storage additives that cause the greatest time constraint on designing the cell-free biosensor. Finally, we characterized the fluorescence kinetics of mNeonGreen compared to the commonly used reporter protein, superfolder green fluorescent protein. We expect that this finely tuned cell-free protein synthesis platform with the new reporter protein can be used with sophisticated synthetic gene circuitry networks to increase the dynamic range of a cell-free biosensor to reach lower detection limits and reduce the false-positive proportion.

Development and validation of health system performance measures for opioid use disorder in British Columbia, Canada.

BACKGROUND: Performance measurement provides an evidence-based means to inform development of interventions to improve the quality of care for people who use opioids. We aimed to develop and assess the predictive validity of health system performance measures for opioid use disorder (OUD) in British Columbia (BC), Canada. METHODS: Performance measures were generated using retrospective population-level administrative datasets (both provincial and regional) and publicly-reported retrospective data according to four domains (care engagement, clinical guideline compliance, integration, and healthcare utilization). The adjusted odds ratio was estimated via generalized linear mixed models to determine predictive validity for all-cause hospitalization or mortality within 6 months of measurement. FINDINGS: A total of 102 performance measures were constructed. We identified 55,470 diagnosed PWOUD, and 39,456 ever engaged in opioid agonist treatment (OAT). We found divergent rates of treatment for concurrent conditions (7.4% for alcohol use disorder to 80.1% for HIV/AIDS), low levels of linkage to OAT and other outpatient care following acute care, and increasing levels of service provision, including increases in OAT prescribers and pharmacies, naloxone kit distribution and overdose prevention site visitation. Our analyses on the predictive validity measures largely supported a priori hypotheses on the direction of effect on the outcome. CONCLUSIONS: We identified a range of priorities to improve the quality of care for PWOUD, with critical gaps in linkage to care through acute care settings and long-term engagement in OAT. The proposed measures can be derived for geographic and clinical subgroups and updated over time, providing a basis to monitor and evaluate efforts to address the public health burden of OUD.

Effect of an arginine-containing nutritional supplement on pressure ulcer healing in community spinal patients.

OBJECTIVE: To determine whether or not the use of an arginine-containing nutritional supplement could result in significantly shorter pressure ulcer (PU) healing times in people with spinal cord injuries living in the community, compared with a comparative historical control group. METHOD: Eighteen spinal-cord-injured patients (all part of a hospital spinal outreach service) received 9 g of a commercial powdered arginine supplement per day until full PU healing occurred. Healing rates were compared against 17 historical control patients (as assessed by medical history audit). RESULTS: Baseline characteristics (age, gender, injury level and time) were similar between groups. Mean ulcer healing times were 10.5 +/- 1.3 weeks versus 21 +/- 3.7 weeks (p<0.05) in the intervention and control groups respectively. Comparison of healing rates in the intervention group against expected healing rates derived from the medical literature showed that intervention patients had a significantly shorter mean healing time (category 2 PU: 5.5+/-1.3 weeks versus 13.4 weeks; category 3 PU: 12.5 +/- 1.9 weeks versus 18.2 weeks; category 4 PU: 14.4 +/- 4.8 weeks versus 22.1 weeks). A diagnosis of diabetes did not significantly alter healing rates in either group. CONCLUSION: Results from this observational study show a promising benefit of arginine supplementation on PU healing for individuals with spinal cord injury living in the community.

Determinants of selection into buprenorphine/naloxone among people initiating opioid agonist treatment in British Columbia.

BACKGROUND: Studies assessing the comparative effectiveness of methadone versus buprenorphine/naloxone for opioid use disorder in real-world settings are rare - challenged by structural differences in delivery across settings and factors influencing treatment selection. We identified determinants of selection into buprenorphine/naloxone and quantified contributions of individual and provider-level covariates in a setting delivering both medications within the same healthcare settings. METHODS: Utilizing linked health administrative datasets, we conducted a retrospective cohort study of people with opioid use disorder (PWOUD) receiving opioid agonist treatment (OAT) in British Columbia, Canada, from 2008-2017. Determinants of buprenorphine/naloxone selection were identified using a generalized linear mixed model with random intercept terms for providers and individuals. We determined the influence of individual demographics, clinical history, measures of provider experience and preference, and dates of key policy changes. RESULTS: A total of 39,605 individuals experienced 178,976 OAT episodes (methadone:139,439(77.9 %);buprenorphine/naloxone:39,537(22.1 %)). Male sex, less OAT experience, younger age, mental health conditions and chronic pain were associated with higher odds of buprenorphine/naloxone prescription. For providers, higher client-attachment, more complex OAT case-mixes, and higher buprenorphine/naloxone prescribing-preference were also associated with higher odds of buprenorphine/naloxone prescription. Observed individual-level covariates explained 9.7 % of variance in odds of buprenorphine/naloxone selection, while observed provider-level covariates explained 20.0 %. Controlling for covariates, residual unmeasured between-individual variance accounted for 18.5 % of the explained variation in the odds of buprenorphine/naloxone selection, while unmeasured between-provider variance accounted for 28.4 %. CONCLUSION: Provider characteristics were more influential in selection of buprenorphine/naloxone over methadone informing subsequent analyses of comparative effectiveness of these regimens.

Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople).

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.