Reduction of early surgical site and other care related infections in 3553 hip fracture patients: lessons learned from the 5-year Safe Hands project.

BACKGROUND: Surgical site infection (SSI) after acute hip fracture surgery is a devastating complication associated with increased suffering and mortality. The aim of the study was to investigate early SSI, sepsis, pneumonia and urinary tract infections over five years, before and after the implementation of the Safe Hands project. METHODS: This was a single-centre observational study with a 5-year longitudinal design, investigating the effects of an infection-prevention intervention targeting the clinical care pathway of individuals with acute hip fracture. Statistical analyses were based on routinely collected patient outcome data comprising 3553 patients. The study conforms to the criteria of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). RESULTS: The incidence of early SSIs decreased from 2.5% in years 1-2 to 1.1% in years 4-5. Similar results were observed for sepsis (2.7% to 1.3%) and urinary tract infections (14.2% to 4.2%). The multivariable regression results suggest that, for every observed year, the odds of early SSIs decreased. Male gender, procedure time, sepsis and preoperative skin damage increased the odds significantly. CONCLUSIONS: Our preventive bundle, based on partnership between researchers, managers and clinicians and a strong commitment to change from the involved professions, appear to be effective in reducing the frequency of potentially devastating SSIs and other hospital acquired infections after hip fracture surgery. The use of external and internal facilitators was crucial to enable individual and organisational learning and overcoming barriers to improvements. TRIAL REGISTRATION: Clinical Trials.gov ID: NCT02983136 Registered 6 December 2016-Retrospectively registered.

Determination of risk factors of postoperative pneumonia in elderly patients with hip fracture: What can we do?

BACKGROUND: Postoperative pneumonia is a serious complication in elderly patients with hip fracture. It is necessary to identify the influencing factors of postoperative pneumonia in patients with hip fracture. METHODS: Elderly patients with hip fractures admitted to a tertiary hospital in China from January 1, 2020 to August 31, 2021 were included. The characteristics of patients with and without postoperative pneumonia were evaluated and compared. Logistic multivariate regression analyses were conducted to assess the risk factors of postoperative pneumonia. RESULTS: 267 patients with hip fracture were included, the incidence of postoperative pneumonia in patients with hip fracture was 13.11%. There were significant differences in the age, diabetes mellitus, anemia, hypoalbuminemia, anesthesia method and duration of surgery between infection and no infection group, no significant differences in the gender, BMI, hypertension, hyperlipidemia, type of fracture, preoperative oxygen saturation, white blood cell count, platelet count, red blood cell count, creatinine, alanine aminotransferase, aspartate aminotransferase, estimated blood loss during surgery were detected between infection and no infection group. Logistic regression analysis showed that age≥70y (OR2.326, 95%CI1.248~3.129), diabetes mellitus (OR2.123, 95%CI1.021~3.551), anemia (OR3.199,95%CI1.943~5.024), hypoalbuminemia (OR2.377, 95%CI1.211~3.398), general anesthesia (OR1.947, 95%CI1.115~3.038), duration of surgery≥120min (OR1.621, 95%CI1.488~2.534) were the risk factors of postoperative pneumonia in elderly patients with hip fracture (all p<0.05). Escherichia Coli (33.33%), Klebsiella pneumoniae (28.57%), Staphylococcus aureus (21.43%) were the most common bacteria of pulmonary infection. CONCLUSION: There are many risk factors for postoperative pneumonia in elderly patients with hip fractures after surgery. In clinical practice, medical workers should take targeted interventions for those risk factors to reduce postoperative pneumonia.

Surgical treatment for fragility hip fractures during the COVID-19 pandemic resulted in lower short-term postoperative functional outcome and a higher complication rate compared to the pre-pandemic period.

The COVID-19 pandemic adversely affected the functional outcomes of fragility hip fracture patients. This study revealed a higher in-hospital complication rate and lower postoperative function at 3 months among patients treated during the pandemic. Therefore, modified in-hospital and post-discharge protocols should be developed for implementation during pandemic crisis periods. INTRODUCTION: This study aims to investigate the in-hospital complication rate and short-term postoperative functional outcomes of fragility hip fracture (FHF) patients compared between during the COVID-19 pandemic and the same 14-month time period 1 year prior to the pandemic. METHODS: Using data from the Siriraj Fracture Liaison Service registry, FHF patients treated during the COVID-19 pandemic (1 March 2020 to 30 April 2021) were time-matched with FHF patients treated during the pre-pandemic period (1 March 2018 to 30 April 2019). We collected the rate of in-hospital postoperative complications and the postoperative functional outcomes at discharge and 3 months as measured by the Barthel Index (BI) and EuroQol visual analog scale (EQ-VAS). Functional outcome measures were compared between the pre-pandemic and pandemic periods. RESULTS: There were 197 and 287 patients in the pre-pandemic and pandemic groups, respectively. At the 3-month postoperative follow-up, the mean postoperative BI score and change in BI score were both significantly lower in the pandemic group indicating poorer postoperative function. Moreover, FHF patients treated during the pandemic had significantly more in-hospital complications (36.6% vs. 22.8%, p = 0.002). There was no significant difference in the 3-month EQ-VAS or change in the EQ-VAS between groups. CONCLUSION: The results of this study revealed a higher in-hospital complication rate and lower postoperative function at 3 months among FHF patients treated during the COVID-19 pandemic compared to the pre-pandemic period. Therefore, modified in-hospital and post-discharge protocols should be developed for implementation during pandemic crisis periods.

The tolerance of physiotherapy treatment in patients with COVID-19 and undergoing surgery for fragility hip fracture: An observational study.

ABSTRACT: The aim of the present work was to evaluate the tolerance of physiotherapy treatment implemented for patients with coronavirus disease (COVID-19) and undergoing hip surgeryCase-control study. During the period between March and May 2020, 9 patients were enrolled in the study with diagnosis of COVID-19 and hip fracture. In order to evaluate the tolerability of physiotherapy treatment a comparison group, involving 27 patients with a hip fracture but in the absence of suspicion of COVID-19 positivity, were put together. Blood saturation and heart rate, number of physiotherapy sessions, start of physiotherapy from surgery, number of healthcare providers, recovery of ambulation, execution of walking training and dyspnea measured by Borg scale were collected before and after each single physiotherapy session to describe the exercise tolerance of the patients.There are no significant differences between the two groups regarding basic characteristics. Average of Borg scale post treatment for COVID patients was 1.3 (DS = 1.3) compared to 0.6 (DS = 0.7) of non-COVID patients (P < .0005) but the breathing difficulty was light during the treatment, only 9% of COVID patients had a worsening superior of two points with Borg scale compared to 3% of non-COVID patients (P = .138). The incidence of walking recovery was 63% in the non-COVID patients group compared to 44.4% in the COVID group (P = .329).Physiotherapy treatment of patients with COVID-19 infection and undergoing surgery for hip fracture is well tolerated and should be encouraged and well monitored.

COVID-19 infection is related to differences in the use of personal protective equipment by orthopaedic specialist trainees caring for hip fracture patients during the second surge of COVID-19 in the North West of England.

INTRODUCTION: Personal protective equipment (PPE) may protect health-care workers from COVID-19 infection and limit nosocomial spread to vulnerable hip fracture patients. METHODS: We performed a cross-sectional survey amongst orthopaedic trainees to explore PPE practice in 19 hospitals caring for hip fracture patients in the North West of England. RESULTS: During the second wave of the pandemic, 14/19 (74%) hospitals experienced an outbreak of COVID-19 amongst staff or patients on the orthopaedic wards. An FFP3 respirator mask was used by doctors in only 6/19 (32%) hospitals when seeing patients with COVID-19 and a cough and in 5/19 (26%) hospitals when seeing asymptomatic patients with COVID-19. A COVID-19 outbreak was reported in 11/13 (85%) orthopaedic units where staff wore fluid resistant surgical masks compared to 3/6 (50%) units using an FFP3 respirator mask (RR 1.69, 95% CI 0.74-3.89) when caring for symptomatic patients with COVID-19. Similarly, a COVID-19 outbreak was reported in more orthopaedic units caring for asymptomatic patients with COVID-19 where staff wore fluid resistant surgical masks (12/14 (86%)) as compared to an FFP3 respirator mask (2/5 (40%)) (RR 2.14, 95% CI 0.72-6.4). CONCLUSION: Urgent re-evaluation of PPE use is required to reduce nosocomial spread of COVID-19, amongst highly vulnerable patients with hip fracture.

Meta-analysis and metaregression of risk factors associated with mortality in hip fracture patients during the COVID-19 pandemic.

Incidence of hip fractures has remained unchanged during the pandemic with overlapping vulnerabilities observed in patients with hip fractures and those infected with COVID-19. We aimed to investigate the independent impact of COVID-19 infection on the mortality of these patients. Healthcare databases were systematically searched over 2-weeks from 1st-14th November 2020 to identify eligible studies assessing the impact of COVID-19 on hip fracture patients. Meta-analysis of proportion was performed to obtain pooled values of prevalence, incidence and case fatality rate of hip fracture patients with COVID-19 infection. 30-day mortality, excess mortality and all-cause mortality were analysed using a mixed-effects model. 22 studies reporting 4015 patients were identified out of which 2651 (66%) were assessed during the pandemic. An excess mortality of 10% was seen for hip fractures treated during the pandemic (OR 2.00, p = 0.007), in comparison to the pre-pandemic controls (5%). Estimated mortality of COVID-19 positive hip fracture patients was four-fold (RR 4.59, p < 0.0001) and 30-day mortality was 38.0% (HR 4.73, p < 0.0001). The case fatality rate for COVID-19 positive patients was 34.74%. Between-study heterogeneity for the pooled analysis was minimal (I2 = 0.00) whereas, random effects metaregression identified subgroup heterogeneity for male gender (p < 0.001), diabetes (p = 0.002), dementia (p = 0.001) and extracapsular fractures (p = 0.01) increased risk of mortality in COVID-19 positive patients.

The effect of the COVID-19 lockdown on the epidemiology of hip fractures in the elderly: a multicentre cohort study.

INTRODUCTION: The COVID-19 pandemic presented extraordinary challenges to the UK healthcare system. This study aimed to assess the impact of the COVID-19 lockdown on the epidemiology, treatment pathways and 30-day mortality rates of hip fractures. Outcomes of COVID-19 positive patients were compared against those who tested negative. METHODS: An observational, retrospective, multicentre study was conducted across six hospitals in the South East of England. Data were retrieved from the National Hip Fracture Database and electronic medical records. Data was collected for the strictest UK lockdown period (period B=23 March 2020-11 May 2020), and the corresponding period in 2019 (period A). RESULTS: A total of 386 patients were admitted during period A, whereas 381 were admitted during period B. Despite the suspension of the 'Best Practice Tariff' during period B, time to surgery, time to orthogeriatric assessment, and 30-day mortality were similar between period A and B. The length of inpatient stay was significantly shorter during period B (11.5 days vs 17.0 days, p<0.001). Comparison of COVID-19 positive and negative patients during period B demonstrated that a positive test was associated with a significantly higher rate of 30-day mortality (53.6% vs 6.7%), surgical delay >36h (46.4% vs 30.8%, p=0.049), and increased length of inpatient stay (15.8 vs 11.7 days, p=0.015). CONCLUSIONS: The COVID-19 lockdown did not alter the epidemiology of hip fractures. A substantially higher mortality rate was observed among patients with a COVID-19 positive test. These findings should be taken into consideration by the healthcare policymakers while formulating contingency plans for a potential 'second wave'.

Effect of Covid-19 on best practice care of hip fracture patients: An analysis from the National Hip Fracture Database (NHFD).

BACKGROUND: Best practice tariff (BPT) has brought significant improvements in hip fracture care; the 2019 report showing a 30-day mortality of 6.1%. Data relating to more than 65,000 patients who sustain a fractured neck of femur (FNOF) are recorded each year in the National Hip Fracture Database (NHFD). The aim of our study was to review the impact of COVID-19 on BPT. METHODS: Data was extracted from the NHFD for England, Wales and Northern Ireland. The months of March to June 2020 (lockdown period related to COVID-19) were compared to the same period in 2019. Data used in this study was collated and analysed between 14th and 17th October 2020. RESULTS: Data for more than 40,000 patients was reviewed. BPT dropped -4.3% in March, -12.6% in April, -12.9% in May 2020, and -7.2% in June. Prompt surgery remained stable (four-month average + 0.1%). The most significant changes were noted for timely orthogeriatric review (-7.6%, p < 0.001), bone health assessment (-7.3%, p < 0.001) and post-operative delirium assessment (-6.6%, p < 0.001). 30-day mortality increased to 13.7% in March 2020 and remained high in April 2020 (11.3%) and May (7.3%). Acute hospital length of stay was lowest in May 2020 (11.7 days). CONCLUSION: Patients sustaining FNOF in March 2020 had an associated 30-day mortality of 13.7%. During the COVID-19 pandemic, there was a significant reduction in BPT. The most significant changes were observed in timely orthogeriatric review. Maintaining a high standard of multidisciplinary care for this vulnerable group of patients is crucial during future spikes of COVID-19.

Study protocol for a multicentre, 2×2 factorial, randomised, controlled trial evaluating the interest of intravenous iron and tranexamic acid to reduce blood transfusion in hip fracture patients (the HiFIT study).

INTRODUCTION: Blood transfusion and anaemia are frequent and are associated with poor outcomes in patients with hip fracture (HF). We hypothesised that preoperative intravenous iron and tranexamic acid (TXA) may reduce the transfusion rate in these patients. METHODS AND ANALYSIS: The HiFIT study is a multicentre, 2×2 factorial, randomised, double-blinded, controlled trial evaluating the effect of iron isomaltoside (IIM) (20 mg/kg) vs placebo and of TXA (intravenously at inclusion and topically during surgery) versus placebo on transfusion rate during hospitalisation, in patients undergoing emergency surgery for HF and having a preoperative haemoglobin between 95 and 130 g/L. 780 patients are expected. The primary endpoint is the proportion of patients receiving an allogenic blood transfusion of packed red blood cells from the day of surgery until hospital discharge (or until D30 if patient is still hospitalised). Enrolment started on March 2017 in 11 French hospitals. The study was stopped between July 2017 and August 2018 (because of investigation of serious AEs with IIM in Spain) and slowed down since March 2020 (COVID-19 crisis). The expected date of final follow-up is May 2022. Analyses of the intent-to-treat and per-protocol populations are planned. ETHICS AND DISSEMINATION: The HiFIT trial protocol has been approved by the Ethics Committee of Comité de Protection des Personnes Ouest II and the French authorities (ANSM). It will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The HiFIT trial will be the largest study evaluating iron and TXA in patients with HF. TRIAL REGISTRATION NUMBER: clinicalTrials.gov identifier: NCT02972294; EudraCT Number 2016-003087-40.

Hip fracture in elderly and COVID-19 infection. Report of 3 cases. / Fractura de cadera en el anciano e infección por COVID-19. Descripción de 3 casos.

Since its first description in china in January 2020, COVID-19 pandemia outbreak has affected health organization and conventional care in all settings as wards, intensive care and surgery. Hip fracture patients usually are older and have a lot of comorbidities. This type of patientes benefit from early surgery. However, surgery in COVID-19 patients with active infection is associate with bad outcomes and mortality. We present three patients with COVID infection undergoing hip fracture surgery. Surgery was performed tree weeks after admission. Despite have risk factor (old age, arterial hypertension, elevated inflammatory parameters) the outcome was good and were discharged from hospital without events.

IMPACT-Restart: the influence of COVID-19 on postoperative mortality and risk factors associated with SARS-CoV-2 infection after orthopaedic and trauma surgery.

AIMS: The primary aim of this study was to assess the independent association of the coronavirus disease 2019 (COVID-19) on postoperative mortality for patients undergoing orthopaedic and trauma surgery. The secondary aim was to identify factors that were associated with developing COVID-19 during the postoperative period. METHODS: A multicentre retrospective study was conducted of all patients presenting to nine centres over a 50-day period during the COVID-19 pandemic (1 March 2020 to 19 April 2020) with a minimum of 50 days follow-up. Patient demographics, American Society of Anesthesiologists (ASA) grade, priority (urgent or elective), procedure type, COVID-19 status, and postoperative mortality were recorded. RESULTS: During the study period, 1,659 procedures were performed in 1,569 patients. There were 68 (4.3%) patients who were diagnosed with COVID-19. There were 85 (5.4%) deaths postoperatively. Patients who had COVID-19 had a significantly lower survival rate when compared with those without a proven SARS-CoV-2 infection (67.6% vs 95.8%, p < 0.001). When adjusting for confounding variables (older age (p < 0.001), female sex (p = 0.004), hip fracture (p = 0.003), and increasing ASA grade (p < 0.001)) a diagnosis of COVID-19 was associated with an increased mortality risk (hazard ratio 1.89, 95% confidence interval (CI) 1.14 to 3.12; p = 0.014). A total of 62 patients developed COVID-19 postoperatively, of which two were in the elective and 60 were in the urgent group. Patients aged > 77 years (odds ratio (OR) 3.16; p = 0.001), with increasing ASA grade (OR 2.74; p < 0.001), sustaining a hip (OR 4.56; p = 0.008) or periprosthetic fracture (OR 14.70; p < 0.001) were more likely to develop COVID-19 postoperatively. CONCLUSION: Perioperative COVID-19 nearly doubled the background postoperative mortality risk following surgery. Patients at risk of developing COVID-19 postoperatively (patients > 77 years, increasing morbidity, sustaining a hip or periprosthetic fracture) may benefit from perioperative shielding. Cite this article: Bone Joint J 2020;102-B(12):1774-1781.

Limited implementation of measures to reduce nosocomial spread of COVID-19 in hip-fracture patients in the North West of England.

Hip-fracture patients are vulnerable to the outcomes of COVID-19. We performed a cross-sectional survey to determine measures employed to limit nosocomial spread of COVID-19 in 23 orthopaedic trauma departments in the North-West of England. Nineteen (87%) hospitals admitted patients to a ward prior to a negative swab, and only 9 (39%) patients were barrier nursed. Hip-fracture patients were operated in non-COVID-19-free theatres in 21 (91%) hospitals. Regular screening of doctors working in trauma and elective areas for COVID-19 was undertaken in three (13%) and five (22%) hospitals, respectively. Doctors moved freely between trauma and elective areas in 22 (96%) hospitals.

Thirty-Day Mortality Rate of Patients With Hip Fractures During the COVID-19 Pandemic: A Single Centre Prospective Study in the United Kingdom.

OBJECTIVES: During the COVID-19 pandemic, the care of hip fracture patients remains a clinical priority. Our study aims to investigate the 30-day mortality rate of hip fracture patients during the first 30 days of the pandemic in the United Kingdom. METHODS: A single-center, observational, prospective study of patients presenting with hip fractures. Data collection started from "day 0" of the COVID-19 pandemic in the United Kingdom and continued for 30 days. We collected data on time to surgery, Clinical Frailty Scale score, Nottingham Hip Fracture Score, COVID-19 infection status, 30-day mortality, and cause of death. For comparison, we collected retrospective data during the same 30-day period in 2018, 2019, and the previous 6 months (Control groups A, B, and C, respectively). RESULTS: Forty-three patients were included in the study. There was no difference in age or gender between the Study and Control groups. The 30-day mortality rate of the Study group was 16.3%, which was higher than Control groups A (P = 0.022), B (P = 0.003) and C (P = 0.001). The prevalence of COVID-19 infection in our Study group was 26%. Of the 7 mortalities recorded, 4 patients tested positive for COVID-19 infection. In our Study group, COVID-19 infection correlated significantly with 30-day mortality (P = 0.002, odds ratio 2.4). CONCLUSIONS: Our study demonstrated a significant increase in 30-day mortality among hip fracture patients during the first 30 days of the COVID-19 pandemic in the United Kingdom. A positive COVID-19 test result in patients with hip fractures is associated with a 2.4-fold increase in risk of 30-day mortality. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Modification of a Validated Risk Stratification Tool to Characterize Geriatric Hip Fracture Outcomes and Optimize Care in a Post-COVID-19 World.

OBJECTIVES: (1) To demonstrate how a risk assessment tool modified to account for the COVID-19 virus during the current global pandemic is able to provide risk assessment for low-energy geriatric hip fracture patients. (2) To provide a treatment algorithm for care of COVID-19 positive/suspected hip fractures patients that accounts for their increased risk of morbidity and mortality. SETTING: One academic medical center including 4 Level 1 trauma centers, 1 university-based tertiary care referral hospital, and 1 orthopaedic specialty hospital. PATIENTS/PARTICIPANTS: One thousand two hundred seventy-eight patients treated for hip fractures between October 2014 and April 2020, including 136 patients treated during the COVID-19 pandemic between February 1, 2020 and April 15, 2020. INTERVENTION: The Score for Trauma Triage in the Geriatric and Middle-Aged ORIGINAL (STTGMAORIGINAL) score was modified by adding COVID-19 virus as a risk factor for mortality to create the STTGMACOVID score. Patients were stratified into quartiles to demonstrate differences in risk distribution between the scores. MAIN OUTCOME MEASUREMENTS: Inpatient and 30-day mortality, major, and minor complications. RESULTS: Both STTGMA score and COVID-19 positive/suspected status are independent predictors of inpatient mortality, confirming their use in risk assessment models for geriatric hip fracture patients. Compared with STTGMAORIGINAL, where COVID-19 patients are haphazardly distributed among the risk groups and COVID-19 inpatient and 30 days mortalities comprise 50% deaths in the minimal-risk and low-risk cohorts, the STTGMACOVID tool is able to triage 100% of COVID-19 patients and 100% of COVID-19 inpatient and 30 days mortalities into the highest risk quartile, where it was demonstrated that these patients have a 55% rate of pneumonia, a 35% rate of acute respiratory distress syndrome, a 22% rate of inpatient mortality, and a 35% rate of 30 days mortality. COVID-19 patients who are symptomatic on presentation to the emergency department and undergo surgical fixation have a 30% inpatient mortality rate compared with 12.5% for patients who are initially asymptomatic but later develop symptoms. CONCLUSION: The STTGMA tool can be modified for specific disease processes, in this case to account for the COVID-19 virus and provide a robust risk stratification tool that accounts for a heretofore unknown risk factor. COVID-19 positive/suspected status portends a poor outcome in this susceptible trauma population and should be included in risk assessment models. These patients should be considered a high risk for perioperative morbidity and mortality. Patients with COVID-19 symptoms on presentation should have surgery deferred until symptoms improve or resolve and should be reassessed for surgical treatment versus definitive nonoperative treatment with palliative care and/or hospice care. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.

Are Hospitals Safe? A Prospective Study on SARS-CoV-2 Prevalence and Outcome on Surgical Fracture Patients: A Closer Look at Hip Fracture Patients.

OBJECTIVES: To describe clinical characteristics of fracture patients, including a closer look to hip fracture patients, and determine how epidemiological variables may have influenced on a higher vulnerability to SARS-CoV-2 infection, as the basis for the considerations needed to reintroduce elective surgery during the pandemic. DESIGN: Longitudinal prospective cohort study. SETTING: Level I Trauma Center in the East of Spain. PATIENTS/PARTICIPANTS: One hundred forty-four consecutive fracture patients 18 years or older admitted for surgery. INTERVENTION: Patients were tested for SARS-CoV-2 with either molecular and/or serological techniques and screened for presentation of COVID-19. MAIN OUTCOME MEASUREMENTS: Patients were interviewed and charts reviewed for demographic, epidemiological, clinical, and surgical characteristics. RESULTS: We interviewed all patients and tested 137 (95.7%) of them. Three positive patients for SARS-CoV-2 were identified (2.1%). One was asymptomatic and the other 2 required admission due to COVID-19-related symptoms. Mortality for the whole cohort was 13 patients (9%). Significant association was found between infection by SARS-CoV-2 and epidemiological variables including: intimate exposure to respiratory symptomatic patients (P = 0.025) and intimate exposure to SARS-CoV-2-positive patients (P = 0.013). No association was found when crowding above 50 people was tested individually (P = 0.187). When comparing the 2020 and 2019 hip fracture cohorts we found them to be similar, including 30-day mortality. A significant increase in surgical delay from 1.5 to 1.8 days was observed on the 2020 patients (P = 0.034). CONCLUSIONS: Patients may be treated safely at hospitals if strict recommendations are followed. Both cohorts of hip fracture patients had similar 30-day mortality. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.