Antibiotic prophylaxis for leptospirosis.

BACKGROUND: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3). OBJECTIVES: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis. SEARCH METHODS: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023. SELECTION CRITERIA: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. MAIN RESULTS: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source. AUTHORS' CONCLUSIONS: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.

Antibiotics for treatment of leptospirosis.

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.

Effective prolonged suppression of HIV-1 viral load using tenofovir alafenamide, emtricitabine and efavirenz in an adult with BMI >59 kg/m2.

Limited information is available regarding the efficacy of antiretrovirals in people with HIV-1 and high or very high Body Mass Index (BMI). This is especially the case for the alafenamide salt of tenofovir as clinical trials have only enrolled patients with BMI ≤30 kg/m2. Lower concentrations of some antiretrovirals are expected in patients with BMI >30 kg/m2 due to potential changes in clearance and distribution of medication. This report describes an individual taking tenofovir alafenamide, emtricitabine and efavirenz in whom HIV-1 viral load was consistently undetectable (<50 copies/ml) over a 2.5 year period. During this period the patient's BMI ranged between 59.8 and 68.1 kg/m2. Further data is required to support the efficacy of antiretrovirals in individuals with high and very high BMI.

Purpura fulminans secondary to Capnocytophaga canimorsus bacteraemia following a dog bite: A case report and review of literature.

Introduction: Infection due to Capnocytophaga canimorsus may result in a wide variety of clinical presentations. We present a case of life-threatening Capnocytophaga canimorsus infection with evolution of ecchymosis to purpura fulminans. Case description: We present a case of a 43-year-old male with a history of excessive alcohol consumption who presented with features of sepsis following a dog bite. This was associated with a striking, widespread purpuric rash. A causative pathogen, C. canimorsus was identified through blood culture and 16S RNA sequencing. His initially purpuric rash underwent bullous transformation and was diagnosed clinically as purpura fulminans, confirmed on skin biopsy. He made a full recovery with prompt antimicrobial therapy, initially with co-amoxiclav but escalated to clindamycin and meropenem due to clinical deterioration and concerns of beta-lactamase resistance. Discussion: ß-Lactamase producing Capnocytophaga strains are of increasing concern. This particular concern is reflected in our case as 5 days into treatment with ß-lactamase inhibitor combination therapy the patients clinical condition deteriorated but demonstrably improved on switching to a carbapenem.The development of biopsy proven purpura fulminans in this immunocompetent case is a rare severe manifestation of the previously reported manifestation of disseminated intravascular coagulation (DIC) in Capnocytophaga bacteraemia. The case reported describes characteristics common with other DIC presentations such as the presence of clinical risk factors (history of excessive alcohol consumption) and symmetrical involvement. However, an unusual feature in that initial purpuric lesions were followed by the development of a bullous appearance and peripheral necrotic features concerning for purpura fulminans and confirmed with skin biopsy.

An economic evaluation of two PCR-based respiratory panel assays for patients admitted to hospital with community-acquired pneumonia (CAP) in the UK, France and Spain.

BACKGROUND: On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used. METHODS: An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed. RESULTS: In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain. CONCLUSION: In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP.

Does Residual Invasive Disease in Wide Local Excision after Diagnosis with Partial Biopsy Technique Influence Survival in Melanoma? Matched-Pair Analysis of Multicenter Selective Lymphadenectomy Trial I and II.

BACKGROUND: Current guidelines recommend excisional/complete biopsy for melanoma diagnosis, owing to high rates of residual disease found at wide local excision (WLE) after partial biopsy techniques. We sought to determine any survival disadvantage associated with the presence of residual invasive melanoma in the WLE after diagnosis with a partial biopsy technique. STUDY DESIGN: Data were examined from Multicenter Selective Lymphadenectomy Trials I and II (MSLT-I and -II), 2 large melanoma trials. Patients diagnosed with excisional/complete biopsy were excluded. Clinicopathologic characteristics, melanoma-specific survival (MSS), distant disease-free survival (DDFS), and disease-free survival (DFS) of those with residual invasive melanoma in the definitive WLE and those with no residual melanoma were compared. Matched pairing was used to reduce variability between groups. RESULTS: From 1994 through 2014, 3,939 patients were enrolled in these trials and 874 (22%) were diagnosed using partial biopsy techniques. Of these, 399 (46%) had residual tumor in the WLE. Only 6 patients had residual tumor in their WLE resulting in T-upstaging of their tumor. Match-pairing formed two cohorts (1:1) of patients with and without residual invasive tumor after WLE. A total of 514 patients were paired; 288 (56%) males, 148 (28.8%) aged 60 or older, 192 (37.4%) with truncal melanomas, 214 (41.6%) had Breslow thickness 2 mm or greater, and 376 (73.2%) had positive sentinel nodes. Kaplan-Meier analysis showed no statistical difference in 10-year MSS (73.6% ± 3.3% vs 73.9% ± 3.7%, p = 0.891), DDFS (68.7% ± 3.4% vs 65.3% ± 4.0%, p = 0.548), or DFS (59.6% ± 3.7% vs 59.4% ± 3.9%, p = 0.783). CONCLUSIONS: Survival in patients with primary melanoma does not appear to be worse in patients who undergo a partial biopsy technique and are later found to have residual invasive tumor in the WLE specimen.

Diagnostic accuracy of Abbott Architect Assay as a screening tool for human T-cell leukaemia virus type-1 and type-2 infection in a London teaching hospital with a large solid organ transplant centre.

AIM: In the United Kingdom, organ donors/recipients are screened for evidence of human T-cell leukaemia virus type-1 and type-2 (HTLV-1/2) infections. Since the United Kingdom is a low prevalence country for HTLV infections, a screening assay with high sensitivity and specificity is required. Samples with repeat reactivity on antibody testing are sent to a reference lab for confirmatory serological and molecular testing. In the case of donor screen, this leads to delays in the release of organs and can result in wastage. We aim to assess whether a signal/cut-off (S/CO) ratio higher than the manufacturer's recommendation of 1.0 in the Abbott Architect antibody assay is a reliable measure of HTLV-1/2 infection. METHODS: We conducted a 5 year retrospective analysis of 7245 patients from which 11 766 samples were tested on the Abbott Architect rHTLV I/II assay. Reactive samples (S/CO >1) were referred for confirmatory serological and molecular detection (Western Blot and proviral DNA) at UK Health Security Agency, (formerly PHE, Colindale), the national reference laboratory. Electronic, protected laboratory and hospital patient databases were employed to collate data. RESULTS: A total of 45 patients had initially reactive samples. 42.2% (n = 19/45) had an S/CO ratio > 20, with HTLV infection confirmed in n = 18/19 and indeterminate confirmatory results in n = 1/19. No samples with an S/CO ratio <4 (48.9%, n = 22/45) or 4-20 (8.9%, n = 4/45) had positive confirmatory results on subsequent confirmatory testing. CONCLUSION: Samples with an S/CO >20 likely represent a true HTLV-1/2 infection. Reactive samples with an S/CO <4 were unlikely to confirm for HTLV infections. Interpretation of these ratios can assist clinicians in the assessment of low reactive samples and reiterates the need for faster access to confirmatory testing.

Chromobacterium violaceum causing disseminated soft tissue and pulmonary abscesses in a traveller returning from the Azores.

This case report describes a 30-year-old male patient presenting with Chromobacterium violaceum cutaneous lesions who develops a subsequent bacteraemia, complicated by soft tissue and pulmonary abscesses. C. violaceum disease is a rare infection that can manifest in a spectrum from cutaneous lesions to disseminated disease and sepsis, the latter associated with high mortality. Although in the available literature there is a recommendation for a prolonged antibiotic course, we describe effective management with a shorter course of antibiotics. This case highlights the importance of not only considering a diagnosis of C. violaceum if there has been a high risk and appropriate exposure, but to also consider the changing epidemiology of the organism due to certain geographical areas becoming warmer due to climate change.

Exposure to televised political campaign advertisements aired in the United States 2015-2016 election cycle and psychological distress.

CONTEXT: Prior research suggests the potential for political campaign advertisements to increase psychological distress among viewers. The current study tests relationships between estimated exposure to campaign advertising and the odds of respondents reporting that a doctor told them they have anxiety, depression, insomnia, or (as a negative control) cancer. METHODS: A secondary analysis of U.S. data on televised campaign ad airings from January 2015 to November 2016 (n = 4,659,038 airings) and five waves of a mail survey on television viewing patterns and self-reported medical conditions from November 2015 to March 2017 (n = 28,199 respondents from n = 16,204 unique households in the U.S.). FINDINGS: A 1 percent increase in the estimated volume of campaign advertising exposure was associated with a 0.06 [95% CI 0.03-0.09] percentage point increase in the odds of a respondent being told by a doctor that they have anxiety in the past 12 months. We observed this association regardless of the political party of the ad sponsor, the political party of the respondent, or their statistical interaction. We also observed this association for both Presidential campaign ads and non-Presidential (including local, state, and U.S. congressional election) campaign ads, providing evidence that these relationships were not driven by the unique divisiveness of the race between Donald Trump and Hilary Clinton. Some topic-specific models offered additional evidence of association between estimated volume of campaign advertising exposure and the odds of being told by a doctor that they have depression or insomnia, but these patterns were less consistent across models that utilized different categories of campaign exposure. Campaign ad exposure was not associated with cancer, which served as a negative control comparison. CONCLUSIONS: There was a consistent positive association between the volume of campaign advertising exposure and a reported diagnosis of anxiety among American adults.

Estimated televised alcohol advertising exposure in the past year and associations with past 30-day drinking behavior among American adults: results from a secondary analysis of large-scale advertising and survey data.

AIMS: To estimate the volume of past-year televised alcohol advertising exposure by product category and demographic group among adults living in the United States and test associations between estimated alcohol advertising exposure and past 30-day drinking behavior. DESIGN: Secondary analysis of data from two national-level US data sets: Kantar data on appearances of televised alcohol advertisements and data from the Simmons National Consumer Survey (NCS), a large national mail survey on television viewing patterns and consumer behavior. SETTING: United States. PARTICIPANTS: A total of 54 671 adults, aged 21 years and older, who were randomly selected to participate in the Simmons NCS. MEASUREMENTS: Estimated exposure to televised advertisements for beer, wine and spirits, self-reported alcohol use in the past year and number of drinks consumed in the past 30 days. FINDINGS: The average respondent was exposed to an estimated 576 [95% confidence interval (CI) = 570-582] televised alcohol advertisements in the year preceding their survey. Exposure was higher among males versus females and African Americans versus whites. A 1% increase in the estimated volume of advertisement exposure was associated with a 0.11 (95% CI = 0.08-0.13) percentage point increase in the odds of having at least one drink in the last 30 days and, among past 30-day drinkers, a 0.05 (95% CI = 0.04-0.07) per cent increase in the number of alcoholic drinks consumed. Associations were consistent across product categories and demographics. CONCLUSIONS: There appears to be a small but consistent positive association between alcohol advertising exposure and drinking behavior among American adults.

An observational report of universal GeneXpert testing of inpatients with diagnosed or presumptive TB in the Philippines.

BACKGROUND: The Philippines is a high TB and multidrug-resistant TB burden country. Although the scale-up of GeneXpert testing is occurring, the benefits of universal Xpert-Mycobacterium tuberculosis/ rifampicin (MTB/RIF) testing in inpatients have not been documented. METHODS: Routine GeneXpert testing irrespective of priority criteria for testing was conducted within a prospective cohort of all adults with known or presumptive TB admitted to a tertiary infectious diseases hospital in Manila. Study-specific TB diagnosis was decided upon bacteriological results, chest x-ray assessment, if already on anti-TB treatment (ATT) at admission and a cough duration of ≥2 wk. RESULTS: Of submitted sputum samples, 87.1% (277/318) had valid acid-fast bacilli (AFB) microscopy and Xpert® MTB/RIF results. Xpert® MTB/RIF was positive in 97.7% (n = 87/89) of AFB-positive patients and 25.5% (n = 48/188) of AFB-negative patients. Bacteriological confirmation in smear negative cases not on ATT prior to admission was 25.2% (34/135). Rifampicin resistance was detected in 26/135 Xpert positive cases (19.3%), including nine who might not otherwise have been detected, representing a 53% increase in yield. CONCLUSION: Universal GeneXpert testing in this setting enhanced the yield of bacterial confirmation, revealing a high incidence of rifampicin resistance and suggesting a need for further investigations in Xpert-negative/smear-positive patients who may not have mycobacterial TB.

Patterns and predictors of co-morbidities in Tuberculosis: A cross-sectional study in the Philippines.

Diabetes and undernutrition are common risk factors for TB, associated with poor treatment outcomes and exacerbated by TB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in Filipino TB outpatients, focusing on malnutrition and diabetes. In a cross-sectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros Occidental (N = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0-11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMI) <17 kg/2) was 20.5% (130/634, 95%CI: 17.4-23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). Central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted Odds Ratio (AOR) = 6.16, 95%CI: 3.15-12.0) than BMI. Undernutrition was less common in men (AOR = 0.44, 95%CI: 0.28-0.70), and associated with previous history of TB (AOR = 1.97, 95%CI: 1.28-3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity.

Physician mistreatment in the clinical learning environment.

BACKGROUND: Mistreatment has been correlated with burnout and poor well-being in medical students, but data regarding residents and faculty are limited. The objective was to investigate the prevalence of mistreatment towards surgical housestaff and faculty and characterize such experiences. METHODS: In 2018, the Department of Surgery surveyed housestaff and faculty on incidents of mistreatment. RESULTS: Clinical faculty (63%) and residents (72%) completed the mistreatment survey. Excluding public embarrassment, 48% of residents and 29% of clinical faculty experienced mistreatment. Residents experienced public embarrassment and public humiliation more frequently than faculty, however faculty were subjected to racially or ethnically offensive remarks/names more frequently than residents (p < .05). Faculty within and external to their department were most cited as instigators of mistreatment. Residents experienced mistreatment most often by faculty, co-residents, and nurses. Reporting of the behaviors was low. CONCLUSIONS: Incidents of mistreatment are frequently occurring for surgical residents and faculty.

Mid-upper arm circumference predicts death in adult patients admitted to a TB ward in the Philippines: A prospective cohort study.

BACKGROUND: The Philippines is ranked 3rd globally for tuberculosis incidence (554/100,000 population). The tuberculosis ward at San Lazaro Hospital, Manila receives 1,800-2,000 admissions of acutely unwell patients per year with high mortality. Objectives of this prospective cohort study were to quantify the association of under-nutrition (primary) and diabetes (secondary) with inpatient mortality occurring between 3-28 days of hospital admission in patients with suspected or previously diagnosed TB. METHODS AND RESULTS: We enrolled 360 adults (≥18 years); 348 were eligible for the primary analysis (alive on day 3). Clinical, laboratory, anthropometric and enhanced tuberculosis diagnostic data were collected at admission with telephone tracing for mortality up to 6 months post-discharge. In the primary analysis population (mean age 45 years, SD = 15.0 years, 70% male), 58 (16.7%) deaths occurred between day 3-28 of admission; 70 (20.1%) between day 3 and discharge and documented total post-day 3 mortality including follow-up was 96 (27.6%). In those in whom it could be assessed, body mass index (BMI) ranged from 11.2-30.6 kg/m2 and 141/303 (46.5%) had moderate/severe undernutrition (BMI<17 kg/m2). A sex-specific cut-off for mid-upper arm circumference predictive of BMI<17 kg/m2 was associated with inpatient Day 3-28 mortality in males (AOR = 5.04, 95% CI: 1.50-16.86; p = 0.009; p = 0.032 for interaction by sex). The inability to stand for weight/height for BMI assessment was also associated with mortality (AOR = 5.59; 95% CI 2.25-13.89; p<0.001) as was severe compared to normal/mild anaemia (AOR = 9.67; 95% CI 2.48-37.76; p<0.001). No TB specific variables were associated with Day 3-28 mortality, nor was diabetes (HbA1c ≥6.5% or diabetes treatment). Similar effects were observed when the same multivariable model was applied to confirmed TB patients only and to the outcome of all post-day 3 in-patient mortality. CONCLUSION: This research supports the use of mid-upper arm circumference for triaging acutely unwell patients and the design and testing of nutrition-based interventions to improve patient outcomes.

Performance of alternative measures to body mass index in the assessment of moderate and severe under-nutrition among acutely unwell patients hospitalized in a TB ward in the Philippines: A cross-sectional study.

Body mass index (BMI) kg/m2 is a key screening tool for under-nutrition in adults, but difficult to obtain in immobile or unwell patients, particuarly in low resource settings, due to inability to accurately measure both weight and height. Mid-upper arm circumference (MUAC) is used to assess under-nutrition in children under 5 years but no standardised cut-off values exist for adults. In a cohort of adult Filipino patients admitted to a tuberculosis ward we assessed (i) cut-offs for MUAC to predict moderate under-nutrition (BMI <17kg/m2), (ii) the performance of limb lengths to predict height and; (iii) associations of body fat percentage from skinfolds and hand grip-strength with BMI. In 303 patients with MUAC and BMI at admission, aged 18-80 years (mean = 45.5, SD:14.8), BMI ranged from 11.2-30.6 kg/m2 and 141 (46.5%) had BMI <17.0 kg/m2. Using receiver operator curves, MUAC cut-offs were identified as <20.5cm for males (sensitivity: 89%, specificity: 84%) and <18.5cm for females (sensitivity: 91%, specificity: 89%), for BMI<17.0 kg/m2. Using published equations, knee height had the lowest mean difference between predicted and measured heights compared to ulnar or demi-span: (-0.98 cm, 95% CI: -1.51/-0.44). Both grip-strength and body fat percentage were positively associated with BMI, in separate linear regression models with exposure-age-sex interactions (adjusted-R-squared values: 0.15, 0.66, respectively). MUAC can predict moderate acute under-nutrition with high positive predictive value. Further research is required to determine the performance of alternative measures to BMI to predict mortality or adverse outcomes in acutely unwell patients.

Otolaryngology Resident Well-Being and Perceptions of the Clinical Learning Environment.

OBJECTIVE: To measure the current state of organizational and well-being factors in otolaryngology residency programs and associate these perceptions with demographics, pursuit of subspecialty fellowships, and performance on the Otolaryngology Training Examination (OTE). MATERIALS AND METHODS: Anonymous mail and online survey study of otolaryngology residents from the Southern, Mid-Atlantic, and East South-Central Regions of the United States. SUMMARY OF RESULTS: A total of 46 otolaryngology residents across 14 residency training programs (22% resident response rate) completed our survey. Residents who scored above the 80th percentile on the OTE perceived greater organizational support (median = 3.84) than residents who scored below the 40th percentile (median = 3.31), U = 48.00, P = .047, η2 = 0.14. Residents interested in fellowship reported less burnout (median = 2.44) compared to those who did not plan to pursue fellowship (median = 3.56), U = 105.00, P = .010, η2 = 0.05. Residents pursuing fellowship also reported less work-life strain (median = 2.56) than those forgoing fellowship (median = 2.89), U = 126.00, P = .044, η2 = 0.10. Residents with children reported greater work-life strain (median = 3.11) compared to those without (median = 2.56), U = 60.50, P = .008, η2 = 0.15. CONCLUSION: For otolaryngology residents in this survey sample, the perception of organizational support and well-being may influence resident performance (on OTE examinations) and ultimate career goals (fellowship applications). Program directors and coordinators can use this information to strengthen the perceptions of organizational support as well as improve the clinical learning environment to optimize training conditions for their residents. Residency program directors can also use the identified study measures to assess resident perceptions of the clinical learning environment and well-being for annual evaluation and improvement purposes.

Surgical Resident Burnout and Job Satisfaction: The Role of Workplace Climate and Perceived Support.

BACKGROUND: Surgical residents train under immense stress, often manifesting into poor well-being. While recent research identifies methods of coping with stress, few studies empirically investigate the role of the environment on surgical resident well-being. We aimed to assess surgical resident perceptions of workplace climate, organizational support, burnout, and job satisfaction to test a mediation model identifying antecedents to well-being. MATERIALS AND METHODS: A convenience sampling of program directors from general surgery within the Eastern region of the United States were emailed to request either agenda time to collection data via paper survey or to forward an electronic survey link to their residents between March 2016 and June 2016. The survey included scales demonstrating validity evidence on well-being, climate, and perceptions of support. RESULTS: Based on 160 general surgery residents (out of 557; 29% response rate) across 19 training programs, our mediation model found that job satisfaction was significantly predicted by workplace climate directly (direct effect = 0.37, 95% CI [0.19, 0.55]) and indirectly (specific indirect effect = 0.07, 95% CI [0.01, 0.13]) through perceived organizational support and burnout, while controlling for training year and gender, F(5,147) = 53.76, P < 0.001, Rsq. = 0.65. CONCLUSIONS: Medical education requires an additional focus on how the clinical learning environment affects surgical resident well-being. Health systems and training programs will need to collaborate on workplace innovations to improve workplace climate for trainees to address the concerns of well-being with a modern surgical workforce.

Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania.

BACKGROUND: The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD. METHODS: Archived samples from 199 Tanzanian children, 56% boys aged 3-18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles. FINDINGS: In univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2-3·93) but which was limited to girls (OR 4·85, 95%CI 1·79-13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or erythropoietin, lower hepcidin remained significantly associated with lowest ASSH quartile, although the hepcidin-sex interaction no longer reached statistical significance. No associations with ASSH quartile were observed for markers of inflammation, hemolysis or potential iron markers except for microcytosis, associated with higher ASSH, but which was confounded by reticulocyte percentage and alpha-thalassaemia status. INTERPRETATION: Hepcidin is lower in more severely anaemic children with SCD independent of inflammation or markers of erythropoiesis. FUNDING: Funding sources include The Wellcome Trust (080025, 095009, 094780 & 070114), MRC-UK (MC-A760-5QX00), NIHR Oxford Biomedical Research Centre, and the Bill and Melinda Gates Foundation ("Hepcidin and Iron in Global Health", OPP1055865).

Sarcopenia predicts poor long-term survival in patients undergoing endovascular aortic aneurysm repair.

OBJECTIVE: Sarcopenia measured by decreased psoas muscle size has been used as a surrogate for frailty and correlates with adverse outcomes in both the short and long term after many major operations. Our aim was to evaluate this measure as a predictor of outcomes in patients undergoing endovascular aortic aneurysm repair (EVAR). METHODS: Once Institutional Review Board approval was obtained, all patients who underwent EVAR from December 2010 to March 2016 at a Veterans Affairs hospital were assessed for sarcopenia by total psoas muscle area (TPA) measured on axial computed tomography scan immediately inferior to the fourth lumbar (L4) superior end plate. Outcomes including length of stay and mortality were collected from the medical record. RESULTS: There were 135 patients who underwent EVAR at a median age of 70 years. Median aneurysm size was 5.5 cm. Length of stay was >2 days in 25% of patients (n = 33), with the most common reasons for delayed discharge including respiratory complications (8.9% [n = 12]) and urinary retention (4.0% [n = 9]). Low TPA was not associated with extended length of stay (P = .40). Patients with lowest tertile TPA had 42% 5-year survival compared with 93% survival observed for the remaining two-thirds of patients (P = .01). Multivariate analysis revealed increased likelihood of mortality at 5 years for patients in the lowest tertile for TPA (odds ratio, 3.9; 95% confidence interval, 1.2-12.9) as well as for patients with chronic kidney disease (odds ratio, 5.2; 95% confidence interval, 1.5-18.0). CONCLUSIONS: Preoperative sarcopenia does not appear to affect length of stay but does portend worse long-term survival. This simple preoperative measurement may help vascular surgeons tailor repair thresholds and avoid nonbeneficial procedures.