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Background and Aims Clostridioides difficile infection (CDI) is associated with a range of outcomes and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia. Methods Eosinopenia was defined as 0 eosinophils/uL on the soonest peripheral blood draw within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of three large, unaffiliated hospital networks, tested positive for CDI by stool PCR and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. Results There were 4,518 unique hospitalized adults with CDI included (2,142 derivation cohort and 2,376 validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts respectively. In the validation cohort, the factors most strongly associated with death were eosinopenia [adjusted OR (aOR) 2.49, 95% CI 1.77-3.50], albumin 1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A six variable clinical prediction model was developed that improved upon existing classification schemes for CDI severity (AUROC of 0.75 vs. 0.68). Conclusions Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

RATIONALE: There is accumulating evidence that higher-than-standard doses of isoniazid are effective against low-to-intermediate–level isoniazid-resistant strains of Mycobacterium tuberculosis, but the optimal dose remains unknown. OBJECTIVES: To characterize the association between isoniazid pharmacokinetics (standard or high dose) and early bactericidal activity against M. tuberculosis (drug sensitive and inhA mutated) and N-acetyltransferase 2 status. METHODS: ACTG (AIDS Clinical Trial Group) A5312/INHindsight is a 7-day early bactericidal activity study with isoniazid at a normal dose (5 mg/kg) for patients with drug-sensitive bacteria and 5, 10, and 15 mg/kg doses for patients with inhA mutants. Participants with pulmonary tuberculosis received daily isoniazid monotherapy and collected sputum daily. Colony-forming units (cfu) on solid culture and time to positivity in liquid culture were jointly analyzed using nonlinear mixed-effects modeling. MEASUREMENTS AND MAIN RESULTS: Fifty-nine adults were included in this analysis. A decline in sputum cfu was described by a one-compartment model, whereas an exponential bacterial growth model was used to interpret time-to-positivity data. The model found that bacterial kill is modulated by isoniazid concentration using an effect compartment and a sigmoidal Emax relationship (a model linking the drug concentration to the observed effect). The model predicted lower potency but similar maximum kill of isoniazid against inhA-mutated compared with drug-sensitive isolates. Based on simulations from the pharmacokinetics-pharmacodynamics model, to achieve a drop in bacterial load comparable to 5 mg/kg against drug-sensitive tuberculosis, 10- and 15-mg/kg doses are necessary against inhA-mutated isolates in slow and intermediate N-acetyltransferase 2 acetylators, respectively. Fast acetylators underperformed even at 15 mg/kg. CONCLUSIONS: Dosing of isoniazid based on N-acetyltransferase 2 acetylator status may help patients attain effective exposures against inhA-mutated isolates. Clinical trial registered with www.clinicaltrials.gov (NCT01936831).

Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as

With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.

We aimed to understand the contemporary changes in the characteristics and the determinants of outcomes among simultaneous liver-kidney transplantation (SLKT) recipients at 6 liver transplantation centers in the United States. We retrospectively enrolled SLKT recipients between 2002 and 2017 in the US Multicenter SLKT Consortium. We analyzed time-related trends in recipient characteristics and outcomes with linear regression and nonparametric methods. Clustered Cox regression determined the factors associated with 1-year and overall survival. We enrolled 572 patients. We found significant changes in the clinical characteristics of SLKT recipients: as compared with 2002, recipients in 2017 were older (59 versus 52years; P&nbsp

Introduction Lung cancer is the most common cause of cancer deaths worldwide, accounting for 1.8 million deaths each year. Only 20% of lung cancer cases are reported to occur in low- and middle-income countries. An estimated 1.5% of all Ethiopian cancers involved the lung; however, no nationwide cancer registry exists in Ethiopia. Thus, accurate data on clinical history, histopathology, molecular characteristics, and risk factors for lung cancer are not available. The aim of this study was to describe the clinical, radiologic, and pathologic characteristics, including available molecular profiles, for lung cancer at Tikur Anbessa Specialized Hospital (TASH), the main tertiary referral center in Addis Ababa, Ethiopia. Methods A cross-sectional study was conducted at TASH among 146 patients with pathologically confirmed primary lung cancer, diagnosed from 2015 to 2019 and recorded in the Addis Ababa Cancer Registry at TASH. Clinical data were extracted from patient medical records, entered into a Research Electronic Data Capture database, and analyzed using Statistical Package for the Social Sciences statistical software. Variables collected included sociodemographics, personal exposures, comorbidities, clinical manifestations at presentation, chest imaging results, diagnostic procedures performed, histopathological classification, cancer staging, and type of treatment (if any). A subset of lung biopsies fixed in formalin for 2 to 7 days, which could be retrieved from the files of the Pathology Department of TASH, were reviewed, and molecular analysis was performed using next-generation sequencing to identify the tumor-oncogenic drivers. Results Among the 146 patients studied, the mean (SD) age was 54 plus or minus 13 years; 61.6% (n = 90) were male and 25.3% (n = 37) had a history of tobacco use. The most common clinical manifestations included cough (88.4%, n = 129), chest pain (60.3%, n = 88), and dyspnea (53.4%, n = 78). The median duration of any symptoms was 6 months (interquartile range: 3–12 mo). The most common radiologic features were lung mass (84.9%, n = 129) and pleural effusion (52.7%, n = 77). Adenocarcinoma accounted for 35.7% of lung cancers (n = 52) and squamous cell carcinoma 19.2% (n = 28) from those specimens was reported. Among patients on whom staging of lung cancer was documented, 92.2% (n = 95) of the subjects presented at advanced stages (stages III and IV). EGFR mutation, exons 19 and 20, was found in 7 of 14 tissue blocks analyzed. No specific risk factors were identified, possibly reflecting the relatively small sample size and limited exposures. Conclusions There are marked differences in the presentation, risk factors, and molecular characteristics of lung cancer in Ethiopia as compared with other African and non-African countries. Adenocarcinoma was the most common histologic type of lung cancer detected in our study, similar to findings from other international studies. Nevertheless, compared with high-income countries, lung cancer in Ethiopia presents at a younger age, a later stage, and without considerable personal tobacco use. The relatively higher prevalence of EGFR mutation, from the limited molecular analyses, suggests that factors other than smoking history, such as exposure to biomass fuel, may be a more important risk factor. Country-specific screening guidelines and treatment protocols, in addition to a national tumor registry and greater molecular mutation analyses, are needed to improve prevention and management of lung cancer in Ethiopia.

Early liver transplantation (LT) for severe alcoholic hepatitis (AH) is a rescue therapy for highly selected patients with favorable psychosocial profiles not responding to medical therapy. Given the expected increase of AH candidate referrals requiring complex care and comprehensive evaluations, increased workload and cost might be expected from implementing an early LT program for AH but have not been determined. Some centers may also view AH as a strategy to expeditiously increase LT volume and economic viability. The aim of this study was to determine the health care use and costs of an early LT program for AH. Analyses of prospective databases of AH, interhospital transfers, and the hospital accounting system at a single center were performed from July 2011 to July 2016. For 5 years, 193 patients with severe AH were evaluated at our center: 143 newly referred transfers and 50 direct admissions. Annual increases of 13% led to 2 to 3 AH transfers/month and AH becoming the top reason for transfer. There were 169 (88%) nonresponders who underwent psychosocial evaluations; 15 (9%) underwent early LT. The median cost of early LT was $297,422, which was highly correlated with length of stay (r = 0.83; P

Atorvastatin is a widely used cholesterol-lowering agent. Although generally safe and well tolerated, a number of drug side effects have been reported. We report only the second case of atorvastatin-induced pleural effusions, presenting as pleurisy, and the first case from Ethiopia. We believe our patient had this association based on the temporal onset of symptoms, the otherwise negative evaluation, and the resolution of findings once atorvastatin was discontinued. Clinicians need to consider this relationship when evaluating unexplained pleurisy and pleural effusions in patients taking atorvastatin.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Globally, non-communicable diseases are increasing in people living with HIV. Pulmonary hypertension is a rare non-communicable disease in people living with HIV with a reported prevalence of

Transplantation in potential candidates who have recently recovered from COVID‐19 is a challenge with uncertainties regarding the diagnosis, multi‐organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID‐19. At the time of transplant, he was SARS‐CoV‐2 PCR negative for 24 days and had a MELD score of 33. His post‐operative course was complicated by acute rejection which responded to intense immune‐suppression using T‐cell depletion and steroids. He was discharged with normal end‐organ function and no evidence of any active infection including COVID‐19. Prospective organ transplant recipients who have recovered from COVID‐19 can be considered for transplantation after careful pre‐transplant evaluation, donor selection, and individualized risk‐benefit analysis.

Background We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis. Methods We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays. Results Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P P P the median were associated with co-prevalent tuberculosis (P P = .03) and smoking (P Conclusions Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.

Objective To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. Design Retrospective manual medical record review. Setting NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. Participants The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. Main outcome measures Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. Conclusions Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.

Background Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. Methods We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. Results Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. Conclusions In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)

ObjectiveTo characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs).DesignRetrospective manual medical record review.SettingNewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC.ParticipantsThe first 1000 consecutive patients with laboratory-confirmed COVID-19.MethodsWe identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record.Main outcome measuresWe describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition.ResultsAmong the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital.ConclusionsHospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Purpose of review This review describes the major developments in the rationale for treating latent tuberculosis infection; new approaches to identifying persons with latent infection who are most likely to progress to active disease; and the development of novel short-course regimens for treatment of latent tuberculosis. Recent findings As many as one-third of the world's population has latent infection with Mycobacterium tuberculosis. Models demonstrate that tuberculosis will not be eliminated without large-scale treatment of persons with latent TB. Current tools for identifying persons at risk for active tuberculosis disease include TST and IGRA, which have poor positive predictive values. Newer approaches using gene expression profiling show promise and are being studied in the ongoing trials. Development of short-course regimens are a major advance in treatment of latent TB. Three months of rifapentine with isoniazid, 4 months of rifampin, and 1 month of rifapentine with isoniazid have been found to be noninferior to the standard 9 months of isoniazid. Summary Progress towards TB elimination can be accelerated by instituting public health measures that take into account new developments in identifying and treating persons with latent tuberculosis infection who are most likely to progress to active disease.

Background Ambulatory based treatment of tuberculosis has been recently introduced in Kazakhstan. We sought to assess the attitudes of the general population, TB patients and their household members towards ambulatory TB treatment and identify how knowledge of TB is associated with these attitudes. Methods New pulmonary TB cases and their household and community controls were recruited from three regions of Kazakhstan in 2012–2014. 1083 participants completed audio computer-assisted self interviews to assess their knowledge of TB and attitudes towards ambulatory care. Mixed effects logistic regression models were used to identify factors associated with attitudes toward ambulatory TB treatment. Results The proportion of people who considered ambulatory TB treatment as appropriate was very low (24.9%). Positive attitudes towards ambulatory TB treatment were significantly associated with region of residence, higher level of education, family support and experience with TB. The association between sufficient tuberculosis knowledge and favorable attitude toward ambulatory treatment was stronger among community controls compared to TB patients and their family members. Conclusions This study provides insight into attitudes toward ambulatory TB treatment among different groups and the specific influence of TB knowledge on these attitudes. Our findings can inform the process of integration of new TB treatment strategies and the development of appropriate education and advocacy programs in the general population.

Despite substantial improvements in global tuberculosis (TB) control over the past 2 decades, TB remains the ninth leading cause of death worldwide and the leading cause of death from a single infectious agent. From the perspective of both TB control programs and treating clinicians, rapid diagnosis

Background Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. Methods Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. Results Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. Conclusions Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.

RATIONALE: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. OBJECTIVES: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). METHODS: Data from reproductive-age (15–51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13%–14%=−1%; 95% confidence interval = −17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% −5% = −5%; 95% confidence interval = −18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSIONS: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).

Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients., Compared to cadaveric liver transplantation, live donor LT (LDLT) is challenged by ethical, medical and surgical considerations, many of which are still unresolved. The aim of this guideline is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT.

Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection. Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis. Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy. Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18–0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05–0.66) compared with those exposed to mono–INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23–2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not. Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.

BackgroundPatient awareness of asthma severity is important for optimal asthma management. However, there is often a discrepancy between physician assessment of asthma control based on guidelines and patient discernment of control. We compared physician and patient perception of asthma control in a clinic population seen at a tertiary hospital in Addis Ababa, Ethiopia.MethodsIn this cross-sectional study, 182 consecutive patients with a physician diagnosis of asthma seen in Chest Clinic at Tikur Anbessa Specialized Hospital (TASH) between July and December 2015 were studied. Demographics, asthma symptoms, medication use in the past month, and self-perception of asthma control in the past 7 days were obtained from the clinic records. Physician assessed asthma control was based on the GINA asthma symptom control assessment tool. Lung function was measured using a Diagnostic EasyOne Plus model 2001 SN spirometer. The institutional review board approved the study protocol.ResultsOf the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years, and the mean (SD) duration of asthma was 19.4 ± 12.7 years. Forty-four (24.2%) patients had physician determined well-controlled asthma and 138 (75.8%) patients had physician determined partly controlled/uncontrolled asthma. One hundred and fifty-one (83%) patients thought their asthma control was good. However, the degree of concordance between physician evaluation and patient perception of asthma control was low (kappa index = 0.09). On multivariate analysis, self-perceived poor asthma control was associated with any activity limitation due to asthma and inconsistent inhaled corticosteroid use.ConclusionIn our study, the first of its kind in Ethiopia, a high percent of patients with physician determined well-controlled asthma has appropriate perception of their disease state. However, those patients with partly controlled/uncontrolled asthma had poor self-perception of their disease, emphasizing the need for further patient education. These conclusions may be especially useful in the care of asthmatics from other low-income countries.

BACKGROUND Clostridioides difficile infection (CDI) is common after solid organ transplant (SOT) and is associated with high morbidity and mortality. METHODS We assessed incidence, risk factors, and outcomes of CDI among SOT patients at a large multi-organ transplant center. Multivariable logistic regression was used to identify risk factors for initial and recurrent CDI. RESULTS A total of 2622 SOT patients were included. 224 (8.5%) had CDI 1 year post-SOT. The highest incidence of CDI was among pancreas recipients (12.5%) followed by lung (11.7%), liver (11.0%), heart (10.8%), and kidney (5.8%). Median time to CDI was 56 days (range 2-354) post-SOT. About 64% of patients had severe CDI. About 56.3% were treated with metronidazole, 13.8% with oral vancomycin, and 28.6% with both. About 28.6% of patients had recurrent CDI. In multivariable modeling, lung transplant recipient status was the only significant predictor of recurrent CDI (OR 4.97, 95% CI 2.11-11.78, P

Summary: Opioid use in the United States and in many parts of the world has reached epidemic proportions. This has led to excess mortality as well as significant changes in the epidemiology of liver disease. Herein, we review the impact of the opioid epidemic on liver disease, focusing on the multifaceted impact this epidemic has had on liver disease and liver transplantation. In particular, the opioid crisis has led to a significant shift in incident hepatitis C virus infection to younger populations and to women, leading to changes in screening recommendations. Less well characterized are the potential direct and indirect hepatotoxic effects of opioids, as well as the changes in the incidence of hepatitis B virus infection and alcohol abuse that are likely rising in this population as well. Finally, the opioid epidemic has led to a significant rise in the proportion of organ donors who died due to overdose. These donors have led to an overall increase in donor numbers, but also to new considerations about the better use of donors with perceived or actual risk of disease transmission, especially hepatitis C. Clearly, additional efforts are needed to combat the opioid epidemic. Moreover, better understanding of the epidemiology and underlying pathophysiology will help to identify and treat liver disease in this high-risk population.

The following guideline represents the position of the International Liver Transplantation Society (ILTS) on key preoperative, operative, and postoperative aspects surrounding living liver donation. These recommendations were developed from experts in the field from around the world. The authors conducted an analysis of the National Library of Medicine indexed literature on "living donor liver transplantation" [Medline search] using Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). ILTS members, and many more nonmembers, were invited to comment. Recommendations have been based on information available at the time of final submission (March 2016). The lack of randomized controlled trials in this field to date is acknowledged and is reflected in the grading of evidence. Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care.

Despite an extensive burden of lung disease in East Africa, there are remarkably few pulmonary physicians in the region and no pulmonary subspecialty training programs. We developed a unique training program for pulmonary medicine in Ethiopia. The East African Training Initiative (EATI) is a 2-year fellowship program at Tikur Anbessa (Black Lion) Specialized Teaching Hospital, the largest public hospital in Ethiopia and the teaching hospital for the Addis Ababa University School of Medicine. The first year is devoted to clinical care and procedural skills. Lectures, conferences, daily inpatient and outpatient rounds, and procedure supervision by visiting faculty provide the clinical knowledge foundation. In the second year, training in clinical research is added to ongoing clinical training. Before graduation, fellows must pass rigorous written and oral examinations and achieve high marks on faculty evaluations. Funding derives from several sources. Ethiopian trainees are paid by the Ethiopian Ministry of Health and the Addis Ababa University School of Medicine. The World Lung Foundation and the Swiss Lung Foundation supply travel and housing costs for visiting faculty, who receive no other stipend. The first two trainees graduated in January 2015, and a second class of three fellows completed training in January 2016. All five presented research abstracts at the annual meetings of the International Union Against Tuberculosis and Lung Disease in 2014 and 2015. The EATI has successfully provided pulmonary medicine training in Ethiopia and has capacity for local leadership. We believe that EATI could be a model for other resource-limited countries.

Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p

Background Central line-associated blood stream infections (CLABSI) have a significant impact on mortality, morbidity and length of stay. Data collected by the Infection Prevention Department revealed progressive increases in the rate of CLABSI on an Abdominal Transplant Unit. Recognizing a drift from best practice, front line staff, the IP team and vascular access specialists, collaborated to identify opportunities for improving care of patients with vascular access devices. Methods An increase in CLABSI rate was observed on the Abdominal Transplant Unit beginning in 2016. An initiative began in 2017 to evaluate whether CLABSI rate reduction was sustainable for at least 1 year and to identify key determinants of this sustainability. Interventions were aimed at infection prevention best practices, care standardization, and team-based monitoring. Interventions included (1) re-education on CLABSI reduction, (2) two RN dressing changes to validate practice during central line dressing change, (3) blood draws from central lines (during non-emergent situations) had to be approved by nurse manager, physician lead and transplant quality physician, (4) CLABSI prevention nurses were chosen as designated phlebotomists for patients with prior approval, (5) daily line review was performed to address line days, indication of line (remove latent lines) and plan of care (transition to permanent access) and this information was shared with the unit physician lead and transplant quality team. Assuring compliance with audits and timely feedback with clinician accountability were vital with compliance with best practices. Results Conclusion During the intervention, CLABSI infection rates dropped from 4.825 to 1.533 in 1,000 CVC days. The sustainability plan for this program is to continue line audits, assessing line necessity and review the effectiveness of the initiatives, review all new CLABSI data with staff and implement new changes as necessary. Joint, ongoing multidisciplinary collaboration is essential to reduce CLABSIs and optimize quality in a challenging, high-acuity patient population. Disclosures All Authors: No reported disclosures

Objective Uncontrolled asthma negatively impacts patients, families, and the community. The level of symptom control among asthmatics in Ethiopia has not been well studied. We investigated the level of asthma control and risk factors for poor asthma control in clinic patients seen in the largest public hospital in Ethiopia. Results In this cross-sectional study, we studied all 182 consecutive subjects with a physician diagnosis of asthma who were seen in chest clinic at Tikur Anbessa Specialized Hospital between July and December 2015. Of the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years and the median duration of asthma was 20 ± 12.7 years. One hundred and seventeen subjects (64.3%) had nighttime awakening due to asthma. Fifty-eight (31%) were not using controller medications and 62 (34.6%) had improper inhaler technique. Only 44 (24.2%) subjects had well-controlled asthma. On multivariate analysis, variables associated with uncontrolled asthma included: use of biomass fuel for cooking, longer duration of asthma (> 30 year), incorrect inhalation technique, and asthma exacerbation in the last 12 months. Most asthmatics attending in the largest public hospital in Ethiopia, had uncontrolled asthma. Several risk factors for poor asthma control were identified. Improved asthma control is possible through directed interventions.

Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown.We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment.Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase.A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively).Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

As described in a recently released report of the Forum of International Respiratory Societies, four of the leading causes of death in the world are chronic obstructive pulmonary disease, acute respiratory tract infections, lung cancer, and tuberculosis. A fifth, asthma, causes enormous global morbidity. Not enough progress has been made in introducing new therapies and reducing disease burden for these illnesses in the last few decades, despite generous investments and some notable progress in biomedical research. Four external and modifiable drivers are responsible for a substantial percentage of the disease burden represented by the major lung diseases: tobacco, outdoor air pollution, household air pollution, and occupational exposures to lung toxins. Especially in low- and middle-income countries, but in highly developed economies as well, pressures for economic development and lax regulation are contributing to the continued proliferation of these drivers. Public health approaches to the most common lung diseases could have enormous effects on reducing morbidity and mortality. There must be increased advocacy from and mobilization of civil society to bring attention to the drivers of lung diseases in the world. The World Health Organization should negotiate accords similar to the Framework Convention on Tobacco Control to address air pollution and occupational exposures. Large increases in funding by government agencies and nongovernmental organizations around the world are needed to identify technologies that will reduce health risks while allowing populations to enjoy the benefits of economic development. This paradigm, focused more on public health than on individual medical treatment, has the best chance of substantial reduction in the burden of lung disease around the world in the next several years.

IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs).Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs.A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011.A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later.Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Introduction 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. Methods This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009–2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). Results Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60–1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14–2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). Conclusions In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations., WHO has assessed regimen recommendations for isoniazid-resistant TB to be of very low certainty. The addition of fluoroquinolones to a 12-month (isoniazid, rifamycin, ethambutol, short-duration pyrazinamide) regimen may be unnecessary in certain settings. http://bit.ly/2XoTgNL

Background Ending the Hepatitis C Virus (HCV) epidemic requires HCV testing as the critical first step. Busy urban Emergency Rooms are uniquely suited for HCV screening programs but numerous barriers to effective program implementation exist. We describe an emergency room physician champion model that utilizes the feedback intervention theory (FIT) to providers to increase HCV screening rates. Methods Due to the changing epidemiology of HCV in 2017 New York Presbyterian supported one-time universal HCV screening. In September 2018, our physician champion provided an educational session to ED providers about the importance of HCV screening and the proposed study. From the end of September to the end of March 2019, providers received a monthly e-mail from the ED champion and an automated text message with their individual and peer HCV screening rates. The number of HCV tests and percent of individuals with documented HCV testing in the ED was compared pre and post this intervention and to HCV testing in the inpatient and outpatient setting where feedback was not provided. Results On average ED providers evaluated approximately 14,000 patients per month. HCV testing increased 1,600% from an average of 40 tests per month in the 18 months prior to the intervention to an average of 640 tests sent per month during the intervention. tests sent in December. This was compared with stable inpatient and outpatient HCV screening during the same time period. Conclusion Individualized provider feedback paired with an ED physician champion can lead to a significant increase in HCV testing. Ongoing studies will determine if this intervention can lead to long-term behavior change. Disclosures All authors: No reported disclosures.

Introduction Rates of tuberculosis in Central Asia are extremely high, and even more alarming are the very high rates of multidrug-resistant tuberculosis (MDR-TB) in Kazakhstan, Uzbekistan, Tajikistan and Kyrgyzstan. In addition, rates of HIV infection related to injection drug use seems to be rising as well, thus creating conditions for a potentially devastating co-epidemic of TB/HIV and MDR-TB/HIV which would have terrible consequences for public health in these countries. Current status In many countries of Central Asia, diagnosis of tuberculosis still rests on clinical grounds or simple technologies such as chest radiograph and sputum smear examination. Modern molecular techniques such as GenExpert are being introduced in Kazakhstan and Uzbekistan, and perhaps soon in Kyrgyzstan. Treatment of TB is still often centered around prolonged inpatient stay at TB hospitals. Only a minority of patients with HIV infection are receiving ART, and TB and HIV services are not well integrated. Needle exchange programs are becoming increasingly available, but opioid substitution therapy is rarely used in Central Asia. TB, drug treatment and HIV services are generally not well-integrated. Conclusions To combat this developing storm, integration of TB services, HIV care, and substance abuse treatment programs is needed urgently to allow efficient and effective diagnosis and treatment of these conditions in a coordinated manner.

The new Kreek–McHugh–Schluger–Kellogg scale (‘KMSK scale’) is designed to quantify self-exposure to opiates, cocaine, alcohol, and/or tobacco. Each section of the KMSK scale assesses the frequency, amount, and duration of use of a particular substance during the individual's period of greatest consumption. The scale also assesses the mode of use, whether the substance use is current or past, and whether each substance is the substance of choice. The administration time is under 5 min. In an initial validation study of this scale, 100 human subjects were administered the KMSK scale concurrently with the Structured Clinical Interview for DSM-IV (SCID-I DSM-IV version). The sensitivity and specificity were very good for opiates, cocaine, and alcohol use. In addition, the correlations between KMSK scores and the number of SCID-I criteria items met were excellent for opiates and cocaine and good for alcohol use. Nicotine dependence was not assessed in this study as there is no SCID-I nicotine criteria. These preliminary results show that the KMSK scale may have both construct validity similar to that of other established self-report measures and the potential to be an effective screening instrument for the assessment of a lifetime diagnosis of alcohol, opiate, or cocaine dependence.

Rationale: Adults with chronic critical illness (tracheostomy after ≥ 10 d of mechanical ventilation) have a high burden of palliative needs, but little is known about the actual use and potential need of palliative care services for the larger population of older intensive care unit (ICU) survivors discharged to post–acute care facilities. Objectives: To determine whether older ICU survivors discharged to post–acute care facilities have potentially unmet palliative care needs. Methods: We examined electronic records from a 1-year cohort of 228 consecutive adults ≥ 65 years of age who had their first medical-ICU admission in 2009 at a single tertiary-care medical center and survived to discharge to a post–acute care facility (excluding hospice). Use of palliative care services was defined as having received a palliative care consultation. Potential palliative care needs were defined as patient characteristics suggestive of physical or psychological symptom distress or anticipated poor prognosis. We examined the prevalence of potential palliative needs and 6-month mortality. Measurements and Main Results: The median age was 78 years (interquartile range, 71–84 yr), and 54% received mechanical ventilation for a median of 7 days (interquartile range, 3–16 d). Six subjects (2.6%) received a palliative care consultation during the hospitalization. However, 88% had at least one potential palliative care need; 22% had chronic wounds, 37% were discharged on supplemental oxygen, 17% received chaplaincy services, 23% preferred to not be resuscitated, and 8% were designated “comfort care.” The 6-month mortality was 40%. Conclusions: Older ICU survivors from a single center who required postacute facility care had a high burden of palliative care needs and a high 6-month mortality. The in-hospital postcritical acute care period should be targeted for palliative care assessment and intervention.