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Purpose: Work-relative-value-units (wRVUs) are a core metric of faculty effort but do not account for the additional work associated with intraoperative teaching. This study introduces and assesses an indexed effort, wRVU per minute (wRVU index). We hypothesize that there is a significant decrease in the calculated wRVU index among teaching cases., Methods: We queried the ACS-NSQIP database for 7 core Emergency General Surgery procedures and records were stratified into teaching vs non-teaching, and emergent vs non-emergent procedures. We utilized multivariable generalized linear models to determine factors associated with increased operative time and decreased wRVU index., Results: Data were available for 953,967 cases from 2005 to 2010. For all cases, teaching vs non-teaching, the median wRVU index was 0.16 vs 0.21 (p ​< ​0.001). There was a positive association between teaching cases and decreased wRVU index for all cases., Conclusion: The wRVU index was 24% lower for teaching cases when compared to non-teaching cases despite controlling for patient-specific factors. This finding highlights the need for further evaluation of the current wRVU framework., Competing Interests: Declaration of competing interest AI technology was not used in the preparation of this manuscript. This manuscript is not under consideration for publication in any other journal., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients play a crucial role in surgical training, but little is known about the public's knowledge of general surgery training structure or opinion of resident assessment. Our aim was to evaluate the public's knowledge of general surgery training and assessment processes., Methods: We administered an anonymous, electronic survey to US adult panelists using SurveyGizmo. We used Dillman's Tailored Design Method to optimize response rate. Questions pertained to demographics, knowledge of general surgery training structure, and opinions regarding resident assessment. Outcome measures included public knowledge of the structure of general surgery residency and the perceptions of resident assessment. Univariate and multivariate statistics were used as appropriate., Results: Survey response rate was 93% (2005 of 2148). Respondents had nationally representative demographics. Most respondents had health insurance (87%). Sixty-one percent of respondents believed that 100% of hospitals trained residents. Age <40 years, Black race (odds ratio 1.48 [95% confidence interval (CI) 1.11-1.96]), working in a hospital/health care field (odds ratio 1.49 [95% CI 1.12-1.97]), and having a family member/close acquaintance working in a hospital/health care field (odds ratio 1.53 [95% CI .20-1.94]) were associated with this belief. There was a preference to obtain online information about medical training (30% television [TV] shows, 24% Internet searches, 5% social media). Eighty percent of respondents felt that resident self-assessment and patient assessment of residents was "important" or "essential" when considering readiness for independent practice., Conclusion: The US public has limited knowledge of general surgery training and competency assessment. Public educational strategies may help inform patients about the structure of training and assessment of trainees to improve engagement of these important stakeholders in surgical training., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite patients being important stakeholders in surgical training, little is known about the public's perception of trainee participation in surgical care. This study evaluates the public's perception of surgical resident autonomy and supervision., Study Design: An anonymous electronic survey was sent to adult panelists older than 18 years in the US using SurveyGizmo. The design of the survey used Dillman's Tailored Design Method to optimize response rate. Participants completed surveys including demographic characteristics and perceptions toward general surgery resident autonomy. Univariable and multivariable analyses were used as appropriate., Results: Survey response rate was 93% (2,005 of 2,148). Demographic characteristics including age, gender, race or ethnicity, and highest level of education were nationally representative. Most respondents (87%) had health insurance. On multivariable logistic regression analysis, factors associated with participants who would never allow a resident to perform any portion of the operation include: female gender (odds ratio [OR] 1.58; 95% CI, 1.28 to 1.95), no health insurance (OR 1.38; 95% CI, 1.03 to 1.84), Black race (OR 1.82; 95% CI, 1.38 to 2.41), and Hispanic ethnicity (OR 1.49; 95% CI, 1.03 to 2.15). Participants who were younger than 50 years (OR 1.57; 95% CI, 1.24 to 1.98), male (OR 1.90; 95% CI, 1.56 to 2.32), of Black race (OR 1.45; 95% CI, 0.10 to 1.91), Hispanic ethnicity (OR 1.49; 95% CI, 1.05 to 2.11), working in healthcare (OR 2.18; 95% CI, 1.67 to 2.86), or insured (OR 1.46; 95% CI, 1.07 to 1.99) were more likely to believe that resident involvement increases complications., Conclusions: Among survey participants broadly representing the US population, resident participation in operations is not universally accepted. Public perception of surgical resident autonomy and supervision is important, as GME continues to evolve to address readiness for independent practice., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background/objectives: US-born non-Hispanic black persons (blacks) (12% of the US population) accounted for 41% of HIV diagnoses during 2008-2014. HIV infection significantly increases TB and TB-related mortality. TB rate ratios were 6 to 7 times as high in blacks versus US-born non-Hispanic whites (whites) during 2013-2016. We analyzed a sample of black and white TB patients to assess the impact of HIV infection on TB racial disparities., Methods: In total, 552 black and white TB patients with known HIV/AIDS status were recruited from 10 US sites in 2009-2010. We abstracted data from the National TB Surveillance System, medical records, and death certificates and interviewed 477 patients. We estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations of TB with HIV infection, late HIV diagnosis (≤3 months before or any time after TB diagnosis), and mortality during TB treatment., Results: Twenty-one percent of the sample had HIV/AIDS infection. Blacks (AOR = 3.4; 95% CI, 1.7-6.8) and persons with recent homelessness (AOR = 2.5; 95% CI, 1.5-4.3) had greater odds of HIV infection than others. The majority of HIV-infected/TB patients were diagnosed with HIV infection 3 months or less before (57%) or after (4%) TB diagnosis. Among HIV-infected/TB patients, blacks had similar percentages to whites (61% vs 57%) of late HIV diagnosis. Twenty-five percent of HIV-infected/TB patients died, 38% prior to TB diagnosis and 62% during TB treatment. Blacks did not have significantly greater odds of TB-related mortality than whites (AOR = 1.1; 95% CI, 0.6-2.1)., Conclusions: Black TB patients had greater HIV prevalence than whites. While mortality was associated with HIV infection, it was not significantly associated with black or white race.

Background: As the most severe form of tuberculosis (TB), TB meningitis (TBM) is still associated with high mortality even in developed countries. In certain areas of the United States (U.S.), more than 50% of the TBM patients die with TB or have neurological sequelae and complications despite the availability of advanced health care. This population-based analysis aimed to determine the risk factors and trends associated with TBM morbidity and mortality using state-wide surveillance data., Methods: De-identified surveillance data of all confirmed TB patients from the state of Texas between 01/2010 and 12/2017 reported to the National TB Surveillance System was analyzed. Spatial distribution of TBM cases was presented by Stata's Geographic Information Systems mapping. Univariate and multiple generalized linear modeling were used to identify risk factors associated with meningitis morbidity and mortality. Non-parametric testing was used to analyze morbidity and mortality trends., Results: Among 10,103 TB patients reported in Texas between 2010 and 2017, 192 (1.9%) had TBM. During this 8-year period, the TBM proportion fluctuated between 1.5% and 2.7% with peaks in 2011 (2.7%) and 2016 (2.1%) and an overall non-significant trend (z = -1.32, p = 0.19). TBM had a higher mortality at diagnosis (8.9%), during treatment (14.1%) and overall (22.9%) compared to non-TBM (1.9%, 5.3%, and 7.2%, respectively, p<0.001). While mortality during treatment was unchanged over time in non-TBM patients (z = 0.5, p = 0.62), it consistently increased in TBM patients after 2013 (z = 3.09, p = 0.002). TBM patients had nearly five times the risk for overall death in multivariate analysis [aRR 4.91 (95% CI 3.71, 6.51), p<0.001]. TBM patients were younger, and more likely to present with miliary TB or HIV (+). Age ≥45 years, resident of a long-term care facility, IDU, diabetes, chronic kidney disease, abnormal chest radiography, positive AFB smear or culture and HIV (+) were independently associated with higher mortality., Conclusion: TBM remains challenging in Texas with significantly high mortality. Risk factors determined by multivariate modeling will inform health professionals and lay a foundation for the development of more effective strategies for TBM prevention and management., Competing Interests: The authors have declared that no competing interests exist.

Background: Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation., Methods: The study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC's National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study's CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1-3) was conducted using logistic regression., Results: Forty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters., Conclusions: We validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.

Background: Centers for Disease Control and Prevention requirements for pre-immigration tuberculosis (TB) screening of children 2- to 14-years old permit a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Few data are available on the performance of IGRAs versus TSTs in foreign-born children., Methods: We compared the performance of TST and QuantiFERON-TB (QFT) Gold In-Tube in children 2- to 14-years old applying to immigrate to the United States from Mexico, the Philippines and Vietnam, using diagnosis of TB in immigrating family members as a measure of potential exposure., Results: We enrolled 2520 children: 664 (26%) were TST+ and 142 (5.6%) were QFT+. One hundred and eleven (4.4%) were TST+/QFT+, 553 (21.9%) were TST+/QFT- and 31 (1.2%) were TST-/QFT+. Agreement between tests was poor (κ = 0.20). Although positive results of both tests were significantly associated with older age (relative risks [RR] TST+, 1.64; 95% confidence interval [CI]: 1.36-1.97; RR QFT+, 3.05; 95% CI: 1.72-5.38) and with the presence of TB in at least 1 immigrating family member (RR TST+, 1.40; 95% CI: 1.12-1.75; RR QFT+ 2.24; 95% CI: 1.18-4.28), QFT+ results were more strongly associated with both predictive variables., Conclusions: The findings support the preferential use of QFT over TST for pre-immigration screening of foreign-born children 2 years of age and older and lend support to the preferential use of IGRAs in testing foreign-born children for latent TB infection., Competing Interests: Research was funded by the Centers for Disease Control and Prevention, Tuberculosis Epidemiologic Studies Consortium. The authors have no conflicts of interest or financial relationships relevant to this manuscript to disclose.

To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.

Objectives: To estimate tuberculosis (TB) rates among young children in the United States by children's and parents' birth origins and describe the epidemiology of TB among young children who are foreign-born or have at least 1 foreign-born parent., Methods: Study subjects were children <5 years old diagnosed with TB in 20 US jurisdictions during 2005-2006. TB rates were calculated from jurisdictions' TB case counts and American Community Survey population estimates. An observational study collected demographics, immigration and travel histories, and clinical and source case details from parental interviews and health department and TB surveillance records., Results: Compared with TB rates among US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. Most TB cases (53%) were among the 29% of children who were US born with foreign-born parents. In the observational study, US-born children with foreign-born parents were more likely than foreign-born children to be infants (30% vs. 7%), Hispanic (73% vs. 37%), diagnosed through contact tracing (40% vs. 7%), and have an identified source case (61% vs. 19%); two-thirds of children were exposed in the United States., Conclusions: Young children who are US born of foreign-born parents have relatively high rates of TB and account for most cases in this age group. Prompt diagnosis and treatment of adult source cases, effective contact investigations prioritizing young contacts, and targeted testing and treatment of latent TB infection are necessary to reduce TB morbidity in this population., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Rationale: 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)., Objectives: Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs., Methods: 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., Measurements and Main Results: 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 (P < 0.001 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., Conclusions: 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.

Tuberculosis genotypic clustering is used as a proxy for recent transmission. The association between clustering and recent transmission becomes problematic when the genotyping method lacks specificity in defining a cluster, as well as for clusters with extensive jurisdictional histories and/or common genotypes. We investigated the four largest spoligotype/12 loci MIRU-VNTR-defined clusters in Harris County, Texas from 2006-2012 to determine their historical contribution to tuberculosis morbidity, estimate the contributions from recent and remote transmission, and determine the impact of secondary genotyping on cluster definition. The clusters contained 189, 64, 51 and 38 cases. Each cluster was linked to cluster(s) previously identified by Houston Tuberculosis Initiative; 3 since 1995 and the fourth in 2002. Among cases for which timing of Mycobacterium tuberculosis transmission relative to tuberculosis disease could be ascertained, nearly equal proportions were associated with recent and remote transmission. The extent to which genotyping with an additional 12 MIRU-VNTR loci modified the cluster definition varied from little or no impact for the two smaller clusters to moderate impact for the larger clusters. Tuberculosis control measures to reduce morbidity associated with large clusters must involve strategies to identify and treat individuals who recently acquired infection, as well as persons infected for years., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Multidrug-resistant (MDR) tuberculosis is a potential threat to tuberculosis elimination, but the extent of MDR tuberculosis disease in the USA that is attributable to transmission within the country is unknown. We assessed transmission of MDR tuberculosis and potential contributing factors in the USA., Methods: In a cross-sectional study, clinical, demographic, epidemiological, and Mycobacterium tuberculosis genotype data were obtained during routine surveillance of all verified cases of MDR tuberculosis reported from eight states in the USA (California from Jan 1, 2007, to Dec 31, 2009; Texas from Jan 1, 2007, to March 31, 2009; and the states of Colorado, Maryland, Massachusetts, New York, Tennessee, and Washington from Jan 1, 2007 to Dec 31, 2008). In-depth interviews and health-record abstraction were done for all who consented to ascertain potential interpersonal connections., Findings: 168 cases of MDR tuberculosis were reported in the eight states during our study period. 92 individuals (55%) consented to in-depth interview. 20 (22%) of these individuals developed MDR tuberculosis as a result of transmission in the USA; a source case was identified for eight of them (9%). 20 individuals (22%) had imported active tuberculosis (ie, culture-confirmed disease within 3 months of entry into the USA). 38 (41%) were deemed to have reactivation of disease, of whom 14 (15%) had a known previous episode of tuberculosis outside the USA. Five individuals (5%) had documented treatment of a previous episode in the USA, and so were deemed to have relapsed. For nine cases (10%), insufficient evidence was available to definitively classify reason for presentation., Interpretation: About a fifth of cases of MDR tuberculosis in the USA can be linked to transmission within the country. Many individuals acquire MDR tuberculosis before entry into the USA. MDR tuberculosis needs to be diagnosed rapidly to reduce potential infectious periods, and clinicians should consider latent tuberculosis infection treatment-tailored to the results of drug susceptibility testing of the putative source case-for exposed individuals., Funding: Centers for Disease Control and Prevention., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to assess kidney dysfunction in general surgical patients and examine the effect on postoperative mortality and morbidity., Background: An estimated 13% of the US population has chronic kidney disease (CKD), but awareness among patients and caregivers is lacking., Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data sets for 2005-2007 were analyzed. Preoperative kidney function was assessed by the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate (eGFR) and staged according to National Kidney Foundation. Cross-sectional analyses were performed for 30-day mortality (Cox proportional hazard) and incidence of major complications (nominal logistic regression). A case-control cohort of colectomy cases was analyzed comparing patients in the stage 4 CKD group and the no CKD group (no-CKD)., Results: Sixty-four percent of evaluable patients had reduced eGFR, but eGFR was not evaluable in 28% of the surgical cases. In the 260,352 evaluable cases, adjusted hazard ratio for 30-day mortality was 2.30 [95% confidence interval (CI), 2.11-2.51] for stage 3 CKD; 3.37 (95% CI, 3.01-3.76) for stage 4 CKD; and 3.05 (95% CI, 2.68-3.47) for stage 5 CKD compared with no-CKD (P < 0.0001). CKD was an independent risk factor for having major complications postsurgery [stage 3, odds ratio (OR) = 1.24 (95% CI, 1.19-1.29); stage 4, OR = 1.65 (95% CI, 1.52-1.78); and stage 5 CKD, OR = 1.40 (95% CI, 1.30-1.51); P < 0.0001]. The case-control for colectomy was confirmatory: increased 30-day mortality in stage 4 CKD versus no-CKD (hazard ratio = 2.58, 95% CI, 1.13-5.92; P = 0.025)., Conclusions: Renal insufficiency may be underrecognized in the general and vascular (noncardiac) surgery population, is a leading independent predictor of poor early postoperative outcomes, and should be routinely assessed in the preoperative setting.

We studied genetic relationships among 5069 Mycobacterium tuberculosis strains recovered from patients enrolled in 4 population-based studies in the United States and Europe, by analysis of 36 synonymous single-nucleotide polymorphisms (SNPs). All strains were assigned to 1 of 9 major genetic clusters based on sSNP profile. The same 9 genetic clusters were revealed by analysis of 227 nonsynonymous SNPs, 121 intergenic SNPs, and concatenated profiles of 578 SNPs available for a subset of 48 representative strains. IS6110 profiles, spoligotypes, and mycobacterial interspersed repetitive unit patterns were nonrandomly associated with SNP-based phylogenetic lineages, together indicating a strongly clonal population structure. Isolates of the 9 genetic clusters were not distributed with equal frequency in all localities, reflecting geographic subdivision. The SNP-based phylogenetic framework provides new insight into the worldwide evolution of M. tuberculosis and a gateway for investigating genotype-disease phenotype relationships in large samples of strains.

Denaturing gradient gel electrophoresis (DGGE) was used to probe for mutations associated with pyrazinamide (PZA) resistance in the pncA gene of Mycobacterium tuberculosis. DGGE scans for mutations across large regions of DNA and rivals sequencing in its ability to detect DNA alterations. Specific mutations can often be recognized by their characteristic denaturation pattern, which serves as a molecular fingerprint. Five PCR target fragments were designed to scan for DNA alterations across 600 bp of pncA in 181 M. tuberculosis isolates from patients residing in the U.S-Mexico border states of Texas and Tamaulipas, respectively. A region of pncA was observed with a high GC content and a melting temperature approaching 90 degrees C that was initially refractory to denaturation, and a DGGE target fragment was specifically designed to detect mutations in this region. DGGE detected pncA mutations in 82 of 83 PZA-resistant isolates. By contrast, only 1 of 98 PZA-susceptible isolates harbored a detectable DNA alteration. The pncA gene was sequenced from 41 isolates, and 32 DNA alterations in 32 PZA-resistant isolates were identified, including 11 new mutations. DGGE also detected nine isolates whose susceptibility to PZA appeared to be incorrect, and DNA sequencing confirmed these apparent errors in drug susceptibility testing. These results demonstrate the power and usefulness of DGGE in detecting mutations associated with PZA resistance in M. tuberculosis.

In order to investigate the role of MBL gene polymorphisms in susceptibility to tuberculosis (TB) we genotyped 487 TB cases and 232 controls. Among African-American individuals, the frequency of B allele was lower among controls than cases (p < 0.01), but we found no differences between cases and controls of white and Hispanic ethnicity.

Background: The increases in extra-pulmonary tuberculosis (EPTB) have been largely due to human immunodeficiency virus co-infection. The rates of EPTB have remained constant despite the decline in pulmonary tuberculosis (PTB) cases., Objective: To evaluate covariates associated with EPTB., Methods: A 4-year cohort of EPTB patients was compared with PTB cases. Enrollees were assessed for TB risk, medical records were reviewed, and Mycobacterium tuberculosis isolates were fingerprinted., Results: We identified 538 EPTB cases (28.6%) in a total of 1878 enrollees. The most common sites of infection were lymph nodes (43%) and pleura (23%). EPTB cases included 320 (59%) males, 382 (71%) patients were culture-positive, and 332 (86.9%) patient isolates were fingerprinted. Fewer EPTB than PTB patients belonged to clustered M. tuberculosis strains (58% vs. 65%; P = 0.02). A multivariate model identified an increased risk for EPTB among African Americans (OR = 1.9, P = 0.01), HIV-seropositive (OR = 3.1, P < 0.01), liver cirrhosis (OR = 2.3, P = 0.02), and age <18 years (OR = 2.0, P = 0.04). Patients with concomitant pulmonary and extra-pulmonary infections were more likely to die within 6 months of TB diagnosis (OR = 2.3, P < 0.01)., Conclusions: African American ethnicity is an independent risk factor for EPTB. Mortality at 6 months is partly due to the dissemination of M. tuberculosis and the severity of the underlying co-morbidity.

To improve understanding of the epidemiology of cryptococcal disease, we analyzed the multilocus genotype distribution of 358 Cryptococcus neoformans isolates obtained from 251 patients through active surveillance in four U.S. geographic areas from 1992 through 1994. Isolates of the predominant enzyme electrophoretic type (ET), ET-1, were recovered in significantly greater proportion from Atlanta, Ga., Houston, Tex., and all major metropolitan areas of Alabama than from San Francisco, Calif. ET-2 and ET-7 complex (serotype AD) isolates were recovered predominantly from San Francisco. ET-3 was recovered less frequently from San Francisco than from the three other locations. These findings may reflect geographic differences in exposure to environmental strains or the identification of previously unrecognized C. neoformans clusters. Analysis by random amplified polymorphic DNA-PCR subtyping further divided 67 ET-1 isolates into 19 additional subtypes, none of which could be associated with a particular geographic region. Multiple isolates from the same patient always revealed the same multilocus enzyme electrophoresis and random amplified polymorphic DNA subtypes. No differences in subtype distribution were found when isolates from AIDS patients were compared with those from persons without or with another underlying disease, although one C. noeformans var. gattii isolate was obtained from an AIDS patient. When body site distribution was analyzed, ET-4 was disproportionately recovered from skin or surface body sites. Evidence for linkage disequilibrium in this fungal population suggests that virulent C. neoformans possesses a clonal population structure. Continued application of molecular subtyping methods will be useful in tracking the source, transmission, and relative virulence of different C. neoformans strains.