Association of Rapid Molecular Testing With Duration of Respiratory Isolation for Patients With Possible Tuberculosis in a US Hospital.

Importance: New guidelines recommend that molecular testing replace sputum-smear microscopy to guide discontinuation of respiratory isolation in patients undergoing evaluation for active tuberculosis (TB) in health care settings. Objective: To evaluate the implementation and impact of a molecular testing strategy to guide discontinuation of isolation. Design, Setting, and Participants: Prospective cohort study with a pragmatic, before-and-after-implementation design of 621 consecutive patients hospitalized at Zuckerberg San Francisco General Hospital and Trauma Center who were undergoing sputum examination for evaluation for active pulmonary TB from January 2014 to January 2016. Interventions: Implementation of a sputum molecular testing algorithm using GeneXpert MTB/RIF (Xpert; Cepheid) to guide discontinuation of isolation. Main Outcomes and Measures: We measured the proportion of patients with molecular testing ordered and completed; the accuracy of the molecular testing algorithm in reference to mycobacterial culture; the duration of each component of the testing and isolation processes; length of stay; mean days in isolation and in hospital; and mean cost. We extracted data from hospital records and compared measures before and after implementation. Results: Clinicians ordered sputum testing for TB for 621 patients at ZSFG during the 2-year study period. Of 301 patients in the preimplementation period with at least 1 sputum microscopy and culture ordered, clinicians completed the rapid TB testing evaluation process for 233 (77%).Among 320 patients evaluated in the postimplementation period, clinicians ordered molecular testing for 234 (73%) patients and received results for 295 of 302 (98%) tests ordered. Median age was 54 years (interquartile range, 44-63 years), and 161 (26%) were women. The molecular testing algorithm accurately diagnosed all 7 patients with culture-confirmed TB and excluded TB in all 251 patients with Mycobacterium tuberculosis (MTB) culture-negative results. Compared with the preimplementation period, there were significant decreases in median times to final rapid test result (39.1 vs 22.4 hours, P < .001), discontinuation of isolation (2.9 vs 2.5 days, P = .001), and hospital discharge (6.0 vs 4.9 days, P = .003), on average saving $13 347 per isolated TB-negative patient. Conclusions and Relevance: A sputum molecular testing algorithm to guide discontinuation of respiratory isolation for patients undergoing evaluation for active TB was safe, feasible, widely and sustainably adopted, and provided substantial clinical and economic benefits. Molecular testing may facilitate more efficient, patient-centered evaluation for possible TB in US hospitals.

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

BACKGROUND: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. METHODS: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. RESULTS: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 µg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 µg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. CONCLUSION: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. IMPACT: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease.

The miR-35-41 family of microRNAs regulates RNAi sensitivity in Caenorhabditis elegans.

RNA interference (RNAi) utilizes small interfering RNAs (siRNAs) to direct silencing of specific genes through transcriptional and post-transcriptional mechanisms. The siRNA guides can originate from exogenous (exo-RNAi) or natural endogenous (endo-RNAi) sources of double-stranded RNA (dsRNA). In Caenorhabditis elegans, inactivation of genes that function in the endo-RNAi pathway can result in enhanced silencing of genes targeted by siRNAs from exogenous sources, indicating cross-regulation between the pathways. Here we show that members of another small RNA pathway, the mir-35-41 cluster of microRNAs (miRNAs) can regulate RNAi. In worms lacking miR-35-41, there is reduced expression of lin-35/Rb, the C. elegans homolog of the tumor suppressor Retinoblastoma gene, previously shown to regulate RNAi responsiveness. Genome-wide microarray analyses show that targets of endo-siRNAs are up-regulated in mir-35-41 mutants, a phenotype also displayed by lin-35/Rb mutants. Furthermore, overexpression of lin-35/Rb specifically rescues the RNAi hypersensitivity of mir-35-41 mutants. Although the mir-35-41 miRNAs appear to be exclusively expressed in germline and embryos, their effect on RNAi sensitivity is transmitted to multiple tissues and stages of development. Additionally, we demonstrate that maternal contribution of miR-35-41 or lin-35/Rb is sufficient to reduce RNAi effectiveness in progeny worms. Our results reveal that miRNAs can broadly regulate other small RNA pathways and, thus, have far reaching effects on gene expression beyond directly targeting specific mRNAs.

Prevalence of hepatitis C virus and HIV infection among injection drug users in two Mexican cities bordering the U. S

OBJECTIVE: To estimate the prevalence of the hepatitis C virus (HCV) and HIV infection and associated risk behaviors among injection drug users (IDUs) in two northern Mexican cities. MATERIAL AND METHODS: Between February and April 2005, IDUs were recruited in Tijuana (N=222) and Ciudad Juarez (N=206) using respondent-driven sampling (RDS), a chain referral sampling approach. Interviewer-administered questionnaires assessed drug-using behaviors during the prior six months. Venous blood was collected for immunoassays to detect HIV and HCV antibodies. For HIV, Western blot or immunofluorescence assay was used for confirmatory testing. Final HCV antibody prevalence was estimated using RDS adjustments. RESULTS: Overall, HCV and HIV prevalence was 96.0 percent and 2.8 percent, respectively, and was similar in both cities. Most IDUs (87.5 percent) reported passing on their used injection equipment to others, and 85.9 percent had received used equipment from others. CONCLUSIONS: HIV prevalence was relatively high given the prevalence of HIV in the general population, and HCV prevalence was extremely high among IDUs in Tijuana and Ciudad Juarez. Frequent sharing practices indicate a high potential for continued transmission for both infections. HCV counseling and testing for IDUs in Mexico and interventions to reduce sharing of injection equipment are needed.

OBJETIVO: Estimar las prevalencias de los virus de hepatitis C (VHC) y de VIH y los comportamientos de riesgo asociados con ellos, entre usuarios de drogas inyectables (UDI) en dos ciudades del norte de México. MATERIAL Y MÉTODOS: Entre febrero y abril de 2005, se reclutaron UDIs en Tijuana (N=222) y en Ciudad Juárez (N=206), mediante un método de muestreo llamado en inglés "respondent-driven sampling" (RDS), lo cual es un sistema basado en cadenas de referencia. Los participantes contestaron una encuesta aplicada por entrevista, la cual indagó acerca de los comportamientos en el uso de drogas durante los seis meses previos. Una muestra de sangre venosa fue colectada de cada individuo, para determinar la presencia de anticuerpos contra VIH y VHC mediante técnicas inmunoenzimáticas. En el caso del VIH la técnica de "Western blot" se aplicó con fines de confirmación. La prevalencia final de anticuerpos contra VHC se hizo mediante un cálculo ajustado, que empleó un estimador poblacional del RDS. RESULTADOS: Las seroprevalencias globales de VHC y VIH, fueron 96 por ciento y 2.8 por ciento, respectivamente. Estas frecuencias fueron similares entre las muestras de ambas ciudades. La gran mayoría de los UDI (87.5 por ciento) manifestó haber transferido a otros sus equipos de inyección usados y a su vez 85.9 por ciento de los participantes declaró haber recibido equipos usados de otros. CONCLUSIONES: La seroprevalencia encontrada de VIH fue relativamente alta dada la prevalencia de VIH en la población general y la de VHC fue extremadamente alta entre los UDI estudiados en Tijuana y en Ciudad Juárez. Las prácticas frecuentes de compartimiento de equipo señalan hacia un alto potencial que favorece la transmisión de ambas infecciones investigadas. Por tanto, son necesarias actividades de consejería y pruebas de laboratorio para VHC dirigidas a UDI en México y asimismo intervenciones para reducir el uso compartido de equipos de inyección.

Prevalence of hepatitis C virus and HIV infection among injection drug users in two Mexican cities bordering the U.S.

OBJECTIVE: To estimate the prevalence of the hepatitis C virus (HCV) and HIV infection and associated risk behaviors among injection drug users (IDUs) in two northern Mexican cities. MATERIAL AND METHODS: Between February and April 2005, IDUs were recruited in Tijuana (N=222) and Ciudad Juarez (N=206) using respondent-driven sampling (RDS), a chain referral sampling approach. Interviewer-administered questionnaires assessed drug-using behaviors during the prior six months. Venous blood was collected for immunoassays to detect HIV and HCV antibodies. For HIV, Western blot or immunofluorescence assay was used for confirmatory testing. Final HCV antibody prevalence was estimated using RDS adjustments. RESULTS: Overall, HCV and HIV prevalence was 96.0% and 2.8%, respectively, and was similar in both cities. Most IDUs (87.5%) reported passing on their used injection equipment to others, and 85.9% had received used equipment from others. CONCLUSIONS: HIV prevalence was relatively high given the prevalence of HIV in the general population, and HCV prevalence was extremely high among IDUs in Tijuana and Ciudad Juarez. Frequent sharing practices indicate a high potential for continued transmission for both infections. HCV counseling and testing for IDUs in Mexico and interventions to reduce sharing of injection equipment are needed.

"Vivo para consumirla y la consumo para vivir" ["I live to inject and inject to live"]: high-risk injection behaviors in Tijuana, Mexico.

Injection drug use is a growing problem on the US-Mexico border, where Tijuana is situated. We studied the context of injection drug use among injection drug users (IDUs) in Tijuana to help guide future research and interventions. Guided in-depth interviews were conducted with 10 male and 10 female current IDUs in Tijuana. Topics included types of drug used, injection settings, access to sterile needles, and environmental influences. Interviews were taped, transcribed verbatim, and translated. Content analysis was conducted to identify themes. Of the 20 IDUs, median age and age at first injection were 30 and 18. Most reported injecting at least daily: heroin ("carga", "chiva", "negra"), methamphetamine ("crico", "cri-cri"), or both drugs combined. In sharp contrast to Western US cities, almost all regularly attended shooting galleries ("yongos" or "picaderos") because of the difficulties obtaining syringes and police oppression. Almost all shared needles/paraphernalia ["cuete" (syringe), "cacharros" (cookers), cotton from sweaters/socks (filters)]. Some reported obtaining syringes from the United States. Key themes included (1) pharmacies refusing to sell or charging higher prices to IDUs, (2) ample availability of used/rented syringes from "picaderos" (e.g., charging approximately 5 pesos or "10 drops" of drug), and (3) poor HIV/AIDS knowledge, such as beliefs that exposing syringes to air "kills germs." This qualitative study suggests that IDUs in Tijuana are at high risk of HIV and other blood-borne infections. Interventions are urgently needed to expand access to sterile injection equipment and offset the potential for a widespread HIV epidemic.

Historical trends in the production and consumption of illicit drugs in Mexico: implications for the prevention of blood borne infections.

Mexico has cultivated opium poppy since before the 1900's and has been an important transit route for South American cocaine for decades. However, only recently has drug use, particularly injection drug use, been documented as an important problem. Heroin is the most common drug used by Mexican injection drug users (IDUs). Increased cultivation of opium poppy in some Mexican states, lower prices for black tar heroin and increased security at U.S.-Mexican border crossings may be contributing factors to heroin use, especially in border cities. Risky practices among IDUs, including needle sharing and shooting gallery attendance are common, whereas perceived risk for acquiring blood borne infections is low. Although reported AIDS cases attributed to IDU in Mexico have been low, data from sentinel populations, such as pregnant women in the Mexican-U.S. border city of Tijuana, suggest an increase in HIV prevalence associated with drug use. Given widespread risk behaviors and rising numbers of blood borne infections among IDUs in Mexican-U.S. border cities, there is an urgent need for increased disease surveillance and culturally appropriate interventions to prevent potential epidemics of blood borne infections. We review available literature on the history of opium production in Mexico, recent trends in drug use and its implications, and the Mexican response, with special emphasis on the border cities of Ciudad Juarez and Tijuana.