Association between Use of Methadone, Other Central Nervous System Depressants, and QT

To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4  cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p0.05). In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval–Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection

Study objectiveTo evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women.DesignMulticenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]).ParticipantsA total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV.Measurements and main resultsData on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p&lt;0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+ &nbsp;cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p&lt;0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p&gt;0.05).ConclusionIn this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population

Evaporation tagging and atmospheric water budget analysis with WRF: A regional precipitation recycling study for West Africa

Regional precipitation recycling is the measure of the contribution of local evaporation E to local precipitation. This study provides a set of two methods developed in the Weather Research and Forecasting WRF model system for investigating regional precipitation recycling mechanisms: (1) tracking of tagged atmospheric water species originating from evaporation in a source region, ie E‐tagging, and (2) three‐dimensional budgets of total and tagged atmospheric water species. These methods are used to quantify the effect of return flow and nonwell vertical mixing neglected in the computation of the bulk precipitation recycling ratio. The developed algorithms are applied to a WRF simulation of the West African Monsoon 2003. The simulated region is characterized by vertical wind shear condition, i.e., southwesterlies in the low levels and easterlies in the mid‐levels, which favors return flow and nonwell vertical mixing. Regional precipitation recycling is investigated in 100 × 100 and 1000 × 1000 km2 areas. A prerequisite condition for evaporated water to contribute to the precipitation process in both areas is that it is lifted to the mid‐levels where hydrometeors are produced. In the 100 × 100 (1000 × 1000) km$^{2}$ area the bulk precipitation recycling ratio is 0.9 (7.3) %. Our budget analysis reveals that return flow and nonwell vertically mixed outflow increase this value by about +0.2 (2.9) and +0.2 (1.6) %, respectively, thus strengthening the well‐known scale‐dependency of regional precipitation recycling