Cross Section Uncertainties in the Gallium Neutrino Source Experiments

The 51Cr neutrino source experiments play a unique role in testing overall operations of the GALLEX and SAGE solar neutrino experiments. Recently Hata and Haxton argued that the excited-state contribution to the 71Ga cross section for 51Cr neutrino absorption might not be known reliably, despite forward-angle (p,n) measurements. A large-basis shell model calculation reported here indicates that the unusual situation they envisioned - destructive interference between weak spin and strong spin-tensor amplitudes - does occur for the transition to the first excited state in 71Ge. The calculation provides a counterexample to procedures previously used to determine the 51Cr cross section: the predicted (p,n) cross section for this state agrees with experiment, while the BGT value is well outside the accepted 3-standard-deviation limit. The results argue for a shift in the interpretation of the source experiments: they become more crucial as measurements of the 71Ga detector response to 7Be solar neutrinos, and less definitive as wholly independent tests of 71Ge recovery and counting efficiencies.Comment: 14 pages, 2 figures, Revte

Sensitivity analyses for effect modifiers not observed in the target population when generalizing treatment effects from a randomized controlled trial: Assumptions, models, effect scales, data scenarios, and implementation details

Background inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population—an assumption that may not hold in practice. Methods The proposed sensitivity analyses address the situation where a treatment effect modifier is observed in the trial but not the target population. These methods are based on an outcome model or the combination of such a model and weighting adjustment for observed differences between the trial sample and target population. They accommodate several types of outcome models: linear models (including single time outcome and pre- and post-treatment outcomes) for additive effects, and models with log or logit link for multiplicative effects. We clarify the methods’ assumptions and provide detailed implementation instructions. Illustration We illustrate the methods using an example generalizing the effects of an HIV treatment regimen from a randomized trial to a relevant target population. Conclusion These methods allow researchers and decision-makers to have more appropriate confidence when drawing conclusions about target population effects

Sensitivity analyses for misclassification of cause of death in the parametric G-formula

Cause-specific mortality is an important outcome in studies of interventions to improve survival, yet causes of death can be misclassified. Here, we present an approach to performing sensitivity analyses formisclassification of cause of death in the parametric g-formula. The g-formula is a useful method to estimate effects of interventions in epidemiologic research because it appropriately accounts for time-varying confounding affected by prior treatment and can estimate risk under dynamic treatment plans.We illustrate our approach using an example comparing acquired immune deficiency syndrome (AIDS)-related mortality under immediate and delayed treatment strategies in a cohort of therapy-naive adults entering care for human immunodeficiency virus infection in the United States. In the standard g-formula approach, 10-year risk of AIDSrelatedmortality under delayed treatment was 1.73 (95% CI: 1.17, 2.54) times the risk under immediate treatment. In a sensitivity analysis assuming that AIDS-related death was measured with sensitivity of 95% and specificity of 90%, the 10-year risk ratio comparing AIDS-related mortality between treatment plans was 1.89 (95% CI: 1.13, 3.14). When sensitivity and specificity are unknown, this approach can be used to estimate the effects of dynamic treatment plans under a range of plausible values of sensitivity and specificity of the recorded event type

Virologic suppression and CD4 + cell count recovery after initiation of raltegravir or efavirenz-containing HIV treatment regimens

Objective: To explore the effectiveness of raltegravir-based antiretroviral therapy (ART) on treatment response among ART-naive patients seeking routine clinical care. Design: Cohort study of adults enrolled in HIV care in the United States. Methods: We compared virologic suppression and CD4 + cell count recovery over a 2.5 year period after initiation of an ART regimen containing raltegravir or efavirenz using observational data from a US clinical cohort, generalized to the US population of people with diagnosed HIV. We accounted for nonrandom treatment assignment, informative censoring, and nonrandom selection from the US target population using inverse probability weights. Results: Of the 2843 patients included in the study, 2476 initiated the efavirenz-containing regimen and 367 initiated the raltegravir-containing regimen. In the weighted intent-To-Treat analysis, patients spent an average of 74 (95% confidence interval: 41, 106) additional days alive with a suppressed viral load on the raltegravir regimen than on the efavirenz regimen over the 2.5-year study period. CD4 + cell count recovery was also superior under the raltegravir regimen. Conclusion: Patients receiving raltegravir spent more time alive and suppressed than patients receiving efavirenz, but the probability of viral suppression by 2.5 years after treatment was similar between groups. Optimizing the amount of time spent in a state of viral suppression is important to improve survival among people living with HIV and to reduce onward transmission

Supermassive Binaries and Extragalactic Jets

Some quasars show Doppler shifted broad emission line peaks. I give new statistics of the occurrence of these peaks and show that, while the most spectacular cases are in quasars with strong radio jets inclined to the line of sight, they are also almost as common in radio-quiet quasars. Theories of the origin of the peaks are reviewed and it is argued that the displaced peaks are most likely produced by the supermassive binary model. The separations of the peaks in the 3C 390.3-type objects are consistent with orientation-dependent "unified models" of quasar activity. If the supermassive binary model is correct, all members of "the jet set" (astrophysical objects showing jets) could be binaries.Comment: 31 pages, PostScript, missing figure is in ApJ 464, L105 (see http://www.aas.org/ApJ/v464n2/5736/5736.html

Who Will Show? Predicting Missed Visits Among Patients in Routine HIV Primary Care in the United States

Missed HIV medical visits predict poor clinical outcomes. We sought to identify patients at high risk of missing visits. We analyzed 2002–2014 data from six large US HIV clinics. At each visit, we predicted the likelihood of missing the next scheduled visit using demographic, clinical, and patient-reported psychosocial variables. Overall, 10,374 participants contributed 105,628 HIV visits. For 17% of visits, the next scheduled appointment was missed. The strongest predictor of a future missed visit was past-year missed visits. A model with only this predictor had area under the receiver operator curve = 0.65; defining “high risk” as those with any past-year missed visits had 73% sensitivity and 51% specificity in correctly identifying a future missed visit. Inclusion of other clinical and psychosocial predictors only slightly improved performance. Past visit attendance can identify those at increased risk for future missed visits, allowing for proactive allocation of resources to those at greatest risk

Compound retention in care and all-cause mortality among persons living with human immunodeficiency virus

Background: To obtain optimal health outcomes, persons living with human immunodeficiency virus (HIV) must be retained in clinical care. We examined the relationships between 4 possible combinations of 2 separate retention measures (missed visits and the Institute of Medicine [IOM] indicator) and all-cause mortality. Methods: The sample included 4162 antiretroviral therapy (ART)–naive patients who started ART between January 2000 and July 2010 at any of 5 US sites of the Center for AIDS Research Network of Integrated Clinical Systems. The independent variable of interest was retention, captured over the 12-month period after the initiation of ART. The study outcome, all-cause mortality 1 year after ART initiation, was determined by querying the Social Security Death Index or the National Death Index. We evaluated the associations of the 4 categories of retention with all-cause mortality, using the Cox proportional hazards models. Results: Ten percent of patients did not meet retention standards for either measure (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.59–3.21). Patients retained by the IOM but not the missed-visits measure (42%) had a higher HR for mortality (1.72; 95% CI, 1.33–2.21) than patients retained by both measures (41%). Patients retained by the missed-visits but not the IOM measure (6%) had the same mortality hazards as patients retained by both measures (HR, 1.01; 95% CI, .54–1.87). Conclusions: Missed visits within the first 12 months of ART initiation are a major risk factor for subsequent death. Incorporating missed visits in clinical and public health retention and viral suppression programming is advised

Estimating multiple time-fixed treatment effects using a semi-Bayes semiparametric marginal structural Cox proportional hazards regression model

Marginal structural models for time-fixed treatments fit using inverse-probability weighted estimating equations are increasingly popular. Nonetheless, the resulting effect estimates are subject to finite-sample bias when data are sparse, as is typical for large-sample procedures. Here we propose a semi-Bayes estimation approach which penalizes or shrinks the estimated model parameters to improve finite-sample performance. This approach uses simple symmetric data-augmentation priors. Limited simulation experiments indicate that the proposed approach reduces finite-sample bias and improves confidence-interval coverage when the true values lie within the central “hill” of the prior distribution. We illustrate the approach with data from a nonexperimental study of HIV treatments

Patterns of efavirenz use as first-line antiretroviral therapy in the United States: 1999-2015

Background: Efavirenz has been a mainstay of antiretroviral therapy (ART) for over 15 years in the US. Its association with neuropsychiatric side effects may influence clinical prescribing and management. Methods: We included HIV-infected adults enrolled in care at seven sites across the US, who initiated combination ART between 1999 and 2015. We examined the proportion initiating and continuing on efavirenz, overall and by mental health status. Log binomial and Cox models were used to estimate associations between mental health, clinical and sociodemographic characteristics and initiating or switching from efavirenz as first-line ART. Results: Of the 8,230 participants included, 3,710 (45%) initiated efavirenz. In multivariable analyses, prior mono- or dual-ART, ART initiation after 2006, being female, intravenous drug use, antidepressant prescription, previous mental health diagnosis and baseline CD4+ T-cell count >350 cells/mm3 were inversely associated with initiating efavirenz. Participants initiating efavirenz had a faster time to a regimen switch, compared with those initiating an efavirenz-free regimen (P-value <0.01). Among efavirenz initiators, starting efavirenz in more recent time periods and a previous mental health diagnosis were associated with faster time to switching from efavirenz. Despite this, 40-50% of participants with a previous mental health diagnosis initiated and continued on efavirenz for much of the follow-up period. Conclusions: Multiple clinical factors, including mental health diagnoses, appeared to influence efavirenz use. While mental health diagnosis status and more recent treatment starts were associated with shorter duration of efavirenz therapy, a previous mental health diagnosis did not preclude efavirenz initiation or continuation in many participants

Marijuana Use Is Not Associated with Changes in Opioid Prescriptions or Pain Severity among People Living with HIV and Chronic Pain

Background:People living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation).Methods:Participants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation.Results:Of 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation.Conclusions:We did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana