Identifying individuals with virologic failure after initiating effective antiretroviral therapy: The surprising value of mean corpuscular hemoglobin in a cross-sectional study

<p>Abstract</p> <p>Objective</p> <p>Recent studies have shown that the current guidelines suggesting immunologic monitoring to determine response to highly active antiretroviral therapy (HAART) are inadequate. We assessed whether routinely collected clinical markers could improve prediction of concurrent HIV RNA levels.</p> <p>Methods</p> <p>We included individuals followed within the Johns Hopkins HIV Clinical Cohort who initiated antiretroviral therapy and had concurrent HIV RNA and biomarker measurements ≥4 months after HAART. A two tiered approach to determine whether clinical markers could improve prediction included: 1) identification of predictors of HIV RNA levels >500 copies/ml and 2) construction and validation of a prediction model.</p> <p>Results</p> <p>Three markers (mean corpuscular hemoglobin [MCH], CD4, and change in percent CD4 from pre-HAART levels) in addition to the change in MCH from pre-HAART levels contained the most predictive information for identifying an HIV RNA >500 copies/ml. However, MCH and change in MCH were the two most predictive followed by CD4 and change in percent CD4. The logistic prediction model in the validation data had an area under the receiver operating characteristic curve of 0.85, and a sensitivity and specificity of 0.74 (95% CI: 0.69-0.79) and 0.89 (95% CI: 0.86-0.91), respectively.</p> <p>Conclusions</p> <p>Immunologic criteria have been shown to be a poor guideline for identifying individuals with high HIV RNA levels. MCH and change in MCH were the strongest predictors of HIV RNA levels >500. When combined with CD4 and percent CD4 as covariates in a model, a high level of discrimination between those with and without HIV RNA levels >500 was obtained. These data suggest an unexplored relationship between HIV RNA and MCH.</p

A qualitative study examining the benefits and challenges of incorporating patient-reported outcome substance use and mental health questionnaires into clinical practice to improve outcomes on the HIV care continuum.

BACKGROUND: Inadequate identification and treatment of substance use (SU) and mental health (MH) disorders hinders retention in HIV care. The objective of this study was to elicit stakeholder input on integration of SU/MH screening using computer-assisted patient-reported outcomes (PROs) into clinical practice. METHODS: We conducted semi-structured interviews with HIV-positive patients who self-reported SU/MH symptoms on a computer-assisted PROs (n = 19) and HIV primary care providers (n = 11) recruited from an urban academic HIV clinic. Interviews were audio-recorded and transcribed. We iteratively developed codes and organized key themes using editing style analysis. RESULTS: Two themes emerged: (1) Honest Disclosure: Some providers felt PROs might improve SU/MH disclosure; more were concerned that patients would not respond honestly if their provider saw the results. Patients were also divided, stating PROs could help overcome stigma but that it could be harder to disclose SU/MH to a computer versus a live person. (2) Added Value in the Clinical Encounter: Most providers felt PROs would fill a practice gap. Patients had concerns regarding confidentiality but indicated PROs would help providers take better care of them. CONCLUSIONS: Both patients and providers indicated that PROs are potentially useful clinical tools to improve detection of SU/MH. However, patients and providers expressed conflicting viewpoints about disclosure of SU/MH using computerized PROs. Future studies implementing PROs screening interventions must assess concerns over confidentiality and honest disclosure of SU/MH to understand the effectiveness of PROs as a clinical tool. More research is also needed on patient-centered integration of the results of PROs in HIV care

Impact of Tobacco Control Interventions on Smoking Initiation, Cessation, and Prevalence: A Systematic Review

Background. Policymakers need estimates of the impact of tobacco control (TC) policies to set priorities and targets for reducing tobacco use. We systematically reviewed the independent effects of TC policies on smoking behavior. Methods. We searched MEDLINE (through January 2012) and EMBASE and other databases through February 2009, looking for studies published after 1989 in any language that assessed the effects of each TC intervention on smoking prevalence, initiation, cessation, or price participation elasticity. Paired reviewers extracted data from studies that isolated the impact of a single TC intervention. Findings. We included 84 studies. The strength of evidence quantifying the independent effect on smoking prevalence was high for increasing tobacco prices and moderate for smoking bans in public places and antitobacco mass media campaigns. Limited direct evidence was available to quantify the effects of health warning labels and bans on advertising and sponsorship. Studies were too heterogeneous to pool effect estimates. Interpretations. We found evidence of an independent effect for several TC policies on smoking prevalence. However, we could not derive precise estimates of the effects across different settings because of variability in the characteristics of the intervention, level of policy enforcement, and underlying tobacco control environment

Heavy Alcohol Use Is Associated With Worse Retention in HIV Care

Poor retention in HIV care is associated with worse clinical outcomes and increased HIV transmission. We examined the relationship between self-reported alcohol use, a potentially modifiable behavior, and retention

HIV primary care providers—Screening, knowledge, attitudes and behaviors related to alcohol interventions

Alcohol has particularly harmful health effects in HIV-infected patients; therefore, HIV clinics are an important setting for integration of brief alcohol intervention and alcohol pharmacotherapy to improve patient outcomes. Current practices of alcohol screening, counseling, and prescription of pharmacotherapy by HIV providers are unknown

Not all non-drinkers with HIV are equal: demographic and clinical comparisons among current non-drinkers with and without a history of prior alcohol use disorders *

Studies of persons living with HIV (PLWH) have compared current non-drinkers to at-risk drinkers without differentiating whether current non-drinkers had a prior alcohol use disorder (AUD). The purpose of this study was to compare current non-drinkers with and without a prior AUD on demographic and clinical characteristics to understand the impact of combining them. We included data from 6 sites across the US from 1/2013–3/2015. Patients completed tablet-based clinical assessments at routine clinic appointments using the most recent assessment. Current non-drinkers were identified by AUDIT-C scores of 0. We identified a prior probable AUD by a prior AUD diagnosis in the electronic medical record (EMR) or a report of attendance at alcohol treatment in the clinical assessment. We used multivariate logistic regression to examine factors associated with prior AUD. Among 2235 PLWH who were current non-drinkers, 36% had a prior AUD with more patients with an AUD identified by the clinical assessment than the EMR. Higher proportions with a prior AUD were male, depressed, and reported current drug use compared to non-drinkers without a prior AUD. Former cocaine/crack (70% vs. 25%), methamphetamine/crystal (49% vs. 16%) and opioid/heroin use (35% vs. 7%) were more commonly reported by those with a prior AUD. In adjusted analyses, male sex, past methamphetamine/crystal use, past marijuana use, past opioid/heroin use, past and current cocaine/crack use and cigarette use were associated with a prior AUD. In conclusion, this study found that among non-drinking PLWH in routine clinical care, 36% had a prior AUD. We found key differences between those with and without prior AUD in demographic and clinical characteristics including drug use and depression. These results suggest non-drinkers are heterogeneous and need further differentiation in studies and that prior alcohol misuse including alcohol treatment should be included in behavioral health assessments as part of clinical care

A Digital Counselor-Delivered Intervention for Substance Use Among People With HIV: Development and Usability Study

BackgroundSubstance use disorders are prevalent and undertreated among people with HIV. Computer-delivered interventions (CDIs) show promise in expanding reach, delivering evidence-based care, and offering anonymity. Use in HIV clinic settings may overcome access barriers. Incorporating digital counselors may increase CDI engagement, and thereby improve health outcomes. ObjectiveWe aim to develop and pilot a digital counselor–delivered brief intervention for people with HIV who use drugs, called “C-Raven,” which is theory grounded and uses evidence-based practices for behavior change. MethodsIntervention mapping was used to develop the CDI including a review of the behavior change research in substance use, HIV, and digital counselors. We conducted in-depth interviews applying the situated-information, motivation, and behavior skills model and culturally adapting the content for local use with people with HIV. With a user interaction designer, we created various digital counselors and CDI interfaces. Finally, a mixed methods approach using in-depth interviews and quantitative assessments was used to assess the usability, acceptability, and cultural relevance of the intervention content and the digital counselor. ResultsParticipants found CDI easy to use, useful, relevant, and motivating. A consistent suggestion was to provide more information about the negative impacts of drug use and the interaction of drug use with HIV. Participants also reported that they learned new information about drug use and its health effects. The CDI was delivered by a “Raven,” digital counselor, programmed to interact in a motivational interviewing style. The Raven was perceived to be nonjudgmental, understanding, and emotionally responsive. The appearance and images in the intervention were perceived as relevant and acceptable. Participants noted that they could be more truthful with a digital counselor, however, it was not unanimously endorsed as a replacement for a human counselor. The C-Raven Satisfaction Scale showed that all participants rated their satisfaction at either a 4 (n=2) or a 5 (n=8) on a 5-point Likert scale and all endorsed using the C-Raven program again. ConclusionsCDIs show promise in extending access to care and improving health outcomes but their development necessarily requires integration from multiple disciplines including behavioral medicine and computer science. We developed a cross-platform compatible CDI led by a digital counselor that interacts in a motivational interviewing style and (1) uses evidence-based behavioral change methods, (2) is culturally adapted to people with HIV who use drugs, (3) has an engaging and interactive user interface, and (4) presents personalized content based on participants’ ongoing responses to a series of menu-driven conversations. To advance the continued development of this and other CDIs, we recommend expanded testing, standardized measures to evaluate user experience, integration with clinician-delivered substance use treatment, and if effective, implementation into HIV clinical care

Progesterone receptors on human spermatozoa

773-780<span style="font-size:12.0pt;mso-bidi-font-size:8.0pt; line-height:115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Progesterone, primarily recognized as a female steroid hormone, is reported to affect several sperm functions especially capacitation, motility and acrosome reaction. These effects of progesterone on the spermatozoa are mediated via the progesterone bindings sites/progesterone receptor (PR) on the acrosomal membrane. These receptors in response to progesterone increase the intercellular Ca2+ levels and stimulate Ca<span style="font-size:10.0pt;mso-bidi-font-size: 6.0pt;line-height:115%;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">2<span style="font-size:12.0pt;mso-bidi-font-size: 8.0pt;line-height:115%;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">+<span style="font-size:12.0pt; mso-bidi-font-size:8.0pt;line-height:115%;font-family:" times="" new="" roman";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"=""> influx in the mature human spermatozoa via non-genomic mode of actions. Characterization of this receptor reveals that the sperm PR is masked protein and is exposed to the surface by some non-ionic detergents. Localized on to the acrosome region of the spermatozoa, these receptors are <span style="font-size:10.0pt;mso-bidi-font-size:6.0pt;line-height:115%;font-family: HiddenHorzOCR;mso-hansi-font-family:" times="" new="" roman";mso-bidi-font-family:="" hiddenhorzocr;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"="">recognized <span style="font-size:12.0pt;mso-bidi-font-size:8.0pt; line-height:115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">by most antibodies directed towards the C-terminal region of the conventional PR. The estimated molecular weight of PR on spermatozoa varies from 27 kDa to 85 kDa. At the molecular level, sequences encoding for the entire DNA and hormone binding domains of the conventional PR are detected in the mRNA derived from spermatozoa. No insertions, deletions or mutations a re detected in this region. These results are suggestive of the fact that at least the C terminal region of the conventional PR is conserved in the sperm. It is hypothesized that post-translational modifications or peptide splicing of the conventional PR in spermatozoa may possibly lead to the variant of the steroid hormone receptor. Detailed characterization of the sperm PR will be important in understanding the alternate non-genomic mode of action of steroid hormone receptors.</span