Search

In many chronic conditions, subjects alternate between an active and an inactive state, and sojourns into the active state may involve multiple lesions, infections, or other recurrences with different times of onset and resolution. We present a biologically interpretable model of such chronic recurrent conditions based on a queueing process. The model has a birth-death process describing recurrences and a semi-Markov process describing the alternation between active and inactive states, and can be fit to panel data that provide only a binary assessment of the active or inactive state at a series of discrete time points using a hidden Markov approach. We accommodate individual heterogeneity and covariates using a random effects model, and simulate the posterior distribution of unknowns using a Markov chain Monte Carlo algorithm. Application to a clinical trial of genital herpes shows how the method can characterize the biology of the disease and estimate treatment efficacy.

When zidovudine and dideoxycytidine (ddC) were given on schedules of 1 week on drug and 1 week off, results differed substantially in effects on HIV (human immunodeficiency virus type 1)-induced immune activation. Zidovudine (200 mg every 4 h) caused marked lowering toward normal of serum neopterin and β2 -microglobulin within I week. This effect was lost within I weekoff zidovudine. Intermittent ddC (0.03 mg/kg every4 h) had a smaller I-week effect but had a delayed cumulative suppressive effect on HIV-associated immune activation that was not seen with intermittent zidovudine therapy. Zidovudine and ddC given in alternating weeks had synergistic effects in the first 10 weeks (e.g., early and rapid reduction followed by cumulatively greater effects on immune cell activation). The identical sawtooth effect of intermittent zidovudine was also evident in serum HIV p24 antigen levels. This is consistent with the hypothesis that the increased serum levels of the immune activation markers seen in HIV infection reflect stimulatory effects of HIV viral components on immune system cells. [ABSTRACT FROM PUBLISHER]

Several letters to the editor are presented in response to articles in previous issues of the "American Journal of Public Health" including results of the epidemiological studies conducted by A. M. Walker and J. L. Fleiss on significance tests and confidence intervals and another on the need for preservation of stocks of variola virus and vaccination of military personnel. Lastly, "On Homelessness and the American Way," by Steven Jonas.

Background Pain among young adult patients with sickle cell disease (PWSCD) is a highly significant public health problem associated with reduced quality of life. Due to issues uniquely affecting PWSCD, including distrust of research, challenging life situations, debilitating pain, stigma, and logistical challenges (e.g., child or elder care and transportation), SCD researchers often find it challenging to meet sample size and enrollment targets. To our knowledge, all known SCD studies have solely recruited participants in person (e.g., clinics and local organizations) and utilized lengthy interventions with suboptimal recruitment and retention results. Newer recruitment methods, such as online recruitment, need to be explored for research among PWSCD. In this pilot project, we sought to address these challenges by investigating: 1) a novel method of using online outreach to recruit/enroll young PWSCD and 2) a novel, brief online mindfulness intervention adapted from Mindfulness-Oriented Recovery Enhancement (MORE): Mini-MORE designed to treat pain among PWSCD.  Methods Participants (N = 32) were recruited online (e.g., paid advertisements on Facebook and NextDoor; free advertisements on Facebook groups and Reddit) and screened by phone from October 25 to November 8, 2022. Participants watched an online Mini-MORE video. Immediately before and after watching the video, participants rated their pain intensity and unpleasantness on an 11-point numeric rating scale (NRS). Afterward, participants were emailed an individualized link to additional audio recordings for ongoing practice. Immediately before and after accessing the additional recordings, participants rated their pain intensity, anxiety, and depression on an 11-point NRS. T-tests were used to examine the impact of Mini MORE on outcomes at two-time points. Results A total of 84 participants completed the self-screening. The majority of self-screeners resulted from free posts in Facebook groups (77%), Reddit (1%), and Craigslist (6%). Thirty-two (32) eligible participants agreed to join a Zoom meeting to watch the video. The entire Mini-MORE video was viewed by 31 of 32 participants (97%). Pain intensity decreased by 1.7 points (p<0.001, Cohen's  d =2.19), and pain unpleasantness decreased by 2.1 points (p<0.001, Cohen's  d =2.20). Listening to the supplemental recordings was associated with significant, immediate decreases in pain intensity by 1.3 points (p=0.015, Cohen's  d =2.05), anxiety by 1.8 points (p=0.022, Cohen's  d =3.10), and depression by 1.74 points (p=0.019, Cohen's  d =2.94). Conclusions Results suggest that online methods are feasible in recruiting and enrolling young PWSCD, and the online Mini-MORE intervention is acceptable among PWSCD. Future research is needed to assess whether Mini-MORE is associated with decreased pain symptomology in young PWSCD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ugarte et al.)

Background: Innovative surveillance methods are needed to assess adherence to COVID-19 recommendations, especially methods that can provide near real-time or highly geographically targeted data. Use of location-based social media image data (eg, Instagram images) is one possible approach that could be explored to address this problem., Objective: We seek to evaluate whether publicly available near real-time social media images might be used to monitor COVID-19 health policy adherence., Methods: We collected a sample of 43,487 Instagram images in New York from February 7 to April 11, 2020, from the following location hashtags: #Centralpark (n=20,937), #Brooklyn Bridge (n=14,875), and #Timesquare (n=7675). After manually reviewing images for accuracy, we counted and recorded the frequency of valid daily posts at each of these hashtag locations over time, as well as rated and counted whether the individuals in the pictures at these location hashtags were social distancing (ie, whether the individuals in the images appeared to be distanced from others vs next to or touching each other). We analyzed the number of images posted over time and the correlation between trends among hashtag locations., Results: We found a statistically significant decline in the number of posts over time across all regions, with an approximate decline of 17% across each site (P<.001). We found a positive correlation between hashtags (#Centralpark and #Brooklynbridge: r=0.40; #BrooklynBridge and #Timesquare: r=0.41; and #Timesquare and #Centralpark: r=0.33; P<.001 for all correlations). The logistic regression analysis showed a mild statistically significant increase in the proportion of posts over time with people appearing to be social distancing at Central Park (P=.004) and Brooklyn Bridge (P=.02) but not for Times Square (P=.16)., Conclusions: Results suggest the potential of using location-based social media image data as a method for surveillance of COVID-19 health policy adherence. Future studies should further explore the implementation and ethical issues associated with this approach., (©Sean D Young, Qingpeng Zhang, Daniel Dajun Zeng, Yongcheng Zhan, William Cumberland. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.03.2022.)

Aim: Reductions in substance use were examined in response to an intensive intervention with people living with human immunodeficiency virus (HIV) (PLH)., Design, Setting and Participants: A randomized controlled trial was conducted with 936 PLH who had recently engaged in unprotected sexual risk acts recruited from four US cities: Milwaukee, San Francisco, New York and Los Angeles. Substance use was assessed as the number of days of use of 19 substances recently (over the last 90 days), evaluated at 5-month intervals over 25 months., Intervention: A 15-session case management intervention was delivered to PLH in the intervention condition; the control condition received usual care., Measurements: An intention-to-treat analysis was conducted examining reductions on multiple indices of recent substance use calculated as the number of days of use., Findings: Reductions in recent substance use were significantly greater for intervention PLH compared to control PLH: alcohol and/or marijuana use, any substance use, hard drug use and a weighted index adjusting for seriousness of the drug. While the intervention-related reductions in substance use were larger among women than men, men also reduced their use. Compared to controls, gay and heterosexual men in the intervention reduced significantly their use of alcohol and marijuana, any substance, stimulants and the drug severity-weighted frequency of use index. Gay men also reduced their hard drug use significantly in the intervention compared to the control condition., Conclusions: A case management intervention model, delivered individually, is likely to result in significant and sustained reductions in substance use among PLH.

ZIP models were used to detect reductions in drug abuse among young people living with HIV (YPLH) over 15 months when most young people abstain from use. YPLH (n = 171) aged 16 to 29 years were randomly assigned to an 18 session intervention or a delayed-intervention condition. The ZIP models showed significant reductions in abuse of multiple substances over time in the non-delayed intervention. Previous analyses did not find significant reductions. Intervention efficacy often cannot be detected if there are highly skewed distributions of outcomes, such as drug abuse. ZIP modeling offers an opportunity to more reliably detect behavioral changes.

Aim: Individuals with human immunodeficiency virus (HIV) infection were evaluated for evidence of abnormal polymorphonuclear leucocyte (PMN) rigidity, which can alter capillary blood flow., Methods: The transit time of individual PMN through 8 microm pores in a cell transit analyser was used as a measure of cell rigidity. PMN transit time was compared between HIV infected individuals (n=45) with and without CMV retinitis and HIV negative controls (n=17)., Results: Transit times were longer for PMN from HIV infected individuals than for PMN from controls (p<0.001). PMN from HIV infected individuals with CMV retinitis (n=13) had longer transit times than PMN from those without CMV retinitis (n=32, p<0.001). Transit times were longer in HIV infected individuals with lower CD4+ T lymphocyte counts (p<0.001). Regression analysis indicated that the relation between transit times and the presence of CMV retinitis could not be explained solely on the basis of low CD4+ T lymphocytes. In HIV infected individuals, mean transit time was not correlated with age, blood pressure, or serum creatinine, cholesterol, or triglycerides., Conclusions: HIV infected individuals appear to have increased PMN rigidity, a cellular change that might be involved in the pathogenesis of HIV related retinal microvasculopathy. PMN rigidity appears to be related to severity of immune dysfunction. PMN rigidity may remain high in patients with CMV retinitis after elevations of CD4+ T lymphocyte counts that result from potent antiretroviral therapy.

B cell hyperactivation accompanies HIV infection and is believed to contribute to the increased incidence of B cell lymphoma in persons with AIDS. To examine B cell activation which precedes the development of AIDS-associated lymphoma, we measured levels of two B cell stimulatory molecules, soluble CD23 (sCD23) and interleukin 6 (IL6), in the serum of HIV-infected individuals prior to the diagnosis of lymphoma. Serum sCD23 was elevated in those subjects who developed lymphoma, compared to AIDS, HIV+, and HIV- controls (P = 0.001). Serum IL6 was significantly elevated in subjects who developed Burkitt's/small noncleaved cell lymphoma (BL/SNC, P = 0.01), but not in those subjects who developed large cell, immunoblastic, or central nervous system lymphomas, compared to CD4-matched AIDS controls who did not have lymphoma. These results suggest that lymphomagenesis of the BL/SNC subtype of AIDS lymphoma reflects B cell hyperactivation of a different nature from that which precedes other subtypes of AIDS-associated B cell lymphoma., (Copyright 1999 Academic Press.)

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers., (Copyright 1999 Academic Press.)

The CD8+ T-cell response is central to control and eventual elimination of persistent viral infections. Although it might be expected that CD8+ T-cell activation would be associated with a better clinical outcome during viral infections, in long-term HIV-1 infection, high levels of CD8+ T-cell activation are instead associated with faster disease progression. In this study, cell surface expression of CD38, a flow cytometric marker of T-cell activation of CD8+ T cells, had predictive value for HIV-1 disease progression that was in part independent of the predictive value of plasma viral burden and CD4+ T-cell number. Measurements of CD38 antigen expression on CD8+ T cells in HIV-1-infected patients may be of value for assessing prognosis and the impact of therapeutic interventions. The pathogenetic reason why CD8+ T-cell activation is associated with poor outcome in HIV-1 disease remains unknown. Possibly CD8+ T-cell activation contributes to immunologic exhaustion, hyporesponsiveness of T cells to their cognate antigens, or perturbations in the T-cell receptor repertoire.

The prognostic value of several immunologic markers were compared in Los Angeles Multicenter AIDS Cohort Study (MACS) participants, most of whom had been infected with HIV for >8 years. Markers studied included CD4+ cell number, flow cytometric measurements of CD8+ cell expression of CD38 and HLA-DR antigens, and serum markers of immune activation including neopterin, beta2-microglobulin, soluble interleukin-2 receptor, soluble CD8, and soluble tumor necrosis factor receptor-alpha (TNF-alpha) type II. Cox proportional hazards models indicated that elevated CD38 on CD8, a flow cytometric measurement of CD8+ T-lymphocyte activation, was the most predictive marker of those studied for development of a clinical AIDS diagnosis and death. As compared with the reference group, who had CD38 on CD8 <2470 molecules per CD8+ cell and in whom 4 of 99 developed clinical AIDS within 3 years, participants with CD38 on CD8 between 2470 and 3899, 3900 and 7250, and >7250 had relative risks (and numbers developing AIDS within 3 years) of 5.0 (15 of 81), 12.3 (24 of 60), and 41.4 (36 of 49), respectively. The strong prognostic value of CD38 on CD8 measurements and the fundamental importance of chronic immune activation in the pathogenesis of HIV disease suggests that this marker might have utility in the clinical management of HIV-infected persons.

Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment of immune function reflected in reduced lymphocyte proliferative responses. Many other immune changes are induced by HIV-1, but their relationship to lymphocyte functional defects is not known. The present study was designed to correlate functional defects with other HIV disease parameters. Cryopreserved samples from 118 HIV-1-positive subjects and 40 seronegative individuals were examined. The main findings were that impaired proliferative responses to mitogens correlated with (i) decreased cell surface expression of the interleukin-2 receptor (CD25), (ii) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and increased CD8 cell numbers, and (iv) increased levels of serum immune complex dissociated p24 antigen. However, impaired function was not associated with increased serum neopterin, beta2-microglobulin, or soluble interleukin-2 receptor or with CD38 antigen expression on lymphocytes. In summary, proliferative functional impairment correlated with some, but not all, immunological changes associated with HIV-1 infection. Most of the phenotypic markers that correlated with altered function are cell surface molecules with significant roles in lymphocyte proliferation and were associated primarily with CD4 cells, compatible with the view that dysregulation of CD4 cells is responsible for impaired function.

Relative fluorescence intensity measurements from a flow cytometer were used to evaluate expression of CD38 and HLA-DR antigens. These molecules are associated with cellular activation and are present at increased levels on the CD8+ lymphocytes of HIV-infected subjects. In the current study, the prognostic value of mean fluorescence intensity measurements of CD38 and HLA-DR on CD8+ cells was compared to results from our previous study in which we reported prognostic value for an elevated percentage of CD8+ cells that were positive for expression of the CD38 antigen (Giorgi et al.: JAIDS 6:904-912, 1993). Using the proportional hazards model, elevated mean fluorescence intensity of CD38 expression on CD8+ cells had prognostic value for development of AIDS that was almost identical to the prognostic value of the percentage of CD8+ cells that were positive for expression of CD38. This prognostic value was in addition to that provided by the patient's CD4+ cell measurement. To our knowledge, this is the first report that a measurement of fluorescence intensity can be used as a prognostic marker in an immunodeficiency disease. Efforts are needed to establish methods that will allow widespread application of this observation in the clinical management of HIV-infected subjects.

A method for estimating a normal range from a set of immunologic measurements on control subjects when there may be more than one observation per subject is described. The method is nonparametric, makes efficient use of all observations, and is very simple to apply. It is illustrated on a set of 152 CD38 measurements from 58 healthy men.