Grace periods and exposure misclassification in self-controlled case-series studies of drug-drug interactions.

The self-controlled case-series (SCCS) research design is increasingly used in pharmacoepidemiologic studies of drug-drug interactions (DDIs), with the target of inference being the incidence rate ratio (IRR) associated with concomitant exposure to the object plus precipitant drug versus the object drug alone. While day-level drug exposure can be inferred from dispensing claims, these inferences may be inaccurate, leading to biased IRRs. Grace periods (periods assuming continued treatment impact after days' supply exhaustion) are frequently used by researchers, but the impact of grace period decisions on bias from exposure misclassification remains unclear. Motivated by an SCCS study examining the potential DDI between clopidogrel (object) and warfarin (precipitant), we investigated bias due to precipitant or object exposure misclassification using simulations. We show that misclassified precipitant treatment always biases the estimated IRR toward the null, whereas misclassified object treatment may lead to bias in either direction or no bias, depending on the scenario. Further, including a grace period for each object dispensing may unintentionally increase the risk of misclassification bias. To minimize such bias, we recommend 1) avoiding the use of grace periods when specifying object drug exposure episodes; and 2) including a washout period following each precipitant exposed period.

A Quantitative Bias Analysis Approach to Informative Presence Bias in Electronic Health Records.

Accurate outcome and exposure ascertainment in electronic health record (EHR) data, referred to as EHR phenotyping, relies on the completeness and accuracy of EHR data for each individual. However, some individuals, such as those with a greater comorbidity burden, visit the health care system more frequently and thus have more complete data, compared with others. Ignoring such dependence of exposure and outcome misclassification on visit frequency can bias estimates of associations in EHR analysis. We developed a framework for describing the structure of outcome and exposure misclassification due to informative visit processes in EHR data and assessed the utility of a quantitative bias analysis approach to adjusting for bias induced by informative visit patterns. Using simulations, we found that this method produced unbiased estimates across all informative visit structures, if the phenotype sensitivity and specificity were correctly specified. We applied this method in an example where the association between diabetes and progression-free survival in metastatic breast cancer patients may be subject to informative presence bias. The quantitative bias analysis approach allowed us to evaluate robustness of results to informative presence bias and indicated that findings were unlikely to change across a range of plausible values for phenotype sensitivity and specificity. Researchers using EHR data should carefully consider the informative visit structure reflected in their data and use appropriate approaches such as the quantitative bias analysis approach described here to evaluate robustness of study findings.

Prevalence and factors associated with fertility desires among HIV-positive MSM.

The National surveillance data showed that homosexual transmission played a considerable role in new HIV infections in China. The emphasis on antiretroviral therapy and prevention of mother-to-child transmission provided chances for reproduction among people living with HIV/AIDS. Issues of fertility desire have a paucity of data among HIV-positive men who have sex with men (MSM). This cross-sectional study has assessed fertility attitudes and associated factors, as well as the reproductive knowledge among HIV-positive MSM. Analysis was mainly based on the multinomial regression model. The study included 129 participants, and almost all of the participants (96.1%) were between 18 and 30 years old and 82.2% of them were single. About 35.6% expressed a fertility desire. MSM without siblings tended to have fertility desire (OR = 0.236, 95%CI: 0.078∼0.712, p = 0.010). Surrogacy (36.4%) was the most desired method among the 86 respondents who had the desire or did not make a decision. While the accuracy of the reproductive knowledge was only 69.6%. In summary, we recommend that providers offer much more professional information and develop assisted reproductive technology to meet the reproductive aspirations of HIV-positive MSM.

Life expectancy and mental related burden of disease among people living with HIV/AIDS.

Mental health problems leads to serious disease burden among people living with HIV/AIDS (PLHIV). The study aimed at measuring the mental disorders-caused burden of disease based on PLHIV in mainland China. The data used was from the national HIV/AIDS case reporting system, life expectancy (LE) and LE-eliminated suicide were evaluated by the life-table method. The total YLLs and YLLs caused by suicide in each age group were calculated. The disability weights were estimated by the scale of depression symptoms (CES-D) from the multi-center cross-sectional survey, then calculated the corresponding YLDs as a burden of mental illness among PLHIV. Results showed that the LE had been prolonged by implementing antiviral therapy for PLHIV. The proportion of YLLs caused by suicide was the highest (5·46%) in the 15-24 age group. The YLDs in the 25-34 age group were the highest. The YLLs caused by suicide in males were higher than those in the same age group of females. The YLDs and YLLs were higher in heterosexual-infected PLHIV than in homosexual-infected PLHIV, except for YLLs in the 25-34 age group. In summary, this study first provided localized data on the disease burden caused by mental health problems among PLHIV.

Incidence of low-level viremia and its impact on virologic failure among people living with HIV who started an integrase strand transfer inhibitors: a longitudinal cohort study.

BACKGROUND: Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. METHODS: A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50-999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. RESULTS: The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137-0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk. CONCLUSION: Our findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies.

Decrease in Haemoglobin in Association with Aneurysm Volume Loss after Endovascular Repair of Abdominal Aortic Aneurysm.

Background: Anaemia (low haemoglobin [Hb]) is well known to be associated with high mortality and adverse cardiac events following surgical treatment of abdominal aortic aneurysm (AAA). However, little is known about the relationship of AAA volume and Hb level alterations with endovascular repair of AAA. This study aimed to examine the changes in the Hb level and aneurysm volume before and after endovascular aneurysm repair (EVAR) for AAA and determine the relationship between the post-operative Hb level and the volume loss of AAA. Methods: This retrospective study reviewed patients with AAA who underwent EVAR between January 2020 and February 2021 at a tertiary medical centre. The clinical features and medical history of the patients were analysed. Alterations in the Hb level were recorded, and the AAA volume was calculated from computed tomography angiography images before and after EVAR to infer the association between the post-operative Hb level and alterations in AAA volume. Moreover, AAA volume, pre-operative Hb level and medical history were studied to identify the risk factors for anaemia 24 h after EVAR. Results: A total of 74 patients (mean age, 67 ± 7.9 years) were included in this study. The Hb level decreased significantly 24 h after EVAR, and the post-operative Hb level was negatively correlated with AAA volume loss (r = -0.252, p = 0.041). No relationship was observed between AAA volume loss and decrease in the Hb level (r = 0.072, p = 0.571) or between pre-operative AAA volume and decrease in the Hb level (r = 0.072, p = 0.566). Furthermore, 59.5% of the patients (n = 44) developed anaemia 24 h after EVAR. The odds ratio (OR) of anaemia 24 h after EVAR was 5.3 times higher in those with hypertension (OR, 5.304; 95% confidence interval [CI], 1.024-27.424) than in those without the condition. The pre-operative Hb level (or normal Hb level) was a protective factor (OR = 0.909; 95% CI, 0.853-0.969). The area under the receiver operating characteristic curve was 0.840. The post-operative Hb level declined significantly, and AAA volume loss contributed to it. Moreover, hypertension was identified to be a risk factor for anaemia 24 h after EVAR, and pre-operative Hb level was discerned to be a protective factor. Conclusions: The findings suggest that decrease in the Hb level in the early post-EVAR stage warrants the attention of surgeons, especially in patients with a history of hypertension or a low pre-operative Hb level.

Efficacy and Incidence of Treatment-Related Adverse Events of Thrombopoietin Receptor Agonists in Adults with Immune Thrombocytopenia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Study.

INTRODUCTION: The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP). METHODS: Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome. RESULTS: In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0. CONCLUSIONS: These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy.

Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier's endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

Neoadjuvant chemotherapy use trends among older women with breast cancer: 2010-2017.

PURPOSE: This study assessed chemotherapy use trends before (neoadjuvant chemotherapy [NAC]) or after surgery (adjuvant chemotherapy [AdC]) among older women with breast cancer and examined factors related to NAC receipt. METHODS: Women (> 65 years) diagnosed with stage I-III breast cancer during 2010-2017 who received NAC or AdC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. All patients were stratified into six strata based on subtype (hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR + /HER2-], HER2 + , and triple-negative breast cancer [TNBC]) and stage (I-II and III). Cochran-Armitage tests were performed to test temporal trends of NAC use in each stratum. Multivariable logistic regression analyses were performed to identify factors (sociodemographic and clinical) related to NAC use. RESULTS: Among included older (mean ± standard deviation: 72.3 ± 5.2 years) women (N = 8,495) with stage I-III breast cancer, NAC use increased from 11.7% (2010) to 32.6% (2017). Significant increases in NAC were found in all strata (p < .0001) with more substantial increases in HER2 + disease and TNBC compared to HR + /HER2- disease. Multivariable logistic regressions identified the youngest age category (66-69 years) and later stage as significant (p < 0.05) predictors of NAC receipt in most strata, in addition to diagnosis year. CONCLUSION: Similar to the overall breast cancer population, NAC use increased among a population of older women. NAC was received by most patients with stage III HER2 + disease or TNBC in more recent years and was more common among younger elderly women and those in stage III.

Prevalence of doravirine cross-resistance in HIV-infected adults who failed first-line ART in China, 2014-18.

OBJECTIVES: To evaluate the prevalence and characteristics of doravirine resistance and cross-resistance in patients who failed first-line ART in China. METHODS: From 2014 to 2108, 4132 patients from five provinces were tested for drug resistance by genotypic resistance testing. Drug resistance mutations were assessed using the Stanford HIVdb algorithm Version 9.0. Sequences classified as having low-level, intermediate and high-level resistance were defined as having drug resistance. RESULTS: Overall, the prevalence of doravirine and other NNRTIs cross-resistance was 69.5%, with intermediate and high-level resistance accounting for 56.4%. Doravirine resistance highly correlated with efavirenz (r = 0.720) and nevirapine (r = 0.721) resistance and moderately correlated with etravirine (r = 0.637) and rilpivirine (r = 0.692) resistance. The most frequent doravirine-associated resistance mutations were V106M (8.7%), K101E (6.8%) and P225H (5.1%). High-level resistance was mainly due to Y188L (3.2%) and M230L (2.7%). There were significant differences between genotypes and provinces. Compared with CRF01_AE, CRF07_BC (OR = 0.595, 95% CI = 0.546-0.648) and CRF08_BC (OR = 0.467, 95% CI = 0.407-0.536) were associated with lower risks of doravirine resistance. Conversely, genotype A (OR = 3.003, 95% CI = 1.806-4.991) and genotype B (OR = 1.250, 95% CI = 1.021-1.531) were associated with higher risks of doravirine resistance. The risk of doravirine resistance was significantly lower in Xinjiang compared with other provinces. CONCLUSIONS: In China, the prevalence of doravirine cross-resistance among patients who have failed first-line ART is high. Therefore, doravirine should not be used blindly without genotypic resistance testing and is not recommended for people who have failed first-line NNRTI-based ART.

Positive Coping as a Mediator of Mobile Health Intervention Effects on Quality of Life Among People Living With HIV: Secondary Analysis of the Randomized Controlled Trial Run4Love.

BACKGROUND: The effectiveness of psychosocial interventions on quality of life (QOL) among people living with HIV has been validated, including mobile health (mHealth) interventions. However, it is unclear which components of such interventions account for these effects. OBJECTIVE: This study aims to examine positive coping as a potential mediator of the effects of an mHealth intervention on QOL among people living with HIV. METHODS: For this secondary analysis, we used data from an mHealth-based randomized controlled trial, Run4Love, which was conducted to improve QOL and mental health outcomes of people living with HIV. A total of 300 participants were randomly assigned to the intervention group to receive the adapted cognitive-behavioral stress management courses and regular physical activity promotion or the waitlist control group in a 1:1 ratio. Our analysis focused on positive coping and QOL, which were repeatedly measured at baseline and at 3-, 6-, and 9-month follow-ups. Latent growth curve models were constructed to explore the mediating role of positive coping in the effects of the mHealth intervention on QOL. RESULTS: Positive coping served as a mediator in the effect of the mHealth intervention on QOL for up to 9 months. The mHealth intervention had a significant and positive indirect effect on the slope of QOL via the slope of positive coping (b=2.592×1.620=4.198, 95% CI 1.189-7.207, P=.006). The direct effect of the intervention was not significant (b=0.552, 95% CI -2.154 to 3.258, P=.69) when controlling for the mediator. CONCLUSIONS: The longitudinal findings suggest that positive coping could be a crucial mediator of the mHealth intervention in enhancing QOL among people living with HIV. These findings underscore the importance of improving positive coping skills in mHealth interventions to improve QOL among people living with HIV.

Efficacy of Psychological Interventions Towards the Reduction of High-Risk Sexual Behaviors Among People Living with HIV: A Systematic Review and Meta-analysis, 2010-2020.

People living with HIV/AIDS (PLWH) may be vulnerable to mental illness. As sexual transmission is the leading cause of HIV infection, evidence-based study for the effect of psychological interventions on the change of sexual is needed. To estimate the efficacy of psychological interventions towards reducing unprotected sex and increasing condom use among PLWH. We systematically searched PubMed, Web of Science, EMBASE (OVID), and PsycINFO (OVID) for studies reporting psychological intervention effects on the outcomes of condom use and/or unprotected sex from 2010 to 2020. This review is registered with PROSPERO, CRD42020193640. Of 949 studies, 17 studies were included in this systematic review. Overall, participants in the intervention group reduced sexual risk or condomless sex relative to control groups. The effect was higher for people having sex with HIV-positive partners comparing with those who had sex with HIV-negative or unknown status partners. Psychological interventions might positively affect the condom use of PLWH and should be prioritized and regularly.

Mediating Effects of Stigma and Depressive Symptoms in a Social Media-Based Intervention to Improve Long-term Quality of Life Among People Living With HIV: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions have been shown to effectively improve the quality of life (QOL) among people living with HIV. However, little is known about the long-term effects of mHealth interventions. OBJECTIVE: This study aims to explore the intervention mechanisms of a social media-based intervention, Run4Love, on the QOL of people with HIV over across a 9-month follow-up period. METHODS: We recruited people living with HIV who were concurrently experiencing elevated depressive symptoms from an HIV outpatient clinic in South China. A total of 300 eligible participants were randomized either to the intervention group or the control group in a 1:1 ratio after they provided informed consent and completed a baseline survey. The intervention group received a 3-month WeChat-based intervention, comprising cognitive-behavioral stress management (CBSM) courses and physical activity promotion. The control group received a printed brochure on nutrition guidelines in addition to the usual care for HIV treatment. Neither participants nor the research staff were blinded to group assignment. All patients were followed at 3, 6, and 9 months. The primary outcome was depressive symptoms. Structural equation model (SEM) with longitudinal data was conducted to examine the sequential mediating effects of HIV-related stigma and depressive symptoms on the long-term intervention effects on participants' QOL. RESULTS: About 91.3% (274/300), 88.3% (265/300), and 86.7% (260/300) of all participants completed follow-up surveys at 3, 6, and 9 months, respectively. Results showed that the intervention had significantly improved participants' QOL at 9 months, via complete mediating effects of reduced HIV-related stigma at 3 months and decreased depressive symptoms at 6 months. No adverse events were reported. CONCLUSIONS: These findings underscore the critical roles of HIV-related stigma and depressive symptoms in an mHealth intervention with long-term effects on QOL improvements. We call for targeted mHealth interventions to improve QOL among people living with HIV, especially social media-based interventions that can address HIV-related stigma and alleviate depressive symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://www.chictr.org.cn/showproj.aspx?proj=21019.

HIV/AIDS Among Female Sex Workers in China: Epidemiology and Recent Prevention Strategies.

PURPOSE OF REVIEW: This review aims to describe the epidemiology of HIV among female sex workers (FSWs) in China over the past decade, to summarize current gaps in knowledge regarding risk factors, and to identify new directions for HIV prevention strategies. RECENT FINDINGS: We summarized national and regional levels of HIV prevalence among FSWs based on reported rates in the literature from 2008 to 2018. Studies identified cases of HIV infection among FSWs in all but one province during this time period, and demonstrated a sporadic pattern in most provinces, with a low overall national HIV prevalence below 1%. However, in Yunnan and Guanxi Zhuang Autonomous Regions, the median-reported prevalence rates were close to or slightly above 1%. National prevention programs have widely promoted male condoms as a primary and practical measure for HIV prevention, but studies evaluating condom use practices among FSWs demonstrated wide variability. A rise in illicit use of synthetic drugs and changing sexual practices in the setting of sex work (e.g., anal sex) may represent newer risk factors for HIV transmission among FSWs; however, more data are needed to better characterize these trends. Limited studies have examined the feasibility and efficacy of innovative prevention tools (e.g., female condoms) or strategies (e.g., pre-exposure prophylaxis, PrEP) to prevent HIV among FSWs. We call for a more comprehensive understanding of current trends in HIV risk among FSWs, as well as more research focuses on innovative strategies to reduce the spread of HIV in this vulnerable population.

Gender differences in the relationship of sexual partnership characteristics and inconsistent condom use among people living with HIV in China.

Few studies have examined the relationship between inconsistent condom use and sexual partnership characteristics among people living with HIV (PLWH). The current study focused on such association and its gender differences. The study was conducted in a large hospital in South China in 2013. A total of 320 dyads (PLWH indexes and their sexual partners) were recruited from an outpatient clinic using convenience sampling. The proportion of inconsistent condom use in the last six months among female indexes was higher than that among male indexes (52.4% vs. 43.6%). Of sexual partnership characteristics, HIV seropositive status was a risk factor for inconsistent condom use for both male and female indexes (aOR = 2.32, 95%CI = 1.15∼4.66, aOR = 3.09, 95%CI = 1.10∼8.67, respectively). For male indexes, lower educational level was also a risk factor (aOR = 2.39, 95%CI = 1.23∼4.67); while having had emotionally intimate relationships was a protective factor (aOR = 0.40, 95%CI = 0.21∼0.77). For female indexes, receiving material support was a risk factor (aOR = 10.17, 95%CI = 2.13∼48.61) and receiving health-related advice was a protective factor (aOR = 0.11, 95%CI = 0.02∼0.55). Future HIV interventions for PLWH need to be gender-sensitive and include their sexual partners.

Effect of a WeChat-Based Intervention (Run4Love) on Depressive Symptoms Among People Living With HIV in China: A Randomized Controlled Trial.

BACKGROUND: People living with HIV (PLWH) have high rates of depressive symptoms. However, only a few effective mental health interventions exist for this vulnerable population. OBJECTIVE: The aim of this study was to assess the efficacy of a WeChat-based intervention, Run4Love, with a randomized controlled trial among 300 people living with HIV and depression (PLWHD) in China. METHODS: We recruited PLWH from the HIV outpatient clinic in South China. Participants were screened based on the Center for Epidemiologic Studies-Depression (CES-D) scale. Those who scored 16 or higher were eligible to participate. A total of 300 eligible patients were enrolled. After obtaining informed consent from the participants, completion of a baseline survey, and collection of participants' hair samples for measuring cortisol, the participants were randomly assigned to an intervention or a control group in a 1:1 ratio. The intervention group received the Run4Love program, delivered via the popular social media app WeChat. Cognitive behavioral stress management courses and weekly reminders of exercise were delivered in a multimedia format. Participants' progress was monitored with timely and tailored feedback. The control group received usual care and a brochure on nutrition for PLWH. Data were collected at 3, 6, and 9 months. The primary outcome was depression, which was measured by a validated instrument. RESULTS: Participants in the intervention and control groups were comparable at baseline; about 91.3% (139/150), 88.3% (132/150), and 86.7% (130/150) participants completed the 3-, 6-, and 9-month follow-ups, respectively. At the 3-month follow-up, a significant reduction in CES-D score was observed in the intervention group (from 23.9 to 17.7 vs from 24.3 to 23.8; mean difference=-5.77, 95% CI -7.82 to -3.71; P<.001; standard effect size d=0.66). The mean changes in CES-D score from baseline to the 6- and 9-month follow-ups between the two groups remained statistically significant. No adverse events were reported. CONCLUSIONS: The WeChat-based mobile health (mHealth) intervention Run4Love significantly reduced depressive symptoms among PLWHD, and the effect was sustained. An app-based mHealth intervention could provide a feasible therapeutic option for many PLWHD in resource-limited settings. Further research is needed to assess generalizability and cost-effectiveness of this intervention. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showproj.aspx?proj=21019 (Archived by WebCite at https://www.webcitation.org/78Bw2vouF).

NIR-Light-Triggered Anticancer Strategy for Dual-Modality Imaging-Guided Combination Therapy via a Bioinspired Hybrid PLGA Nanoplatform.

A promising approach toward cancer therapy is expected to integrate imaging and therapeutic agents into a versatile nanocarrier for achieving improved antitumor efficacy and reducing the side effects of conventional chemotherapy. Herein, we designed a poly(d,l-lactic- co-glycolic acid) (PLGA)-based theranostic nanoplatform using the double emulsion solvent evaporation method (W/O/W), which is associated with bovine serum albumin (BSA) modifications, to codeliver indocyanine green (ICG), a widely used near-infrared (NIR) dye, and doxorubicin (Dox), a chemotherapeutic drug, for dual-modality imaging-guided chemo-photothermal combination cancer therapy. The resultant ICG/Dox co-loaded hybrid PLGA nanoparticles (denoted as IDPNs) had a diameter of around 200 nm and exhibited excellent monodispersity, fluorescence/size stability, and biocompatibility. It was confirmed that IDPNs displayed a photothermal effect and that the heat induced faster release of Dox, which led to enhanced drug accumulation in cells and was followed by their efficient escape from the lysosomes into the cytoplasm and drug diffusion into the nucleus, resulting in a chemo-photothermal combinatorial therapeutic effect in vitro. Moreover, the IDPNs exhibited a high ability to accumulate in tumor tissue, owing to the enhanced permeability and retention (EPR) effect, and could realize real-time fluorescence/photoacoustic imaging of solid tumors with a high spatial resolution. In addition, the exposure of tumor regions to NIR irradiation could enhance the tumor penetration ability of IDPNs, almost eradicating subcutaneous tumors. In addition, the inhibition rate of IDPNs used in combination with laser irradiation against EMT-6 tumors in tumor-bearing nude mice (chemo-photothermal therapy) was approximately 95.6%, which was much higher than that for chemo- or photothermal treatment alone. Our study validated the fact that the use of well-defined IDPNs with NIR laser treatment could be a promising strategy for the early diagnosis and passive tumor-targeted chemo-photothermal therapy for cancer.

Differential effects of unemployment on depression in people living with HIV/AIDS: a quantile regression approach.

Unemployment is associated with depression in people living with HIV (PLWH). However, few studies have examined the effects of unemployment on PLWH with different levels of depression. The current study explores the plausible differential effects of unemployment on the different percentiles of depression in PLWH employing a quantile regression (QR) approach, based on a recent survey of 411 PLWH in China. Among participants, 47.7% had elevated depressive symptoms, and 23.8% were unemployed. The effects of unemployment on depression were statistically significant with a trend of initial increase followed by a decline at the quantile levels of 0.51-0.90 of depression. The maximum effect of unemployment status on depression was statistically significant at the 70th and 75th percentiles of depression (coefficient = 7.0, p < .01). Tailored strategies and interventions should be implemented to address the differential needs of PLWH with various levels of depressive symptoms.

Mechanisms and Effects of a WeChat-Based Intervention on Suicide Among People Living With HIV and Depression: Path Model Analysis of a Randomized Controlled Trial.

BACKGROUND: People living with HIV and depression have high rates of suicide. Studies of mobile health (mHealth) interventions have shown feasibility, acceptability, and efficacy in improving mental health in people living with HIV and depression. However, few studies have examined the mechanisms and effects of mHealth interventions on suicide. OBJECTIVE: This study was designed to examine the mechanisms and effects of a WeChat-based intervention, Run4Love, on suicide among people living with HIV and depression in China, while considering perceived stress and depressive symptoms as mediators. METHODS: A sample of 300 People living with HIV and depression was recruited from the outpatient clinic of a large HIV or AIDS treatment hospital and was randomized to the Run4Love group or a control group. Data were collected at baseline, 3-, 6-, and 9-month follow-ups. Path analysis modeling, with longitudinal data, was used in data analyses. RESULTS: The Run4Love mHealth intervention had a direct effect on reducing suicide rate at the 6-month follow-up (beta=-.18, P=.02) and indirect effect through reducing perceived stress and depressive symptoms at the 3-month follow-up (beta=-.09, P=.001). A partial mediating effect between perceived stress and depressive symptoms accounted for 33% (-0.09/-0.27) of the total effect. CONCLUSIONS: Through path analyses, we understood the mechanisms and effects of an mHealth intervention on suicide prevention. The findings underscored the importance of stress reduction and depression treatment in such a program. We call for more effective suicide prevention, especially mHealth interventions targeting the vulnerable population of people living with HIV and depression. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showprojen.aspx?proj=21019.

A structural equation model of perceived and internalized stigma, depression, and suicidal status among people living with HIV/AIDS.

BACKGROUND: Previous studies have shown positive association between HIV-related stigma and depression, suicidal ideation, and suicidal attempt among people living with HIV/AIDS (PLWH). But few studies have examined the mechanisms among HIV-related stigma, depression, and suicidal status (suicidal ideation and/or suicidal attempt) in PLWH. The current study examined the relationships among perceived and internalized stigma (PIS), depression, and suicidal status among PLWH in Guangzhou, China using structural equation modeling. METHODS: Cross-sectional study by convenience sampling was conducted and 411 PLWH were recruited from the Number Eight People's Hospital from March to June, 2013 in Guangzhou, China. Participants were interviewed on their PIS, depressive symptoms, suicidal status, and socio-demographic characteristics. PLWH who had had suicidal ideation and suicidal attempts since HIV diagnosis were considered to be suicidal. Structural equation model was performed to examine the direct and indirect associations of PIS and suicidal status. Indicators to evaluate goodness of fit of the structural equation model included Chi-square Statistic, Comparative Fit Index (CFI), Root Mean Square Error of Approximation (RMSEA), Standardized Root Mean Square Residual (SRMR), and Weighted Root Mean Square Residual (WRMR). RESULTS: More than one-third (38.4%) of the PLWH had depressive symptoms and 32.4% reported suicidal ideation and/or attempt since HIV diagnosis. The global model showed good model fit (Chi-square value = 34.42, CFI = 0.98, RMSEA = 0.03, WRMR = 0.73). Structural equation model revealed that direct pathway of PIS on suicidal status was significant (standardized pathway coefficient = 0.21), and indirect pathway of PIS on suicidal status via depression was also significant (standardized pathway coefficient = 0.24). There was a partial mediating effect of depression in the association between PIS and suicidal status. CONCLUSIONS: Our findings suggest that PIS is associated with increased depression and the likelihood of suicidal status. Depression is in turn positively associated with suicidal status and plays a mediating role between PIS and suicidal status. Therefore, to reduce suicidal ideation and attempt in PLWH, targeted interventions to reduce PIS and improve mental health status of PLWH are warranted.