Optimal STI controls for HIV patients based on an efficient deep Q learning method.

We investigate an efficient computational tool to suggest useful treatment regimens for people infected with the human immunodeficiency virus (HIV). Structured treatment interruption (STI) is a regimen in which therapeutic drugs are periodically administered and withdrawn to give patients relief from an arduous drug therapy. Numerous studies have been conducted to find better STI treatment strategies using various computational tools with mathematical models of HIV infection. In this paper, we leverage a modified version of the double deep Q network with prioritized experience replay to improve the performance of classic deep learning algorithms. Numerical simulation results show that our methodology produces significantly more optimal cost values for shorter treatment periods compared to other recent studies. Furthermore, our proposed algorithm performs well in one-day segment scenarios, whereas previous studies only reported results for five-day segment scenarios.

Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption.

This study aims to understand the impact of early antiretroviral therapy (ART) on HIV-specific T-cell responses measured after treatment interruption may inform strategies to deliver ART-free immune-mediated viral suppression. HIV-specific T-cell immunity was analysed using gamma interferon enzyme-linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag-directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag-directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol-specific responses post-TI compared with pre-TI. Although early ART in PHI was not associated with major differences in HIV-specific immunity following TI compared with untreated participants, the potential to make more new Gag-directed responses warrants further investigation as this may inform strategies to achieve ART-free control.

Circulating immune and plasma biomarkers of time to HIV rebound in HIV controllers treated with vesatolimod.

Background: Antiretroviral therapy (ART) for HIV-1 treatment has improved lifespan but requires lifelong adherence for people living with HIV (PLWH), highlighting the need for a cure. Evaluation of potential cure strategies requires analytic treatment interruption (ATI) with close monitoring of viral rebound. Predictive biomarkers for HIV-1 rebound and/or duration of control during ATI will facilitate these HIV cure trials while minimizing risks. Available evidence suggests that host immune, glycomic, lipid, and metabolic markers of inflammation may be associated with HIV-1 persistence in PLWH who are treated during chronic HIV-1 infection. Methods: We conducted post-hoc analysis of HIV controllers who could maintain low levels of plasma HIV-1 without ART in a phase 1b vesatolimod trial. Baseline and pre-ATI levels of immune, glycomic, lipidomic, and metabolomic markers were tested for association with ATI outcomes (time of HIV-1 rebound to 200 copies/mL and 1,000 copies/mL, duration of HIV-1 RNA ≤400 copies/mL and change in intact proviral HIV-1 DNA during ATI) using Spearman's correlation and Cox proportional hazards model. Results: Higher levels of CD69+CD8+ T-cells were consistently associated with shorter time to HIV-1 rebound at baseline and pre-ATI. With few exceptions, baseline fucosylated, non-galactosylated, non-sialylated, bisecting IgG N-glycans were associated with shorter time to HIV rebound and duration of control as with previous studies. Baseline plasma MPA and HPA binding glycans and non-galactosylated/non-sialylated glycans were associated with longer time to HIV rebound, while baseline multiply-galactosylated glycans and sialylated glycans, GNA-binding glycans, NPA-binding glycans, WGA-binding glycans, and bisecting GlcNAc glycans were associated with shorter time to HIV rebound and duration of control. Fourteen bioactive lipids had significant baseline associations with longer time to rebound and duration of control, and larger intact proviral HIV-1 DNA changes; additionally, three baseline bioactive lipids were associated with shorter time to first rebound and duration of control. Conclusion: Consistent with studies in HIV non-controllers, proinflammatory glycans, lipids, and metabolites were generally associated with shorter duration of HIV-1 control. Notable differences were observed between HIV controllers vs. non-controllers in some specific markers. For the first time, exploratory biomarkers of ATI viral outcomes in HIV-controllers were investigated but require further validation.

Comparing efficacy and safety of in-house gemcitabine to mitomycin for bladder instillation in intermediate-risk NMIBC.

INTRODUCTION: Intermediate-risk (IR) Non-Muscle Invasive Bladder Cancer (NMIBC) is associated with a high rate of tumor recurrence. To improve patient outcomes, it is recommended to use adjuvant intravesical therapy, by mitomycin C (MMC) or Bacillus Calmette Guerin (BCG). Gemcitabine (GMC) is a known molecule used in urothelial cancer. We aimed to study the efficacy and safety profile of a gemcitabine solution, compared to mitomycin C, in the treatment of IR NMIBC. MATERIAL: In this retrospective study, patients with IR NMIBC treated between 2016 and 2020 were selected from two participating centers using either gemcitabine (center A) as the intravesical chemotherapy regimen or mitomycin C (center B). The primary endpoint was recurrence rate and secondary end points were treatment interruption and its causes. RESULTS: In our cohort of 102 IR NMIBC patients, 49 patients received GMC and 53 MMC with a median follow-up of 30 months. Overall recurrence rate was 42.1% with 22.4% in the GMC group and 60.3% in the MMC group (P<0.01). This difference was also found in the multifactorial analysis. Course interruption was observed in 14.7% of all patients, primarily attributed to adverse events (46.6%), without difference between groups. CONCLUSION: Adjuvant intravesical gemcitabine in patients with IR NMIBC seems to be an interesting option associated with a lower tumor recurrence rate and a favorable tolerance profile when compared to MMC. Larger scale prospective randomized trials are needed to validate our findings. LEVEL OF EVIDENCE: III.

Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption.

A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.

Treatment Interruptions and Mortality among Puerto Rican Women with Gynecologic Cancers in Puerto Rico after Hurricanes Irma and María: A Retrospective Cohort Study.

OBJECTIVE: Cancer patients are among the most vulnerable populations during and after a disaster. We evaluated the impact of treatment interruption on the survival of women with gynecologic cancer in Puerto Rico following hurricanes Irma and María. METHODS: Retrospective cohort study among a clinic-based sample of women diagnosed between January 2016-September 2017 (n=112). Women were followed up from their diagnosis until December 2019, to assess vital status. Kaplan-Meier survival curves and Cox proportional hazards models were performed. RESULTS: Mean age was 56 (±12.3) years; corpus uteri (58.9%) was the most common gynecologic cancer. Predominant treatments were surgery (91.1%) and chemotherapy (44.6%). Overall, 75.9% were receiving treatment before the hurricanes, 16.1% experienced treatment interruptions and 8.9% died during the follow-up period. Factors associated with treatment interruption in bivariate analysis included younger age (≤55 years), having regional/distant disease, and receiving >1 cancer treatment (p<0.05). Crude analysis revealed an increased risk of death among women with treatment interruption (HR: 3.88, 95% CI=1.09-13.77), persisting after adjusting for age and cancer stage (HR: 2.49, 95% CI= 0.69-9.01). CONCLUSIONS: Findings underscore the detrimental impact of treatment interruption on cancer survival in the aftermath of hurricanes, emphasizing the need for emergency response plans for this vulnerable population.

Definition of Virological Endpoints Improving the Design of Human Immunodeficiency Virus (HIV) Cure Strategies Using Analytical Antiretroviral Treatment Interruption.

BACKGROUND: Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral setpoint is commonly used as endpoint to evaluate their efficacy. However, in line with recommendations from a consensus meeting, to minimize the risk of increased viremia without ART, trials often implement short ATI phases and stringent virological ART restart criteria. This approach can limit the accurate observation of the setpoint. METHODS: We analyzed viral dynamics in 235 people with HIV from 3 trials, examining virological criteria during ATI phases. Time-related (eg time to rebound, peak, and setpoint) and viral load magnitude-related criteria (peak, setpoint, and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify (1) surrogate endpoints for setpoint and (2) optimal virological ART restart criteria mitigating the risks of ART interruption and the evaluation of viral control. RESULTS: Comparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC the most strongly correlated with the setpoint, with correlations >0.70. A threshold >100 000 copies/mL for 2 consecutive measures is requested as a virological ART restart criterion. CONCLUSIONS: Our results are in line with recommendations and emphasize the benefits of an ATI phase >12 weeks, with regular monitoring, and a virological ART restart criterion of 10 000 copies/mL to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy to the setpoint.

Analysis of antiretroviral therapy interruption in people living with HIV during the 2010-2021 Period. / [Artículo traducido] Análisis de la interrupción de la terapia antirretroviral en personas que viven con VIH/sida durante el periodo 2010­2021.

OBJECTIVE: In the context of the advancement of antiretroviral therapy and, as the characteristics of people living with HIV progress toward an aging population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term 'interruption' will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilized Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81,5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analyzed to the therapeutic optimization (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV ≥50 years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSIONS: Over the 12 years there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimization being the main reason. Integrase inhibitors-based regimens and singletablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV ≥50 years with comorbidities.

Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

OBJECTIVES: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. METHODS: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. RESULTS: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). CONCLUSION: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Treatment interruption in hypertensive patients during the COVID-19 pandemic: An interrupted time series analysis using prescription data in Okayama, Japan.

Background: The COVID-19 pandemic has impacted healthcare behaviors, leading to fewer pediatric visits in Japan and potentially fewer visits by adult patients. However, existing Japanese studies on treatment interruptions have generally relied on questionnaire-based methods. In this study, we assessed the impact of the pandemic on antihypertensive treatment interruption using real-world prescription data. Methods: We conducted an interrupted time series analysis using the National Health Insurance Database in Okayama Prefecture, Japan. Participants included individuals aged 40-69 years with at least one antihypertensive prescription between 2018 and 2020. Treatment interruption was defined as a 3-month or longer gap in prescriptions after medication depletion. We used segmented Poisson regression with models unadjusted and adjusted for seasonality and over-dispersion to assess monthly treatment interruptions before and after Japan's April 2020 emergency. Results: During the study period, 23.0% of 55,431 participants experienced treatment interruptions. Cyclical fluctuations in interruptions were observed. The crude analysis indicated a 1.2-fold increase in treatment interruptions following the pandemic; however, the adjusted models showed no significant changes. Even among higher-risk groups, such as women, younger adults, and those with shorter prescriptions, no significant alterations were observed. Conclusion: We found no significant impact of the COVID-19 pandemic on antihypertensive treatment interruption in Okayama Prefecture. The less severe outbreak in the area or increased use of telemedicine and extended prescriptions may have contributed to treatment continuity. Further research is needed using a more stable and comprehensive database, broader regional data, and detailed prescription records to validate and extend our findings.

Analysis of antiretroviral therapy interruption in people living with HIV during the 2010-2021 period.

INTRODUCTION: In the context of the advancement of antiretroviral therapy and as the characteristics of people living with HIV progress toward an ageing population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term "discontinuation" is employed synonymously with "interruption". The term "discontinuation" will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilised Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81.5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analysed to the therapeutic optimisation (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV≥50 years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSION: Over the 12 years, there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimisation being the main reason. Integrase inhibitors-based regimens and single-tablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV≥50 years with comorbidities.

Three-stage modeling of HIV infection and implications for antiretroviral therapy.

We consider a deterministic model of HIV infection that involves macrophages as a long-term active reservoir to describe all three stages of the disease process: the acute stage, chronic infection, and the transition to AIDS. The proposed model is shown to retain crucial properties, such as the positivity of solutions, regardless of variations in model parameters. A dynamical analysis is performed to identify the local stability properties of the viral clearance steady state. This analysis illustrates how chronically infected macrophages can explain the progression to AIDS and provoke viral explosion, while previous models do not. We further demonstrate that the infected T-cell population, even if not responsible for the majority of new infections that lead to viral explosion, may contribute significantly to the transition amongst the three stages of infection. Moreover, we explore the implications of the model for the administration of antiretroviral therapy (ART) and provide quantitative estimates that emphasize the time sensitive nature of treatment initiation and the level of drug efficacy. Finally, we study the effects of treatment interruption on the disease dynamics predicted by the model and elucidate the influence of both interruption time and duration.

Comparison of Different Prediction Models for Unplanned Interruption of Continuous Renal Replacement Treatment: A Systematic Review of Qualitative Analyses.

INTRODUCTION: This study will systematically search and evaluate the prediction models for unplanned interruption of continuous renal replacement treatment (CRRT) and to provide a reference for building a higher quality prediction model for unplanned interruption of CRRT. METHODS: PubMed, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang Database were systematically searched for studies on prediction models for unexpected interruption of CRRT. The languages were limited to Chinese and English. The search time limit was from the establishment of the database to June 30, 2023. Two researchers screened the literature and extracted the data independently, and the risk of bias and applicability of the included literature were analyzed using the risk of bias assessment tool for predictive model studies. RESULTS: A total of nine studies were included, and the area under the receiver operating characteristic curve ranged from 0.679 to 0.997. The applicability of the prediction model in seven studies was good and in two studies was poor. CONCLUSION: More attention should be paid to the effectiveness of different risk assessment methods in future construction, so as to obtain better risk prediction models with high accuracy and provide certain reference and basis for formulating relevant prevention strategies.

Recommendations for the individualised management of atypical hemolytic uremic syndrome in adults.

Background: Despite significant advances in therapeutic management of atypical hemolytic uremic syndrome (aHUS), guidelines are not timely updated and achieving a consensus on management recommendations remains a topic of ongoing discussion. Methods: A Scientific Committee with five experts was set up. A literature review was conducted and publications addressing the classification of aHUS, patient profiles and therapeutic approach were selected. Recommendations were proposed at an initial meeting, evaluated through an online questionnaire and validated during a second meeting. Results: Patients with confirmed or clear suspicion of aHUS should be treated with C5 inhibitors within 24 h of the diagnosis or suspicion of aHUS. Treatment monitoring and the decision to interrupt treatment should be individualised according to the risk of relapse and each patient's evolution. aHUS with a genetic variant or associated with pregnancy should be treated for at least 6-12 months; de novo aHUS associated with kidney transplant until renal function is recovered and genetic variants are ruled out; aHUS associated with malignant hypertension until genetic variants are ruled out; aHUS associated with non-kidney transplant, autoimmune diseases, infection-or drug-induced until the thrombotic microangiopathy is resolved. Patients with a high risk of relapse should be treated for longer than 6-12 months. Conclusion: These recommendations provides physicians who are not familiar with the disease with recommendations for the management of aHUS in adults. The experts who participated advocate early treatment, maintenance for at least 6-12 months and treatment interruption guided by genetic background, trigger factors, risk of relapse and evolution.

It's all about connection: Determinants of social support and the influence on HIV treatment interruptions among people living with HIV in British Columbia, Canada.

BACKGROUND: Social support has previously been found to be associated with improved health outcomes of individuals managing chronic illnesses, including amongst people living with HIV (PLWH). For women and people who use injection drugs who continue to experience treatment disparities in comparison to other PLWH, social support may have potential in facilitating better treatment engagement and retention. In this analysis, we examined determinants of social support as measured by the Medical Outcomes Study - Social Support Survey (MOS-SSS) scale, and quantified the relationship between MOS-SSS and HIV treatment interruptions (TIs) among PLWH in British Columbia, Canada. METHODS: Between January 2016 and September 2018, we used purposive sampling to enroll PLWH, 19 years of age or older living in British Columbia into the STOP HIV/AIDS Program Evaluation study. Participants completed a baseline survey at enrolment which included the MOS-SSS scale, where higher MOS-SSS scores indicated greater social support. Multivariable linear regression modeled the association between key explanatory variables and MOS-SSS scores, whereas multivariable logistic regression modeled the association between MOS-SSS scores and experiencing TIs while controlling for confounders. RESULTS: Among 644 PLWH, we found that having a history of injection drug use more than 12 months ago but not within the last 12 months, self-identifying as Indigenous, and sexual activity in the last 12 months were positively associated with MOS-SSS, while being single, divorced, or dating (vs. married), experiences of lifetime violence, and diagnosis of a mental health disorder were inversely associated. In a separate multivariable model adjusted for gender, ethnicity, recent homelessness, sexual activity in the last 12 months, and recent injection drug use, we found that higher MOS-SSS scores, indicating more social support, were associated with a lower likelihood of HIV treatment interruptions (adjusted odds ratio: 0.90 per 10-unit increase, 95% confidence interval: 0.83, 0.99). CONCLUSIONS: Social support may be an important protective factor in ensuring HIV treatment continuity among PLWH. Future research should examine effective means to build social support among communities that have potential to promote increased treatment engagement.

Predictive Factors and Clinical Events Associated with Edoxaban Interruption and Heparin Bridging Strategy: EMIT-AF/VTE.

Patients treated with edoxaban may require diagnostic and therapeutic procedures that involve edoxaban interruption. Although heparin bridging strategies are not recommended, heparin is frequently used in clinical practice. However, whether heparin use decreases thromboembolic risk remains unclear, and the potential for increased periprocedural bleeding remains a concern. Here, we report factors predicting edoxaban interruption and the use of heparin bridging strategies and associated clinical events from Global EMIT-AF/VTE, a multicenter, prospective, noninterventional study (Clinicaltrials.gov NCT02950168). Eligible patients are adults with atrial fibrillation or venous thromboembolism treated with edoxaban who underwent a diagnostic or therapeutic procedure. Edoxaban interruption, heparin bridging strategies, and clinical event data were collected from 5 days before procedure through 29 days afterwards. Edoxaban was interrupted in 1222/2089 procedures (58.5%); a heparin bridging strategy was used during 178 (14.6%) of these interruptions. Patients who received periprocedural heparin had higher baseline HAS-BLED (2.4±1.0 vs 1.9±1.1, P <0.0001) scores and similar CHA2DS2-VASc (3.6±1.6 vs 3.4±1.6, P = 0.09) scores versus patients who did not. HAS-BLED score >3 and high EHRA procedural risk predicted both edoxaban interruption and the use of a heparin bridging strategy, whereas CHA2DS2-VASc scores did not predict either. Bleeding and ischemic event rates were low; the all-bleeding rate was higher with the use of a heparin bridging strategy versus without (6.2% vs 3.1%, P = 0.04). Periprocedural heparin use was associated with higher bleeding rates, but not with lower thromboembolic risk. Individual patient and procedural bleeding risks appear to contribute more than stroke risk to clinicians' consideration of a heparin bridging strategy.

The Effect of Armed Conflict on Treatment Interruption, Its Outcome and Associated Factors Among Chronic Disease Patients in North East, Amhara, Ethiopia, 2022.

Background: The health services delivery system is debilitated in conflict setting areas due to damage of health facilities and attack on health care providers. Armed conflict is a complex phenomenon which causes a large amount of death and disability worldwide. However, there is lack of information towards treatment interruption among chronic disease patients in conflict areas. Hence, this study was conducted to assess the prevalence of armed conflict induced treatment interruption and its outcome among chronic disease patients. Methods: A mixed cross sectional study design was conducted on a total of 399 sample size at North Wollo and Waghimra zone hospitals. To select study participants a consecutive sampling method was used. Multiple logistic regressions were computed to evaluate the association and thematic analysis was used to analyse qualitative data. Results: From the total 399 study participants, 264 (64.6%) study participants interrupted their medication. Treatment interruption is significantly associated with poor service availability and perceived high stress. Conclusion: War has detrimental health effects, both immediate and long term, on populations. Treatment interruptions due to armed conflict were caused by poor health care access, lack of medications and lack of transport and displacement of hospital staff, insecurity and fear. Treatment interruption results in morbidity, mortality, lifelong complications, disability, psychological and economic impact.

HIV remission trial investigators' attitudes towards risk and risk mitigation in trials that include treatment interruption.

Early-phase HIV remission ("cure") trials aim to test interventions developed to eradicate HIV or to sustainably control HIV without antiretroviral treatment (ART). Many remission trials include analytic treatment interruption (ATI) to evaluate interventions, which increases the risk to participants and their sexual partners. We conducted an online questionnaire of international HIV remission trial investigators and other study team members to assess their expectations regarding the time to achieve long-term control of HIV replication without treatment (functional cure) or complete eradication of replication-competent HIV virus (sterilizing cure); attitudes toward HIV remission research and the feasibility, acceptability, and efficacy of six HIV transmission risk mitigation strategies during trials with ATI of fixed duration. Nearly half of respondents (47%) reported expecting a functional cure for HIV to be achieved in 5-10 years, and one-third (35%) reported 10-20 years for a sterilizing cure to be achieved. On a scale of -3 to 3, mean scores indicated greater respondent concern about the risk of HIV transmission to partners during ATI (Time to rebound Mean: 0.4 and Fixed duration Mean: 11), compared to participant health risks from ATI (Time to Rebound Mean: -.9 and Fixed duration Mean: 0.0). With regard to feasibility, acceptability, and efficacy respectively, mitigation efforts rated positively included: requiring counseling for potential participants (Means: 2.3; 2.1; and 1.1), providing partner referrals for PrEP (Means: 1.3; 1.3; 1.5), providing pre-exposure proxylaxis directly to partners (Means: 1.0; 1.5; 1.6), and monitoring participants for new sexually transmitted disease acquisition (Means: 1.9; 1.4; 1.0). Respondents were less positive about requiring that participants' sexual partner(s) participate in risk counseling or limiting participation to those who commit to abstaining from sex during the entire ATI period. Our study demonstrates that HIV remission trial investigators and study team members are concerned about the risk of transmission to sexual partners during ATI. Separating the assessment of risk mitigation strategies for transmission risk into feasibility, acceptability, and efficacy allows the discovery of strategies that may best achieve all three outcomes. Additional research is needed to compare these more fine-grained assessments with views held by other investigators, people living with HIV, and trial participants.

Impact of weight loss on treatment interruption and unplanned hospital admission in head and neck cancer patients undergoing curative (chemo)-radiotherapy in Hong Kong.

PURPOSE: Malnutrition is highly prevalent in head and neck cancer (HNC) patients, with weight loss being one of the major nutritional indicators. The objective of this study was to investigate the impact of weight loss on treatment interruptions and unplanned hospital admissions in HNC patients undergoing radiotherapy (RT) with or without chemotherapy. METHODS: In this retrospective cohort study, consecutive HNC patients who started RT between January 2011 and December 2019 were included. Data from a total of 1086 subjects with 747 (68.8%) nasopharyngeal carcinomas (NPCs) and 31.2% (N=339) non-NPC patients were analysed. Body weight (BW) was measured before, during, and after RT treatment. Factors associated with ≥10% weight loss, treatment interruption, and unplanned admissions were analysed using multivariate logistic regression. RESULTS: The prevalence of ≥10% weight loss was 26.8% (N=288), with 32.7% (N=243) in NPC and 13.5% (N=45) in non-NPC patients. The prevalence of RT delay in patients with ≥10% vs. <10% weight loss was 6.2% vs. 7.0% (p=0.668) in NPC patients and 42.2% vs. 50.5% (p=0.300) in non-NPC patients. The prevalence of unplanned admissions in patients with ≥10% vs. <10% weight loss was 51.9% vs. 25.3% (p<0.001) in NPC patients and 68.9% vs. 27.0% (p<0.001) in non-NPC patients. CONCLUSION: In our study, ≥10% weight loss was found to be associated with a higher rate of unplanned admissions but not with RT delay or chemotherapy interruption. CLINICAL IMPLICATIONS: With the knowledge of the impact of weight loss on hospital admissions and the characteristics of patients with weight loss, nutritional intervention can be effectively focused on the stratification of patients for intensive nutritional support to reduce weight loss.

The Essential Need for Trust When Transmission Risk Cannot Be Eliminated in HIV-Remission Trials.

Analytic treatment interruption (ATI) is scientifically necessary in HIV-remission ("cure") studies to test the effects of new interventions. However, stopping antiretroviral treatment poses risks to research participants and their sexual partners. Ethical debate about whether and how to conduct such studies has largely centered on designing risk-mitigation strategies and identifying the responsibilities of research stakeholders. In this paper, we argue that because the possibility of HIV transmission from research participants to partners during ATI cannot practicably be eliminated-that is, it is ineliminable-the successful conduct of such trials ultimately depends on relationships of trust and trustworthiness. We describe our experiences with conducting and studying HIV-remission trials with ATI in Thailand to examine the strengths, complexities, and limitations of the risk-mitigation and responsibility approaches and to explore ways in which the building of trust-and trustworthiness-may help enhance the scientific, practical, and ethical dimensions of these trials.