Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This ...article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores (
P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively (
P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.
Abstract
Understanding the mediation mechanisms by which an exposure or intervention affects an outcome can provide a look into what has been called a “black box” of many epidemiologic associations, ...thereby providing further evidence of a relationship and possible points of intervention. Rapid methodologic developments in mediation analyses mean that there are a growing number of approaches for researchers to consider, each with its own set of assumptions, advantages, and disadvantages. This has understandably resulted in some confusion among applied researchers. Here, we provide a brief overview of the mediation methods available and discuss points for consideration when choosing a method. We provide an in-depth explication of 2 of the many potential estimators for illustrative purposes: the Baron and Kenny mediation approach, because it is the most commonly used, and a recently developed approach for estimating stochastic direct and indirect effects, because it relies on far fewer assumptions. We illustrate the decision process and analytical procedure by estimating potential school- and peer-based mechanisms linking neighborhood poverty to adolescent substance use in the National Comorbidity Survey Adolescent Supplement.
There is a critical lack of research on violence experienced by women when meeting their daily water and sanitation needs. This short report describes the cumulative lifetime incidence of exposure to ...violence when using the toilet or collecting water (water, sanitation, and hygiene WASH-related violence) and identifies associated health and behavioral risks. Data from 1,870 participants collected in 2013-2015 from a longitudinal cohort of young women in rural South Africa were included in this analysis. We found that exposure to WASH-related violence was high: 25.9% experienced violence when collecting water or when using the toilet. Those who experienced violence were more likely to report pregnancy, an older partner, unprotected sex, experience of intimate partner violence, engaging in transactional sex, depressive symptoms, and anxiety. Future research should investigate the location and type of violence experienced and examine how WASH-related violence is related to health outcomes to identify gender-centered WASH interventions that reduce violence exposure.
Abstract
The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive ...symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13–21 years) in rural Mpumalanga Province, South Africa, during 2011–2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: –0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW.
Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities ...(liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment.
Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence.
Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis.
The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated.
ObjectiveThere is a lack of research on experiences of WASH-related violence. This study aims to quantify the association between experience or worry of violence when using the toilet or collecting ...water and depressive symptoms among a cohort of young women in South Africa.MethodsData are from visit 3 of the HPTN 068 cohort of adolescent girls in rural Mpumalanga Province, South Africa. Participants (n=1798) included in this analysis were aged 13–21 at baseline. Lifetime experience of violence or fear of violence when using the toilet and collecting water was collected by self-report; depressive symptoms in the past week were measured using the Center for Epidemiological Studies Depression Scale (CES-D). We used G-computation to calculate the prevalence difference (PD) and prevalence ratio of depression (CES-D score >15) associated with each domain of violence, controlling for baseline covariates.FindingsA total of 15.1% of respondents reported experiencing violence when using the toilet; 17.1% reported experiencing violence when collecting water and 26.7% reported depression. In adjusted models, those who reported experiencing violence when using the toilet had an 18.1% higher prevalence of depression (95% CI: 11.6% to 24.4%) than those who did not experience violence when using the toilet. Adjusted prevalence of depression was also higher among those who reported violence when collecting water (PD 11.9%, 95% CI: 6.7% to 17.2%), and who worried about violence when using the toilet (PD 12.8%, 95% CI: 7.9% to 19.8%), as compared with those who did not report these experiences. Worrying about violence when collecting water was not associated with depression after adjusting for covariates.ConclusionExperience of WASH-related violence is common among young women in rural South Africa, and experience or worry of experiencing violence is associated with higher prevalence of depressive symptoms.Trial registration numberNCT01233531; Post-results.
Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ...ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation. BLAST-AHF was designed to determine the safety, efficacy, and optimal dose of TRV027 to advance into future studies.
BLAST-AHF was a multi-centre, international, randomized, double-blind, placebo-controlled, parallel group, phase IIb dose-ranging study, enrolling patients with AHF into 4 groups: placebo, 1, 5, or 25 mg/h of TRV027. Treatment was by IV infusion for 48-96 h. The primary composite endpoint was comprised of the following: (i) time from baseline to death through day 30, (ii) time from baseline to heart failure re-hospitalization through day 30, (iii) the first assessment time point following worsening heart failure through day 5, (iv) change in dyspnea visual analogue scale (VAS) score calculated as the area under the curve (AUC) representing the change from baseline over time from baseline through day 5, and (v) length of initial hospital stay (in days) from baseline. Analyses were by modified intention-to-treat. Overall, 621 patients were enrolled. After 254 patients, a pre-specified interim analysis resulted in several protocol changes, including a lower blood pressure inclusion criterion as well as a new allocation scheme of 2:1:2:1, overweighting both placebo, and the 5 mg/h dose. TRV027 did not confer any benefit over placebo at any dose with regards to the primary composite endpoint or any of the individual components. There were no significant safety issues with TRV027.
In this phase IIb dose-ranging AHF study, TRV027 did not improve clinical status through 30-day follow-up compared with placebo.
To present the findings of a risk-stratification survival analysis with use of data collected on a heterogeneous group of patients with hepatocellular carcinoma (HCC) treated with TheraSphere.
...Baseline, treatment, and follow-up data were collected and analyzed from 121 TheraSphere-treated patients. Survival analyses were performed to identify those variables most strongly associated with 3-month mortality. The presence of any of the identified risk variables resulted in the assignment of a patient to the high-risk category.
Five liver reserve and two non-liver reserve variables were identified and used to stratify patients into low- or high-risk groups. Sixteen of the 33 patients assigned to the high-risk group (49%) did not survive the first 3 months after treatment, compared with six of the 88 patients assigned to the low-risk group (7%; Fisher exact test, P < .0001). Median survival for the low- and high-risk groups were 466 days and 108 days, respectively (hazard ratio, 6.0; P < .0001). Eleven of 12 patients who experienced a treatment-related major complication ending in death were included in the high-risk group. No single variable explained the major complication relationship to treatment.
Patients with HCC who are being considered for treatment with TheraSpheres should be evaluated for the presence of the risk variables described herein. The absence of these variables is predictive of improved survival (median of 466 days) compared with patients at high risk (median of 108 days).
Autistic children, adolescents and their younger siblings are less likely to be fully vaccinated compared to their peers in the general population. A focus on the influence of the unfounded link ...between the measles, mumps and rubella (MMR) vaccine and autism has distracted from consideration of unique family experiences and autistic-child related factors, such as emotional and behavioural differences, that may influence caregivers’ vaccination decisions. Without an understanding of the unique challenges and experiences of families with autistic children along the vaccination journey, the scope for appropriate, targeted interventions to support them is limited. To address this gap, in this qualitative research study we explored factors that impact the vaccination journey for autistic children and their families in an Australian context. Participants included 16 caregivers (15 mothers; 1 father) of 25 children who had a diagnosis of autism. Seven families had multiple autistic children. Participants shared their perceptions, experiences, and anticipation related to childhood vaccinations and vaccinating their autistic child and their siblings. Conducting thematic analysis, we identified four themes, comprising eight subthemes. The primary themes were 1) caregiver upskilling and self-assurance, 2) acknowledging unique differences amongst autistic children, 3) trouble behind and trouble ahead, and 4) managing sensory overload. Through these themes, we describe the unique needs of autistic children and their families with regard to emotional and sensory aspects of the vaccination visit across settings. We conclude by making recommendations for adaptation of vaccination services to incorporate the autistic perspective and lived experiences of families of autistic children.
•Recommendations to adapt vaccination services for autistic children.•Families seek accessible vaccine information to make informed decisions.•Parents want to communicate their child's needs to support vaccination experiences.•Managing anxiety related to vaccinations is essential to routine care.•Each autistic child requires a personalised approach to care.
Introduction
Adolescent girls and young women (AGYW) in South Africa bear a disproportionate burden of HIV. Community mobilization (CM), defined as community members taking collective action to ...achieve a common goal related to health, equity and rights, has been associated with increased HIV testing and condom use and has been called a ‘critical enabler’ for addressing the HIV epidemic. However, limited research has examined whether CM is associated with HIV incidence among AGYW.
Methods
We examine the association of CM with incident HIV among AGYW (ages 13 to 21) enrolled in the HPTN 068 cohort in the Agincourt Health and socio‐Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross‐sectional, population‐based surveys were conducted to measure CM among 18‐ to 35‐year‐old residents in 2012 and 2014. HPTN 068 participants completed up to five annual visits that included an HIV test (2011 to 2016). Household‐level data were collected from AGYW parents/guardians and census data is updated annually. Mean village‐level CM scores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village‐level CM score and CM components with incident HIV infection, accounting for village‐level clustering and adjusting for key covariates.
Results
There were 194 incident infections over the follow‐up period. For every additional standard deviation of village‐level CM there was 12% lower HIV incidence (RR: 0.88, 95% CI: 0.79, 0.98) after adjusting for individual, household and community characteristics. CM components associated with lower HIV incidence included critical consciousness (RR: 0.88; CI: 0.79, 0.97) and leadership (RR: 0.87; CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91; CI: 0.81, 1.01), shared concerns (RR: 0.90; CI: 0.81, 1.00), and organizations and networks (RR: 0.91; CI: 0.79, 1.03) may also play a protective role.
Conclusions
These results suggest that having strong community social resources will reduce AGYW's risk of HIV acquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming for AGYW.
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