Sensitivity to change of generic preference-based instruments (EQ-5D-3L, EQ-5D-5L, and HUI3) in the context of treatment for people with prescription-type opioid use disorder in Canada.

PURPOSE: Using data from a randomized controlled trial for treatment of prescription-type opioid use disorder in Canada, this study examines sensitivity to change in three preference-based instruments [EQ-5D-3L, EQ-5D-5L, and the Health Utilities Index Mark 3 (HUI3)] and explores an oft-overlooked consideration when working with contemporaneous responses for similar questions-data quality. METHODS: Analyses focused on the relative abilities of three instruments to capture change in health status. Distributional methods were used to categorize individuals as 'improved' or 'not improved' for eight anchors (seven clinical, one generic). Sensitivity to change was assessed using area under the ROC (receiver operating characteristics) curve (AUC) analysis and comparisons of mean change scores for three time periods. A 'strict' data quality criteria, defined a priori, was applied. Analyses were replicated using 'soft' and 'no' criteria. RESULTS: Data from 160 individuals were used in the analysis; 30% had at least one data quality violation at baseline. Despite mean index scores being significantly lower for the HUI3 compared with EQ-5D instruments at each time point, the magnitudes of change scores were similar. No instrument demonstrated superior sensitivity to change. While six of the 10 highest AUC estimates were for the HUI3, 'moderate' classifications of discriminative ability were identified in 12 (of 22) analyses for each EQ-5D instrument, compared with eight for the HUI3. CONCLUSION: Negligible differences were observed between the EQ-5D-3L, EQ-5D-5L, and HUI3 regarding the ability to measure change. The prevalence of data quality violations-which differed by ethnicity-requires further investigation.

Assessing the Relationship between the Gut Microbiota and Inflammatory Bowel Disease Therapeutics: A Systematic Review.

Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference -1.16 (-1.50, -0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes.

Human Immunodeficiency Virus transmission by HIV Risk Group and Along the HIV Care Continuum: A Contrast of 6 US Cities.

BACKGROUND: Understanding the sources of HIV transmission provides a basis for prioritizing HIV prevention resources in specific geographic regions and populations. This study estimated the number, proportion, and rate of HIV transmissions attributable to individuals along the HIV care continuum within different HIV transmission risk groups in 6 US cities. METHODS: We used a dynamic, compartmental HIV transmission model that draws on racial behavior-specific or ethnic behavior-specific and risk behavior-specific linkage to HIV care and use of HIV prevention services from local, state, and national surveillance sources. We estimated the rate and number of HIV transmissions attributable to individuals in the stage of acute undiagnosed HIV, nonacute undiagnosed HIV, HIV diagnosed but antiretroviral therapy (ART) naïve, off ART, and on ART, stratified by HIV transmission group for the 2019 calendar year. RESULTS: Individuals with undiagnosed nonacute HIV infection accounted for the highest proportion of total transmissions in every city, ranging from 36.8% (26.7%-44.9%) in New York City to 64.9% (47.0%-71.6%) in Baltimore. Individuals who had discontinued ART contributed to the second highest percentage of total infections in 4 of 6 cities. Individuals with acute HIV had the highest transmission rate per 100 person-years, ranging from 76.4 (58.9-135.9) in Miami to 160.2 (85.7-302.8) in Baltimore. CONCLUSION: These findings underline the importance of both early diagnosis and improved ART retention for ending the HIV epidemic in the United States. Differences in the sources of transmission across cities indicate that localized priority setting to effectively address diverse microepidemics at different stages of epidemic control is necessary.

Improving health equity and ending the HIV epidemic in the USA: a distributional cost-effectiveness analysis in six cities.

BACKGROUND: In the USA, Black and Hispanic or Latinx individuals continue to be disproportionately affected by HIV. Applying a distributional cost-effectiveness framework, we estimated the cost-effectiveness and epidemiological impact of two combination implementation approaches to identify the approach that best meets the dual objectives of improving population health and reducing racial or ethnic health disparities. METHODS: We adapted a dynamic, compartmental HIV transmission model to characterise HIV micro-epidemics in six US cities: Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle. We considered combinations of 16 evidence-based interventions to diagnose, treat, and prevent HIV transmission according to previously documented levels of scale-up. We then identified optimal combination strategies for each city, with the distribution of each intervention implemented according to existing service levels (proportional services approach) and the racial or ethnic distribution of new diagnoses (between Black, Hispanic or Latinx, and White or other ethnicity individuals; equity approach). We estimated total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios of strategies implemented from 2020 to 2030 (health-care perspective; 20-year time horizon; 3% annual discount rate). We estimated three measures of health inequality (between-group variance, index of disparity, Theil index), incidence rate ratios, and rate differences for the selected strategies under each approach. FINDINGS: In all cities, optimal combination strategies under the equity approach generated more QALYs than those with proportional services, ranging from a 3·1% increase (95% credible interval [CrI] 1·4-5·3) in New York to more than double (101·9% [75·4-134·6]) in Atlanta. Compared with proportional services, the equity approach delivered lower costs over 20 years in all cities except Los Angeles; cost reductions ranged from $22·9 million (95% CrI 5·3-55·7 million) in Seattle to $579·8 million (255·4-940·5 million) in Atlanta. The equity approach also reduced incidence disparities and health inequality measures in all cities except Los Angeles. INTERPRETATION: Equity-focused HIV combination implementation strategies that reduce disparities for Black and Hispanic or Latinx individuals can significantly improve population health, reduce costs, and drive progress towards Ending the HIV Epidemic goals in the USA. FUNDING: National Institute on Drug Abuse.

Inflammatory bowel disease and the gut microbiota.

Inflammatory bowel disease (IBD) is a group of immune-mediated disorders characterised by a chronic, relapsing-remitting inflammation predominantly affecting the gastrointestinal tract. IBD is incurable, affecting people in their most productive years. IBD is historically seen as a disease of Westernised nations although in recent times other countries have seen an exponential rise in cases. Although the exact pathogenesis remains unclear, evidence suggests that microbiota changes play a critical role in IBD pathogenesis. Over the past two decades, IBD has become one of the most studied human conditions linked to the gut microbiota. However, deciphering the intricate link between the gut microbiota and therapeutic efficacy remains elusive. This review will summarise the current evidence relating to the gut microbiota and its involvement in IBD pathogenesis as well as the impact of IBD treatments including pharmaceutical-, nutraceutical- and microbial-focused regimens on the gut microbiota.

Attributing health benefits to preventing HIV infections versus improving health outcomes among people living with HIV: an analysis in six US cities.

OBJECTIVE: Combination strategies generate health benefits through improved health outcomes among people living with HIV (PLHIV) and prevention of new infections. We aimed to determine health benefits attributable to improved health among PLHIV versus HIV prevention for a set of combination strategies in six US cities. DESIGN: A dynamic HIV transmission model. METHODS: Using a model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City (NYC) and Seattle, we assessed the health benefits of city-specific optimal combinations of evidence-based interventions implemented at publicly documented levels and at ideal (90% coverage) scale-up (2020-2030 implementation, 20-year study period). We calculated the proportion of health benefit gains (measured as quality-adjusted life-years) resulting from averted and delayed HIV infections; improved health outcomes among PLHIV; and improved health outcomes due to medication for opioid use disorder (MOUD). RESULTS: The HIV-specific proportion of total benefits ranged from 68.3% (95% credible interval: 55.3-80.0) in Seattle to 98.5% (97.5-99.3) in Miami, with the rest attributable to MOUD. The majority of HIV-specific health benefits in five of six cities were attributable HIV prevention, and ranged from 33.1% (26.1-41.1) in NYC to 83.1% (79.6-86.6) in Atlanta. Scaling up to ideal service levels resulted in three to seven-fold increases in additional health benefits, mostly from MOUD, with HIV-specific health gains primarily driven by HIV prevention. CONCLUSION: Optimal combination strategies generated a larger proportion of health benefits attributable to HIV prevention in five of six cities, underlining the substantial benefits of antiretroviral therapy engagement for the prevention of HIV transmission through viral suppression. Understanding to whom benefits accrue may be important in assessing the equity and impact of HIV investments.

Empirical Validity of a Generic, Preference-Based Capability Wellbeing Instrument (ICECAP-A) in the Context of Spinal Cord Injury.

BACKGROUND: Assessing the validity of generic instruments across different clinical contexts is an important area of methodological research in economic evaluation and outcomes measurement. OBJECTIVE: Our objective was to examine the empirical validity of a generic, preference-based capability wellbeing instrument (ICECAP-A) in the context of spinal cord injury. METHODS: This study consisted of a secondary analysis of data collected using an online cross-sectional survey. The survey included questions regarding demographics, injury classifications and characteristics, secondary health conditions, quality of life and wellbeing, and functioning in activities of daily living. Analysis comprised the descriptive assessment of Spearman's rank correlations between item-/dimension-level data for the ICECAP-A and four preference-based health-related quality of life (HRQoL) instruments, and discriminant and convergent validity approaches to examine 21 evidence-informed or theoretically derived constructs. Constructs were defined using participant and injury characteristics and responses to a range of health, wellbeing and functioning outcomes. RESULTS: Three hundred sixty-four individuals completed the survey. Mean index score for the ICECAP-A was 0.761; 12 (3%) individuals reported full capability (upper anchor; score = 1), and there were no reports of zero capabilities (lower anchor; score = 0). The strongest correlations were dominated by items and dimensions on the comparator (HRQoL) instruments that are non-health aspects of quality of life, such as happiness and control over one's life (including self-care). Of 21 hypothesised constructs, 19 were confirmed in statistical tests, the exceptions being the exploratory hypotheses regarding education and age at injury. CONCLUSION: The ICECAP-A is an empirically valid outcome measure for assessing capability wellbeing in people with spinal cord injury living in a community setting. The extent to which the ICECAP-A provides complementary information to preference-based HRQoL instruments is dependent on the comparator.

Can the 'Ending the HIV Epidemic' initiative transition the USA towards HIV/AIDS epidemic control?

: Using a dynamic HIV transmission model calibrated for six USA cities, we projected HIV incidence from 2020 to 2040 and estimated whether an established UNAIDS HIV epidemic control target could be met under ideal implementation of optimal combination strategies previously defined for each city. Four of six cities (Atlanta, Baltimore, New York City and Seattle) were projected to achieve epidemic control by 2040 and we identified differences in reaching epidemic control across racial/ethnic groups.