A Systematic Literature Review and Meta-Analysis of Primary Evidence Reporting Health-State Preference Values in Chronic Hepatitis B, C, and D.

OBJECTIVES: Chronic viral hepatitis is associated with severe impairment and reduction in patient health-related quality of life because of the substantial morbidity associated with advanced liver disease. The aim of this study was to identify and synthesize utilities for chronic hepatitis B (cHBV), C (cHCV), and D (cHDV) through a systematic literature review (SLR) and meta-analyses. METHODS: Electronic databases were searched from inception to May 2023 to identify primary studies reporting health-state utilities in English in patients aged 18 years and over, with cHBV, cHCV, or cHDV in the United States, the United Kingdom, Europe, Canada, Australia, or New Zealand. Meta-analyses were conducted for studies reporting a measure of uncertainty; model selection (fixed and random) was based on the observed levels of heterogeneity among studies. RESULTS: A total of 24 studies met the inclusion criteria and were included in the meta-analyses. More studies meeting the inclusion criteria reported utilities for cHCV (n = 20) than for cHBV (n = 8); no studies reported utility values for cHDV. Although mean utilities were higher for cHBV compared with cHCV for any given health state, utilities decreased with disease progression toward cirrhosis health states. Meta-analyses in cHCV found a utility decline of 0.1 and 0.03, based on progression from noncirrhosis to compensated cirrhosis and for decompensation in established cirrhosis, respectively. CONCLUSIONS: Chronic viral hepatitis is associated with a considerable impairment in health-related quality of life. Despite our findings, there is a need for more evidence on the lived experience in patients living with chronic hepatitis, notably in cHBV and cHDV.

Opportunities and Challenges in Screening for Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of mortality in the United States. Outcomes are greatly improved if CRC is detected early; hence, screening is currently recommended for adults aged 45 years and older at average risk for the disease. Despite this recommendation and the availability of accurate screening tests, the CRC screening rates are below those recommended. The goal of this study was to identify temporal trends (from 2015 to 2019) in CRC screening rates and the utilization of screening tests recommended for CRC detection among average-risk individuals within the St Elizabeth Healthcare system in Kentucky, United States. The primary population of interest was patients aged 50-75 years (the CRC screening was recommended for this age group at the time of the study). Deidentified data were sourced from patients' electronic health records, and the results showed that screening rates increased significantly from 26% in 2015 to 49% in 2019 (<0.0001). The incidence of any screening test also increased significantly from 2015 to 2019, for those who were due for screening (P < 0.05) and for the entire cohort (P < 0.1). The use of multitarget stool DNA (mt-sDNA) increased 40-fold over the study timeframe (P < 0.05). These study results confirm that CRC screening rates remain suboptimal, although incidence and adherence improved significantly in those aged 50-75 years from 2015 to 2019. The growing adoption and availability of mt-sDNA may be correlated with an increase in overall screening in this average-risk population.

Beyond Undetectable: Modeling the Clinical Benefit of Improved Antiretroviral Adherence in Persons With Human Immunodeficiency Virus With Virologic Suppression.

Background: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown. Methods: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to <100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up. Results: Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6%-37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to <100% for an additional event to occur over 3- and 5-year follow-up, respectively. Conclusions: Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (eg, via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated.

Corrigendum: Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

[This corrects the article DOI: 10.3389/fimmu.2022.976564.].

The impact of multi-target stool DNA testing in clinical practice in the United States: A real-world evidence retrospective study.

Widely endorsed screening modalities for colorectal cancer (CRC) include structural visualization (e.g. colonoscopy) and stool-based tests including multitarget stool DNA (mt-sDNA), fecal immunochemical tests (FIT), or high-sensitivity guaiac-based fecal occult blood tests (gFOBT). However, CRC screenings are underutilized, hence understanding the screening utilization trends is important, particularly with respect to the newest guideline-endorsed option (mt-sDNA). The objective of this study was to assess patterns in overall CRC screenings following clinical availability of the mt-sDNA test among average-risk individuals in the Ascension Wisconsin healthcare system focusing primarily on individuals aged 50-75 years old. We also reported CRC screening behaviors among individuals < 50 and > 75 years old. Electronic medical records of individuals aged ≥ 40 years from 2015 to 2018 were reviewed to identify average-risk and screen-eligible members. For those with screening data available, we determined the proportion who were up-to-date with any United States Preventive Services Task Force (USPSTF) recommended screening strategy; the number of screening tests performed in the measurement year; and the distribution of screening modalities. Temporal trends were assessed using regression analysis, including subgroup analyses across age groups and screening modalities. A total of 172,045 unique patients aged ≥ 40 years were included, of which 115,708 individuals aged 50-75 years. When considering all individuals up-to-date and screened in the measurement year, overall adherence increased significantly over the 4-year study period, from 39,105 to 49,698 patients or 47 % to 59 % (p < 0.0001). The screening incidence between 2015 and 2018 increased from 19.44 to 23.66 tests per 1,000 persons for gFOBT and FIT, a 1.2-fold increase, and from 6.54 to 29.78 tests per 1,000 persons for mt-sDNA (p < 0.05), a 4.6-fold increase. During the same time period, the screening incidence of colonoscopy decreased from 119.99 to 110.58 tests per 1,000 persons, corresponding to a decrease of 8 %. Similar patterns in screening incidence rates were observed among those aged < 50 and > 75 years old. Growing adoption, higher preference, and the broad availability of mt-sDNA testing may be associated with an increase in overall CRC screening rates in the average-risk population, in parallel with a slight increase in the use of other non-invasive CRC screening tests.

Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

Introduction: Variable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS events (SNAEs)/death by changes in interleukin-6 (IL-6) and D-dimer, we modeled the effects of differences in these markers between specific ART regimens on the long-term risk of clinical outcomes. Methods: We used a Markov model to compare the risk of SNAEs/death with differences in IL-6 and D-dimer levels associated with remaining on specific three-drug regimens versus switching to specific two-drug ART regimens over 5 years of treatment. We used IL-6 and D-dimer data based on trajectories over time from the randomized TANGO and observational AIR studies. Age at model entry was set at 39 years. The primary endpoint was the number needed to treat for one additional SNAE/death. Results: Over 144 weeks, PWH on one of the three-drug regimens studied were predicted to spend 22% more time in the low IL-6 quartile and 13% less time in the high IL-6 quartile compared with those on one of the two-drug regimens. Over 144 weeks, the predicted mean number of SNAEs/deaths per 100 PWH was 5.6 for a three-drug regimen associated with lower IL-6 levels versus 6.8 for a two-drug regimen associated with higher IL-6 levels. The number needed to treat for one additional SNAE/death among PWH receiving a two-drug versus three-drug regimen for 240 weeks was 43. Approximately 2,900 participants would be required for a 240-week clinical study to evaluate the accuracy of the model. Conclusions: Our Markov model suggests that higher IL-6 levels associated with switching from specific three- to two- drug ART regimens may be associated with an increase in the risk of SNAEs/death. Clinical studies are warranted to confirm or refute these results.

Medication related to pigmentation of oral mucosa

Background: The diagnosis of oral melanotic lesions is, more often than not, challenging in the clinical practice due to the fact that there are several reasons which may cause an increase in pigmentation on localized or generalized areas. Among these, medication stands out. Material and Methods: In this work, we have carried out a review in the reference pharma database: Micromedex® followed by a review of the scientific published literature to analyse coincidences and possible discrepancies. Results: Our findings show that there are several prescription drugs that can cause pigmented lesions in the oral mucosa. This must be known by clinicians in order to properly diagnose pigmented lesions. We have identified a set of 21 medicaments which cause these lesions, some of which are used frequently in the clinic, such as Metronidazole, Amitriptyline, conjugated oestrogens and Chlorhexidine gluconate. We also found discrepancies with the data published in specialized literature, some of which wasn’t reflected in the Summary of Product Characteristics. Conclusions: Our work highlights the importance of the proper communication of adverse drug reactions (ADR) by health professionals in order to provide thorough and accurate information and diagnosis.(AU)

Vulvar Tuberculosis-A Rare Manifestation of the Disease.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. According to data from the World Health Organization, this disease remains one of the leading causes of death worldwide. Although it most commonly affects the lungs, tuberculosis can compromise any organ. The present study reports a rare case of vulvar tuberculosis in a postmenopausal woman with a history of asymptomatic pulmonary and pleural tuberculosis, with no prior documented contact with the bacillus. Diagnosis was based on vulvar lesion biopsies, with histological findings suggestive of infection and isolation of M. tuberculosis by microbiological culture and polymerase chain reaction (PCR) essays. The lesions reverted to normal after tuberculostatic therapy.

A tuberculose é uma doença infeciosa causada pelo Mycobacterium tuberculosis. De acordo com dados da Organização Mundial de Saúde, esta doença mantém-se entre as principais causas de morte no mundo. Embora afete mais frequentemente os pulmões, a tuberculose pode comprometer qualquer órgão. O presente artigo relata um caso raro de tuberculose vulvar numa mulher na pós-menopausa, com antecedentes de tuberculose pleural e pulmonar assintomática, sem contato documentado com o bacilo. O diagnóstico foi feito com base na biópsia da lesão vulvar, com achados histológicos sugestivos da infeção e isolamento do M. tuberculosis por meios de cultura e pela técnica da reação em cadeia da polimerase (PCR). Após terapêutica tuberculostática, as lesões reverteram.

Vulvar tuberculosis-A rare manifestation of the disease / Tuberculose vulvar - Uma manifestação rara da doença

Abstract Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. According to data from the World Health Organization, this disease remains one of the leading causes of death worldwide. Although it most commonly affects the lungs, tuberculosis can compromise any organ. The present study reports a rare case of vulvar tuberculosis in a postmenopausal woman with a history of asymptomatic pulmonary and pleural tuberculosis, with no prior documented contact with the bacillus. Diagnosis was based on vulvar lesion biopsies, with histological findings suggestive of infection and isolation of M. tuberculosis by microbiological culture and polymerase chain reaction (PCR) essays. The lesions reverted to normal after tuberculostatic therapy.

Resumo A tuberculose é uma doença infeciosa causada pelo Mycobacterium tuberculosis. De acordo com dados da Organização Mundial de Saúde, esta doença mantém-se entre as principais causas demorte nomundo. Embora afetemais frequentemente os pulmões, a tuberculose pode comprometer qualquer órgão. O presente artigo relata um caso raro de tuberculose vulvar numa mulher na pós-menopausa, com antecedentes de tuberculose pleural e pulmonar assintomática, sem contato documentado com o bacilo. O diagnóstico foi feito com base na biópsia da lesão vulvar, com achados histológicos sugestivos da infeção e isolamento do M. tuberculosis pormeios de cultura e pela técnica da reação em cadeia da polimerase (PCR). Após terapêutica tuberculostática, as lesões reverteram.

Into the wild-WAMBAM goes to Canada.

The sixth Wild Animal Models Bi-Annual Meeting was held in July 2017 in Québec, with 42 participants. This report documents the evolution of questions asked and approaches used in evolutionary quantitative genetic studies of wild populations in recent decades, and how these questions and approaches were represented at the recent meeting. We explore how ideas from previous meetings in this series have developed to their present states, and consider how the format of the meetings may be particularly useful at fostering the rapid development and proliferation of ideas and approaches.

Individual variation in reproductive behaviour is linked to temporal heterogeneity in predation risk.

Variation in predation risk is a major driver of ecological and evolutionary change, and, in turn, of geographical variation in behaviour. While predation risk is rarely constant in natural populations, the extent to which variation in predation risk shapes individual behaviour in wild populations remains unclear. Here, we investigated individual differences in reproductive behaviour in 16 Trinidadian guppy populations and related it to the observed variation in predator biomass each population experienced. Our results show that high heterogeneity in predator biomass is linked to individual behavioural diversification. Increased within-population heterogeneity in predator biomass is also associated with behavioural polymorphism. Some individuals adjust the frequency of consensual mating behaviour in response to differences in sex ratio context, while others display constantly at elevated frequencies. This pattern is analogous to a 'live fast, die young' pace-of-life syndrome. Notably, both high and low mean differences in predator biomass led to a homogenization of individual frequency of consensual mating displays. Overall, our results demonstrate that individual behavioural variation is associated with heterogeneity in predator biomass, but not necessarily with changes in mean values of predator biomass. We suggest that heterogeneity in predator biomass is an informative predictor of adaptive responses to changes in biotic conditions.

Maternal response to environmental unpredictability.

Mothers are expected to use environmental cues to modify maternal investment to optimize their fitness. However, when the environment varies unpredictably, cues may not be an accurate proxy of future conditions. Under such circumstances, selection favors a diversifying maternal investment strategy. While there is evidence that the environment is becoming more uncertain, the extent to which mothers are able to respond to this unpredictability is generally unknown. In this study, we test the hypothesis that Daphnia magna increase the variance in maternal investment in response to unpredictable variation in temperature consistent with global change predictions. We detected significant variability across temperature treatments in brood size, neonate size at birth, and time between broods. The estimated variability within-brood size was higher (albeit not statistically significant) in mothers reared in unpredictable temperature conditions. We also detected a cross-generational effect with the temperature history of mothers modulating the phenotypic response of F1's. Notably, our results diverged from the prediction that increased variability poses a greater risk to organisms than changes in mean temperature. Increased unpredictability in temperature had negligible effects on fitness-correlated traits. Mothers in the unpredictable treatment, survived as long, and produced as many F1's during lifetime as those produced in the most fecund treatment. Further, increased unpredictability in temperature did not affect the probability of survival of F1's. Collectively, we provide evidence that daphnia respond effectively to thermal unpredictability. But rather than increasing the variance in maternal investment, daphnia respond to uncertainty by being a jack of all temperatures, master of none. Importantly, our study highlights the essential need to examine changes in variances rather than merely on means, when investigating maternal responses.