Miracle-dz/UniFAR-FTUs huggingface dataset:
Virologic Outcomes Among People Living With Human Immunodeficiency Virus With High Pretherapy Viral Load Burden Initiating on Common Core Agents

Abstract Background People living with human immunodeficiency virus (PLWH) initiating antiretroviral therapy (ART) with viral loads (VLs) ≥100 000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. Methods ART-naive PLWH with VLs ≥100 000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) between 12 August 2013 and 31 July 2017 were identified from the OPERA database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART; (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks; (iii) 2 consecutive VLs ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks; or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modeling estimated the association between regimen and virologic failure. Results There were 2038 ART-naive patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%), or RAL (2%). Median follow-up was 18.1 (interquartile range, 12.4–28.9) months. EVG and DTG initiators were similar at baseline, but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL, and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% confidence interval) was 1.46 (1.05–2.03) for EVG, 2.24 (1.50–3.34) for DRV, and 4.13 (1.85–9.24) for RAL. Conclusions ART-naive PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL, and DRV initiators. Antiretroviral therapy-naïve people living with HIV (PLWH) initiating therapy with viral loads ≥100,000 copies/mL varied markedly at baseline. In adjusted models, PLWH initiating dolutegravir-based regimens were less likely to experience virologic failure as compared to elvitegravir, raltegravir and darunavir initiators.
Psychometric properties of the German version of the Depressive and Anxious Avoidance in Prolonged Grief Questionnaire (DAAPGQ)

The Depressive and Anxious Avoidance in Prolonged Grief Questionnaire (DAAPGQ) was developed to measure depressive and anxious avoidance behaviors, which, according to cognitive-behavioral models, are supposed to play an important role in the development and maintenance of prolonged grief. The present study aimed to develop a German version of the DAAPGQ and evaluate its psychometric properties and validity within a representative sample of the German general population (N = 2531). The German-language DAAPGQ was developed using a forward-backward translation procedure. Then, a subsample of individuals who reported having lost a significant other (N = 1371) of a representative sample was assessed with the German DAAPGQ, along with information on sociodemographic characteristics, prolonged grief symptom severity (PG-13), general anxiety (GAD-2) and depression (PHQ-2). The factor structure of the DAAPGQ was evaluated using confirmatory factor analyses, reliability by calculating internal consistency on subscale level and convergent validity by correlations between DAAPQG subscale sores with PG-13, GAD-2 and PHQ-2 sum scores. As expected, a two-factor model with correlated latent variables showed good fit to the data, replicating findings from the original version. Internal consistency was high for both subscales (Cronbach’s α .86 and .95, respectively). Convergent validity was established by theoretically expected and statistically significant positive correlations of DAAPGQ subscales with symptom severity of prolonged grief, depression, and anxiety and negative correlations with time since loss. Furthermore, the addition of depressive and anxious avoidance significantly improved the prediction of prolonged grief symptom severity over sociodemographic and loss-related information. In sum, our results suggest that the German-language DAAPGQ is a reliable and valid measure of depressive and anxious avoidance and a useful tool to improve our knowledge on the role of avoidance in prolonged grief. We also provide descriptive data to improve the applicability of the DAAPGQ for individual diagnostics.
The rise in inequality after pandemics: can fiscal support play a mitigating role?

Abstract Major epidemics of the last two decades (SARS, H1N1, MERS, Ebola, and Zika) have been followed by increases in inequality [Furceri et al. (2020), COVID Economics, 12, 138–157]. In this article, we show that the extent of fiscal consolidation in the years following the onset of these pandemics has played an important role in determining the extent of the increase in inequality. Episodes marked by extreme austerity—measured using either the government’s fiscal balance, health expenditures, or redistribution—have been associated with an increase in the Gini measure of inequality three times as large as in episodes where fiscal policy has been more supportive. We survey the evidence thus far on the distributional impacts of the COVID-19 pandemic, which suggests that inequality is likely to increase in the absence of strong policy actions. We review the case made by many observers [IMF (2020), Fiscal Monitor; Stiglitz (2020), Finance & Development, Fall 2020; Sandbu (2020b), Financial Times, 26 November 2020)] that fiscal support should not be withdrawn prematurely despite understandable concerns about high public debt-to-GDP ratios.
Efficacy and cost effectiveness of intravenous ferric carboxymaltose versus iron sucrose in adult patients with iron deficiency anaemia

Background Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. Objective To determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. Data sources Electronic medical record i.e. Cerner® system. Target population Adults patients with iron deficiency anaemia. Time horizon A 12-month period (01/01/2018–31/12/2018). Perspective Hamad Medical Corporation (HMC, a public hospital). Intervention IV Ferric Carboxymaltose versus IV Iron Sucrose. Outcome measures With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. Results of base-case analysis There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. Results of sensitivity analysis Not applicable. Limitations The study did not consider the clinical or humanistic outcome. Conclusions The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.
Metastatic castration-resistant prostate cancer

Patients with metastatic castration-resistant prostate cancer (mCRPC) have an average survival of only 13 months. Identification of novel predictive and actionable biomarkers in the homologous recombination repair (HRR) pathway in up to a quarter of patients with mCRPC has led to the approval of targeted therapies like poly-ADP ribose polymerase inhibitors (PARPi), with the potential to improve survival outcomes. The approval of PARPi has led to guideline bodies such as the National Comprehensive Cancer Network (NCCN) to actively recommend germline and or somatic HRR gene panel testing to identify patients who will benefit from PARPi. However, there are several challenges as genetic testing is still at an early stage especially in lowand middle-income countries, with cost and availability being major impediments. In addition, there are issues such as choice of optimal tissue for genetic testing, archival, storage, retrieval of tissue blocks, interpretation and classification of variants in the HRR pathway, and the need for pretest and post-test genetic counseling. This review provides insights into the HRR gene mutations prevalent in mCRPC and the challenges for a more widespread gene testing to identify actionable germline pathogenic variants and somatic mutations in the HRR pathway, and proposes a clinical algorithm to enhance the efficiency of the gene testing process. Review
Systematic Review of Visual Motor Integration in Children with Developmental Disabilities

Original research articles regarding visual motor integration skills in children with developmental disabilities and the impact of occupational therapy were identified, appraised, and synthesized. Twenty-four articles were chosen for this review. Themes were noted during the critique of articles. Three themes emerged: “age,” “gender,” and “diagnosis. ” Regarding the impact on visual motor integration, there was strong evidence for age, moderate evidence for gender, and strong evidence for diagnosis. Future research investigating visual motor integration in children should control for age and diagnosis.
A Spectrum of Biopsy – Proven Renal Disorders and Their Clinicopathological Correlation in Elderly Population From a Tertiary Care Center in South India

Introduction Chronic kidney disease (CKD) has become a health concern with an extensive burden on incidence and prognosis. While the increasing lifespan contributes to a higher incidence of CKD among the elderly, the diagnostic picture in this age group is complicated by senescence-related changes. A better understanding of the etiology and progression of the disease warrants renal biopsy in such patients. This study aims to explore the histopathological spectrum of native renal biopsies leading to CKD in elderly patients in a tertiary care hospital. Methods Among the list of patients who had undergone renal biopsy at our institute from January 2015 to March 2020, elderly patients aged ≥ 60years were chosen for this study. Their demographic details, lab investigations and histopathological reports were collected. The sex distribution and prevalence of different renal diseases was calculated. The subjects were classified into four broad diagnostic groups - primary glomerular disease, diabetic nephropathy, hypertensive nephropathy, and tubulointerstitial disease. The estimated glomerular filtration rate (eGFR) values were calculated and used to stage chronic kidney disease in these patients. Statistical analysis was carried out to find a correlation between diagnostic groups and CKD presence and between serum C3 values and immunofluorescence for the same on biopsy. Results One hundred thirty-two patients formed the study sample with a male to female ratio of 1.28:1, showing a slight male predominance. The most common diagnostic group was primary glomerular disease (46%), among which focal segmental glomerulosclerosis (FSGS) was the most common entity (12%). 47.7% and 66.6% of patients in the study sample showed elevated serum blood urea nitrogen (BUN) and creatinine values, respectively. 86% of our study sample had low eGFR values, and the majority (35%) of the patients were classified under CKD stage 3. CKD incidence was high among patients with primary glomerular diseases, but no significant statistical correlation was found. 43.5% of all IF positive cases showed low serum C3 values and established a positive correlation between IF and serum C3 values. Conclusion There is no statistically significant correlation of the four diagnostic groups to the CKD. CKD in the elderly may be multifactorial, and a collaborative study across the nations may be needed to further evaluate the etiology.
To achieve 95-95-95 targets we must reach men and youth: High level of knowledge of HIV status, ART coverage, and viral suppression in the Botswana Combination Prevention Project through universal test and treat approach

Background Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence. Methods The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression Results Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end. Conclusions Knowledge of HIV-positive status and ART coverage increased towards 95–95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets. Clinical trial number NCT01965470.
Prevalence of Hepatitis C Virus Infection Identified From Nontargeted Screening Among Adult Visitors in an Academic Appalachian Regional Emergency Department

Abstract Background We describe the initial results of an adult academic emergency department (ED) nontargeted hepatitis C virus (HCV) screening program serving Appalachia, which is disproportionately affected by the opioid epidemic. Methods The study was a retrospective screening study of ED systematic, nontargeted, opt-out HCV testing outcomes from July 2018 through September 2020. Eligibility requirements for “nontargeted” HCV testing included age ≥18 years, verbally able to communicate, receiving bloodwork already as part of routine clinical care, and not opting out of testing. For eligible individuals who did not opt out of testing, an HCV antibody (Ab) test was performed. Reactive Ab tests were confirmed with reflexive HCV RNA testing. The primary study outcome was the characterization of HCV Ab and RNA prevalence. Results There were 75 722 unique adult visitors during the period studied. Of these, 54 931 individuals were verbally engaged regarding testing and did not opt out. A total of 34 848 individuals received HCV Ab testing, with 3665 patients (10.5%) having reactive results. RNA confirmatory testing was reflexively performed in all Ab-positive patients, with 1601 (50.3%) positive. The majority of HCV Ab– and RNA-positive patients were young, born after 1965, and were more likely to be White, male, Medicaid insured, and report a history of injection drug use. Conclusions ED nontargeted, opt-out testing can identify a high prevalence of HCV infection among adult visitors. HCV infection was disproportionately high among younger, White individuals, likely reflecting the escalating syndemic of opioid injection and HCV transmission in Appalachia.
A Bayesian approach to reveal the key role of mask wearing in modulating projected interpersonal distance during the first COVID-19 outbreak

Humans typically create and maintain social bonds through interactions that occur at close social distances. The interpersonal distance of at least 1 m recommended as a relevant measure for COVID-19 contagion containment requires a significant change in everyday behavior. In a web-based experimental study conducted during the first pandemic wave (mid-April 2020), we asked 242 participants to regulate their preferred distance towards confederates who did or did not wear protective masks and gloves and whose COVID-19 test results were positive, negative, or unknown. Information concerning dispositional factors (perceived vulnerability to disease, moral attitudes, and prosocial tendencies) and situational factors (perceived severity of the situation in the country, frequency of physical and virtual social contacts, and attitudes toward quarantine) that may modulate compliance with safety prescriptions was also acquired. A Bayesian analysis approach was adopted. Individual differences did not modulate interpersonal distance. We found strong evidence in favor of a reduction of interpersonal distance towards individuals wearing protective equipment and who tested negative to COVID-19. Importantly, shorter interpersonal distances were maintained towards confederates wearing protective gear, even when their COVID-19 test result was unknown or positive. This protective equipment-related regulation of interpersonal distance may reflect an underestimation of perceived vulnerability to infection; this perception must be discouraged when pursuing individual and collective health-safety measures.
Adaptation of the endemic coronaviruses HCoV-OC43 and HCoV-229E to the human host

Abstract Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins. Thus, understanding the evolutionary dynamics of these human viruses might provide insight into the future trajectories of SARS-CoV-2 evolution. Because the zoonotic sources of HCoV-OC43 and HCoV-229E are known, we applied a population genetics–phylogenetic approach to investigate which selective events accompanied the divergence of these viruses from the animal ones. Results indicated that positive selection drove the evolution of some accessory proteins, as well as of the membrane proteins. However, the spike proteins of both viruses and the hemagglutinin-esterase (HE) of HCoV-OC43 represented the major selection targets. Specifically, for both viruses, most positively selected sites map to the receptor-binding domains (RBDs) and are polymorphic. Molecular dating for the HCoV-229E spike protein indicated that RBD Classes I, II, III, and IV emerged 3–9 years apart. However, since the appearance of Class V (with much higher binding affinity), around 25 years ago, limited genetic diversity accumulated in the RBD. These different time intervals are not fully consistent with the hypothesis that HCoV-229E spike evolution was driven by antigenic drift. An alternative, not mutually exclusive possibility is that strains with higher affinity for the cellular receptor have out-competed strains with lower affinity. The evolution of the HCoV-OC43 spike protein was also suggested to undergo antigenic drift. However, we also found abundant signals of positive selection in HE. Whereas such signals might result from antigenic drift, as well, previous data showing co-evolution of the spike protein with HE suggest that optimization for human cell infection also drove the evolution of this virus. These data provide insight into the possible trajectories of SARS-CoV-2 evolution, especially in case the virus should become endemic.
Reduced Susceptibility to Metronidazole Is Associated With Initial Clinical Failure in Clostridioides difficile Infection

Abstract Background Clinical studies have demonstrated inferior cure rates when metronidazole (MTZ) is used to treat Clostridioides difficile infection (CDI). We hypothesized that a newly identified, heme-inducible form of reduced MTZ susceptibility in C. difficile leads to higher odds of initial clinical failure in patients with CDI treated with MTZ. Methods This multicenter cohort study included adults diagnosed with CDI between 2017 and 2018. C. difficile isolated from stool samples underwent agar dilution MTZ susceptibility testing with incorporation of fresh heme. Blinded investigators reviewed medical records for initial clinical failure and other relevant clinical variables. Classification and regression tree (CART) analysis was used to identify the MTZ minimum inhibitory concentration (MIC) breakpoint that was predictive of initial clinical failure. Results were confirmed using univariate and multivariable logistic regression analyses to account for potential confounders. Results Of the 356 patients included, 72% received MTZ-based therapy and 27% experienced initial clinical failure. CART analysis identified an MTZ MIC ≥1 µg/mL above which patients had a higher rate of initial clinical failure. MTZ MICs ranged from 0.25 to 8 µg/mL (MIC50/90 = 0.25/2 µg/mL), and approximately 18% of isolates had MTZ MICs ≥1 µg/mL. In multivariable analysis, an MTZ MIC ≥1 µg/mL was an independent predictor of initial clinical failure in patients receiving an MTZ-based treatment regimen (odds ratio, 2.27 [95% confidence interval, 1.18–4.34]). Conclusions Using a reproducible method to determine C. difficile MICs to MTZ, a breakpoint of ≥1 µg/mL identified patients at higher risk of initial clinical failure.
Subacute thyroiditis at the time of SARS-CoV-2 pandemic

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-ncnd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Subacute thyroiditis at the time of SARS-CoV-2 pandemic