A Younger Demographic Defines Hepatitis C Patient Profiles in the Recent Direct-Acting Antiviral Era

A Younger Demographic Defines Hepatitis C Patient Profiles in the Recent Direct-Acting Antiviral Era Authors: Minawala, Ria1; Naylor, Paul H.2; Ehrinpreis, Murray N.2; Mutchnick, Milton G.2 Institutions: 1. Wayne State University School of Medicine, Detroit, MI, United States. 2. Wayne State University School of Medicine, Division of Gastroenterology, Detroit, MI, United States. Background: Highly effective and safe direct-acting antivirals (DAAs) against hepatitis C virus (HCV) combined with U.S. Preventive Services Task Force recommendation to screen for HCV in individuals born between 1945 and 1965 (age cohort; 54-79 years of age in 2019) was expected to reduce the number of actively infected patients via identification and treatment. Nevertheless, HCV infections remain a significant health concern. A study of HCV infected patients in our urban internal medicine practice, during the interferon era and prior to the introduction of DAAs, demonstrated a population within the age cohort. The objective of this study was to characterize the current patient population seen in the same practice with respect to age, race, and treatment status to determine the impact of DAA therapy on patient profiles and to test the hypothesis that there would be an increase in younger population among those infected. Methods: Using electronic medical records, we identified patients who presented to our urban GI practice in 2019. Data collected from patient charts included demographics, liver function tests, HCV genotype, viral load, imaging studies, and treatment history. Results: There were 601 patients with HCV seen in 2019 and the majority were African American (AA) (85%) and male (66%). Comparison of age alongside gender and race revealed that non-AA patients (51 years, SEM = 0.9) were significantly younger than AA patients (63 years, SEM = 0.4; p Conclusion: The primary shift in patient demographics as compared to the interferon era has been toward younger, non- AA females. In contrast, the predominant AA patients are still within the age cohort. The emergence of younger patients has important implications for screening, patient outreach, and treatment plans. A more intensive evaluation for risk factors and the role of COVID-19 in treatment is warranted. Many AA and non- AA patients were not started on any treatment in 2019, signifying a need for continued follow-up after initial visit to close the linkage to care gap

FAILURE TO TREAT HCV IN PATIENTS SEEN IN A PREDOMINATELY AFRICAN AMERICAN SOCIOECONOMICALLY CHALLENGED POPULATION

The research objective of this proposal is to investigate the impediment with respect to moving a patient from initial antibody/PCR positive to successful completion of treatment. Secondary objectives include determining the most effective way for patients to progress from initial antibody/PCR positive to treatment and identifying the roadblocks for HCV antibody/PCR positive patients to be treated effectively. Data was collected from 2019 HCV patient EMR charts, including demographics, laboratory studies, and treatment history. Concerning treatment, we evaluated linkage to the care; we defined success as treatment within six months of the initial visit. Thus, data on treatment initiation was collected through the first six months of 2020

Maternal supplementation with LGG reduces vaccine-specific immune responses in infants at high-risk of developing allergic disease

Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N = 31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines

Complexes of tetracyanobiimidazole--V. Self-association of Ir(I) complex anions

The self-association of the planar anion [Ir(CO)2Tcbiim]- where H2Tcbiim is 4,4',5,5'-tetracyano-2,2'-biimidazole has been studied in acetontrile solution by analysis of the charge-transfer spectra. At low concentrations (~ 10-5 M) monomer units prevail. At intermediate concentrations (~ 10-3 M) dimerization is evident and a very strong ([var epsilon] = 18 500 M-1 cm-1) new absorption appears at 475 nm. A novel procedure was used to obtain this value and to estimate the equilibrium constant for dimerization, 13.2 M-1 at 24.4[deg]C. From the temperature dependence of the spectra, [Delta]H is calculated to be -28 to -30 kJ M-1. At higher concentrations (~ 10-2 M) spectral changes consistent with further oligomerization are observed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26436/1/0000524.pd

Association of Group B Streptococcus Colonization and Bovine Exposure: A Prospective Cross-Sectional Cohort Study

While Group B Streptococcus (GBS) human colonization and infection has long been suspected as originating from cows, several investigators have suggested that ongoing interspecies GBS transmission is unlikely due to genotyping data demonstrating that human and bovine-derived GBS strains represent mostly distinct populations. The possibility of ongoing transmission between humans and their livestock has not been systematically examined.To examine ongoing interspecies transmission, we conducted a prospective cross-sectional cohort study of 68 families and their livestock. Stool specimens were collected from 154 people and 115 livestock; GBS was detected in 19 (12.3%) humans and 2 (1.7%) animals (bovine and sheep). Application of multilocus sequence typing (MLST) identified 8 sequence types (STs or clones), with STs 1 and 23 predominating. There were 11 families in which two members submitted stools and at least one had GBS colonization. In 3 of these families, both members (consisting of couples) were colonized, yielding a co-colonization rate of 27% (95% CI: 7%-61%). Two of these couples had strains with identical MLST, capsule (cps) genotype, susceptibility, and RAPD profiles. One couple co-colonized with ST-1 (cps5) strains also had a bovine colonized with the identical strain type. On multivariate analysis of questionnaire data, cattle exposure was a predictor of GBS colonization, with each unit increase in days of cattle exposure increasing the odds of colonization by 20% (P = 0.02). These results support interspecies transmission with additional evidence for transmission provided by the epidemiological association with cattle exposure.Although GBS uncommonly colonizes livestock stools, increased frequency of cattle exposure was significantly associated with human colonization and one couple shared the same GBS strains as their bovine suggesting intraspecies transmission. These results set the framework for GBS as a possible zoonotic infection, which has significant public health implications

Door-to-needle time for thrombolysis : a secondary analysis of the TIPS cluster randomised controlled trial

Objective: The current study aimed to evaluate the effects of a multi-component in-hospital intervention on the door-to-needle time for intravenous thrombolysis in acute ischaemic stroke. Design: This study was a post hoc analysis of door-to-needle time data from a cluster-randomised controlled trial testing an intervention to boost intravenous thrombolysis implementation. Setting: The study was conducted among 20 hospitals from three Australian states. Participant: Eligible hospitals had a Stroke Care Unit or staffing equivalent to a stroke physician and a nurse, and were in the early stages of implementing thrombolysis. Intervention: The intervention was multifaceted and developed using the behaviour change wheel and informed by breakthrough collaborative methodology using components of the health behaviour change wheel. Primary and secondary outcome measures: The primary outcome for this analysis was door-to-needle time for thrombolysis and secondary outcome was the proportion of patients received thrombolysis within 60 min of hospital arrival. Results: The intervention versus control difference in the door-to-needle times was non-significant overall nor significant by hospital classification. To provide additional context for the findings, we also evaluated the results within intervention and control hospitals. During the active-intervention period, the intervention hospitals showed a significant decrease in the door-to-needle time of 9.25 min (95% CI: -16.93 to 1.57), but during the post-intervention period, the result was not significant. During the active intervention period, control hospitals also showed a significant decrease in the door-to-needle time of 5.26 min (95% CI: -8.37 to -2.14) and during the post-intervention period, this trend continued with a decrease of 12.13 min (95% CI: -17.44 to 6.81). Conclusion: Across these primary stroke care centres in Australia, a secular trend towards shorter door-to-needle times across both intervention and control hospitals was evident, however the TIPS (Thrombolysis ImPlementation in Stroke) intervention showed no overall effect on door-to-needle times in the randomised comparison

The Quantity Theory of Money is Valid. The New Keynesians are Wrong!

We test the quantity theory of money (QTM) using a novel approach and a large new sample. We do not follow the usual approach of first differentiating the logarithm of the Cambridge equation to obtain an equation relating the growth rate of real GDP, the growth rate of money and inflation. These variables must then again be ‘integrated’ by averaging in order to obtain stable relationships. Instead we suggest a much simpler procedure for testing directly the stability of the coefficient of the Cambridge equation. For 125 countries and post-war data we find the coefficient to be surprisingly stable. We do not select for high inflation episodes as was done in most empirical studies; inflation rates do not even appear in our data set. Much work supporting the QTM has been done by economic historians and at the University of Chicago by Milton Friedman and his associates. The QTM was a foundation stone of the monetarist revolution. Subsequently belief in it waned. The currently dominant New Keynesian School, implicitly or explicitly denies the validity of the QTM. We survey this history and argue that the QTM is valid and New Keynesians are wrong

Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

Evidence and Ideology in Macroeconomics: The Case of Investment Cycles

The paper reports the principal findings of a long term research project on the description and explanation of business cycles. The research strongly confirmed the older view that business cycles have large systematic components that take the form of investment cycles. These quasi-periodic movements can be represented as low order, stochastic, dynamic processes with complex eigenvalues. Specifically, there is a fixed investment cycle of about 8 years and an inventory cycle of about 4 years. Maximum entropy spectral analysis was employed for the description of the cycles and continuous time econometrics for the explanatory models. The central explanatory mechanism is the second order accelerator, which incorporates adjustment costs both in relation to the capital stock and the rate of investment. By means of parametric resonance it was possible to show, both theoretically and empirically how cycles aggregate from the micro to the macro level. The same mathematical tool was also used to explain the international convergence of cycles. I argue that the theory of investment cycles was abandoned for ideological, not for evidential reasons. Methodological issues are also discussed