Exacerbations of chronic obstructive pulmonary disease (COPD) are a source of substantial morbidity. In this randomized, controlled trial involving patients with moderately severe COPD, daily ...treatment with azithromycin for 1 year was associated with fewer exacerbations.
Acute exacerbations of chronic obstructive pulmonary disease (COPD) result in frequent visits to physicians' offices and emergency rooms and numerous hospitalizations and days lost from work; they also account for a substantial percentage of the cost of treating COPD.
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Patients who have acute exacerbations of COPD, as compared with patients with COPD who do not have acute exacerbations, have an increased risk of death, a more rapid decline in lung function, and reduced quality of life.
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Although inhaled glucocorticoids, long-acting beta
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-agonists, and long-acting muscarinic antagonists reduce the frequency of acute exacerbations of COPD,
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patients receiving . . .
In this study involving patients who were at high risk for exacerbations of chronic obstructive pulmonary disease but had no other indication for statin treatment, simvastatin at a daily dose of 40 ...mg did not affect the exacerbation rate.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States.
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It is characterized by acute exacerbations that are associated with increased hospitalizations and costs of care, worsened quality of life, and increased mortality.
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Effective therapies for the treatment or prevention of exacerbations are limited.
Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that reduce the risks of acute cardiac events and death.
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Although widely used for their lipid-lowering effects, statins are also reported to have antiinflammatory effects.
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Multiple retrospective studies have shown that statins are beneficial in COPD. Reported benefits include . . .
Hepatitis C (HCV) screening is imperative to meet WHO elimination targets including increased detection and reduced mortality. An electronic medical record (EMR) system can be utilized in health care ...centers to indicate if a patient should be targeted for HCV screening, thus increasing the number of those offered testing.
We examined English language publications reporting on the impact of EMR system utilization on HCV screening and the HCV continuum of care. Relevant papers were identified using multiple search engines to search key terms. Clinical outcomes considered included any or no change in HCV screening rates following EMR system introduction, as well as any or no change in rates of patients progressing along the HCV cascade of care after diagnosis once an EMR system was implemented.
From a search pool of 18 studies, 11 meet inclusion criteria and reported on the selected clinical outcomes. Each outcome assessed indicated that use of an EMR system increased the proportion of patients offered and/or receiving HCV testing. We were unable to conclude if an EMR system had an impact on the number of patients progressing along the HCV cascade of care following a positive test result. Overall, all methods of implementation of an EMR system had the same outcome of increasing screening rates.
EMR system utilization had a positive impact on increasing HCV screening. However, the clinical effectiveness of utilizing an EMR system to help eliminate transmission and increase HCV treatment cure rates requires further study.
Chronic hepatitis C virus (HCV) infection disrupts immune functions, including that of cytotoxic CD8
T-cells which are important mediators of immune response. While HCV cure aims to eliminate long ...term sequelae of infection, whether direct-acting antiviral (DAA) treatment results in immune reconstitution remains unclear. We and others have reported generalized CD8
T-cell dysfunction in chronic HCV infection and our research suggests that the degree of liver damage is a factor in this process. Our recent research indicates that liver fibrosis is not readily reversed after DAA-mediated clearance of chronic HCV infection. We therefore examined the function of circulating CD8
T-cell subsets in chronic HCV infection in the context of liver fibrosis severity, determined by ultrasound elastography and Metavir F-score system. We observed progressive shifts in CD8
T-cell subset distribution in HCV-infected individuals with advanced liver fibrosis (F4) compared to minimal fibrosis (F0-1) or uninfected controls, and this remained unchanged after viral cure. Impaired CD8
T-cell function was observed as a reduced proportion of CD107
and perforin
late effector memory cells in HCV
(F4) and HCV
(F0-1) individuals, respectively. In HCV
(F4) individuals, nearly all CD8
T-cell subsets had an elevated proportion of perforin
cells while naïve cells had increased proportions of IFN-γ
and CD107
cells. These exaggerated CD8
T-cell activities were not resolved when evaluated 24 weeks after completion of DAA therapy and HCV clearance. This was further supported by sustained, high levels of cell proliferation and cytolytic activity. Furthermore, DAA therapy had no effect on elevated concentrations of systemic inflammatory cytokines and decreased levels of inhibitory TGF-β in the plasma of HCV
(F4) individuals, suggesting HCV infection and advanced liver disease result in a long-lasting immune activating microenvironment. These data demonstrate that in chronic HCV infection, liver fibrosis severity is associated with generalized hyperfunctional CD8
T-cells, particularly with perforin production and cytotoxicity, and this persists after viral clearance. Whether DAA therapy will eliminate other related long-term sequelae in HCV
(F4) individuals remains an important research question.
Little is known about the effect of combination antiretroviral therapy (cART) on life expectancy in sub-Saharan Africa.
To estimate life expectancy of patients once they initiate cART in Uganda.
...Prospective cohort study.
Public sector HIV and AIDS disease-management program in Uganda.
22 315 eligible patients initiated cART during the study period, of whom 1943 were considered to have died.
All-cause mortality rates were calculated and abridged life tables were constructed and stratified by sex and baseline CD4 cell count status to estimate life expectancies for patients receiving cART. The average number of years remaining to be lived by patients who received cART at varying age categories was estimated.
After adjustment for loss to follow-up, crude mortality rates (deaths per 1000 person-years) ranged from 26.9 (95% CI, 25.4 to 28.5) in women to 43.9 (CI, 40.7 to 47.0) in men. For patients with a baseline CD4 cell count less than 0.050 × 10(9) cells/L, the mortality rate was 67.3 (CI, 62.1 to 72.9) deaths per 1000 person-years, whereas among persons with a baseline CD4 cell count of 0.250 × 10(9) cells/L or more, the mortality rate was 19.1 (CI, 16.0 to 22.7) deaths per 1000 person-years. Life expectancy at age 20 years for the overall cohort was 26.7 (CI, 25.0 to 28.4) additional years and at age 35 years was 27.9 (CI, 26.7 to 29.1) additional years. Life expectancy increased substantially with increasing baseline CD4 cell count. Similar trends are observed for older age groups.
A small (6.4%) proportion of patients were lost to follow-up, and it was imputed that 30% of these patients had died. Few patients with a CD4 cell count greater than 0.250 × 10(9) cells/L initiated cART.
Ugandan patients receiving cART can expect an almost normal life expectancy, although there is considerable variability among subgroups of patients.
Canadian Institutes of Health Research.
A previously healthy 34-year-old woman was admitted to hospital for new mucocutaneous eruptions leading to severe odynophagia. One week before admission, she had experienced a cough with generalized ...malaise, confirmed by radiography as community-acquired pneumonia. An emergency department physician in urgent care prescribed amoxicillin-clavulanic acid, a medication she had taken previously without incident. Within 48 hours, she experienced vaginal discomfort with labial erythema and edema. She was thought to have vulvovaginitis, and fluconazole was prescribed by an emergency department physician on a repeat assessment. Erythema multiforme is an acute, immune-mediated condition affecting the skin and mucosal surfaces. By definition, less than 10% of the body surface area is affected. The disease is typically self-limiting.
Background The impact of chronic hepatic infection on antigen non-specific immune cells in circulation remains poorly understood. We reported lasting global hyperfunction of peripheral CD8 T cells in ...HCV-infected individuals with cirrhosis. Whether gene expression patterns in bulk CD8 T cells are associated with the severity of liver fibrosis in HCV infection is not known. Methods RNA sequencing of blood CD8 T cells from treatment naïve, HCV-infected individuals with minimal (Metavir F0-1 ≤ 7.0 kPa) or advanced fibrosis or cirrhosis (F4 ≥ 12.5 kPa), before and after direct-acting antiviral therapy, was performed. CD8 T cell function was assessed by flow cytometry. Results In CD8 T cells from pre-DAA patients with advanced compared to minimal fibrosis, Gene Ontology analysis and Gene Set Enrichment Analysis identified differential gene expression related to cellular function and metabolism, including upregulated Hedgehog (Hh) signaling, IFN-α, -γ, TGF-β response genes, apoptosis, apical surface pathways, phospholipase signaling, phosphatidyl-choline/inositol activity, and second-messenger-mediated signaling. In contrast, genes in pathways associated with nuclear processes, RNA transport, cytoskeletal dynamics, cMyc/E2F regulation, oxidative phosphorylation, and mTOR signaling, were reduced. Hh signaling pathway was the top featured gene set upregulated in cirrhotics, wherein hallmark genes GLI1 and PTCH1 ranked highly. Inhibition of Smo-dependent Hh signaling ablated the expression of IFN-γ and perforin in stimulated CD8 T cells from chronic HCV-infected patients with advanced compared to minimal fibrosis. CD8 T cell gene expression profiles post-DAA remained clustered with pre-DAA profiles and disparately between advanced and minimal fibrosis, suggesting a persistent perturbation of gene expression long after viral clearance. Conclusions This analysis of bulk CD8 T cell gene expression in chronic HCV infection suggests considerable reprogramming of the CD8 T cell pool in the cirrhotic state. Increased Hh signaling in cirrhosis may contribute to generalized CD8 T cell hyperfunction observed in chronic HCV infection. Understanding the lasting nature of immune cell dysfunction may help mitigate remaining clinical challenges after HCV clearance and more generally, improve long term outcomes for individuals with severe liver disease.
Almost 1% of Canadians are hepatitis C (HCV)-infected. The liver-specific complications of HCV are established but the extra-hepatic comorbidity, multimorbidity, and its relationship with HCV ...treatment, is less well known. We describe the morbidity burden for people with HCV and the relationship between multimorbidity and HCV treatment uptake and cure in the pre- and post-direct acting antiviral (DAA) era.
We linked adults with HCV at The Ottawa Hospital Viral Hepatitis Program as of April 1, 2017 to provincial health administrative data and matched on age and sex to 5 Ottawa-area residents for comparison. We used validated algorithms to identify the prevalence of mental and physical health comorbidities, as well as multimorbidity (2+ comorbidities). We calculated direct age- and sex-standardized rates of comorbidity and comparisons were made by interferon-based and interferon-free, DAA HCV treatments.
The mean age of the study population was 54.5 years (SD 11.4), 65% were male. Among those with HCV, 4% were HIV co-infected, 26% had liver cirrhosis, 47% received DAA treatment, and 57% were cured of HCV. After accounting for age and sex differences, the HCV group had greater multimorbidity (prevalence ratio (PR) 1.38, 95% confidence interval (CI) 1.20 to 1.58) and physical-mental health multimorbidity (PR 2.71, 95% CI 2.29-3.20) compared to the general population. Specifically, prevalence ratios for people with HCV were significantly higher for diabetes, renal failure, cancer, asthma, chronic obstructive pulmonary disease, substance use disorder, mood and anxiety disorders and liver failure. HCV treatment and cure were not associated with multimorbidity, but treatment prevalence was significantly lower among middle-aged individuals with substance use disorders despite no differences in prevalence of cure among those treated.
People with HCV have a higher prevalence of comorbidity and multimorbidity compared to the general population. While HCV treatment was not associated with multimorbidity, people with substance use disorder were less likely to be treated. Our results point to the need for integrated, comprehensive models of care delivery for people with HCV.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
HIV-HCV coinfected individuals are often more deprived than the general population. However, deprivation is difficult to measure, often relying on aggregate data which does not capture individual ...heterogeneity. We developed an individual-level deprivation index for HIV-HCV co-infected persons that encapsulated social, material, and lifestyle factors.
We estimated an individual-level deprivation index with data from the Canadian Coinfection Cohort, a national prospective cohort study. We used a predetermined process to select 9 out of 19 dichotomous variables at baseline visit to include in the deprivation model: income >$1500/month; education >high school; employment; identifying as gay or bisexual; Indigenous status; injection drug use in last 6 months; injection drug use ever; past incarceration, and past psychiatric hospitalization. We fitted an item response theory model with: severity parameters (how likely an item was reported), discriminatory parameters, (how well a variable distinguished index levels), and an individual parameter (the index). We considered two models: a simple one with no provincial variation and a hierarchical model by province. The Widely Applicable Information Criterion (WAIC) was used to compare the fitted models. To showcase a potential utility of the proposed index, we evaluated with logistic regression the association of the index with non-attendance to a second clinic visit (as a proxy for disengagement) and using WAIC compared it to a model containing all the individual parameters that compose the index as covariates.
We analyzed 1547 complete cases of 1842 enrolled participants. According to the WAIC the hierarchical model provided a better fit when compared to the model that does not consider the individual's province. Values of the index were similarly distributed across the provinces. Overall, past incarceration, education, and unemployment had the highest discriminatory parameters. However, in each province different components of the index were associated with being deprived reflecting local epidemiology. For example, Saskatchewan had the highest severity parameter for Indigenous status while Quebec the lowest. For the secondary analysis, 457 (30%) failed to attend a second visit. A one-unit increase in the index was associated with 17% increased odds (95% credible interval, 2% to 34%) of not attending a second visit. The model with just the index performed better than the model with all the components as covariates in terms of WAIC.
We estimated an individual-level deprivation index in the Canadian Coinfection cohort. The index identified deprivation profiles across different provinces. This index and the methodology used may be useful in studying health and treatment outcomes that are influenced by social disparities in co-infected Canadians. The methodological approach described can be used in other studies with similar characteristics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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