Catharina Matheï

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. Methods and Findings We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade. Conclusion Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.

Similar compliance and effect of treatment in chronic hepatitis C resulting from intravenous drug use in comparison with other infection causes.

Objectives There is some reluctance to treat intravenous drug users (IVDUs) with chronic hepatitis C (CHC) because of presumed lower compliance and response to antiviral therapy. We intended to evaluate the compliance and response to antiviral treatment for CHC in IVDUs compared with non-IVDUs. Methods A retrospective cohort study — secondary analysis of the results of a treatment trial — was performed in Belgium and The Netherlands. A total of 406 previously untreated CHC patients, including 98 (24%) IVDUs, were studied for compliance (presentation at the end of treatment), complete response (alanine aminotransferase within normal limits and serum hepatitis C virus polymerase chain reaction negative) at the end of therapy and sustained virological response (SVR). Results Non-compliance (8.2%) in IVDUs was not different from non-IVDUs (6.8%) (relative risk=1.20; 95% confidence interval=0.55–2.62). Complete response after controlling for hepatitis C virus was similar (relative risk=1.19; 95% confidence interval=0.89–1.60). Controlling for treatment arm, age, sex, presence of cirrhosis or hepatitis C virus viral load before treatment did not change these results. There was a marginally significant difference in the sustained virological response between IVDUs (46.6%) and non-IVDUs (34.6%) (relative risk=1.35; 95% confidence interval=1.00–1.81), also disappearing after adjusting for genotype. No difference in compliance or sustained virological response was found between active and non-active IVDUs or between IVDU patients in or without a methadone maintenance program. Conclusions In this group of Benelux patients, IVDUs showed similar compliance and response to treatment with interferon and ribavirin compared with other patients with CHC infection. Therefore, it is no longer justifiable to withhold treatment to chronic hepatitis C patients who use intravenous drugs.

Muscle Strength and Physical Performance as Predictors of Mortality, Hospitalization, and Disability in the Oldest Old

To evaluate the predictive value of muscle strength and physical performance in the oldest old for all‐cause mortality; hospitalization; and the onset of disability, defined as a decline in activities of daily living (ADLs), independent of muscle mass, inflammatory markers, and comorbidities.

Methods to evaluate renal function in elderly patients: a systematic literature review

CONTEXT multiple studies of elderly patients show that the prevalence of chronic renal failure in people aged 65 years and older is dependent on the method used to calculate the glomerular filtration rate. We performed a systematic literature search with research question: What is the best method that could be applicable in clinical practice for evaluating renal function in the elderly? Studies using inulin, Cr-51-EDTA, Tc-DTPA or iohexol assays as the gold standard were included. METHODS we searched the PubMed and EMBASE databases. Articles found were screened first by title and abstract and then by five criteria. Retained articles were scored using an adapted version of QUADAS. RESULTS twelve articles had an identified population or subpopulation aged 65 years and older. The studies were heterogeneous with regard to the population investigated and the statistical procedures used to compare the methods and equations with the gold standard. The Cockcroft-Gault (CG) and MDRD equations and the serum cystatin C concentration produced the highest correlations with the gold standard. CONCLUSIONS no accurate method to evaluate renal function in the elderly was found. Serum cystatin C concentration and the CG and MDRD formula might be valuable parameters, although there is insufficient evidence.

The prevalence of sarcopenia in very old individuals according to the European consensus definition: insights from the BELFRAIL study

BACKGROUND the prevalence of sarcopenia varies widely between studies. The objective of this study was to assess the prevalence of sarcopenia in a representative sample of persons aged 80 years and older according to the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm and the proposed cut-off values. A secondary aim was to investigate the relationship between different individual criteria and low physical performance capacity. METHODS baseline data of the prospective BELFRAIL study (BFC80+) were analysed. Sarcopenia status was determined according to the EWGSOP guidelines. The skeletal muscle mass index (SMI) was assessed according to bioelectrical impedance. Muscle strength and muscle performance were evaluated according to grip strength and the modified short physical performance battery (SPPBm). A logistic regression analysis was performed. RESULTS according to the EWGSOP algorithm, 12.5% of the participants were classified in the sarcopenia group. Sixty percent of the female participants had muscle strength values below the cut-off and 70% had low SPPBm values. In males, these prevalence values were 49.5% for grip strength and 39.7% for SPPB. The logistic regression analysis showed that low SPPBm was associated with grip strength (OR: 0.88, 95% CI: 0.84-0.92) independent of SMI. CONCLUSION in a population-based sample of the very old the prevalence of sarcopenia according to the EWGSOP algorithm is similar to the prevalence of sarcopenia with SMI as a single criterion. A large number of participants with a sufficient SMI value showed low muscle strength and/or a poor SPPBm score. A low SPPBm was associated with grip strength but not with SMI.

Evidence for a substantial role of sharing of injecting paraphernalia other than syringes/needles to the spread of hepatitis C among injecting drug users

Summary.  In industrialized countries, transmission of hepatitis C occurs primarily through injecting drug use. Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of other injecting paraphernalia is increasing. In this paper, the independent effects of sharing paraphernalia other than syringes/needles have been estimated. The prevalence and force of infection were modelled using three serological data sets from drug users in three centres in Belgium as a function of the sharing behaviour. It was found that sharing of materials other than syringes/needles indeed seemed to contribute substantially to the spread of hepatitis C among injecting drug users.

Associations Between Cytomegalovirus Infection and Functional Impairment and Frailty in the BELFRAIL Cohort

To investigate whether an observed association between cytomegalovirus (CMV) exposure and functional impairment and frailty in older adults is reproducible in a cohort of individuals aged 80 and older.

The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons.

The main consequence of the loss of MM and muscle strength is limitations of physical performance and disability in older people. It is unclear whether a decline in functional capacity results from the loss of MM and/or the qualitative impairment of the muscle tissue. The aim of our research was to investigate the relationship between physical performance and grip strength, inflammatory markers and MM in a population of community-dwelling very old persons. This study is a cross-sectional analysis within the BELFRAIL-study, a cohort study of subjects aged 80 years and older (n=567). MM was assessed by bioelectrical impedance. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined on fasting blood samples. Logistic regression analysis was build using a low physical performance level evaluated according to Short Physical Performance Battery (SPPB) (dependent variable) and grip strength, pro-inflammatory status and MM (independent variables) adjusted for age and for the total number of chronic diseases. Low SPPB scores were associated with grip strength scores for women (OR 0.86 (95% CI 0.77-0.96)), and for men (OR 0.89 (95% CI 0.81-0.96)). The relationships between low SPPB and MM or inflammatory profile were not significant. Our results show that low physical performance remains associated with low grip strength even after considering other risk factors for sarcopenia in the oldest old and support the hypothesis that low muscle strength is a better indicator than low MM. The role of an inflammatory component in the age-related loss of muscle strength and function could not be confirmed.

No relation between vitamin D status and physical performance in the oldest old: results from the Belfrail study

BACKGROUND vitamin D deficiency is a well-known cause of bone loss and fractures but its association, especially among the oldest old, with muscle weakness is less obvious. OBJECTIVE to investigate the relationship between 25-hydroxyvitamin D (25-OHD) and muscle performance in persons aged 80 years and older. METHODS baseline results of the Belfrail study, a prospective, population-based cohort study were used to study balance, grip strength and gait speed in relation to 25-OHD serum levels in 367 subjects. RESULTS a sufficient 25-OHD serum level of 30 ng/ml or more was found in 12.8% of the population. The prevalence of vitamin deficiency (20-29 ng/ml), insufficiency (10-19 ng/ml) and severe insufficiency (<10 ng/ml) was 21.5, 33 and 32.7%, respectively. No significant relation between balance, gait speed and grip strength, and serum 25-OHD was detected neither in bivariate analysis nor after adjustment for age, gender, level of education, institutionalisation, smoking status, body mass index, co-morbidity, level of activity, season, CRP, renal function, serum calcium parathyroid hormone levels, vitamin D intake and use of loop or thiazide diuretics. CONCLUSION in this cohort of octogenarians vitamin D deficiency was highly prevalent. We could not confirm the findings of previous studies showing an association between serum 25-OHD and physical performance in elderly.

CD4:8 Ratio >5 Is Associated With a Dominant Naive T-Cell Phenotype and Impaired Physical Functioning in CMV-Seropositive Very Elderly People: Results From the BELFRAIL Study

A subset of older people is at increased risk of hospitalization and dependency. Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8 ratio and cytomegalovirus (CMV) seropositivity plays an important role in the pathophysiology of functional decline. Nevertheless, the relation between CD4:8 ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and T-cell phenotypes of 235 community-dwelling persons aged ≥81.5 years in the BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8 ratio, which was associated with CMV seropositivity, less naive, and more late-differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a phenotype associated with a higher proportion of naive T cells and absent in young donors. In CMV seropositives, this subgroup had lower proportions of late-differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G reactivity. This novel naive T-cell-dominated phenotype was counterintuitively associated with a higher proportion of those with impaired physical functioning in the very elderly people infected with CMV. This underscores the notion that in very elderly people, not merely CMV infection but also the state of its accompanying immune dysregulation is of crucial importance with regard to physical impairment.