Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Increased Emergency Department Utilization and Costs for Medicare Cancer Patients with Malnutrition Diagnoses.

BACKGROUND: Malnutrition or its risk affects up to 70% of cancer patients. Compared to adequately nourished oncology patients, those with malnutrition experience more complications and have poorer prognoses, thus higher needs for healthcare. We compared utilization of emergency department (ED) services and costs for Medicare-covered cancer patients with or without a malnutrition diagnosis. METHODS: We used the Centers for Medicare and Medicaid Services (CMS) Standard Analytic File to identify fee-for-service beneficiaries who had a cancer diagnosis, and had one or more outpatient claims in 2018. We totaled individual claims and costs for ED visits per beneficiary, then calculated mean per-person claims and costs for malnourished vs non-malnourished patients. RESULTS: Using data from over 2.8 million claims of patients with cancer diagnoses, the prevalence of diagnosed malnutrition was 2.5%. The most common cancer types were genitourinary, hematologic/blood, and breast. Cancer patients with a malnutrition diagnosis, compared to those without, had a significantly higher annual total number of outpatient claims (21.4 vs. 11.5, P<.0001), including a 2.5-fold higher rate of ED visits (1.43 vs. 0.56, p<.0001). As result, such patients incurred more than 2-fold higher mean ED claim costs than did their adequately nourished counterparts ($10,724 vs. $4,935, P<.0001). CONCLUSIONS: Our results suggest that malnutrition in cancer patients imposes a high outpatient burden on resource utilization and costs of care in terms of ED use. We propose that nutritional interventions can be used to improve health outcomes for people with cancer and to improve economic outcomes for patients and providers.

Collection and determinants of patient reported outcome measures in haemodialysis patients in Scotland.

BACKGROUND/INTRODUCTION: Patient reported outcome measures (PROMs) can evaluate the quality of health in patients with established renal failure. There is limited experience of their use within national renal registries. AIM: To describe the Scottish Renal Registry's (SRR) experience of collecting PROMS in the haemodialysis population and correlate PROMS to demographic and clinical parameters. DESIGN: Retrospective observational cross-sectional study. METHODS: Haemodialysis patients in Scotland were invited to complete the KDQOL™-36 questionnaire on the day of the annual SRR census in 2015 and 2016. Questionnaires were linked to census demographic and clinical variables. RESULTS: In 2016, 738 questionnaires were linked to census data (39% of prevalent haemodialysis population). Response rates differed with age (≥ 65 years 42%, < 65 years 36%) [χ2P = 0.006]; duration of renal replacement therapy (<1 year 46%, ≥1 < 5 years 38%, ≥ 5 years 33%) [χ2P = 0.002] and social class (Scottish Index of Multiple Deprivation (SIMD) Class 1 32%, Class 2 41%, Class 3 40%, Class 4 48%, Class 5 40%) [χ2P < 0.001]. There were significant differences in PROMs with age, SIMD quintile and primary renal diagnosis. Achieving a urea reduction ratio of >65% and dialysing through arteriovenous access were associated with significantly higher PROMs. PROMs were not affected by haemoglobin or phosphate concentration. DISCUSSION/CONCLUSIONS: Routine collection of PROMs is feasible and can identify potentially under-recognized and treatable determinants to quality of life. The association between attaining recommended standards of care and improved PROMs is striking. Individual and population-wide strategies are required to improve PROMs.

The effect of Toxoplasma gondii infection on expression of chemokines by rat retinal vascular endothelial cells.

Cells infected by Toxoplasma gondii undergo up-regulation of proinflammatory cytokines, organelle redistribution, and protection from apoptosis. During infection in man, the parasite encysts within the retina, a process that results in retinochoroiditis which can lead to permanent loss of sight. The reasons for the parasite to infect retinal tissue and the mechanisms by which it encysts are not clearly understood. We studied the effect of infection with T. gondii of retinal vascular endothelial cells using the Clontech Atlastrade mark array system in order to elucidate changes in gene expression. We compared hybridization of RNA to the array from infected and uninfected cells at two time points; 2 and 24 h. Exposure to T. gondii after 2 h resulted in change of expression of approximately 6% of genes on the array, including those involved in cell structure, protein and vesicle trafficking, cell-cycle regulation, transcriptional and translational machinery, and apoptosis. Among the genes involved in the inflammatory response, chemokine genes such as GRO1 (Growth Regulated Oncogene 1), MCP-1 (Monocyte Chemotactic Protein-1), FKN (Fractalkine) and RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) were found to be up-regulated and protein production was confirmed by ELISA. However after 24 h of infection, GRO1, MCP-1 and FKN were down-regulated, confirmed by RT-PCR. Thus, invasion of retinal vascular endothelium (RVE) cells by T. gondii leads to the production of chemokines important in directing the traffic of inflammatory cells to the infected area.

The effect of cytokines on the replication of T. gondii within rat retinal vascular endothelial cells.

Toxoplasma gondii infection of the eye can result in a recurrent necrotising retinochoroiditis (TR) which may lead to a permanent loss of visual acuity. The mechanisms responsible for the control of TR within the retina are unknown. The aim of this study was to examine the effects of cytokines on the replication of T. gondii RH strain tachyzoites within rat retinal vascular endothelial (rRVE) cells. Pretreatment of rRVE with IFNgamma, TNF or IL-1beta resulted in a significant decrease in T. gondii replication from day 2 onwards. There was no significant difference in nitric oxide (NO) production by IFNgamma, TNF or IL-1beta treated rRVE as compared to controls at any time point. By comparison, the addition of L-tryptophan to IFNgamma treated cultures significantly restored T. gondii replication from 48 h post inoculation. Thus, IFNgamma, TNF and IL-1beta can significantly inhibit the replication of T. gondii within rRVE. However, this inhibition appears to be independent of NO production. L-tryptophan catabolism may have a role in IFNgamma mediated inhibition of T. gondii replication in rRVE cells.

Lipopheresis in the nephrotic syndrome.

BACKGROUND: Experimental models have established a role for lipoproteins in the pathogenesis of progressive renal failure. However, conventional treatment rarely normalizes the high serum cholesterol of the nephrotic syndrome. The removal of low-density lipoprotein by lipopheresis is discussed. METHODS: Lipopheresis may be beneficial in nephrotic patients with focal segmental glomerulosclerosis. The authors studied the long-term effects of low-density lipoprotein cholesterol (LDL-C) removal using the Kaneka Liposorber system, which binds LDL-C to dextran sulfate in a controlled trial in 20 nephrotic patients with different renal diseases. RESULTS: A 21-month clamp of plasma total cholesterol at 6.0 mmol/liter or below was significantly lower than controls (chi 2 = 84.3, P < 0.001), followed 12 aphereses over 6 to 12 weeks in all but three apheresed patients. 1/Cr slopes were unchanged when the 50-day average period of lipopheresis treatments was excluded from analysis. Proteinuria was not reduced, but serum albumin tended to rise (NS). Fibrinogen fell by 29.8%; high-density lipoprotein, apoA1, and Lp(a) were unchanged. Two apheresed patients had a prolonged remission with a reduction of proteinuria to less than 250 mg/24 hr. The reasons for prolonged reduction of total cholesterol include depletion of tissue cholesterol, an improved fractional catabolic rate of very low density lipoprotein (VLDL), increased hepatocyte LDL turnover, and the maintenance of statin therapy. CONCLUSION: Lipopheresis is a safe and effective method for the control of LDL in nephrotic syndrome. Early clamping of total cholesterol in the normal range resulted in a prolonged and significant reduction of LDL compared with controls.

Influenza vaccination coverage in Canterbury rest homes.

AIMS: First, to investigate the effect on Canterbury rest home residents of national policy making influenza vaccination free for those aged 65 years and over. Second, to assess rest home staff influenza vaccination coverage. METHODS: A comparison of influenza vaccination coverage in Canterbury rest home residents during 1996 and 1997 was conducted. Subgroups of rest homes were formed in 1997 to minimise the bias introduced through conducting a coverage survey in 1996. Staff vaccination coverage was also assessed in 1997. RESULTS: Influenza vaccination coverage of Canterbury rest home residents was 74% in 1996 and 76% in 1997. Staff vaccination coverage was 21% in 1997. Significantly more staff were vaccinated in rest homes that offered free influenza vaccination to their staff. CONCLUSIONS: The free influenza vaccination policy had no measurable impact on Canterbury rest home residents' vaccination coverage. This may be due to a ceiling effect of previously high coverage. Coverage was low amongst rest home staff. Providing the vaccination free of charge might improve staff coverage.

Hepatitis C seroprevalence amongst injecting drug users attending a methadone programme.

AIM: To study the seroprevalence of the hepatitis C virus (HCV) amongst a population of injecting drug users and to examine the relationship between potential risk factors and HCV infection. METHODS: A sample of 116 clients attending a methadone treatment clinic in Christchurch took part in this study. Blood samples were analysed to detect antibodies to HCV and to test for HCV RNA: Serum transaminases were also measured. In addition a short questionnaire about sexual behaviour and drug use practices was self completed by all participants in strictest confidence. RESULTS: Slightly more than half the sample were female (54.3%) and most were of European origin (90.6%). The average age was 31.56 years and the average length of time they had been injecting drugs was 9.54 years. HCV antibodies were detected in 84.2% of the sample and HCV RNA in 66.1% of the sample including 75.9% amongst those who were anti-HCV positive and 16.6% amongst those who were anti-HCV negative. AST and ALT levels were elevated amongst 16.8% and 46.2% of the sample respectively. The likelihood of being anti-HCV positive increased with years of drug use and with increased sharing of injecting equipment. No significant relationship between HCV status and sexual practices was evident. Data on the history of drug using practices indicated that sharing of injecting equipment had become less common over time and access to new equipment through reliable sources had become more common with time. CONCLUSIONS: HCV is widespread amongst this population of injecting drug users suggesting the possibility of a major clinical and social problem. Despite evidence of a reduction in the sharing of injecting equipment, HCV transmission is still occurring indicating the potential for other parenterally transmitted diseases, such as HIV, to become established amongst injecting drug users. Those at high risk of HCV should be discouraged from donating blood because of the possibility of HCV seronegative infectivity.

Cumulative incidence of hepatitis C seroconversion in a cohort of seronegative injecting drug users.

AIM: To measure the cumulative incidence of hepatitis C virus seroconversion over a two year period in a group of seronegative injecting drug users. METHODS: The study involved follow-up, in 1996, of a cohort (n=85) of injecting drug users identified as hepatitis C virus seronegative in 1994. Participants were interviewed about risk factors for hepatitis C. A blood sample was also taken for anti-hepatitis C virus antibody and hepatitis C virus RNA testing. RESULTS: Forty-four participants were interviewed and 39 gave blood for testing. Most (80%) were aged 29 years or under and two thirds (n=26) were male. Around half reported borrowing (49%) or lending (57%) needles and syringes since 1994 and both of these behaviours were associated with seroconversion. The majority (88%) also reported sharing other injecting equipment. Nine were anti-hepatitis C virus positive giving a seroconversion rate over two years of 23% (13 per 100 person years). Four out of the nine seropositive specimens tested were also hepatitis C virus RNA positive. CONCLUSIONS: This study demonstrates a high rate of recent hepatitis C virus seroconversion amongst a group of New Zealand injecting drug users. Transmission of hepatitis C virus appears to be unabated by current control measures. These findings confirm the need to develop more effective policy and practices to prevent further spread, not just of hepatitis C, but of other blood-borne viruses in injecting drug user populations.

Interactions between platelet-surface glycoproteins. Identification of glycoproteins capable of binding to platelet surfaces.

1. Platelets have been isolated from plasma and their surface glycoconjugates radioactively-labelled using galactose oxidase and NaB3H4. 2. Conditions have been defined for optimal labelling of glycoproteins and a membrane fraction enriched in plasma membrane has been prepared and characterized by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 3. Desialylated glycoproteins that act as receptors to peanut agglutinin and lentil lectin have been purified from a detergent extract of plasma membrane. 4. Two glycosylated polypeptides that are able to bind to the surfaces of platelets have been identified and some characteristics of the binding have been investigated.

Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus.

The effect of Toxoplasma gondii on neophobic behaviour (the avoidance of novel stimuli) was assessed in four groups of wild rats with naturally occurring Toxoplasma infection. Two groups were placed in individual cages and tested in a series of experiments which examined the effect of Toxoplasma on the rat's reaction to 3 food-related novel stimuli (odour, food-container, food). A trappability study was performed on the other two groups to test whether Toxoplasma had an effect on probability of capture. The results show that low neophobia was significantly associated with positive Toxoplasma titres in 3 out of 4 groups. We suggest that differences between infected and uninfected wild rats arise from pathological changes caused by Toxoplasma cysts in the brains of infected rats. Such behavioural changes may be selectively advantageous for the parasite as they may render Toxoplasma-infected rats more susceptible to predation by domestic cats (the definitive host of Toxoplasma) and, as a side-effect, more susceptible to trapping and poisoning during post control programmes.

Glomerular atherosclerosis.

This paper suggests a two-hit model for lipoprotein-mediated progressive renal disease, in which postsecretory modification of low-density lipoprotein may favour the transformation of mesangial cells, monocytes and macrophages to glomerular foam cells. Proteinuria and lipiduria would mediate tubulointerstitial damage. Based on this, careful treatment with lipid-lowering agents, lipopheresis and antioxidants may ameliorate the progression of glomerular and tubulointerstitial pathology.

Cerebral venous sinus thrombosis in minimal change nephrotic syndrome.

Three cases of cerebral venous sinus thrombosis (CVST) occurring in patients with minimal change nephrotic syndrome (MCNS) are described. Personality change in two of these patients was wrongly attributed to steroid therapy prior to the discovery of the CVST. In addition, von Willebrand factor (vWF) levels were grossly elevated in one patient, during a previous relapse of MCNS, prior to developing CVST, and may be a useful prognostic tool in predicting thrombotic events in nephrotic patients.

Do glomerular atherosclerosis and lipid-mediated tubulo-interstitial disease cause progressive renal failure in man?

The nephrotic syndrome presents the kidney with a new environment in which blood vessels, glomerular structures and tubules are exposed over substantial periods of time to lipoproteins. LDL has charge affinity with glomerular basement membrane glycosaminoglycans, so potentially increases or maintains albumin loss. This in turn stimulates LDL synthesis. HDL is small enough to be passed by the glomerular filter in substantial amounts and has been found to stimulate endothelin-1 production by human proximal tubular cells in culture. LDL also inhibits nitric oxide vasodilatory responses, an action which when added to that of endothelin-1 may result in decreased renal tissue oxygenation. Taken together, these aspects of the nephrotic syndrome broaden conventional definitions of atherosclerosis and offer a number of targets for therapy in progressive renal disease.