Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Management of hepatitis C infection among patients with renal failure.

Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-150 million infected people worldwide and 350,000 to 500,000 HCV-related deaths each year. Chronic kidney disease (CKD) is also a highly prevalent public health issue as the escalating numbers of patients worldwide are developing type 2 diabetes mellitus and hypertension due to high fat diets and a growing obesity epidemic. The high incidence and prevalence of HCV infection leads to substantial morbidity and mortality among renal dialysis patients. Recommendations are to screen for HCV infection among all patients with renal failure especially prior to initiation of hemodialysis and renal transplant evaluation. HCV-antibody enzyme immunoassay (EIA) followed by confirmation with HCV RNA nucleic acid test (NAT) is recommended for low prevalence regions, but in dialysis centers with a high prevalence of HCV, initial testing with NAT is recommended due to higher false positive EIA rates. Liver biopsy is used to assess of liver disease severity. Transjugular liver biopsy, as an effective and safe technique in patients with ESRD can be considered instead of percutaneous approach. Non-invasive approaches to staging fibrosis, including liver stiffness measurement by transient elastography and panels of serum fibrosis biomarkers, are also widely used. Although difficult to manage, combined pegylated- interferon (PEG IFN) and ribavirin therapy was the only treatment modality available for HCV-positive patients until the recently introduced new direct-acting antiviral agents. However, except boceprevir, there are no currently available data to suggest that these new anti-viral drugs are safe and effective among end-stage renal failure patients. IFN-containing regimens were also associated with high rates of renal graft loss in post-renal transplant patients. Therefore, management of HCV infection in renal failure patients is unique and should be tailored individually with calculated risk/benefit ratio. New studies are immediately warranted to determine the safety profile and efficacy of newer anti-HCV drugs not only in patients with end-stage renal failure prior to kidney transplantation but also among kidney transplant recipients.

Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders.

Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid death or progression to Korsakoff syndrome with largely irreversible brain damage. Wernicke Korsakoff syndrome refers to a condition where features of Wernicke encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted guidelines with regard to its optimal dose, mode of administration, frequency of administration or duration of treatment. Currently, different dose recommendations are being made. We present recommendations for the assessment and treatment of Wernicke encephalopathy based on literature review and our clinical experience.

Clinical experience with baclofen in the management of alcohol-dependent patients with psychiatric comorbidity: a selected case series.

AIMS: To illustrate the potential indications for, and adverse effects of, baclofen pharmacotherapy for alcohol dependence in patients with co-existing psychiatric illness. METHODS: Audit of the files of alcohol-dependent patients treated for comorbid non-psychotic psychiatric illness in a specialist detoxification unit with integrated outpatient treatment. Files were selected of patients who had been offered treatment with baclofen because other alcohol pharmacotherapies had previously been unsuccessful in preventing relapse or were contraindicated. RESULTS: Of the 21 selected patients, 13 attended for outpatient treatment, with follow-up periods ranging from 4 days to 27 months, and the outcomes could be rated. Prescribed baclofen doses ranged from 30 to 275 mg daily. Common side effects at lower doses included tiredness and sedation; one patient on 120 mg/day developed reversible severe back pain, and a patient taking up to 275 mg/day developed somnolence, dizziness and incontinence. Seven patients maintained significant periods of abstinence, and one patient reduced daily consumption to non-problematic levels. Two patients consumed an overdose of other central nervous system (CNS) depressants, while taking baclofen in the first week of treatment, were briefly unwell, were given emergency monitoring, but made a full recovery. CONCLUSION: While more than half the patients reported significant reduction in alcohol use, it is not possible to draw definite conclusions about the effectiveness of baclofen, given that it was combined with other psychiatric and alcohol treatments, and because there was no control or comparison group. We recommend caution when offering baclofen to patients with a history of recurrent overdosing or a history of other substance misuse. When prescribing in conjunction with other medications with CNS depressant action, close monitoring is recommended at initiation and during dose escalation.

Hepatitis C in injecting drug-using women during and after pregnancy.

BACKGROUND: A high proportion of female injecting drug users (IDU) have evidence of hepatitis C virus (HCV) infection. We undertook a prospective study of patients attending a clinic for pregnant IDU to determine the impact of pregnancy on the course of HCV infection and whether pregnancy is affected by HCV infection. METHODS: One hundred and thirty-one IDU were recruited and followed up with liver function tests, HCV serology and HCV-RNA tests. RESULTS: Of 131 patients, 125 had HCV antibodies (anti-HCV positive) at delivery, and of these 62% were HCV-RNA positive. The anti-HCV-negative women were younger and had a shorter duration of drug use than the anti-HCV-positive women. There were no differences between viraemic and non-viraemic women with respect to age, ethnicity, duration of injecting drug use, methadone maintenance dose, hepatitis B exposure or reported high-risk behaviour. Alanine aminotransferase (ALT) levels were higher and the proportion with ALT > 55 IU/L higher in viraemic women. Viraemia persisted in all 55 women who were viraemic at term. Eleven had an ALT flare post-partum that was unrelated to viral load and was clinically unsuspected. Four had concurrent elevated gamma-glutamyltranspeptidase and were considered to be drinking alcohol at hazardous levels. Four of 23 women who were HCV-RNA negative at term became positive during follow up. CONCLUSIONS: Pregnancy does not adversely affect the course of hepatitis C. A modest rebound in ALT levels, but not HCV-RNA, occurs after delivery in some viraemic women. This supports the theory that immune mechanisms rather than direct viral cytopathology are involved in hepatocyte injury during HCV infection. Hepatitis C infection did not influence pregnancy complications and outcomes.

Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission.

The risk of perinatal transmission of hepatitis C virus (HCV) from a cohort of 95 human immunodeficiency virus (HIV)-negative intravenous drug users (IVDU) is described, 89 of whom were positive for antibodies to HCV (anti-HCV). Infection, defined as the presence of HCV RNA in a serum sample collected from an infant at any time during follow-up, was detected in six of 63 (9.5%) infants born to HCV antibody-positive viraemic mothers. No mother who was HCV RNA negative at delivery transmitted HCV to her infant. Hepatitis C virus antibodies became undetectable in uninfected infants by 15 months, but persisted in all HCV-infected infants throughout follow-up. An abnormal alanine aminotransferase (ALT) level was observed on at least one occasion in all HCV-infected infants and in six occasions in uninfected infants. Two of the six HCV-infected infants became HCV RNA negative during follow-up by 27 and 29 months. Both of these infants had a large ALT elevation (mean peak ALT 398U l-1) at around 12 months of age. Analysis of a range of potential risk factors revealed that maternal HCV RNA load was important in predicting transmission, but suggested that other factors play a role in perinatal transmission from mother to child. No difference was found between mothers who transmitted HCV to their infants and those who did not for HCV genotype, duration of drug use, duration of methadone use, methadone dose, history of alcohol abuse, past hepatitis B virus (HBV) infection, mode of delivery, maternal and gestational age, birth weight and incidence of breast-feeding. Mothers who transmitted HCV to their infants had a longer duration between membrane rupture and delivery than the mothers who did not transmit (P = 0.03). HCV RNA was not detected in breast milk and colostrum samples from 38 viraemic mothers, including two who transmitted HCV to their infant.

Epidemiology of alcoholic liver disease.

Although mortality from alcoholic liver disease has declined in some Western countries in recent years, elsewhere it is increasing and overall it remains a major health problem. Deaths are predominantly seen in patients with alcoholic hepatitis or cirrhosis, and when they occur in patients with fatty liver are usually unrelated to liver disease. Progression to cirrhosis is correlated with the severity of fatty liver and particularly with the presence of alcoholic hepatitis. Mortality from cirrhosis is strongly correlated with per capita alcohol consumption. The decline in cirrhosis mortality rates seen recently is related in part to decreases in per capita consumption, but probably also to the growth of self-help organizations which facilitate abstinence from alcohol. Recent studies suggest there is not an invariable dose-response relationship between alcohol intake and the severity of liver disease and that alcohol has a permissive effect which allows other aetiological factors to operate. Factors that influence susceptibility to alcoholic liver disease include gender (women develop alcoholic cirrhosis more readily than men), concomitant hepatitis C infection and possibly hepatitis B infection. It is uncertain whether HLA status or immune mechanisms are implicated. The systematic use of screening tests for hazardous consumption combined with early intervention therapies offers a good prospect of reducing morbidity and mortality from alcoholic liver disease.