Joseph Eliahoo

Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV.

Objective:An epidemic of acute hepatitis C virus (HCV) infection among HIV-positive men who have sex with men is occurring in urban centers in Western Europe and the United States. Early diagnosis and treatment of HCV results in improved sustained virological response rates. This study compared the sensitivity of reverse transcriptase PCR (RT–PCR) versus antibody screening for the diagnosis of early HCV infection in HIV-positive patients and estimated the length of time from HCV infection to the development of anti-HCV antibodies. Design:Patients from the St Marys Acute Hepatitis C Cohort (SMACC) were recruited retrospectively and prospectively between 2004 and 2008. Methods:Archived plasma samples, obtained at 1–3 monthly intervals for routine monitoring of HIV viral load were assayed retrospectively for HCV in order to assess the sensitivity of RT–PCR and enzyme-linked immunosorbent assay (ELISA). Results:Forty-three HIV-positive patients with early HCV infection were identified. The median CD4 cell count was 570 cells/μl. The median alanine transaminase at the time of the first positive HCV PCR was 65 IU/ml. At this time, 75% of patients had a negative HCV antibody test. Three months later, 37% of patients still had a negative result. After 9 months, 10% of patients had a negative test and 5% remained negative after 1 year. Conclusion/discussion:Delayed seroconversion in HIV-positive individuals with acute HCV may result in delayed diagnosis and treatment. Where there is a clinical suspicion of recent HCV infection, for example, elevated alanine transaminase levels, HIV-infected patients should be screened for HCV RNA by RT–PCR.

Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men

Objective An epidemic of acute hepatitis C virus (HCV) infection in HIV-positive men-who-have-sex-with-men (MSM) is emerging in Europe, Australia and the USA. The aim of this study was to characterise the natural history of primary HCV in this setting and to assess host and viral factors which predict spontaneous clearance. Methods This prospective longitudinal cohort study was carried out in 112 HIV-positive patients who were followed in a single centre (the St Marys Acute HCV Cohort). Plasma and peripheral blood mononuclear cells (PBMCs) were obtained at monthly intervals for 3 months and at 3-monthly intervals thereafter for a median of 45 months (IQR=29–69 months). The primary end point was spontaneous clearance of HCV. Cox regression was used to assess the impact of clinical and virological variables on outcome, including liver function, CD4 count, rate of HCV RNA decline, T cell response and clonal sequence evolution within the HCV E2 envelope gene. Results 15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. The latter group included a significant proportion of ‘fluctuating’ progressors (37.5%), in whom a fall followed by a rise (>1 log10) in viraemia was observed. This was associated with superinfection with new HCV strains and partially effective T cell responses. Spontaneous clearance was strongly associated with a 2.2 log10 viral load drop within 100 days of infection (HR=1.78; p<0.0001), elevated bilirubin (≥40 μmol/l; HR=5.04; p=0.006), elevated alanine aminotransferase (ALT; ≥1000 IU/ml; HR=2.62; p=0.048) and baseline CD4 count ≥650×106/l (HR=2.66; p=0.045), and only occurred in patients with genotype 1 infection. Evolution to spontaneous clearance occurred in patients with low viral diversity in the presence of an early multispecific T cell response. Conclusions Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.

Socioeconomic and ethnic group differences in self reported health status and use of health services by children and young people in England: cross sectional study

Abstract Objectives: To examine whether self reported health status and use of health services varies in children of different social class and ethnic group. Design: Cross sectional study from the 1999 health survey for England. Subjects: 6648 children and young adults aged 2-20 years. Setting: Private households in England. Main outcome measures: Proportion of children (or their parents) reporting episodes of acute illness in the preceding fortnight and prevalence of self reported longstanding illness. Proportion reporting specific illnesses. Proportion reporting that they had consulted a general practitioner in the preceding fortnight, attended hospital outpatient departments in the three preceding months, or been admitted to hospital in the preceding year. Results: Large socioeconomic differences were observed between ethnic subgroups; a higher proportion of Afro-Caribbean, Indian, Pakistani, and Bangladeshi children belonged to lower social classes than the general population. The proportion of children and young adults reporting acute illnesses in the preceding two weeks was lower in Bangladeshi and Chinese subgroups (odds ratio 0.41, 95% confidence interval 0.27 to 0.61 and 0.46, 0.28 to 0.77, respectively) than in the general population. Longstanding illnesses was less common in Bangladeshi and Pakistani children (0.52, 0.40 to 0.67 and 0.57, 0.46 to 0.70) than in the general population. Irish and Afro-Caribbean children reported the highest prevalence of asthma (19.5% and 17.7%) and Bangladeshi children the lowest (8.2%). A higher proportion of Afro-Caribbean children reported major injuiries than the general population (11.0% v 10.0%), and children from all Asian subgroups reported fewer major and minor injuries than the general population. Indian and Pakistani children were more likely to have consulted their general practitioner in the preceding fortnight than the general population (1.86, 1.35 to 2.57 and 1.51, 1.13 to 2.01, respectively). Indian, Pakistani, Bangladeshi, and Chinese children were less likely to have attended outpatient departments in the preceding three months. No significant differences were found between ethnic groups in the admission of inpatients to hospitals. Acute and chronic illness were the best predictors of childrens use of health services. Social classes did not differ in self reported prevalence of treated infections, major injuries, or minor injuries, and no socioeconomic differences were seen in the use of primary and secondary healthcare services. Conclusions: Childrens use of health services reflected health status rather than ethnic group or socioeconomic status, implying that equity of access has been partly achieved, although reasons why children from ethnic minority groups are able to access primary care but receive less secondary care need to be investigated.

Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID)

OBJECTIVE(S) To assess the effects and cost-effectiveness of haloperidol, risperidone and placebo on aggressive challenging behaviour in adults with intellectual disability. DESIGN A double-blind randomised controlled trial of two drugs and placebo administered in flexible dosage, with full, independent assessments of aggressive and aberrant behaviour, global improvement, carer burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks, and comparison of total care costs in the 6 months before and after randomisation. At 12 weeks, patients were given the option of leaving the trial or continuing until 26 weeks. Assessments of observed aggression were also carried out with key workers at weekly intervals throughout the trial. SETTING Patients were recruited from all those being treated by intellectual disability services in eight sites in England, one in Wales and one in Queensland, Australia. PARTICIPANTS Patients from all severity levels of intellectual disability; recruitment was extended to include those who may have been treated with neuroleptic drugs in the past. EXCLUSION CRITERIA treatment with depot neuroleptics/another form of injected neuroleptic medication within the last 3 months; continuous oral neuroleptic medication within the last week; those under a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000. INTERVENTIONS Randomisation to treatment with haloperidol (a typical neuroleptic drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5-2.0 mg daily. MAIN OUTCOME MEASURES Primary: reduction in aggressive episodes between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary: Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life Questionnaire; Udvalg for Kliniske Undersøgelser scale; Clinical Global Impressions scale. Economic costs recorded using a modified version of Client Service Receipt Inventory for 6 months before and after randomisation. RESULTS There were considerable difficulties in recruitment because of ethical and consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising to 2.94 mg for haloperidol. Aggression declined dramatically with all three treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus 57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence of inferior response in comparison to patients receiving neuroleptic drugs. An additional study found that clinicians who had not participated in clinical trials before were less likely to recruit. Mean total cost of accommodation, services, informal care and treatment over the 6 months of the trial was 16,336 pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for risperidone. CONCLUSIONS There were no significant important benefits conferred by treatment with risperidone or haloperidol, and treatment with these drugs was not cost-effective. While neuroleptic drugs may be of value in the treatment of aggressive behaviour in some patients with intellectual disability, the underlying pathology needs to be evaluated before these are given. The specific diagnostic indications for such treatment require further investigation. Prescription of low doses of neuroleptic drugs in intellectual disability on the grounds of greater responsiveness and greater liability to adverse effects also needs to be re-examined.

Incidental findings in healthy control research subjects using whole-body MRI

AIM Magnetic resonance imaging (MRI) is a powerful clinical tool used increasingly in the research setting. We aimed to assess the prevalence of incidental findings in a sequential cohort of healthy volunteers undergoing whole-body MRI as part of a normal control database for imaging research studies. MATERIALS AND METHODS 148 healthy volunteers (median age 36 years, range 21-69 years; 63.5% males, 36.5% females) were enrolled into a prospective observational study at a single hospital-based MRI research unit in London, UK. Individuals with a clinical illness, treated or under investigation were excluded from the study. RESULTS 43 (29.1%) scans were abnormal with a total of 49 abnormalities detected. Of these, 20 abnormalities in 19 patients (12.8%) were of clinical significance. The prevalence of incidental findings increased significantly with both increasing age and body mass index (BMI). Obese subjects had a fivefold greater risk of having an incidental abnormality on MRI (OR 5.4, CI 2.1-14.0). CONCLUSIONS This study showed that more than one quarter of healthy volunteers have MR-demonstrable abnormalities. There was an increased risk of such findings in obese patients. This has ethical and financial implications for future imaging research, particularly with respect to informed consent and follow-up of those with abnormalities detected during the course of imaging studies.

Assessment of cardiac valve dysfunction in patients receiving cabergoline treatment for hyperprolactinaemia

Objective  Cabergoline is a highly effective medical treatment for patients with hyperprolactinaemia. There is an increased risk of valvular heart disease in patients receiving cabergoline for Parkinson’s disease. This study examined whether cabergoline treatment of hyperprolactinaemia is associated with a greater prevalence of valvulopathy.

Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies

Summary:Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants. We undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments. Testicular function was assessed immediately prior to transplantation and at four time points post-transplant to compare hormonal levels before and after the procedure. Two other groups treated with BEAM- and TBI-related regimes were also included in the study group for comparative purposes. GC function was assessed by measuring basal serum follicle stimulating hormone (FSH). LC function was assessed by measuring basal luteinising hormone (LH) and testosterone (T) levels. LC reserve was assessed by measuring the T/LH ratio. As a group, patients who received a non myeloablative transplant sustained severe damage to the GC compartment, as evident from a substantial elevation in the FSH level post-transplant (12 IU/l vs 18.4 IU/l, P<0.001). Similar to the GC injury, patients as a group sustained significant damage to the LC compartment following the transplant (5.4 IU/l vs 9.6 IU/l, P<0.001). In general, patients had reduced LC reserve post-BMT, as evident from a diminished T/LH ratio (2.6 pretransplant vs 1.6 post-transplant P=0.05). Patients who received a nonmyeloablative transplant had a similar effect on the GC and LC compartments compared to those who had a BEAM autograft. On the other hand, patients who received a TBI-based transplant sustained more damage to their GC and LC compartments compared to those who received a nonmyeloblative transplant; however, this was not statistically significant (P=0.09). Our data suggest that this type of regimen is potentially gonadotoxic and consideration should be given to fertility counselling and testosterone replacement therapy post-transplant.

Ethnic inequalities in the treatment and outcome of diabetes in three English Primary Care Trusts

BackgroundAlthough the prevalence of diabetes is three to five times higher in UK South Asians than Whites, there are no reports of the extent of ethnicity recording in routine general practice, and few population-based published studies of the association between ethnicity and quality of diabetes care and outcomes. We aimed to determine the association between ethnicity and healthcare factors in an English population.MethodsData was obtained in 2002 on all 21,343 diabetic patients registered in 99% of all computerised general practitioner (GP) practices in three NW London Primary Care Trusts (PCTs), covering a total registered population of 720,000. Previously practices had been provided with training, data entry support and feedback. Treatment and outcome measures included drug treatment and blood pressure (BP), total cholesterol and haemoglobin A1c (HbA1c) levels.ResultsSeventy per cent of diabetic patients had a valid ethnicity code. In the relatively older White population, we expected a smaller proportion with a normal BP, but BP differences between the groups were small and suggested poorer control in non-White ethnic groups. There were also significant differences between ethnic groups in the proportions of insulin-treated patients, with a smaller proportion of South Asians – 4.7% compared to 7.1% of Whites – receiving insulin, although the proportion with a satisfactory HbA1c was smaller- 25.6% compared to 37.9%.ConclusionRecording the ethnicity of existing primary care patients is feasible, beginning with patients with established diseases such as diabetes. We have shown that the lower proportion of South Asian patients with good diabetes control, and who are receiving insulin, is at least partly due to poorer standards of care in South Asians, although biological and cultural factors could also contribute. This study highlights the need to capture ethnicity data in clinical trials and in routine care, to specifically investigate the reasons for these ethnic differences, and to consider more intensive management of diabetes and education about the disease in South Asian patients.

Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification.

Aim:  The increasing prevalence of fatty liver disease requires routine assessment methods. Proton magnetic resonance spectroscopy (1H MRS) is increasingly used for steatosis measurement, but due to cost, is unlikely to become a widely‐used screening tool. Ultrasound is cheaper and more widely available, although subject to observer variability. Our aim was to determine the sensitivity and specificity of ultrasound against 1H MRS, using MRS as a gold standard, for the detection and quantification of hepatic fat content.

Patterns of Leydig cell insufficiency in adult males following bone marrow transplantation for haematological malignancies

Gonadal and sexual function are key to quality of life following bone marrow transplantation (BMT), but no large studies have been published on Leydig cell (LC) function in adults. LC insufficiency (LCI) can cause premature andropause with its consequences including sexual morbidity from diminished libido and erectile dysfunction (ED). In addition, LCI can result in generalised fatigue and even osteopenia. We reviewed gonadal function pre-transplant (immediately prior to BMT) and at 3–18 months post BMT in 117 patients who underwent BMT for a variety of haematological malignancies. The patients presented with variable degrees of symptoms of LCI, such as fatigue, diminished sex drive and libido or ED. The results suggest that the patients sustained severe gonadal damage to both their germ cells (GC) as well as the LC compartment (P < 0.001). We characterised two distinct functional subsets of LC insufficiency: Type I: compensated type with high LH and normal T levels and low T/LH ratio: (n = 102); and type II: uncompensated type (premature andropause) with high LH and low testosterone levels with low T/LH ratio (n = 15). Although type II patients had more severe LC damage than type I, patients in both groups were symptomatic. We recommend that symptomatic patients in both groups may benefit from a therapeutic trial with testosterone replacement treatment (TRT) for 3–6 months. Bone Marrow Transplantation (2001) 28, 497–502.