Targeted colonic release formulations of mesalazine - A clinical pharmaco-scintigraphic proof-of-concept study in healthy subjects and patients with mildly active ulcerative colitis.

Colonic targeting of orally applied therapeutic drugs remains a challenge. Tablet coatings relying on gastrointestinal pH and colonic bacterial enzymes as triggers in association with an inner alkaline layer are expected to improve targeting efficiency. Mesalazine release from three differently coated tablets labelled with 1 MBq 153Sm was characterised in a single centre, open-label, parallel group study in nineteen healthy subjects and seven patients with mildly active ulcerative colitis. Two semi-organic and one aqueous-based outer coating with different ratios of enteric polymer and resistant starch were tested. All coatings showed comparable release lagtimes in biorelevant dissolution media and were not affected by neutron-activation of the samarium tracer. Mesalazine pharmacokinetics and gamma scintigraphy were used to characterise drug release, anatomical site of tablet disintegration and gastrointestinal transit. Initial tablet disintegration occurred at the ileo-caecal junction or beyond in 92 % of the subjects. Time to initial tablet disintegration was inversely correlated with maximal plasma concentrations and systemic mesalazine exposure. Although high inter-subject variability precluded detection of differences between solvent types and different enteric polymer to polysaccharide ratios, the dual pH and enzymatic triggered release system in combination with an inner alkaline layer promoted mesalazine release at the target site with high accuracy.

Randomised non-inferiority trial: 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis.

BACKGROUND: High concentration mesalazine formulations are more convenient than conventional low concentration formulations for the treatment of ulcerative colitis (UC). AIM: To compare the efficacy and safety of 1600 mg and 400 mg tablet mesalazine formulations. METHODS: Patients with mild-to-moderate active UC (Mayo Clinic Score >5; N=817) were randomised to 3.2 g of oral mesalazine, administered as two 1600 mg tablets once, or four 400 mg tablets twice daily. We hypothesised that treatment with the 1600 mg tablet was non-inferior (within a 10% margin) to the 400 mg tablet for induction of clinical and endoscopic remission at week 8. Open-label treatment with the 1600 mg tablet continued for 26-30 weeks based on induction response. Predictors of treatment response were also explored. RESULTS: At week 8, remission occurred in 22.4% and 24.6% of patients receiving the 1600 mg and 400 mg tablets, respectively (absolute difference -2.2%, 95% CI: -8.1% to 3.8%, non-inferiority P=.005). Endoscopic and histopathologic disease activity, leucocyte concentration and age were significantly associated with clinical remission (P=.022, .042, .014 and .023, respectively). At week 38, 43.9% (296/675) of patients who continued treatment with the 1600 mg formulation were in remission, including 70.3% (142/202) of patients who received a reduced dose of mesalazine (1.6 g/d). The overall incidence of serious adverse events was low. CONCLUSIONS: Induction therapy with 3.2 mg mesalazine using two 1600 mg tablets once-daily was statistically and clinically non-inferior to a twice-daily regimen using four 400 mg tablets (NCT01903252).

Impact of migration on illness experience and help-seeking strategies of patients from Turkey and Bosnia in primary health care in Basel.

Migration, particularly among refugees and asylum seekers, poses many challenges to the health system of host countries. This study examined the impact of migration history on illness experience, its meaning and help-seeking strategies of migrant patients from Bosnia and Turkey with a range of common health problems in general practice in Basel, Switzerland. The Explanatory Model Interview Catalogue, a data collection instrument for cross-cultural research which combines epidemiological and ethnographic research approaches, was used in semi-structured one-to-one patient interviews. Bosnian patients (n=36) who had more traumatic migration experiences than Turkish/Kurdish (n=62) or Swiss internal migrants (n=48) reported a larger number of health problems than the other groups. Psychological distress was reported most frequently by all three groups in response to focussed queries, but spontaneously reported symptoms indicated the prominence of somatic, rather than psychological or psychosocial, problems. Among Bosnians, 78% identified traumatic migration experiences as a cause of their illness, in addition to a range of psychological and biomedical causes. Help-seeking strategies for the current illness included a wide range of treatments, such as basic medical care at private surgeries, outpatients department in hospitals as well as alternative medical treatments among all groups. Findings provide a useful guide to clinicians who work with migrants and should inform policy in medical care, information and health promotion for migrants in Switzerland as well as further education of health professionals on issues concerning migrants health.

Is social capital a useful conceptual tool for exploring community level influences on HIV infection? An exploratory case study from South Africa.

This paper reports on an exploratory study investigating links between sexual health and social capital in a South African mining community. In this study, social capital is defined in terms of people's membership of voluntary community organizations (e.g. church, residents' associations, youth groups). Using biomedical and social survey data from a stratified random sample of 1,211 Carletonville residents, we tested the hypothesis that organizational members were less likely to have HIV. Multivariate analysis of variance sought to identify significant associations between nine organizational memberships and HIV infection, as well as three risk factors for infection (casual partners, condom use with casual partners and alcohol consumption). Analysis yielded a range of significant results, but findings varied across age and gender, and were not all in the hypothesized direction. For example, young men and young women who belonged to sports clubs were less likely to be HIV-positive, and young women who belonged to sports clubs were more likely to use condoms with casual partners than non-members. Amongst members of stokvels (voluntary savings clubs accompanied by social festivities), however, young men were more likely to be HIV-positive, women of all ages were more likely to have a casual partner, and both young men and young women were more likely to drink alcohol than non-members. While our exploratory study has produced sufficient evidence to justify the need for further research in this area, it also highlights that the interface between HIV infection and social capital is a complex area that defies easy generalization.

The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in Bangladesh.

AIM: To investigate the effect of weekly iron supplementation on anaemia and iron deficiency among adult, female tea pluckers. METHOD: A randomized double-blind intervention trial was conducted in a tea estate in Bangladesh where a total of 280 women received either weekly iron supplementation (200 mg ferrous fumarate and 200 mg folic acid) for 24 weeks or a matching placebo. Capillary blood samples were drawn at baseline and post-trial to determine haemoglobin, haematocrit and ferritin concentration. Mean corpuscular haemoglobin concentration (MCHC) was calculated using the haemoglobin and haematocrit values. RESULTS: The mean haemoglobin concentration in the supplemented group increased by 5.52 g L-1 over the study period, on average, while ferritin values decreased by 0.33 microgram L-1. The control group showed a decrease in both mean haemoglobin (-0.24 g L-1) and ferritin (-5.32 micrograms L-1). Those individuals in the supplemented group with the lowest pretrial haemoglobin and ferritin values experienced the greatest improvements post-trial, whereas nonanaemic individuals showed a decrease in both haemoglobin and ferritin concentrations. A total of 62.2% of women in the supplemented group reported feeling better and more energetic compared to 51.1% in the placebo group; 14.4% of the supplemented group and 22.7% of the control group complained about side-effects. CONCLUSION: Weekly iron supplementation was logistically simpler and cheaper than daily supplementation but would have to be continued on a longer term basis in order to combat both anaemia and iron deficiency.

Intestinal helminth infections, anaemia and labour productivity of female tea pluckers in Bangladesh.

We conducted a randomized clinical intervention trial over 24 weeks on a tea estate in north-east Bangladesh to investigate the effect of iron supplementation and anthelmintic treatment on the labour productivity of adult female tea pluckers. A total of 553 full-time tea pluckers, not pregnant and not breastfeeding, were randomly assigned to one of the four intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half-way through the trial (week 12), group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos. No significant difference in labour productivity was found between the four intervention groups over the trial period. However, there was a negative association for all three worms (Ascaris lumbricoides, Trichuris trichiura and hookworms) between the intensity of helminth infections (eggs/g faeces) and all measures of labour productivity. Lower haemoglobin values and anaemia (< 120 g/l Hb) were both associated with lower labour productivity and more days sick and absent. Taller women with greater arm circumference were able to pluck more green leaves, earn higher wages and were absent less often.

The effect of anthelmintic treatment on helminth infection and anaemia.

A 24-week randomized double blind intervention trial was conducted on adult female tea pluckers from an estate in Bangladesh to investigate the impact of iron supplementation and anthelmintic treatment on changes in ferritin and haemoglobin levels as well as on prevalence and intensity of helminth infections. A total of 553 women were randomly assigned to 1 of 4 intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half way through the trial, group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos for both iron supplementation and anthelmintic treatment. Prevalence and intensity of helminth infections (egg counts/g stool) of Ascaris lumbricoides, Trichuris trichiura and hookworms significantly fell in the 2 groups receiving anthelmintic treatment and there were some reductions in the 2 groups not receiving anthelminthic treatment. Haemoglobin and haematocrit concentrations increased significantly in the iron supplemented groups with smaller increases in the anthelmintic only group. All women showed a decrease in serum ferritin levels post-trial with greater losses in the 2 dewormed groups. Significant negative associations were found between hookworm egg counts and ferritin levels and Trichuris trichiura egg counts and haemoglobin concentration.

Polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with AIDS and AIDS-related complex.

We tried to assess the long-term safety and potential efficacy of passive immunization in AIDS-related-complex (ARC) and AIDS patients. We also wanted to establish whether hyperimmune plasma from healthy human immunodeficiency virus 1 (HIV-1)-infected individuals clears the cell-free virus from circulation. Using the polymerase chain reaction (PCR), we were able to provide conclusive evidence that hyperimmune plasma is effective and maintains long-term neutralization of viremia. Using the cell test, we found that in most patients the total antibody level was maintained; in one of the ARC patients, it actually increased 8-fold and has remained at that level for nearly 2 years. The CD4+ cell count decreased in the AIDS patients but was stable in the ARC patient. Clinically, there was an initial improvement in all patients, but five of six of the advanced/terminal AIDS patients had died by month 17. Our studies suggest that passive immunization may be safe in ARC and AIDS patients. It reduces HIV-1 viremia to levels undetectable even by PCR. To advanced/terminal patients, the benefit is of limited duration, while to ARC patients it may be long-term. Therefore, passive immunization should start early in the disease.

Effects of passive immunization in patients with the acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome.

Infection with the human immunodeficiency virus type 1 (HIV-1) is usually followed by a vigorous immune response that temporarily protects against disease progression. After a variable asymptomatic period, acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and AIDS develop in most infected individuals. We have demonstrated that healthy HIV-1-infected individuals have neutralizing antibodies and a high titer of antiviral antibodies. In contrast, AIDS patients have undetectable levels of neutralizing antibodies, low titers of antiviral antibodies, and, frequently, HIV p24 antigenemia. These observations prompted us to attempt passive immunization in ARC and AIDS patients. Ten consistently viral-antigen-positive patients (mean, greater than 6 months) were treated, resulting in sustained clearance of p24 antigen. Patients either maintained or increased their antiviral antibody titers. The raised titers result from increased antibody synthesis by the recipients. Circulating CD4+ cell counts were unchanged after 2 months. By the third month none of these patients remained in hospital. As this treatment was of minimal toxicity, it merits wider evaluation in ARC and AIDS patients.

The Karpas AIDS Cell Test compared with an enzyme-linked immunosorbent assay for detecting antibody to the human immunodeficiency viruses (HIV-I and HIV-2).

We have compared the Karpas AIDS Cell Test for antibodies to the human immunodeficiency viruses (HIV) with a commercial enzyme-linked immunosorbent assay (ELISA) (Organon Teknika) by testing serum samples from 324 intravenous drug abusers in Turin. The cell test was found to be more sensitive and as specific as the ELISA with the serum samples from the drug abusers. In Lisbon, 30 samples were tested on slides containing cells infected with HIV-1 and/or HIV-2. All 15 samples, which were positive for HIV-2 alone (in the HIV-2 Elavia test and by the Western blotting technique), were also positive in the Karpas AIDS test. In contrast, only one of the 15 samples (7%) gave a positive reading in the ELISA for HIV-1. Results of 30 samples tested in Turin and Lisbon by the Western blotting technique agreed closely with those obtained with the Karpas AIDS Cell Test. We were also able to show that the entire test can be performed at room temperature and completed within 1 hour. Moreover, the cell test requires minimal skill and simple equipment and is inexpensive. It also includes non-infected cells as a control and the specificity of positive samples may be verified with a bench microscope. Furthermore, this test which detects antibodies to both HIV-1 and HIV-2 allows rapid typing of the infecting strain.