1.                Ananworanich J, Gayet-Ageron A, Le Braz M, Prasithsirikul W, Chetchotisakd P, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Sirivichayakul S, Cavassini M, Karrer U, Genne D, Nuesch R, Vernazza P, Bernasconi E, Leduc D, Satchell C, Yerly S, Perrin L, Hill A, Perneger T, Phanuphak P, Furrer H, Cooper D, Ruxrungtham K, Hirschel B; Staccato Study Group; Swiss HIV Cohort Study. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial. Lancet. 2006 Aug 5;368(9534):459-65.

HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

2.                Birks J, Flicker L. Donepezil for mild cognitive impairment. Cochrane Database Syst Rev. 2006 Jul 19;3:CD006104.

University of Oxford, Department of Clinical Geratology, Radcliffe Infirmary, Woodstock Road, Oxford, UK OX2 6HE. jacqueline.birks@geratol.ox.ac.uk

BACKGROUND: Problems with memory which do not meet the diagnostic criteria for dementia, usually called mild cognitive impairment (MCI), can be the first sign of an impending dementia, particularly Alzheimer's disease (AD). There is no consensus on a definition or diagnostic criteria for MCI, and MCI remains a vague term and those so described are a heterogeneous population, consisting of people who may rapidly progress to dementia but also of people with stable cognitive deficits and some who may actually improve.Treatment in the very earliest stages of AD may delay progression to AD. Donepezil (Aricept, E2020), a cholinesterase inhibitor, has been shown to benefit all severities of AD including mild and it would be reasonable to investigate its efficacy for those with MCI. OBJECTIVES: To assess the effects of donepezil in people with mild cognitive impairment but no diagnosis of dementia. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 6 January 2006. This register contains records from major health care databases like CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO and many ongoing trial databases and is updated regularly. SELECTION CRITERIA: All double blind, randomized trials in which treatment with donepezil was compared with placebo for patients with mild cognitive impairment. DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports of the included studies, pooled where appropriate and the treatment effects or the risks and benefits estimated. MAIN RESULTS: The two included studies, with a total of 782 patients, all with a MMSE greater than 23 points, identified similar patients for inclusion, but were quite different with respect to design and objective. Pooling results in a meta-analysis was not possible.In the first study the 13-item ADAS-Cog showed benefit associated with 10 mg/day donepezil compared with placebo at 24 weeks (MD 1.90, 95% CI 0.51 to 3.29, p=0.007), but four other measures of cognitive function did not. The analysis of withdrawals before the end of treatment at 24 weeks, withdrawals due to an adverse event, and numbers experiencing an adverse event, showed a significant difference between the donepezil group and the placebo group in favour of placebo, (43/133 donepezil 23/137 placebo, OR 2.37, 95% CI 1.33 to 4.22, p=0.003), (29/133 donepezil 10/137 placebo, OR 3.54, 95% CI 1.65 to 7.60, p=0.001), (116/133 donepezil, 100/137 placebo, OR 2.52 95% CI 1.34 to 4.76, p=0.004). Various adverse effects were recorded, and several types of event, diarrhoea, nausea, vomiting, leg cramps and abnormal dreams, were reported more frequently in the donepezil group compared with the placebo.In the second study there was a significant difference between the number of patients diagnosed with AD or another dementia between the donepezil group and the placebo group in favour of donepezil after one year of treatment (16/253 donepezil 38/259 placebo) (OR 0.39, 95% CI 0.21 to 0.72, p=0.003), but no difference after 3 years of treatment (63/253 donepezil 73/259 placebo) (OR 0.84, 95% CI 0.57 to 1.25, p=0.4). AUTHORS' CONCLUSIONS: There are two included studies. One study demonstrated a modest treatment effect in cognitive function as assessed by ADAS-Cog13 but not for other outcomes assessing different domains of cognitive function. Donepezil was associated with significantly more adverse effects compared with placebo, mostly gastrointestinal. From the second study, there is no evidence that donepezil delays the onset of AD. There is no evidence to support the use of donepezil for patients with MCI. The putative benefits are minor, short lived and associated with significant side effects.

3.                  Christofides A, Asante KP, Schauer C, Sharieff W, Owusu-Agyei S, Zlotkin S. Multi-micronutrient Sprinkles including a low dose of iron provided as microencapsulated ferrous fumarate improves haematologic indices in anaemic children: a randomized clinical trial. Multi-micronutrient Sprinkles including a low dose of iron provided as microencapsulated ferrous fumarate improves haematologic indices in anaemic children: a randomized clinical trial. Matern Child Nutr. 2006 Jul;2(3):169-80

Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto and Programs in Metabolism and Integrative Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada.

Home-fortification of complementary foods with micronutrients (including iron) as Sprinkles is a new strategy to control iron deficiency and anaemia in developing countries. However, the most effective dose and form of iron is not known. The purpose of this study was to compare the efficacy of various doses (12.5, 20 or 30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18 months were randomly assigned to one of five daily interventions for 8 weeks. Out of the five interventions, four used Sprinkles, and one used iron drops. Of the four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were measured at baseline, week 3 and week 8. The primary outcome measure was Hb concentration at 8 weeks after treatment. We compared differences in Hb and ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(-1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline to 8 weeks within and between groups. Adherence and reporting of side effects (staining of the teeth, ease of use, diarrhoea and darkening of stools) were compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P = 0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in all groups (P = 0.0001-0.0007), with no differences across groups. Geometric means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group differences. Prevalence of iron deficiency anaemia decreased significantly from baseline to 8 weeks in all groups with the exception of the iron drops group, with no group differences. Adherence was lower in the drops group (64%) as compared with Sprinkles groups (84%). Greater staining of the teeth and less ease of use were reported in the drops group as compared with Sprinkles groups. A dose as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be effective in anaemic children.

4.                  Lei V, Friis H, Michaelsen KF. Spontaneously fermented millet product as a natural probiotic treatment for diarrhoea in young children: an intervention study in Northern Ghana. Int J Food Microbiol. 2006 Aug 1;110(3):246-53.

Royal Veterinary and Agricultural University, Dept. of Food Science, Food Microbiology, Rolighedsvej 30, 1958 Frederiksberg C, Denmark. vil@kvl.dk

Indigenous lactic acid fermented foods may have potential as probiotic treatment for diarrhoea, due to high levels of lactic acid bacteria. In this study the effect of a millet drink, spontaneously fermented by lactic acid bacteria, as a therapeutic agent among Ghanaian children with diarrhoea, was assessed. Children below 5 years of age coming to Northern Ghana health clinics for treatment of diarrhoea were randomised to two groups. Children of both groups received treatment for diarrhoea given at the local clinic. The intervention group in addition received up to 300 ml fermented millet drink (KSW) daily for 5 days after enrolment. The clinical outcome of diarrhoea and reported well-being were registered every day for the 5-day intervention and again 14 days after diagnosis. Among 184 children (mean age 17.4, standard deviation 11.3 months) included, no effects of the intervention were found with respect to stool frequency, stool consistency and duration of diarrhoea. However, KSW was associated with greater reported well-being 14 days after the start of the intervention (P=0.02). The fact that no effect of KSW on diarrhoea was observed could be because many children had a mild form of diarrhoea, and many were treated with antibiotics. Either this could have affected the lactic acid bacteria, or the lactic acid bacteria in KSW had no probiotic effects. It is speculated that the effect after two weeks could be due to a preventing effect of KSW on antibiotic-associated diarrhoea which could help reducing persistent diarrhoea.

5.                  Patel K, Rana R. Pedimune in recurrent respiratory infection and diarrhoea--the Indian experience--the pride study. Indian J Pediatr. 2006
Jul;73(7):585-91

Merck Ltd, Mumbai, India.

OBJECTIVE: To evaluate the efficacy and tolerability of bovine colostrum in preventing recurrent episodes of upper respiratory tract infections and diarrhoea in children METHODS: 605 children (1-8 yrs) having recurrent episodes of upper respiratory tract infections or diarrhea received Bovine Colostrum (Pedimune) for 12 weeks. Total no of episodes of recurrent infections, hospitalization rate, overall well being and adverse events were assessed at every 4 weeks. RESULTS: Episodes of URTI and diarrhoea reduced significantly by 91.19 % and 86.60% at the end of therapy respectively. High to average improvement in overall well-being in 96 % of the patients were found by pediatrician while overall well-being stated by the patient/care taker was very good to good in 90.56 % of the patients. CONCLUSION: Bovine colostrum was highly effective in the prophylactic treatment of recurrent URTIs and diarrhea in reducing not only the episodes but also the hospitalization due to them.

Therapy:

15017.  Goodman CA, Mutemi WM, Baya EK, Willetts A, Marsh V. The cost-effectiveness of improving malaria home management: shopkeeper training in rural Kenya. Health Policy Plan. 2006 Jul;21(4):275-88.

15018.  Lanata CF, Franco M.  Nitazoxanide for rotavirus diarrhoea? Lancet. 2006 Jul 8;368(9530):100-1.

15019.  Sharieff W, Bhutta Z, Schauer C, Tomlinson G, Zlotkin S. Micronutrients (including zinc) reduce diarrhoea in children: the Pakistan Sprinkles Diarrhoea Study. Arch Dis Child. 2006 Jul;91(7):573-9.

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