Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years

A randomized, open trial involving 260 Tanzanian children, aged 1–5 years, with acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the combination antimalarial CGP 56697 (artemether and benflumetol), and to compare it with chloroquine, the standard drug used for malaria treatment in the Kilombero area. Children who had received rescue medication within the first 48 h or had a negative slide at the same time were excluded. Seven-day parasitological cure rates were 94% (95% CI 88–97.5) for CGP 56697 and 35.4% (95% CI 25.9–45.8) for chloroquine. Using the same definition, the 14-day parasitological cure rates were 86.4% (95% CI 78.5–92.2) for CGP 56697 and 10.3% (95% CI 5.1–18.1) for chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by chloroquine. There were no major adverse events with either drug. CGP 56697 is highly efficacious against P. falciparum in this area of Tanzania. The study contributes to the discussion on treatment strategies, particularly whether chloroquine may still fulfil its role as first-line drug in an area of high malaria transmission and very high levels of chloroquine resistance.     

Self-help smoking cessation interventions in pregnancy: a systematic review and meta-analysis

Aims   Self-help smoking cessation interventions for pregnant smokers are of importance due to their potential to be wide-reaching, low-cost and their appeal to pregnant smokers who are interested in quitting smoking. To date, however, there has been no systematic assessment of their efficacy. This systematic review aimed to assess the efficacy of self-help interventions for pregnant smokers and to investigate whether self-help material intensity, type or delivery are associated with cessation.
Methods   The literature was searched for randomized and quasi-randomized controlled trials of self-help smoking cessation interventions for pregnant smokers without significant cessation counselling. Fifteen trials met the inclusion criteria and relevant data were extracted independently.
Results   The primary meta-analysis pooled 12 trials comparing usual care (median quit rate 4.9%) with self-help (median quit rate 13.2%) and yielded a pooled odds ratio (OR) of 1.83 [95% confidence interval (CI) 1.23–2.73], indicating that self-help interventions on average nearly double the odds of quitting compared with standard care. However, a further meta-analysis failed to find evidence that intervention materials of greater intensity increase quitting significantly over materials of lesser intensity (pooled OR = 1.25, 95% CI 0.81–1.94). There was insufficient evidence to determine whether the tailoring of materials or levels of one-to-one contact were related to intervention efficacy.
Conclusions   Self-help interventions appear to be more effective than standard care although, due mainly to a lack of trials, it is unclear whether more sophisticated and intensive approaches increase intervention effectiveness.     

Lactitol in treatment of chronic hepatic encephalopathy

The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase-deficient patients. The methodological quality of these studies was high. Meta-analysis showed that lactitol was as effective as other disaccharides in the treatment of encephalopathy: pooled odds ratio was 0.83, 95% confidence interval was 0.38–1.82. Results were not sensitive to the use of alternative methods of counting and attributing events in these trials. Patients experienced fewer side effects during treatment with lactitol, but the pooled odds ratio was not statistically significant. In all studies lactitol was considered more palatable. Clinical effectiveness of lactitol, in long-term treatment of chronic encephalopathy, is similar to those of lactulose. It seems that lactitol has lower side effects than lactulose. Future RCTs with a double-blind design could be mainly aimed at evaluating the side-effect profile of the two disaccharides.This work was supported by grants from the Zyma S. A.     

Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis

OBJECTIVE: To review the effect of risedronate on bone density and fractures in postmenopausal women. DATA SOURCES: We searched MEDLINE from 1966 to the end of 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. STUDY SELECTION: We included eight randomized, placebo-controlled trials of postmenopausal women receiving risedronate or placebo with a follow-up of at least one year and providing data on bone density or fracture rate. DATA EXTRACTION: For each trial, two independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: The major methodological limitation of the trials was the loss to follow-up, which was over 20% in most trials and over 35% in the largest study. However, the magnitude of the treatment effect was unrelated to loss to follow-up, and in one of the largest trials, more high-risk patients were lost to follow-up in the control than in the treatment group. The pooled relative risk (RR) for vertebral fractures in women given 2.5 mg or more of risedronate was 0.64 [95% confidence interval (CI) 0.54, 0.77]. The pooled RR of nonvertebral fractures in patients given 2.5 mg or more of risedronate was 0.73 (95% CI 0.61, 0.87). Risedronate produced positive effects on the percentage change in bone density of the lumbar spine, combined forearm, and femoral neck that were generally larger with the 5-mg daily dose than with cyclical administration or the 2.5-mg dose. The pooled estimate of the difference in percentage change between 5 mg risedronate and placebo after the final year of treatment (1.5-3 yr) was 4.54% (95% CI 4.12, 4.97) for the lumbar spine, and 2.75% (95% CI 2.32, 3.17) at the femoral neck. CONCLUSIONS: Risedronate substantially reduces the risk of both vertebral and nonvertebral fractures. This fracture reduction is accompanied by an increase in bone density of the lumbar spine and femoral neck in both early postmenopausal women and those with established osteoporosis.     

Has the impact of helicobacter pylori therapy on ulcer recurrence in the united states been overstated?

Objective: The aim of this study was to assess the effect of H. pylori eradication on ulcer recurrence in North American duodenal ulcer patients by examining only treatment studies that met rigorous methodologic criteria.
Methods: Data sources were computerized bibliographic searches from 1983, review of reference lists, communication with companies that manufacture medications used for H. pylori therapy in the U.S., and H. pylori investigators, review of open presentations to the Food and Drug Administration, and review of abstracts from annual scientific meetings. Criteria for study inclusion were double blind, randomized North American trials of H. pylori therapy for duodenal ulcer, scheduled endoscopic follow-up exams for ≥6 months, and H. pylori cure documented ≥4 wk after completion of therapy by at least two endoscopic biopsy tests. Seven relevant trials were identified. Data were abstracted independently and disagreement was resolved by consensus. We obtained missing data and identified erroneous assessments through contact with an author or sponsor of all studies.
Results: The common odds ratio for ulcer recurrence was 0.20 (95% CI, 0.13–0.31) and 2.8 patients would need to be successfully treated to prevent one ulcer recurrence at 6 months. The pooled ulcer recurrence rate at 6 months in patients with H. pylori eradication was 20%.
Conclusion: Results of North American studies of highest methodological quality confirm that H. pylori eradication markedly decreases ulcer recurrence. Nevertheless, 20% of patients in these studies had ulcer recurrence within 6 months, despite successful cure of infection and no reported use of NSAIDs. Non- H. pylori , non-NSAID ulcers may be more common in the U.S. than previously believed.     

Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review

To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by electronic and manual searches. Trials of Phyllanthus herb plus interferon (IFN) vs. IFN alone were also included. No blinding and language limitations were applied. The methodological quality of trials was assessed by the Jadad scale plus allocation concealment. Twenty-two randomized trials ( n =1947) were identified. The methodological quality was high in five double-blind trials and low in the 17 remaining trials. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95% CI 1.85–17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and IFN. Phyllanthus species were better than nonspecific treatment or other herbal medicines for the clearance of serum HBsAg, HBeAg, HBV DNA, and liver enzyme normalization. Analyses showed a better effect of the Phyllanthus plus IFN combination on clearance of serum HBeAg (1.56, 1.06–2.32) and HBV DNA (1.52, 1.05–2.21) than IFN alone. No serious adverse event was reported. Based on this review Phyllanthus species may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not strong due to the general low methodological quality and the variations of the herb. Further large trials are needed.     

What does sigmoidoscopy really miss?

The relative effectiveness of flexible sigmoidoscopy compared with colonoscopy to screen for colorectal cancer depends on the magnitude of the association between findings in the proximal and distal colon and the false-negative rate of screening sigmoidoscopy for proximal neoplasia. Lewis et al. performed a systematic review and meta-analysis of screening colonoscopy studies. Published studies through July 31, 2000 of asymptomatic patients undergoing screening colonoscopy were identified from the MEDLINE database. The authors generated pooled estimates of the odds ratio for the association between findings in the distal and proximal colon and the prevalence of isolated proximal adenomatous neoplasia. With the sigmoid–descending colon junction used to identify the beginning of the distal colon, the pooled odds ratio for the association between distal adenomatous polyps and any proximal neoplasia was 2.40 (95% confidence interval [Cl] = 1.42–4.05). Diminutive distal adenomatous polyps were also associated with proximal neoplasia (odds ratio = 2.36; 95% CI = 1.30–4.29). Distal hyperplastic polyps were not associated with proximal neoplasia (odds ratio = 1.44; 95% CI = 0.79–6.62). The prevalence of isolated advanced proximal neoplasia in the three studies was 2%, 3%, and 5%, respectively. When the sigmoid–descending colon junction is used to identify the beginning of the distal colon, this yields a pooled estimate of isolated proximal neoplasia of 16.3% (95% CI = 13.6%–19.1%). Distal adenomatous polyps, including diminutive distal adenomatous polyps, are associated with an increasing prevalence of synchronous proximal neoplasia. From 2% to 5% of patients undergoing screening colonoscopy might have isolated advanced proximal neoplasia.     

Cholangitis following biliary-enteric anastomosis: A systematic review and meta-analysis

BackgroundCholangitis is a serious biliary complication following biliary-enteric anastomosis (BEA). However, the rate of cholangitis in the postoperative period and its associated risk factors are inconclusive. The objective of this systematic review and meta-analysis was to assess the onset and risk factors of cholangitis after biliary-enteric reconstruction in literature.MethodsMEDLINE, EMBASE, and Cochrane databases were searched systematically to identify studies reporting about cholangitis following biliary-enteric anastomosis. Meta-analyses were performed for risk factors using random effects model with odds ratio (OR) and 95% confidence interval (95 %CI) as effect measures. Study quality was assessed by the MINORS (methodological index for non-randomized studies) criteria.Results28 studies involving 6904 patients were included in the study. The pooled rate for postoperative cholangitis (POC) was 10% (95 %CI: 8 %–13%) with studies reporting about an early- and late-onset of cholangitis. Male sex (OR 2.08; 95 %CI: 1.33–3.24; P = 0.001), postoperative hepatolithiasis (OR 137.19; 95 %CI: 29.00–648.97; P < 0.001) and postoperative anastomotic stricture (OR 178.29; 95 %CI: 68.64–463.11; P < 0.001) were associated with a higher risk of a late-onset of POC with a pooled rate of 8% (95 %CI: 6 %–11%) after a median time interval of 12 months. The quality of the included studies was low to moderate.ConclusionCholangitis is a frequent complication after BEA. Consensus definition and prospective trials are required to assess optimal therapeutic strategies. We proposed a standardized definition and grading of POC to enable comparisons between future studies.     

Trichomoniasis treatment in women: a systematic review

objective  To compare the effectiveness of various treatment strategies for trichomoniasis in women.
data sources  Medline from 1966 to1996, Embase from 1986 to 1996, Science Citation Index from 1990 to 1996; reference lists of existing reviews; through the manufacturers of metronidazole and tinidazole in the UK, the Cochrane Controlled Trials Register until October 1997 and informal discovery.
study selection  Any randomized or quasi-randomized trial in nonpregnant women with trichomoniasis where different treatment strategies were compared. 45 of the 124 identified studies met the criteria and were included in the review.
data extraction  Settings, diagnostic methods, exclusions, loss to follow-up and partner treatment strategies were extracted. Outcomes sought were parasitological cure, clinical cure and side-effects of treatment.
results  Most trials were small, with only two trials containing more than 100 women in each comparison group. Only 11 trials followed up women for more than one month. Oral nitroimidazoles were effective in achieving parasitological cure. Fourteen trials compared different treatment strategies with the remainder comparing different doses or different drugs. Partner treatment was effective in decreasing longer-term re-infection rates in the one trial testing this.
conclusions  Parasitological cure can be achieved by a single oral dose of nitroimidazoles. There is, however, very little data on partner treatment strategies and long-term cure rates after initial treatment. Further research should test various partner treatment strategies to prevent re-infections and reduce trichomoniasis prevalence.     

Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials

Summary.  Dual therapy with pegylated interferon and ribavirin is recommended for patients with chronic hepatitis C virus infection who meet criteria for treatment, but it is unclear whether pegylated interferon alfa-2a or pegylated interferon alfa-2b is more effective or associated with fewer adverse events. Because data from head-to-head trials of pegylated interferon regimens are sparse, we performed adjusted indirect analysis using trials comparing dual therapy with pegylated interferon alfa-2a or pegylated interferon alfa-2b vs dual therapy with non-pegylated interferon. We searched for potentially relevant randomized controlled trials using electronic databases and reference lists. A total of 16 trials met inclusion criteria. Adjusted indirect comparisons found no statistically significant differences between dual therapy with pegylated interferon alfa-2a and dual therapy with pegylated interferon alfa-2b on the outcomes sustained virologic response [relative risk (RR) = 1.59, 95% CI: 0.56–4.46], withdrawal due to adverse events (RR = 0.86, 95% CI: 0.29–2.55), anaemia (RR = 1.67, 95% CI: 0.32–8.84), depression (RR = 1.09, 95% CI: 0.41–2.90) or flu-like symptoms (RR = 1.10, 95% CI: 0.53–2.29). Adjusting for potential publication bias and stratifying analyses by indicators of methodological quality, human immunodeficiency virus infection status, hepatitis C virus genotype, dose of ribavirin or dose of pegylated interferon did not change conclusions. There is insufficient evidence to support conclusions that dual therapy with one pegylated interferon is superior to the other. However, because estimates are imprecise, our results also do not rule out a clinically significant difference. Head-to-head trials are needed to verify the results of indirect analyses and provide additional guidance on optimal treatment choices.     

国内人工肝支持系统治疗重型肝炎疗效的Meta分析

目的探讨国内应用人工肝支持系统治疗重型肝炎的疗效。方法检索国内1990-2005年公开发表的人工肝治疗重型肝炎相关论文及会议论文，提取其中的生存率或出院时临床好转率等可以反映远期预后的资料，以比值比（OR）为效应量进行异质性检验和统计量合并分析。结果入选的10项研究中，共包含重型肝炎患者1030例，对照组均给予常规内科治疗，治疗组均为常规内科治疗联合人工肝治疗。早期、中期、晚期治疗组和对照组比较，其合并OR值（95％可信区间）分别为3．72（2．03～6．83）、2．79（2．88～4．14）和1．85（0．96～3．56）。结论和常规内科治疗相比，人工肝支持系统可显著改善早期及中期重型肝炎患者的远期预后，而对晚期重型肝炎患者远期预后无明显改善。     

Efficacy and safety of ceftriaxone for uncomplicated gonorrhoea: a meta-analysis of randomized controlled trials

We conducted a systematic review and meta-analysis of ceftriaxone for treatment of uncomplicated gonorrhoea compared with four other antibiotics. Thirteen randomized controlled trials (RCTs) totalling treatment of 2557 patients with uncomplicated gonorrhoea were included. Statistically significant differences were observed in side-effects, which were increased after ceftriaxone 250 mg versus cefotaxime 500 mg (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.14-3.08). Cure rates of ceftriaxone 250 mg were significantly better than cefixime 400 mg (OR 1.77; 95% CI 1.11-2.80) as was ceftriaxone 125 mg versus spectinomycin 2 g (OR 3.44; 95% CI 1.08-10.90). There was no statistically significant difference between ceftriaxone 250 mg and cefixime 800 mg in cure rates (OR 1.39; 95% CI 0.92-2.10) or adverse effects (OR 1.29, 95% CI 0.58-2.84) for treating uncomplicated gonorrhoea. The cure rate after ceftriaxone 250 mg was not significantly different from that after spectinomycin 2 g (OR 1.96; 95% CI 1.00-3.87). In conclusion, this meta-analysis revealed that 250 mg ceftriaxone had a higher efficacy than 400 mg cefixime for uncomplicated gonorrhoea. Also, ceftriaxone 125 mg is a better choice than spectinomycin 2 g for patients with uncomplicated gonorrhoea, but ceftriaxone had higher side-effect rates than cefotaxime. In the current era further randomized controlled clinical trials of ceftriaxone for uncomplicated gonorrhoea are warranted.     

Glycaemic control and adverse events in patients with type 2 diabetes treated with metformin + sulphonylurea: a meta-analysis

Aim:  The aim of this study was to quantify the effect of a sulphonylurea on glycaemic control and the risk adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on metformin.
Methods:  A systematic review was carried out to identify randomized controlled trials of sulphonylurea therapy in patients with type 2 diabetes whose glycaemic control was inadequate after maximal treatment with metformin. Data on reductions in haemoglobin A_1C (HbA_1C), fasting plasma glucose (FPG) and risk of hypoglycaemic events were extracted from each study and pooled in meta-analyses. Data on weight change were also extracted and tabulated.
Results:  Six studies including 1364 patients were identified. Based on random effects meta-analysis, the pooled estimate of change in HbA_1C from baseline was 0.9% (95% CI 0.7–1.1, p = 0.00011 vs. baseline) and for change in FPG from baseline was 1.8 mmol/l (95% CI 1.1–2.5, p = 0.0026 vs. baseline). The odds of experiencing a hypoglycaemic event was significantly higher in sulphonylurea-treated patients than in those on comparator treatments (OR = 5.3, 95% CI 1.7–16.3, p = 0.03). Mean weight change ranged from +2.5 to −0.1 kg, depending on the comparator treatment.
Conclusions:  This analysis has demonstrated that, in patients with type 2 diabetes whose control is inadequate on metformin monotherapy, the magnitude of incremental HbA_1C reduction achieved by the addition of a sulphonylurea is unlikely to exceed 1%, even after titration to maximum tolerated doses. Additionally, clinically relevant side-effects such as symptomatic hypoglycaemia and weight gain may be experienced.     

Chinese herbal medicine modified xiaoyao san for functional dyspepsia: Meta-analysis of randomized controlled trials

Background:  To critically assess the evidence of modified xiaoyao san (MXS) for treating functional dyspepsia (FD).
Methods:  Systematic literature searches were carried out on the Medline database, CNKI database, Wanfang Data, VIP Information and the Cochrane Library. Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of MXS for treating FD were included. Study selection, data extraction and validation were carried out by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were carried out.
Results:  Thirty-three potentially relevant articles were retrieved for further evaluation. Fourteen were suitable for inclusion in the meta-analysis. There was evidence that MXS compared with prokinetic drugs reduced symptoms (odds ratio 3.26, 95% CI 2.24 to 4. 47). There was evidence that MXS + prokinetic drugs compared with prokinetic drugs reduced symptoms (odds ratio 4.32, 95% CI 2.64 to 7.08).
Conclusion:  MXS appears to be more effective compared to prokinetic drugs in the treatment of FD and no serious side-effects were identified. However, the evidence remains weak due to publication bias and methodological flaws, which may amplify the therapeutic benefit of MXS.     

Yttrium synovectomy: a meta-analysis of the literature

Background: Yttrium synovectomy for chronic synovitis of the knee enjoys widespread usage in Australia with approximately 400 patients receiving yttrium-90 in 1991. Despite abundant anecdotal evidence of its efficacy there is a paucity of controlled trials and those that have been done have produced conflicting results and have been of insufficient sample size.
Aims: To critically and quantitatively evaluate the published English literature on comparative trials of yttrium-90 therapy for chronic synovitis of the knee.
Methods: The technique of meta-analysis was utilised. The literature search was carried out using the MeSH terms of synovectomy and knee; and yttrium. This was augmented by referring to reviews, current textbooks and back-references. Outcome measures varied between trials but could be grouped as treatment success. The Peto modification of Mantel and Haenszl was used for statistical pooling of data yielding a pooled odds ratio (OR).
Results: The literature search revealed ten controlled trials of which two were excluded from further analysis. Yttrium was superior to placebo (OR 2.42, 95% CI 1.02–5.73) but this result should be interpreted with caution due to possible publication bias. Yttrium was not superior to triamcinolone (OR 1.89, 95% CI 0.81-10.55) or other active modalities (OR 1.04, 95% CI 0.72-1.52). Further research comparing yttrium with other modalities is necessary to properly determine its place in rheumatological practice. (Aust NZ J Med 1993; 23: 272–275.)     

Single-dose therapy for giardiasis in school-age children

A randomized controlled trial was carried out to study the efficacy of combined albendazole and praziquantel in the treatment of giardiasis in school-age children. Eighty-four children were randomly allocated to 3 groups: group 1 (n = 31) albendazole 400 mg combined with praziquantel 20 mg/kg; group 2 (n = 26) albendazole 800 mg as a single dose; group 3 (n = 27) tinidazole 50 mg/kg as a single dose. The treatment was considered curative when Giardia was not found in two consecutive stool samples. The parasitological cure rate was 74.2% for combined single-dose albendazole-praziquantel, 50% and 92.6% in the albendazole and tinidazole groups respectively (p = 0.0023). There was no statistically significant difference between the cure rates of the combined regimen and tinidazole (p > 0.05). This combined regimen was considered safe, with only minor side-effects being observed. Of the single-dose regimens, tinidazole still achieves the highest parasitological cure rate for giardiasis. The albendazole-praziquantel combined regimen may be an alternative single-dose therapy for giardiasis in children, especially as this combination will eradicate common intestinal protozoa and co-existing helminths. Whether the dosage of this combination treatment should be adjusted for G. intestinalis remains to be established by further study.     

Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody–associated vasculitis: A meta‐analysis

Objective

Disease relapses are common for patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV). The role of low‐dose glucocorticoids (GC) in relapse prevention is controversial. We undertook a systematic review and meta‐analysis to determine if GC target doses influence relapses of AAV.

Methods

Medline, EMBase, and Cochrane databases were searched for observational studies and randomized controlled trials of treatment of AAV that included a predefined GC treatment plan. The association of GC target dose with the proportion of relapses in studies was assessed using meta‐regression and multilevel generalized linear modeling.

Results

Thirteen studies (983 patients) were identified for inclusion. There were no studies directly comparing GC regimens. We classified 288 patients as having a nonzero GC target dose by study end and 695 patients as having a zero GC target dose by study end. The pooled proportion of patients with a relapse was 36% (95% confidence interval [95% CI] 25–47%). GC regimen was the most significant variable explaining the variability between the proportions of patients with relapses. The proportion of patients with a relapse was 14% (95% CI 10–19%) in nonzero GC target dose studies and 43% (95% CI 33–52%) in zero GC target dose studies. Differences other than GC regimens exist between studies that complicate the comparability of trials and isolation of the variability in relapses due to GC target alone.

Conclusion

Studies with longer courses of GC in AAV are associated with fewer relapses. These results have implications for study design and outcome assessment in clinical trials of AAV.     

Chronic hepatitis C and interferon alpha: conventional and cumulative meta-analyses of randomized controlled trials

OBJECTIVE: The purpose of this study was to evaluate the clinical usefulness of surrogate markers of the interferon effect (i.e., alanine aminotransferase levels and serum HCV-RNA status) as predictors of long term response, and to identify the optimal schedule of treatment for patients with chronic hepatitis C by means of meta-analysis. METHODS: Pertinent randomized clinical trials and prospective studies were selected using MEDLINE (1986-1996), a reference list from published articles or reviews. Twenty-six prospective studies reporting data on surrogate markers of interferon response were selected. Thirty-nine trials comparing interferon alpha to no treatment and 25 trials comparing different schedules of interferon were reviewed. Conventional meta-analysis according to the DerSimonian and Laird method was used for the pooling of results. RESULTS: The pooled probability of late relapse among sustained responders with negative serum HCV-RNA 6 months after treatment was very low (8.7%; 95% confidence interval 5.8-11.6%). The overall risk difference between treated and control groups was 16.63% (95% confidence interval 11.95-21.31%) for sustained aminotransferase normalization. Therapy with higher interferon dose compared with standard dose significantly improves the rate of sustained response (pooled risk difference 10.56%, 95% CI 5.47-15.65%). Cumulative meta-analyses suggest that a clear dose-response relationship exists across a wide range of interferon dosages. The multivariate meta-regression model confirms that the total interferon dose is an independent predictor of sustained response and that it seems more important than the length of treatment. CONCLUSIONS: Testing for serum HCV-RNA, 6 months after interferon therapy in sustained biochemical responders, is useful for predicting long term response. The current standard total interferon dose of 234 mega-units is suboptimal. Further trials that directly compare different schedules of treatment are needed.     

Post-natal incidence of HIV-1 infection among children in a rural Ugandan population: no evidence for transmission other than mother to child

We conducted a prospective cohort study to determine the post‐natal incidence of and possible transmission routes for HIV‐1 infection in rural Ugandan children. The cohort consisted of the population of a cluster of 15 villages in Masaka District, south‐west Uganda, and was enrolled in 1989–1990 through a demographic and serological survey. During the period 1991–1993 the population was resurveyed annually. A total of 5492 children aged 0–12 years were enrolled; of these, 41 (0.7%) were seropositive infants. A total of 3941 (72%) children were HIV‐negative on enrolment and had at least one follow‐up specimen. During 8596 person‐years of observation only 1 seroconversion was observed, an incidence rate of 0.12 (95% CI 0.00–0.35) per 1000 years of observation. The transmission of HIV was most probably through breast milk. The case corresponds to a rate of 1.1 per 1000 in households with one or more HIV‐positive adults (874 years of observation); no incident case was observed in households with only seronegative adults (6423 years of observation). Thus, HIV infection among children aged 0–12 years in this population is virtually exclusively the result of mother‐to‐child transmission. No infections were observed attributable to parenteral exposure, non‐sexual casual or household contact, or insects.