Theory-driven process evaluation of a complementary feeding trial in four countries

We conducted a theory-driven process evaluation of a cluster randomized controlled trial comparing two types of complementary feeding (meat versus fortified cereal) on infant growth in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo. We examined process evaluation indicators for the entire study cohort (N = 1236) using chi-square tests to examine differences between treatment groups. We administered exit interviews to 219 caregivers and 45 intervention staff to explore why caregivers may or may not have performed suggested infant feeding behaviors. Multivariate regression analysis was used to determine the relationship between caregiver scores and infant linear growth velocity. As message recall increased, irrespective of treatment group, linear growth velocity increased when controlling for other factors (P < 0.05), emphasizing the importance of study messages. Our detailed process evaluation revealed few differences between treatment groups, giving us confidence that the main trial’s lack of effect to reverse the progression of stunting cannot be explained by differences between groups or inconsistencies in protocol implementation. These findings add to an emerging body of literature suggesting limited impact on stunting of interventions initiated during the period of complementary feeding in impoverished environments. The early onset and steady progression support the provision of earlier and comprehensive interventions

Cost-minimization analysis in a blind randomized trial on small-incision versus laparoscopic cholecystectomy from a societal perspective: sick leave outweighs efforts in hospital savings

Background: After its introduction, laparoscopic cholecystectomy rapidly expanded around the world and was accepted the procedure of choice by consensus. However, analysis of evidence shows no difference regarding primary outcome measures between laparoscopic and small-incision cholecystectomy. In absence of clear clinical benefit it may be interesting to focus on the resource use associated with the available techniques, a secondary outcome measure. This study focuses on a difference in costs between laparoscopic and small-incision cholecystectomy from a societal perspective with emphasis on internal validity and generalisability Methods: A blinded randomized single-centre trial was conducted in a general teaching hospital in The Netherlands. Patients with reasonable to good health diagnosed with symptomatic cholecystolithiasis scheduled for cholecystectomy were included. Patients were randomized between laparoscopic and small-incision cholecystectomy. Total costs were analyzed from a societal perspective. Results: Operative costs were higher in the laparoscopic group using reusable laparoscopic instruments (difference 203 euro; 95% confidence interval 147 to 259 euro). There were no significant differences in the other direct cost categories (outpatient clinic and admittance related costs), indirect costs, and total costs. More than 60% of costs in employed patients were caused by sick leave. Conclusion: Based on differences in costs, small-incision cholecystectomy seems to be the preferred operative technique over the laparoscopic technique both from a hospital and societal cost perspective. Sick leave associated with convalescence after cholecystectomy in employed patients results in considerable costs to society

Antioxidant therapy to prevent preeclampsia - A Randomized controlled trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The a level for the final analysis, adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, pre-term delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62). CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among'patients with chronic hypertension and/or prior preeclampsia.11061311131

Antioxidant Supplementation And Premature Rupture Of The Membranes: A Planned Secondary Analysis

Objective: The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM). Study Design: A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 120/7 and 196/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo. Results: Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group. Conclusion: Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM. © 2008 Mosby, Inc. All rights reserved.1994433.e1433.e8(2007) Premature rupture of the membranes. ACOG Practice Bulletin, , Number 80. AprilWoods Jr., J.R., Plessinger, M.A., Miller, R.K., Vitamins C and E: missing links in preventing preterm premature rupture of membranes? (2001) Am J Obstet Gynecol, 185, pp. 5-10Woods Jr., J.R., Reactive oxygen species and preterm premature rupture of membranes-a review (2001) Placenta, 22 (SUPPL. A), pp. S38-S44Spinnato, J.A., Freire, S., Pinto e Silva, J.L., Antioxidant therapy to prevent preeclampsia: a randomized controlled trial (2007) Obstet Gynecol, 110, pp. 1311-1318Alexander, G.R., Himes, J.H., Kaufman, R.B., Mor, J., Kogan, M., A United States national reference for fetal growth (1996) Obstet Gynecol, 87, pp. 163-168DeMets, D.L., Lan, K.K.G., Interim analysis: the alpha spending function approach (1994) Stat Med, 13, pp. 1341-1352. , discussion 1353-6Kuritz, S.J., Landis, J.R., Koch, G.G., A general overview of Mantel-Haenszel methods: applications and recent developments (1988) Ann Rev Public Health, 9, pp. 123-160Hosmer, D.W., Lemeshow, S., (2000) Applied logistic regression. 2nd ed., , John Wiley & Sons, Inc, New YorkBarrett, B.M., Sowell, A., Gunter, E., Wang, M., Potential role of ascorbic acid and beta-carotene in the prevention of preterm rupture of fetal membranes (1994) Int J Vitam Nutr Res, 64, pp. 192-197Plessinger, M.A., Woods Jr., J.R., Miller, R.K., Pretreatment of human amnion-chorion with vitamins C and E prevents hypochlorous acid-induced damage (2000) Am J Obstet Gynecol, 183, pp. 979-985Wall, P.D., Pressman, E.K., Woods Jr., J.R., Preterm premature rupture of the membranes and antioxidants: the free radical connection (2002) J Perinat Med, 30, pp. 447-457Siega-Riz, A.M., Promislow, J.H., Savitz, D.A., Thorp Jr., J.M., McDonald, T., Vitamin C intake and the risk of preterm delivery (2003) Am J Obstet Gynecol, 189, pp. 519-525Casanueva, E., Ripoll, C., Tolentino, M., Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial (2005) Am J Clin Nutr, 81, pp. 859-863Chappell, L.C., Seed, P.T., Briley, A.L., Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial (1999) Lancet, 354, pp. 810-816Beazley, D., Ahokas, R., Livingston, J., Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial (2005) Am J Obstet Gynecol, 192, pp. 520-521Rumbold, A.R., Crowther, C.A., Haslam, R.R., Vitamins C and E and the risks of preeclampsia and perinatal complications (2006) N Engl J Med, 354, pp. 1796-1806. , ACTS Study GroupPoston, L., Briley, A.L., Seed, P.T., Kelly, F.J., Shennan, A.H., Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial (2006) Lancet, 367, pp. 1145-1154Kilsztajn, S., Carmo, M.S., Machado Jr., L.C., Lopes, E.S., Lima, L.Z., Caesarean sections and maternal mortality in Sao Paulo (2007) Eur J Obstet Gynecol Reprod Biol, 132, pp. 64-6

Oral cleft prevention program (OCPP)

Abstract Background Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. ClinicalTrials.gov Identifier NCT0039791

Theory-driven process evaluation of a complementary feeding trial in four countries

We conducted a theory-driven process evaluation of a cluster randomized controlled trial comparing two types of complementary feeding (meat versus fortified cereal) on infant growth in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo. We examined process evaluation indicators for the entire study cohort (N = 1236) using chi-square tests to examine differences between treatment groups. We administered exit interviews to 219 caregivers and 45 intervention staff to explore why caregivers may or may not have performed suggested infant feeding behaviors. Multivariate regression analysis was used to determine the relationship between caregiver scores and infant linear growth velocity. As message recall increased, irrespective of treatment group, linear growth velocity increased when controlling for other factors (P < 0.05), emphasizing the importance of study messages. Our detailed process evaluation revealed few differences between treatment groups, giving us confidence that the main trial’s lack of effect to reverse the progression of stunting cannot be explained by differences between groups or inconsistencies in protocol implementation. These findings add to an emerging body of literature suggesting limited impact on stunting of interventions initiated during the period of complementary feeding in impoverished environments. The early onset and steady progression support the provision of earlier and comprehensive interventions