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Table 2 Intervention effects on post-acute (≥7 days after enrollment) mortality, length, weight, and/or diarrhea presence

From: Interventions to reduce post-acute consequences of diarrheal disease in children: a systematic review

Reference Intervention Comparator Relevant Outcomes and Results
Antimicrobial Interventions
 Gilman 1980 [8] Low dose ampicillin (50 mg/kg/day) Standard dose ampicillin (150 mg/kg/day) Mortality Risk Difference (95% CI) −0.11 (− 0.24, 0.03)i
Relative Risk (95% CI) Undefined
 Amadi 2002 [42] 5 mL of 20 g/L nitazoxanide, twice daily for 3 days Placebo Mortality Risk Difference (95% CI) −0.07 (− 0.21, 0.06)
Relative Risk (95% CI) 0.58 (0.21, 1.63)
Dietary Supplements
 Alam 2000 [26] ORS with dietary fiber (Benefiber®) WHO- ORS only Difference in weight gain at day 7, g (95% CI) 52 (−18.73, 122.73)
 Rabbani 2001 [15] Rice-based diet with dietary fiber (green banana or pectin supplement), 7 days Rice-based diet only Proportions recovered from diarrhea (formed stool) at each day to day 10 Higher in banana and pectin groups than in control groupii
 Yalcin 2004 [51] Glutamine supplement, 0.3 g/kg/day, for 7 days Placebo Difference in weight gain at day 30, g (95% CI)iii 130 (12.67, 247.33)
Difference in weight gain at day 60, g (95% CI) 45 (−80.80, 170.80)
Difference in weight gain at day 90, g (95% CI) 107 (−57.30, 271.30)
High Protein Diets
 Datta 1990 [9] High protein diet, length unspecified Standard hospital diet Difference in weight at day 15, kg (95% CI) 0.30 (−0.18, 0.78)
Difference in MUAC at day 15, cm (95% CI) 0.00 (−0.37, 0.37)
 Kabir 1992 [10] High protein diet (15% of total energy from protein), 21 days Standard diet (7.5% of total energy from protein), 21 days Difference in change in weight at day 21 from admission, kg (95% CI) 0.47 (0.12, 0.82)
Difference in change in height at day 21, from admission, cm (95% CI) 0.09 (−0.57, 0.75)
Difference in change in WAZ at day 21 from admission (95% CI) 0.30 (0.03, 0.57)
Difference in change in WHZ at day 21 from admission (95% CI) 0.40 (0.05, 0.75)
Difference in change in MUAC at day 21 from admission, cm (95% CI) 0.44 (0.08, 0.80)
Difference in change in triceps skinfold thickness at day 21 from admission, cm (95% CI) 0.32 (−0.29, 0.93)
 Kabir 1993 [11] High protein diet, 21 days Standard protein diet, 21 days Difference in change in WAZ at day 21, from admission (95% CI) 0.23 (0.07, 0.39)
Difference in change in WHZ at day 21, from admission (95% CI) 0.25 (0.05, 0.45)
Difference in change in HAZ at day 21, from admission (95% CI) 0.90 (0.05, 0.13)
 Mazumder 1997 [12] High calorie & high protein milk-cereal diet, 4960 kJ/l (10 days) Standard diet, 2480 kJ/l (10 days) Difference in percent change in WAZ at day 10 and 40, fromadmission (95% CI) Day 10: 3.50 (1.86, 5.14)
Day 40: 3.11 (0.92, 5.30)
Difference in percent change in WHZ at day 10 and 40, from admission (95% CI) Day 10: 3.76 (1.92, 3.60)
Day 40: 3.34 (0.76, 5.90)
 Nurko 1997 [36] High protein chicken-based diet or high protein soy-based diet (Nursoy formula)iv Calorically equivalent standard “elemental diet” (Vivonex) Difference in weight at end of protocol, gv (95% CI) Comparing soy group to control − 204 (− 1178.40, 770.40)
Comparing chicken group to control −445 (− 1522.70, 632.70)
Difference in weight at discharge from enrollment, g (95% CI) Comparing soy group to control −92 (− 1189.60, 1005.60)
Comparing chicken group to control − 428 (− 1539.80, 683.80)
Proportion with nutritional recoveryvi(RR [95%]) Comparing soy group to control 1.13 (0.79, 1.61)
Comparing chicken group to control 1.20 (0.86, 1.7)
 Kabir 1998 [13] High protein diet (15% of total energy from protein), 21 days Standard protein diet (7.5% of total energy from protein), 21 days Difference in change in weight at 6 mo, from post-intervention weight, kg (95% CI) 0.10 (−0.24, 0.44)
Difference in change in height at 6 mo, from post-intervention height, cm (95% CI) 1.10 (0.56, 1.64)
Difference in change in WAZ at 6 mo, from post-intervention WAZ (95% CI) 0.07 (−0.17, 0.31)
Difference in change in WHZ at 6 mo, from post-intervention WHZ (95% CI) −0.09 (− 0.35, 0.17)
Difference in change in HAZ at 6 mo, from post-intervention HAZ (95% CI) 0.28 (0.12, 0.44)
 Mazumder 2000 [14] High calorie & protein milk-cereal formula (4960 kJ/l), 10 days Control milk-cereal formula (2480 kJ/l), 10 days Difference in percent change in WAZ at day 10, from admission WAZ (95% CI) 3.50 (2.08, 4.91)
 Valentiner-Branth 2001 [43] Counseling on the importance of breastfeeding and of a nutritious diet, and a high protein millet gruel with a multivitamin tablet (including zinc), until the end of a 7 day period without diarrhea Counseling on the importance of breastfeeding and of a nutritious diet Difference in weight gain at end of intervention and day 90, g/wk.vii(95% CI) Day 90 61.50 (49.20, 73.80)
End of intervention 12.50 (7.70, 17.30)
Difference in change in knee heel length at end of intervention and day 90, mm/y (95% CI) Day 90 2.70 (−4.60, 10.00)
End of intervention 7.50 (4.80, 10.20)
Difference in change in height between groups at day 90, (cm/y)2 (95% CI)viii 0.65 (0.11, 1.19)
 Rollins 2007 [44] Standard nutritional support + extra protein to provide 150 kcal/kg/day and 4.0–5.5 g protein/kg/day Standard nutritional support: maize porridge + milk formula Mortality at 26 weeks Relative risk 1.34 (95% CI: 0.79, 2.27)
Risk difference 7.4% (−4.7%,20.5%)
Median change in weight- SDs ixat 26 weeks Greater gain in intervention group (p < 0.001)
Median change in WAZ at 26 weeks Greater gain in intervention group (p < 0.05)
Proportion underweight (WAZ < −2 SDs) at 26 weeks (Prevalence Ratio [95% CI]) 0.48 (0.30, 0.77)
Proportion stunted (LAZ < − 2 SDs) at 26 weeks (Prevalence Ratio[95% CI]) 0.87 (0.67, 1.13)
Lactose Free Diets
 Bhan 1988 [16] Legume and cereal-based formula (lactose-free), until recovery or 7 days min Calorically equivalent milk-based formula, until recovery or 7 days min Difference in weight gain at day 7, g/kg admission weight/24 h (95% CI) −3.20 (−6.86, 0.46)
Difference in weight gain at recovery, g/kg admission weight/24 h (95% CI) −3.80 (−7.15, −0.44)
 Bhutta 1991 [50] Soy milk (lactose-free) for 7 days, followed by khitchri and yogurt for 7 days Khitchri and yogurt for 14 days Difference in weight gain at day 7 and 14, g/wk. (95% CI) Day 7: −400 (− 559.40, − 240.60)
Day 14: 385.7 (209.60, 561.80)
 Lozano 1994 [38] Corn-based (lactose-free) formula, 21 days Milk-based formula, 21 days Difference in weight increment at 6 weeks, kg (95% CI) −0.02 (− 0.30, 0.26)
 Bhatnagar 1996 [17] Rice-based formula with egg white protein (lactose-free), until discharge Rice-based formula with milk protein, until discharge Proportion of patients whose weight on day 7 was lower than at rehydration (Prevalence Ratio [95% CI]) 0.97 (0.06, 15.19)
Probability of continuing diarrhea at each day to day 12 No significant difference (p = 0.76)x
 de Mattos 2009 [37] Amino-acid based diet, isolated soy-based, or hyrolyzed casein-based diet; until discharge Yogurt-based dietxi until discharge Difference in weight gain at discharge among groups at discharge No difference among groupsxii
Change in WHZ at discharge Similar improvement in all groupsxiii
Other Dietary Interventions
 Eichenberger 1984 [35] Semi-elemental diet with low osmolarity and high hydrolyzed lactalbumin, at least 21 days Standard hospital diet Weight at day 21 compared to weight at beginning of therapy Better in intervention groupxiv
 van der Kam 2016 (Uganda) [45] RUTF, plus instructions to feed the child an extra meal/day for 14 d; or micronutrient powder plus instructions to feed the child an extra meal/day for 14 d An instruction to feed the child an extra meal/day for 14 d Relative Risk of first event of malnutrition (95% CI) RUTF vs micronutrient group 0.68 (0.37, 1.22)
RUTF vs control group 0.62 (0.35, 1.10)
Micronutrient group vs control 0.92 (0.54, 1.54)
 van der Kam 2016 (Nigeria) [46] RUTF, plus instructions to feed the child an extra meal/day for 14 d; or micronutrient powder plus instructions to feed the child an extra meal/day for 14 d An instruction to feed the child an extra meal/day for 14 d Relative Risk of first event of malnutrition (95% CI) RUTF vs micronutrient group 1.12 (0.84, 1.50)
RUTF vs control group 0.91 (0.69, 1.20)
Micronutrient group vs control 0.81 (0.61,1.09xv)
ORS Formulations
 Santosham 1983 [39] High potassium/ high chloride ORS, or standard WHO-ORS, with regular diet Standard diet for diarrhea management Difference in weight at day 14, kg (95% CI) Comparing high potassium/chloride to control −0.3 (−1.45, 0.85)
Comparing standard ORS to control −0.50 (− 1.86, 0.76)
Difference in percent weight gain at day 14 (95% CI) Comparing high potassium/chloride to control 2.00 (1.57, 2.42)
Comparing standard ORS to control 2.30 (1.82, 2.77)
 Ribeiro 1991 [40] Alanine-based ORS Standard WHO-ORS Difference in weight gain at day 7, g (95% CI) 18 (−94.37, 130.38)
 Faruque 1997 [21] Glucose-based ORS Rice powder-based ORS, equivalent in electrolyte content Proportion with diarrhea at day 14 (RR [95% CI]) 0.80 (0.21, 2.95)
Difference in weight gain at day 16, g Similar between groupsxvi
 Alam 2009 [55] Glucose-based ORS, or glucose-based ORS with amylase-resistant starch (ARS) Rice-based ORS Difference in time to attain 80% of median WLZ, days (95% CI) Difference between glucose and rice ORS − 0.06 (− 1.19, 1.07)
Difference between glucose with amylase resistant starch and rice ORS − 0.08 (− 1.20, 1.04)
Proportion with diarrhea at or after day 7 (RR [95% CI]) Risk in glucose ORS group compared to rice ORS group (RR, [95% CI]) 1.00 (0.15, 6.86)
Risk in glucose with ARS group compared to rice ORS groups (RR, [95% CI]) 0.49 (0.05, 5.27)
Probiotics
 Boudraa 2001 [47] Milk-based formula fermented with L. bulgaricus S. andthermophilus Milk-based formula only Difference in weight gain at day 7, g (95% CI) 43 (− 109.18, 195.18)
Difference in weight gain at day 7, g/kg (95% CI) 4.4 (−5.50, 14.30)
 Villarruel 2007 [41] S. boulardii capsules Placebo Proportion with diarrhea on day 7 (Prevalence Ratio [95% CI]) 0.39 (0.20, 0.74)
Proportion with diarrhea after day 7 (Prevalence Ratio [95% CI]) 0.25 (0.07, 0.82)
 Misra 2009 [19] L. rhamnosus GG 109 CFU Placebo Difference in change in WHZ at 6 weeks No difference between groups (p = 0.06)
 Sindhu 2014 [20] L. rhamnosus GG 1010 CFU Placebo Proportion with diarrhea at 4 weeks follow up (Prevalence Ratio [95% CI]) 0.65 (0.40, 1.07)
Proportion with severe diarrhea during follow-up (Prevalence Ratio [95% CI]) 1.15 (0.65, 2.05)
Proportion with diarrhea requiring hospitalization during follow-up (Prevalence Ratio [95% CI]) 1.03 (0.54, 1.98)
Proportion stunted (HAZ < −2 SD) at week 4 (Prevalence Ratio [95% CI]) 1.77 (1.00, 3.13)
Proportion wasted (WHZ < − 2 SD) at week 4 (Prevalence Ratio [95% CI]) 0.53 (0.16, 1.71)
Proportion underweight (WAZ < − 2 SD) at week 4 (Prevalence Ratio [95% CI]) 1.66 (0.83, 3.30)
 Dinleyici 2014 [52] ORS with L. reuteri 17,938 108 CFU ORS only Proportion with diarrhea at day 12 (Prevalence Difference [95% CI])xvii 0.17 (0.08, 0.26)
Therapeutic Micronutrients (Vitamin A and Zinc)
 Faruque 1999 [34] Vitamin A (4500 μg retinol equivalent daily for 15 days), zinc acetate (14.2 mg daily for 15 days),xviiior bothxix Placebo Proportion with diarrhea on day 7 (Prevalence Ratio [95% CI]) Zinc-supplemented vs. non-supplemented 0.64 (0.43, 0.96)
Vitamin A –supplemented vs. non-supplemented 0.78 (0.52, 1.49)
Proportion with diarrhea on day 16 (Prevalence Ratio [95% CI]) Zinc-supplemented vs. non-supplemented 0.67 (0.24, 1.85)
Vitamin A –supplemented group vs. non-supplemented 0.67 (0.24, 1.85)
 Khatun 2001 [22] Multivitamin syrup with 20 mg elemental zinc (twice daily for 7 days), or multivitamin syrup with Vitamin Axx or both Multivitamin syrup only Difference in change in weight at day 7 compared to day 1, gxxi Zinc group vs control 0.11 kg (p = 0.045)
Vitamin A group vs control 0.07 kg (p = 0.21)
Zinc+Vitamin A vs. control 0.06 kg (p = 0.074)
Proportion with diarrhea at day 7, (Prevalence Ratio [95% CI]) Zinc group vs. control 0.23 (0.08, 0.71)
Vitamin A group vs. control 0.92 (0.54, 1.59)
Zinc+Vitamin A vs. control 0.62 (0.31, 1.21)
Therapeutic Micronutrients (Zinc alone)
 Sazawal 1995 [23] Multivitamin syrup with 20 mg elemental zincxxii Multivitamin syrup only Proportion of episodes lasting longer than 7 days (Prevalence Ratio [95% CI]) 0.87 (0.65, 1.16)
Proportion of diarrhea episodes taken to a physician during follow up (Prevalence Ratio [95% CI]) 0.78 (0.57, 1.07)
 Roy 1998 [24] Multivitamin syrup with 20 mg elemental zinc, 14 days Multivitamin syrup only Mortality Relative Risk (95% CI) 0.18 (0.02, 1.49)
Risk Difference (95% CI) −0.05 (− 0.11, 0.01)
Change in weight at discharge, gxxiii Mean body weight in intervention group was maintained while body weight decreased in control group
Proportion with diarrhea after day 15 (RR [95% CI])xxiv 0.99 (0.53, 1.88)
 Bhutta 1999 [49] Multivitamin with 3 mg of elemental zinc per kg of body weight, 28 days Multivitamin only Difference in weight at day 7 and 14, kgxxv (95% CI) Day 7: −0.57 (−1.14, − 0.002)
Day 14: −0.46 (− 1.06, 0.14)
Difference in overall weight increment at day 14, g/kg/day 1.60 (− 1.48, 4.68)
Difference in MUAC at day 7 and 14, cm (95% CI) Day 7: −0.30 (− 0.98, 0.38)
Day 14: −0.40 (−1.08, 0.28)
Difference in overall MUAC increment, cm (95% CI) 0.00 (−0.13, 0.13)
 Roy 1999 [25] Multivitamin with 20 mg of elemental zinc, 14 days Multivitamin only Difference in weight gain at each week of 8 week follow up, g (95% CI) Week 1: 30 (−204.70, 264.73)
Week 2: −4 (− 202.60, 194.60)
Week 3: −45 (−303.70, 213.70)
Week 4: −60 (− 347.70, 227.70)
Week 5: −79 (−361.40, 203.40)
Week 6: −57 (− 354.38, 240.40)
Week 7: −53 (− 352.70, 246.70)
Week 8: −19.00 (− 394.15, 356.15)
Difference in gain in length at week 8, mm 4.40 mm, 30% greater gain (p < 0.03)xxvi
 Baqui 2002 [27] ORS with 20 mg zinc per day, 14 days ORS only Incidence of diarrhea during 2 year follow up RR (95% CI) 0.85 (0.76, 0.96)
RD (95% CI)xxvii 2.9 (0.80, 5.10)xxviii
Mortality during 2 year follow up RR (95% CI) 0.49 (0.25, 0.94)
RD (95% CI) 2.2 (0.60, 3.70)xxix
 Walker 2007 [53] ORS with 10 mg zinc, 14 days ORS with placebo Difference in weight at week 4 and 8, kg (95% CI) Week 4: 0.06 (−0.08, 0.20)
Week 8: 0.06 (− 0.08, 0.20)
Difference in length at week 4 and 8, cm (95% CI) Week 4: −0.09 (− 0.61, 0.43)
Week 8: −0.12 (− 0.63, 0.39)
Proportion of infants with ≥1 episode of any diarrhea (RR [95% CI])xxx 1.01 (0.92, 1.12)
Proportion of infants with ≥2 episode of any diarrhea (RR [95% CI]) 0.79 (0.67, 0.95)xxxi
Proportion of infants with ≥1 episode of dysentery (any day with blood in the stool) (RR [95% CI]) 2.10 (0.96, 4.61)
Incidence of diarrhea (episodes/month) Intervention group (mean ± SD) 0.62 ± 0.68
Control group (mean ± SD) 0.61 ± 0.70
Prevalence of diarrhea (days/mo) Intervention group (mean ± SD) 2.68 ± 4.11
Control group (mean ± SD) 2.20 ± 3.19
Mortality RR (95% CI) 0.99 (0.01, 77.9)
RD (95% CI)xxxii −0.18 (−66.42, 66.06)
 Roy 2007 [28] Multivitamin with 10 mg zinc per 5 ml, 14 days Multivitamin only Difference in mean number of diarrhea episodes during 6 mo follow up (95% CI)xxxiii − 0.33 (− 0.39, − 0.27)
Percent gain in length at 12 weeks, mmxxxiv Comparable between groups when all patient were compared (p = 0.6)
24% greater among underweight (WAZ ≤ 70% NCHS median) (p < 0.03)
Mortality RR (95% CI) 0.84 (0.29,2.37)
RD (95% CI) −0.01 (−0.10, 0.07)
 Roy 2008 [29] Multivitamin with 20 mg zinc, 14 days Multivitamin only Geometric mean diarrhea incidence Statistically significantly higher in control group (p = 0.03)
 Fajolu 2008 [48] 20 mg zinc for patients > 1 y; 10 mg zinc for patients < 1 y Placebo Number of subsequent diarrhea episodes during 2 month follow up Difference not significant (p = 0.53)
Weight gain at 2 months, g Higher in intervention group (p < 0.001)
 Larson 2010 [30] 10 days therapeutic zinc (20 mg) followed by 3 mo supplementary zinc (10 mg) 10 days therapeutic zinc (20 mg) followed by 3 mo supplementary zinc placebo Diarrhea episodes during follow up,xxxv months 1–3 Risk Difference, [95% CI]) −1.02 (0.26, 1.79)
Diarrhea episodes during follow up, months 4–6 (Risk Difference, [95% CI]) −0.37 (− 0.35, 1.07)
Diarrhea episodes during follow up, months 7–9 (Risk Difference, [95% CI]) −0.18 (− 0.41, 0.75)
Diarrhea episodes during entire 9 month follow up (Risk Difference, [95% CI]) −0.54 (0.07, 1.01)
 Alam 2011 [31] Short course zinc – 20 mg zinc, 5 days Standard course zinc – 20 mg zinc, 10 days Difference in mean number of diarrhea episodes during 3 month follow up (95% CI) 0.06 (− 0.07, 0.19)
Difference in mean number of days of diarrhea during 3 month follow up (95% CI) 0.2 (−0.35, 0.75)
Proportion of children with at least 1 episode of diarrhea during 3 month follow up (RR [95% CI]) 1.03 (0.95, 1.14)
Proportion of children with prolonged diarrhea (≥ 7 days) (Prevalence Ratio [95% CI])xxxvi 0.63 (0.50, 0.79)
Proportion of children with persistent diarrhea (≥ 14 days) (Prevalence Ratio [95% CI]) 0.63 (0.48, 0.81)
Day of onset of first subsequent diarrhea episode during follow up No difference between groupsxxxvii
 Patel 2013 [32] Zinc (2 mg/kg/day) or zinc + copper (Zn 2 mg/kg/day + Cu 0.2 mg/kg/day), 14 days Placebo Proportion with at least 1 diarrhea episode during 3 month follow up (Prevalence Ratio [95% CI]) Zinc group vs placebo 1.01 (0.76, 1.33)
Zinc + Copper group vs placebo 0.96 (0.72, 1.27)
Proportion with at least 2 episodes of diarrhea during 3 month follow upxxxviii (Prevalence Ratio [95% CI]) Zinc group vs placebo 2.25 (1.10, 4.63)
Zinc group vs Zinc + Copper group 1.12 (0.64, 1.97)
Proportion with at least 1 dysentery episode during 3 month follow up (Prevalence Ratio[95% CI]) Zinc group vs placebo 1.31 (0.30, 5.77)
Zinc group vs Zinc + Copper group 1.37 (0.31, 6.04)
Difference in mean number of subsequent diarrhea episodes per child during 3 month follow up (95% CI) Zinc group vs placebo 0.08 (−0.05, 0.21)
Zinc + copper group vs placebo 0.05 (−0.07, 0.17)
Difference in change in WAZ at month 3 (95% CI) Zinc group vs placebo −0.1 (− 0.12, 0.10)
Zinc + copper group vs placebo 0.06 (−0.04, 0.16)
Difference in change in WHZ at month 3 (95% CI) Zinc group vs placebo −0.01 (− 0.18, 0.16)
Zinc + copper group vs placebo 0.09 (−0.07, 0.25)
Difference in change in HAZ at month 3 (95% CI) Zinc group vs placebo 0.02 (−0.09, 0.13)
Zinc + copper group vs placebo 0.03 (−0.08, 0.14)
 Negi 2015 [33] Zinc (20 mg/day) for 14 days Placebo Risk of having at least 1 episode of diarrhea during 3 mo follow up (Relative risk [95%]) Among all subjects 0.65 (0.37, 1.23)
Among zinc-deficient subjects (n = 60) 0.65 (0.31, 1.38)
  1. iEstimate may be interpreted as 11 fewer deaths per 100 children in the intervention group compared to the control group
  2. iiQuantitative estimates not presented and reported p-values not specific to time-points of interest
  3. iiiData presented were assumed to be mean ± SD
  4. ivDuration of diets was variable. Diets were started at low concentrations and were advanced every 48 hours if no sign of intolerance. If there were signs of intolerance, diets were maintained or decreased as necessary. When full concentrations were reached, the diet was given for an additional 7 days.
  5. vAppropriate data for calculation of weight gain or difference in weight gain not presented
  6. viDefined as when diarrhea had ceased and patient had consistent weight gain for at least 48 hours
  7. viiAll outcome measurements were compared against measurements at entry, when the child had had diarrhea for 14 days
  8. viiiUnits were assumed to be cm/y due to description of results in the manuscript (rather than (cm/y)2 as presented in the study’s Four)
  9. ixDefined as age- and sex-specific weight standard deviation scores, from the National Center for Health Statistics median value
  10. xNo quantitative estimates given
  11. xiAll diets were equivalent in caloric and protein content
  12. xiiNo estimate or statistical significance given
  13. xiiiNo estimate or statistical significance given
  14. xivNo estimates or statistical significance is given
  15. xvConfidence interval states in manuscript is (0.605, 0.090) which does not contain the relative risk estimate of 0.812 therefore have assumed the 0.090 was a typo and replaced with 1.090.
  16. xviNo estimates or statistical significance given
  17. xviiRR was undefined due to a “0” cell
  18. xviiiThe authors changed the dose after 417 children were enrolled (dosages listed, analyzed as "standard strata" of subjects), and the remaining 273 children received a higher dose of zinc (analyzed as "high dose strata"): Vitamin A (4500 ug retinol equivalent daily for 15 days) and/or zinc acetate (40 mg daily for 15 days)
  19. xixResults from comparison of zinc+vitamin A vs. placebo not reported (reported on zinc effect by combing the zinc alone and zinc+vitamin A group and reported on vitamin A effect by combining vitamin A alone with the zinc+vitamin A group).
  20. xxVitamin A dosage was 100000 IU for children < 1 yo, and 200000 for children > 1 yo
  21. xxiNo SDs or CIs given for differences. P-value for the difference between zinc group and control is 0.045; for the difference between vitamin A group and control is 0.207; and for the difference between zinc + vitamin A group is 0.074.
  22. xxiiDuration of intervention is unclear
  23. xxiiiData were presented but were not interpretable due to an ambiguous or incorrect title
  24. xxivAssessed by proportion of patients with delayed recovery, with recovery defined as the passage of formed stool followed by 2 days without diarrhea
  25. xxvFor this and all outcomes, data were not labeled. Data presented were assumed to be mean and SD based on labeled data on another figure in the paper
  26. xxviNo SDs or CIs given. P< 0.05.
  27. xxviiDifference in mean diarrhea incidence rates. Estimate may be interpreted as 2.9 more episodes per 100 child-years of observation were experienced in the control group compared to the intervention group
  28. xxviiiCalculated values of lower and upper limits of 95% CI differed from what was represented in original publication
  29. xxixDifference in mean mortality rates. Estimate may be interpreted as 2.2 more deaths per 1000 child years of observation experienced by the control group compared to the intervention group
  30. xxxAll data presented are unadjusted. The authors’ results are discrepant from this table’s results, as authors adjust for original diarrhea episode lasting > 7 days, exclusive breastfeeding upon enrollment, and WLZ at beginning of follow up
  31. xxxiCalculated values of lower and upper limits of 95% CI use data presented on unadjusted proportions and differed from what was represented in original publication
  32. xxxiiEstimate may be interpreted as 0.18 deaths fewer in intervention group per 100,000 child-weeks of observation compared to control group
  33. xxxiiiData presented was assumed to be mean ± SD
  34. xxxivQuantitative estimates not presented
  35. xxxvRisk differences may be interpreted as excess number of acute diarrhea episodes per child-year attributed to lack of zinc supplementation
  36. xxxviThe authors reported "The proportion of prolonged (>=7 d) and persistent diarrhea episodes (>=14 d) did not vary between the 5-d (19 vs. 16%; P 0.08) and 10-d (12 vs. 10%; P = 0.14) groups" which suggests the p-values correspond to the comparison of persistent and prolonged among children treated with 5-days and among children treated with 10-days. We have instead assumed the appropriate comparisons are proportion of prolonged (19% vs. 12%, p-value=0.0001) and persistent (16% vs. 10%, p-value=0.0004) which would result in statistically significant differences (unlike what was reported).
  37. xxxviiNo estimates or statistical significance given
  38. xxxviiiEstimates calculated for relative risk of at least 1, 2, or dysenteric diarrhea episodes are discrepant from published results