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Table 2 Characteristics and quantitative synthesis of the eligible MAs of MLT for health

From: Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action

First author (year) [reference] Health outcome No of participants included in MA No of primary studies included in MA Reported effect size Random-effects summary effect size (95% CI) P random Fixed-effects summary effect size (95% CI) P fixed 95% PI I2 (%) Estimate of the study with lowest SE in MA (95% CI)1 Small-study effects/excess statistical significance
Addiction
 Wright2 (2015) [36] Withdrawal symptoms 244 4 OR 1.39 (0.42, 4.65) 0.594 1.11 (0.65, 1.90) 0.694 0.01, 277.67 75.9 1.00 (0.37, 2.67) No/No
Cancer
 Basler (2014) [68] Risk of breast cancer 1650 5 RR 0.82 (0.68, 0.99) 0.043 0.82 (0.71, 0.95) 0.01 0.50, 1.34 31.7 0.81 (0.64, 1.02) No/No
 Wang (2012) [31] 761 8 RR 1.95 (1.49, 2.54) 0.0001 1.96 (1.50, 2.56) 0.0001 1.40, 2.71 0 2.25 (1.39, 3.64) No/No
 Wang (2012) [31] 590 5 RR 1.90 (1.28, 2.83) 0.0002 1.82 (1.49, 2.24) 0.0001 0.56, 6.47 61.9 1.26 (0.97, 1.65) No/No
Delirium
 Chen (2015) [35] Incidence of delirium 669 4 RR 0.41 (0.15, 1.13) 0.084 0.73 (0.55, 0.95) 0.021 0.01, 35.8 83.8 1.16 (0.83, 1.61) Yes/No
Dementia
 Jansen3 (2009) [30] Cognition 121 2 MD –2.64 (–5.99, 0.71) 0.123 –2.12 (–3.82, 0.42) 0.015 68.6 –1.15 (–3.16, 0.86) –/No
 Jansen (2009) [30] Mood and behaviour 150 3 MD 0.18 (–0.73, 1.10) 0.698 0.18 (–0.73, 1.10) 0.698 –5.76, –6.12 0 –0.01 (–1.08, 1.06) No/No
Depression/mood disorders
 De Crescenzo (2017) [127] Mood disorders 181 3 SMD 0.37 (–0.05, 0.78) 0.087 0.39 (0.08, 0.70) 0.013 –3.74, 4.47 43 0.32 (–0.14, 0.78) No/No
 Guaiana (2013) [34] Response to treatment 3826 10 RR 1.01 (0.95, 1.08) 0.749 1.00 (0.95, 1.06) 0.881 0.87. 1.17 31.4 1.04 (0.93, 1.15) No/Yes
 Huang (2014) [65] 1871 6 RR 1.07 (1.02, 1.13) 0.01 1.08 (1.03, 1.15) 0.005 0.99, 1.16 0 1.04 (0.93, 1.15) No/No
 Guaiana (2013) [34] Remission 3826 10 RR 0.83 (0.68, 1.02) 0.069 0.87 (0.80, 0.94) 0.0007 0.43, 1.59 77.8 0.95 (0.85, 1.06) No/No
 Huang (2014) [65]   1742 5 RR 1.11 (1.01, 1.23) 0.035 1.12 (1.01, 1.24) 0.038 0.95, 1.31 0 1.09 (0.93, 1.27) No/No
 Hansen3 (2014) [65] Hospital Anxiety and Depression Scale 74 2 MD 0.97 (–0.84, 2.78) 0.293 0.93 (–0.42, 2.28) 0.178 44 0.10 (–1.72, 1.92) –/No
 Hansen3 (2014) [65] Beck Depression Inventory 91 2 MD –1.09 (–2.60, 0.42) 0.157 –1.09 (–2.60, 0.42) 0.157 0 –1.00 (–2.54, 0.54) –/No
Infertility
 Seko (2014) [25] Pregnancy rate 680 5 RR 1.21 (0.98, 1.49) 0.071 1.21 (0.98, 1.50) 0.071 0.86, –1.70 0 1.13 (0.85, 1.51) No/No
 Seko (2014) [25] Oocytes retrieved 680 5 MD 0.57 (–0.22, 1.35) 0.155 0.23 (–0.12, 0.8) 0.2 –1.91, –3.04 68.7 –0.07 (–0.57, 0.43) Yes/No
Pre- and post-operative care
 Andersen (2014) [33] Pre-operative anxiety 761 11 SMD –0.88 (–1.33, –0.44) <0.0001 –0.91 (–1.07, –0.75) <0.0001 –2.53, –0.76 86.7 0.00 (–0.33, 0.33) No/No
 Hansen3 (2015) [169] 122 2 MD –1.18 (–2.59, 0.23) 0.1 –1.18 (–2.59, 0.23) 0.1 0 –1.30 (–2.76, 0.16) –/No
 Hansen3 (2015) [169] Post-operative anxiety 73 2 MD –5.31 (–8.78, –1.84) 0.003 –5.31 (–8.78, –1.84) 0.003 0 –5.40 (–10.12, –0.68) –/No
 Andersen (2014) [33] Post-operative pain 524 8 SMD –1.06 (–1.89, –0.24) 0.012 –0.12 (–0.30, 0.07) 0.205 –3.97, 1.85 94.2 0.43 (0.09, 0.77) Yes/No
 Mihara (2015) [41] Prevention of agitation 170 3 RR 0.31 (0.16, 0.60) <0.0001 0.29 (0.15, 0.56) <0.0001 0.00, 23.06 0 0.40 (0.18, 0.89) No/Yes
Safety
 Liu (2012) [40] Adverse effects 2912 7 RR 1.10 (1.02, 1.20) 0.009 1.11 (1.03, 1.20) 0.006 1.02, 1.20 0 1.13 (0.97, 1.31) No/Yes
Primary sleep disorders
 Liu3 (2012) [40] Sleep latency 405 1 (with six subgroups) MD –14.26 (–18.54, –9.98) <0.0001 –14.26 (–18.54, –9.98) <0.0001 –20.32, –8.19 0 –16.70 (–26.82, –6.58) –/NE
 Kuriyama (2014) [39] 5781 12 WMD –4.15 (–6.82, –1.47) 0.002 –3.30 (–4.88, –1.71) <0.0001 –11.69, 3.39 52.2 –2.40 (–5.28, 0.48) No/No
 Liira (2014) [38] 148 5 MD –0.15 (–2.48, 2.18) 0.899 –0.41 (–2.32, 1.50) 0.674 –5.64, 5.34 21.6 –1.10 (–3.83, 1.63) Yes/No
 Liira (2014) [38] 266 7 MD 24.30 (9.80, 38.80) 0.001 24.30 (9.80, 38.80) 0.001 5.29, 43.32 0 23.00 (–3.13, 49.13) No/No
 Kuriyama (2014) [39] Sleep quality 5812 13 SMD –0.08 (–0.13, –0.03) 0.003 –0.08 (–0.13, –0.03) 0.003 –0.14, –0.02 0 –0.15 (–0.27, –0.02) No/No
 Zhang3 (2016) [157] 18 1 MD 4.20 (0.92, 7.48) 0.012 4.20 (0.92, 7.48) 0.012 4.20 (0.92, 7.48) –/No
Animal studies
 Yang (2016) [32] Spinal cord injury 90 6 MD 1.52 (0.06, 2.98) 0.041 1.29 (0.82, 1.77) <0.0001 –3.69, 6.73 89 0.16 (–0.88, 1.20) Yes/No
  1. CI confidence interval, MA meta-analysis, MD mean difference, MLT melatonin, NE not estimable, OR odds ratio, PI prediction interval, RR risk ratio, SE standard error, SMD standardised mean differences, WMD weighted mean differences
  2. 1Estimate of the largest study with lowest SE from random-effect model
  3. 2Estimates did not match with forest plot in the article
  4. 3The 95% prediction interval and the evidence of small-study effects were calculated for those MAs where ≥3 studies combined (it cannot be calculated for less than three studies as degrees of freedom will be zero for two studies and negative for one study)