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Ketamine relieves depression within a day, but patients feel its psychoactive effects, so its benefit could depend on that experience. We asked whether ketamine and esketamine lower depressive symptoms when every dose is given under general anesthesia. Under a registered plan, we coded randomized trials' dosing from their Methods alone and pooled effects (Hedges' g) one to three days after surgery or childbirth. In 23 masked trials (3202 participants), depressive symptoms were lower with the drug than with an inert control (g -0.61, confidence interval -0.81 to -0.4; Holm-adjusted p < 0.001), though trials varied widely. Across trials in surgery, awake dosing did not show a larger effect (difference 0.12, -0.24 to 0.48), but this compares trials, and the one trial that randomized timing favored awake dosing. Masked doses also lowered pain. Ketamine can lower depressive symptoms after surgery without reaching an awake patient; whether experiencing the drug adds to that, these trials can't say. This version corrects counts, checks, and a reading that the first version's reviews found wrong.

• Published, Reproduced.Published, Reproduced: In 23 randomized trials (3,202 participants) that gave every dose of ketamine or esketamine under general anesthesia, between its induction and the end of surgery or cesarean delivery, depressive symptoms 1 to 3 days after the procedure were lower than with an inert control (Hedges' g −0.61, 95% CI −0.81 to −0.40; Holm-adjusted p < 0.001), though the trials varied widely (95% prediction interval −1.51 to 0.29). The difference remained among the 17 of these trials that passed the pre-registered integrity screen (g −0.48, −0.63 to −0.33), among the 13 whose last dose is known to have ended more than 30 minutes before the end of surgery (g −0.67, −1.04 to −0.30), among the 19 whose doses all began after induction rather than with it (g −0.60, −0.85 to −0.36), and with any single trial left out (largest p < 0.001).
• Published, Reproduced.Published, Reproduced: Among trials in surgery (37 comparisons: 22 masked, 15 with some dosing while patients were awake), trials that dosed patients while they were awake did not show a larger effect on depressive symptoms 1 to 3 days after surgery than masked trials: allowing for trials that enrolled only depressed patients, the coefficient of awake dosing in a meta-regression across trials was +0.12 (95% CI −0.24 to 0.48; p = 0.51), and the pooled effects in surgery were g −0.62 with masked and −0.45 with awake dosing. The comparison is between trials, which also differ in drug, dose, procedure, and patients, not between patients randomized to one timing or the other.
• Published, Reproduced.Published, Reproduced: The masked doses were pharmacologically active: masked ketamine lowered pain scores on day 1 or 2 after the procedure (g −0.55, 95% CI −0.97 to −0.14; 22 trials; g −0.38, −0.54 to −0.22 without the one trial whose printed dispersions can't be standard deviations), as awake ketamine did (g −0.33, −0.54 to −0.11; 32 trials; awake minus masked in surgery +0.32, −0.21 to 0.86). Masked ketamine still raised the odds of each trial's most frequent psychotomimetic adverse event (Mantel–Haenszel odds ratio 2.11, 1.48 to 2.99, in 22 trials), and awake ketamine raised them more (3.63, 2.97 to 4.43, in 40 trials): p = 0.0083 for the difference in the registered comparison, and p = 0.21 when the odds ratio may vary between trials (ratio of odds ratios 1.69, 0.74 to 3.84).

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An observational atlas linked GLP-1 receptor agonists to dozens of outcomes beyond glucose, weight and the heart. We pooled the serious adverse events that 234 placebo-controlled trials, with 161309 participants, posted to ClinicalTrials.gov, coded blind to the results under a registered plan. Reports of serious bacterial infection (ratio 0.88, confidence interval 0.83 to 0.93) and pneumonia (0.87) were less frequent on the drugs, as were pneumonia counted in people and death. The reductions held under random effects, with any trial left out, if infection terms overlapped within participants as all serious events do in each comparison, and in trials not coded as recording only on treatment. Of the atlas's associations with enough events to test, the trials found three in its direction with no difference from it detected, contradicted none, and left most inconclusive, among them every neurological and psychiatric one; its large hazard of drug-induced pancreatitis concerns a subtype the trials don't separate.

• Published, Reproduced.Published, Reproduced: Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants in their adverse-event tables (93,765 on the drugs and 67,544 on placebo). In them, reports of serious gallbladder and biliary disease, counting a participant once for each of the outcome's terms they had, are more frequent on the drugs (Mantel-Haenszel ratio 1.38, 95% CI 1.21 to 1.57), and so are reports of serious nausea and vomiting (2.02, 1.52 to 2.68), as the trials' own publications and the drugs' labels lead one to expect.
• Published, Reproduced.Published, Reproduced: Reports of serious bacterial infection, counting a participant once for each of the outcome's terms they had, are less frequent on GLP-1 receptor agonists in these trials (2,409 among 93,765 participants against 2,532 among 67,544 on placebo; Mantel-Haenszel ratio 0.88, 95% CI 0.83 to 0.93, q < 0.001), and so are reports of serious pneumonia (1,442 against 1,568; 0.87, 0.81 to 0.93, q = 0.0020); both stay significant under random effects and with any single trial left out. Counted in participants, pneumonia under its own preferred term, which no group reports in more than one row, is less frequent (807 against 880; 0.86, 0.79 to 0.95). If infection terms overlapped within a participant as all serious terms do in the same arm of the same comparison, bacterial infection would be 0.89 (0.82 to 0.97).
• Published, Reproduced.Published, Reproduced: In the registered scan without hypotheses of 27 organ systems and 518 preferred terms, with the same variance as the other claims, four organ systems (cardiac disorders; infections and infestations; metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders) and two preferred terms (acute myocardial infarction and cellulitis) are lower on the drugs with q < 0.05 in a random half of the trials and p < 0.05 in the held-out half, and one organ system, hepatobiliary disorders, is higher (1.36 in the first half, 1.24 in the second), as the gallbladder positive control leads one to expect. Among those lower are serious infection reports as a whole (0.88 and 0.89) and cellulitis (0.64 and 0.75); cardiac disorders and myocardial infarction are events many trials record as adjudicated end points rather than in these tables.

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The World Health Organization's 2020 guideline recommended giving mass azithromycin, which lowers child mortality in high-mortality settings of sub-Saharan Africa, only to infants, to limit antibiotic resistance; no trial had then tested that. Under a pre-registered plan we pooled every randomized trial by whom it treated. Treating all children under five lowered their mortality by 14.1% (CI 7.4% to 20.3%), consistently across trials. In the three trials that treated only infants, infant mortality was not detectably lower (rate ratio 0.971, CI 0.867 to 1.086), an interval that excludes the effect of treating all children. Infants had lower mortality when all children were treated, though a between-trial comparison of the two strategies fell short of significance, and giving azithromycin to individual infants at clinic visits showed no effect. The infant-only approach has not lowered mortality in any trial that tested it; treating all children under five has.

• Published, Reproduced.Published, Reproduced: In 5 placebo-controlled comparisons from 3 cluster-randomized trials (MORDOR in Niger, Malawi and Tanzania; AVENIR in Niger; CHAT in Burkina Faso), twice-yearly mass azithromycin to every child 1 to 59 months old lowered mortality among children 1 to 59 months by 14.1% (rate ratio 0.859, 95% CI 0.797 to 0.926; Holm-corrected p = 0.015; I² = 0%), and the reduction held with a common-effect model (0.859, 0.813 to 0.908) and with any one comparison left out (largest p = 0.044).
• Published, Reproduced.Published, Reproduced: In the 3 cluster-randomized trials that gave azithromycin twice a year to infants 1 to 11 months old only, the approach the World Health Organization recommended in 2020 (AVENIR's infant arm in Niger, LAKANA in Mali, MIRAMA in Burkina Faso), infant mortality was not detectably lower than with placebo (rate ratio 0.971, 95% CI 0.867 to 1.086; p = 0.370), an interval that rules out a reduction larger than 13.3% and so excludes the 14.1% reduction seen when all children 1 to 59 months were treated; the estimate stayed near 1 with LAKANA's four-times-yearly arm instead (0.948, 0.856 to 1.050), without MIRAMA (0.963, 0.656 to 1.413), and with the 2 individually randomized infant trials added (0.969, 0.881 to 1.066).
• Published, Reproduced.Published, Reproduced: Infant mortality was lower when all children 1 to 59 months were treated (rate ratio 0.823, 95% CI 0.707 to 0.958; 3 comparisons) than when only infants were (0.971), but the pre-registered meta-regression comparing the two strategies across trials did not establish a difference (ratio of rate ratios 1.187, 95% CI 0.974 to 1.447; p = 0.074; Holm-corrected p = 0.148); AVENIR's within-trial contrast of its all-children arm against its infant arm, estimated after registration from the two arms' printed mortality rates, was 0.830 (0.717 to 0.959).

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