METHODS: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment.
RESULTS: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen.
CONCLUSIONS: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN.
METHODS: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
RESULTS: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
CONCLUSIONS: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
OBJECTIVE: To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.
METHODS: We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.
RESULTS: In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).
CONCLUSIONS: Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics.