Participant Data Meta-analysis Of Studies Research Articles

Development of 24-hour rhythms in cortisol secretion across infancy: a systematic review and meta-analysis of individual participant data.

In adults, cortisol levels show a pronounced 24-hour rhythm with a peak in the early morning. It is unknown at what age this early-morning peak in cortisol emerges during infancy, hampering the establishment of optimal dosing regimens for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency. Therefore, we aimed to characterize daily variation in salivary cortisol concentration across the first year of life. We conducted a systematic review followed by an individual participant data meta-analysis of studies reporting on spontaneous (i.e., not stress induced) salivary cortisol concentrations in healthy infants aged 0-1 year. A one-stage approach using linear mixed-effects modelling was used to determine the interaction between age and time of day on cortisol concentrations. Through the systematic review, 54 eligible publications were identified, reporting on 29,177 cortisol observations. Individual participant data were obtained from 15 study cohorts, combining 17,079 cortisol measurements from 1,904 infants. The morning/evening cortisol ratio increased significantly from 1.7 (95% CI: 1.3-2.1) at birth to 3.7 (95% CI: 3.0-4.5) at 6-9 months (p < 0.0001). Cosinor analysis using all available data revealed the gradual emergence of a 24-hour rhythm during infancy. The early-morning peak in cortisol secretion gradually emerges from birth onwards to form a stable morning/evening ratio from age 6-9 months. This might have implications for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency.

Accuracy of self-assessment in gastrointestinal endoscopy: a systematic review and meta-analysis.

Assessment is necessary to ensure both attainment and maintenance of competency in gastrointestinal (GI) endoscopy, and this can be accomplished through self-assessment. We conducted a systematic review with meta-analysis to evaluate the accuracy of self-assessment among GI endoscopists. This was an individual participant data meta-analysis of studies that investigated self-assessment of endoscopic competency. We performed a systematic search of the following databases: Ovid MEDLINE, Ovid EMBASE, Wiley Cochrane CENTRAL, and ProQuest Education Resources Information Center. We included studies if they were primary investigations of self-assessment accuracy in GI endoscopy that used statistical analyses to determine accuracy. We conducted a meta-analysis of studies using a limits of agreement (LoA) approach to meta-analysis of Bland-Altman studies. After removing duplicate entries, we screened 7138 records. After full-text review, we included 16 studies for qualitative analysis and three for meta-analysis. In the meta-analysis, we found that the LoA were wide (-41.0 % to 34.0 %) and beyond the clinically acceptable difference. Subgroup analyses found that both novice and intermediate endoscopists had wide LoA (-45.0 % to 35.1 % and -54.7 % to 46.5 %, respectively) and expert endoscopists had narrow LoA (-14.2 % to 21.4 %). GI endoscopists are inaccurate in self-assessment of their endoscopic competency. Subgroup analyses demonstrated that novice and intermediate endoscopists were inaccurate, while expert endoscopists have accurate self-assessment. While we advise against the sole use of self-assessment among novice and intermediate endoscopists, expert endoscopists may wish to integrate it into their practice.

Salt intake and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.

Growth Disorders in Twins: An Individual Participant Data Meta-Analysis of Perinatal Mortality

In uncomplicated dichorionic (DC) and monochorionic (MC) twin pregnancies with normally grown fetuses, the optimal time of delivery is 37 and 36 weeks, respectively. The influence of growth discordance on the optimal time of birth, with or without small for gestational age (SGA, < 10th centile), is unknown. We aimed to determine the optimal timing of birth by evaluating the rates of stillbirth (SB) and neonatal death (NND) in women with DC and MC twins with different levels of growth discordance and in relation to SGA. We performed an Individual Participant Data Meta-Analysis of studies reporting rates of SB and NND in women with twin pregnancies from 34-41 weeks (PROSPERO ID: CRD42018090866). Monoamniotic twin pregnancies were excluded. The prospective risk of perinatal death was calculated as the difference between the prospective risk of SB and risk of NND per gestational week. Analyses were stratified by chorionicity, different intervals of growth discordance and presence of SGA in one or both twins. We did not analyse data about associated obstetric complications or abnormal ultrasound findings. We included 20 studies reporting on 7474 women with DC and 2281 women with MC twin pairs. For both DC and MC twins the absolute risks of SB and NND were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance or presence of SGA, women with DC and MC twins had higher risk of SB than NND from 37 weeks onwards (Fig. 1, Fig. 2). For MC twins, the nadir was between 36-37 weeks. The nadir for perinatal mortality risk for women with DC twins with growth discordance or SGA is around 37 weeks. For MC twins this is between 36-37 weeks, favouring delivery from 37 weeks onward. Growth discordance or SGA is associated with higher absolute SB and neonatal risks but does not largely influence the optimal timing of birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Using data from food challenges to inform management of consumers with food allergy: A systematic review with individual participant data meta-analysis

BackgroundEliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown.ObjectiveOur aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge.MethodsWe conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists.ResultsA total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis.ConclusionAround 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population of individuals with peanut allergy.

Accuracy of the PHQ-2 Alone and in Combination With the PHQ-9 for Screening to Detect Major Depression

The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9. To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018). Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview. Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27. Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%). In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.

Meat intake and risk of gastric cancer in the Stomach cancer Pooling (StoP) project.

The consumption of processed meat has been associated with noncardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Our study aims to quantify the association between meat consumption, namely white, red and processed meat, and the risk of gastric cancer, through individual participant data meta-analysis of studies participating in the "Stomach cancer Pooling (StoP) Project". Data from 22 studies, including 11,443 cases and 28,029 controls, were used. Study-specific odds ratios (ORs) were pooled through a two-stage approach based on random-effects models. An exposure-response relationship was modeled, using one and two-order fractional polynomials, to evaluate the possible nonlinear association between meat intake and gastric cancer. An increased risk of gastric cancer was observed for the consumption of all types of meat (highest vs. lowest tertile), which was statistically significant for red (OR: 1.24; 95% CI: 1.00-1.53), processed (OR: 1.23; 95% CI: 1.06-1.43) and total meat (OR: 1.30; 95% CI: 1.09-1.55). Exposure-response analyses showed an increasing risk of gastric cancer with increasing consumption of both processed and red meat, with the highest OR being observed for an intake of 150 g/day of red meat (OR: 1.85; 95% CI: 1.56-2.20). This work provides robust evidence on the relation between the consumption of different types of meat and gastric cancer. Adherence to dietary recommendations to reduce meat consumption may contribute to a reduction in the burden of gastric cancer.

Antiplatelet Agents and the Prevention of Spontaneous Preterm Birth: A Systematic Review and Meta-analysis.

Spontaneous preterm birth is an important cause of neonatal mortality and morbidity. An increasing body of evidence suggests that uteroplacental ischemia plays an important role in the etiology of spontaneous preterm birth. We aimed to study whether antiplatelet agents reduce the risk of spontaneous preterm birth. We included data from an individual participant data meta-analysis of studies that had evaluated the effect of antiplatelet agents to reduce preeclampsia (Perinatal Antiplatelet Review of International Studies Individual Participant Data). The meta-analysis included 31 studies that randomized women to low-dose aspirin-dipyridamole or placebo-no treatment as a primary preventive strategy for preeclampsia. For the current study we analyzed data from 17 trials (28,797 women) that supplied data on type of delivery (spontaneous compared with indicated birth). Primary endpoints were spontaneous preterm birth at less than 37 weeks, less than 34 weeks, and less than 28 weeks of gestation. We analyzed outcomes for each trial separately using χ statistics and combined in an individual participant data meta-analysis using a binary logistic regression model. Women assigned to antiplatelet treatment compared with placebo or no treatment had a lower risk of spontaneous preterm birth at less than 37 weeks (relative risk [RR] 0.93, 95% confidence interval [CI] 0.86-0.996) and less than 34 weeks of gestation (RR 0.86, 95% CI 0.76-0.99). The RR of having a spontaneous preterm birth at less than 37 weeks of gestation was 0.83 (95% CI 0.73-0.95) for women who have had a previous pregnancy and 0.98 (95% CI 0.89-1.09) for women in their first pregnancy. The treatment effect was stable in all other prespecified subgroups. Antiplatelet agents reduce spontaneous preterm birth in pregnant women at risk for preeclampsia.