Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis

Abstract BACKGROUND Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age. OBJECTIVE AND RATIONALE The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1–18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls. SEARCH METHODS PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as ‘offspring’ and ‘PCOS’ were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (β) as outcome. OUTCOMES Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (β = 0.21(95%CI: 0.01–0.41), P = 0.05), insulin-resistance (β = 0.21(95%CI: 0.01–0.42), P = 0.04), triglycerides (β = 0.19(95%CI: 0.02–0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (β = 0.31(95%CI: 0.08–0.54), P < 0.01), but a reduced birthweight (β = −116(95%CI: −195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (βf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((βm) = −0.20(95%CI: −0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein–cholesterol differences in OPCOS versus controls were lower among females (βf = −0.39(95%CI: −0.62 to 0.16)), but comparable between male OPCOS and male controls (βm = 0.27(95%CI: −0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (βf = −0.31(95%CI: −0.57 to 0.06), βm = 0.28(95%CI: −0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (βf = 0.53(95%CI: 0.18–0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (βm = 0.13(95%CI: −0.05−0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: βf = −0.14(95%CI: −1.05 to 0.77)) or males (OPCOS versus controls: βm = 0.85(95%CI: −0.10 to 1.79)), with P-value < 0.01. WIDER IMPLICATIONS We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may—next to a genetic predisposition—influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood.

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Arthroscopic meniscectomy versus non-surgical or sham treatment in patients with MRI confirmed degenerative meniscus lesions: a protocol for an individual participant data meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-031864 ◽

2020 ◽

Vol 10 (3) ◽

pp. e031864

Author(s):

Stan R W Wijn ◽

Maroeska M Rovers ◽

Jan J Rongen ◽

Håvard Østerås ◽

May A Risberg ◽

...

Keyword(s):

Surgical Treatment ◽

Meta Analysis ◽

Trial Data ◽

Individual Participant Data ◽

Sham Treatment ◽

Meniscus Tears ◽

Meniscus Lesions ◽

Individual Participant ◽

The Difference ◽

Non Surgical Treatment

IntroductionArthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients thatdoneed APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment.Methods and analysisAn existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with knee symptoms and degenerative meniscus tears. Time and effort will be spent in contacting principal investigators of the original trials and encourage them to collaborate in this project by sharing their trial data. All individual participant data will be validated for missing data, internal data consistency, randomisation integrity and censoring patterns. After validation, all datasets will be combined and analysed using a one-staged and two-staged approach. The RCTs’ characteristics will be used for the assessment of clinical homogeneity and generalisability of the findings. The most important outcome will be the difference between APM and control groups in knee pain, function and quality of life 2 years after the intervention. Other outcomes of interest will include the difference in adverse events and mental health.Ethics and disseminationAll trial data will be anonymised before it is shared with the authors. The data will be encrypted and stored on a secure server located in the Netherlands. No major ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal.PROSPERO registration numberCRD42017067240.

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Initial severity of depression and efficacy of cognitive–behavioural therapy: Individual-participant data meta-analysis of pill-placebo-controlled trials

The British Journal of Psychiatry ◽

10.1192/bjp.bp.116.187773 ◽

2017 ◽

Vol 210 (3) ◽

pp. 190-196 ◽

Cited By ~ 25

Author(s):

Toshi A. Furukawa ◽

Erica S. Weitz ◽

Shiro Tanaka ◽

Steven D. Hollon ◽

Stefan G. Hofmann ◽

...

Keyword(s):

Major Depression ◽

Meta Analysis ◽

Behavioural Therapy ◽

Controlled Trials ◽

Individual Participant Data ◽

Baseline Severity ◽

Cognitive Behavioural ◽

Individual Participant ◽

Initial Severity ◽

The Difference

BackgroundThe influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive–behavioural therapy (CBT) in comparison with pill placebo.AimsTo synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression.MethodA systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data.ResultsWe identified five RCTs, and we were given access to individual-level data (n= 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interactionP= 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of −0.22 (95% CI −0.42 to −0.02,P= 0.03,I2= 0%).ConclusionsPatients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.

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Variability of glucose, insulin, and lipid disturbances in first-episode psychosis: a meta-analysis

Psychological Medicine ◽

10.1017/s0033291721005213 ◽

2022 ◽

pp. 1-7

Author(s):

Toby Pillinger ◽

Robert A. McCutcheon ◽

Oliver D. Howes

Keyword(s):

Insulin Resistance ◽

Total Cholesterol ◽

Meta Analysis ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Metabolic Parameters ◽

First Episode ◽

Fasting Insulin ◽

Metabolic Outcomes ◽

Episode Psychosis

Abstract Background First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation. Methods We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change. Results Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12–1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10–1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09–1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12–1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06–1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01–1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09–1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00–1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes. Conclusions Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.

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Comparison of different scoring methods based on latent variable models of the PHQ-9: an individual participant data meta-analysis

Psychological Medicine ◽

10.1017/s0033291721000131 ◽

2021 ◽

pp. 1-12

Author(s):

Felix Fischer ◽

Brooke Levis ◽

Carl Falk ◽

Ying Sun ◽

John P. A. Ioannidis ◽

...

Keyword(s):

Latent Variable ◽

Meta Analysis ◽

Factor Models ◽

Validation Dataset ◽

Individual Participant Data ◽

Two Dimensional ◽

Calibration Dataset ◽

Sum Score ◽

Individual Participant ◽

Screening Accuracy

Abstract Background Previous research on the depression scale of the Patient Health Questionnaire (PHQ-9) has found that different latent factor models have maximized empirical measures of goodness-of-fit. The clinical relevance of these differences is unclear. We aimed to investigate whether depression screening accuracy may be improved by employing latent factor model-based scoring rather than sum scores. Methods We used an individual participant data meta-analysis (IPDMA) database compiled to assess the screening accuracy of the PHQ-9. We included studies that used the Structured Clinical Interview for DSM (SCID) as a reference standard and split those into calibration and validation datasets. In the calibration dataset, we estimated unidimensional, two-dimensional (separating cognitive/affective and somatic symptoms of depression), and bi-factor models, and the respective cut-offs to maximize combined sensitivity and specificity. In the validation dataset, we assessed the differences in (combined) sensitivity and specificity between the latent variable approaches and the optimal sum score (⩾10), using bootstrapping to estimate 95% confidence intervals for the differences. Results The calibration dataset included 24 studies (4378 participants, 652 major depression cases); the validation dataset 17 studies (4252 participants, 568 cases). In the validation dataset, optimal cut-offs of the unidimensional, two-dimensional, and bi-factor models had higher sensitivity (by 0.036, 0.050, 0.049 points, respectively) but lower specificity (0.017, 0.026, 0.019, respectively) compared to the sum score cut-off of ⩾10. Conclusions In a comprehensive dataset of diagnostic studies, scoring using complex latent variable models do not improve screening accuracy of the PHQ-9 meaningfully as compared to the simple sum score approach.

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