Integration of observational and causal evidence for the association between adiposity and 17 gastrointestinal outcomes: An umbrella review and meta-analysis.

We systematically reviewed observational and Mendelian randomization (MR) articles that evaluated the association between obesity and 17 gastrointestinal (GI) diseases to integrate causal and observational evidence. A total of 594 observational studies from 26 systematic reviews and meta-analyses and nine MR articles were included. For every 5 kg/m2 increase in body mass index (BMI), there was an increased risk of GI diseases ranging from 2% for rectal cancer (relative risk [RR]: 1.02, 95% confidence interval [CI]: 1.01 to 1.03) to 63% for gallbladder disease (RR: 1.63, 95% CI: 1.50 to 1.77). MR articles indicated that risks of developing GI diseases elevated with each 1 standard deviation increase in genetically predicted BMI, ranging from 11% for Crohn's disease to 189% for nonalcoholic fatty liver disease. Moreover, upper GI conditions were less susceptible, whereas hepatobiliary organs were more vulnerable to increased adiposity. Among the associations between obesity and the 17 GI conditions, causal relationships were inferred from only approximately half (10/17, 59%). This study reveals a substantial gap between observational and causal evidence, indicating that a combined approach is necessary to effectively inform public health policies and guide epidemiological research on obesity and GI diseases.

Prenatal and infant exposure to antibiotics and subsequent risk of neuropsychiatric disorders in children: A nationwide birth cohort study in South Korea.

We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study(infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05-1.08]) and postnatal life (1.05 [1.03-1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09-1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05-1.08]) and severe outcomes (1.17 [1.09-1.26]), especially for intellectual disability (1.12 [1.07-1.17]), ADHD (1.10 [1.07-1.13]), anxiety (1.06 [1.02-1.11]), mood (1.06 [1.00-1.12]), and autism (1.03 [1.01-1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6-12) and 12 % (7-17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription.

Association between sedentary behavior and wish to die among adults aged ≥50 years: Findings from the Irish Longitudinal Study on Ageing.

We investigated the association between sedentary behavior (SB) and wish to die (WTD; i.e., feeling that one would be better off dead or wishing for one's own death), and the extent to which this can be explained by sleep problems, depression, anxiety, loneliness, perceived stress, and social network in a nationally representative sample of adults aged ≥50 years from Ireland. Cross-sectional data from Wave 1 of the Irish Longitudinal Study on Ageing 2009-2011 were analyzed. WTD was defined as answering affirmatively to the question "In the last month, have you felt that you would rather be dead?" SB was used as a continuous variable (hours/day), and also as a categorical (< or ≥8 h/day) variable. Multivariable logistic regression and mediation analyses were conducted. Data on 8163 adults aged ≥50 years were analyzed [mean (SD) age 63.6 (9.1) years; 48.0% males]. Overall, ≥8 (vs. <8) hours/day of SB was associated with a significant 2.04 (95%CI = 1.50-2.76) times higher odds for WTD, while a 1-h increase in SB per day was associated with 1.11 (95%CI = 1.06-1.16) times higher odds for WTD. Mediation analysis showed that sleep problems, depression, loneliness, perceived stress, and social network explained a modest proportion of the association between SB and WTD (mediated percentage 9.3%-14.8%). The present cross-sectional study found that increasing or higher levels of SB is positively associated with WTD. Addressing the identified potential mediators may reduce WTD among people who are sedentary. However, future longitudinal and intervention studies are needed to make concrete recommendations.

Risk Factors for Depression in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a widespread chronic condition. Depression frequently occurs among patients with KOA. The objective of this meta-analysis was to identify risk factors associated with comorbid depression in patients with KOA. MATERIALS AND METHODS: A comprehensive search of the PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science databases was conducted for studies related to comorbid depression in patients with KOA. We conducted statistical analyses to obtain relevant results, followed by heterogeneity tests and assessment for publication bias. RESULTS: The prevalence of comorbid depression among patients with KOA was 34% (95% CI, 28%-41%). Notable risk factors linked to comorbid depression in patients with KOA included female sex (relative risk [RR], 1.17; 95% CI, 1.11-1.23), obesity (mean difference [MD], 1.30; 95% CI, 0.88-1.71), use of analgesics (RR, 1.50; 95% CI, 1.38-1.63), comorbidities (MD, 0.20; 95% CI, 0.10-0.31), unmarried or widowed status (RR, 1.72; 95% CI, 1.56-1.91), bilateral knee pain (RR, 1.38; 95% CI, 1.11-1.71), high total Western Ontario and Mc-Master Universities Arthritis Index (WOMAC) score (MD, 14.92; 95% CI, 10.02-19.82), high WOMAC pain score (MD, 5.76; 95% CI, 2.86-8.67), low gait velocity (MD, -0.12; 95% CI, -0.16 to -0.09), and extended duration in the Timed Up and Go Test (MD, 1.56; 95% CI, 0.87-2.25). CONCLUSION: Based on the current evidence, female sex, obesity, use of analgesics, comorbidities, unmarried or widowed status, bilateral knee pain, high total WOMAC score, high WOMAC pain score, low gait velocity, and prolonged time on the Timed Up and Go Test were identified as risk factors for depression in patients with KOA. Focus should be given to these aspects when preventing depression among these patients. [Orthopedics. 2024;47(5):e225-e232.].

The synergy of depression and flourishing/languishing on suicidal thoughts and behaviors: Findings from a national sample of emerging adult students in higher education in the United States.

BACKGROUND: Suicide is a leading cause of death among students in higher education, driven in large part by mental illness, but also mental wellness. Relatively few studies have examined the extent to which depression and flourishing/languishing interact in relation to suicidal thoughts and behaviors. METHODS: We analyzed data from the Healthy Minds Study (2020-2021; emerging adult students aged 18-29; N = 101,435), and calculated interaction contrast ratios to estimate the interaction between depression and flourishing/languishing on suicidal thoughts and behaviors, using an additive scale, adjusting for age, gender, race/ethnicity, and food insecurity. RESULTS: When compared with students who were flourishing without depression, the students who were languishing without depression, and the students who were depressed but still flourishing had significantly greater odds of suicidal thoughts and behaviors. However, students who were depressed and languishing had the greatest odds, exceeding the sum of the individual effects. CONCLUSION: The interaction of depression and flourishing/languishing produced a synergy that increased odds of suicidal thoughts and behaviors. Flourishing interventions may prove to be an effective strategy for universal suicide prevention.

Cardiovascular and Cerebrovascular Adverse Events Associated with Intravitreal Anti-VEGF Monoclonal Antibodies: A World Health Organization Pharmacovigilance Study.

PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-VEGF (aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. PARTICIPANTS: VigiBase, a World Health Organization (WHO) global safety report database. DESIGN: Pharmacovigilance study. METHODS: The individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, there were 23 129 ADRs after intravitreal anti-VEGF therapy and 25 015 132 ADRs associated with any drug (full database). MAIN OUTCOME MEASURES: The reporting odds ratio (ROR) and information components (ICs) were calculated, and the 95% lower credibility interval end point of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odds ratio (rOR). RESULTS: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI, 1.70-1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI, 1.47-1.77]), arrhythmias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 > 0,.ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI, 4.82-5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI, 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI, 22.10-24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI, 3.98-6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI, 5.03-5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI, 4.14-5.6]). Inter-drug comparison indicated that compared with ranibizumab, patients receiving aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI, 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI, 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI, 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI, 0.40-0.65]). CONCLUSIONS: In this pharmacovigilance case-noncase study, there was significantly increased reporting of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment. Although ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Mild Cognitive Impairment and Suicidal Ideation Among Adults Aged 65 Years or Older From Low- and Middle-Income Countries.

OBJECTIVES: Mild cognitive impairment (MCI) is a unique indicator of underlying distress that may be strongly associated with suicide risk. Despite this, to date, no study has examined the association between MCI and suicidal ideation. Therefore, the present study aimed to examine the association between MCI and suicidal ideation among adults aged ≥65 years from 6 low- and middle-income countries (LMICs; China, Ghana, India, Mexico, Russia, and South Africa). METHODS: Cross-sectional, nationally representative data from the World Health Organization's Study on Global Ageing and Adult Health were analyzed. MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Self-reported information on past 12-month suicidal ideation was collected. Multivariable logistic regression and meta-analysis were conducted to assess associations. RESULTS: Data on 13,623 individuals aged ≥65 years were analyzed. The prevalence of suicidal ideation ranged from 0.5% in China to 6.0% in India, whereas the range of the prevalence of MCI was 9.7% (Ghana) to 26.4% (China). After adjustment for potential confounders, MCI was significantly associated with 1.66 (95% confidence interval [95% CI] = 1.12-2.46) times higher odds for suicidal ideation. DISCUSSION: Mild cognitive impairment was significantly associated with higher odds for suicidal ideation among older adults in LMICs. Future longitudinal studies from LMICs are necessary to assess whether MCI is a risk factor for suicidal ideation.

Efficacy and safety of zoledronic acid in the treatment of osteoporosis: A meta-analysis of randomized controlled trials.

Purpose: Zoledronic acid can inhibit the activity of osteoclasts, and thus, may slow or inhibit bone loss. The purpose of this study was to systematically evaluate the efficacy and safety of zoledronic acid in the treatment of osteoporosis. Methods: Four databases, PubMed, Embase, Cochrane Library, and Web of Science, were systematically searched up to December 26, 2022. The primary outcomes included bone mineral density (BMD), carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal prope-ptide (P1NP), adverse events, and fracture. Secondary outcomes included serum sclerostin level, Visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI). Results: A total of 22 randomized controlled trials were included in this meta-analysis. Meta-analysis results showed that zoledronic acid was effective in increasing BMD of the lumbar spine, femoral neck, trochanter and serum sclerostin level; and reduced CTX, BSAP, P1NP, VAS score, and ODI in patients with osteoporosis. Regarding safety, zoledronic acid could reduce the incidence of fractures but had relatively more adverse events. Conclusion: Zoledronic acid can significantly improve BMD of the lumbar spine, femoral neck and trochanter, and effectively reduce incidence of fracture in patients with osteoporosis, thereby significantly improving patients' quality of life. However, the incidence of adverse events was higher than that of patients treated with placebo.

Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs. total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.00001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.02), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.00001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.01) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P = 0.0002) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS: In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.

Comorbid health conditions in people with attention-deficit/hyperactivity disorders: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: We aimed to systematically review meta-analyses on the link between attention-deficit/hyperactivity disorder (ADHD) and a broad range of psychiatric, physical, and behavioral health conditions (PROSPERO; no.CRD42023448907). RESULTS: We identified 22 meta-analyses that included 544 primary studies, covering 76 unique conditions in over 234 million participants across 36 countries and six continents. We found high-certainty evidence for the associations between ADHD and neuropsychiatric conditions (bipolar disorders, personality disorders, schizophrenia, and pragmatic language skills), night awakenings, obesity, decayed incipient surfaces, asthma, astigmatism, hyperopia and hypermetropia, strabismus, and suicide ideation. Moderate-certainty evidence suggested that ADHD was associated with headache, mood/affective disorders, depression, bruxism, bone fractures, atopic rhinitis, vision problems, suicide attempts, completed suicide, and all-cause mortality. Low-certainty evidence indicated associations with eating disorders, sleep efficiency, type 2 diabetes, dental trauma prevalence, atopic diseases, and atopic dermatitis. Very low-certainty evidence showed associations between ADHD and several sleep parameters. CONCLUSION: We found varied levels of evidence for the associations of ADHD with multiple health conditions. Therefore, clinicians should consider a wide range of neurological, psychiatric, sleep and suicide-related, metabolic, musculoskeletal, oral, allergic, and visual conditions, as well as the increased risk of mortality when assessing individuals with ADHD.

Association between self-reported visual symptoms (suggesting cataract) and self-reported fall-related injury among adults aged ≥ 65 years from five low- and middle-income countries.

BACKGROUND: Cataracts may increase risk for falls but studies on this topic from low- and middle-income countries (LMICs) are scarce. Therefore, we examined the cross-sectional association between self-reported visual symptoms (suggesting cataract) and self-reported injurious falls in nationally representative samples of adults aged ≥ 65 years from five LMICs (China, Ghana, India, Mexico, and Russia). METHODS: Data from the WHO Study on global AGEing and adult health (SAGE) were analysed. Self-reported information on past 12-month fall-related injury and cataract based on symptoms were collected. Multivariable logistic regression and meta-analyses were conducted to assess associations. RESULTS: Data on 13,101 people aged ≥ 65 years were analysed [mean (SD) age 72.5 (11.3) years; 45.2% males]. The overall prevalence of self-reported fall-related injury and visual symptoms (suggesting cataract) were 4.9% and 29.4%, respectively. There was a positive association between self-reported visual symptoms (suggesting cataract) and fall-related injury (i.e., OR > 1) in all five countries but statistical significance was reached in three: China (OR = 1.60; 95% CI = 1.08-2.35), India (OR = 1.96; 95% CI = 1.15-3.35), and Russia (OR = 3.58; 95% CI = 2.06-6.24). The pooled OR including all five countries based on a meta-analysis was OR = 1.88 (95% CI = 1.32-2.68). CONCLUSIONS: Self-reported visual symptoms (suggesting cataract) were associated with higher odds for self-reported injurious falls among older adults in LMICs. Expanding availability of cataract surgery in LMICs may also have the additional benefit of reducing falls among older people.

Protocol for the development of a reporting guideline for umbrella reviews on epidemiological associations using cross-sectional, case-control and cohort studies: the Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC).

INTRODUCTION: Observational studies are fraught with several biases including reverse causation and residual confounding. Overview of reviews of observational studies (ie, umbrella reviews) synthesise systematic reviews with or without meta-analyses of cross-sectional, case-control and cohort studies, and may also aid in the grading of the credibility of reported associations. The number of published umbrella reviews has been increasing. Recently, a reporting guideline for overviews of reviews of healthcare interventions (Preferred Reporting Items for Overviews of Reviews (PRIOR)) was published, but the field lacks reporting guidelines for umbrella reviews of observational studies. Our aim is to develop a reporting guideline for umbrella reviews on cross-sectional, case-control and cohort studies assessing epidemiological associations. METHODS AND ANALYSIS: We will adhere to established guidance and prepare a PRIOR extension for systematic reviews of cross-sectional, case-control and cohort studies testing epidemiological associations between an exposure and an outcome, namely Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC). Step 1 will be the project launch to identify stakeholders. Step 2 will be a literature review of available guidance to conduct umbrella reviews. Step 3 will be an online Delphi study sampling 100 participants among authors and editors of umbrella reviews. Step 4 will encompass the finalisation of PRIUR-CCC statement, including a checklist, a flow diagram, explanation and elaboration document. Deliverables will be (i) identifying stakeholders to involve according to relevant expertise and end-user groups, with an equity, diversity and inclusion lens; (ii) completing a narrative review of methodological guidance on how to conduct umbrella reviews, a narrative review of methodology and reporting in published umbrella reviews and preparing an initial PRIUR-CCC checklist for Delphi study round 1; (iii) preparing a PRIUR-CCC checklist with guidance after Delphi study; (iv) publishing and disseminating PRIUR-CCC statement. ETHICS AND DISSEMINATION: PRIUR-CCC has been approved by The Ottawa Health Science Network Research Ethics Board and has obtained consent (20220639-01H). Participants to step 3 will give informed consent. PRIUR-CCC steps will be published in a peer-reviewed journal and will guide reporting of umbrella reviews on epidemiological associations.

Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan.

We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.

Association between sedentary behavior and dynapenic abdominal obesity among older adults from low- and middle-income countries.

BACKGROUND: Sedentary behavior, or time spent sitting, may increase risk for dynapenic abdominal obesity (DAO), but there are currently no studies on this topic. AIMS: Therefore, we investigated the association between sedentary behaviour and DAO in a nationally representative sample of older adults from six low- and middle-income countries. METHODS: Cross-sectional data from the Study on Global AGEing and Adult Health were analysed. Dynapenia was defined as handgrip strength < 26 kg for men and < 16 kg for women. Abdominal obesity was defined as waist circumference of > 88 cm (> 80 cm for Asian countries) for women and > 102 cm (> 90 cm) for men. DAO was defined as having both dynapenia and abdominal obesity. Self-reported sedentary behavior was categorized as ≥ 8 h/day (high sedentary behaviour) or < 8 h/day. Multivariable multinomial logistic regression was conducted. RESULTS: Data on 20,198 adults aged ≥ 60 years were analyzed [mean (SD) age 69.3 (13.1) years; 54.1% females]. In the overall sample, ≥ 8 h of sedentary behavior per day (vs. <8 h) was significantly associated with 1.52 (95%CI = 1.11-2.07) times higher odds for DAO (vs. no dynapenia and no abdominal obesity), and this was particularly pronounced among males (OR = 2.27; 95%CI = 1.42-3.62). Highly sedentary behavior was not significantly associated with dynapenia alone or abdominal obesity alone. DISCUSSION: High sedentary behaviour may increase risk for DAO among older adults. CONCLUSIONS: Interventions to reduce sedentary behaviour may also lead to reduction of DAO and its adverse health outcomes, especially among males, pending future longitudinal research.

The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.

Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea.

OBJECTIVE: To investigate the potential association between prenatal opioid exposure and the risk of neuropsychiatric disorders in children. DESIGN: Nationwide birth cohort study. SETTING: From 1 January 2009 to 31 December 2020, birth cohort data of pregnant women in South Korea linked to their liveborn infants from the National Health Insurance Service of South Korea were collected. PARTICIPANTS: All 3 251 594 infants (paired mothers, n=2 369 322; age 32.1 years (standard deviation 4.2)) in South Korea from the start of 2010 to the end of 2017, with follow-up from the date of birth until the date of death or 31 December 2020, were included. MAIN OUTCOME MEASURES: Diagnosis of neuropsychiatric disorders in liveborn infants with mental and behaviour disorders (International Classification of Diseases 10th edition codes F00-99). Follow-up continued until the first diagnosis of neuropsychiatric disorder, 31 December 2020 (end of the study period), or the date of death, whichever occurred first. Eight cohorts were created: three cohorts (full unmatched, propensity score matched, and child screening cohorts) were formed, all of which were paired with sibling comparison cohorts, in addition to two more propensity score groups. Multiple subgroup analyses were performed. RESULTS: Of the 3 128 571 infants included (from 2 299 664 mothers), we identified 2 912 559 (51.3% male, 48.7% female) infants with no prenatal opioid exposure and 216 012 (51.2% male, 48.8% female) infants with prenatal opioid exposure. The risk of neuropsychiatric disorders in the child with prenatal opioid exposure was 1.07 (95% confidence interval 1.05 to 1.10) for fully adjusted hazard ratio in the matched cohort, but no significant association was noted in the sibling comparison cohort (hazard ratio 1.00 (0.93 to 1.07)). Prenatal opioid exposure during the first trimester (1.11 (1.07 to 1.15)), higher opioid doses (1.15 (1.09 to 1.21)), and long term opioid use of 60 days or more (1.95 (1.24 to 3.06)) were associated with an increased risk of neuropsychiatric disorders in the child. Prenatal opioid exposure modestly increased the risk of severe neuropsychiatric disorders (1.30 (1.15 to 1.46)), mood disorders, attention deficit hyperactivity disorder, and intellectual disability in the child. CONCLUSIONS: Opioid use during pregnancy was not associated with a substantial increase in the risk of neuropsychiatric disorders in the offspring. A slightly increased risk of neuropsychiatric disorders was observed, but this should not be considered clinically meaningful given the observational nature of the study, and limited to high opioid dose, more than one opioid used, longer duration of exposure, opioid exposure during early pregnancy, and only to some neuropsychiatric disorders.

Physical activity and prevention of mental health complications: An umbrella review.

The potential of physical activity in preventing mental health issues has garnered interest among health professionals. We conducted a systematic umbrella review of evidence supporting the relationship between physical activity and the prevention of mental health complications. Our findings revealed a significant association between higher physical activity levels and reduced risk of depression (OR = 0.77, 95% CI 0.72 - 0.82). This association was consistent across various age groups, sex, and geographical regions. Interestingly, low and moderate-intensity physical activity showed the most significant protective effects against depression (low-intensity: OR = 0.81, 95% CI: 0.75-0.56; moderate-intensity: OR = 0.79, 95% CI: 0.72-0.87). Our analysis also showed significant associations between higher physical activity levels and prevention of anxiety disorders (OR = 0.71, 95% CI: 0.61-0.82). However, the evidence regarding the association between physical activity and psychosis/schizophrenia risk was less clear. These findings underscore the physical activity's potential as a preventative measure against mental health complications, highlighting the importance of promoting physical activity in mental health interventions.

Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study.

BACKGROUND: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. OBJECTIVE: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. DESIGN: Binational, longitudinal, propensity-matched cohort study. SETTING: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). PARTICIPANTS: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. MEASUREMENTS: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. RESULTS: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. LIMITATIONS: Referral bias due to the pandemic; residual confounding. CONCLUSION: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. PRIMARY FUNDING SOURCE: National Research Foundation of Korea.