Somatic multicomorbidity and disability in patients with psychiatric disorders in comparison to the general population: a quasi-epidemiological investigation in 54,826 subjects from 40 countries (COMET-G study).

BACKGROUND: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders. METHODS: The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions. RESULTS: About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15-20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome. CONCLUSIONS: The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease.

BACKGROUND: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26). RESULTS: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. CONCLUSIONS: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Effect of calcitriol treatment on arterial stiffness in people with type 2 diabetes and stage 3 chronic kidney disease.

AIMS: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. METHODS: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. RESULTS: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001. CONCLUSION: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.

Results of the COVID-19 mental health international for the health professionals (COMET-HP) study: depression, suicidal tendencies and conspiracism.

INTRODUCTION: The current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak. MATERIALS AND METHODS: The data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Clinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p < 0.0001). Suicidal tendencies were at least doubled in terms of RASS scores. Approximately one-third of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop clinical depression was associated with a history of Bipolar disorder (RR = 4.23). CONCLUSIONS: The current study reported findings in health care professionals similar in magnitude and quality to those reported earlier in the general population although rates of clinical depression, suicidal tendencies, and adherence to conspiracy theories were much lower. However, the general model of factors interplay seems to be the same and this could be of practical utility since many of these factors are modifiable.

Adherence to facemask use in public places during the autumn-winter 2020 COVID-19 lockdown in Greece: observational data.

BACKGROUND: Wearing facemasks is of proven efficacy as a public health protective measure against COVID-19. Currently there are no observational data concerning the wearing of facemasks and the adherence to guidelines concerning their handling. METHODS: Registration of the way passers-by were wearing facemasks at 26 different locations of five major cities in Greece. The results were correlated with the rate of COVID-19 deaths in the region. RESULTS: In total, 119,433 passers-by were registered, 57,043 females (47.8%) and 62,390 males (52.2%). From the total sample, 81.1% were wearing the mask properly, 10.8% had their nose out, 6.2% were wearing it under the jaw, and 1.9% had no mask at all . There was a significant difference between males and females concerning any use of mask. Inappropriate use of was correlated with COVID-19 death rate in the studied region. CONCLUSION: Our findings suggest that under conditions of mandatory wearing and in central locations of major cities, during walking, proper use of masks is suboptimal, but still contributes with some protection. Fear and risk perception seem to be strong factors contributing to adherence to proper mask wearing.

Mental health and conspirasism in health care professionals during the spring 2020 COVID-19 lockdown in Greece.

INTRODUCTION: The aim of the study was to investigate mental health and conspiracy theory beliefs concerning COVID-19 among health care professionals (HCPs). MATERIAL AND METHODS: During lockdown, an online questionnaire gathered data from 507 HCPs (432 females aged 33.86 ± 8.63 and 75 males aged 39.09 ± 9.54). STATISTICAL ANALYSIS: A post-stratification method to transform the study sample was used; descriptive statistics were calculated. RESULTS: Anxiety and probable depression were increased 1.5-2-fold and were higher in females and nurses. Previous history of depression was the main risk factor. The rates of believing in conspiracy theories concerning the COVID-19 were alarming with the majority of individuals (especially females) following some theory to at least some extend. CONCLUSIONS: The current paper reports high rates of depression, distress and suicidal thoughts in the HCPs during the lockdown, with a high prevalence of beliefs in conspiracy theories. Female gender and previous history of depression acted as risk factors, while the belief in conspiracy theories might act as a protective factor. The results should be considered with caution due to the nature of the data (online survey on a self-selected but stratified sample).

Factors determining different death rates because of the COVID-19 outbreak among countries.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, all European countries were hit, but mortality rates were heterogenous. The aim of the current paper was to identify factors responsible for this heterogeneity. METHODS: Data concerning 40 countries were gathered, concerning demographics, vulnerability factors and characteristics of the national response. These variables were tested against the rate of deaths per million in each country. The statistical analysis included Person correlation coefficient and Forward Stepwise Linear Regression Analysis (FSLRA). RESULTS: The FSLRA results suggested that 'days since first national death for the implementation of ban of all public events' was the only variable significantly contributing to the final model, explaining 44% of observed variability. DISCUSSION: The current study suggests that the crucial factor for the different death rates because of COVID-19 outbreak was the fast implementation of public events ban. This does not necessarily mean that the other measures were useless, especially since most countries implemented all of them as a 'package'. However, it does imply that this is a possibility and focused research is needed to clarify it, and is in accord with a model of spreading where only a few superspreaders infect large numbers through prolonged exposure.

Reducing the incidence of predictors of cardio-metabolic disease and dysglycaemia with lifestyle modification in at-risk persons - results of further analyses of DIABRISK-SL in those below 18 years of age.

BACKGROUND: We have previously demonstrated in the DIABRISK-SL trial that a trimonthly pragmatic lifestyle modification (P-LSM), as compared to a 12-monthly LSM advice (C-LSM), significantly reduced the primary composite endpoint of predictors of cardio-metabolic disease (new onset type 2 diabetes (T2DM), hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia and markers of cardio-renal disease) in urban participants aged below 40 years with risk factors for T2DM. MAIN TEXT: We now report results of post hoc analyses for those aged below 18 (n = 1725) in three age groups, specifically of 6-10 years (P-LSM n = 77, C-LSM n = 59), 10-14 years (P-LSM n = 534, C-LSM n = 556) and 14-18 years (P-LSM n = 239, C-LSM n = 260). There was no effect of P-LSM on the primary endpoint in participants aged below 10 years. Participants aged 10-14 years in the P-LSM intervention as compared to C-LSM had a lower incidence of the primary combined endpoint (87 vs. 106 cases; incident rate ratio (IRR) = 0.85, 95% confidence intervals (CI) 0.72-1.01; P = 0.07), driven mainly by the lower incidence of new onset hypertension (24 vs. 37 cases; IRR = 0.67, 95% CI 0.49-0.91; P = 0.012). Participants aged 14-18 years in the P-LSM intervention had a lower incidence of the composite endpoint (36 vs. 54 cases; IRR = 0.73, 95% CI 0.57-0.94; P = 0.015) as well as a lower incidence of IGT (12 vs. 21 cases; IRR = 0.6, 95% CI 0.39-0.92; P = 0.02), new onset hypertension (6 vs. 15 cases; IRR = 0.43, 95% CI 0.25-0.76; P = 0.004), and new onset dysglycaemia (composite of new T2DM, IGT and impaired fasting glycaemia) (30 vs. 46 cases; IRR = 0.74, 95% CI 0.56-0.97; P = 0.03) compared to those assigned to the C-LSM intervention. Limitations of the analyses are the post hoc approach and the small number of events in each group. There were no differences in retention between the two groups. CONCLUSIONS: Our results suggest that, in young South Asians aged between 10 and 18 years at risk of T2DM, a pragmatic lifestyle modification programme may reduce the incidence of predictors of T2DM and hypertension. There is a need for further studies in younger populations to evaluate the impact and feasibility of interventions to reduce the burden of T2DM and associated cardio-metabolic risk. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0905-6.

The P274S Mutation of Lecithin-Cholesterol Acyltransferase (LCAT) and Its Clinical Manifestations in a Large Kindred.

RATIONALE & OBJECTIVE: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 2 (related) index patients with clinically apparent FLD were initially identified. 110 of 122 family members who consented to genetic analysis were also studied. PREDICTORS: Demographic and laboratory parameters (including lipid profiles and LCAT activity) and full sequence analysis of the LCAT gene. Kidney histologic examination was performed with samples from 6 participants. OUTCOMES: Cardiovascular and renal events during a median follow-up of 12 years. Estimation of annual rate of decline in glomerular filtration rate. ANALYTICAL APPROACH: Analysis of variance, linear regression analysis, and Fine-Gray competing-risk survival analysis. RESULTS: 9 homozygous, 57 heterozygous, and 44 unaffected family members were identified. In all affected individuals, full sequence analysis of the LCAT gene revealed a mutation (c.820C>T) predicted to cause a proline to serine substitution at amino acid 274 (P274S). Homozygosity caused a complete loss of LCAT activity. Kidney biopsy findings demonstrated lipid deposition causing glomerular basement membrane thickening, mesangial expansion, and "foam-cell" infiltration of kidney tissue. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with worse kidney outcomes. Estimated glomerular filtration rate deteriorated among homozygous family members at an average annual rate of 3.56 mL/min/1.73 m2. The incidence of cardiovascular and renal complications was higher among homozygous family members compared with heterozygous and unaffected members. Mild thrombocytopenia was a common finding among homozygous participants. LIMITATIONS: The presence of cardiovascular disease was mainly based on medical history. CONCLUSIONS: The P274S LCAT mutation was found to cause FLD with renal involvement. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with a worse renal prognosis.

Associations between sleep duration and cognitive impairment in mild cognitive impairment.

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. A subsample of 271 participants with a diagnosis of probable Alzheimer's disease (AD; N = 50) or mild cognitive impairment (MCI; N = 121) and 100 persons who were not cognitively impaired (NI) were recruited from a large population-based cohort in the island of Crete, Greece (3140 older adults aged >60 years). All participants underwent extensive neuropsychiatric/neuropsychological evaluation and a 3-day 24-hr actigraphy. Objective sleep variables and their association with neuropsychological performance were examined across the three groups, controlling for demographics, body mass index, depression, sleep apnea symptoms and psychotropic medications. Patients with AD had significantly longer 24-hr total sleep time (TST) compared to the MCI and NI groups. Long 24-hr TST was associated with reduced performance on tasks that placed significant demands on attention and processing speed in the MCI group and the AD group. Elderly patients with MCI have similar objective sleep duration to normal controls, whereas AD patients sleep longer. Long sleep duration in patients with multidomain subtypes of MCI is associated with critical non-memory cognitive domains. It appears that within the MCI group those that sleep longer have more severe cognitive impairment.

Annexin A1 attenuates microvascular complications through restoration of Akt signalling in a murine model of type 1 diabetes.

AIMS/HYPOTHESIS: Microvascular complications in the heart and kidney are strongly associated with an overall rise in inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory molecule that limits and resolves inflammation. In this study, we have used a bedside to bench approach to investigate: (1) ANXA1 levels in individuals with type 1 diabetes; (2) the role of endogenous ANXA1 in nephropathy and cardiomyopathy in experimental type 1 diabetes; and (3) whether treatment with human recombinant ANXA1 attenuates nephropathy and cardiomyopathy in a murine model of type 1 diabetes. METHODS: ANXA1 was measured in plasma from individuals with type 1 diabetes with or without nephropathy and healthy donors. Experimental type 1 diabetes was induced in mice by injection of streptozotocin (STZ; 45 mg/kg i.v. per day for 5 consecutive days) in C57BL/6 or Anxa1 -/- mice. Diabetic mice were treated with human recombinant (hr)ANXA1 (1 µg, 100 µl, 50 mmol/l HEPES; 140 mmol/l NaCl; pH 7.4, i.p.) or vehicle (100 µl, 50 mmol/l HEPES; 140 mmol/l NaCl; pH 7.4, i.p.). RESULTS: Plasma levels of ANXA1 were elevated in individuals with type 1 diabetes with/without nephropathy compared with healthy individuals (66.0 ± 4.2/64.0 ± 4 ng/ml vs 35.9 ± 2.3 ng/ml; p < 0.05). Compared with diabetic wild-type (WT) mice, diabetic Anxa1 -/- mice exhibited a worse diabetic phenotype and developed more severe cardiac (ejection fraction; 76.1 ± 1.6% vs 49.9 ± 0.9%) and renal dysfunction (proteinuria; 89.3 ± 5.0 µg/mg vs 113.3 ± 5.5 µg/mg). Mechanistically, compared with non-diabetic WT mice, the degree of the phosphorylation of mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) was significantly higher in non-diabetic Anxa1 -/- mice in both the heart and kidney, and was further enhanced after STZ-induced type 1 diabetes. Prophylactic treatment with hrANXA1 (weeks 1-13) attenuated both cardiac (ejection fraction; 54.0 ± 1.6% vs 72.4 ± 1.0%) and renal (proteinuria; 89.3 ± 5.0 µg/mg vs 53.1 ± 3.4 µg/mg) dysfunction associated with STZ-induced diabetes, while therapeutic administration of hrANXA1 (weeks 8-13), after significant cardiac and renal dysfunction had already developed, halted the further functional decline in cardiac and renal function seen in diabetic mice administered vehicle. In addition, administration of hrANXA1 attenuated the increase in phosphorylation of p38, JNK and ERK, and restored phosphorylation of Akt in diabetic mice. CONCLUSIONS/INTERPRETATION: Overall, these results demonstrate that ANXA1 plasma levels are elevated in individuals with type 1 diabetes independent of a significant impairment in renal function. Furthermore, in mouse models with STZ-induced type 1 diabetes, ANXA1 protects against cardiac and renal dysfunction by returning MAPK signalling to baseline and activating pro-survival pathways (Akt). We propose ANXA1 to be a potential therapeutic option for the control of comorbidities in type 1 diabetes.

Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.

AIMS/HYPOTHESIS: Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown. METHODS: In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin-angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs). All participants had an eGFR >45 ml/min, duration of diabetes >20 years and no history of CVD. Serum soluble Klotho levels were measured by a validated immunoassay. RESULTS: Participants with microalbuminuria had significantly lower levels of serum Klotho compared with those without microalbuminuria (median [interquartile range], 659.3 [525.3, 827.6] vs 787.7 [629.5, 1007]; p = 0.023). This difference persisted after adjustment for variables including age and eGFR. In a subgroup of 30 individuals with and without microalbuminuria, other markers of phosphate balance were not significantly different. CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes, microalbuminuria is associated with soluble Klotho deficiency. Further studies are required to determine whether soluble Klotho is causally related to the development of cardio-renal disease in type 1 diabetes.

A pragmatic lifestyle modification programme reduces the incidence of predictors of cardio-metabolic disease and dysglycaemia in a young healthy urban South Asian population: a randomised controlled trial.

BACKGROUND: There is an increasing incidence of type 2 diabetes mellitus (T2DM) in young urban South-Asians. We tested the effect of a pragmatic trimonthly lifestyle modification (LSM) programme (P-LSM) versus a less-intensive 12-monthly control LSM (C-LSM) intervention on a primary composite endpoint of predictors of cardio-metabolic disease (new onset T2DM, hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and markers of cardio-renal disease) in participants aged 5-40 years with risk factors for T2DM. METHODS: This was a randomised controlled trial performed at the National Diabetes Centre, Sri-Lanka. We individually randomised 4672 participants at risk of T2DM, of whom 3539 (mean age 22.5 (range 6-40 years, 48% males) received either trimonthly (P-LSM n = 1726) or 12-monthly (C-LSM n = 1813) peer educator advice aimed at reducing weight, improving diet, reducing psychological stress and increasing physical activity. RESULTS: During a median follow-up of 3 years, the cumulative incidence of the primary endpoint was n = 479 in P-LSM (74 per 1000 person years) vs. 561 in C-LSM (96 per 1000 person years), with an incident rate ratio (IRR) of 0.89 (95% CI 0.83-0.96, P = 0.02). In post hoc analyses, new onset dysglycaemia (T2DM, IFG and IGT), was the major contributor to the composite and was significantly reduced by P-LSM (IRR 0.9, 95% CI 0.83-0.97, P = 0.01). A significant impact of P-LSM on the incidence of the composite endpoint was noted in 1725 participants (P-LSM n = 850, C-LSM n = 875) aged below 18; P-LSM n = 140 (48 per 1000 person years) versus C-LSM n = 174 (55.4 per 1000 person years), with an IRR of 0.83 (95% CI 0.73-0.94, P = 0.004). CONCLUSIONS: In a young at-risk South-Asian population, a pragmatic LSM programme significantly reduces the incidence of predictors of cardio-metabolic disease. Our results highlight the importance of early intervention in young at-risk subjects. TRIAL REGISTRATION: World Health Organization international clinical trial registry platform ( SLCTR/2008/003 ). Registration Date: March 28, 2008. Retrospectively registered.

Non-binary gender, vulnerable populations and mental health during the COVID-19 pandemic: Data from the COVID-19 MEntal health inTernational for the general population (COMET-G) study.

BACKGROUND: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations. METHODS: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them. RESULTS: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use. CONCLUSIONS: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research. LIMITATIONS: Online data collection may have resulted in the underrepresentation of certain population groups.

Reduced Levels of the Antiaging Hormone Klotho are Associated With Increased Aortic Stiffness in Diabetic Kidney Disease.

Introduction: Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown. Methods: In a cross-sectional cohort study, the correlation of sKlotho measured by a validated immunoassay, and Ao-PWV measured by applanation tonometry, was investigated in 172 participants with T2D and early stage DKD (all had estimated glomerular filtration rate [eGFR] >45 ml/min) on stable renin angiotensin system (RAS) inhibition. In cultured human aortic smooth muscle cells (HASMCs) stimulated with angiotensin II (AngII), the effects of recombinant human sKlotho pretreatment were assessed on intracellular calcium ([Ca2+]i) responses and expression of proteins associated with proosteogenic HASMC phenotypes. Results: Mean (range) age of the cohort was 61.3 years (40-82) and 65% were male. Mean (±SD) Ao-PWV was 11.4 (±2.3) m/s, eGFR 78.8 (±23.5) and median (interquartile range) sKlotho of 358.5 (194.2-706.3) pg/ml. In multivariable linear regression analyses, we observed a statistically significant inverse relationship between sKlotho and Ao-PWV, which was independent of clinical risk factors for cardiorenal disease. Pretreatment of cultured HASMC with sKlotho significantly attenuated AngII-stimulated [Ca2+]i transients and reduced osteogenic collagen (Col1a2) expression. Conclusions: In individuals with T2D and early DKD, lower levels of sKlotho are associated with increased Ao-PWV. Taken together with the direct effect of sKlotho on mediators of aortic wall stiffness in vitro, these findings may explain the enhanced risk of cardiorenal disease in DKD.

People With Type 1 Diabetes of African Caribbean Ethnicity Are at Increased Risk of Developing Sight-Threatening Diabetic Retinopathy.

OBJECTIVE: There is limited information on the effect of ethnicity on the development of referable sight-threatening diabetic retinopathy (STDR) in people with type 1 diabetes. This study describes the risk factors for STDR in a diverse cohort of people with type 1 diabetes attending a regional diabetes eye screening service. RESEARCH DESIGN AND METHODS: Clinical and digital retinal imaging data from 1,876 people with type 1 diabetes (50% women, 72.1% Caucasian, 17.3% African Caribbean, 2.9% Asian, and 7.6% other) with no retinopathy at baseline, attending surveillance eye screening were reviewed. Referable STDR was defined as the presence of any moderate to severe nonproliferative or preproliferative diabetic retinopathy or proliferative diabetic retinopathy or maculopathy in either eye as per U.K. National Diabetic Eye Screening criteria. Median follow-up was 6 years. RESULTS: The median (interquartile range) age of the cohort was 29 (21, 41) years. Of the cohort of 1,876 people, 359 (19%) developed STDR. People who developed STDR had higher baseline HbA1c, raised systolic blood pressure (SBP), longer diabetes duration, and were more often of African Caribbean origin (24% vs. 15.6%; P < 0.05 for all). In multivariable Cox regression analyses, African Caribbean ethnicity (hazard ratio [HR] 1.39, 95% CI 1.09-1.78, P = 0.009), baseline SBP (HR 1.01, 95% CI 1.00-1.01, P = 0.033), and baseline HbA1c (HR 1.01, 95% CI 1.00-1.01, P = 0.0001) emerged as independent risk factors for STDR. CONCLUSIONS: We observed that people with type 1 diabetes of African Caribbean ethnicity are at significantly greater risk of STDR. Further research is required to understand the mechanisms that explain this novel observation.

Students' mental health during the pandemic: results of the observational cross-sectional COVID-19 MEntal health inTernational for university Students (COMET-S) study.

Introduction: The aim of the study was to search rates of depression and mental health in university students, during the COVID-19 pandemic. Materials and methods: This is an observational cross-sectional study. A protocol gathering sociodemographic variables as well as depression, anxiety and suicidality and conspiracism was assembled, and data were collected anonymously and online from April 2020 through March 2021. The sample included 12,488 subjects from 11 countries, of whom 9,026 were females (72.2%; aged 21.11 ± 2.53), 3,329 males (26.65%; aged 21.61 ± 2.81) and 133 "non-binary gender" (1.06%; aged 21.02 ± 2.98). The analysis included chi-square tests, correlation analysis, ANCOVA, multiple forward stepwise linear regression analysis and Relative Risk ratios. Results: Dysphoria was present in 15.66% and probable depression in 25.81% of the total study sample. More than half reported increase in anxiety and depression and 6.34% in suicidality, while lifestyle changes were significant. The model developed explained 18.4% of the development of depression. Believing in conspiracy theories manifested a complex effect. Close to 25% was believing that the vaccines include a chip and almost 40% suggested that facemask wearing could be a method of socio-political control. Conspiracism was related to current depression but not to history of mental disorders. Discussion: The current study reports that students are at high risk for depression during the COVID-19 pandemic and identified specific risk factors. It also suggested a role of believing in conspiracy theories. Further research is important, as it is targeted intervention in students' groups that are vulnerable both concerning mental health and conspiracism.

Climate rather than economic variables might have caused increase in US homicide but not suicide rates during the Great Depression.

BACKGROUND: It is widely believed that during the Great Depression (1929-1933) there was a rise in suicidal rates which was causally related to the increase in unemployment. There are no studies on the effect the Great Depression had on homicidal rates METHODS: The data concerning suicide, homicide, economic and climatic variables for the years 1900-1940 for the whole of the US were gathered from the US Center for Disease Control, the Maddison Project, the National Bureau of Economic Research and the National Climatic Data Center. Time Series Analysis was performed. RESULTS: The results are inconclusive on the role of economic factors but preclude any role of climate on suicidal rates during the years 1900-1940 in the US. Suicidal rates might have a 24-years periodicity, however much longer time series are needed to confirm this. On the contrary they strongly suggest an effect of higher temperatures on homicidal rates after 1922. CONCLUSIONS: The results of the current study suggest a direct and clear effect of climate (higher temperatures) on the increasing homicidal rates in the US after 1922 but failed to establish a causal relationship between suicide rates and economic or climate variables. These should be considered together with increasing concerns on the possible effect of climate change on mental health.

African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes.

OBJECTIVE: The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. CONCLUSIONS: We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.