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Diabetes and Psychiatry

Evidence-based screening, clinical care and health education recommendations for Alaska Native peoples with prediabetes living in southcentral Alaska: findings from the Alaska EARTH follow-up study
Koller KR, Nash SH, Beans JA, Day GM, Hiratsuka VY, Lin AL, Narayanan M, Patten CA, Hammock SA, Howard BV and Umans JG
Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.
Effects of paradoxical sleep deprivation on oxidative parameters in the serum and brain of mice submitted to the animal model of hyperglycemia
Rosa JP, Sandrini IG, Possamai-Della T, Aguiar-Geraldo JM, Machado-Laureano ML, Zugno AI, Quevedo J and Valvassori SS
The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36 h. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.
The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study
Shapiro ALB, Tjaden AH, Edelstein SL, Kahn SE, Srikanthan P, Knowler WC, Venditti EM, Golden SH, Carmichael O, Luchsinger JA and
Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function.
Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: a study using data from the UK Biobank
Xiang Y, Feng Y, Qiu J, Zhang R and So HC
To explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease.
Increased regional body fat is associated with depressive symptoms: a cross-sectional analysis of NHANES data obtained during 2011-2018
Zhang G, Wang S, Ma P, Li S, Sun X, Zhao Y and Pan J
The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES).
Skin assessment in congenital untreated isolated GH deficiency
Barros-Oliveira CS, de Jesus MJM, Campos VC, Salvatori R, de Souza Araújo AA, Neto RFS, Bartke A, Batista VO, Schneider A, Villar-Gouy KR, Masternak MM, Leal ÂC, Santos LB, Oliveira CRP, Santos EG, Oliveira Simões DA, de Santana Silva B and Aguiar-Oliveira MH
The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort.
Eight-year nationwide study of the bidirectional association between type 2 diabetes and depression in nearly 8 million German outpatients
Chae WR, Kohring C, Rohde C, Köhler-Forsberg O, Otte C and Holstiege J
Research linking type 2 diabetes and depression mostly relied on hospital-based diagnoses or prescription data, overlooking many outpatient diagnoses. We aimed to quantify the risks of depression in individuals newly diagnosed with type 2 diabetes, and type 2 diabetes in those newly diagnosed with depression, while exploring potential risk differences depending on age, sex, and follow-up time.
Integrating Electronic Health Records and Polygenic Risk to Identify Genetically Unrelated Comorbidities of Schizophrenia That May Be Modifiable
Vessels T, Strayer N, Lee H, Choi KW, Zhang S, Han L, Morley TJ, Smoller JW, Xu Y and Ruderfer DM
Patients with schizophrenia have substantial comorbidity that contributes to reduced life expectancy of 10 to 20 years. Identifying modifiable comorbidities could improve rates of premature mortality. Conditions that frequently co-occur but lack shared genetic risk with schizophrenia are more likely to be products of treatment, behavior, or environmental factors and therefore are enriched for potentially modifiable associations.
Quercetin Ameliorates Myocardial Injury in Diabetic Rats by Regulating Autophagy and Apoptosis through AMPK/mTOR Signaling Pathway
Chen YF, Qiu Q, Wang L, Li XR, Zhou S, Wang H, Jiang WD, Geng JY, Qin-Gao , Tang B, Wang HJ and Kang PF
A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet . Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group and . Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.
Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration
Owsley C, McGwin G, Swain TA, Clark ME, Thomas TN, Goerdt L, Sloan KR, Trittschuh EH, Jiang Y, Owen JP, Lee CS and Curcio CA
Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD.
Liraglutide-associated depression in a patient with type 2 diabetes: A case report and discussion
He Y, Liang F, Wang Y, Wei Y and Ma T
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide are primarily used for managing blood sugar levels in type 2 diabetes and aiding weight loss. Typically, their adverse effects are gastrointestinal, with limited exploration into their impact on mental health.
Weight Loss Surgery Increases Kidney Transplant Rates in Patients With Renal Failure and Obesity
Kukla A, Sahi SS, Navratil P, Benzo RP, Smith BH, Duffy D, Park WD, Shah M, Shah P, Clark MM, Fipps DC, Denic A, Schinstock CA, Dean PG, Stegall MD, Kudva YC and Diwan TS
To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT.
The diabetes body project: Study protocol of a multi-site trial of a virtually delivered eating disorder prevention program for young women with type 1 diabetes
Haugvik S, Hennekes M, Stice E, de Wit M, Toschi E and Wisting L
Young women with type 1 diabetes are a high-risk population for eating disorders (ED). Prevention programs are lacking. In young women without diabetes, the Body Project has produced reductions in ED risk factors, ED symptoms and future ED onset. Therefore, the Body Project was adapted to type 1 diabetes, the Diabetes Body Project (DBP). In this protocol, we describe the multi-site randomized controlled trial (RCT) to evaluate efficacy of the DBP.
Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials
Rubino D, Bjorner JB, Rathor N, Sharma AM, von Huth Smith L, Wharton S, Wadden T, Zeuthen N and Kolotkin RL
To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning.
Association between biological aging and diabetic retinopathy
Tang H, Luo N, Zhang X, Huang J, Yang Q, Lin H and Zhang X
The impact of aging on diabetic retinopathy (DR) remains underestimated. The current study aimed to investigate the association between biological aging and DR, in contrast to chronological age (CA). Using the National Health and Nutrition Survey data from 2005 to 2008. Biological aging was evaluated through the biological age (BA) and phenotypic age (PA), which were calculated from clinical markers. DR was identified in participants with diabetes mellitus (DM) when they exhibited one or more retinal microaneurysms or retinal blot hemorrhages under retinal imaging, with or without the presence of more severe lesions. Survey-weighted multivariable logistic regression was performed, and the regression model was further fitted using restricted cubic splines. The discriminatory capability and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Based on weighted analyses, of the 3100 participants included in this study, of which 162 had DR. In the adjusted model, BA (odds ratio [OR] = 1.12, 95% CI, 1.06-1.18) and PA (OR = 1.11, 95% CI, 1.07-1.14) were associated with DR, while CA was not significantly (OR = 1.01, 95% CI, 0.99-1.03). Narrowing the analysis to DM participants and adjusting for factors like insulin showed similar results. ROC and DCA analyses indicate that BA/PA predicted DR better than CA and offer greater clinical utility. The positive association between BA/PA and DR was consistent across subgroups despite potential interactions. Biological aging heightens DR risk, with BA/PA showing a stronger association than CA. Our findings underscored the importance of timely anti-aging interventions for preventing DR.
Patient Characteristics Associated with Receiving Gender-Affirming Hormone Therapy in the Veterans Health Administration
Wolfe HL, Vimalananda VG, Wong DH, Reisman JI, Rao SR, Shipherd JC, Blosnich JR, Livingston NA and Jasuja GK
This study aimed to examine patient characteristics associated with receipt of gender-affirming hormone therapy in the Veterans Health Administration (VHA).
Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2
Littleton SH, Trang KB, Volpe CM, Cook K, DeBruyne N, Maguire JA, Weidekamp MA, Hodge KM, Boehm K, Lu S, Chesi A, Bradfield JP, Pippin JA, Anderson SA, Wells AD, Pahl MC and Grant SFA
The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets. Using a luciferase reporter assay, we observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. We generated isogenic human embryonic stem cell lines homozygous for either rs7132908 allele to assess changes in gene expression and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. The rs7132908 obesity risk allele influenced expression of FAIM2 and other genes and decreased the proportion of neurons produced by differentiation. We have functionally validated rs7132908 as a causal obesity variant that temporally regulates nearby effector genes and influences neurodevelopment and survival.
PTSD, Comorbidities, Gender, and Increased Risk of Cardiovascular Disease in a Large Military Cohort
Krantz DS, Gabbay FH, Belleau EA, Aliaga PA, Wynn GH, Stein MB, Ursano RJ and Naifeh JA
Posttraumatic stress disorder (PTSD) is a prevalent mental health problem that increases risk of cardiovascular disease (CVD). It is not known whether gender or comorbidities modify associations between PTSD and CVD.
Putting a label on someone: impact of schizophrenia stigma on emotional mimicry, liking, and interpersonal closeness
Parisi M, Raffard S, Slangen P, Kastendieck T, Hess U, Mauersberger H, Fauviaux T and Marin L
Affiliation is both an antecedent and a consequence of emotional mimicry (i.e. imitating a counterpart's emotional expression). Thus, interacting with a disliked partner can decrease emotional mimicry, which in turn can further decrease liking. This perpetuating circle has not been investigated in the context of mental health stigma yet. The present study tested the influence of the label "schizophrenia" on liking, interpersonal closeness, and emotional mimicry. In an online experiment ( = 201), participants recruited from the general population saw several videos of actors displaying emotional expressions. Actors were described with one of four labels: "schizophrenia", "healthy", "diabetes", and a negative adjective (e.g. "hot-tempered"). Emotional mimicry was measured using OpenFace 2.2. Liking and interpersonal closeness were assessed with questionnaires. Overall, compared to other labels, participants reported less liking and interpersonal closeness to the actor with the schizophrenia label. However, no effect on emotional mimicry was found. The decreased liking of the schizophrenia actors was explained by a lack of knowledge about schizophrenia and the explicit stigma of schizophrenia. Our study contributes to the literature by highlighting the need to reduce the stigma of schizophrenia.
Referrals For Gender-Affirming Hormone Treatment in Croatia's National Network for Transgender Healthcare
Altabas V, Galjuf V, Žegura I, Jokić Begić N, Moravek D, Arbanas G and Begić D
A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response.
Goals, Barriers, and Facilitators of Caregivers Who Participated in an In-Home Intervention to Improve Food Parenting Practices and Child Diet Quality
Ramirez A, Fox K, Melo Herrera Y, Gans KM, Risica PM, McCurdy K, Jennings E and Tovar A
To explore the goals, barriers, and facilitators set by caregivers of preschool-aged children to improve food parenting practices and household food environments.
Association of sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression: A five-year cohort study
Narita Z, Hidese S, Kanehara R, Tachimori H, Hori H, Kim Y, Kunugi H, Arima K, Mizukami S, Tanno K, Takanashi N, Yamagishi K, Muraki I, Yasuda N, Saito I, Maruyama K, Yamaji T, Iwasaki M, Inoue M, Tsugane S and Sawada N
Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample.
Self-reported chronic conditions and COVID-19 public health measures among Canadian adults: an analysis of the Canadian longitudinal study on aging
De Rubeis V, Griffith LE, Duncan L, Jiang Y, de Groh M and Anderson LN
During the COVID-19 pandemic, public health measures were used to reduce the spread of COVID-19; it is unknown whether people with chronic conditions differentially adhered to public health measures. The objectives of this study were to evaluate the association between chronic conditions and adherence and to explore effect modification by sex, age, and income.
Lithium versus anticonvulsants and the risk of physical disorders - Results from a comprehensive long-term nation-wide population-based study emulating a target trial
Kessing LV, Knudsen MB, Rytgaard HCW, Torp-Pedersen C and Berk M
Bipolar disorder is associated with increased rates of many physical disorders, but the effects of medication are unclear. We systematically investigated the associations between sustained use of first line maintenance agents, lithium versus lamotrigine and valproate, and the risk of physical disorders using a nation-wide population-based target trial emulation covering the entire 5.9 million inhabitants in Denmark. We identified two cohorts. Cohort 1: patients with a diagnosis of bipolar disorder prior to first purchase (N = 12.607). Cohort 2: all 156.678 adult patients who had their first ever purchase (since 1995) of either lithium, lamotrigine or valproate between 1997 and 2021 regardless of diagnosis. Main analyses investigated the effect of sustained exposure defined as exposure for all consecutive 6-months periods during a 10-year follow-up. Outcomes included a diagnosis of incident stroke, arteriosclerosis, angina pectoris, myocardial infarction, diabetes mellitus, myxedema, osteoporosis, dementia, Parkinson's disease, chronic kidney disease and cancer (including subtypes). In both Cohorts 1 and 2, there were no systematic statistically significant differences in associations between sustained use of lithium versus lamotrigine and valproate, respectively, and any physical disorder, including subtypes of disorders, except myxedema, for which exposure to lithium increased the absolute risk of myxedema with 7-10 % compared with lamotrigine or valproate. In conclusion, these analyses emulating a target trial of "real world" observational register-based data show that lithium does not increase the risk of developing any kind of physical disorders, except myxedema, which may be a result of detection bias.
The psychosocial outcomes of advanced hybrid closed-loop system in children and adolescents with type 1 diabetes
Jalilova A, Pilan BŞ, Demir G, Özbaran B, Balkı HG, Arslan E, Köse SG, Özen S, Darcan Ş and Gökşen D
The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70-180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8-12 years) and parents; the Quality of Life for Youth scale for adolescents (13-18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients' HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients' PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months.  Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D. What is Known: • Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements. • Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D. • Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context. What is New: • First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients. • Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life.
Outcomes of long-acting injectable antipsychotics use in pregnancy: A literature review
Pejčić AV, Stefanović SM, Milosavljević MN, Janjić VS, Folić MM, Folić ND and Milosavljević JZ
Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy. Long-acting injectable (LAI) antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders, but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.
Comorbid depression among adults with heart failure in Ethiopia: a hospital-based cross-sectional study
Mulugeta H, Sinclair PM and Wilson A
Depression is a common comorbidity in adults with heart failure. It is associated with poor clinical outcomes, including decreased health-related quality of life and increased morbidity and mortality. There is a lack of data concerning the extent of this issue in Ethiopia. Consequently, this study aimed to assess the prevalence of comorbid depression and associated factors among adults living with heart failure in Ethiopia.
Targeting GLP-1 receptors to reduce nicotine use disorder: Preclinical and clinical evidence
Herman RJ and Schmidt HD
Nicotine use disorder (NUD) remains a leading cause of preventable death in the U.S. Unfortunately, current FDA-approved pharmacotherapies for smoking cessation have limited efficacy and are associated with high rates of relapse. One major barrier to long-term smoking abstinence is body weight gain during withdrawal. Nicotine withdrawal-induced body weight gain can also lead to development of chronic disease states like obesity and type II diabetes mellitus. Therefore, it is critical to identify novel pharmacotherapies for NUD that decrease relapse and nicotine withdrawal symptoms including body weight gain. Recent studies demonstrate that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate voluntary nicotine taking and seeking and prevent withdrawal-induced hyperphagia and body weight gain. Emerging evidence also suggests that GLP-1R agonists improve cognitive deficits, as well as depressive- and anxiety-like behaviors, which contribute to smoking relapse during withdrawal. While further studies are necessary to fully characterize the effects of GLP-1R agonists on NUD and understand the mechanisms by which GLP-1R agonists decrease nicotine withdrawal-mediated behaviors, the current literature supports GLP-1R-based approaches to treating NUD.
Dysregulation of interleukin-8 is involved in the onset and relapse of schizophrenia: An independent validation and meta-analysis
Yan J, Xia Q, Sun X, Yang P, Gao H, Pan Z, Gao J, Zhang L, Wang M, Wang K, Li C, Zhang X, Ju P and Zhu C
As a major mental health disorder, symptoms of schizophrenia (SCZ) include delusions, reduced motivation, hallucinations, reduced motivation and a variety of cognitive disabilities. Many of these symptoms are now known to be associated with abnormal regulation of the immune system. Low blood levels of cytokines and chemokines have been suggested to be one of the underlying causes of SCZ. However, their biological roles at different stages of SCZ remain unclear. Our objective was to investigate expression patterns of cytokines and chemokines at different stages of onset and relapse in SCZ patients and to conduct an analysis of their relationship to disease progression. We also aimed to identify immune features associated with different disease trajectories in patients with SCZ. Gene set enrichment analysis (GSEA) was used to interrogate the GSE27383 dataset and identify key genes associated with inflammation. These results led us to recruit 36 healthy controls, 40 patients with first-episode psychosis (FEP), and 39 patients with SCZ relapse. Meso Scale Discovery technology was used to independently validate serum levels of 35 cytokines and chemokines. This was followed by a meta-analysis to gain a more comprehensive understanding of the role of interleukin-8 (IL-8/CXCL8) in SCZ. Analysis of the GSE27383 database revealed 3596 genes with distinct expression patterns. A significant portion of these genes were identified as inflammation-related and showed remarkable enrichment in three key pathways: IL-17, cytokine-cytokine receptor, and AGE-RAGE signaling in diabetic complications. We observed co-expression of CXCL8 and IL-16 within these three pathways. In a subsequent analysis of independently validated samples, a notable discrepancy was detected in the inflammatory status between individuals experiencing FEP and those in relapse. In particular, expression of CXCL8 demonstrated superior predictive capability in FEP and relapsed patients. Notably, results of the meta-analysis confirmed that Chinese and European populations were consistent with the overall results (Z = 4.60, P < 0.001; Z = 3.70, P < 0.001). However, in the American subgroup, there was no significant difference in CXCL8 levels between patients with SCZ compared to healthy controls (Z = 1.09, P = 0.277). Our findings suggest that the inflammatory response in patients with SCZ differs across the different stages, with CXCL8 emerging as a potential predictive factor. Collectively, our data suggest that CXCL8 has the potential to serve as a significant immunological signature of SCZ subtypes. Trial registration: The clinical registration number for this trial is ChiCTR2100045240 (Registration Date: 2021/04/09).
Income variability and incident cardiovascular disease in diabetes: a population-based cohort study
Park YM, Baek JH, Lee HS, Elfassy T, Brown CC, Schootman M, Narcisse MR, Ko SH, McElfish PA, Thomsen MR, Amick BC, Lee SS and Han K
Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D).
Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era
Ross EJ, Jimenez DE, Ghanooni D, Mendez A, Hirshfield S, Horvath KJ, DeVries B, Dilworth SE, Carrico AW and Martinez CA
Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV.
Complex visual hallucinations associated with ranolazine treatment: a case report
Prebil K, Palandacic AK and Rus Prelog P
Ranolazine is a piperazine derivative and is indicated for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies. Visual hallucinations together with neurological symptoms have been described with ranolazine treatment. In this case report, we describe a case of an elderly diabetic patient with chronic angina pectoris who developed visual hallucinations during an acute worsening of kidney function after tolerating ranolazine well for six years. Regular monitoring of electrocardiograms, kidney function, and psychiatric and neurological adverse effects in elderly patients on ranolazine is advised.
The National Sleep Research Resource: making data findable, accessible, interoperable, reusable and promoting sleep science
Zhang Y, Kim M, Prerau M, Mobley D, Rueschman M, Sparks K, Tully M, Purcell S and Redline S
This paper presents a comprehensive overview of the National Sleep Research Resource (NSRR), a National Heart Lung and Blood Institute-supported repository developed to share data from clinical studies focused on the evaluation of sleep disorders. The NSRR addresses challenges presented by the heterogeneity of sleep-related data, leveraging innovative strategies to optimize the quality and accessibility of available datasets. It provides authorized users with secure centralized access to a large quantity of sleep-related data including polysomnography, actigraphy, demographics, patient-reported outcomes, and other data. In developing the NSRR, we have implemented data processing protocols that ensure de-identification and compliance with FAIR (Findable, Accessible, Interoperable, Reusable) principles. Heterogeneity stemming from intrinsic variation in the collection, annotation, definition, and interpretation of data has proven to be one of the primary obstacles to efficient sharing of datasets. Approaches employed by the NSRR to address this heterogeneity include (1) development of standardized sleep terminologies utilizing a compositional coding scheme, (2) specification of comprehensive metadata, (3) harmonization of commonly used variables, and (3) computational tools developed to standardize signal processing. We have also leveraged external resources to engineer a domain-specific approach to data harmonization. We describe the scope of data within the NSRR, its role in promoting sleep and circadian research through data sharing, and harmonization of large datasets and analytical tools. Finally, we identify opportunities for approaches for the field of sleep medicine to further support data standardization and sharing.
The impact of low-energy total diet replacement with behavioural support for remission of type 2 diabetes on disordered eating (ARIADNE): Protocol for a non-inferiority randomised controlled trial
Tsompanaki E, Aveyard P, Park RJ and Koutoukidis DA
The National Health Service (NHS) in England is currently piloting a weight loss programme for remission of newly diagnosed type 2 diabetes (T2D), where participants replace all food with low-energy nutritionally complete formula products for 12 weeks (total diet replacement, TDR) and receive behavioural support. In a clinical trial, this programme led to remission in nearly half the participants. However, this weight loss programme might also worsen disordered eating and prompt eating disorders in susceptible people. We aim to investigate if the TDR programme is non-inferior to standard care in terms of disordered eating in susceptible individuals.
Assessing quality of direct-to-consumer telemedicine in China: a cross-sectional study using unannounced standardised patients
Zeng Z, Xu DR, Cai Y and Gong W
Direct-to-onsumer telemedicine (DTCT) has become popular as an alternative to traditional care. However, uncertainties about the potential risks associated with the lack of comprehensive quality evaluation could influence its long-term development. This study aimed to assess the quality of care provided by DTCT platforms in China using unannounced standardised patients (USP) between July 2021 and January 2022. The study assessed consultation services on both hospital and enterprise-sponsored platforms using the Institute of Medicine quality framework. It employed 10 USP cases, covering conditions such as diabetes, asthma, common cold, gastritis, angina, low back pain, child diarrhoea, child dermatitis, stress urinary incontinence and postpartum depression. Descriptive and regression analyses were employed to examine platform characteristics and compare quality across platform types. The results showed that of 170 USP visits across 107 different telemedicine platforms, enterprise-sponsored platforms achieved a 100% success in access, while hospital-sponsored platforms had a success rate of only 47.5% (56/118). Analysis highlighted a low overall correct diagnosis rate of 45% and inadequate adherence to clinical guidelines across all platforms. Notably, enterprise-sponsored platforms outperformed in accessibility, response time and case management compared with hospital-sponsored platforms. This study highlights the suboptimal quality of DTCT platforms in China, particularly for hospital-sponsored platforms. To further enhance DTCT services, future studies should compare DTCT and in-person care, aiming to identify gaps and potential risks associated with using DTCT as alternatives or supplements to traditional care. The potential of future development in enhancing DTCT services may involve exploring the integration of hospital resources with the technology and market capabilities of enterprise-sponsored platforms.
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Keaton JM, Kamali Z, Xie T, Vaez A, Williams A, Goleva SB, Ani A, Evangelou E, Hellwege JN, Yengo L, Young WJ, Traylor M, Giri A, Zheng Z, Zeng J, Chasman DI, Morris AP, Caulfield MJ, Hwang SJ, Kooner JS, Conen D, Attia JR, Morrison AC, Loos RJF, Kristiansson K, Schmidt R, Hicks AA, Pramstaller PP, Nelson CP, Samani NJ, Risch L, Gyllensten U, Melander O, Riese H, Wilson JF, Campbell H, Rich SS, Psaty BM, Lu Y, Rotter JI, Guo X, Rice KM, Vollenweider P, Sundström J, Langenberg C, Tobin MD, Giedraitis V, Luan J, Tuomilehto J, Kutalik Z, Ripatti S, Salomaa V, Girotto G, Trompet S, Jukema JW, van der Harst P, Ridker PM, Giulianini F, Vitart V, Goel A, Watkins H, Harris SE, Deary IJ, van der Most PJ, Oldehinkel AJ, Keavney BD, Hayward C, Campbell A, Boehnke M, Scott LJ, Boutin T, Mamasoula C, Järvelin MR, Peters A, Gieger C, Lakatta EG, Cucca F, Hui J, Knekt P, Enroth S, De Borst MH, Polašek O, Concas MP, Catamo E, Cocca M, Li-Gao R, Hofer E, Schmidt H, Spedicati B, Waldenberger M, Strachan DP, Laan M, Teumer A, Dörr M, Gudnason V, Cook JP, Ruggiero D, Kolcic I, Boerwinkle E, Traglia M, Lehtimäki T, Raitakari OT, Johnson AD, Newton-Cheh C, Brown MJ, Dominiczak AF, Sever PJ, Poulter N, Chambers JC, Elosua R, Siscovick D, Esko T, Metspalu A, Strawbridge RJ, Laakso M, Hamsten A, Hottenga JJ, de Geus E, Morris AD, Palmer CNA, Nolte IM, Milaneschi Y, Marten J, Wright A, Zeggini E, Howson JMM, O'Donnell CJ, Spector T, Nalls MA, Simonsick EM, Liu Y, van Duijn CM, Butterworth AS, Danesh JN, Menni C, Wareham NJ, Khaw KT, Sun YV, Wilson PWF, Cho K, Visscher PM, Denny JC, , , , , Levy D, Edwards TL, Munroe PB, Snieder H and Warren HR
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.
Association between white matter hyperintensity and anxiety/depression
Zhou R, Cai Q, Liu C, Hui J, Kang M, Gou Y, Liu Y, Shi P, Wang B and Zhang F
Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: β = 0.152, deep white matter hyperintensity: β = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: β = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.
Time-varying associations of gestational and childhood triclosan with pubertal and adrenarchal outcomes in early adolescence
Laue HE, Lanphear BP, Calafat AM, Cecil KM, Chen A, Xu Y, Kalkwarf HJ, Madan JC, Karagas MR, Yolton K, Fleisch AF and Braun JM
Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage.
Glycemic Control, Cognitive Aging, and Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (Hispanic Community Health Study/Study of Latinos)
González HM, Tarraf W, Stickel AM, Morlett A, González KA, Ramos AR, Rundek T, Gallo LC, Talavera GA, Daviglus ML, Lipton RB, Isasi C, Lamar M, Zeng D and DeCarli C
Hispanics/Latinos in the United States have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanics/Latinos of diverse heritages.
Disordered eating in adolescents with type 1 diabetes: risk factors and screening recommendations
Chad-Friedman E, Clary L and Jhe G
Adolescents with Type 1 diabetes (T1D) are at significantly greater risk for disordered eating behaviors compared to their peers without T1D. Given that this is a dangerous and potentially lethal combination, this review aims to support pediatric medical providers in increasing competence in identification, assessment, and prevention of disordered eating behaviors in adolescents with T1D.
The role of peer social relationships in psychological distress and quality of life among adolescents with type 1 diabetes mellitus: a longitudinal study
Luo D, Cai X, Wang H, Wang Y and Xu J
Adolescents with type 1 diabetes mellitus suffer from diabetes distress and poor health-related quality of life (HRQOL) since living with the condition that differentiates them from their peers. The present study investigated the effects of peer support and stress on diabetes distress and HRQOL and whether positive coping mediated the effects.
Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening
Milatz F, Klotsche J, Niewerth M, Sengler C, Windschall D, Kallinich T, Dressler F, Trauzeddel R, Holl RW, Foeldvari I, Brück N, Temming S, Hospach T, Warschburger P, Berendes R, Erbis G, Kuemmerle-Deschner JB, Weller-Heinemann F, Haas JP, Müller-Stierlin AS, Mutter A, Meissner T, Baumeister H and Minden K
Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results.
Population incidence and associated mortality of urinary tract infection in people living with dementia
Lai H, Kolanko M, Li LM, Parkinson ME, Bourke NJ, Graham NSN, David MCB, Mallas EJ, Su B, Daniels S, Wilson D, Golemme M, Norman C, Jensen K, Jackson R, Tran M, Freemont PS, Wingfield D, Wilkinson T, Gregg EW, Tzoulaki I, Sharp DJ and Soreq E
Urinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality.
Assessing We-Disease Appraisals of Health Problems: Development and Validation of the We-Disease Questionnaire
Vogt AJ, Bartels L, Bertschi IC, Mahler F, Grotzer M, Konrad D, Leibundgut K, Rössler J, Bodenmann G and Landolt MA
In couples dealing with health problems, we-disease appraisals can influence dyadic coping strategies to alleviate distress. This study describes the development and validation of a self-report scale to assess we-disease appraisals of health problems. The newly developed We-Disease Questionnaire (WDQ) was administered in three samples: parents of children with type 1 diabetes ( = 240) or cancer ( = 125) and individuals with visual impairment and their partners ( = 216). Reliability was measured by coefficient omega. To assess construct validity, correlations with other measures of individual and dyadic adjustment were examined. Descriptive statistics across all samples were compared. A 4-item version of the WDQ demonstrated good reliability and validity and showed meaningful associations with established scales. We-disease appraisals were highest among parents of children with cancer and lowest among couples with visual impairment. The WDQ is a reliable and valid measure that can be used across different health problems.
Insights from animal models on insulin signalling disturbances and related diseases in neurological and mental conditions
Slattery DA
There has been a growing awareness of the need for scientific research to focus on somatic and mental comorbidities in recent years due to the emerging evidence showing their substantial overlap at numerous levels. In this special issue, initiated by members of the EU-funded PRIME consortium ("Prevention and Remediation of Insulin Multimorbidity in Europe; www.prime-study.eu), the focus is on the comorbidities of metabolic disturbances, especially related to insulin signalling dysregulation and mental and neurological disorders. Thus, while obesity, type 2 diabetes, and metabolic syndrome are commonly known to be insulin-related disorders, the last decades have shown that neurodegenerative disorders, such as Alzheimer's disease, as well as neurodevelopment disorders, such as obsessive-compulsive disorder (OCD), autism spectrum disorders (ASDs) and attention deficit / hyperactivity disorder (ADHD) also fall into this category. The special issue draws together a series of basic and clinical review articles that describe the current knowledge and future perspectives regarding insulin comorbidities across a multidisciplinary group of experts.
Antidepressant treatment and mortality in people with comorbid depression and type 2 diabetes: UK electronic health record study
Jeffery A, Walters K, Wong ICK, Osborn D and Hayes JF
Depression is associated with higher rates of premature mortality in people with physical comorbidities, such as type 2 diabetes. Conceptually, the successful treatment of depression in people with type 2 diabetes could prevent premature mortality.
The past, present, and future of behavioral obesity treatment
Chao AM, Moore M and Wadden TA
Over the last century, hundreds of evaluations have been conducted to examine weight-management interventions related to diet, physical activity, and behavior therapy. These investigations have contributed to a growing body of knowledge that has consistently advanced the field of obesity treatment, while also revealing some persistent challenges. This narrative review summarizes key findings from randomized controlled trials conducted in adults that have combined diet, physical activity, and behavior therapy, an approach variously referred to as behavioral treatment, comprehensive lifestyle modification, or intensive lifestyle intervention. The review shows that current behavioral approaches induce average reductions in baseline body weight of 5 to 10% at 6 to 12 months. Such losses have proven effective in reducing the risk of type 2 diabetes in persons with impaired glucose tolerance and in improving other obesity-related complications. These benefits have also been associated with reductions in healthcare costs. Despite these advances, behavioral treatment is challenged by the need for larger losses to achieve optimal improvements in health, by difficulties associated with maintaining weight loss, and by barriers limiting access to treatment. New anti-obesity medications, when combined with behavioral obesity treatment, hold promise of addressing the first two issues.
Gut microbiome predicts cognitive function and depressive symptoms in late life
Kolobaric A, Andreescu C, Jašarević E, Hong CH, Roh HW, Cheong JY, Kim YK, Shin TS, Kang CS, Kwon CO, Yoon SY, Hong SW, Aizenstein HJ, Karim HT and Son SJ
Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
ESCAP statement on the care for children and adolescents with gender dysphoria: an urgent need for safeguarding clinical, scientific, and ethical standards
Drobnič Radobuljac M, Grošelj U, Kaltiala R, , , Vermeiren R, Crommen S, Kotsis K, Danese A, Hoekstra PJ and Fegert JM
National Cohort Data Suggests an Association Between Serious Mental Illness and Audiometric Hearing Loss
Alter IL, Tucker LH, Dragon JM, Grewal MR, Saperstein A, Stroup TS, Medalia AA and Golub JS
To explore whether there is an association between serious mental illness (SMI) and hearing loss (HL) among US Hispanic adults.
Clinical trajectories preceding incident dementia up to 15 years before diagnosis: a large prospective cohort study
You J, Guo Y, Wang YJ, Zhang Y, Wang HF, Wang LB, Kang JJ, Feng JF, Yu JT and Cheng W
Dementia has a long prodromal stage with various pathophysiological manifestations; however, the progression of pre-diagnostic changes remains unclear. We aimed to determine the evolutional trajectories of multiple-domain clinical assessments and health conditions up to 15 years before the diagnosis of dementia.
Continuous alcohol withdrawal delirium and physical illness-associated delirium in a man brought to the emergency department after a disaster: A case report
Kikuchi K, Hasegawa C, Sasaki T, Sato Y, Owada T, Shindo Y, Kawamata Y, Sugawara N and Yasui-Furukori N
Risk factors for alcohol withdrawal delirium include heavy drinking, prior alcohol withdrawal delirium or convulsions, nondrug sedative use, and a history of tachycardia, withdrawal, and infections.
FREE: A randomized controlled feasibility trial of a cognitive behavioral therapy and technology-assisted intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes
Martyn-Nemeth P, Duffecy J, Quinn L, Park C, Reutrakul S, Mihailescu D, Park M and Penckofer S
The purpose of this study was to test the preliminary effectiveness of a cognitive behavioral therapy intervention (Fear Reduction Efficacy Evaluation [FREE]) designed to reduce fear of hypoglycemia in young adults with type 1 diabetes. The primary outcome was fear of hypoglycemia, secondary outcomes were A1C, and glycemic variability.
The Association Between Unintended Pregnancy and Perinatal Outcomes in Low-Risk Pregnancies: A Retrospective Registry Study in the Netherlands
van Tintelen AMG, Jansen DEMC, Bolt SH, Warmelink JC, Verhoeven CJ and Henrichs J
People with unintended pregnancies might be at increased risk of adverse perinatal outcomes due to structural factors, distress, or delayed prenatal care. Existing studies addressing this association yielded inconsistent findings. Using contemporary data from a large Dutch midwifery care registry, we investigated the association between unintended pregnancy ending in birth and neonatal outcomes, parental morbidity, and obstetric interventions. We extend previous research by exploring whether delayed initiation of prenatal care mediates these associations.
Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus
Obeid R, Andrès E, Češka R, Hooshmand B, Guéant-Rodriguez RM, Prada GI, Sławek J, Traykov L, Ta Van B, Várkonyi T, Reiners K and The Vitamin B Consensus Panelists Group
: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. : We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. : The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. : There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.
The role of immuno-metabolic depression features in the effects of light therapy in patients with depression and type 2 diabetes mellitus: A randomized controlled trial
Vreijling SR, Neuhaus L, Brouwer A, Penninx BWJH, Beekman ATF, Lamers F, Jansen R and Bremmer M
Immuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored.
Psychiatric disorders in pregnant women admitted to the high-risk obstetric service in a Colombian university clinic between 2013 and 2017
Constaín GA, Ocampo Saldarriaga MV, Franco Vásquez JGF, Naranjo LF, Restrepo Conde C, Estrada Muñoz D, Chaverra López L and Buriticá González JB
To determine the psychiatric diagnoses and treatments of patients admitted to the high-risk obstetric service who underwent a consultation with a liaison psychiatrist.
Assessing ChatGPT 4.0's test performance and clinical diagnostic accuracy on USMLE STEP 2 CK and clinical case reports
Shieh A, Tran B, He G, Kumar M, Freed JA and Majety P
While there is data assessing the test performance of artificial intelligence (AI) chatbots, including the Generative Pre-trained Transformer 4.0 (GPT 4) chatbot (ChatGPT 4.0), there is scarce data on its diagnostic accuracy of clinical cases. We assessed the large language model (LLM), ChatGPT 4.0, on its ability to answer questions from the United States Medical Licensing Exam (USMLE) Step 2, as well as its ability to generate a differential diagnosis based on corresponding clinical vignettes from published case reports. A total of 109 Step 2 Clinical Knowledge (CK) practice questions were inputted into both ChatGPT 3.5 and ChatGPT 4.0, asking ChatGPT to pick the correct answer. Compared to its previous version, ChatGPT 3.5, we found improved accuracy of ChatGPT 4.0 when answering these questions, from 47.7 to 87.2% (p = 0.035) respectively. Utilizing the topics tested on Step 2 CK questions, we additionally found 63 corresponding published case report vignettes and asked ChatGPT 4.0 to come up with its top three differential diagnosis. ChatGPT 4.0 accurately created a shortlist of differential diagnoses in 74.6% of the 63 case reports (74.6%). We analyzed ChatGPT 4.0's confidence in its diagnosis by asking it to rank its top three differentials from most to least likely. Out of the 47 correct diagnoses, 33 were the first (70.2%) on the differential diagnosis list, 11 were second (23.4%), and three were third (6.4%). Our study shows the continued iterative improvement in ChatGPT's ability to answer standardized USMLE questions accurately and provides insights into ChatGPT's clinical diagnostic accuracy.
Intersectional stigma and the non-communicable disease syndemic in the context of HIV: protocol for a multisite, observational study in the USA
Friedman MR, Badri S, Bowleg L, Haberlen SA, Jones DL, Kempf MC, Konkle-Parker D, Kwait J, Martinson J, Mimiaga MJ, Plankey MW, Stosor V, Tsai AC, Turan JM, Ware D and Wu K
The increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic. In the USA, there are substantial disparities by social position (ie, racial, ethnic and socioeconomic status) in the prevalence and/or control of non-communicable diseases and HIV. Intersecting stigmas, such as racism, classism and homophobia, may drive these health disparities by contributing to healthcare avoidance and by contributing to a psychosocial syndemic (stress, depression, violence victimisation and substance use), reducing success along the HIV and non-communicable disease continua of care. Our hypothesis is that marginalised populations experience disparities in non-communicable disease incidence, prevalence and control, mediated by intersectional stigma and the psychosocial syndemic.
Association of Pregnant Women's Perinatal Depression with Sociodemographic, Anthropometric and Lifestyle Factors and Perinatal and Postnatal Outcomes: A Cross-Sectional Study
Jacovides C, Papadopoulou SK, Pavlidou E, Dakanalis A, Alexatou O, Vorvolakos T, Lechouritis E, Papacosta E, Chrysafi M, Mitsiou M, Mentzelou M, Kosti RI and Giaginis C
In recent decades, the incidence of depression has gradually increased in the general population globally. Depression is also common during gestation and could result in detrimental gestational complications for both the mother and the fetus. The survey presented aimed to evaluate whether pregnant women's perinatal depression could be associated with socio-demographic, anthropometry and lifestyle factors, and perinatal and postnatal outcomes. This is a cross-sectional survey conducted on 5314 pregnant women. Socio-demographic and lifestyle factors were recorded by relevant questionnaires via face-to-face interviews. Anthropometric parameters were measured by qualified personnel. Perinatal depressive symptomatology status was evaluated by Beck's Depression Inventory (BDI-II) questionnaire. Depressive symptoms throughout gestation were found in 35.1% of the enrolled women. Perinatal depression was significantly associated with lower educational and economic level, pre-pregnancy regular smoking and reduced levels of Mediterranean diet adherence levels, a higher prevalence of gestational diabetes and preterm birth, as well as a higher incidence of delivering by caesarean section and abnormal childbirth weight. Perinatal depression was also significantly associated with a higher prevalence of maternal postpartum depression and lower prevalence of exclusive breastfeeding practices, as well as with a higher incidence of childhood asthma. Pregnant women's perinatal depression appears to be associated with various socio-demographic, anthropometry, and lifestyle characteristics and with a higher frequency of several adverse pregnancy complications. The present findings emphasize the importance of pregnant women's perinatal mental health, highlighting the need to develop and apply public strategies and policies for psychological counseling and support of future mothers to minimize probable risk factors that may trigger perinatal depression. Novel well-organized, follow-up surveys of enhanced validity are highly recommended to establish more definitive conclusions.
Evaluation of the possible impact of the fear of hypoglycemia on diabetes management in children and adolescents with type 1 diabetes mellitus and their parents: a cross-sectional study
Andreopoulou O, Kostopoulou E, Kotanidou E, Daskalaki S, Vakka A, Galli-Tsinopoulou A and Spiliotis BE
Hypoglycemia represents a significant source of anxiety for children with type 1 diabetes mellitus (T1DM) and their caretakers. Fear of hypoglycemia (FoH) was measured in children and adolescents with T1DM as well as in their parents using an established research instrument, the Hypoglycemia Fear Survey (HFS).
Severe Maternal Morbidity and Mental Health Hospitalizations or Emergency Department Visits
Blackman A, Ukah UV, Platt RW, Meng X, Shapiro GD, Malhamé I, Ray JG, Lisonkova S, El-Chaâr D, Auger N and Dayan N
Severe maternal morbidity (SMM) can have long-term health consequences for the affected mother. The association between SMM and future maternal mental health conditions has not been well studied.
Associations between Sleep Disturbances, Personality Traits and Self-Regulation in a Sample of Healthy Adults
Zakiei A, Sadeghi-Bahmani D, Khazaie H, Lorestani Z, Sadeghi M, Korani D, Sahraei Z, Komasi S, Stanga Z, Brühl AB and Brand S
Scientific evidence and everyday experience show that sleep disturbances and self-regulation as a proxy of stress reactivity are linked. Particular personality traits such as neuroticism, internalizing and externalizing problems are also associated with sleep disturbances. Here, we combined self-regulation and personality traits and associated these variables with subjective sleep disturbances. A total of 846 adults (mean age: 33.7 years; 78.7% females) completed questionnaires covering sleep disturbances, self-regulation and personality traits. Higher scores for sleep disturbances were associated with higher scores for externalization, internalization, and instability and with lower scores for stability (all trait variables) and with poorer self-regulation (state variable). The regression model showed that higher scores for externalization and internalization (traits), and lower scores for self-regulation (state) predicted higher scores for sleep disturbance. Next, self-regulation had both a direct effect on sleep disturbance, and an indirect effect via personality traits. Sleep disturbances were related to both state (i.e., self-regulation) and trait (e.g., internalization and instability) dimensions. The current data analysis leapfrogs the state-trait dichotomy discussion and reconciles the state-and-trait approach in the prediction of poor sleep, though self-regulation appeared to have both direct and indirect effects on sleep disturbances.
Impact of Long-COVID in children: a large cohort study
Hersh Z, Weisband YL, Bogan A, Leibovich A, Obolski U, Nevo D and Gilad-Bachrach R
The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3-6 months after the date of diagnosis.
Depressive disorder and elevated risk of bell's palsy: a nationwide propensity score-weighting study
Fann LY, Wen YL, Huang YC, Cheng CC, Huang YC, Fang CC, Chen WT, Yu PY, Pan HY and Kao LT
Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy.
DNA methylation-based telomere length is associated with HIV infection, physical frailty, cancer, and all-cause mortality
Liang X, Aouizerat BE, So-Armah K, Cohen MH, Marconi VC, Xu K and Justice AC
Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality.
Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden
Metsälä J, Risnes K, Persson M, Veijola R, Pulakka A, Heikkilä K, Alenius S, Gissler M, Opdahl S, Sandin S and Kajantie E
Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth.
Liraglutide 3.0 mg once daily for the treatment of overweight and obesity in patients hospitalised at a forensic psychiatric department: A 26-week open-label feasibility study
Sass MR, Christensen AMB, Christensen ML, Gruber E, Nerdrum H, Pedersen LM, Resch M, Jørgensen TH, Ekstrøm CT, Nielsen J, Vilsbøll T and Fink-Jensen A
Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry.
Genital Surgery Outcomes Using an Individualized Algorithm for Hormone Management in Transfeminine Individuals
Herndon J, Gupta N, Davidge-Pitts C, Imhof N, Gonzalez C, Carlson S, Will M, Martinez-Jorge J, Fahradyan V, Tamire L, Lin A, Nippoldt TB and Chang AY
Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender affirming providers.
Methods to predict heart failure in diabetes patients
Berezin AE, Berezina TA, Hoppe UC, Lichtenauer M and Berezin AA
Type 2 diabetes mellitus (T2DM) is one of the leading causes of cardiovascular disease and powerful predictor for new-onset heart failure (HF).
Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis
Lemche E, Killick R, Mitchell J, Caton PW, Choudhary P and Howard JK
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Healthcare Utilization and Its Correlates in Comorbid Type 2 Diabetes Mellitus and Generalized Anxiety Disorder
Huang CJ, Lin CH, Liu TL, Lin PC, Chu CC, Wang JJ, Wei CW and Weng SF
This study investigated the healthcare utilization and medical expenditure of type 2 diabetes mellitus (T2DM) patients with generalized anxiety disorder (GAD) and identified the associated factors. The healthcare utilization and expenditure of T2DM patients with (case group) and without (control group) GAD between 2002 and 2013 were examined using the population-based Taiwan National Health Insurance Research Database. Healthcare utilization included outpatient visits and hospitalization; health expenditure included outpatient, inpatient, and total medical expenditure. Moreover, nonpsychiatric healthcare utilization and medical expenditure were distinguished from total healthcare utilization and medical expenditure. The average healthcare utilization, including outpatient visits and hospitalization, was significantly higher for the case group than for the control group (total and nonpsychiatric). The results regarding differences in average outpatient expenditure (total and nonpsychiatric), inpatient expenditure (total and nonpsychiatric), and total expenditure (total and nonpsychiatric) between the case and control groups are inconsistent. Sex, age, income, comorbidities/complications, and the diabetes mellitus complication severity index were significantly associated with outpatient visits, medical expenditure, and hospitalization in the case group (total and nonpsychiatric). Greater knowledge of factors affecting healthcare utilization and expenditure in comorbid individuals may help healthcare providers intervene to improve patient management and possibly reduce the healthcare burden in the future.
Adolescent gender dysphoria management: position paper from the Italian Academy of Pediatrics, the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, the Italian Society of Adolescent Medicine and the Italian Society of Child and Adolescent Neuropsychiatry
Calcaterra V, Tornese G, Zuccotti G, Staiano A, Cherubini V, Gaudino R, Fazzi EM, Barbi E, Chiarelli F, Corsello G, Esposito SMR, Ferrara P, Iughetti L, Laforgia N, Maghnie M, Marseglia G, Perilongo G, Pettoello-Mantovani M, Ruggieri M, Russo G, Salerno M, Striano P, Valerio G, Wasniewska M and
In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD.
Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes
Edmonston D, Mulder H, Lydon E, Chiswell K, Lampron Z, Shay C, Marsolo K, Jones WS, Butler J, Shah RC, Chamberlain AM, Ford DE, Gordon HS, Hwang W, Chang A, Rao A, Bosworth HB and Pagidipati N
Placebo-controlled trials of sodium-glucose co-transporter-2 inhibitors demonstrate kidney and cardiovascular benefits for patients with type 2 diabetes and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4is), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare the outcomes for empagliflozin and DPP4i initiators with type 2 diabetes between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate decrease, incident end-stage kidney disease, or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Of 62,197 new users, 20,279 initiated empagliflozin and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.65 to 0.87) than DPP4is. The risks for mortality (HR 0.76, 95% CI 0.62 to 0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70 to 0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 to 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53 to 0.88) and those without CKD (HR 0.79, 95% CI 0.67 to 0.94). In conclusion, the initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes than DPP4is over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for patients without known CKD at baseline.
Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study
Scheuer SH, Andersen GS, Carstensen B, Diaz L, Kosjerina V, Lindekilde N, Wild SH, Jackson CA, Pouwer F, Benros ME and Jørgensen ME
To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year.
Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic.
Improving support for university students with type 1 diabetes
Stoet G, Foster E, Kerr C, Jiang L, Thornhill MA, Cyranka K, Matejko B, Sarna-Palacz D, Płonka-Stępień M and Klupa T
Comparing targeted memory reactivation during slow wave sleep and sleep stage 2
Carbone J, Bibian C, Born J, Forcato C and Diekelmann S
Sleep facilitates declarative memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) in a declarative memory design by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.
PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis
Alnuaimi S, Reljic T, Abdulla FS, Memon H, Al-Ali S, Smith T, Serdarevic F, Velija Asimi Z, Kumar A and Semiz S
The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.
A randomised controlled trial to evaluate the effectiveness of a culture and disease-specific, patient-centric multi-component tobacco cessation intervention package for the patients attending non-communicable disease clinics in Punjab, India
Bhatt G, Goel S, Yadav SK, Patial A, Medhi B, Grover S, Attri S, Kaur R, Singh G and Gill SS
Developing an infrastructure to support tobacco cessation through existing systems and resources is crucial for ensuring the greatest possible access to cessation services. The present study aims to evaluate the effectiveness of a newly developed multi-component cessation among tobacco users in Non- Communicable Disease (NCD) clinics, functioning under the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases, & Stroke (NPCDCS) of the Government of India.
Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency
Villar-Gouy KR, Salmon CEG, Salvatori R, Kellner M, Krauss MPO, Rocha TO, de Souza EA, Batista VO, Leal ÂC, Santos LB, Melo EV, Oliveira-Santos AA, Oliveira CRP, Campos VC, Santos EG, Santana NO, Pereira FA, Amorim RS, Donato-Junior J, Filho JASB, Santos AC and Aguiar-Oliveira MH
Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI.
Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration
Kresge HA, Blostein F, Goleva S, Albiñana C, Revez JA, Wray NR, Vilhjálmsson BJ, Zhu Z, McGrath JJ and Davis LK
While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS and PGS scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.
GAUSS: a summary-statistics-based R package for accurate estimation of linkage disequilibrium for variants, Gaussian imputation, and TWAS analysis of cosmopolitan cohorts
Lee D and Bacanu SA
As the availability of larger and more ethnically diverse reference panels grows, there is an increase in demand for ancestry-informed imputation of genome-wide association studies (GWAS), and other downstream analyses, e.g. fine-mapping. Performing such analyses at the genotype level is computationally challenging and necessitates, at best, a laborious process to access individual-level genotype and phenotype data. Summary-statistics-based tools, not requiring individual-level data, provide an efficient alternative that streamlines computational requirements and promotes open science by simplifying the re-analysis and downstream analysis of existing GWAS summary data. However, existing tools perform only disparate parts of needed analysis, have only command-line interfaces, and are difficult to extend/link by applied researchers.
Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump
Corrado A, Scidà G, Vitale M, Caprio B, Costabile G, Annuzzi E, Della Pepa G, Lupoli R and Bozzetto L
Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM).
KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease
Lu QS, Ma L, Jiang WJ, Wang XB and Lu M
Epidemiological studies have revealed a correlation between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D). Insulin resistance in the brain is a common feature in patients with T2D and AD. KAT7 is a histone acetyltransferase that participates in the modulation of various genes.
The Prevalence and Predictors of Atherosclerotic Coronary Artery Disease in Rheumatic and Non-rheumatic Valvular Heart Disease Patients
Shafi S, Aouabdi S, Taher ZA, Alghamdi AE, Ahmed MA, Ahmed FA, Alghamdi S and Haneef A
The paradox of concurrent coronary artery disease (CAD) among patients with rheumatic and non-rheumatic valvular heart disease (RVHD; non-RVHD) is unclear. We aimed to evaluate the impact of the RVHD and non-RVHD on the prevalence of CAD and various risk factors, assess the number of diseased coronaries, clinical profile and the possible predictors of CAD in these patients, which may clarify the paradox and provide an insight for the prevention of CAD.
Primary Care Clinic Approaches to Facilitating Patient Health Behavior Change in Alabama
Distler KR, Lindsey MJ, Mims MH, Taylor MA and Hollingsworth JC
Background  Non-communicable chronic diseases (NCCDs), such as cardiovascular disease, diabetes, and cancer, are the leading cause of death and disability and the leading driver of healthcare costs in the U.S. It is estimated that 80% of chronic diseases and premature deaths are attributable to modifiable lifestyle factors related to smoking and alcohol intake, poor eating patterns, and physical inactivity. Inadequate sleep also plays a significant role. Among other directives, primary care providers (PCPs) have the opportunity to contribute to preventing and treating NCCD in their patients. Comprehensive, evidence-based behavioral counseling interventions are recommended to PCPs as a first-line approach to improving outcomes. However, presumably due to a lack of PCP time, training or resources, most patients report not receiving such services. Currently, the extent to which PCPs in Alabama offer or refer patients to health behavior change (HBC) services is unknown.  Objectives  This study aims to assess the following: (1) Alabama PCPs' current approaches in facilitating patient HBC in the domains of eating patterns, physical activity, sleep, and stress and (2) the likelihood of the Alabama PCPs referring patients to virtual HBC programs, once developed by an osteopathic medical school in the state.  Methods  Data were collected from clinic personnel who were knowledgeable regarding the clinic's approach to facilitating patient HBC via scripted telephone interviews and online surveys sent via email. The clinic list utilized for the study was derived from a list of VCOM-Auburn clinical preceptors. Primary care and specialty clinics were included. Data were analyzed descriptively to determine the number of clinics that (1) provide, recommend, or refer programs, services, or resources to patients to facilitate HBC related to eating patterns, physical activity, sleep, and stress management and (2) are likely to refer patients to free virtual HBC programs, once developed by an osteopathic medical school in the state. Results  Of the 198 clinics that were contacted, 75 were excluded, 46 were "no response," 53 agreed to participate, and 50 completed the survey. Of the 50 clinics that completed the survey, 33 indicated offering resources or referrals for diet, 29 stated they offered resources or referral services for physical activity, 33 indicated offering resources or referrals for sleep, and 28 indicated offering or recommending resources for stress management to patients. Most of the clinics (29/50) felt that their patients would benefit most from a program that facilitates improvement in eating patterns, and 41/50 clinics said that they are either "somewhat" or "extremely" likely to refer patients to a free VCOM-Auburn HBC program, once available.  Conclusions Findings indicate that a significant percentage of PCP clinics are not offering HBC resources to patients and that most PCP clinics would consider referring patients to free VCOM-Auburn HBC programs, once available. Phone data were significantly different from email data. The primary limitations were a low response rate and potential response bias.
Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent
Light V, Jones SL, Rahme E, Rousseau K, de Boer S, Vermunt L, Soltaninejad M, Teunissen C, Pijnenburg Y, Ducharme S and Consortium FS
Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking.
Inflammatory Dietary Potential Is Associated with Vitamin Depletion and Gut Microbial Dysbiosis in Early Pregnancy
Alvernaz SA, Wenzel ES, Nagelli U, Pezley LB, LaBomascus B, Gilbert JA, Maki PM, Tussing-Humphreys L and Peñalver Bernabé B
Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as , and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.
Depression in Polycystic Ovary Syndrome: Focusing on Pathogenesis and Treatment
Xing L, Xu J, Wei Y, Chen Y, Zhuang H, Tang W, Yu S, Zhang J, Yin G, Wang R, Zhao R and Qin D
Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies. Appeared originally in .
Interest in an Instagram-delivered gestational weight gain intervention among pregnant women with pre-pregnancy overweight or obesity
Waring ME, Arigo D, Rudin LR, Pagoto SL, Moore Simas TA and Horkachuck AB
Barriers to attending in-person lifestyle interventions are common during pregnancy. The majority of young adults use Instagram, and pregnancy-related content abounds on this social media platform. The aims of this study were to assess interest in an Instagram-delivered gestational weight gain (GWG) intervention, examine characteristics associated with program interest, describe interest in specific program components, and to explore perceived advantages of and concerns about the proposed intervention.
A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis
Motamed N, Zamani F, Maadi M, Ajdarkosh H, Roozafzai F, Keyvani H, Poustchi H, Shakeri R, Ashrafi GH, Perumal D, Rabiee B, Moradi-Lakeh M, Khoonsari M, Kheyri Z, Sohrabi MR, Doustmohammadian A, Amirkalali B, Safarnezhad Tameshkel F, Gholizadeh E, Hosseini SH and Karbalaie Niya MH
Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population.
Traumatic stress symptoms, mental splitting and burnout in health care professionals: a cross-sectional study
Riethof N and Bob P
Burnout syndrome usually begins with feelings of enthusiasm and idealized visualizations, and it is in contrast with subsequent disillusionment, disappointment, and symptoms which are related to chronic stress experienced later. This tendency to idealization is a parallel to the concept of "mental splitting" described by Kernberg with a pronounced "black and white" perceptual dichotomy between the early idealization and later disillusionment. This study intends examination of relationships between burnout syndrome, traumatic stress and Kernberg's concept of splitting.
Impact of depression on self-efficacy, illness perceptions and self-management among people with type 2 diabetes: A systematic review of longitudinal studies
Derese A, Gebreegzhiabhere Y, Medhin G, Sirgu S and Hanlon C
Treating comorbid depression does not always improve outcomes for people with type 2 diabetes. Evidence is lacking on potential psychological and behavioural intermediaries of the impact of depression on diabetes outcomes.
Self-reported symptom burden among patients attending public health care facilities in India: Looking through ICPC-3 lens
Gupta P, Bharati B, Sundar Sahu K, Mahapatra P and Pati S
The objectives of this study were: 1) to describe the socio-demographics and classify the chief complaints and reasons to encounter facilities of patients presenting to public healthcare facilities; 2) to explore differences in these complaints and: International Classification of Primary Care-3 (ICPC-3) groups across socio-demographic and health system levels.
Correlation between maternal and umbilical cord 25-hydroxy-vitamin D levels over a range of values. A prospective observational study from the United Arab Emirates
Jutell M, Bhat S, Bagge ML, Isberg PE and Wiberg N
Worldwide vitamin D insufficiency is remarkably prevalent in both children and adults, including pregnant women. The total amount of the vitamin is best measured by 25-hydroxy-vitamin D (25(OH)D), which is a measurement of total serum cholecalciferol 25(OH)D3 and ergocalciferol 25(OH)D2. There is a known correlation between maternal and umbilical cord blood (UCB) 25(OH)D; however, whether specific maternal demographics or comorbidities influence the correlation remains uncertain. This prospective observational study was designed to study if maternal 25(OH)D levels, maternal age and BMI, amount of supplementation, mode of delivery, diabetes, hypertension/preeclampsia, or sunlight exposure had an impact on the correlation. Women were enrolled in the study at admission to the labor ward. If they agreed to participate, venous blood was directly collected and analyzed for 25(OH)D. The UCB was sampled after delivery from the unclamped cord and immediately analyzed for 25(OH)D. ANOVA, Fisher's exact test, Pearson's correlation, and test of the differences between correlations using Fisher's z-transformation with Bonferroni correction were used accordingly. Of the 298 women enrolled, blood from both the mother and umbilical cord was analyzed successfully for 25(OH)D in 235 cases. The crude correlation between maternal and UCB 25(OH)D was very strong over all values of 25(OH)D (r = 0.905, R2 = 0.821, p <0,001) and remained strong independently of maternal demographics or co-morbidities (r ≥ 0.803, R2 ≥ 0.644, p <0.001). For women who delivered by caesarean section in second stage the correlation was strong (r ≥ 0.633, R2 ≥ 0.4, p <0.037). Test of differences between correlations showed significant stronger correlation in women with unknown 25(OH)D3 supplementation compared to women receiving 10.000 IU/week (p = 0.02) and 20.000IU/week (p = 0.01) and that the correlation was significantly stronger for women with a BMI of 25-29.9 compared to women with a BMI of <24.9 (p = 0.004) and 30-34.9 (p = 0.002). 213 (91%) women had lower 25(OH)D compared to the neonate, with a mean difference of -13.7nmol/L (SD = 15.6). In summary, the correlation between maternal and UCB 25(OH)D is very strong throughout low to high maternal levels of 25(OH)D with lower levels in maternal blood. Typical maternal demographics and comorbidities did not affect the transition.
A Systematic Guideline by the ASPN Workgroup on the Evidence, Education, and Treatment Algorithm for Painful Diabetic Neuropathy: SWEET
Sayed D, Deer TR, Hagedorn JM, Sayed A, D'Souza RS, Lam CM, Khatri N, Hussaini Z, Pritzlaff SG, Abdullah NM, Tieppo Francio V, Falowski SM, Ibrahim YM, Malinowski MN, Budwany RR, Strand NH, Sochacki KM, Shah A, Dunn TM, Nasseri M, Lee DW, Kapural L, Bedder MD, Petersen EA, Amirdelfan K, Schatman ME and Grider JS
Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN.
Assessing cognitive impairment in home-dwelling Chinese elders aged 80+: a detailed survey of 13,000 participants focusing on demographic factors, social engagement, and disease prevalence
Bian S, Tian X, Meng F, Xu C, Zhao Y, Gao Q and Bian C
Cognitive Impairment (CI) in the elderly, encompassing conditions ranging from Mild Cognitive Impairment (MCI) to dementia, represents a growing public health concern globally. This study aims to investigate the prevalence and correlates of CI among individuals aged 80 and above.
Patterns and predictors of female sexual dysfunction in diabetes mellitus
Sachdeva A, Kumar V, Khullar S, Sharma A and DAS A
Background Sexual complications of people with diabetes mellitus (DM) are often neglected by the patients as well as clinicians. The neglect is more in women due to the associated stigma and taboo. Indian studies are scanty, varied and inconsistent, regarding the impact of DM on sexual functioning in women. We studied the patterns and predictors of sexual dysfunction in women with DM. Methods We did a cross-sectional questionnaire-based study comprising 50 participants in both the study (women with DM1 and DM2) and control groups (relatives/caregivers of patients and the hospital staff), selected randomly from the medicine outpatient department from May to August 2016. Approval from the institutional ethics committee was obtained. Clinical anxiety and depression were screened using the hospital anxiety and depression scale. Sexual dysfunction was assessed through female sexual function index scale (FSFI), and predictors were assessed by correlating FSFI scores with sociodemographic and clinical parameters. Results We found that 44% of women with DM had sexual dysfunction compared with 20% in the control group (p<0.01). The pattern of sexual dysfunction was seen across the domains of desire, arousal, lubrication and orgasm. High body mass index, higher age, duration of DM, treatment with insulin and complications of DM predicted a greater degree of sexual dysfunction among women. Conclusion Sexual dysfunction is common in women with DM, irrespective of the type of DM and coexisting psychological factors such as depression and anxiety.
A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia
Selvan P, Devkare P, Shetty A, Dharmadhikari S, Khandhedia C, Mane A, Mehta S and Andrade C
Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.
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