Comorbid Group Research Articles

FRI527 Timing Of Thyroxine Dose During Ramadan: A Randomized Controlled Trial

Abstract Disclosure: R.M. Alamoudi: None. S.M. Nawar: None. H.S. Alharbi: None. A.A. Al Qarni: None. A. Alzahrani: None. A.K. Almulla: None. W.T. Busaad: None. N.F. Alahmari: None. N.D. Alshamrani: None. L. Alkhalifa: None. Y.M. Saleh: None. M. Ramadan: None. A. Borai: None. Background: The effect of Ramadan fasting on the thyroid profile, and the best time for L-thyroxine (LT4) intake in relation to fasting during Ramadan remains undetermined. Objectives: To compare two different time points of taking LT4 therapy during fasting the month of Ramadan in regards to thyroid profile and patient satisfaction. Methods: A multicenter open-label randomized controlled trial. Patients with primary hypothyroidism were recruited from three centers in three cities in Saudi Arabia (Jeddah, Riyadh, and Alhasa). Patients with thyroid cancer were excluded. TSH and FreeT4 (FT4) were measured two weeks before Ramadan, and four to six weeks after Ramadan. Results: 303 patients with primary hypothyroidism were randomized; 156 to take the LT4 dose at sunset with sips of water at the time of breaking fast and wait 30-60 minutes to eat the main Iftar meal (pre-Iftar), and 147 to take the LT4 dose just before the start of fasting (pre-dawn) regardless of their last meal intake. There were no significant differences between the two groups in demographics or comorbidities. The mean age was 49 ±12 years, 87% were female, and the average duration of hypothyroidism was 9.7 ±8.25 years. The mean weekly LT4 dose in the pre-Iftar vs. pre-dawn group was 753.3 ±349.4 vs. 733.2 ±265.6 mcg, p=0.001, and the Pre-Ramadan thyroid profile was: TSH 2.56 ±2.16 vs. 2.46 ±1.72 mIU/L, p=0.3, FT4 13.45 ±2.1 vs 13.08 ±2.4 pmol/L, p=0.16. Post-Ramadan thyroid profile values were: TSH 3.64 ± 4.1 vs. 4.07 ±4.17 mIU/L, p=0.78, FT4 12.96 ±0.1 vs. 12.64 ±0.22 pmol/L, p=0.003. The estimated difference within the group means post-Ramadan was - 0.41 ±0.51 mIU/L, p=0.43 for TSH, and 0.32 ±0.28 pmol/L, p=0.24 for FT4. Generalized linear model repeated measures analysis of variance showed no significant difference over time in TSH or FT4 within or between groups (p = 0.47 vs. 0.81). Patient compliance and satisfaction with the regimens were similar between groups. Conclusion: There is no significant change nor difference in thyroid profile between the two regimens related to the change in LT4 intake during the fasting months of Ramadan. Both regimens can be utilized depending on patient preferences. ClinicalTrials.gov: NCT05421468. Saudi FDA: SCTR # 22041002 Presentation: Friday, June 16, 2023

ADHD and anxiety symptom comorbidity from an event segmentation lens

ADHD and anxiety present high comorbidity, including symptom overlap and related diagnostic and treatment challenges. The current study aimed to extend this area of research by investigating the event segmentation patterns of those with ADHD and anxiety symptoms. Event segmentation is the process of parsing a continuous flow of information into meaningful events, providing the opportunity to examine similarities and differences in how these groups organize their perception of daily experiences. Participants performed an event segmentation task consisting of watching four short movies and identifying large and small events. We used the total number of button presses and segmentation agreement scores in a multivariate analysis, and results indicated that the High ADHD group identified significantly more events in the large condition than the High Anxiety group and had significantly higher agreement scores than the Comorbid group. This study furthers our understanding of the cognitive overlap of ADHD and anxiety symptoms.

Towards a personalized health care using a divisive hierarchical clustering approach for comorbidity and the prediction of conditioned group risks.

The objective was to assess risk of hospitalization and mortality of comorbidities using divisive hierarchical risk clustering to advice clinical interventions. Subjects and Methods: Data from the EHR of a general population, 3799885 adults, followed by 5 years. Model were performed using Spark and Scikit-learn and accuracy for the models was analyzed. Results: The number of models generated depends in part on the number of chronic diseases included (ex testing a sample of six diseases, a total number of 397 models for all-cause mortality and 431 models for hospitalization). The estimated models offered an ordered selection for the relevant clinical variables and their estimated risk as a group and for the individual patient in the group. Accuracy was assessed according to age, sex and the cardinality of the comorbid groups. A mobile version and dashboard were developed. Conclusion: The software developed stratified hospital admission and mortality risk in clusters of chronic diseases, and for a given patient, it could advise intensifying treatment or reallocating the patient risk.

Beyond Attention-Deficit Hyperactivity Disorder: Exploring Psychiatric Comorbidities and Their Neuropsychological Consequences in Adults.

This study aimed to identify the psychiatric comorbidity status of adult patients diagnosed with attention-deficit hyperactivity disorder (ADHD) and determine the impact of comorbidities on neuropsychological outcomes in ADHD. The study participants were 124 adult patients with ADHD. Clinical psychiatric assessments were performed by two boardcertified psychiatrists in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. All participants were assessed using the Mini-International Neuropsychiatric Interview Plus version 5.0.0 to evaluate comorbidities. After screening, neuropsychological outcomes were assessed using the Comprehensive Attention Test (CAT) and the Korean version of the Wechsler Adult Intelligence Scale, Fourth Edition (K-WAIS-IV). Mood disorders (38.7%) were the most common comorbidity of ADHD, followed by anxiety (18.5%) and substance use disorders (13.7%). The ADHD with comorbidities group showed worse results on the Perceptual Organization Index and Working Memory Index sections of the K-WAIS than the ADHD-alone group (p=0.015 and p=0.024, respectively). In addition, the presence of comorbidities was associated with worse performance on simple visual commission errors in the CAT tests (p=0.024). These findings suggest that psychiatric comorbidities are associated with poor neuropsychological outcomes in adult patients with ADHD, highlighting the need to identify comorbidities in these patients.

Analysis of IFN-γ and CD4+ responses in comorbid and adult immunized cynomolgus monkey with inactivated SARS-CoV-2 vaccine candidate

Context: Vaccination as prevention to hold back the spread of COVID-19 is important since it is the most concerning health issue in the last decade. Inactivated vaccine platforms considered safer, especially for elderly and comorbid patients. Comorbidities especially Tuberculosis and Hepatitis B, has a major impact to COVID-19 infections and vaccination. To evaluate infections or vaccine response IFN- γ and CD4+ are important. IFN-γ has a role in antiviral innate response, including initiation of other cytokines, increasing MHC expression, increasing presentation of macrophage, and increasing presentation of antigen to T cell Naïve. CD4+ is associated with humoral immune response. Cynomolgus Monkey or known as Macaca fascicularis. Specifying to comorbid patients, adult Macaca fascicularis that are detected to have hepatitis B and Tuberculosis (TBC) by PCR were treated as a comorbid group. Adult Macaca fascicularis that used in this research have range from 6 to 9 years old. This study was analysed with SPSS 26 general linear model repeated measures analysis with p<0.05 Objectives: To evaluate IFN- γ and CD4+ response of vaccination Result: The result of this study showed significant (p < 0.05) increase in IFN-γ and CD4+ evaluation in both comorbid and adult groups. The elevating concentration and percentage could be the sign of induced humoral and adaptive immune system in the body. Conclusion: SARS-CoV-2 inactivated vaccine candidate that used in this study can increase the number of IFN-γ concentration as well as percentage of CD4+ in adult and comorbid groups of Cynomolgus Macaques.

The impact of dual VA-Medicare use on a data-driven clinical management tool for older Veterans with multimorbidity.

Healthcare systems are increasingly turning to data-driven approaches, such as clustering techniques, to inform interventions for medically complex older adults. However, patients seeking care in multiple healthcare systems may have missing diagnoses across systems, leading to misclassification of resulting groups. We evaluated the impact of multi-system use on the accuracy and composition of multimorbidity groups among older adults in the Veterans Health Administration (VA). Eligible patients were VA primary care users aged ≥65 years and in the top decile of predicted 1-year hospitalization risk in 2018 (n = 558,864). Diagnoses of 26 chronic conditions were coded using a 24-month lookback period and input into latent class analysis (LCA) models. In a random 10% sample (n = 56,008), we compared the resulting model fit, class profiles, and patient assignments from models using only VA system data versus VA with Medicare data. LCA identified six patient comorbidity groups using VA system data. We labeled groups based on diagnoses with higher within-group prevalence relative to the average: Substance Use Disorders (7% of patients), Mental Health (15%), Heart Disease (22%), Diabetes (16%), Tumor (14%), and High Complexity (10%). VA with Medicare data showed improved model fit and assigned more patients with high accuracy. Over 70% of patients assigned to the Substance, Mental Health, High Complexity, and Tumor groups using VA data were assigned to the same group in VA with Medicare data. However, 41.9% of the Heart Disease group and 14.7% of the Diabetes group were reassigned to a new group characterized by multiple cardiometabolic conditions. The addition of Medicare data to VA data for older high-risk adults improved clustering model accuracy and altered the clinical profiles of groups. Accessing or accounting for multi-system data is key to the success of interventions based on empiric grouping in populations with dual-system use.

Association of high-risk comorbidity with overall survival among patients with gastric cancer and its sex-specific differences in China: a retrospective observational cohort study

BackgroundConcomitant diseases often occur in cancer patients and are important in decision-making regarding treatments. However, information regarding the prognostic relevance of comorbidities for mortality risk is still limited among Chinese gastric cancer (GC) patients. This study aimed to investigate the association between comorbidities and 3-year mortality risk.MethodsThis retrospective study enrolled 376 GC patients undergoing radical gastrectomy at the Affiliated Zhongshan Hospital of Dalian University from January 2011 to December 2019. Demographic and clinicopathological information and treatment outcomes were collected. Patients were divided into low-, moderate- and high-risk comorbidity groups based on their Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) scores. Kaplan-Meier survival and Cox regression analyses were used to examine 3-year overall survival (OS) and mortality risk for each group.ResultsThe median follow-up time was 43.5 months, and 40.2% (151/376) of GC patients had died at the last follow-up. There were significant differences in OS rates between ACCI-based comorbidity groups (76.56; 64.51; 54.55%, log-rank P = 0.011) but not between CCI-based comorbidity groups (log-rank P = 0.16). The high-risk comorbidity group based on the ACCI remained a significant prognostic factor for 3-year OS in multivariate analysis, with an increased mortality risk (hazard ratio [HR], 1.99; 95% CI, 1.15–3.44). Subgroup analysis revealed that this pattern only held for male GC patients but not for female patients.ConclusionThe present study suggested that high-risk comorbidities were significantly associated with a higher mortality risk, particularly in Chinese male GC patients. Moreover, the ACCI score was an independent prognostic factor of long-term mortality.

Consequences of Type-2 diabetes mellitus and Malaria co-morbidity on sperm parameters in men; a case-control study in a district hospital in the Ashanti Region of Ghana.

Type-2 diabetes mellitus (T2DM) and malaria infection are highly prevalent in Africa particularly, in the Sub-Saharan Region. A greater number of people in the Ghanaian population who have T2DM are also reported to harbor malaria parasites. This study aimed to investigate the influence of T2DM & Malaria co-morbidity on sperm parameters among patients in the Ashanti Region of Ghana. This hospital-based cross-sectional analytic case-control study comprised 254 adult male study participants comprising 80 T2DM & Malaria co-morbidity, 80 T2DM only, and 94 normal controls. A blood sample (10mL) was drawn from each participant to measure FBG, HbA1c levels, Testosterone levels, Total cholesterol, and determination of Malaria parasite density. Seminal fluid was also collected from each participant for semen analysis. Sperm kinetics of the T2DM & Malaria co-morbidity group particularly; total motility, rapid progressive motility, and slow progressive motility were negatively affected compared to both T2DM only (p<0.0001) and the Normal control (p<0.0001). Normal sperm morphology was significantly affected in the co-morbidity group compared to T2DM only (p<0.0001). Sperm vitality was also statistically significantly reduced in the T2DM & Malaria co-morbidity than in T2DM only (t (64) = -8.62; p<0.001). There was a significant decline in testosterone levels in the T2DM & Malaria co-morbidity group than in the T2DM only (p<0.0001) and the control (p <0.0001). In conclusion, T2DM and malaria infection have a stronger propensity to alter sperm morphology and lower sperm motility and vitality.

Comorbidities and clinical response to cardiac resynchronization therapy: Patient-level meta-analysis from eight clinical trials.

Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT). Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081). In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present. NCT00271154, NCT00251251, NCT00267098, NCT00180271.

Altered resting-state brain activity in major depressive disorder comorbid with subclinical hypothyroidism: A regional homogeneity analysis

BackgroundMajor depressive disorder (MDD), a common mental disorder worldwide, frequently coexists with various physical illnesses, and recent studies have shown an increased prevalence of subclinical hypothyroidism (SHypo) among MDD patients. However, the neural mechanisms shared and unique to these disorders and the associated alterations in brain function remain largely unknown. This study investigated the potential brain function mechanisms underlying comorbid MDD and SHypo. MethodThirty MDD patients (non-comorbid group), 30 MDD patients comorbid with SHypo (comorbid group), 26 patients with SHypo, and 30 healthy controls were recruited for resting-state functional magnetic resonance imaging (rs-fMRI). We used regional homogeneity (ReHo) to examine differences in internal cerebral activity across the four groups. ResultsCompared with the non-comorbid group, the comorbid group exhibited significantly higher ReHo values in the right orbital part of the middle frontal gyrus (ORBmid) and bilateral middle frontal gyrus; decreased ReHo values in the right middle temporal gyrus, right thalamus, and right superior temporal gyrus, and right insula. Within the comorbid group, serum TSH levels were negatively associated with the ReHo values of the right insula; the ReHo values of the right Insula were negatively associated with the retardation factor score; the ReHo values of the right ORBmid were positively correlated with the anxiety/somatization factor scores. ConclusionsThese findings provide valuable clues for exploring the shared neural mechanisms between MDD and SHypo and have important implications for understanding the pathophysiological mechanisms of the comorbidity of the two disorders.

Identifying clusters of coexisting conditions and outcomes among adults admitted to hospital with community-acquired pneumonia: a multicentre cohort study.

Little is known about patterns of coexisting conditions and their influence on clinical care or outcomes in adults admitted to hospital for community-acquired pneumonia (CAP). We sought to evaluate how coexisting conditions cluster in this population to advance understanding of how multimorbidity affects CAP. We studied 11 085 adults admitted to hospital with CAP at 7 hospitals in Ontario, Canada. Using cluster analysis, we identified patient subgroups based on clustering of comorbidities in the Charlson Comorbidity Index. We derived and replicated cluster analyses in independent cohorts (derivation sample 2010-2015, replication sample 2015-2017), then combined these into a total cohort for final cluster analyses. We described differences in medications, imaging and outcomes. Patients clustered into 7 subgroups. The low comorbidity subgroup (n = 3052, 27.5%) had no comorbidities. The DM-HF-Pulm subgroup had prevalent diabetes, heart failure and chronic lung disease (n = 1710, 15.4%). One disease category defined each remaining subgroup, as follows: pulmonary (n = 1621, 14.6%), diabetes (n = 1281, 11.6%), heart failure (n = 1370, 12.4%), dementia (n = 1038, 9.4%) and cancer (n = 1013, 9.1%). Corticosteroid use ranged from 11.5% to 64.9% in the dementia and pulmonary subgroups, respectively. Piperacillin-tazobactam use ranged from 9.1% to 28.0% in the pulmonary and cancer subgroups, respectively. The use of thoracic computed tomography ranged from 5.7% to 36.3% in the dementia and cancer subgroups, respectively. Adjusting for patient factors, the risk of in-hospital death was greater in the cancer (adjusted odds ratio [OR] 3.12, 95% confidence interval [CI] 2.44-3.99), dementia (adjusted OR 1.57, 95% CI 1.05-2.35), heart failure (adjusted OR 1.66, 95% CI 1.35-2.03) and DM-HF-Pulm subgroups (adjusted OR 1.35, 95% CI 1.12-1.61), and lower in the diabetes subgroup (adjusted OR 0.67, 95% CI 0.50-0.89), compared with the low comorbidity group. Patients admitted to hospital with CAP cluster into clinically recognizable subgroups based on coexisting conditions. Clinical care and outcomes vary among these subgroups with little evidence to guide decision-making, highlighting opportunities for research to personalize care.

Shoulder arthroplasty outcomes in patients with major depressive disorder or generalized anxiety disorder

BackgroundAnxiety and depression are among the most common mental health disorders in the United States and have been linked to increased health-care utilization and poorer clinical outcomes. However, data on the relationship between anxiety and depression and outcomes after shoulder arthroplasty (SA) are both limited and conflicting. MethodsThis retrospective cohort study examined the influence of a preoperative diagnosis of anxiety and/or major depressive disorder (MDD) on outcomes following shoulder arthroplasty, such as range of motion, pain, perioperative and postoperative complications, and readmission rates. A retrospective chart review of our health system’s electronic medical record was performed for dates of service January 2014–December 2019. Patients who underwent primary total shoulder arthroplasty or reverse total shoulder arthroplasty were considered for inclusion. These patients were then divided into two groups based on the presence or absence of an anxiety disorder and/or MDD in their past medical history. Results595 patients with a minimum follow-up of one year were considered for analysis. Of these, 205 patients (34.5%) had diagnoses of an anxiety and/or MDD and were assigned to the psychiatric comorbidity group, while 390 (65.5%) were assigned to the control group. The psychiatric comorbidity group was significantly younger (68.3 ± 9.3 vs. 70.5 ± 10.0, P = .008) and more heavily female (68.7% vs. 48.7%, P < .001). The length of stay was significantly longer in the psychiatric comorbidity group than in the control group (1.9 ± 2.4 vs. 1.5 ± 0.9 days, P = .023). Postoperative range of motion, visual analog scale pain scores (1.8 ± 2.7 vs. 1.3 ± 2.3, P = .059), complication rates (7.8% vs. 6.9%, P = .681), and revision rates (4.9% vs. 3.6%, P = .448) were not significantly different between the psychiatric comorbidity and control groups, respectively. All-cause emergency department visitation and hospital readmission rates were also similar between the two groups at 30, 60, and 90 days postoperatively. ConclusionOur results suggest that a preoperative diagnosis of MDD or anxiety does not affect pain, postoperative outcomes, complications, or readmission rates following shoulder arthroplasty.

Depression and Anxiety in Association with Polypharmacy in Patients with Multiple Sclerosis.

Polypharmacy (intake of ≥5 drugs) is an important issue for patients with chronic diseases such as multiple sclerosis (MS). We aimed to assess the prevalence of polypharmacy with regard to the severity of anxiety/depression and to comorbidities. Therefore, 374 MS patients from two German neurological sites were examined for drug burden, comorbidities, disability level and psychopathological measures capturing depression and anxiety using the Hospital Anxiety and Depression Scale (HADS-A and HADS-D). We found that patients with a higher HADS-D score take more medication (r = 0.217, p < 0.001). Furthermore, patients with higher depression severity were more likely to show polypharmacy (p < 0.001). These differences were not significant for anxiety. (p = 0.413). Regarding the frequency of ≥1 comorbidities, there were no significant differences between patients with different HADS-A (p = 0.375) or HADS-D (p = 0.860) severity levels, whereas the concrete number of comorbidities showed a significant positive linear correlation with HADS-A (r = 0.10, p = 0.045) and HADS-D scores (r = 0.19, p < 0.001). In conclusion, symptoms of depression pose a relevant issue for MS patients and are correlated with polypharmacy and comorbidities. Anxiety is not correlated with polypharmacy but with the frequency of several comorbidity groups in MS patients.

Age-Accelerated Increase of White Matter Hyperintensity Volumes Is Exacerbated by Heavy Alcohol Use in People Living With HIV

BackgroundAntiretroviral treatment has enabled people living with HIV infection to have a near-normal life span. With longevity comes opportunities for engaging in risky behavior, including initiation of excessive drinking. Given that both HIV infection and alcohol use disorder (AUD) can disrupt brain white matter integrity, we questioned whether HIV infection, even if successfully treated, or AUD alone results in signs of accelerated white matter aging and whether HIV+AUD comorbidity further accelerates brain aging. MethodsLongitudinal magnetic resonance imaging-FLAIR data were acquired over a 15-year period from 179 control individuals, 204 participants with AUD, 70 participants with HIV, and 75 participants with comorbid HIV+AUD. White matter hyperintensity (WMH) volumes were quantified and localized, and their functional relevance was examined with cognitive and motor testing. ResultsThe 3 diagnostic groups each had larger WMH volumes than the control group. Although all 4 groups exhibited accelerating volume increases with aging, only the HIV groups showed faster WMH enlargement than control individuals; the comorbid group showed faster acceleration than the HIV-only group. Sex and HIV infection length, but not viral suppression status, moderated acceleration. Correlations emerged between WMH volumes and attention/working memory and executive function scores of the AUD and HIV groups and between WMH volumes and motor skills in the 3 diagnostic groups. ConclusionsEven treated HIV can show accelerated aging, possibly from treatment sequelae or legacy effects, and notably from AUD comorbidity. WMH volumes may be especially relevant for tracking HIV and AUD brain health because each condition is associated with liability for hypertensive processes, for which WMHs are considered a marker.

The Co-Occurrence of Post-Traumatic Stress Disorder and Depression in Individuals with and without Traumatic Brain Injury: A Comprehensive Investigation.

Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder that often occurs following war trauma. Despite its high prevalence, there is still a lack of comprehensive understanding regarding the mechanisms underlying its progression and treatment resistance. Recent research has shed light on the biological basis of PTSD, with neuroimaging studies revealing altered brain connectivity patterns in affected individuals. In war contexts, traumatic brain injury (TBI) is a common occurrence and is associated with a high prevalence of PTSD. This study aimed to compare the severity of PTSD and depression in patients with and without a history of TBI to shed light on the impact of comorbid TBI on the presentation of PTSD symptoms. To achieve this goal, a cross-sectional study was conducted involving a sample of 60 outpatients who were diagnosed with both PTSD and Depressive Disorder. The inclusion criteria required participants to meet the diagnostic criteria for both disorders using validated tools. The severities of PTSD and depressive symptoms were assessed using scales that have been widely used and validated in previous research. By utilizing these standardized assessment tools, this study aimed to ensure the reliability and validity of the obtained data. The results of this study revealed that patients with comorbid PTSD and TBI exhibited a significantly higher severity of PTSD symptoms compared to those with PTSD only. Specifically, the comorbid group demonstrated higher ratings of symptom intensity across all symptom clusters. These findings are consistent with previous research that has highlighted the impact of comorbid TBI on the intensity and persistence of PTSD symptoms. When controlling for PTSD severity, no significant differences were observed in the severity of depressive symptoms between the two groups. This suggests that the increased depressive symptoms observed in the comorbid group may be primarily driven by the presence of more intense PTSD symptoms rather than TBI per se. The findings highlight the need for an accurate diagnosis of TBI in individuals with PTSD to guide appropriate treatment interventions. Further research is warranted to delve into the underlying mechanisms that contribute to the interaction between TBI and PTSD and to develop targeted interventions for individuals with comorbid PTSD and TBI.

Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study

BackgroundComorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning.MethodsWe studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9–10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort.ResultsSmaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT differences, while those patient groups without comorbidity had significantly higher thickness compare to healthy controls. Distinct biological pathways were implicated in regional SA and CT differences. Specifically, CT differences were associated with immune-related processes implicating astrocytes and oligodendrocytes, while SA-related differences related mainly to inhibitory neurons.ConclusionThe emergence of comorbidity across distinct clusters of psychopathology is unlikely to be due to a simple additive neurobiological effect alone. Distinct developmental risk moderated by immune-related adaptation processes, with unique genetic and cell-specific factors, may contribute to underlying SA and CT differences. Children with the highest risk but lowest resilience, both captured in their developmental morphometry, may develop a comorbid illness pattern.

The International Initiative to Measure Perceived Risk in Arthroplasty: The Results From a Multinational Survey

BackgroundThere is an inherent moral imperative to avoid complications from arthroplasty. Doing so at ideal cost is also associated with surgeon reputation, and, increasingly in health care delivery systems that measure and competitively score outcomes, reimbursement to the surgeons and their hospitals. As a result, patients who are perceived to be in higher risk comorbidity groups, such as the obese and diabetics, as well as those challenged by socioeconomic factors may face barriers to access elective arthroplasty. MethodsIn this initiative, surveys were sent to surgeons in 8 different countries, each adapted for their own unique payment, remuneration, and punitive models. The questions in the surveys pertained to surgeons’ perception of risk regarding medical and socioeconomic factors in patients indicated for total hip or knee arthroplasty. This paper primarily reports on the results from Canada, Ireland, and the United Kingdom. ResultsThe health care systems varied between a universal/state funded health care system (Canada) to those that were almost exclusively private (India). Some health care systems have “bundled” payment with retention of fees for postoperative complications requiring readmission/reoperation and including some with public publication of outcome data (United States and the United Kingdom), whereas others had none (Canada). There were some major discrepancies across different countries regarding the perceived risk of diabetic patients, who have variable Hemoglobin A1c cut-offs, if any used. However, overall the perception of risk for age, body mass index, age, sex, socioeconomic, and social situations remained surprisingly consistent throughout the health care systems. Any limitations set were primarily driven by surgeon decision making and not external demands. ConclusionSurgeons will understandably try and optimize the health status of patients who have reversible risks as shown by best available evidence. The evidence is of variable quality, and, especially for irreversible social risk factors, limited due to concerns over cost and quality outcomes that can be influenced by experience-driven perceptions of risk. The results show that perceptions of risk do have such influence on access across many health care delivery environments. The authors recommend better risk-adjustment models for medical and socioeconomic risk factors with possible stratification/exclusions regarding reimbursement adjustments and reporting to help reverse disparities of access to arthroplasty.

Early Discontinuation of Apremilast in Patients with Psoriasis and Gastrointestinal Comorbidities: Rates and Associated Risk Factors.

Apremilast, the first oral targeted treatment for moderate to severe psoriasis, is associated with diarrhea, nausea, and vomiting, which have contributed to treatment discontinuation. This study describes early apremilast discontinuation rates in patients with psoriasis, including a cohort with gastrointestinal (GI) comorbidities, and associated characteristics. This retrospective cohort study used IBM® (now Merative™) MarketScan® commercial and Medicare claims data to identify adults with psoriasis who filled their first apremilast prescription between September1, 2014 and March31, 2020. Discontinuation was defined as a gap of > 30days after exhausting the days' supply of a prescription fill. The GI comorbidity cohort included patients with ≥ 1 claim for inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or other GI comorbidity during the study period. Discontinuation rates were high, regardless of previous biologic treatment or GI comorbidities. Among all patients, 25.5% discontinued within 60days and 56.4% discontinued within 180days. Patients who discontinued were more likely to be younger, female, and have IBD, Crohn's disease, or a mental health disorder. At 180days, patients who used biologics previously were more likely to discontinue than biologic-naive patients. Patients with IBD discontinued at a greater rate than those without IBD at 60days (30.3% vs 24.4%; P = 0.018) and 180days (63.6% vs 57.2%; P = 0.026). Differences in discontinuation rates were minimal between GI comorbidity groups; patients with IBS discontinued at numerically higher rates than those without IBS. High rates of early discontinuation were observed for patients with and without GI comorbidities. Early discontinuation, whether attributable to poor tolerability or effectiveness, suggests the need for additional oral treatment options.

The impact of obstructive sleep apnea and comorbidity status on cardiovascular outcomes in patients with acute coronary syndrome

Background and aimsThe association of comorbidities on the prognosis of patients with acute coronary syndrome (ACS) was well documented. However, the impact of obstructive sleep apnea (OSA) on this association has been less studied. Methods and resultsBetween June 2015 to Jan 2020, we included consecutively eligible patients with ACS who underwent cardiorespiratory polygraphy. The definition of OSA was apnea-hypopnea index (AHI) ≥15 events/hour. Charlson Comorbidity Index (CCI) was used to evaluate the comorbidities. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, and hospitalization for unstable angina or heart failure. In the 1927 ACS patients, 1014 (52.6%) had OSA. The prevalence of the mild (CCI = 0), moderate (CCI = 1–2), and severe (CCI≥3) comorbidity were 23.6%, 65.9%, and 10.5%, respectively. During a median follow-up of 2.9 (1.5, 3.6) years, compared with patients without OSA, the presence of OSA increased the risk of MACCE in the moderate comorbidity group (22.6% vs. 17.5%; adjusted HR: 1.327; 95% CI: 1.019–1.728, p = 0.036) and severe comorbidity group (36.2% vs. 18.6%; adjusted HR: 2.194; 95% CI: 1.170–4.117, p = 0.014). There was no significant difference between OSA and non-OSA patients in the mild comorbidity group. ConclusionAmong ACS patients, OSA was associated with an increased risk of subsequent events in the moderate and severe comorbidity groups but not in the mild comorbidity group. ACS patients with comorbidities should not be overlooked for OSA screening.

Neurocognitive Profile in Children with Attention Deficit/Hyperactivity Disorder and Dyslexia

Objective: The current study aimed to examine the neurocognitive deficits of children with ADHD and/or Developmental Dyslexia (DD) using neurocognitive tests. Material and Methods: The participants of the study consisted of children diagnosed with Dyslexia (N=33), ADHD (N=32), and DD+ADHD (N=37) who applied to the Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ankara University. The control group consists of 30 primary school children aged 7-11 with similar sociodemographic data. K-SADS-PL is used for the DSM-5 diagnoses of the patients and the control group. Stroop Test, Trail Making Test, Verbal Cancellation Test, and Wechsler Intelligence Scale for Children-Revised (WISC-R) were used to evaluate the cognitive functions of the groups in detail. Results: Children with ADHD and/or Dyslexia were evaluated to have significant deficits in all neurocognitive measures such as reaction inhibition, selective attention, sustained attention, shifting attention, and visuospatial short-term memory compared to the healthy control group (p&lt;0.001). Children with ADHD-only revealed the most significant weaknesses in reaction inhibition, and visuospatial short-term memory measures (p&lt;0.001). The comorbid group exhibited significant weakness on almost all neurocognitive measures compared with the control group, but did not perform significantly lower than the ADHD-only and Dislexia-only groups. Conclusion: It has been shown that children with ADHD and/or Dyslexia have multiple neurocognitive deficits, and our study supports the multiple cognitive deficit hypothesis.