Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease

: Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.

Post-Vaccination Symptoms after A Third Dose of mRNA SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease

Symptoms after SARS-CoV-2 primary vaccination among patients with inflammatory bowel disease (IBD) are generally of similar frequency, severity, and duration to those reported in the general population. The symptom profile after a 3rd mRNA vaccine dose in the predominantly immune-compromised IBD population is unknown. We aimed to assess symptomology after a 3rd or booster dose of mRNA vaccination in adults with IBD. We surveyed participants of the Coronavirus Risk Associations and Longitudinal Evaluation in IBD (CORALE-IBD) post-vaccination registry for symptom frequency and severity after a 3rd mRNA vaccine dose in an observational cohort study. In total, 524 participants (70% female, mean age 45 years) reported a third dose of mRNA vaccination through October 11, 2021. Overall, 41% reported symptoms after a third dose, with symptoms generally more frequent and more severe among participants younger than 55 years. The most frequent postvaccination symptoms were injection site pain (39%), fatigue or malaise (34%), and headache (23%). These symptoms were all less frequently reported after dose 3 than after dose 2. Gastrointestinal symptoms were reported by 8.8%, which was slightly more frequent than after dose 2 (7.8%). Those with severe symptoms after dose 2 were more likely to have severe symptoms after dose 3. These findings can reassure the IBD patient and provider communities that the likelihood and distribution of symptoms after a third mRNA vaccine dose are generally similar to those after a second dose, and that the frequency of postvaccination symptoms after dose 3 are generally lower than after dose 2.

Poor Separation of Clinical Symptom Profiles by DSM-5 Disorder Criteria

Assessment of mental illness typically relies on a disorder classification system that is considered to be at odds with the vast disorder comorbidity and symptom heterogeneity that exists within and across patients. Patients with the same disorder diagnosis exhibit diverse symptom profiles and comorbidities creating numerous clinical and research challenges. Here we provide a quantitative analysis of the symptom heterogeneity and disorder comorbidity across a sample of 107,349 adult individuals (aged 18–85 years) from 8 English-speaking countries. Data were acquired using the Mental Health Quotient, an anonymous, online, self-report tool that comprehensively evaluates symptom profiles across 10 common mental health disorders. Dissimilarity of symptom profiles within and between disorders was then computed. We found a continuum of symptom prevalence rather than a clear separation of normal and disordered. While 58.7% of those with 5 or more clinically significant symptoms did not map to the diagnostic criteria of any of the 10 DSM-5 disorders studied, those with symptom profiles that mapped to at least one disorder had, on average, 20 clinically significant symptoms. Within this group, the heterogeneity of symptom profiles was almost as high within a disorder label as between 2 disorder labels and not separable from randomly selected groups of individuals with at least one of any of the 10 disorders. Overall, these results quantify the scale of misalignment between clinical symptom profiles and DSM-5 disorder labels and demonstrate that DSM-5 disorder criteria do not separate individuals from random when the complete mental health symptom profile of an individual is considered. Greater emphasis on empirical, disorder agnostic approaches to symptom profiling would help overcome existing challenges with heterogeneity and comorbidity, aiding clinical and research outcomes.

Vitamin D levels in hospice in-patients

ObjectiveSerum 25-hydroxyvitamin D was obtained alongside routine blood tests in all suitable patients admitted to the St Cuthbert’s Hospice Inpatient Unit for a period of 12 months. Supplementation was offered to exclude vitamin D insufficiency or deficiency as a contributor to the complex pain and symptom profile of our patients.MethodsDuring admission, and alongside routine blood tests, a serum 25-hydroxyvitamin D test was requested for suitable patients. Supplementation was offered to patients with serum 25-hydroxyvitamin D less than 50 nmol/L.ResultsThis audit identified that 79.73% of patients assessed had a 25-hydroxyvitamin D level less than 50 nmol/L and were therefore insufficient or deficient in vitamin D. The results of the audit were discussed within the clinical team at the hospice and guidance changed to obtain serum 25-hydroxyvitamin D levels in all suitable patients. A reaudit highlighted that some patients were missed from testing and therefore reminders were sent to the clinical team.ConclusionsMost patients admitted to St Cuthbert’s Hospice had either insufficient or deficient levels of vitamin D. It seems reasonable for all suitable palliative care patients to have their vitamin D level checked and to be started on a suitable dose of vitamin D replacement therapy.

Management of sleep disorders in the menopausal transition

The menopausal transition is associated with increasing sleep disorders including sleep apnoea and restless leg syndrome. Insomnia is the most common and is recognised as a core symptom of the menopause. Guidelines to support decision making for women with sleep problems during the menopausal transition are lacking. Sleep problems are associated with negative impacts on healthcare utilisation, quality of life and work productivity. Sleep deprivation is a risk factor for cardiovascular disease, diabetes, obesity and neurobehavioral dysfunction. Declining oestrogen is implicated as a cause of menopausal sleep disruption. Vasomotor symptoms (VMS) and menopausal mood disturbance are also factors in the complex aetiology. VMS commonly precipitate insomnia and, due to their prolonged duration, they often perpetuate the condition. Insomnia in the general population is most effectively treated with cognitive behavioural therapy (CBT) (also effective in the menopausal transition.) The associations of menopausal sleep disturbance with VMS and depression mean that other treatment options must be considered. Existing guidelines outline effectiveness of hormone replacement therapy (HRT), CBT and antidepressants. HRT may indirectly help with sleep disturbance by treating VMS and also via beneficial effect on mood symptoms. The evidence base underpinning menopausal insomnia often references risks associated with HRT that are not in line with current international menopause guidelines. This may influence clinicians managing sleep disorders, leading to hesitation in offering HRT, despite evidence of effectiveness. Viewing sleep symptoms on an axis of menopausal symptoms – towards vasomotor symptoms or towards mood symptoms may help tailor treatment options towards the symptom profile.

N-Methyl-d-aspartate (NMDA) receptor antibody in relation to autism spectrum disorder (ASD): presence and association with symptom profile

Background Several studies pointed to immune dysregulation abnormalities linked to autism spectrum disorders (ASD). Of those, several autoantibodies had been identified. Recent findings of N-methyl d-aspartate (NMDA) antibodies in autoimmune encephalitis suggested that it caused symptoms like autistic regression. Thus, the purpose of the study was to test for the presence of anti-NMDAR antibodies in the ASD disorder population and to correlate this with the clinical findings. Results Eighty-seven autistic children, 4–12 years old, were enrolled in the study and were matched with sixty typically developing children used as controls. The diagnosis of cases was confirmed by ADOS-2 and clinical evaluation. None of the control children had positive anti-NMDAR antibodies, while 26.4% (23 children) of the patients’ group were positive for serum anti-NMDA receptor antibodies (> 200 pg/ml, p = 0.0157). The positive anti-NMDAR antibody was statistically correlated with better speech stage (p = 0.017), more severe stereotyped behavior (p ≤ 0.001), and abnormal EEG findings (p = 0.025). Conclusions There is a possibility of the presence of anti-NMDAR antibodies in the autism spectrum disorder population with certain characteristics, especially the severity of the stereotyped behaviors.

466. Symptom Profile of Hospitalized, Adult Patients with COVID-19 – Findings From COVID-Net Database

Background According to the Center for Disease Control and Prevention (CDC), there is a disproportional number of COVID-19 deaths in hospitalized patients that increases based on age. Among COVID-19 related deaths in hospitalized patients, 8 of 10 patients are age 65 years and older. By looking at the latest data, the objective of this retrospective analysis is to evaluate the symptom profile in patients hospitalized with COVID-19 and determine if certain symptoms are seen more in older patients. Methods We performed a retrospective analysis using the COVID-Net database. This database contains information involving COVID-19 laboratory-confirmed hospitalization across 14 states. Medical history, signs, and symptoms at admission were collected by COVID-NET surveillance officers and reported during the period of March 1st to May 31st. For our analysis, we only included adults patients age 18 and above. Further descriptive statistics were stratified by age into two groups: age 18-64, and age ≥ 65. Results We identified 60,363 patients age 18 and above with COVID-19 confirmed hospitalizations. Cough, shortness of breath, and fevers/chills were the most common symptoms at respectively 67%, 66%, and 65%. Patients age ≥ 65, when compared to patients age 18-64, were less likely to have cough (56.7% vs 73.8%), shortness of breath (58.1% vs 72.1%), fever/chills (54.7% vs 71.%), dysgeusia (2.3% vs 7%), and anosmia (1.2% vs 6%). The only presentation that was more common in patients age 65+, than in patients age 18-64, was altered mental status (26.9% vs 5.2%). Overall inpatient mortality was higher in the age ≥ 65 group (8.9% vs 2%). Among the 2,922 COVID-19 decedents, 75.3% were age ≥65. Conclusion Published in April 2020, preliminary data from COVID-Net on approximately 180 patient reported that only 8.2% of patients age ≥ 65 had altered mental status2. Since then, our analysis noted that altered mental status is more commonly seen in the age group ≥ 65 than previously reported. The percentage of decedents age ≥ 65 in this analysis is similar to the 74.8% (N= 10,647) reported in a large study that focused specifically on COVID-19-related deaths3. Our analysis highlights that altered mental status is a common neurologic manifestation in elderly patients hospitalized with COVID-19. Disclosures All Authors: No reported disclosures