Post traumatic stress and sleep disorders in long COVID: Patient management and treatment.

Post traumatic stress disorder (PTSD) and sleep disorders are prevalent among patients with long COVID. The intersection of PTSD and/or sleep disorders with long COVID is complex. Thus, use of a biopsychosocial lens for assessment and treatment along with a trauma-informed approach to clinical care is recommended. This review provides an overview of the literature on PTSD and sleep disorders among patients with long COVID, including prevalence rates, risk factors, and potential pathophysiology. Pharmacological and non-pharmacological treatment options are reviewed. Also, we provide actionable steps clinicians can integrate into their practice to help effectively assess and treat PTSD and sleep disorders, including validated symptom assessments, recommended referrals, and specific components of non-pharmacological interventions.

Irreversible Electroporation in Treating Colorectal Liver Metastases in Proximity to Critical Structures.

PURPOSE: To evaluate the safety, efficacy, and oncological outcomes of irreversible electroporation (IRE) of unresectable colorectal liver metastases (CRLMs) close to critical structures. MATERIALS AND METHODS: This is a single-center, institutional review board (IRB)-approved, retrospective analysis of patients who underwent percutaneous computed tomography (CT)-guided IRE of CRLM. Between August 2018 and October 2023, 26 patients had 46 tumors treated with percutaneous IRE in 30 ablation sessions. Primary end points were tumor response and local progression-free survival analyzed using Kaplan-Meier survival curves. Secondary end points were overall survival (OS), distant progression-free survival (DPFS) analyzed using Kaplan-Meier survival curves, adverse events rated according to the Common Terminology Criteria for Adverse Events (CTCAE), and length of hospital stay. RESULTS: All tumors were close to critical structures, including the portal and hepatic veins, inferior vena cava, bile ducts, and gallbladder. All patients received preprocedural systemic therapy (median 10 cycles). Median length of hospital stay was 1 night. Adverse events occurred in 7 (23%) of 30 procedures, with four Grade 1 and two Grade 2 adverse events, including pleural effusions (n = 2), ileus (n = 1), small hematoma (n = 1), and pneumothorax (n = 2) requiring chest tube placements. Following IRE, the 1- and 2-year local tumor progression-free survival rates were 55.0% and 51.3%. The median DPFS was 3.5 months, with 1- and 2-year DPFS rates of 23.3% and 9.7%. Six patients (23.1%) died during follow-up, with a median OS of 40.4 months. The 1- and 2-year OS rates were 90.9% and 83.9%. CONCLUSIONS: IRE is a safe and viable option in the treatment of unresectable CRLMs in locations close to critical structures, but carries a risk of local recurrence.

Race, Ethnicity, and Gender Differences in Patient Reported Well-Being and Cognitive Functioning Within 3 Months of Symptomatic Illness During COVID-19 Pandemic.

BACKGROUND: Differences in acute COVID-19 associated morbidity based on race, ethnicity, and gender have been well described; however, less is known about differences in subsequent longer term health-related quality of life and well-being. METHODS: This prospective cohort study included symptomatic adults tested for SARS-CoV-2 who completed baseline and 3-month follow-up surveys. Using the PROMIS-29 tool, a validated measure of health and well-being, we compared outcomes at 3 months and change in outcomes from baseline to 3 months among groups with different races, ethnicities, and/or sexes. RESULTS: Among 6044 participants, 4113 (3202 COVID +) were included. Among COVID + participants, compared to non-Hispanic White participants, Black participants had better PROMIS T-scores for cognitive function (3.6 [1.1, 6.2]) and fatigue (- 4.3 [- 6.6, - 2.0]) at 3 months and experienced more improvement in fatigue over 3 months (- 2.7 [- 4.7, - 0.8]). At 3 months, compared with males, females had worse PROMIS T-scores for cognitive function (- 4.1 [- 5.6, - 2.6]), physical function (- 2.1 [- 3.1, - 1.0]), social participation (- 2.8 [- 4.2, - 1.5]), anxiety (2.8 [1.5, 4.1]), fatigue (5.1 [3.7, 6.4]), and pain interference (2.0 [0.9, 3.2]). Females experienced less improvement in fatigue over 3 months (3.1 [2.0, 4.3]). Transgender/non-binary/other gender participants had worse 3-month scores in all domains except for sleep disturbance and pain interference. CONCLUSIONS: Three months after the initial COVID-19 infection, Black participants reported better cognitive function and fatigue, while females and other gender minoritized groups experienced lower well-being. Future studies are necessary to better understand how and why social constructs, specifically race, ethnicity, and gender, influence differences in COVID-19-related health outcomes. Trials Registration ClinicalTrials.gov Identifier: NCT04610515.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection.

Importance: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objective: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness. Design, Setting, and Participants: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023. Exposure: COVID-19 status (positive vs negative) at enrollment. Main Outcome and Measures: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms. Results: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]). Conclusions and Relevance: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

Safety and Effectiveness of Irreversible Electroporation in Lymph Node Metastases.

PURPOSE: Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases. MATERIALS AND METHODS: An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS). RESULTS: Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively. CONCLUSION: IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.

Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience.

PURPOSE: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment. MATERIAL AND METHODS: Between 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm). RESULTS: IRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement. CONCLUSION: The current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.

Irreversible Electroporation of the Hepatobiliary System: Current Utilization and Future Avenues.

Liver cancer remains a leading cause of cancer-related deaths worldwide despite numerous advances in treatment. While surgical resection remains the gold standard for curative treatment, it is only possible for a minority of patients. Thermal ablation is an effective option for the treatment of smaller tumors; however, its use is limited to tumors that are not located in proximity to sensitive structures due to the heat sink effect and the potential of thermal damage. Irreversible electroporation (IRE) is a non-thermal ablative modality that can deliver targeted treatment and the effective destruction of tumors that are in close proximity to or even surrounding vascular or biliary ducts with minimal damage to these structures. IRE produces short pulses of high-frequency energy which opens pores in the lipid bilayer of cells leading to apoptosis and cell death. IRE has been utilized clinically for over a decade in the treatment of liver cancers with multiple studies documenting an acceptable safety profile and high efficacy rates.

Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms.

Background: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. Methods: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. Results: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. Conclusions: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.

Postacute Sequelae of SARS-CoV-2: Musculoskeletal Conditions and Pain.

Musculoskeletal and pain sequelae of COVID-19 are common in both the acute infection and patients experiencing longer term symptoms associated with recovery, known as postacute sequelae of COVID-19 (PASC). Patients with PASC may experience multiple manifestations of pain and other concurrent symptoms that complicate their experience of pain. In this review, the authors explore what is currently known about PASC-related pain and its pathophysiology as well as strategies for diagnosis and management.

Embolization for the treatment of large, complex fibroids in an outpatient setting: A report of 2 cases.

Uterine leiomyomas are the most common benign pelvic tumors in premenopausal women, causing significant morbidity. Uterine fibroid embolization is a minimally invasive alternative to traditional open or laparoscopic surgeries for the management of symptomatic uterine leiomyoma. For large fibroids, hospitalization after treatment is often required. However, there are limited data on patients with large, complex uterine leiomyomas treated by embolization. This report of 2 cases describes 2 females with large, complex fibroids causing pain and decreased quality of life who were evaluated and treated with embolization in the outpatient setting. Each patient underwent transradial cannulation and uterine artery embolization under local anesthesia or conscious sedation and returned home without complication. For women wishing to preserve their uterus, uterine fibroid embolization is an effective nonsurgical alternative to hysterectomy and myomectomy in an outpatient setting. If standard protocols are followed, embolization by way of transradial artery catheterization is safe for the treatment of large, complex, symptomatic fibroids in the outpatient setting; however, additional studies with larger cohorts are warranted. Accessing the uterine arteries transradially reduces the risk of intra- and post-operative complications for patients, reduces their time spent in a hospital, and minimizes operating costs.

Associations Between Physical Activity Vital Sign in Patients and Health Care Utilization in a Health Care System, 2018-2020.

BACKGROUND: Physical inactivity is a risk factor for many chronic conditions. This retrospective cohort study examined associations between physical activity (PA) with health care utilization (HU). METHODS: A PA vital sign was recorded in clinics from January 2018 to December 2020. Patients were categorized as inactive, insufficiently active, or sufficiently active by US PA aerobic guidelines. Associations between PA vital sign and visits (inpatient admissions, emergency department, urgent care, and primary care) were estimated using population average regression by visit type. RESULTS: 23,721 patients had at least one PA vital sign recorded, with a mean age of 47.3 years and mean body mass index (BMI) of 28; 52% were female and 63% were White. Sufficiently active patients were younger, male, White, and had lower BMI than insufficiently active patients. Achieving 150 minutes per week of moderate to vigorous PA per 1000 patient years was associated with 34 fewer emergency department visits (P < .001), 19 fewer inpatient admissions (P < .001), and 38 fewer primary care visits (P < .001) compared with inactive patients. Stronger associations between lower PA and higher HU were present among those who were older or had a higher comorbidity. BMI, sex, ethnicity, and race did not modify the association between PA and HU. CONCLUSIONS: Meeting aerobic guidelines was associated with reduced HU for inpatient, primary care, and emergency department visits.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Ethnic and racial differences in self-reported symptoms, health status, activity level, and missed work at 3 and 6 months following SARS-CoV-2 infection.

Introduction: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. Methods: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. Results: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). Discussion: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

Importance: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. Objective: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. Exposures: SARS-CoV-2 status (positive or negative test result) at enrollment. Main Outcomes and Measures: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. Results: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (ß = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: ß = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: ß = 4.16; 95% CI, 2.12-6.20; P < .001). Conclusions and Relevance: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Nonsteroidal anti-inflammatory drug exposure and the risk of microscopic colitis.

BACKGROUND: Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. METHODS: A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. RESULTS: In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65-5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found. CONCLUSIONS: In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations.

BACKGROUND: Prospective genetic evaluation of patients at this referral research hospital presents clinical research challenges. OBJECTIVES: This study sought not only a single-gene explanation for participants' immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune phenotype and other heritable comorbidities relevant to their presentation and health. METHODS: This study developed a program integrating exome sequencing, chromosomal microarray, phenotyping, results return with genetic counseling, and reanalysis in 1505 individuals from 1000 families with suspected or known inborn errors of immunity. RESULTS: Probands were 50.8% female, 71.5% were ≥18 years, and had diverse immune presentations. Overall, 327 of 1000 probands (32.7%) received 361 molecular diagnoses. These included 17 probands with diagnostic copy number variants, 32 probands with secondary findings, and 31 probands with multiple molecular diagnoses. Reanalysis added 22 molecular diagnoses, predominantly due to new disease-gene associations (9 of 22, 40.9%). One-quarter of the molecular diagnoses (92 of 361) did not involve immune-associated genes. Molecular diagnosis was correlated with younger age, male sex, and a higher number of organ systems involved. This program also facilitated the discovery of new gene-disease associations such as SASH3-related immunodeficiency. A review of treatment options and ClinGen actionability curations suggest that at least 251 of 361 of these molecular diagnoses (69.5%) could translate into ≥1 management option. CONCLUSIONS: This program contributes to our understanding of the diagnostic and clinical utility whole exome analysis on a large scale.

Implementation of a Physical Activity Vital Sign in Primary Care: Associations Between Physical Activity, Demographic Characteristics, and Chronic Disease Burden.

INTRODUCTION: Physical activity is important to prevent and manage multiple chronic medical conditions. The objective of this study was to describe the implementation of a physical activity vital sign (PAVS) in a primary care setting and examine the association between physical activity with demographic characteristics and chronic disease burden. METHODS: We extracted data from the electronic medical records of patients who had visits from July 2018 through January 2020 in a primary care clinic in which PAVS was implemented as part of the intake process. Data collected included self-reported physical activity, age, sex, body mass index, race, ethnicity, and a modified Charlson Comorbidity Index score indicating chronic disease burden. We classified PAVS into 3 categories of time spent in moderate to strenuous intensity physical activity: consistently inactive (0 min/wk), inconsistently active (<150 min/wk), and consistently active (≥150 min/wk). We used χ2 tests of independence to test for association between PAVS categories and all other variables. RESULTS: During the study period, 13,704 visits, corresponding to 8,741 unique adult patients, had PAVS recorded. Overall, 18.1% of patients reported being consistently inactive, 48.3% inconsistently active, and 33.7% consistently active. All assessed demographic and clinical covariates were associated with PAVS classification (all P < .001). Larger percentages of consistent inactivity were reported for female, older, and underweight or obese patients. Larger percentages of consistent activity were reported for male, younger, and normal weight or overweight patients. CONCLUSION: Using PAVS as a screening tool in primary care enables physicians to understand the physical activity status of their patients and can be useful in identifying inactive patients who may benefit from physical activity counseling.

The impact of a rapid home test on telehealth decision-making for influenza: a clinical vignette study.

BACKGROUND: Home testing for influenza has the potential to aid triage and management decisions for patients with influenza-like illness. As yet, little is known about the effect of the home influenza testing on clinical decision-making via telehealth. The goal of this study was to determine the clinicians' decision thresholds for influenza and whether the availability of a home influenza test affects clinical decisions. METHODS: We identified primary care physicians at 4 different sites in the US, largely via in-person continuing education meetings. Clinicians were asked for each vignette whether to treat empirically ("rule in"), ask the patient come to the clinic for further evaluation ("test"), or neither test nor treat ("rule out"). They were then given the results of a home influenza test, and were again asked to select from these three options. We measured the agreement of physician estimates of the likelihood of influenza with the probability based on a clinical prediction model. The test and treatment thresholds of influenza were determined based on mixed-effect logistic regressions. RESULTS: In total, 202 clinicians made 570 sets of clinical decisions. Agreement between estimated and actual probability of influenza was fair. The test and treatment thresholds were 24% (95% CI: 22% to 25%) and 63% (95% CI: 58% to 65%) before revealing the actual likelihood of influenza. After providing the results of a home flu test the thresholds were similar, 26% (95% CI: 24% to 29%) and 59% (95% CI: 56% to 62%). However, approximately half of clinicians changed their cliical management decision after being given the home influenza test result, largely by categorizing more patients in the "rule out" and "rule in" groups, and reducing the need for in-person evaluation from 41% of patients to only 20%. CONCLUSION: In the context of a telehealth visit for a patient with influenza-like illness, we identified a test threshold of approximately 25% and a treatment threshold of approximately 60%. Adding the home influenza test results reduced uncertainty and significantly decreased the need for in-person visits.

Immune thrombocytopenic purpura secondary to Helicobacter pylori.

Immune thrombocytopenic purpura is a disorder characterized by decreased platelet count that may be secondary to infectious or autoimmune etiologies. We present a patient with upper gastrointestinal bleeding complicated by severe thrombocytopenia. Endoscopy revealed gastritis with pathology positive for Helicobacter pylori. Platelet count normalized after triple antibiotic therapy. The precise mechanism by which H. pylori causes immune thrombocytopenic purpura remains unclear; however, there are several plausible mechanisms. This case highlights the importance of keeping H. pylori in the differential in patients presenting with thrombocytopenia.

Bile Acid Sequestrant Therapy in Microscopic Colitis.

GOALS: There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS). BACKGROUND: MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment. STUDY: Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing. RESULTS: The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness. CONCLUSIONS: BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.