Outpatient Laboratory Research Articles

The Impact of Outpatient Laboratory Alerting Mechanisms in Patients with AKI.

AKI is an abrupt decrease in kidney function associated with significant morbidity and mortality. Electronic notifications of AKI have been utilized in patients who are hospitalized, but their efficacy in the outpatient setting is unclear. We evaluated the effect of two outpatient interventions: an automated comment on increasing creatinine results (intervention I; 6 months; n=159) along with an email to the provider (intervention II; 3 months; n=105), compared with a control (baseline; 6 months; n=176). A comment was generated if a patient's creatinine increased by >0.5 mg/dl (previous creatinine ≤2.0 mg/dl) or by 50% (previous creatinine >2.0 mg/dl) within 180 days. Process measures included documentation of AKI and clinical actions. Clinical outcomes were defined as recovery from AKI within 7 days, prolonged AKI from 8 to 89 days, and progression to CKD with in 120 days. Providers were more likely to document AKI in interventions I (P=0.004; OR, 2.80; 95% CI, 1.38 to 5.67) and II (P=0.01; OR, 2.66; 95% CI, 1.21 to 5.81). Providers were also more likely to discontinue nephrotoxins in intervention II (P<0.001; OR, 4.88; 95% CI, 2.27 to 10.50). The median time to follow-up creatinine trended shorter among patients with AKI documented (21 versus 42 days; P=0.11). There were no significant differences in clinical outcomes. An automated comment was associated with improved documented recognition of AKI and the additive intervention of an email alert was associated with increased discontinuation of nephrotoxins, but neither improved clinical outcomes. Translation of these findings into improved outcomes may require corresponding standardization of clinical practice protocols for managing AKI.

S2708 Hydroxycut-Induced Autoimmune Liver Disease

Introduction: Hydroxycut is an herbal supplement marketed as a “fat burner” that was voluntarily recalled in 2009 after a warning was issued by the FDA for potential hepatotoxicity. The product reappeared on the market in 2010 and subsequently, case reports have emerged describing Hydroxycut induced hepatotoxicity. We present a patient with a rare presentation of Hydroxycut induced liver injury. Case Description/Methods: A 64-year-old woman with a history of cholecystectomy and obesity presented with a 1-month history of worsening right upper quadrant abdominal pain, jaundice and nausea. Symptoms occurred approximately 1 month after starting Hydroxycut. Labs (summarized in Table 1) revealed elevated liver enzymes, positive ANA titer, elevated ASMA and IgG. Alcoholic liver disease, viral hepatitis, hemochromatosis, and Wilson disease were ruled out. Liver biopsy showed acute cholestatic injury and mixed inflammatory cells including plasma cells and eosinophils in the portal and lobular areas consistent with drug induced liver injury (DILI), but autoimmune hepatitis (AIH) could not be ruled out. During the hospitalization, she received NAC and prednisone, with subsequent improvement of her symptoms and liver tests. She was discharged on a prednisone taper. Outpatient labs 10 days later showed improvement of liver enzymes (Table 1). Discussion: Our patient had recently started Hydroxycut, presented with acute liver injury consistent with DILI, had positive serological markers consistent with simplified AIH score of 7 points, and responded appropriately to the prednisone taper. These findings suggest drug-induced autoimmune liver disease (DIAILD), which have been previously reported with other drugs. DIAILD remains a poorly understood entity, and several theories have been suggested to explain its pathophysiology. First, drug-induced development of autoantibodies leading to AIH that continues to progress and require lifelong immunosuppressive therapy (IST). Second, drug- induced autoantibodies that are exclusively associated with the presence of the drug, and resolves spontaneously with drug withdrawal or with IST. Third, the DILI can trigger the reactivation of a quiescent AIH or unmask a new diagnosis of AIH. It is not yet clear how our patient will respond to withdrawal of IST or if she will develop chronic AIH requiring lifelong IST. This case demonstrates the potential of dietary supplements to result in DILI with long term negative outcomes including AIH and sustained liver damage.Table 1.: Lab results compared from on admission to 10 days post discharge. ALP: Alkaline phosphatase; AST: Aspartate transaminase, ALT: Alanine aminotransferase; INR: International normalized ratio; ANA: Antinuclear antibody; ASMA: Anti-smooth muscle antibody; IgG: Immunoglobulin G; DC: Discharge.

S2352 An Uncommon Presentation of Hemorrhagic Cholecystitis

Introduction: Hemorrhagic Cholecystitis (HC) is a rare subtype of acute cholecystitis often seen in malignancy, trauma and anticoagulation use, presenting with abdominal pain and melena. Given the rarity of HC many cases are preliminarily misdiagnosed as infectious or acalculous cholecystitis based on symptomatology and imaging. This case presents with symptoms and imaging atypical for HC and discusses interventions that can be used to aide in diagnosis. Case Description/Methods: A 46 year-old man with a history of right peroneal vein thrombosis on warfarin, GERD, and alcohol abuse presented after outpatient labs showed a hemoglobin of 4.4. The patient had been experiencing fatigue, dyspnea, palpitations, and constipation with brown stool for several days. Physical exam was significant for pale mucosa and sinus tachycardia. Bloodwork showed: normocytic normochromic anemia of 4.2, total bilirubin of 1.5, negative guaiac stool and normal: reticulocyte index, LDH, and haptoglobin. Urinalysis showed urobilinogen and bilirubin and CT abdomen and pelvis without contrast was normal. To evaluate for a source of bleeding, the patient underwent CT Angiogram abdomen and pelvis that was normal. The patient underwent endoscopy and colonoscopy. A single angioectasia was seen in the gastric antrum and a patchy area of friable mucosa without active bleeding was found in the duodenal bulb and first part of the duodenum. Active bleeding from the major papilla was seen concerning for hemobillia or hemosuccus pancreaticus. Interventional radiology performed urgent angiography; however, no active source of bleeding, vascular shunting, or vascular malformation was found. The patient continued to require blood transfusions and underwent ERCP with successful hemostasis achieved by metal biliary stent placement. The patient returned to the hospital one week later, complaining of severe epigastric and right upper quadrant pain. He underwent laparoscopic cholecystectomy and was found to have hemorrhagic cholecystitis thought to be secondary to chronic anticoagulation use. Discussion: HC should not only be suspected in cases of severe abdominal pain or melena as has been documented in prior case reports. Anticoagulated patients are at an increased risk of bleeding especially from hollow organs like the esophagus, stomach and intestine. When traditional workup for source of bleeding is inconclusive, rare sources of bleeding such as HC should be suspected, with hemostasis achieved by cholecystectomy as seen in this case.Figure 1.: Endoscopy Images of Major Duodenal Papilla Bleeding.

Financial burden and impact of atopic dermatitis out-of-pocket healthcare expenses among black individuals in the United States

Black race is associated with increased atopic dermatitis (AD) severity and healthcare resource utilization. However, the burden of out-of-pocket (OOP) expenses among black individuals with AD is not well understood. We sought to characterize the categories and impact of OOP healthcare expenses associated with AD management among black individuals. A 25-question voluntary online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (US residents age ≥ 18 years; self-report of AD or primary caregivers of individuals with AD) was met by 77.3% (1118/1447) of respondents. Black individuals with AD were younger, had lower household income, Medicaid, urban residence, poor AD control and frequent skin infections (P ≤ 0.02). Blacks vs. non-blacks reported more OOP costs for prescription medications covered (74.2% vs. 63.6%, P = 0.04) and not covered (65.1% vs. 46.5%, P = 0.0004) by insurance, emergency room visits (22.1% vs. 11.8%, P = 0.005), and outpatient laboratory testing (33.3% vs. 21.8%, P = 0.01). Black race was associated with increased household financial impact from OOP expenses (P = 0.0009), and predictors of financial impact included minimally controlled AD (adjusted OR [95% CI] 13.88 [1.63–117.96], P = 0.02), systemic therapy (4.34 [1.63–11.54], 0.003), > $200 monthly OOP expenses (14.28 [3.42–59.60], P = 0.0003), and Medicaid (4.02 [1.15–14.07], P = 0.03). Blacks with Medicaid had higher odds of harmful financial impact (3.32 [1.77–6.24], P = 0.0002) than those of black race (1.81 [1.04–3.15], P = 0.04) or with Medicaid (1.39 [1.02–1.88], P = 0.04) alone. Black race is associated with increased OOP costs for AD and significant household financial impact. Targeted interventions are needed to address financial disparities in AD.

Invisibility in the Outpatient Laboratory

If you are a Harry Potter fan, you are familiar with the term “cloak of invisibility”: a magical cloth that renders the object it covers or the person who dons it invisible. What does this fictional artefact have to do with patient safety? Well, in this case it serves as a metaphor for patients (including me) who have felt their identities were overlooked (cloaked) during the blood draw process.

Coverage Denials for Medical Necessity Rules in Medicare

Research ObjectiveCoverage policy may be an important tool to reduce spending while discouraging low‐value medical services. Government and private insurers may also differ in their scope of coverage restrictions for suspected low‐value services. However, basic facts about coverage denials are unknown because denials are not identifiable in standard research datasets. In this study, we characterized fundamental features of coverage denials for medical necessity using data on all claims denied by a large Medicare Advantage health insurer.Study DesignWe analyzed medical benefit claims for Medicare Advantage beneficiaries. We detected all claims that were denied for failing to meet medical necessity rules. Some rules were made by the government (i.e. national or local coverage determinations) and other rules were made by the private insurer. We measured the frequency of denials, associated spending, affected service types and provider specialties, the reasons for denials, and temporal trends in denials. We also quantified differences between denials due to government coverage rules and denials due to private insurer coverage rules.Population StudiedWe analyzed 2014–2019 claims for all Medicare Advantage beneficiaries enrolled with the health insurer Aetna. Our sample included 2.9 million unique beneficiaries (mean age = 73, 56% female, 5% Medicaid dual eligible).Principal FindingsThere were 0.84 denials per beneficiary per year (95% CI 0.83–0.84), corresponding to 1.45% of claims (95% CI 1.44–0.46), with 31.8% of beneficiaries affected each year (95% CI 31.8–31.9). Denied claims accounted for $64 per beneficiary per year (95% CI 63–65), or 0.73% of medical spending (95% CI 0.71–0.76). Denial rates increased over time, from 0.59% of spending in 2014 to 0.85% of spending in 2019 (p &lt; 0.01). Government coverage rules accounted for 83% of denied claims, but only 60% of denied spending, and private insurer coverage rules accounted for the remaining denials. Most services denied under private insurer coverage rules were categorized as experimental/investigational (49%), not a treatment for disease (20%), or without proven efficacy (16%); denials for services categorized as cosmetic were rare (1%). A large majority of claims denied under Medicare coverage rules were for laboratory tests (75%), most of which were for chemistry studies. Denials under private insurer coverage rules were more widely distributed across service types; home care and chemotherapy accounted for the greatest shares of denied spending (14% and 11%). The provider types with the greatest share of denied spending were hospital outpatient departments (34%) and laboratories (19%).ConclusionsFor a large Medicare Advantage insurer, denials under medical necessity rules accounted for a small but growing fraction of annual spending. While most spending was denied under government coverage rules, additional private insurer rules targeted different types of services and accounted for additional denied spending.Implications for Policy or PracticeTo the authors' knowledge, this study presents the first comprehensive evidence on how often medical services are denied for failing to meet medical necessity criteria. In Medicare Advantage, coverage denials appear to contribute to modest savings, derived from both government‐produced and private insurer‐produced coverage criteria.Primary Funding SourceNIH, CVS Health, Phyllis &amp; Jerome Rappaport Foundation.

Utilization of the healthcare system by gynecologic oncology patients during the SARS-CoV-2 pandemic surge in New York City

Objectives:COVID-19 is characterized by rapid human-to-human transmission via contaminated respiratory droplets and therefore presents unique challenges in all aspects of healthcare delivery. This is especially true for patients with conditions, such as gynecologic cancer, which require frequent interface with healthcare centers. To further decrease the risk of exposure to these patients, alternate models of care delivery have been implemented and quickly adopted by medical centers. We sought to report the impact of modifications to traditional gynecologic cancer care at our institution.Methods:We identified women with suspected or confirmed gynecologic malignancy, age 18 or older, who received care at Montefiore Medical Center between March 16, 2020 and June 7, 2020; these dates reflect a series of executive orders issued by the governor of New York allowing the State Commissioner of Health to cancel elective procedures at hospitals, ambulatory surgery centers, and in the outpatient setting. Clinical data was abstracted from each patient's chart. Patients with incomplete treatment records were excluded.Results:A total of 111 women were identified to be undergoing active treatment and were included in our analysis, representing a total of 703 virtual or in-person patient encounters. More televisit encounters were performed compared to in-person encounters (209 vs 153). The average number of televisits per patient was significantly greater than the average number of in-person outpatient visits per patient (1.88±0.28 vs 1.38±0.42, p=0.047). Other encounters included 173 outpatient laboratory encounters, 112 outpatient radiology encounters, 30 emergency department encounters, 23 hospitalizations, and 3 ambulatory surgeries. Per patient, the median number of interactions was 5 (interquartile range 3-10). Patients with endometrial cancer (n=38) were more likely to be seen in person at least once in an outpatient visit than those with ovarian cancer (n=57) (OR 3.56, 95% CI 1.50-8.43). No significant difference between endometrial and ovarian cancer was seen in other types of encounters, including televisits (OR 0.94, 95% CI 0.32-2.74), inpatient admissions (OR 0.60, 95% CI 0.22-1.70), emergency room encounters (OR 0.77, 95% CI 0.28-2.09), ambulatory radiology encounters (OR 0.67, 95% CI 0.30-1.55), or ambulatory laboratory encounters (OR 0.96, 95% CI 0.42-2.24).Conclusions:The majority of patient encounters for gynecologic cancer at our institution during the SARS-COV-2 pandemic surge were conducted by telemedicine. Prior to the pandemic, telemedicine was not an active method of cancer care delivery within our institution. We predict that gynecologic oncology practice patterns will shift to include telemedicine as an integral part of patient care, even after SARS-COV-2 is no longer prevalent in the community.

A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans.

Preclinical studies demonstrate that cannabidiol (CBD) elicits an antinociceptive response in animal models of neuropathic pain; in humans, limited data are available to support such analgesic effects. Few studies have examined CBD's analgesic effects when administered without other compounds, and little is known regarding dose-dependent effects in noncannabis users. This double-blind, placebo-controlled, within-subject outpatient clinical laboratory study sought to determine the analgesic effects, abuse liability, safety and tolerability of acute CBD (0, 200, 400 and 800 mg orally) in healthy noncannabis-using volunteers (n = 17; 8 men, 9 women). Outcomes included experimental pain threshold and pain tolerance using the cold pressor test (CPT), subjective ratings of CPT painfulness and bothersomeness, subjective ratings of abuse liability and mood, and cardiovascular measures, which were assessed at baseline and several time points after drug administration. Data analyses included repeated measures analysis of variance (ANOVA) with planned comparisons. CBD failed to consistently affect pain threshold and tolerance in the CPT relative to placebo. All doses of CBD increased ratings of painfulness compared to placebo (P < .01). Further, CBD had dose-dependent, modest effects on mood and subjective drug effects associated with abuse liability. Oral CBD was safe and well tolerated, producing small decreases in blood pressure (P < .01). CBD did not elicit consistent dose-dependent analgesia and in fact increased pain on some measures. Future studies exploring CBD-induced pain relief should consider using a more extensive pain assessment paradigm in different participant populations.

Outpatient healthcare utilization among incident cases of systemic sclerosis: results from a population-based US cohort (1988–2016)

Objective Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease with multiorgan dysfunction. This study aimed to compare healthcare utilization among incident cases of SSc versus age- and gender-matched comparators. Method A population-based cohort of physician-diagnosed patients with SSc in Olmsted County, MN, USA, from 1 January 1988 to 31 December 2016 was assembled. A 2:1 cohort of age- and gender-matched non-SSc subjects was randomly selected for comparison. Patients were followed until death, migration from Olmsted County, or 31 December 2017. Outpatient utilization data were obtained beginning 12 months before the SSc incidence/index date and compared using negative binomial and multinomial models. Services were summarized as visit-days to avoid overestimation of services provided. Results The study included 69 incident SSc cases and 138 non-SSc comparators (mean ± sd age 57 ± 16 years at diagnosis/index, 90% female). Patients with SSc had higher utilization of outpatient physician, laboratory, and combined radiology visit-days annually for the year before and for each of the first 5 years after diagnosis than comparators. Among patients with SSc, healthcare utilization was highest during the year of SSc diagnosis. Rate ratios comparing utilization in patients with and without SSc ranged from 1.8 to 3.0 for all comparisons. Conclusion Higher utilization of outpatient physician, laboratory, and radiology visit-days was observed among patients with SSc compared to non-SSc subjects throughout 5 years of disease duration, indicating high and continued care needs in this patient population. The highest utilization of services among SSc patients occurred during the year of SSc diagnosis.

Diabetes Care and Glycemic Control During the COVID-19 Pandemic in the United States

Dramatic reductions in outpatient visits and laboratory testing early in the COVID-19 pandemic1,2 raised concerns about gaps in diabetes management and glycemic control.3 We therefore compared weekly rates of diabetes-related outpatient visits, screening tests, medication fills, and patients’ hemoglobin A1c (HbA1c) levels in 2020 vs 2019 in a national cohort of adults with type 2 diabetes.

CT-Based Risk Factors for Mortality of Patients With COVID-19 Pneumonia in Wuhan, China: A Retrospective Study.

Purpose: Computed tomography (CT) characteristics associated with critical outcomes of patients with coronavirus disease 2019 (COVID-19) have been reported. However, CT risk factors for mortality have not been directly reported. We aim to determine the CT-based quantitative predictors for COVID-19 mortality. Methods: In this retrospective study, laboratory-confirmed COVID-19 patients at Wuhan Central Hospital between December 9, 2019, and March 19, 2020, were included. A novel prognostic biomarker, V-HU score, depicting the volume (V) of total pneumonia infection and the average Hounsfield unit (HU) of consolidation areas was automatically quantified from CT by an artificial intelligence (AI) system. Cox proportional hazards models were used to investigate risk factors for mortality. Results: The study included 238 patients (women 136/238, 57%; median age, 65 years, IQR 51-74 years), 126 of whom were survivors. The V-HU score was an independent predictor (hazard ratio [HR] 2.78, 95% confidence interval [CI] 1.50-5.17; p = 0.001) after adjusting for several COVID-19 prognostic indicators significant in univariable analysis. The prognostic performance of the model containing clinical and outpatient laboratory factors was improved by integrating the V-HU score (c-index: 0.695 vs. 0.728; p < 0.001). Older patients (age ≥ 65 years; HR 3.56, 95% CI 1.64-7.71; p < 0.001) and younger patients (age < 65 years; HR 4.60, 95% CI 1.92-10.99; p < 0.001) could be further risk-stratified by the V-HU score. Conclusions: A combination of an increased volume of total pneumonia infection and high HU value of consolidation areas showed a strong correlation to COVID-19 mortality, as determined by AI quantified CT.

Economic burden of lung cancer in Turkey: a cost of illness study from payer perspective

BackgroundThis study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice.MethodsIn this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers.ResultsCost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively.ConclusionsOur findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments.

Detecting Cases of Monoclonal Gammopathy of Undetermined Significance in Electronic Health Data

Introduction: Multiple myeloma (MM) is known to be preceded by the largely asymptomatic and incidentally diagnosed condition monoclonal gammopathy of undetermined significance (MGUS). Retrospective studies estimate that 3% of all US adults aged ≥50 years have this premalignant condition, and that MGUS patients have a lifelong risk of progression to MM of about 1% per year. This persistent uncertainty results in heightened anxiety and clinical surveillance, and the associated financial burden. Recent population-based studies of MGUS have identified cases through testing stored blood specimens, an expensive and inefficient process that hinders initiation of large-scale studies of MGUS etiology and outcome. Thus, to facilitate population-based MGUS research, we are developing an algorithm to efficiently and accurately identify patients diagnosed with MGUS in longitudinally-collected automated healthcare claims and electronic health record (EHR) data. Our aim is to achieve maximum positive predictive value (PPV) with an algorithm that can be applied to large electronic health datasets to accurately identify MGUS cases for longitudinal studies of MGUS etiology, natural history, and health service utilization, minimizing the need for individual chart review.Methods: Men and women aged ≥50 years who sought care at a large, community-based healthcare provider group in central Massachusetts at least once between 2007 and 2015 and were enrolled for ≥12 months were eligible for this analysis. Patients diagnosed with MM prior to, or ≤3 months after the first MGUS diagnosis (ICD-9 code 273.1) were excluded. The MGUS case-finding algorithm was constructed using the Virtual Data Warehouse (VDW) at the Meyers Primary Care Institute. The VDW, which has been adopted by healthcare systems participating in the NCI-funded Cancer Research Network, is a distributed, standardized resource comprised of clinical and administrative data, and populated with linked demographic, administrative, outpatient laboratory, and healthcare utilization data.The first step of the algorithm identified all eligible patients with ≥2 MGUS diagnosis codes entered on different dates within a 12 month period. Next, we selected those patients who, within 90 days of MGUS diagnosis, had: A) ≥1 code for a serum protein electrophoresis test (CPT code 84155 or 84156); B) a serum or urine immunofixation test (CPT 86334 or 86335); and C) an office visit with an oncologist. Relevant protein electrophoresis test results, which typically appear as text in the EHR, were not extractable from available data, and thus patients met the algorithm criteria if the corresponding CPT code was present in their EHR. A targeted manual chart review, conducted by three nurse abstractors and adjudicated by two clinicians, validated the algorithm and constituted the gold standard for subsequent calculations of PPV.Results: The algorithm identified 833 subjects with ≥2 MGUS diagnosis codes in their EHR within a 12 month period; 429 (52%) patients met all four algorithm criteria. Records for 250 of the latter patients (58%) were selected for review. Potential MGUS cases meeting all four algorithm criteria were 85% white, 51% female, had a median of 10 MGUS diagnosis codes in their EHR, and a mean age of 74 years at diagnosis. In the underlying patient population, immunofixation was routinely ordered for patients with abnormal protein electrophoresis test results; thus, 98% of patients who had a protein electrophoresis test also had an immunofixation test, reducing the discriminatory capacity of this algorithm step. Review of the first 2% of charts suggests a preliminary PPV of 75% or greater for the four-step algorithm; chart review is ongoing.Conclusions: Early results from this single-site study suggest that MGUS cases can be identified with reasonable accuracy in electronic health data through a four-step algorithm. However, in light of the frequent use of immunofixation noted above, the incorporation of specific lab test results may be required to improve the PPV. Following completion of ongoing chart review, the algorithm will be applied to a second Cancer Research Network healthcare system with a shared data structure for further refinement, and to evaluate its performance in an independent population. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of SARS-CoV-2 IgG antibody reactivity in patients with systemic lupus erythematosus: analysis of a multi-racial and multi-ethnic cohort.

BackgroundPatients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection.MethodsFor this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits.Findings329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vsz 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset.InterpretationMost patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2.FundingNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.

P512 Safety of reduced clinical monitoring in patients with stable Inflammatory Bowel Disease on maintenance thiopurine therapy

Abstract Background Thiopurine-treated inflammatory bowel disease (IBD) patients are monitored every 3 to 4 months with outpatient visits and laboratory assessments to evaluate disease activity and safety of therapy. However, the risk of thiopurine-related adverse events decreases after the initiation phase. The aim of this study was to assess the safety of reduced clinical monitoring in steroid-free quiescent IBD patients on stable maintenance thiopurine monotherapy. Methods This single-centre prospective cohort study evaluated a reduced monitoring strategy that involved 6-monthly laboratory assessment combined with alternating outpatient and phone appointments, during 104 weeks. We enrolled IBD patients who were in steroid-free remission &amp;gt; 6 months on thiopurine monotherapy including azathioprine, 6-mercaptopurine or tioguanine. The primary outcome was thiopurine-related adverse events (AE) requiring change or discontinuation of thiopurine therapy after 104 weeks of follow-up. Secondary outcomes were assessed at week 52 and included other thiopurine-related AEs and laboratory abnormalities. Results We included 85 patients (42 years median age, 61.2% Crohn’s disease, 62% female) with a median disease duration of 12.5 years. At baseline, 47 patients were treated with azathioprine (55.3%), 25 with 6-mercaptopurine (29.4%) and 13 with tioguanine (15.3%) for a median duration of 6.7 years. During 104 weeks of follow-up, thiopurine therapy was ceased in two patients because of multiple infections (n=1) and gastrointestinal complaints (n=1). Other reasons for thiopurine cessation (n=37) were stable remission (n=26), patient preferences (n=9) and high 6-TGN levels (n=2). In total, 20 patients underwent thiopurine dose adjustments due to high metabolite levels (n=9), remission (n=3), disease flare (n=3), patient preferences (n=3), and low metabolite levels (n=2). At 52 weeks, 27 laboratory abnormalities were observed, yet none required therapy adjustments. In 13 patients (15.3%) myelotoxicity was detected, including mild leukopenia (n=11), mild and moderate thrombopenia (n=2). In 16.5%, hepatoxicity was observed (n=14) including mild (n=9) and moderate (n=1) elevated aspartate aminotransferase and mild elevated alkaline phosphatase (n=4). Conclusion A reduced monitoring strategy appeared relatively safe in a strictly selected cohort of stable thiopurine-treated IBD patients. Overall, two patients had to cease thiopurine therapy due to thiopurine-related AEs independent of monitoring frequency. No laboratory abnormalities required therapy adjustments and 57.1% of patients continued therapy throughout 104 weeks of follow-up. This strategy may contribute to safe reduction of time and health care costs for both IBD patients and physicians in daily IBD practice.

P490 The impact of the COVID-19 pandemic on gastroenterologists providing care to inflammatory bowel disease patients in Canada: preliminary data of a cross-sectional survey

BackgroundWe aim to explore the impact of COVID-19 pandemic-related restrictions on gastroenterologists providing care to inflammatory bowel disease (IBD) patients in Canada.MethodsWe invited 28 Canadian gastroenterology societies, 14 academic centres and 101 community hospitals and private clinics to have their gastroenterologists engage in an online mixed methods survey from December 2020 - March 2021. The survey explored the impact of pandemic-related restrictions on gastroenterologists managing IBD patients and the impact on clinical decision-making, rates of consultation, investigations and endoscopies conducted before and during the pandemic.Results59 gastroenterologists (59.3% male) participated in our study with 40.7% having completed additional training in IBD. Respondents mean age was 43.7 years with 30.5% practising independently for a duration of less than or equal to 5 years. The majority of respondents were from Ontario (43.1%), Quebec (31%) and British Columbia (13.8%) with 62.7% practising primarily at an academic centre.93.2% of respondents reported that their practice was affected by the pandemic. 44.6% note a reduction in the number of total consultations completed. Only 60% were able to arrange endoscopies for patients in an active IBD flare at an appropriate time interval compared to their pre-COVID practice. During the pandemic, 87.3% reported a reduction in the total endoscopies performed, with 43.8% of those individuals noting a minimum reduction of 25% of previous volumes. The following barriers attributed to the decrease in endoscopies performed during the pandemic: institutional-imposed restriction on daily allowed endoscopies (97.9%), indication for endoscopy was non-urgent (68.8%) and patient-requested cancellation due to a fear of contracting COVID-19 (87.5%).63.6% of respondents were able to arrange outpatient laboratory investigations in less than 1-week prior to the pandemic vs. 41.8% arranging similar tests in 1–2 weeks during the pandemic. 50.9% were able to arrange diagnostic investigations in 1–2 months before the pandemic vs. 65% arranging similar tests in 3-months or more during the pandemic.When advancing drug therapy in IBD patients before versus during the pandemic, respondents reported the following factors as playing a crucial role in clinical decision making: patient symptomatology (87% vs. 79.3%), laboratory investigations (94.8% vs. 96.6%), diagnostic imaging (89.7% vs. 81%) and endoscopy findings (89.7% vs 72.4%).ConclusionWe illustrate that Canadian gastroenterologists have been affected by the pandemic, with decreases in endoscopy performance related to access and patient preference and less decision-making guided by endoscopy. Outpatient access to urgent investigations was reduced.

Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study

ObjectiveTo evaluate the excess risk and relative hazards for developing incident clinical sequelae after the acute phase of SARS-CoV-2 infection in adults aged 18-65.DesignRetrospective cohort study.SettingThree merged data sources from...

Economic Study of 2-Stage Exchange in Patients With Knee or Hip Prosthetic Joint Infection Managed in a Referral Center in France: Time to Use Innovative(s) Intervention(s) at the Time of Reimplantation to Reduce the Risk of Superinfection.

Objective: Chronic prosthetic joint infections (PJI) are serious complications in arthroplasty leading to prosthesis exchange and potential significant costs for health systems, especially if a subsequent new infection occurs. This study assessed the cost of chronic PJI managed with 2-stage exchange at the Lyon University Hospital, CRIOAc Lyon reference center, France. A threshold analysis was then undertaken to determine the reimbursement tariff of a hypothetical preventive device usable at the time of reimplantation, which possibly enables health insurance to save money according to the risk reduction of subsequent new infection. This analysis was also performed for a potential innovative device already available on the market, a dual antibiotic loaded bone cement used to fix cemented prosthesis that releases high concentrations of gentamicin and vancomycin locally (G+V cement).Method: Patients >18 years, admitted for a hip or knee chronic PJI managed with 2-stage exchange, between January 1, 2013, and December 31, 2015, were retrospectively identified. Following, resource consumption in relation to inpatient hospital stay, hospitalization at home, rehabilitation care, outpatient antibiotic treatments, imaging, laboratory analysis, and consultations were identified and collected from patient records and taken into account in the evaluation. Costs were assessed from the French health insurance perspective over the 2 years following prosthesis reimplantation.Results: The study included 116 patients (median age 67 y; 47% hip prosthesis). Mean cost of chronic PJI was estimated over the 2 years following prosthesis reimplantation at €21,324 for all patients, and at €51,697 and €15,745 for patients with (n = 18) and without (n = 98) a subsequent new infection after reimplantation, respectively. According to the threshold analysis the reimbursement tariff (i) should not exceed €2,820 for a device which can reduce the risk of a new infection by 50% and (ii) was between €2,988 and €3,984 if the G + V cement can reduce the risk of a new infection by 80% (this reduction risk is speculative and has to be confirmed by clinical trials).Conclusion: This study revealed that chronic PJI requiring a 2-stage revision is costly, with significant costs in relation to the reimplantation procedure (about 15 k€). However, following reimplantation the rate of subsequent new infection remained high, and the cost of reimplantation following a new infection is considerable, reaching 50k€ per patient. These first cost estimates of managing chronic PJI with 2-stage exchange in France underline the economic interest of preventing new infections.

Refractory Postsurgical Hypothyroidism in Nephrotic Syndrome

Abstract 62-year-old female with a history of thyroid cancer of unknown type s/p thyroidectomy 30 years prior to presentation, who had 2 months of worsening generalized edema and increasing need of dose escalation of her oral thyroid replacement by her PCP. Despite increasing her thyroxine dose multiple times and adding Armour thyroid based on increasing TSH and decreasing FT4 on outpatient labs, her edema continued to get worse. She presented to the Emergency Department. She takes no other medications. Symptoms include malaise, cold intolerance, weight gain, hair loss, bloating without constipation,“feeling foggy” and that her memory seemed a bit “off”, and she felt her mood was more “sensitive”, and she had atypical non-exertional chest discomfort. On exam she was was bradycardic to 56 and hypertensive to 175 systolic, had faint bibasilar crackles were present bilaterally, had significant pitting edema of the bilateral lower extremities, 3+ up to the level of her abdomen, as well as pitting edema of her bilateral upper extremities, and no periorbital edema was seen. Her neurologic exam was non-focal. Outpatient labs included TSH 178, free T4 0.35, albumin 1.2, and BNP level of 57. Her liver and kidney function tests were normal. Hospital labs included a normal CBC, chemistry with an albumin of 2.2 and normal range liver and kidney function. Thyroid function tests included a very high TSH level of 141, low free T4 level of 0.37, and a free T3 toward the lower end of normal. Lipid panel showed severe hypercholesterolemia. Urine studies showed microhematuria as well as the equivalent of proteinuria to the level of 10 grams per day. HIV was negative and complement levels were within normal limits. CXR, renal US, transvaginal US, and CT chest/abdomen/pelvis were performed to investigate the proteinuria and potential secondary causes of the proteinuria, all of which were unremarkable for acute or pertinent findings. Pathology results from a kidney biopsy showed membranous nephropathy. The patient initially received IV steroids and IV thyroxine as well as an albumin infusion. She was quickly transitioned to oral thyroxine due to her stability on presentation. She was given a statin and ACE inhibitor as well as IV Lasix. And she was discharged on thyroxine, with Armour thyroid being discontinued. She had severe hypothyroidism in a patient dependent on exogenous thyroid hormone which was exacerbated by severe proteinuria due to a new-onset nephrotic syndrome. Her hospital course uneventful. She responded well to intravenous diuretics. After her diagnosis of membranous nephropathy, Nephrology recommended continued conservative treatment due to her normal renal function and improving edema with outpatient follow up. She only received a single dose of IV thyroxine and remained stable after switching to oral thyroxine.

SARS-CoV-2 seroprevalence, and IgG concentration and pseudovirus neutralising antibody titres after infection, compared by HIV status: a matched case-control observational study

BackgroundMost cohorts show similar or lower COVID-19 incidence among people living with HIV compared with the general population. However, incidence might be affected by lower testing rates among vulnerable populations. We aimed to compare SARS-CoV-2 IgG seroprevalence, disease severity, and neutralising antibody activity after infection among people with and without HIV receiving care in a county hospital system over a 3-month period.MethodsIn this matched case-control observational study, remnant serum samples were collected between Aug 1 and Oct 31, 2020, from all people living with HIV who underwent routine outpatient laboratory testing in a municipal health-care system (San Francisco General Hospital, CA, USA). Samples from people living with HIV were date of collection-matched (same day) and age-matched (±5 years) to samples from randomly selected adults (aged 18 years or older) without HIV receiving care for chronic conditions at the same hospital. We compared seroprevalence by HIV status via mixed-effects logistic regression models, accounting for the matched structure of the data (random effects for the matched group), adjusting for age, sex, race or ethnicity, and clinical factors (ie, history of cardiovascular or pulmonary disease, and type 2 diabetes). Severe COVID-19 was assessed in participants with past SARS-CoV-2 (IgG or PCR) infection by chart review and compared with multivariable mixed-effects logistic regression, adjusting for age and sex. SARS-CoV-2 IgG, neutralising antibody titres, and antibody avidity were measured in serum of participants with previous positive PCR tests and compared with multivariable mixed-effects models, adjusting for age, sex, and time since PCR-confirmed SARS-CoV-2 infection.Findings1138 samples from 955 people living with HIV and 1118 samples from 1062 people without HIV were tested. SARS-CoV-2 IgG seroprevalence was 3·7% (95% CI 2·4 to 5·0) among people with HIV compared with 7·4% (5·7 to 9·2) among people without HIV (adjusted odds ratio 0·50, 95% CI 0·30 to 0·83). Among 31 people with HIV and 70 people without HIV who had evidence of past infection, the odds of severe COVID-19 were 5·52 (95% CI 1·01 to 64·48) times higher among people living with HIV. Adjusting for time since PCR-confirmed infection, SARS-CoV-2 IgG concentrations were lower (percentage change −53%, 95% CI −4 to −76), pseudovirus neutralising antibody titres were lower (−67%, −25 to −86), and avidity was similar (7%, −73 to 87) among people living with HIV compared with those without HIV.InterpretationAlthough fewer infections were detected by SARS-CoV-2 IgG testing among people living with HIV than among those without HIV, people with HIV had more cases of severe COVID-19. Among people living with HIV with past SARS-CoV-2 infection, lower IgG concentrations and pseudovirus neutralising antibody titres might reflect a diminished serological response to infection, and the similar avidity could be driven by similar time since infection.FundingUS National Institute of Allergy and Infectious Diseases, US National Institutes of Health.