Disease-related Hospitalization Research Articles

Prognostic Relevance of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Arterial Pressure Ratio and Its Association With Exercise Hemodynamics in Patients With Normal or Mildly Elevated Resting Pulmonary Arterial Pressure

BackgroundEchocardiographic TAPSE/sPAP ratio is a non-invasive surrogate for right ventricular-pulmonary arterial (RV-PA) coupling. It has been related to outcome in patients with moderate to severe pulmonary hypertension (PH). Research QuestionIs RV-PA coupling of prognostic relevance in patients with suspected PH but only normal or mildly elevated mean pulmonary arterial pressure (mPAP) and is it associated with impaired exercise capacity and exercise hemodynamics? Study Design and MethodsPatients with mPAP<25mmHg who underwent echocardiography and exercise right heart catheterization in our PH-clinic, were retrospectively analyzed. Mild PH was defined by mPAP 21-24mmHg and exercise PH (EPH) by a mPAP/cardiac-output (CO) slope >3mmHg/L/min. Multivariate analysis was performed to identify independent predictors for clinical worsening, defined by disease-related hospitalization, transplantation, or death. Results237 patients (female: N=155; median age: 64 (IQR 54-73) years, no PH N=147; mild PH N=90; EPH N=202) were included. During the observation time of 63 (IQR:29-104) months, 36 patients died and 126 events of clinical worsening occurred. TAPSE/sPAP ratio turned out as age- and sex independent predictor of mortality (HR 0.09 95% CI: (0.01 – 0.62) p=0.014) and clinical worsening (HR 0.05 95% CI: (0.35-0.78); p=0.002). TAPSE/sPAP was also significantly correlated to 6-minute walk distance (r= 0.33; p<0.001) and exercise hemodynamics (mPAP/CO slope: rρ=-0.56, p<0.001). The best multivariate predictive model for clinical worsening in this patient collective consisted of TAPSE/sPAP ratio (HR: 0.71 (0.53-0.95), p=0.021), NT-proBNP (HR 1.15 (0.99-1.34), p=0.065) and 6MWD (HR: 0.998 (0.995-1.00), p=0.042). InterpretationIn patients with suspected PH but normal or only mildly elevated resting mPAP, TAPSE/sPAP ratio is an independent predictor of outcome. In addition, it is significantly associated with exercise capacity and exercise hemodynamics and may be a helpful tool in the prediction of future clinical worsening of this patient population.

Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.

Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD. Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm. Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively. Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.

Clinical characteristics and long-term disease course in patients with Crohn's disease as diagnosed by video capsule endoscopy: a multicenter retrospective matched case-control study.

Video capsule endoscopy is rarely used to diagnose Crohn's disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases. This multicenter study included patients with Crohn's disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn's disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393-1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn's disease-related hospitalization, and surgeries (log-rank test P< 0.05). Patients with Crohn's disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.

Green and blue space exposure and non-communicable disease related hospitalizations: A systematic review

Green and blue space exposure and non-communicable disease related hospitalizations: A systematic review

Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan - Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease. This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

Efficacy and Safety of Endoscopic Stricturotomy in Inflammatory Bowel Disease-Related Strictures: A Systematic Review and Meta-Analysis.

Luminal strictures, common in inflammatory bowel disease (IBD), especially Crohn's disease (CD), are typically treated with endoscopic balloon dilatation (EBD). The newer endoscopic stricturotomy (ESt) approach shows promise, but data is limited. This systematic review and meta-analysis assess the effectiveness and safety of ESt in IBD-related strictures. A comprehensive literature search was conducted until November 2023 for studies assessing ESt efficacy and safety in IBD. Primary outcomes were clinical and technical success, with secondary endpoints covering adverse events, subsequent stricture surgery, additional endoscopic treatments (ESt or EBD), medication escalation, disease-related emergency department visits, and hospitalization post-ESt. Technical success was defined as passing the scope through the stricture, and clinical success was defined as symptom improvement. Single-arm meta-analysis (CMA version 3) calculated the event rate per patient with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Nine studies were included, involving 640 ESt procedures on 287 IBD patients (169 CD, 118 ulcerative colitis). Of these, 53.3% were men, with a mean age of 43.3 ± 14.3years and a mean stricture length of 1.68 ± 0.84cm. The technical success rate was 96.4% (95% CI 92.5-98.3, p-value < 0.0001), and the clinical success rate was 62% (95% CI 52.2-70.9, p-value = 0.017, I2 = 34.670). The bleeding rate was 10.5% per patient, and the perforation rate was 3.5%. After an average follow-up of 0.95 ± 1.1years, 16.4% required surgery for strictures post-ESt, while 44.2% needed additional endoscopic treatment. The medication escalation rate after ESt was 14.7%. The disease-related emergency department visit rate was 14.7%, and the disease-related hospitalization rate post-procedure was 21.3%. Our analysis shows that ESt is safe and effective for managing IBD-related strictures, making it a valuable addition to the armamentarium of endoscopists. Formal training efforts should focus on ensuring its widespread adoption.

Mobile monitoring system detects the disease activity pattern and shows the association with clinical outcomes in patients with newly diagnosed Crohn’s disease

We aimed to determine whether Crohn’s disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5–10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86–203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49–85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.

Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease

Autosomal dominant polycystic liver disease is a rare condition with a female preponderance, based mainly on pathogenic variants in 2 genes, PRKCSH and SEC63. Clinically, autosomal dominant polycystic liver disease is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and US centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease. We analyzed an international multicenter cohort of 265 patients with autosomal dominant polycystic liver disease harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes and polycystic liver disease-related hospitalization (liver event) as primary clinical end points. Classifying individual total liver volumes into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. In addition, disease severity, defined by age at first liver event, was considerably more pronounced in female patients and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease, in addition to imaging-based prognostication. Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid total liver volume progression is associated with the greatest odds of polycystic liver disease-related hospitalization.

Dose Escalation of Biologics in Biologic-Naïve Patients With Ulcerative Colitis: Outcomes From the ODESSA-UC Study.

Dose escalation of biologics may regain treatment response in patients with ulcerative colitis (UC). However, dose escalation rates and associated outcomes and costs are not well characterized in biologic-naïve patients receiving antitumor necrosis factor-alpha (anti-TNF-α) treatments, such as infliximab or adalimumab or vedolizumab. ODESSA-UC, a retrospective cohort study investigating dose escalation in patients with UC who had received first-line biologics, used data from IBM MarketScan databases. Adults with UC and ≥1 claim for an index drug (adalimumab, infliximab, or vedolizumab) were eligible. A Cox proportional hazards model was used to evaluate the adjusted rate of dose escalation. Logistic regression was used to evaluate the odds of experiencing adverse outcomes (corticosteroid use, infection, sepsis, or inflammatory bowel disease-related hospitalization) and incurring index drug costs. A year after the start of maintenance, a lower proportion of patients experienced dose escalation with vedolizumab (22.3%) than adalimumab (43.0%). The dose escalation risk was significantly higher for infliximab (hazard ratio [HR], 1.894; 95% confidence interval [CI], 1.486-2.413) and adalimumab (HR, 2.120; 95% CI, 1.680-2.675) than for vedolizumab. The odds of experiencing an adverse outcome after dose escalation were higher for anti-TNF-α treatments than for vedolizumab (odds ratio, 2.052; 95% CI, 1.200-3.507). Index drug costs after dose escalation were lowest for vedolizumab. Patients with UC receiving vedolizumab had a lower risk of dose escalation and lower subsequent costs than patients receiving anti-TNF-α treatments. Our study demonstrates the possible clinical and economic implications of dose escalation.

S1587 The Impact of Nonalcoholic Fatty Liver Disease on Inflammatory Bowel Disease-Related Hospitalization Outcomes: A Systematic Review

S1587 The Impact of Nonalcoholic Fatty Liver Disease on Inflammatory Bowel Disease-Related Hospitalization Outcomes: A Systematic Review

Telenursing and Remote Patient Monitoring in Cardiovascular Health.

Background: Since the decline in death rates from cardiovascular diseases has slowed down recently, promoting cardiovascular health in patients and the general public has become more important than ever, particularly for elder and rural patients. This study is a collaborative effort between a regional health network in Virginia and associated organizations to implement and assess telenursing and remote patient monitoring (RPM) to help home care patients better manage their own cardiovascular related diseases and promote sustainable health delivery options. Method: Eighty cardiovascular patients with diabetes, congestive heart failure, or both who had a recent disease-related hospital stay were enrolled in the RPM program to receive services, including care coordination, coaching, referral for behavioral health, and aging-related services for 90+ days. The program used telenursing and RPM through home care monitoring equipment to coach patients on effective measures to stay compliant with posthospitalization regimens, track and evaluate readmissions, and assess physiological status and mental health. Result: There was a decline in hospital admissions of 65%, 85% for observations and related inpatient services for enrolled CVD patients in the RPM program. In addition, the longer the patient was enrolled the less likely they were to readmit. The program saved ∼$615,127 in patient claims costs and had net savings of $390,296, ∼173% of the total program expenses. Discussion: Evidence showed that 90+ day enrollments are sufficient for realization of readmissions and Emergency Department reductions, increased health care access, and lower costs. This resulted from consistent monitoring using the technology to alert nurses and care coordinators who were able to respond and facilitate patients accessing care in the most helpful and generally less costly care environment. Conclusion: The study has confirmed that care coordination and RPM are effective in supporting self-management of chronic conditions and cost reductions through telenursing and RPM.

Efficacy and safety of inebilizumab in Asian participants with neuromyelitis optica spectrum disorder: Subgroup analyses of the N-MOmentum study

BackgroundInebilizumab, an anti-CD19 B cell-depleting antibody, reduced the risk of a neuromyelitis optica spectrum disorder (NMOSD) attack, disability worsening, magnetic resonance imaging (MRI) lesion activity, and disease-related hospitalizations in participants with NMOSD in the N-MOmentum study (NCT02200770). However, the efficacy and safety outcomes of inebilizumab specific to an Asian population were not fully reported. Therefore, subgroup analyses of the N-MOmentum study were conducted post hoc to evaluate the efficacy and safety of inebilizumab in Asian participants with NMOSD. MethodsThe N-MOmentum study was a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial with an open-label extension period (OLP). In the subgroup analyses, data from Asian participants from the N-MOmentum study were compared with those of non-Asian participants. Eligible participants were randomly allocated (3:1) to receive 300 mg intravenous (IV) inebilizumab or placebo on Days 1 and 15. Participants who had an NMOSD attack or completed the randomized controlled period (RCP) could enter the OLP, where they received inebilizumab for ≥2 years. All participants who entered the OLP received inebilizumab 300 mg IV every 6 months. ResultsOverall, 230 participants received treatment (174 received inebilizumab and 56 received placebo), of whom 47 were Asian (39 received inebilizumab and 8 received placebo). Baseline characteristics were similar between the Asian and non-Asian subgroups, except for disease duration, annualized relapse rate prior to randomization in this study, and previous maintenance therapy. In the Asian subgroup, the risk of NMOSD attacks was reduced with inebilizumab versus placebo (hazard ratio, 0.202) and the attack-free rate at 28 weeks was 82.1% with inebilizumab versus 37.5% with placebo, in the 6-month RCP. NMOSD attack rates were comparable between the Asian and non-Asian subgroups. In the Asian subgroup, the rates of Expanded Disability Status Scale worsening from baseline, active MRI lesions, and disease-related hospitalizations tended to be lower in the inebilizumab group than in the placebo group; similar results were shown in the non-Asian subgroup. For long-term efficacy and safety (RCP and OLP), the annualized adjudicated NMOSD attack rate in Asian participants treated with inebilizumab was reduced (0.096) compared with that at baseline (1.04), with a mean follow-up period of inebilizumab treatment of 3.38 years, which was consistent with the results in the non-Asian subgroup. The risk of NMOSD attack decreased with prolonged duration of treatment in both the inebilizumab/inebilizumab and placebo/inebilizumab groups in the Asian and non-Asian subgroups. The incidence of treatment-emergent adverse events (TEAEs) was similar between the Asian and non-Asian subgroups. In the Asian and non-Asian subgroups, 15.2% and 35.2% of participants, respectively, had at least one serious TEAE and/or Grade ≥3 TEAE during long-term therapy. No deaths occurred in the Asian subgroup whereas three deaths occurred in the non-Asian subgroup. ConclusionInebilizumab reduced the risk of an NMOSD attack, progression of disability, MRI lesion activity, and disease-related hospitalizations in Asian participants with NMOSD. The efficacy of inebilizumab in reducing NMOSD attacks continued without any unexpected safety signals or concerns during long-term use in Asian participants.

Association between fresh fruit consumption and the risk of chronic obstructive pulmonary disease-related hospitalization and death in Chinese adults: A prospective cohort study.

Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China. Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders. During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively. High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.

The Burden of Streptococcus pneumoniae-Related Admissions and In-Hospital Mortality: A Retrospective Observational Study between the Years 2015 and 2022 from a Southern Italian Province.

Streptococcus pneumoniae (SP) has high worldwide incidence and related morbidity and mortality, particularly among children and geriatric patients. SP infection could manifest with pneumonia, bacteremia, sepsis, meningitis, and osteomyelitis. This was a retrospective study aimed at evaluating the incidence, comorbidities, and factors associated with in-hospital mortality of pneumococcal disease-related hospitalization in a province in southern Italy from the years 2015 to 2022. This study was performed in the Local Health Authority (LHA) of Pescara. Data were collected from hospital discharge records (HDRs): this database is composed of 288,110 discharge records from LHA Pescara's hospitals from 2015 to 2022. Streptococcus Pneumoniae-related hospitalizations were about 5% of the hospitalizations; 67% of these were without comorbidities; 21% were with one comorbidity; and 13% were with two or more comorbidities. Regarding mortality of SP infection, the most affected age group was older people, with the percentage of cases among the over-65s being more than 50% compared to the other age groups. HDRs represent a valid and useful epidemiological tool for evaluating the direct impact of pneumococcal disease on the population and also indirectly for evaluating the effectiveness of vaccination strategies and directing them.

COVID-19 Proactive Disease Management Using COVID Virtual Hospital in a Rural Community.

A community teaching hospital serving a rural population established an intensive "hospital at home" program for patients with COVID-19 utilizing disease risk stratification and pulse oximeter readings to dictate nurse and clinician contact. Herein, we report patient outcomes and provider experiences resulting from this "virtual" approach to triaging pandemic care. COVID-19-positive patients appropriate for outpatient management were enrolled in our COVID Virtual Hospital (CVH). Patients received pulse oximeters and instructions for home monitoring of vital signs. CVH nurses contacted the patient within 12-48 hours. The primary care provider was alerted of the patient's diagnosis and held a virtual visit with patient within 2-3 days. Nurses completed a triage form during each patient call; the resulting risk score determined timing of subsequent calls. CVH-relevant patient outcomes included emergency department (ED) visits, mortality, and disease-related hospitalization. Additionally, a survey of providers was conducted to assess CVH experience. From April 22, 2020, to December 21, 2020, 1916 patients were enrolled in the CVH, of which 195 (10.2%) had subsequent visits to the ED. Among those 195 ED visits, 102 (52.3%) were nurse-directed while 93 (47.7%) were patient self-directed; 88 (86.3%) nurse-directed ED visits were subsequently admitted to inpatient care and 14 were discharged home. Of the 93 self-directed ED visits, 3 (3.2%) were admitted. A total of 91 CVH patients (4.7%) were ultimately admitted to inpatient care. Seven deaths occurred among CVH patients, 5 of whom had been admitted for inpatient care. Among 71 providers (23%) who responded to the survey, 94% and 93% agreed that the CVH was beneficial to providers and patients, respectively. Proactive in-home triage of patients with COVID-19 utilizing a virtual hospital model minimized unnecessary presentations to ED and likely prevented our rural hospital from becoming overwhelmed during year one of the pandemic.

Psychological morbidity in patients with pemphigus and its clinicodemographic risk factor: A comparative study.

Due to the long disease duration, impact on appearance, social stigmatization, and numerous side effects of treatment, pemphigus, an autoimmune bullous disease, often has a significant psychological impact on patients. On the other hand, mood disorders may exacerbate the disease by affecting the patient's self-management, forming a vicious circle. To investigate anxiety and depressive disorders in patients with pemphigus, a total of 140 patients with pemphigus were recruited for this cross-sectional retrospective study between March 2020 and January 2022. A control group of 118 patients with psoriasis, a commonly known psychosomatic dermatosis, was established. Patients were evaluated at the visiting day with the Beck Anxiety Inventory and Beck Depression Inventory second edition for mood disorders, the Dermatology Life Quality Index and the EuroQol Five Dimensions Questionnaire for disease-related life quality, and the Visual Analogue Scale for pain and itching symptoms. In our cohort, 30.7% of patients with pemphigus suffered from either anxiety disorder (25%) or depressive disorders (14.3%). Propensity score matching was implemented to create a comparable cohort of pemphigus and psoriasis groups considering the baseline discrepancy. Thirty-four comparable pairs of pemphigus and psoriasis patients were extracted. The prevalence and severity of depressive disorder in pemphigus patients were significantly higher than in psoriasis patients, while anxiety disorder levels appeared to be similar in two groups. Multivariate logistic regression analysis further revealed that disease-related hospitalization history, active mucosal damage, and concomitant thyroid disease are independent risk factors for mood disorders in pemphigus patients. Our results showed that pemphigus patients had a high prevalence and severity of mood disorders. Relevant clinicodemographic indicators may be valuable for prediction and early identification of mood disorders in pemphigus. Better disease education from physicians may be important for these patients to achieve overall disease management.

A phase I study of isunakinra, an IL-1 alfa/beta inhibitor, in combination with nivolumab for patients with solid tumors refractory to standard therapies.

e14580 Background: Interleukin-1 is a master cytokine produced by macrophages (IL-1 β) and released upon cell death (IL-1 α). IL-1 upregulates other cytokines in the tumor microenvironment (i.e. IL-6 and IL-8), drives chronic non-resolving inflammation in the tumor, induces cancer cell invasion and metastasis (EMT), has profound effects on immune cells and cancer associated fibroblasts and can attract granulocytic myeloid suppressor cells to the tumor (PMN-MDSC), that in turn inhibit cytotoxic T cell responses. Isunakinra is a small recombinant protein resembling IL-1Ra, with an inhibitory potency 10-20 times higher, that binds to the IL1-R1 and blocks activation of the receptor by both IL-1α and IL-1β. We conducted a phase I dose escalation study with isunakinra as monotherapy and in combination with a PD-1 inhibitor in patients with locally advanced or metastatic solid tumors that had exhausted all treatment options. Methods: Enrolled patients with refractory metastatic solid tumor, ECOG 0-2, on a 3 + 3 dose-escalation trial at three dose levels of isunakinra (15, 25 or 50 mg). Isunakinra was self-administered once daily SC for three weeks followed by 4 additional weeks in combination with nivolumab Q4W at 480 mg, flat dose to complete the DLT period of 7 weeks. Thereafter, isunakinra/nivolumab was continued until week 28. Primary endpoints: DLTs, safety, and pharmacokinetics. Secondary endpoints: tumor and immune monitoring. Results: Enrolled fifteen patients with metastatic or unresectable locally advanced solid tumors (colorectal, pancreatic, triple-negative BC, anal, prostatic, CCA, and appendix) that had received 2-5 prior lines of therapy. Seven SAE occurred in three rapidly deteriorating subjects, all disease related hospitalizations, leading to study withdrawal during the DLT period. No DLTs, irAE or predefined laboratory deviations occurred in any subject. The highest dose, 50 mg, was selected as RP2D. Twelve subjects completed visit week 8, six of them week 12, and four completed the trial. One patient with metastatic colon cancer (MSS, KRAS mut, high TMB) was granted extended treatment for PR and continued response at end of study. Isunakinra exposure totaled 1575 daily doses, 81% during combination with nivolumab, t 1/2 5 hours with no accumulation over time. At 50mg of isunakinra, plasma levels where well above 100 ng/mL, a target for complete IL-1 inhibition. Conclusions: Isunakinra is safe and well-tolerated in combination with standard dose nivolumab. Ongoing expansion cohorts and future studies will explore the safety and efficacy of isunakinra in specific tumors and with other immunotherapy combinations. Clinical trial information: NCT04121442 .

Risk and distribution of chronic obstructive pulmonary disease-related hospitalizations among primary care patients.

To determine the extent of chronic obstructive pulmonary disease (COPD) hospitalization in easily identifiable high-risk subgroups within a typical primary care practice. Prospective cohort analysis of administrative claims data. British Columbia. British Columbia residents who were 50 years or older on December 31, 2014, and received a physician diagnosis of COPD between 1996 and 2014. Rate of acute exacerbation of COPD (AECOPD) or pneumonia hospitalization in 2015, broken down by risk identifiers including previous AECOPD admission, 2 or more community respirologist consultations, nursing home residence, or none of these. Of the 242,509 identified COPD patients (12.9% of British Columbia residents ≥50 years), 2.8% were hospitalized for AECOPD in 2015 (0.038 AECOPD hospitalizations per patient-year). The 12.0% with prior AECOPD hospitalization accounted for 57.7% of new AECOPD hospitalizations (0.183 hospitalizations per patient-year); the 7.7% with respirologist involvement accounted for 20.4% (0.102 hospitalizations per patient-year); and the 2.2% in nursing homes accounted for 3.6% (0.061 hospitalizations per patient-year). Those with any of the 3 risk identifiers accounted for only 1.5% more COPD hospitalizations (59.2%) than those with prior AECOPD hospitalization, suggesting prior AECOPD hospitalization is the most important indication of risk. A typical primary care practice held a median of 23 (interquartile range=4 to 65) COPD patients, of whom roughly 20 (86.4%) had none of these risk identifiers. This low-risk majority had only 0.018 AECOPD hospitalizations per patient-year. Most AECOPD hospitalizations occur in patients with previous such admissions. When time and resources are limited, COPD initiatives targeting primary care practices should focus more on the 2 to 3 patients with prior AECOPD hospitalization or more symptomatic disease, and less on the low-risk majority.

Trends in aetiology-based hospitalisation for cirrhosis before and during the COVID-19 pandemic in the United States.

Patients with pre-existing cirrhosis and exposure to coronavirus disease-19 (COVID-19) may portend a poor prognosis. We evaluated the temporal trends in aetiology-based hospitalisations and potential predictors of in-hospital mortality in hospitalisation with cirrhosis before and during the COVID-19 pandemic. Based on the US National Inpatient Sample 2019-2020, we determined quarterly trends in aetiology-based hospitalisations with cirrhosis and decompensated cirrhosis and identified predictors of in-hospital mortality in hospitalisation with cirrhosis. We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID-19 era. Hospitalisation rates for alcohol-related liver disease (ALD)-related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%-5.1%), with a notably higher rate during the COVID-19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)-related cirrhosis decreased steadily with a trend of -1.4% of QPC (95% CI: -2.5% to -0.1%). Quarterly trends in the proportion of ALD- (QPC: 1.7%, 95% CI: 0.9%-2.6%) and nonalcoholic fatty liver disease-related (QPC: 0.7%, 95% CI: 0.1%-1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID-19 era and COVID-19 infection were independent predictors of in-hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV-related cirrhosis, ALD-related cirrhosis was associated with a 40% higher risk of in-hospital mortality. In-hospital mortality in cirrhosis was higher in the COVID-19 era than in the pre-COVID-19 era. ALD is the leading aetiology-specific cause of in-hospital mortality in cirrhosis with an independent detrimental impact of the COVID-19 infection.

The prognostic value of gastroesophageal reflux disorder in interstitial lung disease related hospitalizations

BackgroundGastroesophageal reflux disease (GERD) is a common comorbidity in patients with interstitial lung disease (ILD). We built and validated a model using the national inpatient sample (NIS) database to assess the contributory role of GERD in ILD-related hospitalizations mortality.MethodsIn this retrospective analysis, we extracted ILD-related hospitalizations data between 2007 and 2019 from the NIS database. Univariable logistic regression was used for predictor selection. Data were split into the training and validation cohorts (0.6 and 0.4, respectively). We used decision tree analysis (classification and regression tree, CART) to create a predictive model to explore the role of GERD in ILD-related hospitalizations mortality. Different metrics were used to evaluate our model. A bootstrap-based technique was implemented to balance our training data outcome to improve our model metrics in the validation cohort. We conducted a variance-based sensitivity analysis to evaluate GERD's importance in our model.FindingsThe model had a sensitivity of 73.43%, specificity of 66.15%, precision of 0.27, negative predictive value (NPV) of 93.62%, accuracy of 67.2%, Matthews Correlation Coefficient (MCC) of 0.3, F1 score of 0.4, and area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.76. GERD did not predict survival in our cohort. GERD contribution to the model was ranked the eleventh among twenty-nine variables included in this analysis (importance of 0.003, normalized importance of 5%). GERD was the best predictor in ILD-related hospitalizations who didn’t receive mechanical ventilation.InterpretationsGERD is associated with mild ILD-related hospitalization. Our model-performance measures suggest overall an acceptable discrimination. Our model showed that GERD does not have a prognostic value in ILD-related hospitalization, indicating that GERD per se might not have any impact on mortality in hospitalized ILD patients.