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PURPOSE: A remotely delivered cognitive behavioral coaching (CBC) program was offered as a service benefit for commercial health plan members with low back pain (LBP). This study describes changes in self-rated functional disability in a sample of plan members participating in the program (N=423). METHODS: Independent measures included demographics, length of program enrollment, total CBC sessions, and baseline self-reported patient activation and presenteeism levels. Participants rated their functional disability level due to LBP using the Oswestry Disability Index (ODI). Dependent outcomes quantified change in participant functional disability rating (final ODI score minus baseline ODI score). Nonparametric tests compare differences between groups and within-group ODI score change. Two generalized linear models test for associations between independent variables and the ODI change score. RESULTS: A significant difference between baseline and final ODI scores was observed at the overall program level (p

The challenge of delabeling amoxicillin allergy is an important issue for patients and clinicians, especially when anaphylaxis is reported. A recent study has proposed a clinical decision rule, PEN-FAST, to identify low-risk penicillin allergies.To validate the PEN-FAST clinical decision rule in a population with high risk of suspected immediate amoxicillin allergy and to identify clinical predictive factors of amoxicillin immediate hypersensitivity.We retrospectively analyzed medical records of patients with a suspected immediate amoxicillin allergy who carried out an allergologic evaluation by a specialist in the Allergy Unit of Strasbourg University Hospital from 2015 to 2020.A total of 142 adult patients (88 women [62.0%]; median age, 52 [interquartile range, 40.3-62.0] years) were analyzed. Most of them reported anaphylaxis (68.8%). Internal validation of PEN-FAST score revealed a good discrimination with area under the curve of 0.86 (95% confidence interval, 0.79-0.92). A cutoff of less than 3 points for PEN-FAST was used to classify 29 from 142 patients at low risk of allergy, of whom only 2 (6.9%) received positive results of allergy testing. The negative predictive value for successful delabeling was 0.93 (95% confidence interval, 0.77-0.99). Predictive clinical features for immediate amoxicillin hypersensitivity were time since reaction (P.001), time elapsed between drug intake and first symptom (P.001), severity grade reaction (P.001), and treatment or hospitalization required (P.001).PEN-FAST has been validated to identify low-risk penicillin allergies in our European cohort of patients mainly reporting anaphylaxis. This is the first reported external validation of a penicillin allergy clinical decision rule internationally.

OBJECTIVE To estimate the actual excess costs of care for delivery admissions complicated by severe maternal morbidity (SMM) compared with uncomplicated deliveries. STUDY DESIGN This is a retrospective cohort study of all deliveries between October 2015 and September 2018 at a single tertiary academic center. Pregnant individuals ≥ 20 weeks' gestation who delivered during a hospital admission (i.e., a "delivery admission") were included. The primary exposure was SMM, as defined by Centers for Disease Control and Prevention (CDC) criteria, CDC criteria excluding blood transfusion, or by validated hospital-defined criteria (intensive care unit admission or ≥ 4 units of blood products). Potential SMM events identified via administrative and blood bank data were reviewed to confirm SMM events had occurred. Primary outcome was total actual costs of delivery admission derived from time-based accounting and acquisition costs in the institutional Value Driven Outcomes database. Cost of delivery admissions with SMM events was compared with the cost of uncomplicated delivery using adjusted generalized linear models, with separate models for each of the SMM definitions. Relative cost differences are reported due to data restrictions. RESULTS Of 12,367 eligible individuals, 12,361 had complete cost data. Two hundred and eighty individuals (2.3%) had confirmed SMM events meeting CDC criteria. CDC criteria excluding transfusion alone occurred in 1.0% (n = 121) and hospital-defined SMM in 0.6% (n = 76). In adjusted models, SMM events by CDC criteria were associated with a relative cost increase of 2.45 times (95% confidence interval [CI]: 2.29-2.61) the cost of an uncomplicated delivery. SMM by CDC criteria excluding transfusion alone was associated with a relative increase of 3.26 (95% CI: 2.95-3.60) and hospital-defined SMM with a 4.19-fold (95% CI: 3.64-4.83) increase. Each additional CDC subcategory of SMM diagnoses conferred a relative cost increase of 1.60 (95% CI: 1.43-1.79). CONCLUSION SMM is associated with between 2.5- and 4-fold higher cost than uncomplicated deliveries. KEY POINTS · Severe maternal morbidity as defined by CDC criteria confers a 2.5-fold increase in delivery hospitalization costs.. · Intensive care unit admission or ≥ 4 units of blood products confer a fourfold increase in cost.. · Costs of maternal morbidity may motivate SMM review..

PURPOSE OF REVIEW: To characterize current concepts in capsular repair and hip instability, and examine findings from biomechanical and clinical studies on hip capsular management strategies as they pertain to hip stability, patient outcomes, and hip arthroscopy failure. Further, we discuss the clinical evaluation and treatment of capsular deficiency. RECENT FINDINGS: There remains debate regarding the optimal capsular management strategies in hip arthroscopy, particularly concerning the necessity of routine capsular repair. A variety of capsulotomy techniques exist and may be used to access the hip joint. Additionally, a wide variety of techniques are employed to repair the hip capsule. Biomechanical evidence supports capsular closure restores hip joint stability to that of the intact, native state. Several clinical studies in both primary and revision hip arthroscopy settings have demonstrated improved pain and functional outcomes in patients who underwent capsular repair or capsular reconstruction. Studies have shown capsular repair may be especially important in patients with ligamentous laxity and hip dysplasia, and in competitive athletes. SUMMARY: Post-surgical hip instability secondary to capsular insufficiency is increasingly recognized as a cause of hip arthroscopy failure. Capsular closure restores native biomechanical stability to the hip joint, and several clinical studies report improved pain and functional outcomes following capsular repair or capsular reconstruction in both the primary and revision hip arthroscopy settings. There remains much to learn regarding capsular hip instability as it relates to optimal capsular management surgical technique, intra-operative capsular management decision-making, clinical diagnosis, and related advanced imaging findings.

Background The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. Methods A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1–3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. Results Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0–3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708). Conclusions Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2–related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates., There was a significant positive correlation between SARS-CoV-2 positivity rates in obstetric inpatient units and their surrounding county and state. Healthcare resource utilization related to SARS-CoV-2 testing in obstetric inpatient units may be best informed by surrounding community infection rates.

Bruton’s tyrosine kinase (BTK) is crucial for FceRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35 ) randomized 93 adults with antihistamine-refractory CSU to 50 mg daily, 150 mg daily and 200 mg twice daily of fenebrutinib or placebo for 8 weeks. The primary end point was change from baseline in urticaria activity score over 7 d (UAS7) at week 8. Secondary end points were the change from baseline in UAS7 at week 4 and the proportion of patients well-controlled (UAS7 ≤ 6) at week 8. Fenebrutinib efficacy in patients with type IIb autoimmunity and effects on IgG-anti-FceRI were exploratory end points. Safety was also evaluated. The primary end point was met, with dose-dependent improvements in UAS7 at week 8 occurring at 200 mg twice daily and 150 mg daily, but not at 50 mg daily of fenebrutinib versus placebo. Asymptomatic, reversible grade 2 and 3 liver transaminase elevations occurred in the fenebrutinib 150 mg daily and 200 mg twice daily groups (2 patients each). Fenebrutinib diminished disease activity in patients with antihistamine-refractory CSU, including more patients with refractory type IIb autoimmunity. These results support the potential use of BTK inhibition in antihistamine-refractory CSU. Fenebrutinib, an oral Bruton’s tyrosine kinase inhibitor, reduces disease activity in patients with chronic spontaneous urticaria refractory to antihistamines, suggesting that this treatment type could be an alternative to standard of care anti-IgE therapy.

Background Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). Objective Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if urinary metabolites change during recovery in patients with mild to severe TBI; (2) whether changes in urinary metabolites correlate to injury severity; (3) whether biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery. Methods Urine samples were collected within 7 days and at 6-months post-injury in male participants (n = 8) with mild-severe TBI. Samples were analyzed with NMR-based quantitative spectroscopy for metabolomic profiles and analyzed with multivariate statistical and machine learning-based analyses. Results Lower levels of homovanillate (R = −0.74, p ≤ 0.001), L-methionine (R = −0.78, p, Highlights • NMR-based metabolomics of urine can identify metabolic fingerprints associated with functional recovery following TBI. • Metabolic profiles in urine correlate to injury severity. • Biological pathway analysis reflects mechanisms that mediate neural damage and repair processes throughout recovery. • Metabolomics provides insight into the neuropathophysiology of injury in TBI patients.

BACKGROUND AND AIMS: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.

Introduction: To determine the effects of a novel lifestyle intervention combining lifestyle behavioral education with the complementary–integrative health modality of guided imagery (GI) on dietary and physical activity behaviors in adolescents. The primary aim of this study was to determine the incremental effects of the lifestyle education, stress reduction GI (SRGI), and lifestyle behavior GI (LBGI) components of the intervention on the primary outcome of physical activity lifestyle behaviors (sedentary behavior, light, moderate, and vigorous physical activity), as well as dietary intake behaviors, at the completion of the 12-week intervention. The authors hypothesized that the intervention would improve obesity-related lifestyle behaviors. Materials and Methods: Two hundred and thirty-two adolescent participants (aged 14–17 years, sophomore or junior year of high school) were cluster randomized by school into one of four intervention arms: nonintervention Control (C), Lifestyle education (LS), SRGI, and LBGI. After-school intervention sessions were held two (LS) or three (SRGI, LBGI) times weekly for 12 weeks. Physical activity (accelerometry) and dietary intake (multiple diet recalls) outcomes were assessed pre- and postintervention. Primary analysis: intention-to-treat (ITT) mixed-effects modeling with diagonal covariance matrices; secondary analysis: ad hoc subgroup sensitivity analysis using only those participants adherent to protocol. Results: ITT analysis showed that the Healthy Eating Index (HEI) increased in the LS group compared with C (p = 0.02), but there was no additional effect of GI. Among adherent participants, sedentary behavior was decreased stepwise relative to C in SRGI (d = −0.73, p = 0.004) > LBGI (d = −0.59, p = 0.04) > LS (d = −0.41, p = 0.07), and moderate + vigorous physical activity was increased in SRGI (d = 0.58, p = 0.001). Among adherent participants, the HEI was increased in LS and SRGI, and glycemic index reduced in LBGI. Conclusions: While ITT analysis was negative, among adherent participants, the Imagine HEALTH lifestyle intervention improved eating habits, reduced sedentary activity, and increased physical activity, suggesting that GI may amplify the role of lifestyle education alone for some key outcomes. Clinical Trials.gov ID: NCT02088294

The evaluation by the emergency doctor of the patient presenting with a psychiatric symptom before being taken care of by the psychiatric team is described by the term medical clearance. There is little work on the performance of complementary examinations on these patients. A retrospective multicentre study conducted at the Metz-Thionville regional hospital (57) shows that at least one complementary examination was carried out in 61% of hospitalised patients, compared with 28% of non-hospitalised patients. For 2.4% of patients, the final diagnosis was organic.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Awards (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University of Paris. P.B. was supported by the FRM (EA20170638020). P.B., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the NIAID and NIDCR, NIH (grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (reference ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (AJF202019), Dubai, UAE, and a COVID-19 research grant (CoV19-0307) from the University of Sharjah, UAE. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a UNSW Sydney COVID Rapid Response Initiative Grant. L.I. reported funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). L.I. and G. L. Marseglia reported funding from Regione Lombardia, Italy (project Risposta immune in pazienti con COVID-19 e co-morbidità). This research was partially supported by the Instituto de Salud Carlos III (COV20/0968). J.R.H. reported funding from Biomedical Advanced Research and Development Authority HHSO10201600031C. S.O. reports funding Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (grant number JP20fk0108531). G.G. was supported by ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The Three-City (3C) Study was conducted under a partnership agreement among the INSERM, the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under contract no. 75N91019D00024, task order no. 75N91021F00001. J.W. is supported by an FWO Fundamental Clinical Mandate (1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF). C.R.-G. and colleagues of the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017 and OA20/024), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). C.M.B. is supported by a MSFHR Health Professional-Investigator Award. P.Q.H. and L.H. were funded by the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX (806-2018) and Colciencias contract 713-2016 (code 111574455633)]. A.K. was in part supported by grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies; by the KU Leuven C1 grant C16/18/007; by a VIB-GC PID grant; by the FWO frants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). M.Vi received funding from the São Paulo Research Foundation (FAPESP) (grant number 2020/09702-1) and JBS SA (grant number 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation

Objectives Venlafaxine, a specific inhibitor of both noradrenaline and serotonin, is commonly used in human medicine to treat depression, anxiety and social phobia. Its formulation in small granules renders it interesting to test on cats, which are usually reluctant to take medication. Venlafaxine was administered at 1 mg/kg for 60 days, using a double-blind, placebo-controlled protocol, to cats aged ⩾6 months exhibiting aggressiveness, fear or house-soiling. Methods After one cat’s withdrawal, 21 cats were included in the study: 11 in the venlafaxine group and 10 in the placebo group. Three consultations were conducted, on day 0, day 30 and day 60. Each visit consisted of (1) veterinarian- and owner-based scoring of the cat’s behavioural improvement; (2) scoring of the cat’s compliance with removal from its carrier and compliance with manipulation; and (3) owner scoring of the ease of administration and recording of the potential adverse effects of the treatment. Results Improvement was significantly higher in the venlafaxine group; as early as day 30, according to the veterinarian scoring, and at day 60, according to both the veterinarian and owner scoring. In contrast, neither the removal nor the manipulation scores were significantly different between the two treatment groups. Venlafaxine seemed to improve all three studied signs, as early as day 30 for fear and aggressiveness, and at day 60 for house-soiling. The adverse effects of venlafaxine were limited to drowsiness in one cat. All cats tolerated the treatment well during the 60-day period. Conclusions and relevance These results suggest that venlafaxine is efficient in treating several behavioural problems and is easy to administer. More studies should be conducted to explore its effects at different dosages on specific diagnoses.

Objectives Multicentre international trials relying on diagnoses derived from biochemical results may overlook the importance of assay standardisation from the participating laboratories. Here we describe a study protocol aimed at harmonising results from total bile acid determinations within the context of an international randomised controlled Trial of two treatments, URsodeoxycholic acid and RIFampicin, for women with severe early onset Intrahepatic Cholestasis of pregnancy (TURRIFIC), referred to as the Bile Acid Comparison and Harmonisation (BACH) study, with the aims of reducing inter-laboratory heterogeneity in total bile acid assays. Methods We have simulated laboratory data to determine the feasibility of total bile acid recalibration using a reference set of patient samples with a consensus value approach and subsequently used regression-based techniques to transform the data. Results From these simulations, we have demonstrated that mathematical recalibration of total bile acid results is plausible, with a high probability of successfully harmonising results across participating laboratories. Conclusions Standardisation of bile acid results facilitates the commutability of laboratory results and collation for statistical analysis. It may provide the momentum for broader application of the described techniques in the setting of large-scale multinational clinical trials dependent on results from non-standardised assays.

Care for pregnant patients with substance use disorder must be provided in a nonjudgmental manner with recognition of addiction as a chronic medical illness in order to establish a therapeutic relationship and improve outcomes. All pregnant patients should be screened for substance use during prenatal care. Screening can be accomplished through several validated screening tools. Patients who screen positive need to be evaluated and referred for treatment as appropriate. This article reviews specific adverse perinatal outcomes associated with the use of a variety of substances and provides guidance on exposure with continued breastfeeding.

Objective Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. Study Design A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as “suggestive” (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. Results Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p Conclusion Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. Key Points

Objective Evaluate how emotional intelligence (EI) has been measured among surgeons and to investigate interventions implemented for improving EI. Summary background EI has relevant applications in surgery given its alignment with non-technical skills. In recent years, EI has been measured in a surgical context to evaluate its relationship with measures such as surgeon burnout and the surgeon-patient relationship. Methods A systematic review was conducted by searching MEDLINE, EMBASE, CINAHL, and PSYCINFO databases using PRISMA guidelines. MeSH terms and keywords included "emotional intelligence," "surgery," and "surgeon." Eligible studies included an EI assessment of surgeons, surgical residents, and/or medical students within a surgical context. Results The initial search yielded 4,627 articles. After duplicate removal, 4,435 articles were screened by title and abstract and 49 articles proceeded to a full-text read. Three additional articles were found via hand search. A total of 37 articles were included. Studies varied in surgical specialties, settings, and outcome measurements. Most occurred in general surgery, residency programs, and utilized self-report surveys to estimate EI. Notably, EI improved in all studies utilizing an intervention. Conclusions The literature entailing the intersection between EI and surgery is diverse but still limited. Generally, EI has been demonstrated to be beneficial in terms of overall well-being and job satisfaction while also protecting against burnout. EI skills may provide a promising modifiable target to achieve desirable outcomes for both the surgeon and the patient. Future studies may emphasize the relevance of EI in the context of surgical teamwork.

AIMS To explore the safety, tolerability, pharmacokinetics and pharmacodynamics (PD) of GSK2646264 using skin challenge models. METHODS Healthy volunteers (HV) with a positive allergen skin prick test received GSK2646264 (0.5% or 1% ww) and placebo creams on up to 10% body surface area (BSA). Cold (ColdU) or chronic spontaneous (CSU) urticaria patients received 1% GSK2646264 or placebo on up to 10% BSA. PD assessments included weal characteristics after skin allergen challenge, critical temperature threshold (CTT) in ColdU patients and defined area urticaria activity score in CSU patients. RESULTS Thirty-four patients were randomised (17 HV, 12 ColdU, 5 CSU). Topical application of GSK2646264 and placebo was well tolerated. Systemic pharmacokinetics (AUC [0-24] h*ng/mL) was similar between HVs (Geomean 97.9 [%CV 37]) and ColdU patients (Geomean 68.2 [%CV 14; 3.5% BSA] or 167 [%CV 120; 10% BSA]). Whilst in HVs a similar reduction in skin allergen challenge weal area was observed following 3 applications of GSK2646264 and placebo, a trend towards a greater reduction was seen in ColdU with GSK2646264 compared to placebo. A clinically meaningful reduction in CTT, in ColdU patients treated with GSK2646264, was observed in 4 of 9 patients, who demonstrated either a complete inhibition of ColdU to ≤4°C (n = 2) or partial response (reduction by >4°C, n = 2). Due to the small number of CSU patients recruited, no meaningful conclusions could be drawn from the defined area urticaria activity score PD endpoint. CONCLUSION This Phase 1/1b study confirms that GSK2646264 cream applied topically penetrates the skin and some reduction in CTT was observed. (NCT02424799).

Background and purpose While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS. Methods One hundred and forty-two CIS participants were categorized into DAWM and non-DAWM groups at baseline and followed for up to 24 months or until MS diagnosis. The primary outcome was conversion to MS (2005 McDonald criteria) within 6 months. Results DAWM was present in 27.5% of participants, and was positively associated with brainstem symptom onset, receiving corticosteroids, dissemination in space, and T2 lesion volume. DAWM was associated with an increased risk of conversion to MS over 6 months after adjustment for age and disability (hazard ratio [HR] = 2.24, p = 0.004). This association remained at a trend-level after adjustment for high-risk imaging features (HR = 1.68, p = 0.10). Conclusions DAWM is present in a similar proportion of patients with CIS and clinically definite MS, and it is associated with increased risk of conversion to MS over 6 months.

Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan–Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions (“low-risk”) were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.

While the influence of surgical flow disruptions (SFDs) on surgical performance has been observed in live cardiovascular surgery and their influence on cognitive workload has been evaluated in high-fidelity simulations, the relationship between SFDs and cognitive workload of surgical providers in the live cardiac surgery operating room has yet to be explored. Recent evidence suggests that preventable surgical errors often have a cognitive basis, warranting investigation into the association between SFDs and workload. This study aimed to characterize SFDs according to auditory and cognitive domains and further to compare the frequency and nature of SFDs within periods of high team cognitive workload and low team cognitive workload. Overall, the presence of cognitive distractions was associated more with high team cognitive workload states, while the frequency of auditory distractions was significantly higher during periods of low team cognitive workload states. Future work should consider the types, frequency, and sources of SFDs as well as their impact on surgical procedures and outcomes in order to devise appropriate methods to mitigate or manage potential disruptions to surgical workflow.

Background Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. Methods This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. Results Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. Interpretation There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. Trial registration ClinicalTrials.gov, no. NCT04329611.

Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p, Highlights • 1H nuclear magnetic resonance (NMR) spectroscopy identified robust urine biomarkers in patients with spinal cord injury (SCI). • Quantitative NMR-based metabolomics identified metabolic profiles linked to the extent of recovery among SCI patients. • Changes in urine metabolites correlated with patient functional outcomes. • Metabolomic biomarker analysis addresses the need for reliable prognostic biomarkers of spinal cord injury.

Background: Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy. Objective: To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods: This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post-treatment for 48 weeks. Results: Overall, ligelizumab was well-tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment-emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion: The long-term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re-treatment efficacy was shown. Trial registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.

Background. In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19, accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially as the majority of these pathogens are specifically treatable. Case Presentation. We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms, after completing a half-marathon one week before admission. As infection with SARS-CoV-2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed, and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. Conclusion. Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance to adhere to established treatment guidelines, scrutinize treatment modalities, and not to forget other potential causes of severe pneumonia or ARDS.

Purpose The on-body injector (OBI) automatically delivers pegfilgrastim the day after chemotherapy (CTx), thus eliminating the need of return visits to the medical office for guideline-compliant pegfilgrastim administration. The CONVENIENCE study aimed to evaluate patient, nurse, and physician preferences as well as health economics for pegfilgrastim administration either with OBI or manually using a pre-filled syringe (PS). Methods Patients with early breast cancer, receiving two or three weekly anthracycline/cyclophosphamide or three weekly taxane-based CTx, and patients with Non-Hodgkin lymphoma (NHL) receiving first-line R-CHOP-14 or -21 were randomized 1:1 to receive both pegfilgrastim application forms for four consecutive CTx cycles in an alternating sequence starting either with OBI or PS. Primary endpoint was patient preference, assessed by questionnaires. Results A total of 308 patients were evaluable in the per-protocol analysis. Patients slightly preferred OBI over PS (OBI, n = 133, 43.2%; vs. PS, n = 111, 36.0%; p-value = 0.159), while study nurses slightly preferred PS (n = 19, 46.3%) over OBI (n = 18, 43.9%) and physicians clearly preferred PS (n = 24, 58.8%) over OBI (n = 15, 36.6%). Among patients with preference for OBI, saving of time was their major reason for preference (53.4%). Pegfilgrastim was administered 24–72 h after each CTx cycle in 97.6% of OBI and 63.1% of PS applications. Conclusion The OBI was slightly preferred by patients and saving time was the major reason for their preference. PS was physicians’ most preferable choice and slightly preferred by nurses. Using OBI, pegfilgrastim was almost always administered within the time period recommended by current guidelines, while it was often not applied as specified using PS. Trial registration No: ClinicalTrials.gov No. NCT03619993. Registered on June 25, 2018

Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival.Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996-2018), rising from 109 to 278/year. Relating these numbers to all pediatric CNS tumors registered at the German Childhood Cancer Registry, the LGG fraction and annual crude incidence rates increased (32% to 51%; 0.94 to 2.12/100,000 children/adolescents15 years). The consecutive LGG studies recruited 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004), and 1836 (LGG-registry) patients with similar distribution of tumor-sites, histology, and dissemination. 5-year overall survival was 96%-98% at median observation time of 8.1 years. Acknowledging unequal follow-up periods, 589/899 (66%), 1089/1582 (69%), and 1387/1836 (76%) patients remained under observation, while 1252/4317 received adjuvant treatment with decreasing frequency of front-line radiotherapy from 16% to 5%.Pediatric LGG incidence rates in Germany are now comparable to other European countries. The rise in patient numbers followed implementation of standard-of-care treatment protocols, but did not result in relevant changes of epidemiologic or clinical parameters or survival. Shifts in patient distribution between treatment arms reflect growing acceptance of the LGG therapy algorithm.In den vergangenen 20 Jahren hat sich die jährliche Patientenrekrutierung in den aufeinanderfolgenden multizentrischen Studien für pädiatrische niedrig-gradige Gliome (LGG) in Deutschland verdoppelt. Wir haben untersucht, ob sich mit dieser Zunahme auch epidemiologische Merkmale oder das Überleben verändert haben.Zwischen 1996 und 2018 meldeten die teilnehmenden Zentren insgesamt 4634 Patienten mit der radiologischen/histologischen Diagnose eines LGG. Die Zahl stieg von anfangs 109 bis 278 Patienten pro Jahr. Gleichzeitig stieg der Anteil der LGGs an allen am Deutschen Kinderkrebsregister gemeldeten pädiatrischen Hirntumoren von 32 auf 51%, die jährliche Inzidenz erhöhte sich von 0,94 auf 2,12/100 000 Kinder/Jugendliche15 Jahre. Die aufeinanderfolgenden LGG-Studien rekrutierten 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004) und 1836 (LGG-Register) Patienten mit vergleichbarer Verteilung von Tumorsitz, Histologie und Disseminierung. Das 5-Jahres-Überleben lag bei einer medianen Nachbeobachtungszeit von 8,1 Jahren zwischen 96 und 98%. Unter Berücksichtigung der ungleich langen Follow-up-Zeit wurden 589/899 (65,5%), 1089/1582 (68,8%) und 1387/1836 (75,5%) Patienten bislang beobachtet, während 1252/4317 eine adjuvante Therapie erhielten. Dabei sank der Anteil der primären Radiotherapie von 16 auf 5%.Die Rekrutierung pädiatrischer LGG ist dank Implementierung verbindlicher Therapiestandards in Deutschland gestiegen, ohne zu relevanten Veränderungen epidemiologischer oder klinischer Merkmale oder des Überlebens zu führen. Die Inzidenz ist mit anderen europäischen Ländern vergleichbar. Verschiebungen der Patientenzuteilung zwischen den Therapiearmen spiegeln die zunehmende Akzeptanz des LGG-Therapie-Algorithmus wider.Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival.Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996–2018), rising from 109 to 278/year. Relating these numbers to all pediatric CNS tumors registered at the German Childhood Cancer Registry, the LGG fraction and annual crude incidence rates increased (32% to 51%; 0.94 to 2.12/100,000 children/adolescents15 years). The consecutive LGG studies recruited 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004), and 1836 (LGG-registry) patients with similar distribution of tumor-sites, histology, and dissemination. 5-year overall survival was 96%-98% at median observation time of 8.1 years. Acknowledging unequal follow-up periods, 589/899 (66%), 1089/1582 (69%), and 1387/1836 (76%) patients remained under observation, while 1252/4317 received adjuvant treatment with decreasing frequency of front-line radiotherapy from 16% to 5%.Pediatric LGG incidence rates in Germany are now comparable to other European countries. The rise in patient numbers followed implementation of standard-of-care treatment protocols, but did not result in relevant changes of epidemiologic or clinical parameters or survival. Shifts in patient distribution between treatment arms reflect growing acceptance of the LGG therapy algorithm.In den vergangenen 20 Jahren hat sich die jährliche Patientenrekrutierung in den aufeinanderfolgenden multizentrischen Studien für pädiatrische niedrig-gradige Gliome (LGG) in Deutschland verdoppelt. Wir haben untersucht, ob sich mit dieser Zunahme auch epidemiologische Merkmale oder das Überleben verändert haben.Zwischen 1996 und 2018 meldeten die teilnehmenden Zentren insgesamt 4634 Patienten mit der radiologischen/histologischen Diagnose eines LGG. Die Zahl stieg von anfangs 109 bis 278 Patienten pro Jahr. Gleichzeitig stieg der Anteil der LGGs an allen am Deutschen Kinderkrebsregister gemeldeten pädiatrischen Hirntumoren von 32 auf 51%, die jährliche Inzidenz erhöhte sich von 0,94 auf 2,12/100 000 Kinder/Jugendliche15 Jahre. Die aufeinanderfolgenden LGG-Studien rekrutierten 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004) und 1836 (LGG-Register) Patienten mit vergleichbarer Verteilung von Tumorsitz, Histologie und Disseminierung. Das 5-Jahres-Überleben lag bei einer medianen Nachbeobachtungszeit von 8,1 Jahren zwischen 96 und 98%. Unter Berücksichtigung der ungleich langen Follow-up-Zeit wurden 589/899 (65,5%), 1089/1582 (68,8%) und 1387/1836 (75,5%) Patienten bislang beobachtet, während 1252/4317 eine adjuvante Therapie erhielten. Dabei sank der Anteil der primären Radiotherapie von 16 auf 5%.Die Rekrutierung pädiatrischer LGG ist dank Implementierung verbindlicher Therapiestandards in Deutschland gestiegen, ohne zu relevanten Veränderungen epidemiologischer oder klinischer Merkmale oder des Überlebens zu führen. Die Inzidenz ist mit anderen europäischen Ländern vergleichbar. Verschiebungen der Patientenzuteilung zwischen den Therapiearmen spiegeln die zunehmende Akzeptanz des LGG-Therapie-Algorithmus wider.

The Society for Maternal-Fetal Medicine Publications Committee first adopted the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in 2013. This document provides an update on the Society for Maternal-Fetal Medicine Publications Committee process for creating evidence-based practice recommendations and describes the GRADE process as it is currently implemented in the SMFM Consult and Guidelines series.

Introduction SARS-CoV-2 is a novel coronavirus that was first isolated in Wuhan, China, and resulted in a rapidly spreading pandemic worldwide. Currently there is only limited evidence on the effect of COVID-19 on pregnant women. Case Here we present one of the first serious COVID-19 cases in pregnancy at term with subsequent delivery. Postpartum the mother required antibiotic and symptomatic treatment. She experienced acute worsening of symptoms and developed acute respiratory failure requiring endotracheal intubation and subsequently extracorporeal membrane oxygenation. Conclusion COVID-19 affects all medical disciplines, requiring interdisciplinary approaches and development of patient care regimes. Obstetricians should be aware and be prepared for the special needs of pregnant women with potential prenatal and postnatal issues. Ideally pregnant COVID-19 patients should be cared for at a tertiary perinatal center with experienced perinatologists and neonatologists.

Background Pruritus often accompanies chronic skin diseases, exerting considerable burden on many areas of patient functioning; this burden and the features of pruritus remain insufficiently characterized. Objective To investigate characteristics, including localization patterns, and burden of pruritus in patients with chronic dermatoses. Methods We recruited 800 patients with active chronic skin diseases. We assessed pruritus intensity, localization, and further characteristics. We used validated questionnaires to assess quality of life, work productivity and activity impairment, anxiety, depression, and sleep quality. Results Nine out of every 10 patients had experienced pruritus throughout their disease and 73% in the last 7 days. Pruritus often affected the entire body and was not restricted to skin lesions. Patients with moderate to severe pruritus reported significantly more impairment to their sleep quality and work productivity, and they were more depressed and anxious than control individuals and patients with mild or no pruritus. Suicidal ideations were highly prevalent in patients with chronic pruritus (18.5%) and atopic dermatitis (11.8%). Conclusions Pruritus prevalence and intensity are very high across all dermatoses studied; intensity is linked to impairment in many areas of daily functioning. Effective treatment strategies are urgently required to treat pruritus and the underlying skin disease.

Hintergrund: Die chronische Urtikaria (CU) ist eine häufige und für viele Patienten stark belastende Erkrankung. Die aktuelle Urtikaria-Leitlinie beschreibt die evidenzbasierte Diagnostik und Therapie der CU. Darüber hinaus treten jedoch oftmals Fragen im praktischen Alltag auf, die durch die Leitlinie nicht beantwortet werden. Methoden: Im Mai 2020 fand ein digitales Treffen deutscher Urtikaria-Experten statt, in dem praxisrelevante Aspekte der Behandlung der CU erörtert und unterstützende Hilfestellungen für den klinischen Behandlungsalltag formuliert wurden. Die resultierenden Hinweise dieses Dokumentes fokussieren auf praktische Fragen und der hierzu verfügbaren Literatur und Erfahrungen der Teilnehmer. Ergebnisse: Die Diagnose einer CU kann in kurzer Zeit mittels gründlicher Anamnese, einer körperlichen Untersuchung und einer laborchemischen Basisdiagnostik gestellt werden. Hierzu werden in dieser Arbeit praktische Empfehlungen für den Praxisalltag gegeben. Eine erweiterte Diagnostik ist nur in wenigen Fällen indiziert und sollte grundsätzlich parallel zu einer effektiven Therapie erfolgen. Generell gilt, dass die CU immer auf gleiche Weise zu therapieren ist, unabhängig davon, ob Quaddeln, Angioödeme oder beides auftreten. Eine symptomatische Therapie sollte nach dem von den Leitlinien empfohlenen Stufenschema erfolgen. Die vorliegende Publikation gibt hierzu praktische Hinweise für Fragen in der Praxis, wie zum Beispiel dem Vorgehen in der aktuellen COVID-19-Pandemie, dem kardialen Risiko unter höher dosierten H 1-Antihistaminika, der Selbstapplikation von Omalizumab sowie dem Impfen unter Omalizumab-Therapie. Zusätzlich zu den Behandlungsempfehlungen werden Themen wie die Dokumentation in der Praxis und Familienplanung bei Urtikaria besprochen. Diskussion: Diese unterstützenden Behandlungsempfehlungen dienen als Ergänzung zu den aktuellen Leitlinien der CU und geben beim Umgang mit Patienten mit CU eine Hilfestellung für den Praxisalltag. Ziel ist es, dass Patienten, die unter einer CU leiden, mithilfe einer optimalen Therapie eine vollständige Beschwerdefreiheit erreichen. Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1007/s15007-021-4772-2 für autorisierte Leser zusätzliche Dateien abrufbar.

Currarino syndrome (CS) is an autosomal dominant syndrome caused by mutations in MNX1 and characterized by anorectal abnormalities, partial sacral agenesis, and presacral masses. The presacral masses are typically benign; however, malignant degeneration can occur, and presacral neuroendocrine tumors (NETs) have been reported in six cases. We report three individuals from two families affected by CS in which multiple individuals developed presacral NETs. The first family, 491, had six members with features of CS, including two siblings who presented with presacral, Grade 2 NETs, one of which had metastasized to bone and lymph nodes. A germline c.874C>T (p.Arg292Trp) mutation was found in a highly conserved region of MNX1 in three affected members who underwent sequencing. A second somatic variant/deletion in MNX1 was not detected in either patient's tumor. In the second family, 342, the proband presented with an incidentally discovered presacral NET. The proband's father had previously undergone resection of a presacral NET, and so genetic testing was performed, which did not reveal an MNX1 mutation or copy number variants. The lack of a second, somatic mutation in the tumors from family 491 argues against MNX1 acting as a tumor suppressor, and the absence of a germline MNX1 mutation in family 342 suggests that other genetic and anatomic factors contribute to the development of presacral NETs. These cases highlight the variable presentation of CS, and the potential for malignancy in these patients.

Background Chronic urticaria (CU) is a common disease which represents a considerable burden for many patients. The current urticaria guideline describes the evidence-based diagnosis and treatment of CU. In addition, however, questions often arise in everyday practice that are not addressed by the guideline. Methods In May 2020, a digital meeting with German urticaria experts was held, in which practical aspects of CU treatment were discussed and supporting aids for everyday clinical treatment formulated. The resulting advice in this document focus on practical questions and the available literature and experiences of the participants. Results The diagnosis of CU can be made in a short time by means of a thorough anamnesis, a physical examination, and a basic laboratory chemical diagnosis. For this purpose, practical recommendations for everyday practice are given in this paper. An extended diagnosis is only indicated in a few cases and should always be carried out in parallel with an effective therapy. In general, CU should always be treated in the same way, regardless of whether wheals, angioedema or both occur. Symptomatic therapy should be carried out according to the treatment steps recommended by the guidelines. This publication provides practical advice on issues in everyday practice, such as the procedure in the current coronavirus disease 2019 (COVID-19) pandemic, the cardiac risk under higher dosed H1 antihistamines, the self-administration of omalizumab as well as vaccination under omalizumab therapy. In addition to treatment recommendations, topics such as documentation in the practice and family planning with urticaria will be discussed. Discussion These supporting treatment recommendations serve as an addendum to the current CU guideline and provide support in dealing with CU patients in everyday practice. The aim is to ensure that patients suffering from CU achieve complete freedom of symptoms with the help of an optimal therapy.

Pregnant patients with severe or critical coronavirus disease 2019 (COVID-19), but not those with mild or moderate COVID-19, were at increased risk for perinatal complications compared with asymptomatic patients., OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race–ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2–11%) incidence of venous thromboembolism among those with severe–critical illness compared with 0.2% in mild–moderate and 0% in asymptomatic (P

The association of pain and suffering seems intuitive, but evidence substantiating this association is lacking. In studies of cancer patients, fatigue, rather than pain, is the most prevalent and debilitating symptom. This study aimed to compare the correlation of pain and fatigue to suffering, and identify other potential sources of suffering in cancer patients treated in a palliative care unit. One hundred fifty cancer patients were surveyed. Fifteen variables were measured on a 0- to 10-point scale: suffering, pain, level of acceptable pain, effect of pain on quality of life, fatigue, level of acceptable fatigue, effect of fatigue on quality of life, and specific types of suffering. Univariable associations with suffering were made with Pearson correlation (continuous variables) or t test (binary predictors). Multivariable associations with suffering were assessed with linear regression analysis and bootstrapping. In multivariable analysis, highest pain (parameter estimate 0.38) had a greater impact on suffering than highest fatigue (parameter estimate 0.21). When other variables were assessed, 38% of the variability in suffering was accounted for by pain “now”, fatigue in the past 24 hours, and age. The most important predictors of greater suffering in hospitalized cancer patients are pain, younger age, and fatigue. Despite their significant effect on suffering, other underlying contributors to suffering have yet to be identified. Designing interventions to reduce fatigue, in addition to pain management, may help in alleviating overall suffering.

The median number of medications taken by adults aged 65 and older is four, but may be higher in older adults with cancer. A high number of prescribed medications increases risk for adverse drug reactions (ADRs), drug-drug interactions, drug-disease interactions, and overall healthcare utilization, emphasizing the need for frequent review of medications. There are many tools available to help the health care team assess medication appropriateness; however, none of the currently available tools have been validated in the geriatric oncology population. Older adults with cancer are at increased risk for ADRs and potentially inappropriate medications (PIMs) given the common need for multiple medications to manage cancer and cancer-related symptoms. Frequently used PIM identification tools, such as the American Geriatrics Society's (AGS) Beers criteria, often identify medications as "potentially inappropriate", although many of these medications are considered necessary to provide adequate supportive care in older patients with cancer. There are currently no specific guidelines to help direct application of available tools. This review summarizes literature available on the use of PIM identification tools in geriatric oncology and highlights a theoretical case and proposed medication management strategy, which combines the use of objective review with Beer's criteria and clinical judgement with the Medication Appropriateness Index (MAI). This two-pronged approach can serve to identify PIMs while recognizing factors unique to the geriatric oncology population.

BACKGROUND AND AIMS: Increasing demand for inpatient endoscopic services results in performing more non-emergent endoscopic cases after-hours, which poses risks to patient safety and negatively impacts patient and provider satisfaction. This study sought to quantify the existing state using quality improvement (QI) methodology, design targeted interventions, and determine their effectiveness. METHODS: We conducted an existing state evaluation through a process map, time-series study, and caseload analysis from 7/2017–12/2018. Using end-of-workday (EOW) as a proxy for patient/provider dissatisfaction and risk for patient safety events, we performed a prospective evaluation of a staged interdisciplinary multimodal intervention aimed to decrease the proportion of days with EOW after 7PM, decrease the proportion of cases begun after 5PM, and decrease EOW variability. The post-intervention period was 6/2019–2/2020. RESULTS: Based on existing state analyses, we implemented a series of targeted interventions: (1) provider workflow tips, (2) expedited transport for select patients, (3) pathway to reschedule appropriate cases to outpatient endoscopy, and (4) increased staffing for high caseload days through resource pooling. The proportion of days with EOW after 7PM decreased from 42.4% to 29.3% (caseload-adjusted odds ratio of 0.39, p< 0.001). Despite increased caseload, cases begun after 5PM decreased from 17.5% to 14.2% (OR 0.75, p = 0.009). EOW SD decreased from 2:20 hours to 1:36 hours. CONCLUSIONS: The multimodal intervention reduced days with EOW after 7PM and the proportion of cases begun after 5PM, despite increased caseload. This study shows how applying research methods to implement QI interventions successfully decreases late inpatient endoscopic cases.

In chronic spontaneous urticaria (CSU), itchy wheals, angioedema, or both occur regularly, often daily, and for years. An effective therapy for CSU aims at achieving complete symptom control. The current guideline for the management of CSU patients recommends non-sedative anthistamines in standard or up to 4-fold higher dosages as 1 and 2 line treatment. For most CSU patients this treatment is not sufficient; for them, the anti-IgE antibody omalizumab is the therapy of choice. Although good to very good symptom control can be achieved in most cases, there are many patients with insufficient response. For these patients, but also as an alternative to therapy with omalizumab, numerous other biologicals are currently under development. In this review, we provide an overview of possible future biologic therapies for chronic urticaria.

OBJECTIVE Recent studies indicate that sodium-glucose cotransporter 2 (SGLT-2) inhibition increases endogenous glucose production (EGP), potentially counteracting the glucose-lowering potency, and stimulates lipid oxidation and lipolysis. However, the acute effects of SGLT-2 inhibition on hepatic glycogen, lipid, and energy metabolism have not yet been analyzed. We therefore investigated the impact of a single dose of dapagliflozin (D) or placebo (P) on hepatic glycogenolysis, hepatocellular lipid (HCL) content and mitochondrial activity (kATP). RESEARCH DESIGN AND METHODS Ten healthy volunteers (control [CON]: age 30 ± 3 years, BMI 24 ± 1 kg/m2, HbA1c 5.2 ± 0.1%) and six patients with type 2 diabetes mellitus (T2DM: age 63 ± 4 years, BMI 28 ± 1.5 kg/m2, HbA1c 6.1 ± 0.5%) were investigated on two study days (CON-P vs. CON-D and T2DM-P vs. T2DM-D). 1H/13C/31P MRS was performed before, 90–180 min (MR1), and 300–390 min (MR2) after administration of 10 mg dapagliflozin or placebo. EGP was assessed by tracer dilution techniques. RESULTS Compared with CON-P, EGP was higher in CON-D (10.0 ± 0.3 vs. 12.4 ± 0.5 μmol kg−1 min−1; P < 0.05) and comparable in T2DM-D and T2DM-P (10.1 ± 0.7 vs. 10.4 ± 0.5 μmol kg−1 min−1; P = not significant [n.s.]). A strong correlation of EGP with glucosuria was observed (r = 0.732; P < 0.01). The insulin-to-glucagon ratio was lower after dapagliflozin in CON-D and T2DM-D compared with baseline (P < 0.05). Glycogenolysis did not differ between CON-P and CON-D (−3.28 ± 0.49 vs. −2.53 ± 0.56 μmol kg−1 min−1; P = n.s.) or T2DM-P and T2DM-D (−0.74 ± 0.23 vs. −1.21 ± 0.33 μmol kg−1 min−1; P = n.s.), whereas gluconeogenesis was higher after dapagliflozin in CON-P compared with CON-D (6.7 ± 0.6 vs. 9.9 ± 0.6 μmol kg−1 min−1; P < 0.01) but not in T2DM. No significant changes in HCL and kATP were observed. CONCLUSIONS The rise in EGP after SGLT-2 inhibition is due to increased gluconeogenesis, but not glycogenolysis. Changes in glucagon and the insulin-to-glucagon ratio are not associated with an increased hepatic glycogen breakdown. HCL and kATP are not significantly affected by a single dose of dapagliflozin.

OBJECTIVE To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. METHODS We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. RESULTS Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). CONCLUSIONS Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT00388297.

BACKGROUND AND AIMS: Recent studies show promise for endoscopic submucosal dissection (ESD) in the US, but do not identify the potential impact of ESD among newly diagnosed gastric cancers. We utilize the Veterans Health Administration to identify cancers suitable for ESD, to define the role of ESD in the US. METHODS: Retrospective cohort study using the Veterans Affairs Central Cancer Registry to identify patients with gastric cancer who underwent surgical resection from 1995–2018. TNM stage was used to categorize those who would meet absolute vs expanded indications for ESD. Primary outcome was lymph node status. Secondary analysis was performed with death as outcome. RESULTS: Of 12,584 primary gastric cancers, 4,735 (37.6%) were non-metastatic gastric adenocarcinomas. Median age at diagnosis was 70.3 years, 4,676 (98.8%) male. 2,306 (48.7%) underwent surgical resection, of which 636 (27.6%) were T1 lesions or cancer in situ. Of these, 44 (6.9%) met absolute indications for resection, 99 (15.6%) met established expanded criteria, and 98 (15.4%) may meet expanded criteria. Half of all tumors in each group were proximal in location. Rate of lymph node positivity was: 4.5%; 95% CI:0.5–15.5% in absolute group; 8.1%; 95% CI:3.6–15.3% in expanded group; 13.3%; 95% CI:7.3–21.6 in those potentially meeting expanded criteria. Lymph nodes positivity was associated with death (HR 1.49; 95% CI:1.36–1.62, p

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.

Chronic pruritus of unknown origin (CPUO) is defined by chronic itch lasting for longer than 6 weeks in the absence of skin manifestations or other known causes.1 CPUO poses a challenge to dermatologists, as the condition is refractory to conventional treatments and patients' quality of life is severely impaired.2 We present the case of a woman whose CPUO responded rapidly to baricitinib and did not reappear after discontinuation of the drug after 2 weeks of treatment.

AIM We sought to determine the frequency and patterns of delayed medical care seeking for young children with skull fractures. METHODS We identified accidental skull fractures

Pruritus ani (analer Juckreiz) ist ein in der Praxis haufig auftretendes Symptom, das bei Chronifizierung mit hohem Leidensdruck einhergeht. In der Regel tritt analer Pruritus sekundar als Symptom verschiedener Krankheitsbilder, u. a. aus dem Spektrum dermatologischer, proktologischer, allergologischer oder mikrobieller Erkrankungen, auf. Die Identifikation und spezifische Behandlung der zugrundeliegenden Ursache ist in diesen Fallen essenziell. Lasst sich keine zugrundeliegende Erkrankung eruieren, spricht man von einem idiopathischen (primaren) Pruritus ani. Wie auch bei der Behandlung des Analekzems hangt der mittel- und langfristige Therapieerfolg im Management des Pruritus ani von verschiedenen Elementen der Behandlung ab, die sich grob in kausale, unterstutzende und symptomatische Masnahmen unterteilen lassen. Im vorliegenden Beitrag werden u. a. die Empfehlungen der aktualisierten Leitlinie „Analer Pruritus“ (AWMF-Reg. 013/063) vorgestellt.

The purpose of this study was to examine differences between perceived harm of cigarette and electronic cigarette (e-cigarette) use while pregnant and differences between healthcare providers’ communication about these products during pregnancy. A convenience sample of gestational women (n = 218; ages 18–45) living in the US completed an online survey between May and December 2017. Participants reported perceived likelihood of adverse health outcomes (e.g., low birth weight, sudden infant death syndrome) among infants/children born to mothers who used cigarettes/e-cigarettes. T-tests and two-way ANOVAs examined differences between risk perceptions of using cigarettes/e-cigarettes while pregnant based on pregnancy status (previously pregnant, currently pregnant, future pregnant). Chi-square analyses examined differences between healthcare provider communication about cigarette/e-cigarette use during pregnancy. Overall, participants believed adverse health outcomes were significantly more likely to be caused by maternal use of cigarettes than e-cigarettes. Participants who planned to be pregnant reported higher endorsement that smoking combustible cigarettes would cause a miscarriage (p

Metastatic patterns have been linked with prognosis in colorectal cancer. We aim to determine the distribution of metastases, their dynamics during disease and their prognostic impact for specific clinical treatment scenarios (resection of metastasis and/or systemic treatment, best supportive care).978 patients diagnosed with metastatic colorectal adenocarcinoma treated at three oncological centers from 2006 to 2018 were included. Overall survival was assessed depending on tumor load, distribution of metastases and treatment of the patients.Most patients had single site metastasis (The number of organs involved in metastasis at diagnosis but not the total cumulative number of involved organs is of prognostic relevance in colorectal adenocarcinoma. This prognostic relevant initial metastasis distribution remains unchanged in the majority of patients during the disease. However, the prognostic impact of the metastatic pattern is potentially altered by treatment modality.

Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as an important method for obtaining a preoperative tissue diagnosis for suspected cholangiocarcinoma. However, doubts remain about test sensitivity. This study assessed the value and limitations of EUS-FNA in clinical practice. Patients and methods Patients undergoing EUS-FNA for biliary strictures/masses at a UK tertiary referral center from 2005 to 2014 were prospectively enrolled. Data on EUS-FNA findings, histology, and endoscopy and patient outcomes were collected to evaluate test performance and identify factors predictive of an inaccurate diagnostic result. Results Ninety-seven patients underwent a total of 112 EUS-FNA procedures. Overall test sensitivity for an initial EUS-FNA for suspected cholangiocarcinoma was 75 % (95 % CI 64 %–84 %), with specificity 100 % (95 % CI 85 %–100 %) and negative predictive value 0.62 (95 % CI 0.47–0.75). Hilar lesions, the presence of a biliary stent, and a diagnosis of PSC were significantly independently associated with an inaccurate result. For the most difficult cases, repeat sampling and use of the Papanicolaou cytopathology grading scale led to an increase in test sensitivity from 17 % to 100 % (P = 0.015) with no loss of specificity. Conclusions EUS-FNA was found to be a useful method for obtaining a preoperative tissue diagnosis for patients with suspected cholangiocarcinoma. This study identified markers that can reduce test accuracy and measures that can improve test performance of EUS-FNA.

Purpose The TELEACE study showed reductions in tumor size in patients with neuroendocrine tumors, receiving telotristat ethyl in US clinical practice. Here, we report progression-free survival, time to tumor progression, changes in carcinoid syndrome symptoms, and indictors of overall health. Patients and methods This was a retrospective, single arm, pre-post medical chart review of patients with locally advanced or metastatic neuroendocrine tumors and documented carcinoid syndrome receiving telotristat ethyl for at least 6 months. Patients with poorly differentiated tumors, mixed tumor types or conflicting clinical trial enrollment were excluded. Descriptive statistics, Kaplan-Meier and chi-square tests were used to evaluate PFS, tumor progression, changes in symptoms, body weight and ECOG performance status before and after telotristat ethyl initiation. Subgroup analyses were conducted in patients with the same pre- and post-telotristat ethyl background treatment. Results Anonymized data for 200 patients were provided by 114 physicians; patients received telotristat ethyl for a median of 9 months. Median time to tumor progression was 39.8 months (IQR, 18.7-39.8); most had no tumor progression at 6 (92%) and 12 months (87%). Median progression-free survival was 23.7 months (17.8-39.8); most had progression-free survival at 6 (90%) and 12 months (80%). Results were consistent in the subgroup of 65 patients with the same pre/post background treatment. Nearly all patients had improved carcinoid syndrome symptoms, stable or improved weight and ECOG performance status. Conclusion Patients showed improvements in clinical outcomes and indicators of overall health following treatment with telotristat ethyl in this exploratory pilot study, consistent with previously observed reductions in tumor size.