The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Understanding Determinants of Patient Preferences Between Stool Tests and Colonoscopy for the Assessment of Disease Activity in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Evidence is now available in support of using fecal biomarkers to monitor disease activity in inflammatory bowel disease (IBD). Patient adherence is often cited as a barrier to implementation. We assessed patient determinants for using stool tests to monitor disease activity. METHODS: Prospective interview of IBD patients using an analytic hierarchy matrix survey built to understand preferences for choosing between stool testing or colonoscopy for monitoring disease activity, after considering different test criteria (accuracy, preparation, pain, complications). Theoretical thresholds of misclassification were posed to patients to see how they might consider shifting from colonoscopy to stool testing. RESULTS: A total of 100 patients (n = 51 CD, n = 46 male) were interviewed with median age and disease duration of 44 years (IQR 27-63) and 9 years (IQR 5-21), respectively. Stool-based testing was preferred over colonoscopy by 60% initially; however, a majority of participants changed their choice to colonoscopy after learning more about the diagnostic performance of currently available stool tests for disease monitoring (p < 0.001). Across all sub-groups, accuracy was ranked as the top criterion when choosing between stool-based testing and colonoscopy for disease activity assessments. Most patients were willing to choose stool-based testing over colonoscopy for disease monitoring if the stool test was wrong at most 1 in 20 times (5% misclassification rate). DISCUSSION: Accuracy is the most important criteria for IBD patients when choosing monitoring strategies, and a high degree of confidence is required of stool test results for patients to choose this strategy.

Incorporating Fecal Calprotectin Into Clinical Practice for Patients With Moderate-to-Severely Active Ulcerative Colitis Treated With Biologics or Small-Molecule Inhibitors.

INTRODUCTION: We applied the Grading of Recommendations, Assessment, Development, and Evaluation framework to evaluate the performance of fecal calprotectin (FC) as an alternative to endoscopy in patients with moderate-to-severe ulcerative colitis (UC) treated with a biologic agent or tofacitinib. METHODS: Individual participant data from the trials of infliximab, golimumab, vedolizumab, and tofacitinib for UC were pooled to generate prevalence of endoscopic activity (Mayo endoscopy score) across different combinations of the rectal bleeding score (RBS) and stool frequency score (SFS). These estimates were then combined with the data from an updated systematic review of the operating properties of FC to generate clinical scenario-specific assessments of the performance of FC as a predictor of endoscopic disease activity. A prespecified threshold of acceptability for false-negative (FN) and false-positive (FP) test results was set at 5%. RESULTS: For patients with UC achieving RBS 0 + SFS 0/1, FC ≤ 50 µg/g may avoid endoscopy in 50% patients with a FN rate <5%. Similarly, for patients with RBS 2/3 + SFS 2/3, FC ≥ 250 µg/g potentially avoids endoscopy in approximately 50% patients with an FP rate <5%. The greatest uncertainty in the diagnostic performance for FC was observed in patients with UC achieving RBS 0 but having SFS 2/3, where FN and FP rates were consistently >10%, and endoscopic evaluation may be warranted. DISCUSSION: Two clinical scenarios were identified where FC can be used with confidence for monitoring treatment response to biologics or tofacitinib in patients with UC without the requirement for endoscopy.

Discontinuation of antidepressants during attempts to conceive: a pilot trial of cognitive behavioral therapy for the prevention of recurrent depression.

BACKGROUND: Many women discontinue antidepressants (ADs) when trying to conceive, although risk of depressive relapse is high. We examined the feasibility and potential clinical effect of cognitive behavioral therapy for the prevention of recurrence (CBT-PR) for women with a history of recurrent major depressive disorder (MDD) who planned to discontinue maintenance AD treatment for pregnancy. METHODS: This was an open preliminary study of CBT-PR in women (N = 12) planning or early in pregnancy with remitted MDD on maintenance ADs with a plan to discontinue ADs for pregnancy. Participants received 12 sessions of CBT-PR during the acute phase and optional monthly booster sessions during follow-up. Participants were assessed monthly during the acute phase and then twice additionally during follow-up by an independent rater using mood scales (depression module of the Mini-International Neuropsychiatric Interview and Montgomery-Åsberg Depression Rating Scale); pregnancy status was also assessed. RESULTS: Over the 24 weeks of the trial, 75% (n = 9) of participants did not restart ADs and did not relapse to depression. Of the 3 who reintroduced AD, 2 experienced a depressive relapse, whereas one did not meet full criteria for MDD. Adherence to the intervention was very good with all participants completing all therapy sessions and assessments. CONCLUSIONS: Cognitive behavioral therapy for the prevention of recurrence seems feasible and may provide protection for women with recurrent depression on ADs who discontinue their medication while trying to conceive. The extent to which euthymia is sustainable with CBT-PR requires further study; the results of which may broaden treatment choices for women in anticipation of and during pregnancy.

Classifying and Disclosing Medical Errors.

Medical errors are an unfortunate but common occurrence in health care. It is important to understand what medical errors are and what types of harm can occur to patients. Along with recognition of the error, disclosure is an equally important part of the process. Clinicians should provide open and honest discussion about the events that occurred to patients along with feedback to institutions on ways to prevent such errors in the future.

A Case of COVID-19-Associated Free-Floating Aortic Thrombus Successfully Treated with Thrombectomy.

BACKGROUND COVID-19 caused by SARS-CoV-2 infection has been associated with a hypercoagulable state in which patients can be at risk for developing venous and arterial thromboembolic events at a rate as high as 31%. A free-floating aortic thrombus (FFT) is a rare life-threatening complication of a hypercoagulable state. These thrombi require medical, endovascular, or surgical treatment. The optimal treatment modality for FFT occurring in the setting of COVID-19 remains unknown. We present a patient with a COVID-19-associated free-floating descending aortic thrombus that was treated with percutaneous vacuum-assisted thrombectomy (angio-VAC). CASE REPORT A 61-year-old man presented to the hospital with dyspnea and hypoxia and was diagnosed with severe COVID-19 pneumonia. Initial chest computed tomography angiography (CTA) did not show pulmonary emboli or thrombi. Inflammatory markers (D-dimer, lactate dehydrogenase, ferritin, fibrinogen) were tracked every other day. After several measurements of decreasing D-dimer values, there was a noticeable increase in D-dimer level and continued dependence on high levels of supplemental oxygen. A repeat chest CTA showed an FFT, confirmed by transesophageal echocardiogram. Cardiothoracic surgery and interventional radiology teams performed successful angio-VAC percutaneous removal, confirmed with intravascular ultrasound. The patient was subsequently discharged with a 3-month supply of apixaban. CONCLUSIONS Minimally invasive endovascular removal of an FFT is a therapeutic option, as anticoagulation alone carries the risk of partial lysis and repeat embolization. Clinicians can consider this endovascular treatment option paired with therapeutic anticoagulation. Further guidelines on monitoring and treatment of possible COVID-19-associated thrombosis are needed, particularly when the risk of embolization is high.

In the absence of head-to-head trials, what do real world studies tell us about the comparative effectiveness of biologics in Crohn's disease.

Head-to-head clinical trials are the highest quality of evidence to support comparative effectiveness. However, there are currently no head-to-head phase 3 clinical trials of biologics in Crohn's Disease. With a need for direct comparisons but lagging RCTs, Real World Data (RWD) can provide evidence on the comparative effectiveness of biologics for a diverse population that is more generalizable to routine practice. The majority of available real-world comparative analyses show no significant difference in effectiveness outcomes-primarily clinical remission and CD related complications. Real-world data is limited by its susceptibility to bias and clinicians must critically evaluate the methods and data sources utilized. Moving forward, it is important to note that comparisons including newer biologics may be limited by significant prior biologic exposure. Additionally, shared decision making incorporates efficacy, safety, and tolerability with patient preference and clinicians should use data from real-world comparative analyses as a part of this equation.

A Case of Mania Presenting with Hypersexual Behavior and Gender Dysphoria that Resolved with Valproic Acid.

Hypersexuality and gender dysphoria have both been described in the literature as symptoms of mania. Hypersexuality is listed in the Diagnostic and Statistical Manual of Mental Disorders 5 as part of the diagnostic criteria for bipolar disorder. Gender dysphoria is less often described and its relation to mania remains unclear. This case report describes a young homosexual man presenting in a manic episode with co-morbid amphetamine abuse whose mania was marked by hypersexuality and the new onset desire to be a woman. Both of these symptoms resolved with the addition of valproic acid to antipsychotics. This case report presents the existing literature on hypersexuality and gender dysphoria in mania and describes a treatment option that has not been previously reported.

Armodafinil for fatigue associated with menopause: an open-label trial.

OBJECTIVE: This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. METHODS: Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. RESULTS: Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. CONCLUSIONS: These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

A feasibility study to determine if minimally trained medical students can identify markers of chronic parasitic infection using bedside ultrasound in rural Tanzania.

BACKGROUND: Parasitic infections pose a significant health risk in developing nations and are a major cause of morbidity and mortality worldwide. In the Republic of Tanzania, the CDC estimates that 51.5% of the population is infected with one or more intestinal parasites. If diagnosed early, the consequences of chronic parasitic infection can potentially be avoided. METHODS: Six first-year medical students were recruited to enroll patients in the study. They underwent ten hours of formal, hands-on, ultrasound which included basic cardiac, hepatobiliary, renal, pulmonary and FAST scan ultrasound. A World Health Organization protocol with published grading scales was adapted and used to assess for pathology in each patient's liver, bladder, kidneys, and spleen. RESULTS: A total of 59 patients were enrolled in the study. Students reported a sensitivity of 96% and specificity of 100% for the presence of a dome shaped bladder, a sensitivity and specificity of 100% for bladder thickening, a sensitivity and specificity of 100% for portal hypertension and ascites. The sensitivity was 81% with a specificity of 100% for presence of portal vein distention. The sensitivity was 100% with a specificity of 90% for dilated bowel. CONCLUSIONS: Ultrasound has shown a promise at helping to identify pathology in rural communities with limited resources such as Tanzania. Our data suggest that minimally trained first year medical students are able to perform basic ultrasound scans that can identify ultrasonographic markers of parasitic infections.

A feasibility study to determine if minimally trained medical students can identify markers of chronic parasitic infection using bedside ultrasound in rural Tanzania / 世界急诊医学杂志（英文）

@#BACKGROUND: Parasitic infections pose a significant health risk in developing nations and are a major cause of morbidity and mortality worldwide. In the Republic of Tanzania, the CDC estimates that 51.5％ of the population is infected with one or more intestinal parasites. If diagnosed early, the consequences of chronic parasitic infection can potentially be avoided. METHODS: Six first-year medical students were recruited to enroll patients in the study. They underwent ten hours of formal, hands-on, ultrasound which included basic cardiac, hepatobiliary, renal, pulmonary and FAST scan ultrasound. A World Health Organization protocol with published grading scales was adapted and used to assess for pathology in each patient's liver, bladder, kidneys, and spleen. RESULTS: A total of 59 patients were enrolled in the study. Students reported a sensitivity of 96％ and specificity of 100％ for the presence of a dome shaped bladder, a sensitivity and specificity of 100％ for bladder thickening, a sensitivity and specificity of 100％ for portal hypertension and ascites. The sensitivity was 81％ with a specificity of 100％ for presence of portal vein distention. The sensitivity was 100％ with a specificity of 90％ for dilated bowel. CONCLUSIONS: Ultrasound has shown a promise at helping to identify pathology in rural communities with limited resources such as Tanzania. Our data suggest that minimally trained first year medical students are able to perform basic ultrasound scans that can identify ultrasonographic markers of parasitic infections.