Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.

BACKGROUND: Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. METHODS: We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. RESULTS: A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. CONCLUSIONS: In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

Ustekinumab was shown to be efficacious and safe in a population of patients with refractory ulcerative colitis. Those patients with exposure to multiple drug classes and higher disease burden at baseline are less likely to respond.

Chronic Mesenteric Ischemia in a Patient With Limited Systemic Sclerosis.

Chronic mesenteric ischemia typically develops secondary to the development of atherosclerosis within mesenteric vessels leading to the insufficient blood supply. While autoimmune conditions are an established independent risk factor for developing atherosclerotic plaques, the association between scleroderma and chronic mesenteric ischemia has been less studied. We present a case of a 64-year-old female with limited systemic sclerosis and atherosclerotic cardiovascular disease who presented to the Gastroenterology Clinic with progressive abdominal pain who was subsequently diagnosed with chronic mesenteric ischemia secondary to superior mesenteric artery stenosis and successfully treated with endovascular stenting.

Net Remission Rates with Biologic Treatment in Crohn's Disease: A Reappraisal of the Clinical Trial Data.

Biologic therapies have greatly advanced the medical care of patients with Crohn's disease (CD); however, up to 50% of patients have no response and up to 80% fail to achieve remission.1-4 One way to investigate this treatment gap in CD is to look at the "net" remission rates in clinical trials defined as the actual percentage of patients enrolled during induction who are in remission at the end of maintenance. Indeed, most of the seminal clinical trials in CD used a "responder" methodology, where only patients who responded during induction were rerandomized to maintenance.

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. METHODS: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs. RESULTS: AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4-30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9-11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day). CONCLUSIONS: Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs.

Association of Renal Clearance with Cerebral White Matter Vascular Disease in Hospitalized Veterans With and Without Delirium.

OBJECTIVES: To assess the relation between renal function and delirium and to assess and compare the relation between cerebral white matter lesion (WML) and renal function as estimated by three formulas for the estimated glomerular filtration rate (eGFR) in older adult hospitalized veterans with and without delirium. METHODS: Commonly used formulas to assess renal function-the four-variable Modification of Diet in Renal Disease (MDRD), the six-variable MDRD, and the Cockcroft-Gault eGFR equations-were used to assess renal function in 100 older adult hospitalized veterans with delirium (delirium group) and 100 hospitalized veterans without delirium (nondelirium group) that were age, sex, and race matched. WML location and volumes were assessed using brain computed tomography imaging for each of the 200 veterans in the study. One radiologist, blinded to the diagnoses of the veterans, examined head computed tomography scans for WML in the cortex, subcortex (frontal, temporal, parietal, occipital lobes), basal ganglia (globus pallidus, caudate, putamen), and internal capsule. WML were graded as not present, <1 cm, 1 to 2 cm, or >2 cm. Exploratory χ2 analyses were used to determine the association between the stage of chronic kidney disease and WML. Simple logistic regression analyses were then used to estimate the strength of association between the stages of kidney disease and WML for particular regions of the brain. RESULTS: The mean age of delirium group and nondelirium group veterans was 66 years. χ2 tests revealed no reliable relation between stages of renal disease and delirium. χ2 exploratory analyses of WML in brain regions by renal disease stages demonstrated significant differences in associations among the MDRD-4, MDRD-6, and Cockcroft-Gault formulas for measuring eGFR. The MDRD-4 formula was least associated with the presence or absence of WML. The Cockcroft-Gault estimation of eGFR was most associated with the presence or absence of WML. Simple logistic regressions showed notable increases in the association between stages of renal failure and WMLs in specific areas of the brain, with the MDRD-4 being the least associative with the fewest specific areas and the Cockcroft-Gault formula being the most associative with the most specific areas. CONCLUSIONS: The association between stages 2 through 5 of chronic kidney disease and WLM support the role of kidney function as a potential risk factor for WML in older adult military veterans. The Cockcroft-Gault formula is an important renal index of suspected WML and renal stages 2 through 5, superior to the MDRD-6 and MDRD-4, respectively, in association with WML in older adult military veterans.

Association of White Matter Lesions, Cerebral Atrophy, Intracranial Extravascular Calcifications, and Ventricular-Communicating Hydrocephalus with Delirium Among Veterans.

OBJECTIVES: The literature regarding the underlying neuropathogenesis of delirium on head computed tomography (CT) is limited. The aim of this research was to investigate, using case-control retrospective chart review, the association of white matter lesions (WML), cerebral atrophy, intracranial extravascular calcifications, and ventricular-communicating hydrocephalus in older adult military veterans with and without delirium hospitalized in a Veterans Affairs Medical Center. METHODS: Head CT scans were examined for WML, atrophy, and intracranial extravascular calcifications globally in the cortex, subcortex (frontal, temporal, parietal, occipital lobes), basal ganglia (globus pallidus, caudate, putamen), and internal capsule, in addition to the presence of ventricular-communicating hydrocephalus. WML were graded as not present, <1 cm, 1 to 2 cm, or >2 cm. Atrophy, cerebral atrophy, intracranial extravascular calcifications, and ventricular-communicating hydrocephalus were graded as present or not present. RESULTS: There was a significant association of WML in the temporal lobe periventricular cortical and subcortical brain and a significant association of atrophy in the parietal lobes and the cerebellum in hospitalized older adult military veterans with delirium compared with hospitalized older adult military veterans without delirium. There were no differences between the delirium and nondelirium groups for intracranial extravascular calcifications and ventricular-communicating hydrocephalus. CONCLUSIONS: The results suggest that atrophy in the parietal lobes and the cerebellum of hospitalized older adult military veterans may be associated with an elevated risk of delirium when compared with age, race, and sex-matched control veterans. Continuing efforts are needed to clarify the role of atrophy during delirium in the veteran and nonveteran older adult population to reduce progressive frailty and decreased quality of life secondary to hospital and posthospital-discharge delirium.

Can improved intra- and inter-team communication reduce missed delirium?

To assess the prevalence and the team interaction in cases of missed delirium in acute care veterans coded as not having a diagnosis of delirium in admission or discharge notes. In this retrospective study, the records of 183 hospitalized veterans admitted to the emergency department (ED), medicine, surgery and psychiatry services and coded as not having a diagnosis of delirium were analyzed. Clinical notes of each case were examined using DSM IV TR criteria for delirium. Of the 52 cases assessed to have delirium, 5 cases had been miscoded as not having delirium. In the remaining 47 cases the diagnosis of delirium had been missed. The rates of undiagnosed delirium were ED 46/160, medicine 39/132, surgery 4/17, psychiatry 4/29 and consult liaison (CL) 0/9. Of the 5 cases of delirium identified by the CL service, 2 consult diagnoses were accepted and 3 were rejected. Nursing notes had words suggesting delirium in 70.2 % of 47 cases compared to 41.3 and 43.6 % of the clinician case notes for these patients admitted to ED and medicine respectively. No delirium or cognitive screening scales were utilized in the work up of the 52 cases involving delirium. The study results suggest that continuing education by the CL service of all hospital personnel involved in patient care may improve the diagnosis of delirium. Also, increased clinician-nursing intra-team communication, in addition to careful scrutiny of the nursing and clinician notes may contribute to the reduced incidence of missed delirium.

Delirious mania and malignant catatonia: a report of 3 cases and review.

Delirious mania is often difficult to distinguish from excited catatonia. While some authors consider delirious mania a subtype of catatonia, the distinction between the two entities is important as treatment differs and effects outcome. It appears that as catatonia is described as having non-malignant and malignant states, the same division of severity may also apply to delirious mania. Non-malignant delirious mania meets the criteria for mania and delirium without an underlying medical disorder. The patients are amnestic, may lose control of bowel and bladder, but still respond to atypical antipsychotics and mood stabilizers. However, with increasing progression of the disease course and perhaps with an increasing load of catatonic features, delirious mania may convert to a malignant catatonic state (malignant delirious mania) which is worsened by antipsychotics and requires a trial of benzodiazepines and/or ECT. Three case reports are presented to illustrate the diagnostic conundrum of delirious mania and several different presentations of malignant catatonia.

Treatment of delirium in older adults with quetiapine.

Delirium is a neuropsychiatric syndrome characterized by impairment of consciousness, changes in cognition, or perceptual disturbances. In addition, delirium is often accompanied by delusions, hallucinations, and agitation. In this study, 12 older patients with delirium were treated for neuropsychiatric symptoms with quetiapine. The mean duration for stabilization was 5.91 +/- 2.22 days, and the mean dose was 93.75 +/- 23.31 mg/day. None of the 12 patients developed extrapyramidal symptoms. There were significant improvements on all measures used in this study. Interestingly, the Delirium Rating Scale scores along with scores of the Mini-Mental State Examination and Clock Drawing Test continued to improve throughout the 3-month study period. In our study, we found that quetiapine was a safe and effective treatment in hospitalized older patients with delirium.