Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

Use of Bladder Antimuscarinics in Older Adults with Impaired Cognition.

OBJECTIVE: To examine the use of antimuscarinics for treating urinary incontinence (UI) in older adults with varying levels of cognition. DESIGN: Cross-sectional. SETTING: National Alzheimer's Coordinating Center from 2005 through 2015. PARTICIPANTS: Community-dwelling men and women aged 65 and older (N = 24,106). MEASUREMENTS: Clinicians and staff evaluated each participant's dementia status during annual in-person assessments. Participants or their informants reported all medications taken in the 2 weeks before each study visit. RESULTS: Overall, 5.2% (95% confidence interval (CI) = 4.9-5.5%) of the cohort took a bladder antimuscarinic. Participants with impaired cognition were more likely to be taking an antimuscarinic than those with normal cognition. Rates of bladder antimuscarinic use were 4.0% (95% CI = 3.6-4.4%) for participants with normal cognition, 5.6% (95% CI = 4.9-6.3%) for those with mild cognitive impairment, and 6.0% (95% CI = 5.5-6.4%) for those with dementia (p < .001). Of 624 participants with dementia who took antimuscarinics, 16% (95% CI = 13-19%) were simultaneously taking other medicines with anticholinergic properties. CONCLUSION: Use of bladder antimuscarinics was more common in older adults with impaired cognition than in those with normal cognition. This use is despite guidelines advising clinicians to avoid prescribing antimuscarinics in individuals with dementia because of their vulnerability to anticholinergic-induced adverse cognitive and functional effects. A substantial proportion of cognitively impaired individuals who took antimuscarinics were simultaneously taking other anticholinergic medications. These findings suggest a need to improve the treatment of UI in individuals with impaired cognition.

unfulfilled interacting genes display branch-specific roles in the development of mushroom body axons in Drosophila melanogaster.

The mushroom body (MB) of Drosophila melanogaster is an organized collection of interneurons that is required for learning and memory. Each of the three subtypes of MB neurons, γ, α'/ß', and α/ß, branch at some point during their development, providing an excellent model in which to study the genetic regulation of axon branching. Given the sequential birth order and the unique patterning of MB neurons, it is likely that specific gene cascades are required for the different guidance events that form the characteristic lobes of the MB. The nuclear receptor UNFULFILLED (UNF), a transcription factor, is required for the differentiation of all MB neurons. We have developed and used a classical genetic suppressor screen that takes advantage of the fact that ectopic expression of unf causes lethality to identify candidate genes that act downstream of UNF. We hypothesized that reducing the copy number of unf-interacting genes will suppress the unf-induced lethality. We have identified 19 candidate genes that when mutated suppress the unf-induced lethality. To test whether candidate genes impact MB development, we performed a secondary phenotypic screen in which the morphologies of the MBs in animals heterozygous for unf and a specific candidate gene were analyzed. Medial MB lobes were thin, missing, or misguided dorsally in five double heterozygote combinations (;unf/+;axin/+, unf/+;Fps85D/+, ;unf/+;Tsc1/+, ;unf/+;Rheb/+, ;unf/+;msn/+). Dorsal MB lobes were missing in ;unf/+;DopR2/+ or misprojecting beyond the termination point in ;unf/+;Sytß double heterozygotes. These data suggest that unf and unf-interacting genes play specific roles in axon development in a branch-specific manner.