Social vs. practical problems in attaining a colonoscopy: Different patient profiles?

Background: Colonoscopy is an effective procedure for identifying precancerous polyps and cancerous lesions, but it is unlike other cancer screening tools in that it requires sedation and thus assistance from at least one other individual. The intent of this paper was to identify logistical problems in completing the colonoscopy and to examine their relationships with sociodemographic characteristics. Methods: All eligible patients (n = 2500) from two academic-affiliated colonoscopy centers (one free standing, one hospital-based) were invited to participate in an onsite, pre-colonoscopy survey; patients agreeing to participate (n = 1841, RR = 73.6%) received a $5.00 gift card. Multiple correspondence analysis (MCA) was used to identify the underlying dimensional structure of the problems. Bivariate statistics were performed to compare demographic variables and health literacy levels among patients reporting problems. Multivariate logistic regression with a backwards conditional solution was used to determine the demographic variables independently associated with problems. Results: Multiple correspondence analyses indicated two dimensions of problems (social and practical). Using logistic regression, social problems (e.g., finding someone to accompany the patient) were associated with not living in the same home as the driver, not working due to disability, and younger age. Practical problems (e.g., making an appointment) were associated with “other” minority race, poorer health, lower health literacy, and younger age. Conclusion: Patients experience different problems completing the colonoscopy based on socio-demographics. Particularly at risk are patients who find it difficult to navigate the system, are of younger age, or who may have smaller social networks

Bouveret's Syndrome: Case Report and Review of the Literature

Bouveret's syndrome is defined as gastric outlet obstruction caused by duodenal impaction of a large gallstone which passes into the duodenal bulb through a cholecystogastric or cholecystoduodenal fistula. Initial attempts at endoscopic retrieval with or without mechanical or extracorporeal lithotripsy should be performed as first-line treatment, though success rates with endoscopic treatment are variable. We describe a case of Bouveret's Syndrome in an elderly patient that was successfully treated with endoscopic extraction combined with mechanical lithotripsy, and review the literature on this uncommon condition

Evaluating preferences for colorectal cancer screening in individuals under age 50 using the Analytic Hierarchy Process

In 2021, the United States Preventive Services Task Force updated their recommendation, stating that individuals ages 45-49 should initiate screening for colorectal cancer. Since several screening strategies are recommended, making a shared decision involves including an individual’s preferences. Few studies have included individuals under age 50. In this study, we use a multicriteria decision analysis technique called the Analytic Hierarchy Process to explore preferences for screening strategies and evaluate whether preferences vary by age. Participants evaluated a hierarchy with 3 decision alternatives (colonoscopy, fecal immunochemical test, and computed tomography colonography), 3 criteria (test effectiveness, the screening plan, and features of the test) and 7 sub-criteria. We used the linear fit method to calculate consistency ratios and the eigenvector method for group preferences. We conducted sensitivity analysis to assess whether results are robust to change and tested differences in preferences by participant variables using chi-square and analysis of variance. Of the 579 individuals surveyed, 556 (96%) provided complete responses to the AHP portion of the survey. Of these, 247 participants gave responses consistent enough (CR < 0.18) to be included in the final analysis. Participants that were either white or have lower health literacy were more likely to be excluded due to inconsistency. Colonoscopy was the preferred strategy in those < 50 and fecal immunochemical test was preferred by those over age 50 (p = 0.002). These results were consistent when we restricted analysis to individuals ages 45-55 (p = 0.011). Participants rated test effectiveness as the most important criteria for making their decision (weight = 0.555). Sensitivity analysis showed our results were robust to shifts in criteria and sub-criteria weights. We reveal potential differences in preferences for screening strategies by age that could influence the adoption of screening programs to include individuals under age 50. Researchers and practitioners should consider at-home interventions using the Analytic Hierarchy Process to assist with the formulation of preferences that are key to shared decision-making. The costs associated with different preferences for screening strategies should be explored further if limited resources must be allocated to screen individuals ages 45-49.https://doi.org/10.1186/s12913-021-06705-

Contribution of patient, physician, and environmental factors to demographic and health variation in colonoscopy follow-up for abnormal colorectal cancer screening test results

BACKGROUND: Patient, physician, and environmental factors were identified, and the authors examined the contribution of these factors to demographic and health variation in colonoscopy follow-up after a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT-positive patients were identified from 120 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011 and were followed for 6 months. Patient demographic (race/ethnicity, sex, age, marital status) and health characteristics (comorbidities), physician characteristics (training level, whether primary care provider) and behaviors (inappropriate FOBT/FIT screening), and environmental factors (geographic access, facility type) were identified from VHA administrative records. Patient behaviors (refusal, private sector colonoscopy use) were estimated with statistical text mining conducted on clinic notes, and follow-up predictors and adjusted rates were estimated using hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a colonoscopy at a VHA facility within 6 months. Age and comorbidity score were negatively associated with follow-up. Blacks were more likely to receive follow-up than whites. Environmental factors attenuated but did not fully account for these differences. Patient behaviors (refusal, private sector colonoscopy use) and physician behaviors (inappropriate screening) fully accounted for the small reverse race disparity and attenuated variation by age and comorbidity score. Patient behaviors (refusal and private sector colonoscopy use) contributed more to variation in follow-up rates than physician behaviors (inappropriate screening). CONCLUSIONS: In the VHA, blacks are more likely to receive colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up rates markedly decline with advancing age and comorbidity burden. Patient and physician behaviors explain race variation in follow-up rates and contribute to variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017. This article is a US Government work and is in the public domain in the USA

Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions

Cyclic vomiting syndrome (CVS) is characterized by severe episodic emesis in adults and children. Cannabinoid hyperemesis syndrome is an increasingly recognized CVS‐like illness that has been associated with chronic cannabis use. There are significant gaps in our understanding of the pathophysiology, clinical features, comorbidities, and effective management options of CVS. Recommendations for treating CVS are based on limited clinical data, as no placebo‐controlled, randomized trials have yet been conducted. Diseases associated with CVS, including migraine, mitochondrial disorders, autonomic dysfunction, and psychiatric comorbidities, provide clues about pathophysiologic mechanisms and suggest potential therapies. We review our current understanding of CVS and propose future research directions with the aim of developing effective therapy. Establishing a multicenter, standardized registry of CVS patients could drive research on multiple fronts including developing CVS‐specific outcome measures to broaden our understanding of clinical profiles, to serve as treatment end points in clinical trials, and to provide a platform for patient recruitment for randomized clinical trials. Such a robust database would also facilitate conduct of research that aims to determine the underlying pathophysiological mechanisms and genetic basis for CVS, as well as identifying potential biomarkers for the disorder. Soliciting government and industry support is crucial to establishing the necessary infrastructure and achieving these goals. Patient advocacy groups such as the Cyclic Vomiting Syndrome Association (CVSA), which partner with clinicians and researchers to disseminate new information, to promote ongoing interactions between patients, their families, clinicians, investigators, to support ongoing CVS research and education, must be an integral part of this endeavor.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149751/1/nmo13607.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149751/2/nmo13607_am.pd

Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association

The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence‐based guidelines on the management of CVS in adults, which was sponsored by the American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly  recommends that adults with moderate‐to‐severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first‐line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L‐carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well‐being and patient care outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149730/1/nmo13604.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149730/2/nmo13604_am.pd

Management of cyclic vomiting syndrome in adults: Evidence review

BackgroundThis evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults.MethodsWe followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant?ResultsWe found very low‐quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co‐morbid conditions and complementary therapies.ConclusionsThis evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149694/1/nmo13605.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149694/2/nmo13605_am.pd

Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome

Cannabis is commonly used in cyclic vomiting syndrome (CVS) due to its antiemetic and anxiolytic properties. Paradoxically, chronic cannabis use in the context of cyclic vomiting has led to the recognition of a putative new disorder called cannabinoid hyperemesis syndrome (CHS). Since its first description in 2004, numerous case series and case reports have emerged describing this phenomenon. Although not pathognomonic, a patient behavior called “compulsive hot water bathing” has been associated with CHS. There is considerable controversy about how CHS is defined. Most of the data remain heterogenous with limited follow‐up, making it difficult to ascertain whether chronic cannabis use is causal, merely a clinical association with CVS, or unmasks or triggers symptoms in patients inherently predisposed to develop CVS. This article will discuss the role of cannabis in the regulation of nausea and vomiting, specifically focusing on both CVS and CHS, in order to address controversies in this context. To this objective, we have collated and analyzed published case series and case reports on CHS in order to determine the number of reported cases that meet current Rome IV criteria for CHS. We have also identified limitations in the existing diagnostic framework and propose revised criteria to diagnose CHS. Future research in this area should improve our understanding of the role of cannabis use in cyclic vomiting and help us better understand and manage this disorder.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149684/1/nmo13606_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149684/2/nmo13606.pd

Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

Background: Pathogenic variants of GNB5 encoding the β5 subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia. Methods: We used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse. Results: We delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5-/- mice were smaller and had a smaller heart than Gnb5+/+ and Gnb5+/-, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5-/- mice. In contrast, Gnb5-/- mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients. Conclusions: Our data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5-/- mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function