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Benzodiazepines are commonly used for behavioral and psychiatric symptoms of dementia, despite their numerous adverse effects and the lack of evidence regarding their efficacy in this context. We studied longitudinal benzodiazepines exposure in incident cases of Alzheimer's disease and related syndromes (ADRS) in France. We used a cohort of incident ADRS patients identified in 2012 within the national health data system. Benzodiazepines exposure was measured 1 year before, to 5 years after ADRS identification. Quarterly benzodiazepines prevalence and incidence were computed. We identified factors associated with long half-life benzodiazepines initiation. A total of 106 508 subjects were included. Quarterly benzodiazepines prevalence was stable (around 25%) but we saw an important decrease in long half-life benzodiazepines compensated by an increase in short half-life benzodiazepines. In most benzodiazepine initiations, the first episode lasted less than 3 months. Factors associated with initiating a long half-life benzodiazepine were young age, male gender, no registration with ADRS as a long-term disease, having consulted an ADRS specialist, antipsychotic reimbursement before the index date, no admission in nursing home. Prevalence of benzodiazepines use remains high in subjects with ADRS despite guidelines for their avoidance. However, indicators regarding benzodiazepine initiations (duration, benzodiazepine type) suggest some caution in their use.OBJECTIVES Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%-20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P less then 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.A cost-utility analysis in the current issue of AJG examines the ramifications of the overuse of surveillance endoscopy in Barrett's esophagus (BE). This study suggests that excess surveillance is expensive, increasing costs by 50% or more, with only nominal increases in quality-adjusted life expectancy. This study joins a growing literature of cost-utility analyses that suggest that more is not likely better when it comes to surveillance endoscopy. Given the plentiful literature showing overutilization of surveillance endoscopy in BE, the authors argue for a focus on the quality of endoscopy rather than increased frequency of surveillance to improve returns on our healthcare investment.We report a case of a 4-year-old Brazilian boy, who presented with an erythematous and painful nodule involving the skin of his left arm. Immunohistochemistry was performed for S100, SOX10, CD34, desmin, SMA, HMB-45, CD1a, and CD163, and fluorescence in situ hybridization for EWSR1 gene rearrangement using a break-apart probe was completed. Immunohistochemistry showed bland spindle cells with "floret-like" appearance simulating a giant cell fibroblastoma; tumor cells were positive for S100 and SOX10; neoplastic cells were negative for CD34, desmin, SMA, HMB-45, CD1a, and CD163; and fluorescence in situ hybridization showed an EWSR1 gene rearrangement. We report the youngest known case of cutaneous involvement of clear cell carcinoma at the age of 4.Syphilis is a sexually transmitted disease caused by Treponema pallidum. The primary stage of the disease (the chancre) mainly involves the genital areas. Extragenital areas are involved in 5%-14% of cases, many of which occur in the oral cavity. Among the extragenital locations, the lip is the most frequent; however, despite this, published cases of the chancre of the lip are few. We present a case of a chancre presenting on the lip of a nonimmunocompromised 55-year-old male patient with immunohistochemical confirmation.BACKGROUND Conditional survival (CS) is a relevant prognostic measure and may be particularly important for young adult patients with colorectal cancer (CRC), whose incidence is rising. We sought to compare CS among young versus older adults with CRC. METHODS Patients diagnosed with CRC between 2004 and 2010 were identified from the Surveillance, Epidemiology, and End Results registry. Smoothed yearly hazards of death due to CRC, other causes and any cause were estimated, stratified by age at diagnosis (below 50 vs. 50 y and above) and stage (I-III vs. IV). Stage-specific conditional 5-year overall survival and cancer-specific survival given that patients had already survived 1 to 5 years after diagnosis was calculated. RESULTS Among 161,859 patients with median follow-up of 54 months, 35,411 (21.9%) were aged below 50 years. For older adults with nonmetastatic CRC, hazards of death due to noncancer causes exceeded that of rectal and colon cancer ∼6.1 and 3.8 years after diagnosis, respectively. Patients experienced improved CS over time with greater improvement seen for more advanced stages. However, young adults had less CS improvement over time than older adults. For example, the 5-year cancer-specific survival for stage IV colon cancer improved from 15.6% to 77.2% (change=61.6%) 0 to 5 years after diagnosis for older adults but only 20.3% to 67.7% (change=47.4%) for young adults. CONCLUSIONS Prognosis for CRC improves over time for all patients, although the increase in survival appears to be less for young than older adults. RU58841 ic50 Up to 10 years after diagnosis, the primary cause of death in young adults with CRC remains their incident cancer.OBJECTIVE We aimed to explore possible drivers for urban-rural disparities in colon cancer outcomes in a single-payer health care system where all patients had access to universal health care coverage. METHODS Patients diagnosed with stage II/III colon cancer between 2004 and 2015 in Alberta, Canada were reviewed. On the basis of postal code, patients were categorized as living in urban, rural, or suburban areas based on travel distance to the cancer center. Kaplan-Meier methods and Cox regression models assessed the associations among the area of residence, receipt of treatment, and overall survival (OS). RESULTS Of 6163 patients identified, there were 3691, 1779, and 693 from urban, rural, and suburban areas, respectively. There was a larger proportion of younger patients (P=0.033) and left-sided colon cancers (P=0.042) in urban areas. Urban patients experienced shorter times from diagnosis to surgery (P less then 0.001), but longer delays from surgery to adjuvant chemotherapy (P=0.001). A significant difference in outcomes was identified among urban, rural, and suburban populations where median OS were 104, 94, and 83 months, respectively (P less then 0.001). In multivariate analysis, the location of residence continued to predict for worse OS in suburban (hazard ratio=1.60, 95% confidence interval 1.24-2.07, P less then 0.001) and rural areas (hazard ratio=1.24, 95% confidence interval 1.02-1.50, P=0.042), when compared with urban areas. CONCLUSIONS In this population-based study, urban-rural differences in colon cancer survival persist, even in settings with universal health care coverage. These findings may be partly driven by a younger population with more left-sided colon cancers as well as expedited surgical intervention in urban populations, but these factors do not fully explain the disparities.PURPOSE OF REVIEW Apolipoprotein C-III (ApoC-III) and angiopoietin like protein 3 (angptl3) have emerged as key regulators of triglyceride metabolism. Based on Mendelian randomisation studies, novel therapeutic strategies inhibiting these proteins using monoclonal antibodies or gene silencing techniques might reduce residual cardiovascular disease (CVD) risk in dyslipidemic patients. This article aims to review the role of apoC-III and angptl3 in triglyceride metabolism and combine early clinical evidence of CVD reducing potential of these new therapeutic targets. RECENT FINDINGS Angptl3 inhibition by mAb or antisense therapy has recently completed phase I and II studies, respectively and demonstrate robust apolipoprotein B (apoB) lowering up to 46%. Volanesorsen is an antisense therapy approved for patients with extremely elevated plasma triglyceride levels in which it showed no consistent apoB reduction. However, the GalNAc-conjugated oligonucleotide showed moderate (up to ∼30%) apoB reduction in a phase 1/2a dose-finding study. SUMMARY Angptl3 and apoC-III are novel targets in lipoprotein metabolism that reduce triglycerides when inhibited. The expected CVD risk reduction may be mediated through reduced triglyceride-rich lipoprotein particle number, reflected by apoB, rather than triglyceride reduction per se. Limited human evidence shows that apoC-III and angptl3 inhibition both potently lower triglycerides, but since angptl3 inhibition reduces apoB more robustly it may be expected to confer more favorable CVD risk reduction.BACKGROUND The Coronavirus Disease-2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak in China. The host immunity of COVID-19 patients is unknown. METHODS The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS A total of 65 SARS-CoV-2-positive patients were classified as mild (n=30), severe (n=20), and extremely severe (n=15) illness. Many routine laboratory tests such as ferritin, lactate dehydrogenase and D-dimer were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells and B cells were all gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The co-stimulatory molecule CD28 had opposite results. The percentage of natural regulatory T cells was decreased in extremely severe patients.