Thiopurine therapy, commonly used in autoimmune conditions, can be complicated by life-threatening leukopenia. This leukopenia is associated with genetic variation in TPMT (encoding thiopurine S-methyltransferase). Despite a lower frequency of TPMT mutations in Asians, the incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent. Here we performed an Immunochip-based 2-stage association study in 978 Korean subjects with Crohn’s disease treated with thiopurines. We identified a nonsynonymous SNP in NUDT15 (encoding p.Arg139Cys) that was strongly associated with thiopurine-induced early leukopenia (odds ratio (OR) = 35.6; Pcombined = 4.88 × 10−94). In Koreans, this variant demonstrated sensitivity and specificity of 89.4% and 93.2%, respectively, for thiopurine-induced early leukopenia (in comparison to 12.1% and 97.6% for TPMT variants). Although rare, this SNP was also strongly associated with thiopurine-induced leukopenia in subjects with inflammatory bowel disease of European descent (OR = 9.50; P = 4.64 × 10−4). Thus, NUDT15 is a pharmacogenetic determinant for thiopurine-induced leukopenia in diverse populations.

Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People’s Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26–96% declines). Total outpatient visits declined by 9–40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.

BACKGROUND & AIMS: Q6Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndromecoronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19. METHODS:We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29-41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens. RESULTS:Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%).Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative. CONCLUSIONS:In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients.

Korean patients with CD may have a similar clinical course to Westerners, as indicated by the intestinal resection rate. The surgery rate has decreased over time, and early use of azathioprine/6-mercaptopurine was related to its decrease.

In a retrospective analysis of 72,356 asymptomatic persons under 40 years of age evaluated by colonoscopy in Korea, we found modifiable factors, such as smoking, alcohol intake, obesity, and metabolic syndrome, to be significant risk factors for CRN-even in persons of 20-39 years old. Colorectal cancer screening strategies should consider these risk factors.

Most countries have implemented restrictions on mobility to prevent the spread of Coronavirus disease-19 (COVID-19), entailing considerable societal costs but, at least initially, based on limited evidence of effectiveness. We asked whether mobility restrictions were associated with changes in the occurrence of COVID-19 in 34 OECD countries plus Singapore and Taiwan. Our data sources were the Google Global Mobility Data Source, which reports different types of mobility, and COVID-19 cases retrieved from the dataset curated by Our World in Data. Beginning at each country’s 100th case, and incorporating a 14-day lag to account for the delay between exposure and illness, we examined the association between changes in mobility (with January 3 to February 6, 2020 as baseline) and the ratio of the number of newly confirmed cases on a given day to the total number of cases over the past 14 days from the index day (the potentially infective ‘pool’ in that population), per million population, using LOESS regression and logit regression. In two-thirds of examined countries, reductions of up to 40% in commuting mobility (to workplaces, transit stations, retailers, and recreation) were associated with decreased cases, especially early in the pandemic. Once both mobility and incidence had been brought down, further restrictions provided little additional benefit. These findings point to the importance of acting early and decisively in a pandemic.

Background/AimsColonoscopic polypectomy is the best diagnostic and therapeutic tool to detect and prevent colorectal neoplasms. However, previous studies have reported that 17% to 28% of colorectal polyps are missed during colonoscopy. We investigated the miss rate of neoplastic polyps and the factors associated with missed polyps from quality-adjusted consecutive colonoscopies.MethodsWe reviewed the medical records of patients who were found to have colorectal polyps at a medical examination center of the Kangbuk Samsung Hospital between March 2012 and February 2013. Patients who were referred to a single tertiary academic medical center and underwent colonoscopic polypectomy on the same day were enrolled in our study. The odds ratios (ORs) associated with polyp-related and patient-related factors were evaluated using logistic regression analyses.ResultsA total of 463 patients and 1,294 neoplastic polyps were analyzed. The miss rates for adenomas, advanced adenomas, and carcinomas were 24.1% (312/1,294), 1.2% (15/1,294), and 0% (0/1,294), respectively. Flat/sessile-shaped adenomas (adjusted OR, 3.62; 95% confidence interval [CI], 2.40–5.46) and smaller adenomas (adjusted OR, 5.63; 95% CI, 2.84– 11.15 for ≤5 mm; adjusted OR, 3.18; 95% CI, 1.60–6.30 for 6–9 mm, respectively) were more frequently missed than pedunculated/sub-pedunculated adenomas and larger adenomas. In patients with 2 or more polyps compared with only one detected (adjusted OR, 2.37; 95% CI, 1.55–3.61 for 2–4 polyps; adjusted OR, 11.52; 95% CI, 4.61–28.79 for ≥5 polyps, respectively) during the first endoscopy, the risk of missing an additional polyp was significantly higher.ConclusionsOne-quarter of neoplastic polyps was missed during colonoscopy. We encourage endoscopists to detect smaller and flat or sessile polyps by using the optimal withdrawal technique.

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