Summary Background Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly ...understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. Methods In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive13 C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01906879. Findings Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 95% CI 87·6–92·6) for 10-day bismuth quadruple therapy, 85·9% (464/540 82·7–88·6) for 10-day concomitant therapy, and 83·7% (452/540 80·4–86·6) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% 95% CI 2·7–10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. Interpretation Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. Funding National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
Summary Background Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for ...10 days and 14 days with triple therapy for 14 days in first-line treatment. Methods For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov , number NCT01042184. Findings Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4–94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2–90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0–86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 95% CI 7·2–34·5; p=0·003) and PP analyses (13·7 8·3–40, p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. Interpretation Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. Funding National Taiwan University Hospital and National Science Council.
Background Abelmoschus manihot , a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess ...its efficacy and safety in patients with primary glomerular disease. Study Design Prospective, open-label, multicenter, randomized, controlled, clinical trial. Setting & Participants From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. Interventions A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks. Outcomes & Measurements The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. Results Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot , losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2 , respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively ( P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups ( P > 0.05), and there were no severe adverse events in any group. Limitations Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. Conclusions A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.
The aim of this study was to investigate the effect of outdoor activity during class recess on myopia changes among elementary school students in a suburban area of Taiwan.
Prospective, comparative, ...consecutive, interventional study.
Elementary school students 7 to 11 years of age recruited from 2 nearby schools located in a suburban area of southern Taiwan.
The children of one school participated in the interventions, whereas those from the other school served as the control group. The interventions consisted of performing a recess outside the classroom (ROC) program that encouraged children to go outside for outdoor activities during recess. The control school did not have any special programs during recess.
Data were obtained by means of a parent questionnaire and ocular evaluations that included axial length and cycloplegic autorefraction at the beginning and after 1 year.
Five hundred seventy-one students were recruited for this study, of whom 333 students participated in the interventional program, and 238 students were in the control school. At the beginning of the study, there were no significant differences between these 2 schools with regard to age, gender, baseline refraction, and myopia prevalence (47.75% vs. 49.16%). After 1 year, new onset of myopia was significantly lower in the ROC group than in the control group (8.41% vs. 17.65%; P<0.001). There was also significantly lower myopic shift in the ROC group compared with the control group (-0.25 diopter D/year vs. -0.38 D/year; P = 0.029). The multivariate analysis demonstrated that the variables of intervention of the ROC program and higher school year proved to be a protective factor against myopia shift in nonmyopic subjects (P = 0.020 and P = 0.017, respectively). For myopic subjects, school year was the only variable significantly associated with myopia progression (P = 0.006).
Outdoor activities during class recess in school have a significant effect on myopia onset and myopic shift. Such activities have a prominent effect on the control of myopia shift, especially in nonmyopic children.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Background Endoscopic papillary balloon dilation (EPBD) has a lower risk of hemorrhage than sphincterotomy and is easier to perform in altered/difficult anatomy. However, the sphincter of Oddi (SO) ...is only stretched but not cut after EPBD. Therefore, the biliary orifice is less opened, and failed stone extraction with EPBD alone occurs in up to 20% of patients. An uncut SO also may exacerbate pancreatic duct compression from edema after EPBD, and it increases the risk of pancreatitis. Objective To determine whether a longer duration for EPBD (5-minute vs conventional 1-minute) can further weaken the SO and reduce the rates of failed stone extraction and pancreatitis. Design Prospective, randomized trial. Setting Two tertiary-care referral centers. Patients This study involved 170 consecutive patients with common bile duct stones. Intervention EPBD for 1 minute (n = 86) or 5 minutes (n = 84). Main Outcome Measurements Failed stone extraction with EPBD alone and post-ERCP pancreatitis. Results Failed stone extraction with EPBD alone was less frequent with 5-minute EPBD (6 of 84, 7.1%) than with 1-minute EPBD (17 of 86, 19.8%), with a relative risk (RR) of 0.36 ( P = .024). The risk of pancreatitis was also lower with 5-minute EPBD (4 of 84, 4.8%) than with 1-minute EPBD (13 of 86, 15.1%), with an RR of 0.32 ( P = .038). Multivariable logistic regression analyses reaffirmed that 5-minute EPBD reduced the risk of failure with EPBD alone (odds ratio OR 0.19, P = .010) and pancreatitis (OR 0.28, P = .035). Limitations Endoscopists could not be blinded after the dilation durations were randomly assigned. Conclusion Compared with conventional 1-minute EPBD, 5-minute EPBD improves efficacy of stone extraction and reduces the risk of pancreatitis. ( Clinical trial registration number: NCT00451581 )
Background The functions of regulatory T (Treg) cells are important in immunity, and the regulatory mechanisms of Treg cell activities are not fully understood yet. Objectives We sought to ...investigate the role of insulin-like growth factor (IGF) 2 in the upregulation of Treg cell function. Methods The expression of insulin-like growth factor 2 receptor (IGF2R) on T cells was assessed by using flow cytometry. Treg cell functions were evaluated by assessing the suppressor effect on proliferation of other effector T (Teff) cells. The effect of IGF2 on regulating Treg cell functions were evaluated with a cell-culture model and a food allergy mouse model. Results Expression of IGF2R was observed in more than 90% of murine and human Treg cells but in less than 10% of effector CD4+ T cells. Activation of IGF2R and T-cell receptor induced marked Treg cell proliferation and release of TGF-β from Treg cells, which enhanced Treg cell immune suppressor effects on other Teff cell activities and allergic inflammation in the intestine. Conclusions Activation of IGF2R enhances Treg cell functions in suppressing other Teff cell activities and inhibiting allergic inflammation in the intestine.
Background Malfunction of the arteriovenous fistula (AVF) is an important cause of morbidity and hospitalization in hemodialysis (HD) patients. The aim of this study is to evaluate the effect of far ...infrared therapy on the maturation and patency of newly created AVFs in patients with chronic kidney disease stage 4 or 5. Study Design Randomized controlled study. Setting & Participants Patients with estimated glomerular filtration rate of 5-20 mL/min/1.73 m2. Intervention 40 minutes of far infrared therapy 3 times weekly for a year. Outcomes The primary outcome is the rate of AVF malfunction within 12 months, with malfunction defined as either: (1) thrombosis without thrill for AVFs not undergoing HD or (2) receiving any type of interventional procedure due to a lower Kt/V (<1.2) for patients undergoing HD. Secondary outcomes include: (1) cumulative primary unassisted AVF patency, defined as time from creation of the AVF to the first episode of AVF malfunction; (2) physiologic maturation of the AVF by the definition of AVF access blood flow (Qa) ≥500 mL/min and AVF diameter ≥4 mm at 3 months; and (3) clinical maturation of the AVF suitable for HD at 1 year. Measurements AVF Qa was measured by Doppler ultrasonography at 2 days and 1, 2, 3, and 12 months. Results We enrolled 122 patients who were randomly allocated to the intervention (n = 60) and control (n = 62) groups. In comparison to controls, patients in the intervention group had higher Qa values at 1, 2, 3, and 12 months; a higher rate of physiologic maturation (90% vs 76%; P = 0.04) at 3 months; and a lower rate of AVF malfunction (12% vs 29%; P = 0.02) but higher rates of AVF cumulative unassisted patency (87% vs 70%; P = 0.01) and clinical maturation (82% vs 60%; P = 0.008) within 12 months. Limitations This is a single-center nonblinded study. Conclusions Far infrared therapy improves the access flow, maturation, and patency of newly created AVFs in patients with chronic kidney disease stages 4 and 5.
Summary Background The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be ...mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. Methods An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. Findings The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26–45) for H7N9 and 70% (56–83%) for H5N1. Interpretation The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
The aberrant expression in some of the circadian clock-related proteins is associated with the pathogenesis of immune disorders.5 On the basis of results of Fig E1, we reasoned that one or some of ...the circadian clock-related proteins interfered with the expression of Foxp3 in CD4+ T cells. ...after treating with ACC, we isolated CD4+ T cells from the mouse intestine; the cells were analyzed by chromatin immunoprecipitation assay. Occurrence of food allergy after the career of day-/night-shift rotation Time (y) Patients with food allergy Percent Participants, n 668 668 40 Sex: male/female, n 334/334 334/334 20/20 Age (y), mean ± SD 38.5 ± 16 37.8 ± 15 38.8 ± 18 Total food allergy patients 86 (12.9) 26 (3.9)low * 0 Allergen distribution    Fish 18 (20.9) 5 (19.2) 0 Shell fish 12 (13.9) 3 (11.5) 0 Milk 11 (12.8) 3 (11.5) 0 Tree nuts 10 (11.6) 3 (11.5) 0 Soy 10 (11.6) 1 (3.8) 0 Fruit 8 (9.3) 6 (23.1) 0 Sesame seed 6 (6.9) 0 0 Wheat 6 (6.9) 0 0 Egg 6 (6.9) 5 (19.2) 0 Peanut 5 (5.8) 5 (19.2) 0 With other allergies    Asthma 1 (0.15) 1 (0.15)  Allergic rhinitis 2 (0.3) 0  Allergic dermatitis 1 (0.15) 2 (0.3)  Serum vitamin D (ng/mL) 30.8 ± 1.9 30.5 ± 1.3  Serum cortisol (ng/mL) 19.8 ± 2.4 20.2 ± 2.3  Height (m) 1.59 ± 0.06 1.58 ± 0.06  Weight (kg) 61.5 ± 3.5 60.6 ± 3.2  BMI (kg/m2) 24.2 ± 2.8 23.9 ± 2.1  Specific IgE (kU/L) 15.3 ± 21.6 <0.35 12.5 ± 18.2 <0.35 <0.35 Regulatory T cells (%) 2.14 ± 2.06 5.95 ± 5.14 2.28 ± 2.35 6.28 ± 7.29 6.68 ± 6.26 Serum IL-4 (pg/mL) 45.8 ± 25.9 12.6 ± 18.6 39.5 ± 31.3 9.8 ± 15.4 10.5 ± 8.6 SPT diameter (mm) 6.58 ± 4.87 2.11 ± 1.14 5.74 ± 3.85 1.86 ± 1.47 1.17 ± 1.08 1-2 5 5.8 3-4 70 81.4 5-6 9 10.5 >7 1 1.2 Table I Clinical features of human subjects Some patients were allergic to more than 1 allergen.
Summary Background Afatinib is an irreversible ErbB-family blocker with preclinical activity in non-small-cell lung cancer (NSCLC) with EGFR mutations. We aimed to assess the efficacy of afatinib in ...patients with lung adenocarcinoma and EGFR mutations. Methods In this phase 2 study, we enrolled patients from 30 centres in Taiwan and the USA with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) with EGFR mutations, who had no more than one previous chemotherapy regimen for advanced disease, an Eastern Cooperative Oncology Group performance status of 0–2, and no previous treatment with EGFR tyrosine-kinase inhibitors. We tested two afatinib starting doses: 50 mg daily and subsequently 40 mg daily, introduced to establish whether tolerability could be improved with retention of anti-tumour activity. The primary endpoint was the proportion of patients with a confirmed objective response (complete response or partial response), on the basis of Response Evaluation Criteria in Solid Tumors 1.0 (independent review). This study is registered with ClinicalTrials.gov , number NCT00525148. Findings 129 patients were treated with afatinib, 99 with a starting dose of 50 mg and 30 with a starting dose of 40 mg. 79 (61%) of 129 patients had an objective response (two complete responses, 77 partial responses). 70 (66%) of the 106 patients with the two common activating EGFR mutations (deletion 19 or L858R) had an objective response, as did nine (39%) of 23 patients with less common mutations. Similar proportions of patients had an objective response when analysed by starting dose (18 60% of 30 patients at 40 mg vs 61 62% of 99 patients at 50 mg). Of the two most common adverse events (diarrhoea and rash or acne), grade 3 events were more common in patients receiving a 50 mg starting dose (22 22% of 99 patients for diarrhoea and 28 28% of 99 patients for rash or acne) than they were in those receiving a 40 mg starting dose (two 7% of 30 patients for both diarrhoea and rash or acne); possibly treatment-related serious adverse events were also less common in patients receiving a 40 mg starting dose (two of 30 patients vs 14 of 99 patients). We recorded one possibly drug-related death (interstitial lung disease). Interpretation Afatinib shows activity in the treatment of patients with advanced lung adenocarcinoma with EGFR mutations, especially in patients with deletion 19 or L858R mutations. The efficacy of afatinib 40 mg should be compared with chemotherapy or other EGFR tyrosine-kinase inhibitors in EGFR-mutation-positive NSCLC. Funding Boehringer Ingelheim Inc.
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