Objective To evaluate whether very early treatment in our patients would result in better clinical outcomes and to compare these data with other infantile-onset Pompe disease (IOPD) cohort studies. ...Methods In this nationwide program, 669 797 newborns were screened for Pompe disease. We diagnosed IOPD in 14 of these newborns, and all were treated and followed in our hospital. Results After 2010, the mean age at first enzyme-replacement therapy (ERT) was 11.92 days. Our patients had better biological, physical, and developmental outcomes and lower anti-rh acid α-glucosidase antibodies after 2 years of treatment, even compared with one group that began ERT just 10 days later than our cohort. No patient had a hearing disorder or abnormal vision. The mean age for independent walking was 11.6 ± 1.3 months, the same age as normal children. Conclusions ERT for patients with IOPD should be initiated as early as possible before irreversible damage occurs. Our results indicate that early identification of patients with IOPD allows for the very early initiation of ERT. Starting ERT even a few days earlier may lead to better patient outcomes.
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 Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five ...stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. Methods The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. Findings The national prevalence of chronic kidney disease was 11·93% (95% CI 11·66–12·28), but only 3·54% (3·37–3·68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19·87% 19·84–19·91 vs 7·33% 7·31–7·35). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1·83 1·73–1·93) and 100% higher for cardiovascular diseases (2·00 1·78–2·25), in a cohort that was observed for 13 years with median follow-up of 7·5 years (IQR 4·0–10·1). 10·3% (95% CI 9·57–11·03) of deaths in the entire population were attributable to chronic kidney disease, but 17·5% (16·27–18·67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1·20 1·16–1·24) increased risk of developing chronic kidney disease. Interpretation The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic. Funding None.
Background Immune system dysregulation is associated with end-stage renal disease. Although decreased cellular immunity increases susceptibility to herpes zoster, the risk of herpes zoster in ...patients with earlier stages of chronic kidney disease (CKD) is unclear. Study Design A matched-cohort study. Setting & Participants Data from the Taiwan Longitudinal Health Insurance Database (LHID) for 2004-2006 were analyzed. The study cohort included patients 18 years or older given a diagnosis of CKD (excluding patients treated by dialysis or transplant) in 2004-2005 (n = 13,321). The comparison cohort (n = 66,605) included 5 randomly selected age- and sex-matched controls for each patient in the study cohort. Predictor CKD. Incident cases of CKD were identified using the Taiwan LHID. CKD was ascertained from International Classification of Diseases , Ninth Revision, Clinical Modification ( ICD-9-CM ) codes. Outcomes Herpes zoster, ascertained from ICD-9-CM codes. All participants were followed up from the date of cohort entry until they developed herpes zoster or the end of 2006. Cox proportional hazard regressions were performed to compare the hazard rates of herpes zoster in the CKD cohort and the age- and sex-matched comparison cohort. Results We identified 13,321 patients with a diagnosis of CKD who matched the inclusion criteria. 1,602 patients developed herpes zoster during the study period, of whom 353 were from the CKD cohort and 1,249 were from the comparison cohort. After adjusting for potential confounding factors, CKD was associated independently with greater risk of herpes zoster (HR, 1.60; 95% CI, 1.41-1.81). Limitations Some patients with CKD or herpes zoster may have chosen not to seek medical care. Misclassification of CKD due to use of diagnostic codes also is a limitation. Conclusions This population-based cohort study indicated that patients with CKD are at increased risk of herpes zoster compared with the general population.
Many studies have investigated the association between markers for peripheral inflammation and risk of dementia, but the results have been conflicting. We aimed to evaluate the association between a ...specific inflammation marker, C-reactive protein (CRP), and dementia in an elderly Asian community cohort.
The cohort included 1436 individuals (ages 65 and older) from a national representative sample in Taiwan. Dementia incidence was identified using International Classification of Diseases, Ninth Revision codes for vascular dementia, Alzheimer disease, and nonvascular dementia. Baseline characteristics and CRP levels were determined. A Cox proportional hazard model and Fine and Grays model were adjusted for stroke and competing risk of death to estimate the association between inflammation and development of dementia.
During 11.04 years (median) of follow-up, 607 individuals (50.77%) died and 260 individuals (18.11%) were diagnosed with dementia. Those with high CRP had a 55% higher risk of dementia (hazard ratio 1.55; 95% confidence interval 1.21-2.00) compared with those with normal CRP. After adjusting for possible confounding cardiovascular risk factors, high CRP was independently associated with vascular dementia but not Alzheimer disease.
In this prospective study of an elderly Asian community cohort with more than 10 years of follow-up, the baseline serum CRP level was associated with future development of vascular dementia, but not Alzheimer disease after adjusting for common cardiovascular risk factors, stroke, and competing risk of death.
Abstract Purpose The safety and efficacy of continuous infusion vs bolus injection of intravenous loop diuretics to treat acute decompensated heart failure were debated. Our aim is to compare the ...administration routes of diuretics in hospitalized patients with acute decompensated heart failure. Methods A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of continuous infusion vs bolus administration of loop diuretics in patients with acute decompensated heart failure. The primary end points were urine outputs, body weight loss, all causes of mortality, and death from cardiovascular causes. Secondary end points were electrolyte imbalance, change in creatinine levels, tinnitus or hearing loss, and days of hospitalization. Results Ten randomized controlled trials with 518 patients were identified. Continuous infusion of diuretics was associated with a significantly greater weight loss (weighted mean difference, 0.78; 95% confidence interval, 0.03-1.54) compared with bolus injection. Urine output, the incidence of electrolyte imbalance, change in creatinine level, length of hospitalization, the incidence of ototoxicity, cardiac mortality, and all-cause mortality showed no significant differences between the 2 groups. Conclusion Meta-analysis of the existing limited studies did not confirm any significant differences in the safety and efficacy with continuous administration of loop diuretic, compared with bolus injection in patients with acute decompensated heart failure.
Abstract Background Recently, several studies revealed a much higher prevalence of later onset Fabry disease (FD) than previously expected. It suggested that later onset FD might present as an ...important hidden health issue in certain ethnic or demographic populations in the world. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement. Objectives The study analyzed a large-scale newborn screening program for FD to understand the natural course of later onset FD. Methods To date, 916,383 newborns have been screened for FD in Taiwan, including more than 1,200 individuals with the common, later onset IVS4+919G>A (IVS4) mutation. Echocardiography was performed in 620 adults with the IVS4 mutation to analyze the prevalence of left ventricular hypertrophy (LVH), and gadolinium-enhanced cardiac magnetic resonance imaging was performed in 129 patients with FD, including 100 IVS4 adults. Results LVH was observed in 67% of men and 32% of women older than 40 years. Imaging evidenced significant late gadolinium enhancement in 38.1% of IVS4 men and 16.7% of IVS4 women with the IVS4 mutation but without LVH. Seventeen patients underwent endomyocardial biopsies, which revealed significant globotriaosylceramide substrate accumulation in their cardiomyocytes. Conclusions Significant cardiomyocyte substrate accumulation in IVS4 patients led to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start enzyme replacement therapy after the occurrence of LVH or other significant cardiac manifestations in patients with later onset FD. This study also indicated the importance of newborn screening for early detection of the insidious, ongoing, irreversible cardiac damage in patients with later onset FD.
Objective To investigate the factors predicting spontaneous clearance of hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort from childhood into adult life. Study design ...Children with chronic hepatitis B virus (HBV) infection without treatment were followed longitudinally every 6 months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B vaccination history and the maternal HBV markers also were studied. Results A total of 349 children (205 male) were followed for 20.6 ± 4.4 years with initial ages of 8.4 ± 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The HBsAg titers decayed with age, with an average annual clearance rate of 0.58%. Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers ( P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for spontaneous HBsAg clearance ( P = .04). Those with HBsAg titer ≤1000 IU/mL at enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio = 5.23; P < .001). Using HBsAg titer ≤1000 IU/mL to predict HBsAg clearance, the sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%, and negative predictive value is 91.4%. Conclusions During long-term follow-up, spontaneous HBsAg clearance is most likely to occur in a patient born to a non-HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an initial HBsAg level ≤1000 IU/mL.
Growth-differentiation factor (GDF)-15 is a strong predictor of cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). However, the effects of GDF-15 on left ventricular ...(LV) remodeling have not been clearly elucidated. The aim of this study is to investigate whether GDF-15 will be of benefit in predicting LV remodeling, heart failure and death in patients with STEMI.
The authors enrolled 216 patients with STEMI who received measurement of GDF-15 level on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Clinical events, including all-cause death and readmission for heart failure, were followed up for a maximum of 3 years.
Patients with GDF-15 levels above the median had lower LV ejection fraction at baseline (43.9% versus 48.0%, P = 0.041) and at 6 months (51.5% versus 56.9%, P = 0.025). In univariable regression model, log-transformed GDF-15 level was not a predictor of increase in LV end-diastolic volume index at 6 months (P = 0.767). Kaplan-Meier survival curves showed that the combination of high GDF-15 and high N-terminal pro-B-type natriuretic peptide was a strong predictor of death and heart failure (P < 0.001). In multivariable Cox regression model, the independent predictors of death and heart failure were age, GDF-15 level and diabetes mellitus.
High GDF-15 level is a strong predictor of death and heart failure in patients with STEMI. Although patients with higher GDF-15 levels tend to have lower LV ejection fraction, they have similar degree of the increase in LV end-diastolic volume index at 6 months.
Objective To investigate the impact of menarche on the natural course of chronic hepatitis B virus (HBV) infection in women. Study design Young women who are positive for hepatitis B e antigen ...(HBeAg; n = 101) chronically infected with genotypes B and C HBV were recruited at a mean age of 4.57 ± 3.08 years, and a mean follow-up duration of 23.98 ± 3.77 years. Clinical data, including age at menarche, HBV genotypes, serum HBV viral loads, hepatitis B surface antigen (HBsAg) titers, and serial liver functional profiles were analyzed. Results Women with earlier onset of menarche had earlier spontaneous HBeAg seroconversion than others (hazard ratio, 2.0; P = .02) adjusting for HBV genotype and peak alanine aminotransferase levels before HBeAg seroconversion. The annual decrease in HBsAg titer from 15 to 20 years of age also was greater in the early menarche group compared with the late menarche group (0.11 ± 0.11 vs 0.05 ± 0.11 log10 IU/mL, P = .04). The baseline HBV viral load was also borderline low in female subjects with earlier menarche as compared with others ( P = .06). Earlier menarche onset was associated with higher spontaneous HBeAg seroconversion, HBsAg seroclearance, and HBsAg seroconversion rate before 15 years of age in females with chronic HBV infection. Conclusions Earlier puberty-onset, indicated by menarche-onset, was associated with earlier spontaneous HBeAg seroconversion and greater rate of HBV clearance before 15 years of age in female subjects with chronic HBV infection.
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