Trends in the incidence of urothelial carcinoma in Taiwan after the ban on aristolochic acid-containing Chinese herbal preparations, 2001-2018: a national population-based cohort study.

PURPOSE: Urothelial carcinoma (UC) of the bladder (BUC) and the upper urinary tract (UTUC) are the two most common UCs. The incidence of UTUC in Taiwan is the highest worldwide. Aristolochic acid (AA) was identified as the main cause of UTUC in Taiwan. To explore trends in the incidence of UC in Taiwan after the ban on Chinese herbal preparations containing AA in 2003. METHODS: We used data from the Taiwanese National Health Insurance Research Database-linked Taiwanese National Cancer Registry for 2001-2018. UC was defined in accordance with the International Classification of Disease for Oncology. The age-standardized incidence was calculated on the basis of the World Health Organization standard population. Trends in the incidence were calculated as the annual percent change (APC) by using the Joinpoint regression program. RESULTS: Over the investigated period, the incidence of UC decreased at an average annual percent change (AAPC) of - 1.19% (95% CI - 1.47 ~ - 0.91, P < 0.001). However, the incidence in UTUC significantly increased, with the AAPC being 1.47% (95% CI 1.03 ~ 1.90, P < 0.001). In contrast, the incidence of BUC significantly decreased, with the overall AAPC being - 1.92% (95% CI - 2.3 ~ - 1.54, P < 0. 001). From 2001 to 2018, the overall incidence of UCs and BUC decreased in Taiwan, but the incidence of UTUC significantly increased. CONCLUSION: We suggest to apply the same review standards of new drug development process to herbal preparations and incorporate them into the adverse drug reaction or poison surveillance system. Most importantly, raise public awareness of the potential toxicity of phytotherapy.

Protein supplementation increases adaptations to endurance training: A systematic review and meta-analysis.

BACKGROUND: Trials that assessed the impact of protein supplementation on endurance training adaptations have reported conflicting findings. OBJECTIVE: To determine the impact of protein supplementation during chronic endurance training on aerobic capacity, body composition and exercise performance in healthy and clinical populations. DESIGN: A systematic database search was conducted for randomised controlled trials addressing the effects of protein supplementation during endurance training on aerobic capacity, body composition and exercise performance in PubMed, Embase, Web of Science, and CINAHL. Meta-analyses were performed to outline the overall effects of protein supplementation with all studies containing endurance training components. The effects of endurance training and add-on effects of protein supplementation were evaluated by the meta-analyses with endurance training-focused studies. RESULTS: Nineteen studies and 1162 participants contributed to the analyses. Compared with the control group, the protein supplementation group demonstrated greater improvements in aerobic capacity measured by mixed peak oxygen uptake (V̇O2peak) and peak workload power (Wpeak) (standardised mean difference [SMD] = 0.36, 95% confidence interval [CI]: 0.05 to 0.67), and V̇O2peak (mean difference [MD] = 0.89 mL‧kg-1‧min-1, 95% CI: 0.07 to 1.70); had a greater lean mass gain (MD = 0.32 kg, 95% CI: 0.07 to 0.58); and had a greater improvement in time trial performance (MD = -29.1s, 95% CI:-55.3 to -3.0). Secondary analyses showed that, in addition to the substantial improvement in V̇O2peak (MD = 3.67 mL‧kg-1‧min-1, 95% CI: 2.32 to 5.03) attributed to endurance training, protein supplementation provided an additional 26.4% gain in V̇O2peak (MD = 0.97 mL‧kg-1‧min-1, 95% CI: -0.03 to 1.97). CONCLUSION: Protein supplementation further increased aerobic capacity, stimulated lean mass gain, and improved time trial performance during chronic endurance training in healthy and clinical populations. PROSPERO REGISTRATION NUMBER: (CRD42020155239).

Effects of dextrose prolotherapy on tendinopathy, fasciopathy, and ligament injuries, fact or myth?: A systematic review and meta-analysis.

OBJECTIVES: Prolotherapy or proliferative therapy is a treatment option for damaged connective tissues involving the injection of a solution (proliferant) which theoretically causes an initial cell injury and a subsequent "proliferant" process of wound healing via modulation of the inflammatory process. Nonetheless, the benefits of dextrose prolotherapy have not been adequately evaluated. Therefore, the present study assesses the effectiveness and superiority of prolotherapy separately in treating dense fibrous connective tissue injuries. METHODS: PubMed, Scopus, and Embase were searched from the earliest record to February 18, 2019. This study included randomized controlled trials whichBoth analysis at individual studies level and pooled meta-analysis were performed. RESULTS: Ten trials involving 358 participants were included for review. At study level, the majority of comparisons did not reveal significant differences between dextrose prolotherapy and no treatment (or placebo) regarding pain control. The meta-analysis showed dextrose prolotherapy was effective in improving activity only at immediate follow-up (i.e., 0-1 month) (standardized mean difference [SMD]: 0.98; 95% confidence interval [CI]: 0.40-1.50; I = 0%); and superior to corticosteroid injections only in pain reduction at short-term follow-up (i.e., 1-3 month) (SMD: 0.70; 95% CI: 0.14-1.27; I = 51%). No other significant SMDs were found in this analysis. CONCLUSIONS: There is insufficient evidence to support the clinical benefits of dextrose prolotherapy in managing dense fibrous tissue injuries. More high-quality randomized controlled trials are warranted to establish the benefits of dextrose prolotherapy. REVIEW REGISTRATION: PROSPERO (CRD42019129044).

The effects of correction of vitamin D deficiency on arterial stiffness: A systematic review and updated meta-analysis of randomized controlled trials.

It is unclear whether nutritional vitamin D supplementation in vitamin d-deficient persons improves arterial stiffness. To conduct a meta-analysis of the effects of the nutritional vitamin D therapy on arterial stiffness in adults with vitamin D deficiency, the Scopus, PUBMED, EMBASE, and Cochrane databases were searched for systematic reviews conducted up to October 5, 2018. Randomized clinical trials that compared nutritional vitamin D therapy with placebo in adults with vitamin D deficiency were eligible. Two reviewers independently evaluated eligibility of all retrieved studies based on titles and abstracts. Meta-analysis was performed using random effect or fixed effects model and inverse variance method was used to calculate the effect using standardized mean difference (SMD) and weighted mean difference. A leave-one-out method was used for sensitivity analysis. The main outcome was arterial stiffness, indicated by the carotid-femoral pulse wave velocity (PWV). We identified 237 records, of which 9 satisfied the inclusion criteria of the study. Our meta-analysis included relatively high-quality placebo-controlled randomized trials. In a random-effects model, nutritional vitamin D was associated with significant reductions in the pooled difference of PWV [(SMD: -0.29; 95 % CI: -0.51 to -0.06), p = 0.01; Cochran's Q test: chi2 = 21.85; df = 9; p = 0.009; I2 = 59 %; n = 909 from 9 studies]. All sensitivity analyses yielded similar results. Nutritional vitamin D supplementation significantly improved arterial stiffness (PWV) in several subgroups by correcting vitamin D deficiency, for a study duration of ≥4 months and a daily dose of vitamin D3 ≥ 2000 IU. The study indicated that the correction of vitamin D deficiency by nutritional vitamin D supplementation may improve arterial stiffness in vitamin d-deficient persons, especially by the correction of vitamin D deficiency with a daily dose of vitamin D3 ≥ 2000 IU. However, further studies are required to confirm this.

Effects of protein supplementation on aerobic training-induced gains in cardiopulmonary fitness, muscle mass, and functional performance in chronic stroke: A randomized controlled pilot study.

BACKGROUND & AIMS: The beneficial effects of protein supplementation on aerobic exercise-induced gains in patients with stroke are currently unknown. This study evaluated the feasibility and potential value of protein supplementation with aerobic exercise among stroke survivors. METHODS: This double-blinded randomized controlled pilot study included 20 ambulatory persons with chronic (>6 months) stroke randomly assigned to either the protein (PRO) or carbohydrate (CHO) group. All participants received three 40-min cycling ergometric training sessions a week for 8 weeks. Training intensity at 60%-80% heart rate reserve was determined using cardiopulmonary exercise pretests. Immediately before and after each session, the PRO group received a 20-g protein-rich supplement, and the CHO group received a 20-g calorie-matched carbohydrate-rich supplement. Outcomes included changes in body composition, cardiopulmonary capacity, and clinical functional performance. RESULTS: Those completing the protocol (n = 18) received 18-24 cycling training sessions, achieving target training intensity without major adverse effects. Of the two groups, the PRO group tended to obtain greater aerobic capacity (effect size [ES]>0.5 in every cardiopulmonary index), greater improvements in functional performance (0.25 < ES < 1.00 in various clinical tests), and greater total lean mass versus total fat mass (ES = 0.52). CONCLUSIONS: Protein supplementation with aerobic exercise training tends to improve body composition, cardiopulmonary fitness, and function among persons with stroke. This study protocol is feasible, and future trials with larger sample sizes could confirm these results. TRIAL REGISTRATION: NCT03244527.

Effectiveness and Superiority of Rehabilitative Treatments in Enhancing Motor Recovery Within 6 Months Poststroke: A Systemic Review.

OBJECTIVE: To investigate the effects of various rehabilitative interventions aimed at enhancing poststroke motor recovery by assessing their effectiveness when compared with no treatment or placebo and their superiority when compared with conventional training program (CTP). DATA SOURCE: A literature search was based on 19 Cochrane reviews and 26 other reviews. We also updated the searches in PubMed up to September 30, 2017. STUDY SELECTION: Randomized controlled trials associated with 18 experimented training programs (ETP) were included if they evaluated the effects of the programs on either upper extremity (UE) or lower extremity (LE) motor recovery among adults within 6 months poststroke; included ≥10 participants in each arm; and had an intervention duration of ≥10 consecutive weekdays. DATA EXTRACTION: Four reviewers evaluated the eligibility and quality of literature. Methodological quality was assessed using the PEDro scale. DATA SYNTHESIS: Among the 178 included studies, 129 including 7450 participants were analyzed in this meta-analysis. Six ETPs were significantly effective in enhancing UE motor recovery, with the standard mean differences (SMDs) and 95% confidence intervals outlined as follow: constraint-induced movement therapy (0.82, 0.45-1.19), electrostimulation (ES)-motor (0.42, 0.22-0.63), mirror therapy (0.71, 0.22-1.20), mixed approach (0.21, 0.01-0.41), robot-assisted training (0.51, 0.22-0.80), and task-oriented training (0.57, 0.16-0.99). Six ETPs were significantly effective in enhancing LE motor recovery: body-weight-supported treadmill training (0.27, 0.01-0.52), caregiver-mediated training (0.64, 0.20-1.08), ES-motor (0.55, 0.27-0.83), mixed approach (0.35, 0.15-0.54), mirror therapy (0.56, 0.13-1.00), and virtual reality (0.60, 0.15-1.05). However, compared with CTPs, almost none of the ETPs exhibited significant SMDs for superiority. CONCLUSIONS: Certain experimented interventions were effective in enhancing poststroke motor recovery, but little evidence supported the superiority of experimented interventions over conventional rehabilitation.

Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass.

CONTEXT: Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. OBJECTIVE: This study aimed to evaluate the short-term effect of coadministration of calcitriol and denosumab on PTH secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. DESIGN AND SETTING: This was a 24-week, open-label study at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan. PATIENTS: Dialysis patients with SHPT (intact parathyroid hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled. INTERVENTION: Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH < 300 pg/mL. MAIN OUTCOME MEASURES: Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (Day 7, 14, and 21, and every month thereafter). RESULTS: iPTH significantly decreased (mean decrease, 58.28 ± 6.12%) with denosumab/calcitriol administration (P < .01) but not in the controls (patients not receiving denosumab). Parathyroid gland volume decreased (mean decrease, 21.98 ± 5.54%) with denosumab/calcitriol administration (P < .01) and progressively increased (20.58 ± 4.48%) in the controls (P < .05). Serum alkaline phosphatase and iPTH levels were significantly correlated to decreased iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse events were hypocalcemia (33.33%) and respiratory tract infection (4.17%). Hypocalcemia rapidly resolved with calcium and calcitriol supplements. CONCLUSIONS: Denosumab allows for supra-physiologic doses of calcitriol resulting in decreased parathyroid secretion and parathyroid hyperplasia. Supervised administration and weekly laboratory and clinical monitoring of serum calcium are recommended during the first month to prevent hypocalcemia.