International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011.

AIMS: Public controversy regarding the potential overdiagnosis and overmedication of children with attention-deficit/hyperactivity disorder (ADHD) has continued for decades. This study used the National Health Insurance Research Database of Taiwan (NHIRD-TW) to explore trends in ADHD diagnosis in youths and the proportion of those receiving medication, with the aim of determining whether ADHD is overdiagnosed and overmedicated in Taiwan. METHOD: Youths (age ≤18 years) who had at least two NHIRD-TW claims records with ADHD diagnosis between January 2000 and December 2011 were selected as the subject cohort. In total, the study sample comprised 145 018 patients with ADHD (mean age at a diagnosis of ADHD: 7.7 ± 3.1 years; 21.4% females). The number of cases of ADHD were calculated annually for each year (from 2000 to 2011), and the number of cases per year who received medication was determined as those with at least one record of pharmacotherapy (immediate-release methylphenidate, osmotic controlled-release formulation of methylphenidate, and atomoxetine) in each year. RESULTS: The prevalence rates of a diagnosis of ADHD in the youths ranged from 0.11% in 2000 to 1.24% in 2011. Compared with children under 6 years of age, the ADHD diagnosis rates in children aged between 7 and 12 years (ratio of prevalence rates = 4.36) and in those aged between 13 and 18 years (ratio of prevalence rates = 1.42) were significantly higher during the study period. The prevalence in males was higher than that in females (ratio of prevalence rates = 4.09). Among the youths with ADHD, 50.2% received medications in 2000 compared with 61.0% in 2011. The probability of receiving ADHD medication increased with age. More male ADHD patients received medications that females patients (ratio of prevalence rates = 1.16). CONCLUSIONS: The rate of ADHD diagnosis was far lower than the prevalence rate (7.5%) identified in a previous community study using face-to-face interviews. Approximately 40-50% of the youths with ADHD did not receive any medications. These findings are not consistent with a systematic public opinion about overdiagnosis or overmedication of ADHD in Taiwan.

Secular trends in incidence and recurrence rates of hip fracture: a nationwide population-based study.

We assessed the incidence of hip fracture and second hip fractures in Taiwan from 2001 to 2012. Age-standardized incidence rates decreased after 2005. However, mortality rate after first hip fracture was substantial compared to second hip fracture rate in a competing risk model. INTRODUCTION: The aim of the study is to assess the incidence rates (IRs) of hip fractures, including changes in trends and medical costs, and second hip fractures in the Taiwanese population. METHODS: The number of hip fractures and the associated medical costs were obtained from the annual report of the Ministry of Health and Welfare, Taiwan, for individuals ≥50 years of age. The data of population at risk were retrieved from annual population reports from the Ministry of the Interior, Taiwan. The incidence of second hip fractures was evaluated from the National Health Insurance Research Database of Taiwan for insured individuals aged ≥50 years from 2001 to 2011 with follow-up until 2013 using a competing risk model. RESULTS: The IR for the entire population increased from 332.7 to 336.5 per 100,000 person-years during 2001-2005 and decreased thereafter. This secular change was driven by a decrease in hip fractures for both men and women. The 10-year cumulative incidence rate of second hip fracture was 11.2% (95% CI 11.0-11.5%) in women and 7.9% (95% CI 7.6-8.1%) in men. Adjusted by consumer price index (CPI), the costs of hospitalization due to hip fracture increased from NTD 1.17 billion in 2001 to NTD 1.43 billion in 2012. However, the CPI-adjusted costs of each admission decreased from NTD 74944 in 2001 to NTD 65791 in 2012. CONCLUSIONS: Since 2006, the IR of hip fractures has been declining in Taiwan. The 10-year cumulative IR of mortality is substantial for individuals who with first hip fracture.

A systematic review and meta-analysis of adjuvant interferon therapy after curative treatment for patients with viral hepatitis-related hepatocellular carcinoma.

The efficacy of adjuvant interferon treatment for the management of patients with viral hepatitis-related hepatocellular carcinoma (HCC) following curative treatment is controversial. We have conducted a systematic review with meta-analysis to assess the effects of adjuvant interferon therapy on survival outcomes. Randomized and nonrandomized studies (NRSs) comparing adjuvant interferon treatment with the standard of care for viral hepatitis-related HCC after curative treatment were included. CENTRAL, Medline, EMBASE and the Science Citation Index were searched with complementary manual searches. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS). Nine randomized trials and 13 NRSs were included in the meta-analysis. These nine randomized trials included 942 participants, of whom, 490 were randomized to the adjuvant interferon treatment group and 452 to the control group. The results of meta-analysis showed unexplained heterogeneity for both RFS and OS. The 13 NRSs included 2214 participants, of whom, 493 were assigned to the adjuvant interferon treatment group and 1721 to the control group. The results of meta-analysis showed that, compared with controls, adjuvant interferon treatment significantly improved the RFS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.52-0.84, I(2) = 29%] and OS (HR 0.43, 95% CI 0.34-0.56, I(2) = 0%) of patients with hepatitis C virus-related HCC following curative treatment. There was little evidence for beneficial effects on patients with hepatitis B virus-related HCC. Future research should be aimed at clarifying whether the effects of adjuvant interferon therapy are more prominent in hepatitis C patients with sustained virological responses.

Cloning, sequencing, expression and characterization of the manganese superoxide dismutase gene from Vibrio alginolyticus.

The sodA gene coding for manganese superoxide dismutase from the marine microorganism Vibrio alginolyticus was cloned, sequenced and over-expressed in Escherichia coli using the pET20b (+) expression vector. The full-length gene was consisted of 603bp open reading frame, which encoded a polypeptide of 201 amino acid residues, with a calculated molecular weight of 22672Da. The deduced amino acid sequence of the sodA showed considerable homology to other Mn-SODs. The recombinant enzyme was efficiently purified from crude E. coli cell lysate by the metal ion affinity chromatography. The recombinant VAMn-SOD resisted thermo-denaturation up to 60 degrees C and was insensitive to inhibitors such as H2O2, NaN3 and diethyldithiocarbamic acid.

Cloning and characterization of manganese superoxide dismutase gene from Vibrio parahaemolyticus and application to preliminary identification of Vibrio strains.

The sodA gene coding for manganese superoxide dismutase (Mn-SOD) from the marine microorganism Vibrio parahaemolyticus was cloned, sequenced, and overexpressed in Escherichia coli by use of the pET20b (+) expression vector. The full-length gene consisted of a 588-bp open reading frame and encoded a polypeptide of 196 amino acid residues, with a calculated molecular mass of 21,713 Da. The recombinant enzyme was efficiently purified from crude E. coli cell lysate by metal ion affinity chromatography. The recombinant VPMn-SOD resisted thermo-denaturation up to 60 degrees C and was insensitive to such inhibitors as EDTA, NaN3 and diethyldithiocarbamic acid. The specificity of V. parahaemolyticus Mn-SOD gene probe was analyzed by cross-species polymerase chain reaction to provide information for Vibrio strain identification.

Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line.

To better understand the mechanism(s) underlying lung cancer invasion and metastasis, a Transwell invasion chamber was used to select progressively more invasive cancer cell populations from a clonal cell line of human lung adenocarcinoma, CL1. Five sublines with progressive invasiveness, designated CL1-1, CL1-2, CL1-3, CL1-4, and CL1-5, were obtained through this in vitro selection process. Their invasive abilities through basement membrane matrix showed a 4- to 6-fold increase over that of the parental cells. Moreover, the sublines manifested an increase in their colony-forming ability on soft agar, tumorigenicity, and metastatic potency in severe combined immunodeficiency (SCID) mice. Examining the phenotypes of the cell lines revealed increased expression of 92 kD gelatinase and an increase in the cell population stained with anti-keratin-8 and -18 antibodies. Clonal isolation of anti-keratin-18-antibody-positive and -negative cell populations demonstrated a correlated enhancement of the invasiveness of these cells and their expression of keratin-18. These results support the notion that the metastatic behavior of lung cancer cells can be characterized with this in vitro system, and that the properties of these progressively invasive cancer cells can be clonally studied.