The association between season of birth, age at onset, and clozapine use in schizophrenia.

OBJECTIVE: This study aimed to determine whether the rate of clozapine use, an indicator of refractoriness in schizophrenia, is associated with the season of birth and age at onset in patients with schizophrenia based on nationwide data. METHODS: Patients with schizophrenia (n = 114 749) who received prescriptions for antipsychotic medication between 2008 and 2014 were retrospectively identified from the Korean National Health Insurance Service database. The study population was divided into three groups based on their age at the onset of schizophrenia (early, middle, and late onset). We assessed differences in the month of birth between patients and the general population. In addition, the cumulative clozapine use was calculated. RESULTS: Compared to the late-onset schizophrenia group, the early- and middle-onset groups showed a higher probability of birth during the winter season. In addition, the early-onset group showed the highest cumulative clozapine use rate. In the middle-onset group, the initiation of clozapine use was significantly earlier for patients born in winter compared to those born in summer. CONCLUSION: Our results indicate that the age at onset is an important factor in predicting the prognosis of schizophrenia patients. The season of birth also affects the prognosis, but with less robustness. Specifically, it appears that early disease onset and winter birth might be associated with poor outcomes in Korean patients with schizophrenia.

Current trends and future projections of hip fracture in South Korea using nationwide claims data.

UNLABELLED: Incidence of hip fracture increased in Korean populations over age 50 between 2008 and 2012, and the number of fractures was predicted to increase by 1.4 times by 2025. This is important information for public health planning. INTRODUCTION: The purposes of this study were to evaluate the trends in the incidence and mortality of hip fracture between 2008 and 2012 and predict the number of hip fractures in Korea through 2025 using nationwide claims data. METHODS: The data managed by the National Health Insurance Service were used to identify the hip fractures in patients aged >50 years between 2008 and 2012. Projections of hip fractures were conducted using the Poisson distribution from 2016 to 2025 in Korea. RESULTS: The incidence of hip fractures (per 100,000) increased by 14.1 % over the 5 years of the study, by 15.8 % in women and 10.9 % in men; the older age group showed a steep rise and shift in the incidence from 2008 to 2012. The cumulative mortality rates at 1 year after hip fractures were 17.2 % (3575/20,849) in 2008 and 16.0 % (4547/28,426) in 2012. Overall standardized mortality ratios (SMRs) for hip fracture were higher in men (11.93) than in women (11.22) and were higher than those in the general population in all age groups. In 2016, the total number of hip fractures was estimated to increase an overall of 1.4 times by 2025. CONCLUSIONS: The incidence of hip fracture continues to increase, and the related mortality is still high, although it has decreased over time. The socioeconomic burden of hip fracture is expected to increase in Korea along with the increased estimated number of fractures. Nationwide strategies should include attempts to reduce the future socioeconomic burdens of hip fractures.

Current and historical involvement of dentistry in child protection and a glimpse of the future.

Dental teams have been involved with child protection for over 40 years. This brief review summarises their involvement in the detection of various types of child abuse and goes on to discuss the gap between the proportions of dental professionals who suspect child abuse or neglect in their paediatric patients and those who refer such cases on. Potential reasons for this discrepancy are discussed, and a glimpse of the future is given as to where further research may be necessary to tackle this existing gap.

Skin tests in patients with hypersensitivity reaction to iodinated contrast media: a meta-analysis.

BACKGROUND: Patients with a previous history of hypersensitivity reaction (HSR) to iodinated contrast media (ICM) are at high risk of the development of HSR to ICM. Many studies have tried to evaluate the diagnostic potential of skin tests in this population but have not yet reached a common conclusion. We investigated the role of skin tests in patients with HSR to ICM in terms of positive rate, cross-reactivity rate, and tolerability to skin test-negative ICM according to the type of HSR. METHODS: We performed literature searches of the MEDLINE and EMBASE databases and included studies where skin tests were performed in patients with HSR to ICM, with extractable outcomes. Outcomes were pooled using a random-effects model. RESULTS: Twenty-one studies were included. Pooled per-patient positive rates of skin tests were 17% (95% CI, 10-26%) in patients with immediate HSR, and up to 52% (95% CI, 31-72%) when confined to severe immediate HSR. Among patients with nonimmediate HSR, the positive rate was 26% (95% CI, 15-41%). The pooled per-patient cross-reactivity rate was higher in nonimmediate HSR (68%; 95% CI, 48-83%) than that in immediate HSR (39%; 95% CI, 29-50%). Median per-test cross-reactivity rates between pairs of ICM were 7% (IQR, 6-9%) in immediate HSR and 38% (IQR, 22-51%) in nonimmediate HSR. Pooled per-patient recurrence rates of HSR to skin test-negative ICM were 7% (95% CI, 4-14%) in immediate HSR and 35% (95% CI, 19-55%) in nonimmediate HSR. CONCLUSION: Skin tests may be helpful in diagnosing and managing patients with HSR to ICM, especially in patients with severe immediate HSR.

Rupture of an endometrioma with extremely high serum CA-125 level (> 10,000 IU/ml) and ascites resembling ovarian cancer.

Carbohydate antigen 125 (CA-125) is a type of cell surface glycoproteins present in more than 80% of non-mucinous epithelial ovarian carcinomas; however, benign gynecologic conditions commonly cause a smaller increase in CA-125 level. This report presents the details regarding a 44-year-old woman with extremely high serum CA-125 level and ascites. She complained of having abdominal pain and abdominal distension. Her serum CA-125 level had been markedly elevated (> 10,000 IU!ml) and computed tomograpgy (CT) revealed an ovarian tumor and massive ascites. The cytological analysis showed no evidence of malignancy, however, the positron emission CT (PET-CT) scan suggested ovarian malignancy with peritoneal carcinomatosis. Under the impression that the patient had ovarian cancer, the present surgical team carried out an explorative laparotomy and discovered the ruptured bilateral ovarian endometriomas. In this study, it is suggested that clinicians carrying out differential diagnosis of pelvic mass with high serum CA-125 level and ascites should consider not only ovarian cancer but also ruptured endometrioma.

Fecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae in Korean community and hospital settings.

PURPOSE: The assessment and early recognition of risk factors for infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are important for infection control and proper treatment. The aim of the present study was to investigate the prevalence of fecal carriage of ESBL-E in healthy individuals and hospitalized high-risk patients in Korea and to compare the characteristics of ESBL-E in these two groups. METHODS: A total of 384 samples from 290 healthy individuals and 94 high-risk patients were collected. The screening of ESBL-E was performed using a commercial chromogenic medium. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 system. RESULTS: The prevalence of ESBL-E carriage was 20.3 % in healthy individuals and 42.5 % in high-risk patients. Escherichia coli comprised a large majority (96.6 %) of the isolates from healthy individuals, but Klebsiella pneumoniae was more commonly detected (45.0 %) in high-risk patients than in healthy individuals. K. pneumoniae isolates exhibited significantly higher resistance to ceftazidime, ampicillin, and carbapenem, and E. coli exhibited higher resistance to cefotaxime. E. coli from high-risk patients exhibited significantly higher resistance to levofloxacin and cefepime than that from healthy individuals. CONCLUSIONS: We demonstrated the high prevalence of ESBL-E carriage in Korea and clarified the characteristics of ESBL-E carriage in healthy individuals and high-risk patients. The distribution and antibiotic susceptibility of colonizing ESBL-E were different between the group of healthy individuals and the high-risk patients. Active surveillance of ESBL-E carriage is suggested for infection control, and the use of chromogenic agar appears to be an efficient method.

Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle.

The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle.

Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation.

The BRCA1 and BRCA2 genes are the strongest susceptibility genes identified for breast cancer worldwide. However, BRCA1/BRCA2 have been incompletely investigated due to their large size and the genomic rearrangements that occasionally occur within them. Here we performed a comprehensive mutational analysis for BRCA1/BRCA2 in 206 Korean patients with breast cancer. We analyzed all exons and flanking regions of BRCA1/BRCA2 by direct sequencing and screened deletions or duplications involving BRCA1/BRCA2 by multiplex ligation-dependent probe amplification. We reconstructed haplotypes using intragenic single nucleotide polymorphisms (SNPs) to investigate the possibility of a founder effect among recurrent mutations. In our series, 38 patients (18.4%) had one or more BRCA1/BRCA2 mutations including 10 novel ones. Three additional patients carried novel distinct unclassified variants with potentially harmful effects. No large deletions or duplications involving BRCA1/BRCA2 were identified in our series. Haplotype analyses and allele separation suggested that the most frequent mutation in Koreans, BRCA2:c.7480C>T, might have originated from a common ancestor. BRCA1/BRCA2 mutations were more frequent in a group with family history, bilateral cancer or multiple site cancer than in a group without the risk factors described or an unknown risk group. In contrast, mutation frequencies in the early-onset cancer group were not higher than in the unknown risk group. Our results will be helpful to understand the mutation spectrum in BRCA1/BRCA2 genes and establish a genetic screening strategy. In addition, this study suggests the possibility of the first true founder mutation of BRCA1/BRCA2 identified in the Korean population.

Usefulness of concurrent reading using thin-section and thick-section CT images in subcentimetre solitary pulmonary nodules.

AIM: To evaluate the differences in the characterization and recommendation for follow-up of subcentimetre solitary pulmonary nodules (SSPNs) between 5 and 1mm section CT, and to compare the assessments generated by four radiologists MATERIALS AND METHODS: Five hundred and twenty-nine patients who had SSPNs on chest CT reconstructed using both 5 and 1mm sections were enrolled. Two image subsets of 5 and 1mm CT images of each nodule were interpreted independently by four radiologists. Nodule size, consistency (solid, partly solid, non-solid), the presence of calcification, and recommendations for follow-up were evaluated. If a non-calcified solid nodule was confirmed using CT, recommendation for follow-up was based on Fleischner Society guidelines. Data assessed by each radiologist were compared, and interobserver agreements were determined using the intraclass correlation coefficients and kappa value. RESULTS: Using 1mm CT images, the nodule sizes were significantly larger than on 5mm CT images (paired t-test, p<0.01). The presence of calcification and nodule consistency were significantly different between 5 and 1mm CT images (McNemar test for the presence of calcification, p<0.01; Wilcoxon signed test for nodule consistency, p<0.01). On 1mm CT images there was significantly higher agreement regarding nodule consistency than on 5mm CT (kappa=0.78 and 0.67, respectively). CONCLUSIONS: Concurrent use of thin-section and thick-section CT can provide more accurate nodule assessment and higher interobserver agreement in SSPN.

Abscisic acid-mediated phytochrome B signaling promotes primary root growth in Arabidopsis.

Plant photomorphogenic responses have been studied mostly using the shoots, the core part of plant architecture that perceives light for photosynthesis and influences the overall processes of growth and development. While the roots are also known to respond to aboveground light through multiple routes of light signal transduction, root photomorphogenesis has been less highlighted until recently. A long-standing, critical question was how the underground roots are capable of sensing aerial light and how the root-sensed light signals trigger root photomorphogenesis. When the roots are directly exposed to light, reactive oxygen species (ROS) are rapidly produced to promote primary root elongation, which helps the roots to escape from the abnormal growth conditions. However, severe or long-term exposure of the roots to light causes ROS burst, which impose oxidative damages, leading to a reduction of root growth. We have recently found that phytochrome B (phyB) promotes abscisic acid (ABA) biosynthesis in the shoots and the shoot-derived ABA signals mediate ROS detoxification in the roots, lessening the detrimental effects of light on root growth. On the basis of these observations we propose that the phyB-mediated ABA signaling contributes to the shoot-root synchronization that is essential for optimal growth and performance in plants.

Prognostic significance of beta-catenin in colorectal cancer with liver metastasis.

AIMS: A decreased expression of beta-catenin has been known to be associated with tumour metastasis. The prognostic value of beta-catenin expression in colorectal cancer (CRC) patients with liver metastasis was evaluated. MATERIALS AND METHODS: Seventy patients who underwent curative resection for CRC with liver metastasis were included. Tissue samples from normal colon mucosa, primary CRC and metastatic liver lesions were prepared in tissue microarrays, and were stained by immunohistochemistry with beta-catenin antibody. The beta-catenin expression of primary CRC tissues and metastatic liver tissues was analysed. RESULTS: A high expression of beta-catenin (score > 6) was observed in 42.0% and 21.9% of primary colorectal tissues and metastatic liver tissues, respectively. The beta-catenin expression in metastatic liver tissues was significantly lower than in primary CRC tissues (P = 0.022). The patients were classified into two groups according to the difference in the beta-catenin expression score between the primary CRC and the liver metastasis. Group A was defined as patients showing a remarkably decreased expression of beta-catenin in their metastatic liver tissue and group B was defined as patients showing a maintained or increased beta-catenin expression in their metastatic liver tissue in comparison with their primary CRC. The overall survival and disease-free survival rates were better in group B than in group A, and this was statistically significant (P = 0.02, P = 0.002). CONCLUSION: The decreased expression of beta-catenin in a metastatic liver lesion may be a poor prognostic marker in CRC with liver metastasis and further investigation is necessary.

Development of a finger-like mechanism of end-effector for micro surgery.

Neurosurgery had been considered nearly impossible due to its technical difficulty and the danger to its special target organ, but with endoscopic methods, many such surgeries can be made safely through the nose. Endoscopic neurosurgery is limited by available instruments, however, and there remain some areas of the human body inaccessible to standard surgical tools. To overcome some of these limitations, in this study we developed a simple mechanism that could form a high curvature in a narrow space. The end product is a finger-like mechanism consisting of five body parts and four joints. All body parts are connected in series, having a total length of 20mm and a diameter of φ4mm. A four-bar linkage internally connects the body parts and joints, and a nitinol backbone was used to improve repeatability. The first joint is driven by a rod or wire, and the shape of the mechanism is determined by rotating the first joint, because the position of each joint depends on the position of the joint before it. The study verified that an image sensor in the end of the finger-like mechanism has a wider range of view, 210 degrees than a conventional endoscope of 100 degrees. Finally, skull model simulation suggests that this device could be used in real neurosurgical applications.

Growth factor-induced retinal regeneration in vivo.

It is apparent from a number of studies that the RPE has a remarkable ability to regenerate neural retina. While retinal regeneration from the RPE has not been reported in adult vertebrates, with the exception of the newt, there is evidence that many vertebrate species have the ability to regenerate a new neural retina during the early development. Studies of retinal regeneration in the chicken embryo have provided some insight into the requirements for this process. Recent investigations using copolymer implants as an intraocular delivery system for growth factors have demonstrated that the state of differentiation of RPE cells in the stage 22-24 chicken embryo can be altered in vivo by specific growth factors, aFGF and bFGF. These results raise the distinct possibility that variations in the local production of FGFs and their receptors in the eye during development may, in part, regulate the pathway of differentiation of RPE and neural retina precursors. Further research on the role of FGFs and their receptors in retinal development and regeneration will not only contribute to our understanding of how the differentiated state is achieved and maintained but may provide a foundation for future attempts to develop methods of treatment for various degenerative and proliferative diseases of the eye.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: July 2004. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Twenty-three randomised trials involving 3115 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% versus 58%) than six month therapy (Odds ratio (OR) 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR 0.75, 95% CI 0.39 to 1.43). Twelve trials examined the effect of Block-Replace versus Titration regimen. The relapse rates were similar in both groups at 51% in the Block-Replace group and 54% in the Titration group (Peto OR 0.86, 95% CI 0.68 to 1.08). Participants reporting rashes (10% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up with relapse rates being 31% (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR 1.15, 95% CI 0.79 to 1.67). AUTHORS' CONCLUSIONS: The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. The incidence of hypothyroidism was not reported and there were no deaths reported in the study populations.

Establishing comprehensive oral assessments for children with safeguarding concerns.

The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input.

A family of Ustilago maydis expression vectors: new selectable markers and promoters.

The cDNA expression system for Ustilago maydis has been expanded to include different selectable markers and promoters. These new elements allow the simultaneous expression of two genes in the same transformant.

Inhibition of human neutrophil bacteriocidal activity by extracellular substance from slime-producing Staphylococcus epidermidis.

The role of slime produced by Staphylococcus epidermidis as a virulence factor has been investigated by preincubating human neutrophils in fractions of extracellular material from cultures of slime-producing and non-slime-producing S. epidermidis. Extracellular product (molecular weight greater than 300,000) from slime-producing S. epidermidis did not affect neutrophil phagocytosis but did produce a generalized loss of bacteriocidal activity which was not found with non-slime-producing S. epidermidis, or broth.

Efficacy of allyl isothiocyanate in killing enterohemorrhagic Escherichia coli O157:H7 on alfalfa seeds.

Volatile compounds occurring in the essential oil of plants were tested for their efficacy in killing Escherichia coli O157:H7. Experiments using an agar disk assay revealed that exposure of the pathogen to 50 microl of eugenol, carvacrol, linalool, or methyl jasmonate in a 950-cc jar at 20, 37 or 47 degrees C for up to 48 h failed to inhibit colony formation. However, exposure to 8 microl of allyl isothiocyanate (AIT) (equivalent to 8.4 ppm in the air within the jar, if completely volatilized) resulted in more than a 7-log10 reduction in population of E. coli O157:H7 at 37 degrees C within 48 h; significant (P < or = 0.05) reduction in populations also occurred in the presence of 4 microl of AIT compared to 2 microl, which had no lethal affect. At 20 degrees C, the lethality of AIT was substantially less, although significant reduction occurred when disks were exposed to 8 or 10 microl of AIT compared to 4 or 6 microl and when exposed to 4 or 6 microl compared to 2 microl. Treatment with 10 microl of AIT for 5 h at 47 degrees C resulted in death of 6 log10 of E. coli O157:H7. The efficacy of AIT in killing E. coli O157:H7 on dry and wet alfalfa seeds was investigated. The pathogen, at an initial population of 2.7 log10 cfu/g of seed, was not recovered by direct plating (< 0.7 log10 cfu/g) or enrichment of wet seeds exposed to 50 microl of AIT/950-cc jar for 24 h at 37 or 47 degrees C. Exposure of dry seeds containing 2.9 log10 cfu of E. coli O157:H7 per g to an atmosphere containing 100 microl of AIT/950-cc jar (ca. 105 ppm AIT if completely volatilized) for 24 h at 47 degrees C did not eliminate viable E. coli O157:H7 cells. Unfortunately, the enhanced effectiveness of AIT in killing the pathogen on wet alfalfa seeds is offset by a dramatic reduction in seed viability. Nevertheless, the use of AIT as an alternative to chlorine for the purpose of killing E. coli O157:H7 and perhaps other pathogens on alfalfa seed holds promise. Factors that may influence conditions rendering increased sensitivity of E. coli O157:H7 to AIT without compromising seed viability should be investigated.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWERS' CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWER'S CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.