Testing of Newly Developed Wide-Field Dual-Array Suprachoroidal-Transretinal Stimulation Prosthesis in Dogs.

Purpose: This study was conducted to investigate the feasibility of a newly developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in dogs and to examine its biocompatibility and stability over a 4-month period. Methods: Three types of STS dual arrays were designed and tested. The STS dual-array was implanted into a scleral pocket of the left eye of six healthy beagle dogs. Ophthalmic examinations, fundus photography, fluorescein angiography (FA), electroretinography (ERG), and functional testing of this system were conducted postoperatively. The dogs were euthanatized at the end of the experiment, and their eyes were enucleated and histologically examined. Results: All prostheses were successfully implanted without complications, and no serious adverse event occurred during the postoperative period. Fundus photographs and FA showed no serious damage in the retina surrounding the arrays. The ERGs recorded from the implanted eyes showed no significant differences from those from control eyes. Histological evaluations demonstrated good preservation of the retina over the array. However, system failure occurred in 50% of the dogs owing to dog-specific habits. Conclusions: Implantation of this prosthesis system in dogs is feasible and can be performed without significant damage to the eye. The biocompatibility and stability of the array were good during the observation period, but the low durability of the system against dogs (not humans) is an issue to be resolved in the future. Translational Relevance: This study suggests that this wide-field dual-array prosthesis might widen the visual field and might be useful for patients with retinitis pigmentosa.

Association of Low Sputum Smear Positivity among Tuberculosis Patients with Interferon-Gamma Release Assay Outcomes of Close Contacts in Japan.

Risk prediction and response measures may differ in tuberculosis (TB) patients with low sputum smear positivity for acid-fast bacillus (AFB) compared to those who are smear negative. However, previous studies using the tuberculin skin test (TST) did not show that differences in measures are important. This study compared results of interferon-gamma release assays (IGRA) between contacts of pulmonary TB patients with AFB smear positivity and those with smear negativity using QuantiFERON®-TB Gold In-Tube (QFT) assays. Close contacts of TB patients with culture-confirmed infections between April 2010 and December 2012 in Ibaraki, Japan, were enrolled, and 439 Japanese contacts of 129 index TB patients were examined. Adjusted odds ratios of QFT in contacts were 0.68 (95% confidence interval: 0.17-2.8) for AFB scanty patients, 1.12 (0.45-2.8) for AFB 1+, 1.20 (0.48-3.0) for AFB 2+, and 4.96 (1.9-12.9) for AFB 3+, compared to those who were smear negative. Differences in IGRA positivity were not significant between close contacts of TB patients with low positive and negative smears.

[TREATMENT OF LATENT TUBERCULOSIS INFECTION WITH A COMBINATION OF ISONIAZID AND RIFAMPICIN].

[Purpose] To conduct a literature review on clin- ical studies and national guidelines in various countries, for the purposes of facilitating discussion regarding whether latent tuberculosis infection (LTBI) treatment regimens com- posed of isoniazid and rifampicin should be introduced in Japan. [Methods] For clinical studies, 23 non-randomized studies and 10 randomized studies in the literature were reviewed. [Results] In patients who had received treatments com- posed of isoniazid and rifampicin ([HR]; largely 3 months), compared with those who had received isoniazid monother- apy ([H]; largely 6 to 9 months), both frequency and sever- ity of liver dysfunction tended to be reduced, but adverse drug effects increased in general. Treatment completion rate tended to be higher in those who had received HR than in those who had received H. Preventive effects of HR seemed to be at least equivalent, or somewhat superior, to H. Many national guidelines of the European Union and other coun- tries reviewed in this study recommended HR as an LTBI treatment regimen, and generally provided a high level of evidence. [Conclusion] 3HR treatment has been well studied in many clinical and randomized studies, and seems to have garnered a high level of merit in order to be introduced as one of the LTBI treatment regimens in Japan.

[FREQUENCY AND RISK FACTORS OF SEVERE LIVER DYSFUNCTION IN ISONIAZID MONO-THERAPY FOR LATENT TUBERCULOSIS INFECTION].

[Purpose] To investigate the frequency and risk factors of severe liver dysfunction in patients receiving isoniazid (INH) mono-therapy for latent tuberculosis infection (LTBI). [Objectives and Methods] A retrospective study of patients receiving INH mono-therapy for LTBI in the single medical institute in Japan. [Results] A total of 845 subjects, aged between 20 and 70 years old, were enrolled in this study. Grade 3 liver dysfunction (the highest value between AST and ALT [=M], 500 IU/L≤ and less than 1000 IU/L) was found in 1.9% (16/845) of cases. Grade 4 liver dysfunction (M≥ 1000 IU/L) was found in 1.4% (12/845) of cases. The frequency of Grade 3-4 liver dysfunction increased with age, in patients above 40 years of age. The frequency of Grade 3 and Grade 4 liver dysfunc- tion was 2.0% (4/202) and 1.0% (2/202), respectively, in patients aged between 40 and 49 years, and 2.4% (3/123) and 3.3% (4/123), respectively, in patients aged between 60 and 69 years. The following factors were associated with an increased risk of severe liver dysfunction: hepatobiliary abnormalities, consumption of alcohol 5 times or more per week before commencing INH, and abnormal high values of ALP before commencing INH. [Conclusion] Severe liver dysfunction is not rare in patients above 40 years of age, and the indication for LTBI treatment in these patients should be evaluated carefully, balancing the risk of severe liver dysfunction and the benefits of preven- tive effects.

[[LIVER TOXICITY DUE TO RIFAMPICIN MONOTHERAPY IN LATENT TUBERCULOSIS INFECTION].]

To investigate the outcome of rifam- picin (RFP) monotherapy for latent tuberculosis infection (LTBI) and the incidence of RFP-induced liver toxicity. [Method] We conducted a retrospective chart review of patients who received RFP monotherapy as LTBI treatment at the Daiichi Dispensary Clinic. [Result] Of 61 patients who received RFP monotherapy, the treatment completion rate was 88.5%, self-termination rate was 3.3%, abandonment rate due to adverse drug effects was 8.2% (5 cases: 3 cases of skin eruption and 2 cases of liver dysfunction). Among the 2 cases of liver dysfunction, I was not associated with abnormal alkaline phosphatase (ALP) or gamma-glutamyl transferase (y GTP) levels. Among patients with liver dysfunction who did not discontinue RFP mono- therapy, no cases-of severely abnormal ALP and/or y GTP levels were reported. [Conclusion] The incidence of liver toxicity due to RFP is lower than that observed with isoniazid, and liver dysfunction due to RFP was not always associated with abnormal of ALP and/or yGTP levels.

[INCREASE IN THE NUMBER OF INFANTS WITH KOCH PHENOMENON AFTER BCG VACCINATION].

PURPOSE: To investigate the trends in the number of infants diagnosed with Koch phenomenon after BCG vaccination following the change in the timing of the vaccination. METHOD: We extracted and analyzed data from infants aged ≤ 1 year diagnosed with latent tuberculosis infection (LTBI) or active tuberculosis, registered in the Japanese tuberculosis surveillance system, from May 2012 to the end of the year, and from May 2013 to the end of the year. RESULT: There was no increase in active tuberculosis cases between the two periods (5 patients each). However, the number of infants with LTBI doubled (45 to 90), presumably because Koch phenomenon developed after BCG vaccination. CONCLUSION: After changing the timing of vaccination, the number of infants experiencing Koch phenomenon appears to have increased. However, more in-depth analysis of this finding is required.

Cross-sectional studies of tuberculosis prevalence in Cambodia between 2002 and 2011.

OBJECTIVE: To measure trends in the pulmonary tuberculosis burden between 2002 and 2011 and to assess the impact of the DOTS (directly observed treatment, short-course) strategy in Cambodia. METHODS: Cambodia's first population-based nationwide tuberculosis survey, based on multistage cluster sampling, was conducted in 2002. The second tuberculosis survey, encompassing 62 clusters, followed in 2011. Participants aged 15 years or older were screened for active pulmonary tuberculosis with chest radiography and/or for tuberculosis symptoms. For diagnostic confirmation, sputum smear and culture were conducted on those whose screening results were positive. FINDINGS: Of the 40,423 eligible subjects, 37,417 (92.6%) participated in the survey; 103 smear-positive cases and 211 smear-negative, culture-positive cases were identified. The weighted prevalences of smear-positive tuberculosis and bacteriologically-positive tuberculosis were 271 (95% confidence interval, CI: 212-348) and 831 (95% CI: 707-977) per 100,000 population, respectively. Tuberculosis prevalence was higher in men than women and increased with age. A 38% decline in smear-positive tuberculosis (P = 0.0085) was observed with respect to the 2002 survey, after participants were matched by demographic and geographical characteristics. The prevalence of symptomatic, smear-positive tuberculosis decreased by 56% (P = 0.001), whereas the prevalence of asymptomatic, smear-positive tuberculosis decreased by only 7% (P = 0.7249). CONCLUSION: The tuberculosis burden in Cambodia has declined significantly, most probably because of the decentralization of DOTS to health centres. To further reduce the tuberculosis burden in Cambodia, tuberculosis control should be strengthened and should focus on identifying cases without symptoms and in the middle-aged and elderly population.

[Investigation of a new treatment outcome index for tuberculosis].

PURPOSE: To investigate a new treatment outcome index that may be useful in the Japanese tuberculosis surveillance system. OBJECTIVE AND METHOD: For sputum smear-positive primary tuberculosis patients, we estimated (a) treatment completion rates at the end of the next year of registration, and (b) treatment completion rates within 1 year from starting treatment in cases in which ≥ 1 year of treatment are indicated. For (a), we estimated treatment completion rates for newly registered cases during 2009 in the Japanese tuberculosis surveillance system, specifically at Fukujuji Hospital, which has a highly specialized tuberculosis treatment unit. For (b), we estimated the above-mentioned cases as well as those of "A" Public Health Center. RESULT: (a): The treatment completion rate at the end of the next year of registration was estimated to be 88.7% for newly registered cases during 2009 in the Japanese tuberculosis surveillance system. Among 66 jurisdictions, the highest and lowest completion rates were 100% and 58.3%, respectively, with a standard deviation of 6.7%. For Fukujuji Hospital cases, the completion rate was 93.1%. (b): The treatment completion rate within 1 year from the start of treatment was estimated to be 76.4% for newly registered cases during 2009 in the Japanese tuberculosis surveillance system. Among 66 jurisdictions, the highest and lowest completion rates were 90.9% and 44.1%, respectively, with a standard deviation of 8.8%. For Fukujuji Hospital and "A" Public Health Center cases, the completion rates were 91.1% and 80.0%, respectively. CONCLUSION: As a new treatment outcome index, treatment completion rates within 1 year might be more accurate than the treatment completion rate at the end of the next year of registration.

[Importance of monitoring the drug dosage and treatment duration for the management of tuberculosis patients at public health centers].

PURPOSE: On the basis of actual field data, we investigated the importance of monitoring the drug dosage and treatment duration for the supportive care of patients with tuberculosis who were being treated at public health centers. PATIENTS & METHODS: Data of the drug dosage of principal anti-tuberculosis drugs and the treatment duration for the registered patients with tuberculosis at the Shinjuku-ku Public Health Center were analyzed. RESULTS: The actual dosage of rifampicin and isoniazid according to the "recommended" dosage was administered to 57.3% (67/117) and 82.0% (114/139), respectively, patients with tuberculosis registered at the Shinjuku-ku Public Health Center. In contrast, in patients with tuberculosis who were treated at a highly specialized tuberculosis hospital, the rates were 81.0% (98/121) and 93.5% (86/92), respectively; for both drugs, the rates were significantly higher in this hospital than in the Shinjuku-ku Public Health Center. For the treatment duration, of 92 patients registered at the Shinjuku-ku Public Health Center who could have completed standard treatment in the standard duration, the actual treatment durations were shorter than the standard duration in 15.2% of the patients (14/92; -32 to -1 days), and longer than the standard duration in 77.2% (71/92; 2 to 146 days); the total superfluous treatment days for the latter 71 patients were 1,877 days. The treatment durations were more than 2 weeks shorter or longer than the standard duration for 31 patients, and in 71.0% (22/31) of these patients, no specific reason could be determined as to why the treatment durations were not standard. CONCLUSION: In a significant number of patients, the drug dosage and treatment duration were not according to the standard values. By using this data about the management of the drug dosage and treatment duration for the supportive care of patients with tuberculosis treated at public health centers, we may improve quality of the provided supportive care.

Antithyroid drug treatment for graves' disease in children: a long-term retrospective study at a single institution.

BACKGROUND: The management of Graves' disease (GD) in children is associated with a dilemma. Although the established initial treatment for GD in children is antithyroid drug (ATD) treatment, the remission rate in children is said to be lower than in adults, and severe propylthiouracil-induced adverse events (AEs) are an issue. Definitive treatments are effective, but they often result in permanent hypothyroidism and the need for lifelong T4 supplementation. OBJECTIVE: The objective of this study was to investigate the outcome of ATD treatment, identify significant predictors of a remission, and evaluate the AEs of ATDs in a large pediatric population of GD patients. METHODS: We retrospectively assessed the reports of 1138 children up to 18 years of age who had been newly diagnosed with GD at our institution between 1982 and 2006. Their median age at diagnosis was 16 years (range: 3-18 years), and there were 995 females and 143 males. All patients were initially treated with an ATD. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing ATD treatment and the absence of any relapses during the follow-up period. RESULTS: Of the 1138 patients, 723 continued on ATD treatment, 271 underwent surgery or radioactive iodine therapy, and 144 dropped out. Of the 723 patients who continued on ATD treatment, ATD treatment was subsequently ongoing in 84 and was discontinued in 639 (median duration of treatment: 3.8 years; range: 0.3-24.8 years). Of the 639 patients who discontinued ATD treatment, 334 (46.2%) achieved a remission, 247 (34.2%) experienced a relapse, and 58 (8.0%) dropped out. The cumulative remission rate increased with the duration of ATD treatment up until five years. No significant predictors of a remission were identified. The overall incidences of AEs associated with methimazole and propylthiouracil were 21.4% and 18.8% respectively. There were no fatal AEs in our population. While most AEs (91.6%) occurred within the first three months of ATD treatment, 2.7% developed more than two years after the start of ATD treatment. Seven of the eight late-onset AEs were induced by propylthiouracil. CONCLUSION: Long-term ATD treatment is a useful treatment option for GD in children.

[Use of regular check-ups after completion of treatment for latent tuberculosis infection].

PURPOSE: To evaluate the efficacy of regular examination (primarily by chest radiography) following treatment for latent tuberculosis infection (LTBI), we attempted to estimate the frequency and time to onset of active tuberculosis after completion of LTBI treatment. OBJECTS & METHODS: From the Japanese national surveillance data of 2008-2011, we extracted and analyzed the number of active tuberculosis cases after the end of LTBI treatment that was registered during 2008-09. RESULTS: Among LTBI cases registered during 2008-09 (n = 8951), 56 active tuberculosis cases following LTBI treatment were detected by the end of 2011. Frequency of onset of active tuberculosis by the end of the second year after registration of LTBI cases were as follows: 0.57% (51/8951), all active tuberculosis cases; 0.10% (9/8951), smear-positive lung tuberculosis cases; and 0.22% (20/8951), all bacteria-positive lung tuberculosis cases. In 37 active tuberculosis cases for which the date of completion of LTBI treatment was available, 12 cases were diagnosed within 1 year and 22 within 2 years of the completion of LTBI treatment. CONCLUSION: The frequency of onset of active tuberculosis after completion of LTBI treatment was relatively low, but it did not decrease with time in the following 2 years. Hence, the validity of regular examination should be assessed, rather than specifying the duration of regular examinations after completion of LTBI treatment.

Characteristics and treatment outcomes of tuberculosis cases by risk groups, Japan, 2007-2010.

INTRODUCTION: We studied the characteristics and treatment outcomes of the following risk groups for tuberculosis (TB): those with HIV and diabetes mellitus (DM), contact cases, the homeless, foreigners, health care workers (HCW) and the elderly. METHOD: A descriptive cross-sectional study was conducted by analysing the Japanese tuberculosis surveillance data of all cases registered between 2007 and 2010 (n = 96 689). RESULTS: The annual proportion of TB cases by risk group was stable over the study period, although there was a slight but significant increase observed for foreigners and elderly cases. Homeless and elderly TB cases had the highest DM co-morbidity (16.6% and 15.3%). HIV co-infection was low in all TB cases (0.2%) yet highest in foreigners (1.3%). HIV status of 45% of TB cases was unknown. The proportion of multi drug resistant (MDR) TB was similar among all risk groups (0.0-0.9%) except foreigners, at 3.4%. Males in most risk groups had higher mortality than females; the mortality of all TB cases in all age groups for both males and females were 3.6-24 times higher than the general population. DISCUSSION: Reasons for the high proportion of "HIV status unknown" should be investigated and improved. Contact tracing among foreign cases with MDR-TB should be a priority. Homeless persons should be screened for DM together with TB. Programs to enhance health and nutrition status may benefit tuberculosis prevention among the elderly. Tuberculosis screening and TB education are important for HCW.

Determination of pediatric reference levels of FT3, FT4 and TSH measured with ECLusys kits.

Reference ranges for serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in children were set using the assay kits currently used in clinical settings. A total of 342 children (111 males and 231 females) who were negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonographic examination of the thyroid gland were divided into 6 age groups: 4-6 years (45 children), 7-8 years (40), 9-10 years (53), 11-12 years (65), 13-14 years (83), and 15 years (56) for the study. FT3, FT4 and TSH levels were determined by electrochemiluminescence immunoassay (ECLIA) (ECLusys FT3, FT4 and TSH).The reference range for FT3 (pg/mL) was 2.91-4.70 for the age group of 4-6 years, 3.10-5.10 for the age group of 7-8 years, 3.10-4.87 for the age group of 9-10 years, 2.78-4.90 for the age group of 11-12 years, 2.77-4.59 for the age group of 13-14 years, and 2.50-4.64 for the age group of 15 years . The reference range for FT4 (ng/dL) was 1.12-1.67, 1.07-1.61, 0.96-1.60, 1.02-1.52, 0.96-1.52, 0.95-1.53. The reference range for TSH (µU/mL) was 0.62-4.90, 0.53-5.16, 0.67-4.52, 0.62-3.36, 0.54-2.78, 0.32-3.00. Serum FT3, FT4 and TSH levels in children differ from those in adults. It is, therefore, of importance to perform evaluation of thyroid function in children using reference values appropriate for the chronological ages, because misdiagnosis of hypothyroidism or inappropriate secretion of TSH (SITSH) and oversight of mild subclinical hypothyroidism could occur if the diagnosis is made using reference values for adults.

Does Hürthle cell carcinoma of the thyroid have a poorer prognosis than ordinary follicular thyroid carcinoma?

BACKGROUND: Hürthle cell carcinoma (HCC) is a rare form of thyroid carcinoma and is considered an oxyphilic variant of follicular thyroid carcinoma. However, little is known about its biological characteristics or clinical behavior. We conducted a retrospective study to determine whether the prognosis of HCC differs from that of ordinary follicular thyroid carcinoma (OFC). METHODS: The subjects were the 558 patients with follicular thyroid carcinoma who underwent initial surgery at our institution between 1989 and 2010 and consisted of 73 patients with HCC and 485 patients with OFC. There were 410 females and 148 males, and their median age was 51 years. A univariate analysis was conducted in relation to cumulative cause-specific survival (CSS) according to the Kaplan-Meier method for the following variables: age at the time of initial surgery, gender, tumor size, invasiveness, distant metastasis at presentation, and histological type (HCC vs OFC). Differences between groups were analyzed for significance by the log-rank test. Multivariate analysis was performed by using the Cox proportional hazard model. RESULTS: A total of 4 patients (5.5%) in the HCC group had distant metastasis compared with 106 patients (21.9%) in the OFC group. Significant factors in relation to CSS in the univariate analyses were age, tumor size, and invasiveness, but there were no significant differences between the HCC group and the OFC group. Multivariate analysis showed that age, tumor size, and distant metastasis at presentation were significant factors. CONCLUSIONS: HCC does not have a poorer prognosis than OFC.

Diagnostic accuracy of fine needle aspiration biopsy cytology and ultrasonography in patients with thyroid nodules diagnosed as benign or indeterminate before thyroidectomy.

Fine-needle aspiration biopsy cytology (FNABC) and ultrasonography (US) play an important role in differentiating benign thyroid nodules from malignant nodules. We retrospectively investigated the prevalence of follicular thyroid carcinoma (FTC) in patients with thyroid nodules whose FNABC and US readings were not malignant before thyroidectomy. Between 2007 and 2008, 3333 patients underwent thyroidectomy at our institution, and the 737 of them who had thyroid nodule that had been diagnosed as hyperplastic nodule or follicular tumor by FNABC and US preoperatively were the subjects in this study. Postoperative histopathology showed hyperplastic nodule in 416 patients, follicular adenoma in 200 patients, FTC in 99 patients, and other disease in 22 patients. By FNABC, 34 (6.7%) of the 505 patients with diagnosis as benign and 65 (28%) of the 232 patients with diagnosis as indeterminate, were diagnosed as having FTC. The diagnosis was FTC in 56 (9.6%) of the 582 patients with a preoperative diagnosis of hyperplastic nodule by US and 43 (27.7%) of the 155 patients with a diagnosis of follicular tumor by US. The diagnosis of FTC was made in 21 (4.8%) of 438 patients who were concurrently diagnosed as benign by FNABC and as hyperplastic nodule by US, and in 30 (34.1%) of 88 patients who were diagnosed as indeterminate by FNABC and follicular tumor by US. FNABC has been the mainstay for the preoperative evaluation of thyroid nodule. The results of this study showed that US can also be a useful tool for diagnosing FTC.

Characteristics and treatment outcomes of tuberculosis cases by risk groups, Japan, 2007-2010

Introduction: We studied the characteristics and treatment outcomes of the following risk groups for tuberculosis (TB): those with HIV and diabetes mellitus (DM), contact cases, the homeless, foreigners, health care workers (HCW) and the elderly. Method: A descriptive cross-sectional study was conducted by analysing the Japanese TB surveillance data of all cases registered between 2007 and 2010 (N = 96 689). Results: The annual proportion of TB cases by risk group was stable over the study period, although there was a slight but significant increase observed for foreigner and elderly cases. Homeless and elderly TB cases had the highest DM co-morbidity (16.6% and 15.3%), respectively. HIV co-infection was low in all TB cases (0.2%) yet highest in foreigners (1.3%). HIV status of 45% of TB cases was unknown. The proportion of multidrug-resistant TB (MDR-TB) was similar among all risk groups (0.0%–0.9%) except foreigner, at 3.4%. Males in most risk groups had higher mortality than females; the mortality of all TB cases in all age groups for both males and females was 3.6–24 times higher than the general population. Discussion: Reasons for the high proportion of “HIV status unknown” should be investigated and improved. Contact tracing among foreign cases with MDR-TB should be a priority. Homeless persons should be screened for DM together with TB. Programmes to enhance health and nutrition status may benefit TB prevention among the elderly. Tuberculosis screening and TB education are important for HCW.

[Medical service systems for tuberculosis in low-incidence countries].

OBJECTIVES: Currently, Japan has a near low incidence of tuberculosis (TB); the incidence is below 20/100,000. Considering this incidence, the medical service provision system needs to be restructured and related policies need to be revised. The Revised National Guidelines for TB Control, issued in May 2011 by the Ministry of Health, Labour, and Welfare, provided the policy towards achieving a low incidence of TB. This study aims to provide suggestions for restructuring the medical service system in Japan by analyzing the systems in selected countries with low incidence. METHOD: Between 2004 and 2010, we conducted tours to study TB control and medical services in the UK, the USA, Germany, The Netherlands, and Norway. In these tours, we visited the medical facilities, agencies implementing preventive activities, health departments of central and local governments, reference laboratories, technical agencies, non-governmental organizations, and other organizations involved in TB control in these countries. In addition, we collected information from published papers and related documents through the internet. This paper reports the policies and strategies adopted in these low-incidence countries, especially pertaining to medical service systems, directly observed treatment, short-course (DOTS) services, hospital beds and facilities, objectives and duration of hospitalization, and mechanisms for maintaining quality medical services. RESULTS: In all the visited countries, except Germany, TB patients were diagnosed and treated, as well as provided support such as DOTS, by a single organization or agency. In the US and Norway, DOTs was provided to all TB patients at chest centers and/or health centers. On the other hand, in the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) stated that DOT is not necessary for managing most active TB cases. In these countries there were 3 modes of treating infectious patients: home isolation, hospitalization for the first 2 weeks after initiating treatment, and hospitalization until smear examination results are negative. None of the countries had official standards for hospitalization. Measures to maintain service quality were integrating service providers, strengthening technical support, training and/or educating experts, and networking of personnel in charge. DISCUSSION: The study tours were conducted over 6 years, but no follow-up surveys were conducted. In each visit, we visited only a limited number of medical facilities, which may not be representative of that country. Obviously, this report does not aim to be a comparative study but to provide useful information for discussing the future direction of the medical service system in Japan. In Japan, TB is diagnosed and treated in hospitals and clinics, but contact surveys and other preventive activities are conducted in health centers. In this regard, Japan seems to be unique in that the ways to achieve collaboration among hospitals, health centers, and related organizations are emphasized in the revised National Guidelines for TB Control. Regardless of the DOT target group of a patient, healthcare providers in Japan are expected to ensure patient's adherence through patient-centered support in order to achieve successful treatment. In Japan, the central Government is expected to take responsibility to prevent infection. We suggest that the standards for lengths of hospital stay of TB patients should be revised such that the lengths are based on each patient's bacteriological condition and social setting. The revised National Guidelines for TB Control provide frameworks for ensuring the quality of medical services, but further discussions are warranted in order to plan and implement an effective strategy.

Changes in the thyroid function of Graves' disease patients treated by subtotal thyroidectomy.

The extent of thyroidectomy in Graves' disease is still a matter of controversy. Subtotal thyroidectomy has been used as the standard surgical procedure for Graves' disease in Japan, but high hyperthyroidism relapse rates have been reported. We retrospectively studied serial changes in the thyroid function Graves' disease patients after they had been treated by subtotal thyroidectomy and assessed whether subtotal thyroidectomy should be recommended as the standard surgical procedure for the treatment of Graves' disease. The subjects were 478 Graves' disease patients who underwent subtotal thyroidectomy at our institution between 1994 and 1997 and were followed up on a regular basis, and their thyroid function 2-3 years after surgery (the early period) and 8-10 years after surgery (the late period) was evaluated and compared. The evaluations in the late period showed that 57% of the euthyroid patients in the early period remained euthyroid, 30% had developed a relapse of hyperthyroidism, and 13 % had become hypothyroid. Approximately 80% of the patients who were overtly hyperthyroid or overtly hypothyroid in the early period remained so in the late period. During the entire periods 47 patients had subclinical hyperthyroidism and were followed up without any postoperative medication. Twenty (42.6%) of them developed overt hyperthyroidism, 11 (23.4%) experienced a spontaneous remission, and 16 (34%) continued to be subclinically hyperthyroid. Because thyroid function after subtotal thyroidectomy is unstable and reduces quality of life, subtotal thyroidectomy is concluded not to be suitable as a standard surgical procedure for the treatment of Graves' disease.

Outcomes and prognostic factors of 251 patients with minimally invasive follicular thyroid carcinoma.

BACKGROUND: Radioiodine ablation after total thyroidectomy is the generally accepted treatment for patients with widely invasive follicular thyroid carcinoma (FTC). The therapeutic strategy for minimally invasive FTC, on the other hand, is still a matter of controversy. The histological diagnosis of minimally invasive FTC is often made after lobectomy. The aim of this study was to determine the factors associated with the development of distant metastases in patients with minimally invasive FTC. METHODS: Between 1989 and 2006, 251 patients with minimally invasive FTC underwent initial surgery at our hospital. Their median follow-up period was 7.2 years. There were 194 women and 57 men. Their mean age at the time of surgery was 46 years. Distant metastases were diagnosed in 54 patients (21.5%). In 22 of them distant metastases were diagnosed at the time of the initial surgery (M1), and in the other 32 they were diagnosed during the follow-up period. Age at initial surgery, sex, primary tumor size, histological findings (differentiation, and extent of vascular and capsular invasion), completion total thyroidectomy, and distant metastases at initial surgery were assessed as prognostic factors for distant-metastases-free survival (DMFS) and cause-specific survival (CSS). The Kaplan-Meier method and log-rank test were used to analyze time-dependent variables. The Cox proportional hazard model was used to perform the multivariate analysis. RESULTS: Univariate analysis showed that age (45 years or older) and primary tumor size (4 cm or more) were significant prognostic factors related to postoperative distant metastases in the group of 229 patients without distant metastases at time of the initial surgery. The cumulative survival rate was significantly poorer in M1 patients, patients aged 45 years or older, and patients whose primary tumor size was 4 cm or more. Multivariate analysis showed that age was a significant prognostic factor both for DMFS and CSS. CONCLUSIONS: Age was the most powerful prognostic factor for patients with minimally invasive follicular thyroid cancer. The prognoses of patients younger than 45 years old were excellent and distant metastases rarely occurred. Routine completion total thyroidectomy and radioiodine ablation is thought unnecessary for these patients.