[[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.

[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.

[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.

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.

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.

[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.

Hepatotoxicity and cutaneous reactions after antithyroid drug administration.

OBJECTIVE: Use of the antithyroid drugs (ATDs) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). We investigated side effects associated with the 1st and 2nd ATDs. DESIGN AND PATIENTS: Four hundred forty-nine patients with untreated Graves' disease (GD) were randomly assigned to three groups according to ATD type and/or dosage: 15 mg/day MMI, 30 mg/day MMI and 300 mg/day PTU. The type, frequency and onset of side effects were assessed. We also studied the side effects associated with the 2nd ATD after cessation of the 1st ATD. MEASUREMENTS: Cutaneous reactions, liver dysfunction and other side effects were examined every 2 weeks after starting ATD administration. RESULTS: The overall frequency of side effects in patients taking 15 mg/day MMI was low. The frequencies of cutaneous reactions in patients taking 30 mg/day MMI and hepatotoxicity in those taking 300 mg/day PTU were high. Hepatotoxicity developed later than cutaneous reactions with PTU. Hepatotoxicity developed earlier in the 30 mg/day MMI group than in the other two groups. The frequency of side effects did not differ between the 2nd and 1st ATDs. Hepatotoxicity occurred at a higher frequency in patients who were switched from MMI to PTU because of hepatotoxicity of the former. CONCLUSION: Attention to the onset times of side effects and cross-reactivity of ATDs can lead to safer treatment of GD.

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.

[Nationwide survey of suitability of tuberculosis wards for in-hospital care of tuberculosis patients].

PURPOSE: To clarify the situation and suitability of tuberculosis wards for in-hospital tuberculosis care, with a view toward establishing a national standard for tuberculosis wards. METHODS: Data were obtained by sending questionnaires to all 321 tuberculosis wards in Japan. RESULTS: Of the hospitals to which questionnaires were sent, 69.3% returned their responses. In most of these hospitals, the total number of beds in one tuberculosis ward was either less than 20 or more than 40. In approximately two-thirds of the hospitals, tuberculosis wards were incorporated into another (non-tuberculosis) ward. In more than 70% of the hospitals, the mean hospital stay of tuberculosis patients exceeded 40 days. This relatively long hospital stay implies that amenities are a very important issue in tuberculosis wards; however, amenities were generally far from sufficient in most of the hospitals. Of all the tuberculosis beds, 18.2% were in single-occupant rooms and 19.4% had a sufficient floor area (more than 15 m2). Beds in single-occupant rooms with sufficient floor area, equipped with a toilet, bath or shower, washstand, negative-pressure control, and HEPA filter in an air exhaust duct, comprised 2.4% of all tuberculosis beds. CONCLUSION: In spite of the relatively long hospital stays, amenities were generally less than adequate. The conditions in most tuberculosis wards were far below the presumptive recommended standards. When national standards for tuberculosis wards are established, these findings should be taken into consideration.

[Nationwide survey of the use of class 2 infectious disease beds for in-hospital care of tuberculosis patients].

PURPOSE: To investigate the possibility of employing in-hospital care for tuberculosis (TB) patients in beds meant for patients with Class 2 infectious diseases and determine the obstacles facing the same. SUBJECTS & METHODS: We conducted a questionnaire survey of all 225 hospitals that had beds meant for patients with Class 2 infectious disease but did not have tuberculosis wards. RESULT: Responses were obtained from 83.1% of the targeted hospitals. Around 60% of the hospitals had used these beds for patients other than those with Class 2 infectious disease (including TB patients). Around 50% and 30% of the hospitals had used these beds for suspected TB patients to ensure hospital infection control, and for treatment of patients diagnosed with TB, respectively. In response to the question on how they would use these hospital beds for TB or suspected TB patients if the regulations allowed such use, around 60% of the hospitals answered that the beds will be used for suspected TB patients until their diagnosis was confirmed, and 25% of the hospitals responded that they will never use their beds for TB patients. Only 10% of the hospitals answered that the beds will be used for in-hospital care of TB patients. With regard to the reasons why the beds cannot be easily used for in-hospital care of TB patients, several issues were pointed out, such as difficulty in appointing sufficient staff for care of TB patients, and a lack of doctors who had sufficient experience in TB medicine. However, there was no single predominant reason. CONCLUSION: To ensure that hospital beds for patients with Class 2 infectious diseases are utilized for in-hospital TB care, we need a flexible policy, which is suited to the specific conditions in each community and hospital.

[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.

[The background of drug-resistant tuberculosis patients on the basis of the annual report database for 2007-2009 in Japan].

In this study, the background of drug-resistant tuberculosis (TB) patients in Japan was analyzed using the annual report database for 2007-2009. The results of the drug susceptibility test of 15,425 patients who were diagnosed with pulmonary TB between 2007 and 2009 were obtained and analyzed. The chi-square test for independence between susceptibility test results and parameters (i.e., sex, age, nationality, etc.) was conducted. Logistic regression analysis was performed using the variables (20s, 30s, 40s ..., new treatment, retreatment, etc.) of parameters that were statistically significant by chi-square test. The risk of multi-drug resistance (MDR) among TB patients who underwent retreatment was significantly high (odds ratio = 11.3, 95% CI: 7.7-16.6, p < 0.001, reference = new treatment), and the risk of MDR among foreigners who had entered Japan within the last 5 years was also high (odds ratio = 9.5, 95% CI: 4.6-19.4, p < 0.001, reference = Japanese). Moreover, logistic regression analysis was performed for TB patients who had previously undergone treatment. The risk of MDR was higher among the patients treated after 1970 than those treated before 1970. Especially, the risk of MDR among the patients previously treated in 1990-1999 was extremely high (odds ratio = 20.8, 95% CI: 5.7-75.0, p < 0.001, reference = before 1970). The risk of MDR among previously treated foreigners who had entered Japan within the last 5 years was also high (odds ratio = 3.8, 95% CI: 1.1-13.2, p = 0.036). Similar to the results for MDR, the risk of resistance to one or more drugs was significantly high among TB patients who underwent retreatment for TB (odds ratio = 2.2, 95% CI: 1.9-2.6, p < 0.001) and foreigners who had entered Japan within the last 5 years (odds ratio = 1.8, 95% CI: 1.3-2.5, p < 0.001); however, their risk of resistance to one or more drugs was lower than that for MDR. In addition, the odds ratios of age groups younger than 80 years to those over 80 years were obtained. They were 2.1 (95% CI: 1.5-2.9) in 0-29 years, 2.2 (95% CI: 1.6-3.0) in 30-39 years, 2.2 (95% CI: 1.7-3.0) in 40-49 years, 2.1 (95% CI: 1.6-2.8) in 50-59 years, 1.9 (95% CI: 1.4-2.5) in 60-69 years, and 1.5 (95% CI: 1.2-1.8) in 70-79 years. With respect to the background of high MDR among TB patients who underwent retreatment and foreigners who have recently entered Japan, the usage of RFP and poor adherence to drugs and entry from high-prevalence countries with high MDR risk were suspected. Regarding the background of generational differences in resistance to one or more drugs, it was suspected that most people over 80 years of age had been infected with TB bacilli in the distant past, before anti-TB drugs were available, when drug-resistant bacilli had not yet emerged. However, the younger generations have become more susceptible to drug-resistant TB bacilli because anti-TB drugs were being widely used when they were born, and drug-resistant bacilli were prevalent in the world.

Computerized surveillance system of tuberculosis in Japan: its evolution, achievement and challenges.

The nationwide computerized tuberculosis (TB) surveillance system was revised in 2007. It was developed to be user-friendly and to allow the evaluation of current TB problems and control issues in Japan. All public health centers in Japan (518 as of April 2007) have system terminals connected to a central computer, and the data entered at these terminals are sent to the online central computer excluding personal identification data. All the figures and tables in this paper were created using the annual report database which are compiled from this system. The revision in 2007 added many new functions to the system, such as a function for automatically sending data upon transfer. The monitoring information for assisting case management of TB patients by the DOTS was also enhanced. The algorithm for classifying treatment outcomes automatically based on data entered regarding cancellations from registration, bacteriological results and drug usage each month was revised. The proportion of "Failed" and "Defaulted" combined was 4.6% among new sputum smear positive pulmonary TB patients newly registered in 2009, while "Died" accounted for as high as 19.3%, due largely to a high percentage of the elderly. A new system for contact examination management is provided as a subsystem. Feedback of data analyses has been strengthened by various methods. This TB surveillance system is indispensable for implementing the evidence-based TB control program in Japan. An important role of the Research Institute of Tuberculosis is to support the planning and execution of TB control with provision of useful epidemiological information from the system.

Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24553 patients with Hashimoto's disease.

There are few large-scale reports of primary thyroid lymphoma (PTL). This study clinically and pathologically reviewed 171 patients with PTL and 24,553 patients with Hashimoto's disease at Ito Hospital between January 1990 and December 2004, to investigate the clinical features and the treatment outcomes of PTL. The median age of the patients with PTL was 67 years (range, 27-90 years). The pathological diagnosis of PTL patients included diffuse large B-cell lymphoma (DLBCL) (n=74), DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma (n=13), MALT lymphoma (n=80) and others (n=4). Of the 167 patients with B-cell lymphoma, treatment included combined modality therapy (CMT) (n=95), radiation therapy (RT) alone (n=60) and chemotherapy alone (n=6). Information on treatment was not available in six patients. Information on treatment response was available in 154 patients; 149 patients (97%) responded to treatment. According to the institutional treatment strategy of Ito Hospital, 45 of 54 patients with stage IE disease received RT alone, and 87 of 113 stage IIE patients received CMT. The 5-year overall survival rate was 85% (95% confidence interval, 79-91%). This study demonstrated that PTL showed good response to radiotherapy and chemotherapy and had a favourable prognosis.

Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism.

Serum levels of TSH receptor antibody (TRAb) often increase after radioiodine treatment for Graves' disease, and high-serum levels of maternal TRAb in late pregnancy indicate a risk of neonatal hyperthyroidism. The aim of this retrospective study is to investigate the characteristics of Graves' women who had a history of radioiodine treatment for intractable Graves' disease, and whose neonates suffered from hyperthyroidism. The subjects of this study were 45 patients with Graves' disease who became pregnant during the period from 1988 to 1998 after receiving radioiodine treatment at Ito Hospital. 25 of the 45 subjects had had a relapse of hyperthyroidism after surgical treatment for Graves' disease. 19 pregnancies were excluded because of artificial or spontaneous abortion. In the remaining 44 pregnancies of 35 patients, neonatal hyperthyroidism developed in 5 (11.3%) pregnancies of 4 patients. Serum levels of TRAb at delivery were higher in patients whose neonates suffered from hyperthyroidism (NH mother) than those of patients who delivered normal infants (N mother). Furthermore, serum levels of TRAb in NH mother did not change during pregnancy, although those of 4 patients of N mother, in which serum levels of TRAb before radioiodine treatment were as high as in NH mother, decreased significantly during pregnancy. In conclusion, women who delivered neonates with hyperthyroidism following radioiodine treatment seem to have very severe and intractable Graves' disease. Persistent high TRAb values during pregnancy observed in those patients may be a cause of neonatal hyperthyroidism.