[Evaluation of the quality of public health nurses' community DOTS practices and its relationship with individual and organizational factors].

Objectives　By targeting the public health nurses (PHNs) who are expected to be actively involved in the implementation of community DOTS practices, we evaluated the quality of the regional DOTS practices based on the three aspects of "enhancing tuberculosis (TB) treatment adherence," "patient-centered support other than treatment," and "coordination with related organizations." We examined the individual and organizational factors that affect the quality of these practices. Further, we clarified the challenges related to the abilities of PHNs.Methods　A self-report questionnaire survey of 958 PHNs from local governments with a TB incidence rate of 15 or more was administered in 2015. This resulted in there being 410 valid responses with a valid response rate of 42.8%.　The quality of the community DOTS practices was evaluated based on the three aspects by reviewing the literature on expert PHNs for TB patient support. After a preliminary survey, each was evaluated based on a scale of 10 points. A multiple regression analysis was conducted to understand the relationship between these and the TB control implementation system (organizational factors), the experience and motivation of PHNs to support tuberculosis patients, and the learning situation (individual factors).Results　The quality of the community DOTS practices was 7.54±1.69 for "enhancing TB treatment adherence," was 6.91±1.63 for "coordination with related organizations," and was 6.68±1.53 for "patient-centered support." The scores for the first factor were higher than those for the latter two factors (P<0.05). With regard to "patient-centered support," one-fourth of the surveyed PHNs rated their practices as low. Each predictor showed a strong relationship with the quality of community DOTS practices, especially "coordination with related organizations" and "patient-centered support" (r=0.787). The significant organizational factors associated with the quality of the community DOTS practices in terms of each aspect were "making an individual support plan for TB patients" (ß=0.112-0.270), "reporting own practices at the DOTS conference as a responsible PHN" (ß=0.113-0.173), "attending cohort study meetings" (ß=0.129-0.167), and the individual factor of "many years of experience as a PHN" (ß=0.210-0.316). Additionally, in the model of "coordination with related organizations," "reading specialized books and journals" (ß=0.108) was found to be significant and positively related.Conclusion　To improve the quality of the community DOTS practices based on the self-evaluation of PHNs, "patient-centered support" with a low score and high relevance to other aspects is a priority. It was also suggested that it would be useful if the PHNs participated in DOTS evaluations, developed individual patient support plans, presented support plans, and participated in performance evaluations to improve the quality of DOTS practices.

[The association between smoking and sputum smear-positive pulmonary tuberculosis in Osaka City].

PURPOSE: This study aimed to analyze and evaluate the association between tuberculosis (TB) and smoking in order to obtain basic information for the control of smoking. METHODS: Of the 637 patients with sputum smear-positive pulmonary tuberculosis who were newly registered in Osaka City in 2009, 581 patients whose smoking status was identified were selected as study subjects. Data on the following were collected: patient characteristics, presence or absence of underlying conditions, patient's delay and doctor's delay in the diagnosis of TB, presence or absence of cavities, and degree of smear positivity. The patients were divided into the following three groups according to their smoking status: (1) never smokers (those who have never smoked), (2) former smokers (those who had smoked, but quitted), and (3) current smokers (those who smoke currently). RESULTS: (1) PATIENT CHARACTERISTICS: The subjects consisted of 413 males and 168 females, with mean ages of 65.7, 55.4, and 70.2 years for never smokers, current smokers, and former smokers, respectively. (2) Comparison with the national adult smoking rate (National health and nutrition survey 2009, Ministry of Health, Labour and Welfare): The prevalence of current smoking among male patients with sputum smear-positive pulmonary TB in Osaka was 62.4-82.4% among men in their 20s to 60s, and 27.5% among men in their 70s, which is higher than the national average. For female patients, the prevalence of current smoking was 46.2% among women in their 20s and 45.5% among women in their 30s, which is clearly higher than the national average. This was also true for those aged 40 years or older. (3) Severity of TB disease and smoking status: The presence of a cavity was significantly associated with being a male patient, being a current smoker, and longer patient's delay. Sputum smear grades (2+) and (3 +) were significantly correlated with being under 59 years old, being a current smoker, and longer patient's delay. CONCLUSION: The prevalence of current smokers was significantly higher among sputum smear-positive pulmonary TB patients in Osaka than the national average. More smokers had cavitary lesions and a high degree of smear positivity, which may lead to poorer treatment outcomes, and may also expose more surrounding people to infection.

[Examination of onset cases in contact investigation].

OBJECTIVES: To analyze and evaluate onset cases of tuberculosis detected in contact investigations and to apply the results to future countermeasures. METHODS: Index and secondary cases in contact investigations in which the secondary cases occurred in Osaka City between 2005 and 2008 were enrolled. The tuberculin skin test or QFT (QuantiFERON-TB Gold) was conducted to diagnose whether the contacts were infected with tuberculosis. X-ray examination of the chest was conducted to determine whether tuberculosis had developed, immediately or 6 months, 1 year or 2 years after the contact investigation. RESULTS: (1) Index cases: Index cases followed by secondary cases numbered 131 patients. Regarding the chest X-ray findings, a cavity was observed in 67.7% of the index cases, and a sputum smear of 3 + was observed in 51.5% of the index cases. A 3-month or longer delay in index case-finding was noted in 50.4% of the index cases. (2) Secondary cases: Secondary cases numbered 177 patients, consisting of 107 patients who showed an onset of less than 6 months after their last contact with index cases. Of 70 secondary cases in whom tuberculosis was detected in the investigation conducted 6 months to 2 years after the contact investigation, 50% of them were not tested for infection due to their older age, consisting of 11 patients in their 40's, 8 in their 50's, and 16 in their 60's or over, and 17.1% of them refused or discontinued the treatment for latent tuberculosis infection, leading to onset. DISCUSSION: Many secondary cases were detected immediately after the contact investigation, suggesting the importance of reducing the delay in index case-finding. Regarding the onset of secondary cases who showed an onset 6 months after the last contact with index cases, many cases showed an onset without being tested for infection due to their older age. More attention should be paid to the cases who refused or discontinued the treatment for latent tuberculosis infection, leading to onset.

[Assessment of self-discharge of homeless patients with tuberculosis].

OBJECTIVES: Factors responsible for the premature self-discharge of homeless tuberculosis (TB) patients from the hospital and the association between the self-discharge and treatment interruption were assessed. METHODS: A total of 205 homeless patients with TBs who were newly registered between January, 2007 and June, 2008 were evaluated. The subjects were divided into two groups (those who were discharged themselves from the hospital prematurely ["case" group] and those who were not [control group]), and the difference between the groups regarding the factors possibly responsible for the self-discharge was evaluated. RESULTS: i) Patient's characteristics: The subjects were all men; there were 45 in the "case" group and 160 in the control group. The proportion of subjects aged under 60 years was significantly higher in the "case" group (84.4%) than in the control group (52.5%). The proportion of subjects who consumed 360 mL or more of sake a day was significantly higher in the "case" group (64.4%) than in the control group (38.8%). ii) Questionnaire survey on admission: All of the patients were hospitalized for treatment of TB. In the interview on admission, more "case" group patients reported "I do not know much about TB" or "I am dissatisfied with my hospitalization", as shown by multiple logistic regression analysis. A review of troubles with inmates or healthcare workers over alcohol drinking or smoking showed that the proportion of subjects who had such troubles was significantly higher in the "case" group (55.6%) than in the control group (5.0%). iii) The association between the treatment outcomes and the self-discharge: The proportion of subjects with treatment outcomes of "cured" or "treatment completed" was significantly lower in the "case" group (46.7%) than in the control group (78.8%). The proportion of subjects with a treatment outcome of "defaulted" was significantly higher in the "case" group (42.2%) than in the control group (3.8%). CONCLUSION: The patients who were aged under 60 years or who consumed 360 mL or more of sake a day were shown to be significantly more likely to discharge themselves prematurely, which warrants a more careful handling of such problems. The poor understanding of disease necessitates more adequate explanation of TB, or education, considering each patient's level of understanding. In addition, the patients' dissatisfaction with their hospital stay, as seen in the case group, should be more carefully addressed in order to avoid the higher rate of trouble.

[An outbreak of tuberculosis in which environmental factors influenced tuberculosis infection].

OBJECTIVE: We encountered a contact group investigation in which differences in environmental factors, including the ventilation frequency and the airflow, led to differences in the infection risk. MATERIALS AND METHODS: The index case was diagnosed with tuberculosis after cough and sputum persisted for 9 months. The patient was an instructor working at vocational schools A and B. Sixty-six instructors/staff and 446 students had contact with this patient at the schools. The patient taught 24 regular courses and 21 short-term courses at the 2 schools after symptom onset through to the final day of work. RESULTS: In a contact investigation of instructors/staff, one person with latent tuberculosis infection (LTBI) was identified. Subsequently, 30 and 240 students with the closest contacts and those with 8-hour or longer contact with the index case, respectively, were examined. In School A, of the 162 students examined, one student developed tuberculosis, 7 were QFT-positive, one was QFT-doubtful, 147 were QFT-negative or judged as not infected (either QFT-negative, or a tuberculin skin test of erythema less than 20 mm, including past history of LTBI treatment or TB treatment), and 6 were not examined. In School B, of the 108 students examined, no one developed tuberculosis nor was QFT-positive, 4 were QFT-doubtful, 98 were either QFT-negative or judged as not infected, one was QFT-indeterminate, and 5 were not examined. Since the onset of tuberculosis and QFT-positivity occurred in only School A, the difference in the incidence of infection between the 2 schools, despite the levels of contact being similar, was assumed to be due to environmental factors. Thus, the ventilation frequency, which had been not reported initially, was reinvestigated. The frequency of air change was as low as 0.45-1/hour in School A, whereas it was better (3.57-7/hour) in School B. Moreover, the air flew from the instructor side toward students in School A, while it was reversed in School B. DISCUSSION: It was clarified that the ventilation frequency and airflow markedly influenced infection. It is important to investigate environmental factors on epidemiological investigations and to educate people regarding the importance of ventilation.

[Comparative performance of tuberculin skin test and QuantiFERON TB-gold in contact investigations for tuberculosis].

OBJECTIVES: To evaluate the performances of the QuantiFERON TB-Gold assay (QFT) and tuberculin skin test (TST) and to examine how a latent tuberculosis infection (LTBI) should be diagnosed in contact investigations of children aged 6 to 17 years. METHODS: A total of 232 boys and girls aged 6 to 17 years who were in contact with 134 culture-confirmed pulmonary tuberculosis patients (index cases) were examined both with QFT and TST. Factors influencing the results of the tests and their interactions were evaluated with multivariate analyses. RESULTS: Two variables (whether household contact and with/without contact with a cavitary disease patient) were found to significantly predict a positive QFT result. Positive TST defined with erythema being either greater than 20 mm or 30mm correlated significantly with two variables (whether household contact and with/without contact with a smear positive patient). There was moderate agreement between QFT and TST (positivity defined as with erythema greater than 30mm), with kappa=0.49, for contacts aged 6 to 11 years. Among contacts aged 6 to 11 years, 14 had a negative QFT result and TST with erythema greater than 30 mm. Of these 14, 7 contacts (50%) of smear positive index case were not indicated for LTBI treatment. CONCLUSIONS: When diagnosing LTBI among contacts aged 6 to 11 years who show negative QFT and strong TST reactions, we should take into consideration the factors related with a higher probability to the risk of infection. Because a history of past BCG vaccination is more likely to affect TST results in those aged 12 to 17 years than in younger subjects, greater care must be taken when evaluating the TST of these contacts.

[Examination of latent tuberculosis infection treatment status].

OBJECTIVE: To clarify factors involved in the refusal or discontinuation of treatment for latent tuberculosis infection (LTBI), we reviewed LTBI treatment. METHOD: The subjects were 193 patients for whom LTBI treatment was indicated on a family contact investigation in 2006. We examined the subjects' backgrounds and reasons for treatment refusal or discontinuation. In addition, we investigated the incidence of the onset of tuberculosis within 2 years after the final contact with the source of infection. RESULTS: i) Patient background: The state of treatment could be evaluated in 185 patients. Of these, drug therapy was completed in 138 (75%), whereas 47 (25%) refused or discontinued treatment. The mean ages of the former and latter were 21.0 and 26.2 years, respectively, showing a significant difference. Concerning the state of contact, 9 (8%) of 114 patients who had lived with and 12 (17%) of 71 who had lived apart from the source of infection refused treatment, showing a significant difference. ii) Onset within 2 years: We analyzed 180 patients for whom follow-up was possible. Drug therapy was completed in 137 patients. No patient developed tuberculosis onset. On the other hand, drug therapy was not completed in 43 patients, and 6 (14%) developed tuberculosis onset. iii) The reasons were investigated in 47 patients who did not complete drug therapy. There were 15 episodes associated with side effects, followed by 14 related to personal circumstances, such as being busy, disliking medicines, and the absence of confidence regarding the completion of drug therapy, and 6 associated with either insufficient explanations regarding the diagnosis or an absence of symptoms. CONCLUSION: Treatment refusal/discontinuation was more frequent in the more advanced age groups and patients who had lived apart from the source of infection. It may therefore be necessary to more closely explain the importance of treatment to these patients. Most reasons for treatment refusal/discontinuation were associated with side effects or insufficient explanations, suggesting the necessity of providing sufficient information to aid in patient understanding.

[Tuberculosis infection by tuberculin skin test or QuantiFERON and related factors in contact investigations].

OBJECTIVE: We investigated the factors related to secondary infections in contact group investigations. METHOD: From March, 2008 to February, 2009, a total of 457 tuberculosis (TB) notifications were reviewed by the Health Examination Committee of the Health Centers of Osaka City over indications of a contact investigation. A contact investigation was considered necessary for 92 cases with 620 contacts. For the contacts of these cases, the tuberculin skin test (TST) or/and QuantiFERON-TB 2nd Generation (QFT) was used. The contacts testing positive for QFT were classified as "infected". The contacts with "doubtful" QFT were classified as either "infected" or "non-infected" according to the QFT-positive rate of the group as a whole. Those with blisters in TST were classified as "infected". RESULTS: Among the total of 84 "infected" cases thus defined, 56 were QFT-positive, 17 were doubtful, and 11 had blisters with TST. On the other hand, among the total of 515 "uninfected" cases, 18 were doubtful on the QFT test, 323 were QFT-negative and 174 were cases with TST of erythema less than 30 mm without QFT test. The relationship between characteristics of index cases and whether a contact was infected or not was as follows: Severe chest X-ray findings, sputum smear positivity, and a cough persisting for more than two months were significantly associated with infection of the contacts. The closeness of contact was also significantly related with a higher risk of infection, so that contact with an index case for more than 100 hours, and contact in a space less than 100 square meters were more likely to cause transmission of infection. CONCLUSION: Severity of chest X-ray findings, degree of smear positivity and period of cough were confirmed to be important in judging whether investigations are necessary. The time and space of contact were also considered to be important factors. We should consider these factors comprehensively in order to decide on indications for a contact investigation.

[Investigation on "patient's delay" in TB detection].

OBJECTIVE: The causes of delay in receiving medical examinations (for a period of more than 2 months between the appearance of tuberculosis symptoms and the first examination at a medical institution) were investigated. METHOD: Interviews of 127 smear positive pulmonary tuberculosis patients (study period: June-December, 2008). Subjects were divided into 2 groups: those who showed delay in receiving medical examination (hereinafter referred to as "case") and those who did not show delay in receiving medical examination (hereinafter referred to as "control"), and the factors causing differences between the two groups were investigated. RESULTS: There were 44 case examples and 83 control examples. There were higher rates of "aged under 60", "employed" and "have no family doctor" among cases, however, none of them were statistically significant. The rate of smokers was significantly higher in cases. At the time of diagnosis, chest X-ray findings were significantly aggravated in cases and cases were also significantly higher in the degree of smear positivity. It was mostly cases that replied "they were not the symptoms of a serious illness" concerning the initial symptoms and, concerning the timing of medical examinations, the reply "I was busy at work and couldn't take time off" was significantly higher. CONCLUSION: It is considered that cases do not take symptoms seriously and that many of them do not receive medical examinations. Further, it is also considered necessary to carefully educate smokers in particular. There were many cases diagnosed as serious on chest X-ray findings and showed higher degree of smear positivity, so it is considered important to reduce delays in receiving medical examinations in order to treat patients early and prevent the spread of infection.

Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus.

Matrix metalloproteinases (MMP) are capable of degrading a variety of extracellular matrix (ECM) proteins and are also involved in the processing of a number of bioactive molecules. Our findings indicate that the functions of MMP in the ovary and uterus are organ-specific and time-dependently vary during the reproductive cycle. Prolactin induces structural luteolysis indicated by loss of luteal weight, protein and DNA within 36 h after pretreatment with ergot alkaloid. MMP activation appears crucial for the selective depletion of protein during luteal involution, which entails loss of ECM accompanied by apoptosis. During GnRHagonist-induced luteolysis, this response was also associated with marked increases in MMP-2, which degraded collagen type IV, and MT1-MMP, which in addition to activating MMP-2 also degrades collagen type I, III and V. We also found that the level of MT1-MMP and MMP-2 expression in the human CL is greater during the late luteal phase than during either the early mid luteal phases or during gestation, respectively. That dehydroepiandrosterone (DHEA) treatment caused the formation of cysts from antral follicles in the ovaries of immature rats while depressing MMP-2 collagenolytic activity and enhancing lysyl oxidase expression highlights the importance of collagen degradation in the process of ovulation and suggests that changes in the activities of these enzymes play a key role in ovarian cystogenesis in polycystic ovary syndrome patients. Furthermore, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive apoptotic granulosa cells in rats treated with DHEA, that the Fas/FasL/Caspase-8 (death receptor-dependent) pathway is pivotal for follicular atresia and that increased levels of MT1-MMP likely play an important role in tissue remodeling during follicular atresia. After parturition, the uterus undergoes involution, a conspicuous feature characterized by a rapid reduction in the collagen content mediated by degradation of extracellular collagen bundles. Our findings strongly suggest that MT1-MMP, MMP-2 and MMP-9 are each time-dependently regulated and play important roles in tissue remodeling during postpartum uterine involution. (Reprod Med Biol 2006; 5: 235-243).

Secretion of keratinocyte growth factor by cultured human endometrial stromal cells is induced through a cyclic adenosine monophosphate-dependent pathway.

OBJECTIVE: To evaluate the effects of known modulators of endometrial function on the production of keratinocyte growth factor by endometrial stromal cells. DESIGN: The effects of dibutyryl-cyclic adenosine monophosphate (db-cAMP), 12-O-tetradecanoylphorbol 13-acetate (TPA), ethinyl estradiol-17alpha (EE), and medroxyprogesterone acetate (MPA) on the secretion of keratinocyte growth factor by endometrial stromal cells were investigated. SETTING: Research laboratory at a university medical school. PATIENT(S): Eleven endometrial specimens in the late proliferative phase. INTERVENTION(S): Endometrial stromal cells were incubated for 24 hours with db-cAMP, TPA, EE, or MPA. MAIN OUTCOME MEASURE(S): The concentration of keratinocyte growth factor in the culture media was measured using an ELISA. RESULT(S): Small amounts of keratinocyte growth factor were detected in the culture media of unstimulated endometrial stromal cells. The production of keratinocyte growth factor by endometrial stromal cells was stimulated with db-cAMP in a dose-dependent manner. The stimulatory effect of db-cAMP was inhibited by Rp-adenosine 3',5'-cyclic monophosphothioate. None of TPA, EE, nor MPA affected the keratinocyte growth factor production by these cells. CONCLUSION(S): These results suggest that a cAMP-dependent pathway may play an important role in the regulation of keratinocyte growth factor production by endometrial stromal cells. Keratinocyte growth factor secreted by endometrial stromal cells may be involved in the regeneration of the endometrium during the normal menstrual cycle and early pregnancy.