Activity of omadacycline in vitro against Clostridioides difficile and preliminary efficacy assessment in a hamster model of C. difficile-associated diarrhoea.

OBJECTIVES: Antibiotics are associated with increased risk of Clostridioides difficile infection, which has limited treatment options. We assessed in vitro activity of omadacycline (an aminomethylcycline antibiotic) against the C. difficile infection strain and efficacy in a hamster model of C. difficile-associated diarrhoea. METHODS: Omadacycline, clindamycin, tigecycline, vancomycin, and metronidazole minimum inhibitory concentrations (MICs) for the infection-model strain (C. difficile ATCC 43596) were determined. Hamsters were pretreated with subcutaneous clindamycin (10 mg/kg) and infected 24 h later with C. difficile ATCC 43596; 24 h post infection, they received oral omadacycline (50 mg/kg/day), vancomycin (50 mg/kg/day), or vehicle for 5 days. Efficacy was reported as survival. RESULTS: Omadacycline was as active as tigecycline, vancomycin, and metronidazole (MIC 0.06 mg/L); clindamycin showed no activity. Median survival in hamsters was: 12 days, omadacycline; 2 days, vancomycin; 4 days, clindamycin pretreatment only. CONCLUSION: Omadacycline exhibited potent in vitro activity against C. difficile and showed efficacy in a model of C. difficile-associated diarrhoea.

Health state utility values and patient-reported outcomes before and after vertebral and non-vertebral fractures in an osteoporosis clinical trial.

We assessed the health state utility value (HSUV) reductions associated with vertebral fractures using data collected in the Japanese Osteoporosis Intervention Trial-03 (JOINT-03). Our analysis revealed that assessment of HSUVs after morphometric vertebral fracture is important to capture the burden of vertebral fractures. INTRODUCTION: Evaluation of the HSUV after fracture is important to calculate the quality-adjusted life years (QALYs) of osteoporosis patients, which is essential information in the context of health economic evaluation. METHODS: JOINT-03 study patients were aged ≥65 years and treated with risedronate and vitamin K2 or risedronate alone. Radiographic information and patient-reported outcomes measured by EQ-5D and a visual analogue scale (VAS) were assessed at registration and followed up after 6, 12, and 24 months. According to differences among the dates of these assessments and the radiographic information, we classified the follow-up HSUVs calculated based on EQ-5D results into before or after fracture categories regardless of clinical symptoms. RESULTS: Among 2922 follow-up HSUVs, 201 HSUVs were categorized as HSUVs that were observed after incident vertebral fractures on X-ray films. The median time from the detection of an incident vertebral fracture until the EQ-5D assessment was 53 days (25th percentile, 0 day; 75th percentile, 357 days). The impact of incident vertebral fractures on HSUVs was quantified as -0.03. Among the five health profile domains on the EQ-5D, an incident vertebral fracture had significant effects on anxiety/depression, self-care, and usual activities. CONCLUSIONS: The results suggest that incident morphometric vertebral fracture was associated with impairment of the HSUV for patients with osteoporosis not only immediately but also several months after the fracture.

Transition of fertilizer application and agricultural pollution loads: a case study in the Nhue-Day River basin.

Rapid socio-economic development in suburban areas of developing countries has induced changes in agricultural waste and nutrient management, resulting in water pollution. The study aimed at estimating agricultural nutrient cycles and their contribution to the water environment. A material flow model of nitrogen (N) and phosphorus (P) was developed focusing on agricultural activities from 1980 to 2010 in Trai hamlet, an agricultural watershed in Nhue-Day River basin, Vietnam. The model focused on the change in household management of human excreta and livestock excreta, and chemical fertilizer consumption. The results showed that the proportion of nutrients from compost/manure applied to paddy fields decreased from 85 to 41% for both N and P between 1980 and 2010. The nutrient inputs derived from chemical fertilizer decreased 6% between 1980 and 2000 for both N and P. Then, these nutrients increased 1.4 times for N and 1.2 times for P from 2000 to 2010. As of 2010, the total inputs to paddy fields have amounted to 435 kg-N/ha/year and 90 kg-P/ha/year. Of these nutrient inputs, 40% of N and 65% of P were derived from chemical fertilizer. Thirty per cent (30%) of total N input was discharged to the water bodies through agricultural runoff and 47% of total P input accumulated in soil.

Leveraging non-binding instruments for global health governance: reflections from the Global AIDS Reporting Mechanism for WHO reform.

As countries contend with an increasingly complex global environment with direct implications for population health, the international community is seeking novel mechanisms to incentivize coordinated national and international action towards shared health goals. Binding legal instruments have garnered increasing attention since the World Health Organization adopted its first convention in 2003. This paper seeks to expand the discourse on future global health lawmaking by exploring the potential value of non-binding instruments in global health governance, drawing on the case of the 2001 United Nations General Assembly Special Session Declaration of Commitment on HIV/AIDS. In other realms of international concern ranging from the environment to human rights to arms control, non-binding instruments are increasingly used as effective instruments of international cooperation. The experience of the Global AIDS Reporting Mechanism, established pursuant to the Declaration, evidences that, at times, non-binding legal instruments can offer benefits over slower, more rigid binding legal approaches to governance. The global AIDS response has demonstrated that the use of a non-binding instrument can be remarkably effective in galvanizing increasingly deep commitments, action, reporting compliance and ultimately accountability for results. Based on this case, the authors argued that non-binding instruments deserve serious consideration by the international community for the future of global health governance, including in the context of WHO reform.

Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6).

AIMS/HYPOTHESIS: The aims of this study were to assess the clinical significance of introducing HbA(1c) into a risk score for diabetes and to develop a scoring system to predict the 5 year incidence of diabetes in Japanese individuals. METHODS: The study included 7,654 non-diabetic individuals aged 40-75 years. Incident diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/l, HbA(1c) ≥6.5% (48 mmol/mol) or self-reported clinician-diagnosed diabetes. We constructed a risk score using non-laboratory assessments (NLA) and evaluated improvements in risk prediction by adding elevated FPG, elevated HbA(1c) or both to NLA. RESULTS: The discriminative ability of the NLA score (age, sex, family history of diabetes, current smoking and BMI) was 0.708. The difference in discrimination between the NLA + FPG and NLA + HbA(1c) scores was non-significant (0.836 vs 0.837; p = 0.898). A risk score including family history of diabetes, smoking, obesity and both FPG and HbA(1c) had the highest discrimination (0.887, 95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity were high at 83.7% and 79.0%, respectively. After initial screening using NLA scores, subsequent information on either FPG or HbA(1c) resulted in a net reclassification improvement of 42.7% or 52.3%, respectively (p < 0.0001). When both were available, net reclassification improvement and integrated discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%) and 10.9% (9.7%, 12.1%), respectively. CONCLUSIONS/INTERPRETATION: Information on HbA(1c) or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification.

Evidence-based therapy according to the guideline for gastric ulcers is cost-effective in Japan.

Helicobacter pylori (H. pylori) infection is a major cause of gastric ulcers (GU) and eradication of the infection controls the ulcer with no requirement for maintenance therapy. In Japan, an evidence-based guideline (GL) was first published in 2003 (1(st) version) and then again in 2007 (2(nd) version) with a minor revision under support of the Japanese Ministry of Health, Labor and Welfare (GUGLJ). Adherence to its standards is high, estimated at 80%. GU patients aged 18 or older with active ulcers at the time of diagnosis by an endoscopic examination at National Hospital Organization (NHO) hospitals of Japan were enrolled between September 2004 and April 2005. Subjective and endoscopic outcome, medical treatments and medical costs during the following nine months were analyzed, retrospectively. As a result, 935 patients and 270 doctors in charge from 62 NHO hospitals were analyzed. Among H. pylori-positive GU patients, the endoscopic recurrence rate of 24 patients with failure of eradication was 29.2%, which was significantly higher than 8.8% of 194 patients with successful eradication. Successful eradication of H. pylori resulted in significantly lower endoscopic recurrence rates for GU patients either with or without administration of non-steroidal anti-inflammatory drugs (NSAID). GUGLJ adherence scores were significantly related to the specialty or knowledge on the GUGLJ of doctors in charge, and the total medical cost consumed. These results suggest that the therapy of GU along with an evidence-based GL is essential to implement cost-effective treatment and the GI experts or the doctors that understand the GUGLJ very well should perform it.

Morphological assessment of the interface between tumor and neighboring tissues, by magnetic resonance imaging, before and after radiotherapy in patients with locally advanced rectal cancer.

BACKGROUND: Magnetic resonance imaging (MRI) in rectal cancer is sometimes performed after radiotherapy (MRI 2) to evaluate tumor response and to choose alternative forms of surgery. The accuracy of MRI 2 in distinguishing tumor delineation might be difficult due to fibrosis. PURPOSE: To evaluate the morphological changes in the interface between the tumor and neighboring organs on MRI 2 performed after radiotherapy, and to assess the accuracies of MRI before and after radiotherapy compared to histopathology after surgery. MATERIAL AND METHODS: Sixteen patients with locally advanced primary rectal cancer, with MRI before and after radiotherapy, were retrospectively studied, concerning the interface between the tumor and neighboring structures. The accuracies of MRI before and after radiotherapy were compared based on histopathology as a reference. RESULTS: The accuracies of both MRI before and after radiotherapy were moderate, with no additional value of MRI after radiotherapy compared to MRI before radiotherapy. The most predictive form of interface for involvement of a neighboring organ after radiotherapy was nodular growth of the tumor into a neighboring structure. CONCLUSION: The morphological assessment of pelvic MRI after preoperative radiotherapy does not provide any significant new information about tumor extent in patients with locally advanced rectal cancer.

Development of a fully automated network system for long-term health-care monitoring at home.

Daily monitoring of health condition at home is very important not only as an effective scheme for early diagnosis and treatment of cardiovascular and other diseases, but also for prevention and control of such diseases. From this point of view, we have developed a prototype room for fully automated monitoring of various vital signs. From the results of preliminary experiments using this room, it was confirmed that (1) ECG and respiration during bathing, (2) excretion weight and blood pressure, and (3) respiration and cardiac beat during sleep could be monitored with reasonable accuracy by the sensor system installed in bathtub, toilet and bed, respectively.

Preoperative assessment of gastric cancer vascularity by flash echo imaging.

BACKGROUND: Tumor vascularity as indicated by immunohistochemical staining is a significant prognostic factor in gastric and other cancers. Non-invasive preoperative assessment of the vascularity of gastric cancers has not been possible. We aim to determine the reliability of harmonic flash echo imaging (FEI) for assessment of vascularity of gastric cancers by comparison with CD34 staining of resected specimens. METHODS: Twelve patients undergoing surgical resection of advanced gastric cancer were studied. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic image) was used for harmonic FEI. Approximately 30 s after intravenous injection of ultrasonic contrast medium (SHU 508A, Levovist), second harmonics (4.6 MHz) emitted from microbubbles were obtained to enhance the B-mode images. Using the tumor image showing strongest enhancement in each FEI series, regions of interest were determined to measure mean echo intensity in the tumor. Immunohistochemistry using antibodies against CD34 was carried out in resected specimens. Tumor vascularity was determined by counting stained microvessels. RESULTS: A significant positive correlation was noted between sonographic amplitude determined preoperatively by FEI analysis and number of CD34-stained microvessels in tumor specimens (r = 0.869, P = 0.004). CONCLUSION: Vascularity of gastric cancers now can be evaluated non-invasively by harmonic FEI.

Summary of the JCO criticality accident in Tokai-mura and a dose assessment.

A criticality accident occurred on September 30, 1999, in a conversion test facility at the JCO Tokai site. The accident was triggered by pouring an 18.8% enriched uranyl nitrate solution into a precipitation vessel beyond the critical mass. The accident continued for about 19 hours before the criticality could be stopped. during which time neutrons and gamma-rays were emitted continuously due to fission reactions. The total number of fission reactions was 2.5 x 10(18), which was estimated by an activity analysis of the fission products in the solution of the precipitation vessel. The accident gave serious radiation dose to 3 employees and fatal dose to 2 of them. Neutrons and gamma-rays emitted by the accident caused meaningful doses to the residents of the surrounding area of JCO. The dominant dose to the residents and JCO employees was brought by neutrons and gamma-rays from the precipitation vessel, while the contribution of radioactive plume was negligible. The individual dose was estimated for 234 resident, 169 JCO employees and 260 emergency personnel. The maximum doses were 21 mSv for the residents, 48mSv for the JCO employees, and 9.4mSv for the emergency personnel, respectively. No deterministic effect, however, has been observed, except for the 3 workers.

Developmental assessment-based surgical intervention for intractable epilepsies in infants and young children.

PURPOSE: To define the most appropriate time for surgery for medically intractable epilepsies in infants and young children. METHODS: First we examined retrospectively the changes in developmental quotients (DQs) during the clinical course and the clinical factors affecting the DQ in 39 consecutive patients younger than 15 years, who underwent surgical treatment for intractable epilepsy. Second, we examined prospectively five new patients for early detection of developmental arrest or regression by periodic developmental assessments and whether this could lead to early surgical intervention, eventually resulting in minimal developmental defects. RESULTS: Retrospective studies revealed that the DQ progressively decreased with age and that the reduction of DQ was related to continuing frequent seizures in many patients. The prospective studies demonstrated that periodic developmental assessments could detect the reduction of DQ at 5 months or later after onset of frequent seizures in three patients. In two other patients, operations were performed before reduction of DQs, and their postoperative DQ levels were normal. The post-operative recovery of DQ was complete in one patient whose operation was performed 3 months after reduction of DQ, whereas it was incomplete in two others whose operations were carried out at 12 and 14 months after reduction, respectively. Furthermore, three patients with normal developmental outcome had shorter periods between the onset of frequent seizures and the operation (< or = 7 months) than those of two patients with developmental delay (> or = 17 months). CONCLUSIONS: To minimize the developmental defects, periodic developmental assessments should be initiated when frequent seizures have occurred, and surgery should be considered as soon as possible when DQ reduction is recognized.

Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, p<.001). Values for the glomerular pressure and the resistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

Expression of alpha-smooth muscle actin in small bronchioloalveolar adenocarcinoma of the lung: assessment and comparison with noguchi criteria.

The Noguchi criteria are useful in assessing the prognosis of patients with small lung adenocarcinoma. Although there is a significant difference in prognosis between type A or B and type C, it is difficult in some cases to distinguish these types accurately by microscopy. In this study, we used immunohistochemistry to examine alpha-smooth muscle actin (alpha-SMA) produced by active fibroblasts in 25 pulmonary adenocarcinomas less than 2 cm in diameter. Eleven of type C (61%) showed positive staining for alpha-SMA, whereas no positive cases were seen in type A or B. The incidence of cancerous blood vessel and lymphatic invasion were significantly higher in alpha-SMA positive cases than in negative cases, and the positive cases showed poorer prognosis. These findings indicate that immunohistochemical detection of alpha-SMA is useful and essential for histological typing by the Noguchi criteria.

Back pain prevalence in US industry and estimates of lost workdays.

OBJECTIVES: Back pain is the most common reason for filing workers' compensation claims and often causes lost workdays. Data from the 1988 National Health Interview Survey were analyzed to identify high-risk industries and to estimate the prevalence of work-related back pain and number of workdays lost. METHODS: Analyses included 30074 respondents who worked during the 12 months before the interview. A case patient was defined as a respondent who had back pain every day for a week or more during that period. RESULTS: The prevalence of lost-workday back pain was 4.6%, and individuals with work-related cases lost 101.8 million workdays owing to back pain. Male and female case patients lost about the same number of workdays. Industries in high-risk categories were also identified for future research and intervention, including those seldom studied. CONCLUSIONS: This study provides statistically reliable national estimates of the prevalence of back pain among workers and the enormous effect of this condition on American industry in terms of lost workdays.

Health status and satisfaction of asymptomatic HIV-positive haemophiliacs in Kyushu, Japan.

The purpose of this study was to elucidate the effects of human immunodeficiency virus (HIV) on haemophiliacs with physical functional disabilities induced by haemophilia in Kyushu, Japan. The subjects were 38 adult haemophiliacs who were selected from 129 patients registered with the North Kyushu Haemophilia Centre. They were divided into 21 asymptomatic HIV-positive and 17 HIV-negative adult haemophiliacs. Coagulation factor levels, modified DePalma classification, Arthritis Impact Measurement Scale 2 (AIMS 2), and a satisfaction in daily life (SDL) questionnaire were used to investigate the clinical severity of their haemophilia and arthropathy, physical functional disabilities, and satisfaction. Although there were no significant differences in the objective assessments of health status between the HIV-positive and -negative haemophiliacs, the HIV-positive haemophiliacs were significantly more dissatisfied with their social activities and mood, according to AIMS 2, and with social intercourse, job, self-development, and social security and pension according to SDL assessment. These dissatisfactions were due to the effects of HIV, in addition to the physical functional disabilities that were caused by haemophilia. Dissatisfaction with social security and pension may be a specific feature in HIV-positive haemophiliacs in Japan resulting from the origin of HIV infection.

[Experience as a model hospital for new good clinical practice (GCP) regulations].

The new good clinical practice (GCP) regulations established by the Ministry of Health and welfare aim to promote clinical trials of new drugs that are ethical, reliable, and scientifically sound. According to these regulations, utmost importance should be placed on considerations of trial participant safety, welfare and the protection of his or her human rights. To this end, the responsibilities of the sponsor, the institution at which the trials are conducted, and the physician in charge have been clarified. These regulations stipulate that a system must be established which makes it possible for a third party to verify the course and conduct of a clinical trial. The new GCP regulations not only set standards for the development of new drugs, they also mark the beginning of a new era in medical science and treatment in Japan.