Assessment of antimicrobial resistance laboratory-based surveillance capacity of hospitals in Zambia: findings and implications for system strengthening.

BACKGROUND: A well-established antimicrobial resistance (AMR) laboratory-based surveillance (LBS) is of utmost importance in a country like Zambia which bears a significant proportion of the world's communicable disease burden. This study assessed the capacity of laboratories in selected hospitals to conduct AMR surveillance in Zambia. METHODS: This cross-sectional exploratory study was conducted among eight purposively selected hospitals in Zambia between August 2023 and December 2023. Data were collected using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. FINDINGS: Of the assessed facilities, none had full capacity to conduct AMR surveillance with varying capacities ranging from moderate (63% (5/8)) to low (38% (3/8)). Some of the barriers of AMR-LBS were the lack of an electronic laboratory information system (63% (5/8)) and the lack of locally generated antibiograms (75% (6/8)). Quality control for antimicrobial susceptibility testing (AST), pathogen identification and media preparation had the lowest overall score among all of the facilities with a score of 14%, 20% and 44%, respectively. The highest overall scores were in specimen processing (79%), data management (78%), specimen collection, transport and management (71%), and safety (70%). Most facilities had standard operating procedures in place but lacked specimen-specific standard operating procedures. CONCLUSION: The absence of laboratories with full capacity to conduct AMR surveillance hinders efforts to combat AMR and further complicates the treatment outcomes of infectious diseases. Establishing and strengthening LBS systems are essential in quantifying the burden of AMR and supporting the development of local antibiograms and treatment guidelines.

Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer.

PURPOSE: Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. METHODS: Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). RESULTS: The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). CONCLUSIONS: Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry 000026140.

New physician specialty training system impact on distribution of trainees in Japan.

OBJECTIVES: The problem of uneven distribution of medical services and inequitable distribution of physicians is drawing much attention worldwide. Revealing how changes in the specialty training system in Japan have affected the distribution of doctors could help us understand this problem. In 2018, a new and standardized specialty training system was implemented by the Japanese Medical Specialty Board, which is recognized by the Ministry of Health, Labor and Welfare. The purpose of this study was to investigate how this new system has affected the geographical distribution of doctors commencing specialty training (trainees) and choice of specialty in Japan. STUDY DESIGN: Retrospective observational study. METHODS: The change in the number of trainees between the control period (2012-2014) and 2018 was investigated, taking into account the prefecture and specialty selected. Population, the proportion of residents aged 65 years or older (aging rate), and the total number of overall doctors in each prefecture were considered as the background characteristics of each prefecture. We created a Lorenz curve and calculated the Gini coefficient for the distribution of trainees. RESULTS: In 2018, the number of trainees per 100,000 population increased to 6.6 nationwide compared with 5.5 during the control period. The number of trainees per 100,000 population in 2018 increased in prefectures with a large population of ≧ 2,000,000, a low aging rate (<27%), and a high doctor density (≧ 250 doctors per 100,000 population). The Gini coefficient showed an increase to 0.226 in 2018 compared with only 0.160 during the control period. CONCLUSIONS: After the implementation of the new training system, there was an increase in the number of doctors enrolling in specialty programs, and the specialties other than internal medicine and surgery have attracted more trainees. Inequality in the distribution of doctors between urban and rural prefectures worsened. This indicates the need to explore new ways of balancing distribution while maintaining optimal opportunities for specialist training.

Risk assessment of recent Egyptian H5N1 influenza viruses.

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are enzootic in poultry populations in different parts of the world, and have caused numerous human infections in recent years, particularly in Egypt. However, no sustained human-to-human transmission of these viruses has yet been reported. We tested nine naturally occurring Egyptian H5N1 viruses (isolated in 2014-2015) in ferrets and found that three of them transmitted via respiratory droplets, causing a fatal infection in one of the exposed animals. All isolates were sensitive to neuraminidase inhibitors. However, these viruses were not transmitted via respiratory droplets in three additional transmission experiments in ferrets. Currently, we do not know if the efficiency of transmission is very low or if subtle differences in experimental parameters contributed to these inconsistent results. Nonetheless, our findings heighten concern regarding the pandemic potential of recent Egyptian H5N1 influenza viruses.

Occurrence of selected pharmaceuticals in river water in Japan and assessment of their environmental risk.

The existence of pharmaceuticals in the water environment is thought to be a potential problem for aquatic organisms. In this study, we conducted a nationwide survey to clarify the occurrence of 24 selected pharmaceuticals in major Japanese rivers and evaluated their environmental risk to aquatic organisms. We found a total of 22 substances in river waters at concentrations from several nanograms per liter to several micrograms per liter. We found the highest, which was 2.4 µg/L of caffeine, followed by 1.5 µg/L of crotamiton and 1.4 µg/L of sulpiride. We conducted an environmental risk assessment of the 22 pharmaceuticals detected in river water, for which predicted no-effect concentration (PNEC) values for crustacea and algae had been obtained. The measured environmental concentration/PNEC values of four substances, caffeine, carbamazepine, clarithromycin, and ketoprofen, exceeded 0.1 with the maximum value of 9.0 for clarithromycin. As clarithromycin exhibits a high environmental risk to aquatic organisms, particular attention is required.

Assessment of serum KL-6 as a prognostic marker in pulmonary tuberculosis patients.

Although serum Krebs von den Lungen-6 (KL-6) levels are reported to increase in pulmonary tuberculosis (PTB) patients according to disease activity, the relationship between serum KL-6 levels and prognosis remains unclear. In this study, we prospectively examined serum KL-6 levels in 188 PTB patients and assessed 60-day mortality. Univariate and multivariate logistic regression analysis demonstrated that serum KL-6 levels were not significantly associated with prognosis. For receiver operating characteristic analysis, the area under the curve had low accuracy for predicting mortality. These findings indicate that serum KL-6 levels do not perform adequately for use as a prognostic marker in patients with PTB.

SU-E-T-488: Dose Calculation Model Using the Simplified Monte Carlo Method with an Initial Beam Model Adapted to a Beam-Wobbling System.

PURPOSE: We have developed an accurate dose calculation model based on a simplified Monte Carlo (SMC) method adapted to a beam-wobbling delivery system at National Cancer Center Hospital East (NCCHE). We used an initial beam model specific to the beam-wobbling system to reproduce accurately different dose distributions in two lateral directions (x- and y-directions) perpendicular to each other. METHODS: The SMC calculates a dose distribution by tracking individual protons. The SMC starts tracking protons at an entrance of a range compensator. Protons are generated in an initial phase space adapted to the wobbler system. Since two wobbling-magnets are located at separate places with different distances from the iso-center, different dose distributions are formed in x- and y-directions. We derived an initial phase space distribution for the beam-wobbling system using an analytical method. We used the SMC method with the initial beam model to calculate dose distributions accurately. To verify accuracy of the calculation method, we measured the dose distribution in a homogeneous phantom formed by 235 MeV protons passing through a L-shaped range compensator. We used a 2D-array of parallel-plate ionization chambers (2D Array seven29®) to measure dose distributions with a sampling period of 5 mm. RESULTS: The measured dose distribution in the x-direction was different from that in the y-direction. Our calculation model reproduces the measurement results well in both lateral directions. In addition, the calculation reproduced the dose increments in edge regions contributed by edge-scattered protons in collimator. It indicates the advantage of the SMC. CONCLUSIONS: A dose calculation model has been developed based on the simplified Monte Carlo method applied to a beam-wobbling system. By adapting the initial beam model to the wobbling system, the SMC method is found to reproduce observed different dose distributions in x- and y-directions well.

Assessment of the use of a diffuser in propagation-based x-ray phase contrast imaging.

A rotating random-phase-screen diffuser is sometimes employed on synchrotron x-ray imaging beamlines to ameliorate field-of-view inhomogeneities due to electron-beam instabilities and beamline optics phase artifacts. The ideal result is a broader, more uniformly illuminated beam intensity for cleaner coherent x-ray images. The spinning diffuser may be modeled as an ensemble of transversely random thin phase screens, with the resulting set of intensity maps over the detector plane being incoherently averaged over the ensemble. Whilst the coherence width associated with the source is unaffected by the diffuser, the magnitude of the complex degree of second-order coherence may be significantly reduced [K. S. Morgan, S. C. Irvine, Y. Suzuki, K. Uesugi, A. Takeuchi, D. M. Paganin, and K. K. W. Siu, Opt. Commun. 283, 216 (2010)]. Through use of a computational model and experimental data obtained on x-ray beamline BL20XU at SPring-8, Japan, we investigate the effects of such a diffuser on the quality of Fresnel diffraction fringes in propagation-based x-ray phase contrast imaging. We show that careful choice of diffuser characteristics such as thickness and fiber size, together with appropriate placement of the diffuser, can result in the ideal scenario of negligible reduction in fringe contrast whilst the desired diffusing properties are retained.

Assessment of haemophilia treatment practice pattern in Japan.

The current status of replacement therapy for haemophilia and the role played by nurses in Japan were investigated at 16 facilities (17 specialties) each providing care to 20 or more haemophilia A or B patients without inhibitor. The questionnaire was mailed to the nurse or physician in charge of haemophilia at each facility in August 2006, asking the nurse to fill in the questionnaire. Responses were collected on 1318 patients (haemophilia A: 1078 patients; haemophilia B: 240 patients). About 70% of these patients were reported to be severe haemophilia A or B. Overall, 26% were receiving regular prophylaxis while 74% received on-demand therapy with or without temporary prophylaxis before special events. The percentage of patients receiving primary prophylaxis was only 2%. The percentage of adherence to prophylaxis decreased with age (lowest at age 19-29) but this percentage for each age group in Japan was higher than that in the western countries. Of the nurses working at the facilities surveyed, 88% considered prophylaxis as an optimal therapy for severe haemophilia patients, although the percentage of patients receiving prophylaxis for the entire population surveyed was lower than that in the western countries. The main factor precluding introduction of prophylaxis was 'difficulty in venous access' for infants and small children. On the other hand, 'unwillingness of family members' and 'poor adherence' were the main factors precluding introduction of this therapy for those aged over 6 years.

Assessment of the corona radiata sensory tract using awake surgery and tractography.

Anatomical localization of brain function can be achieved by functional changes during awake surgery combined with tractography constructed by diffusion tensor imaging studies. We aimed to use these techniques to characterize the sensory tract in the corona radiata in patients with closely associated brain tumors. Of nine patients who had brain tumors in the primary sensory area (S1) and who underwent awake surgery between October 2004 and July 2007, two patients showed deterioration in deep sensation during and after awake surgery. Both of these patients also developed involuntary movements (for patient 1 this was myoclonus of the left hand, while patient 2 experienced unintentional lifting of the arm). In these two patients, tumors were located just beside the sensory tract in the corona radiata of the right hemisphere. In patient 2, Wallerian degeneration of the sensory tract and concomitant deterioration of superficial and deep sensation were observed at 6 months after awake surgery. These results suggest that damage to a closely associated sensory tract in the corona radiata is critical to the development of sensory deficits and involuntary movements. For patients who undergo surgical resection of S1 brain tumors, pre-operative tractography to detect the sensory tract in the corona radiata may allow protection of the sensory tract during awake surgery, thereby preventing post-operative sensory deficits.

Comparing two methods for assessment of perfusion-diffusion mismatch in a rodent model of ischaemic stroke: a pilot study.

This stroke experiment was designed to define the mismatch between perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in MRI by applying early or instantly acquired PWI. Eight rats were induced with stroke through photothrombotic occlusion of the middle cerebral artery and scanned serially between 1 h and day 3 after induction using DWI and PWI with a 1.5 T MR scanner. The relative lesion volumes (rLV) on MRI and triphenyl tetrazolium chloride-stained specimens were defined as the proportion of lesion volume over brain volume. Discrepancies in the rLV between PWI- and DWI-derived apparent diffusion coefficient (ADC) maps were expressed by subtraction of the ADC from PWI, resulting in three possible patterns: (i) (PWI-ADC > 10% of PWI) denoting a mismatch; (ii) (-(10% of PWI)

Effect of implant support on distal extension removable partial dentures: in vitro assessment.

The implants in implant-supported removable partial dentures (RPDs) are placed in the edentulous ridge to stabilize the RPD and minimize the resultant rotational movement. This study investigated the effect of implant placement on RPD stability. A model simulating a mandibular bilateral distal extension missing was fabricated using epoxy resin and silicone impression material as thin (1 mm) and thick (2 mm) soft tissues. Five pressure sensors (PS-10K, Kyowa, Tokyo, Japan) were attached near the left and right first molars (#36 and #46), first premolars (#34 and #44) and medio-lingual alveolar crest. Five bilateral distal extension RPDs with Co-Cr frameworks were conventionally fabricated. After the implants were placed at the bilateral second molar areas, healing caps (4.5 mm high) were connected to the denture base with autopolymerized resin to support the RPD. As in a conventional RPD, sealing screws were placed without connecting them. Loads up to 5 kg were applied, and the pressure and displacement of the RPDs (n = 5) were simultaneously measured and analysed using the Wilcoxen test (alpha = 0.05). There was less pressure on both thin and thick soft tissues, the #36, #46 and the medio-lingual alveolar crest from the implant-supported RPD than from the conventional RPD (P < 0.05). There were no significant differences in pressure on #34 and #44 between the two RPDs (P > 0.05). There was significantly less denture displacement of the implant-supported RPD than of the conventional denture (P < 0.05). Implant support helped prevent the displacement of distal extension RPDs and decreased the pressure on soft tissues.

Study on risk management of heavy metals for reuse of biosolids.

The behaviour of heavy metals was investigated at 22 wastewater treatment plants (WWTPs). In addition, the survey of heavy metal balance was conducted in detail at one WWTP. For the measurement, 22 types of heavy metals were selected from the chemical materials of pollutant release and transfer register (PRTR). There were some heavy metals, which were detected not in wastewater but in dewatered sludge. By means of the detailed survey at one WWTP, 60 to 80% of some heavy metals, such as B, Mn, Co, Ni and Mo, were discharged with treated water. According to the results of PRTR, Zn, B and Mn accounted for a large part of the discharge into the water course. To estimate the behaviour of heavy metals in the environment, leaching tests were applied to the products made of biosolids. During a series of leaching tests for building materials, it was observed that the concentration of heavy metals was very small, but the ratio of increase keeps a constant value. Therefore, it was considered that the acid extractable contents of heavy metal would be important.

Laparoscopic Heller myotomy and Dor fundoplication for the treatment of achalasia. Assessment in relation to morphologic type.

BACKGROUND: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed. METHODS: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor. RESULTS: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor. CONCLUSIONS: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types.

Prognostic value of nuclear area index in combination with the World Health Organization grading system for patients with renal cell carcinoma.

OBJECTIVES: To assess the diagnostic accuracy of the World Health Organization (WHO) grading system for renal cell carcinoma (RCC) in terms of nuclear size evaluation. Furthermore, the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal tubular cells, is investigated. METHODS: Measurement of the nuclear areas of cancer and normal tubular cells was performed on the histologic slides from the 76 patients with RCC, and the distribution of MNA and NAI was compared among the WHO grades. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the progression-free and cause-specific survival of the patients was examined. RESULTS: MNA for cancer cells and NAI significantly increased according to the grade. NAI was 1.0 or less in 9 of the 10 patients with G1 tumors and more than 1.0 in 12 of the 13 patients with G3 tumors, whereas the NAI ranged widely from 0.53 to 2.0 in 53 patients with G2 tumors. By multivariate analysis, including grade and TNM categories, NAI and MNA were independent variables for survival in all the patients as well as for cancer progression in localized disease. CONCLUSIONS: WHO G2 RCCs are actually composed of tumors with varying nuclear size, and the prognosis of the patients with G2 tumors varied as well. NAI could provide improved prognostic information for the patients with RCC, especially in G2 cases.

Heart transplantation in children in foreign countries with reference to medical, transportation, and financial issues.

Heart transplantation is increasingly becoming accepted worldwide as therapy for end-stage heart failure not only in adult patients but also in pediatric practice. The new law in Japan for organ transplantation from brain-dead patients was established on 16 October 1998, but there is no definite law or protocol for brain death in children under the age of 6 years and children less than 15 years of age cannot become donors. These facts make organ transplantation from the cadavers of neonates, infants and young children almost impossible in Japan, even though there are children who need heart or heart-lung transplantation. The present authors have to date transferred 8 patients to the USA or Germany for heart transplantation: 4 successfully underwent heart transplantation, but 4 died during the waiting period overseas. There are many things to consider; not only the medical problems involved in transportation, but also the financial issues when transferring patients to other countries. This report details the experience with the 8 cases that were transferred overseas for heart transplantation, and highlights the problems that need to be considered.

Easy assessment of ES cell clone potency for chimeric development and germ-line competency by an optimized aggregation method.

Production of germ-line competent chimeric mice from embryonic stem (ES) cells is an inevitable step in establishing gene-manipulated mouse lineages. A common method used for creating chimeric mice is the injection of ES cells into the blastocoelic cavity (blastocyst injection). The aggregation method is an alternative way to introduce ES cells to the host embryo which is less difficult than blastocyst injection. Here we re-examined the condition of embryo-ES cell coculture on the aggregation method and found improvement of germ-line competent chimeric production by a simple modification of the coculture medium. Moreover, R1 ES cell and its 10 gene-manipulated subclones were tested by this method. Although all ES cell clones showed good morphology and a normal karyotype, the efficiency of chimeric development and germ-line transmission varied among clones and were classified into three grades according to germ-line competency. In the first group (class A), both the incidence of chimera with high ES cell contribution and the rate of germ-line transmission were fairly high. Germ-line competent chimeras were obtained but with rather low efficiency in the second group (class B), while another group (class C) showed an absence of high ES cell-contributed chimeras and no germ-line transmission. These results suggest the usefulness of this modified aggregation method to predict the potency of ES cell clones for germ-line competency.

[Assessment of global and regional LV function obtained by quantitative gated SPECT using 99mTc-tetrofosmin: comparison with left ventricular cineangiography and echocardiography].

The quantitative gated SPECT (QGS) software that has automatic edge detection algorithm of the left ventricle, is able to calculate LV volumes and visualize LV wall motion with perfusion throughout the cardiac cycle. We evaluated the reliability of global and regional LV function derived from QGS using 99mTc-tetrofosmin by comparing with left ventricular cineangiography (LVG) and echocardiography (ECHO). In 22 cardiac patients, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were calculated. Using cinematic display, regional LV wall motion were scored on a 3-point scale (1 = normal, 2 = hypokinesis, 3 = akinesis; WMS). EDV, ESV and LVEF correlated well with those by LVG (p < 0.001 for each). Correlation between WMS derived from QGS and ECHO was high (r = 0.85, p < 0.001). There was an inverse correlation between WMS and LVEF (r = 0.77, p < 0.001). In conclusion, QGS is useful to evaluate global LV function. Regional wall motion evaluated by QGS is good enough for clinical application.

Determination of 8-hydroxy-deoxyguanosine formation in rat organs: assessment of paraquat-evoked oxidative DNA damage.

Paraquat has previously been shown to cause the oxidative damage to DNA in variety of cells and tissues. However, although paraquat-evoked strand breaks has been extensively studied to assess the DNA damage, the effect of paraquat on base modifications, another marker for the oxidative damage, has not yet been investigated. To further characterize paraquat-evoked DNA damage, the effect of paraquat on 8-hydroxy-deoxyguanosine (8-OH-dG) formation in various rat organs was examined. Paraquat markedly increased 8-OH-dG contents in various organs, particularly in brain, lung and heart, and this increase reached the maximum levels at 5 days after the drug administration. In contrast, the formation of 8-hydroxy-guanosine (8-OH-G), a marker for the oxidative damage to RNA, was not significantly affected by paraquat. These results indicate that paraquat causes base modifications as well as strand breaks as a consequence of the oxidative damage to DNA.