[An analysis of the outbreak situation and background risk factors for drug-resistant urinary tract infection in nursing homes].

AIM: The present study clarified the outbreak situation and background risk factors for drug-resistant bacteria infection in nursing homes. METHODS: Subjects were 48 elderly individuals with urinary tract infections in 3 nursing homes during the 12-month period from January to December 2020. We analyzed the drug resistance of cultured bacteria using medical records. RESULTS: Escherichia coli was the most frequently cultured bacteria (37.1%), and extended-spectrum ß-lactamase (ESBL) -producing E. coli accounted for 26.1% of specimens. E. coli susceptibility to levofloxacin (LVFX) was seen in 47.8%, resistance in 47.8%, and intermediate response in 4.4%. E. coli susceptibility to ceftriaxone (CTRX) was seen in 73.9%, and resistance in 26.1%. E. coli susceptibility to sulfamethoxazole trimethoprim (ST) mixture was seen 81.8%, while resistance was seen in 18.2%. In addition, among ESBL-producing E. coli, susceptibility to LVFX was seen in 0% and resistance in 83.3%, and an intermediate response was seen in 16.7%, while susceptibility to ST mixture was seen in 83.3% and resistance in 16.7%. No marked differences in background risk factors were seen between the groups with LVFX-resistant and LVFX-susceptible E. coli. However, the body mass index was significantly lower (p=0.0389), and significantly more patients were treated with antimicrobial agents during the 1-year period preceding the sample acquisition and analysis (p=0.0418) in the group with CTRX-resistant E. coli than in the group with CTRX-susceptible E. coli. CONCLUSION: In the nursing homes examined, LVFX-resistant E. coli were highly prevalent, and ESBL-producing bacteria were also common. When we treat urinary tract infections, refraining from the use of LVFX is desirable, and antimicrobials should be chosen with care.

Comparison of the Causes of Death Identified Using Automated Verbal Autopsy and Complete Autopsy among Brought-in-Dead Cases at a Tertiary Hospital in Sub-Sahara Africa.

BACKGROUND: Over one-third of deaths recorded at health facilities in Zambia are brought in dead (BID) and the causes of death (CODs) are not fully analyzed. The use of automated verbal autopsy (VA) has reportedly determined the CODs of more BID cases than the death notification form issued by the hospital. However, the validity of automated VA is yet to be fully investigated. OBJECTIVES: To compare the CODs identified by automated VA with those by complete autopsy to examine the validity of a VA tool. METHODS: The study site was the tertiary hospital in the capital city of Zambia. From September 2019 to January 2020, all BID cases aged 13 years and older brought to the hospital during the daytime on weekdays were enrolled in this study. External COD cases were excluded. The deceased's relatives were interviewed using the 2016 World Health Organization VA questionnaire. The data were analyzed using InterVA, an automated VA tool, to determine the CODs, which were compared with the results of complete autopsies. RESULTS: A total of 63 cases were included. The CODs of 50 BID cases were determined by both InterVA and complete autopsies. The positive predictive value of InterVA was 22%. InterVA determined the CODs correctly in 100% cases of maternal CODs, 27.5% cases of noncommunicable disease CODs, and 5.3% cases of communicable disease CODs. Using the three broader disease groups, 56.0% cases were classified in the same groups by both methods. CONCLUSION: While the positive predictive value was low, more than half of the cases were categorized into the same broader categories. However, there are several limitations in this study, including small sample size. More research is required to investigate the factors leading to discrepancies between the CODs determined by both methods to optimize the use of automated VA in Zambia.

Verification of Usefulness of Pediatric Head Trauma Imaging Protocol Combining Computerized Tomography, Observation Unit, and Magnetic Resonance Imaging.

METHODS: This prospective observational study conducted in our hospital between October 2016 and September 2019 included 1946 patients aged 0 to 15 years with head trauma, of whom 1137 were analyzed. Computed tomography scan rate and imaging examination (CT or MRI) rate of our protocol were investigated. Sensitivity and negative predictive value (NPV) were calculated. We also compared our protocol and other clinical decision rules with respect to CT scan rate, sensitivity, and NPV in the same cohort and outcomes. RESULTS: The CT scan rate of our protocol was 7.9%, and the imaging examination rate, including MRI, was 12.2%. When the outcome was set to intracranial injury, the sensitivity and NPV of our protocol were each 100%. The CT scan rates in each cohort were 14.5% for PECARN (8.1% for our protocol), 34.7% for CATCH (23.2% for ours), and 13.6% for CHALICE (7.9% for ours). The sensitivity and NPV in each cohort were 100% and 100% for PECARN (92.3% and 100% for ours), 64.7% and 92.6% for CATCH (100% and 100% for ours), and 83.9% and 99.5% for CHALICE (100% and 100% for ours), respectively. CONCLUSIONS: The protocol we created by combining CT, observation unit, and MRI was considered to be useful for practice in pediatric head injury cases.

Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL. Methods: We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke. They underwent quantitative single-photon emission computed tomography using an autoradiographic method at rest and after acetazolamide (ACZ) administration. Regional cerebral blood flow (rCBF) in the cerebral cortex, lenticular nucleus, thalamus, and cerebellum was measured. We compared the rCBF parameters between patients with and without stroke. Results: The baseline characteristics and magnetic resonance imaging findings were similar between the two groups, except for a higher frequency of pyramidal tract sign (75% vs. 0%) and a larger number of old lacunes (15.4 ± 8.8 vs. 2.2 ± 1.8) in the patients with stroke. Of the rCBF parameters measured, significantly lower flow (mL/100 g/min) was observed in ACZ-rCBF in the thalamus (35.6 ± 9.4 vs. 51.1 ± 7.6, p = 0.01) and ΔrCBF in the thalamus (10.6 ± 3.7 vs. 21.0 ± 7.9, p = 0.02) in the patients with stroke. Conclusion: Cerebrovasoreactivity in the thalamus was significantly associated with stroke in patients with CADASIL.

Rapid assessment of the civil registration and vital statistics performance of health facilities in the five districts of Zambia: A cross-sectional study.

BACKGROUND: Civil registration and vital statistics (CRVS) are essential administrative tools for accurate statistical data on vital events. However, civil registration coverage is particularly poor in low- and middle-income countries. Currently, CRVS are attracting global attention, as their improvement is considered a priority. While health facility is one of the important actors involved in the management of quality CRVS, its function in CRVS remains unclear. Therefore, this work aims to investigate the CRVS performance of the health facility in Zambia, a low-income country, and identify the gaps for effective policy-making. METHODS: To assess the health facilities' CRVS performance, a questionnaire was developed based on existing assessment tools for the whole CRVS; this comprised 21 multiple-choice questions in 10 areas with four choices awarded between 0 and 3 points according to performance. These questionnaire-based interviews were conducted by information officers in all health facilities per first, secondary, and tertiary-level in five target districts of Zambia, selected via socioeconomic and geographic features. The average points were calculated in each area by each level of healthcare system and summarized in a single chart. RESULTS: The results indicated low scores in the following areas: staff compliance with standard reporting procedures, infrastructure, capacity of coding based on International Classification of Diseases among health personnel, documentation of the cause of death in medical records, and absence of a system to identify the cause of death of brought-in-dead cases. CONCLUSION: The tool developed in this work to evaluate the CRVS performance of health facilities was useful for identifying the gaps that need to be overcome to ensure the quality of CRVS in Zambia. However, its validity should be further investigated in other areas in Zambia as well as in other countries.

Analysis of causes of death among brought-in-dead cases in a third-level Hospital in Lusaka, Republic of Zambia, using the tariff method 2.0 for verbal autopsy: a cross-sectional study.

BACKGROUND: Over one third of deaths in Zambian health facilities involve someone who has already died before arrival (i.e., Brough in Dead), and in most BiD cases, the CoD have not been fully analyzed. Therefore, this study was designed to evaluate the function of automated VA based on the Tariff Method 2.0 to identify the CoD among the BiD cases and the usefulness by comparing the data on the death notification form. METHODS: The target site was one third-level hospital in the Republic of Zambia's capital city. All BiD cases who reached the target health facility from January to August 2017 were included. The deceased's closest relatives were interviewed using a structured VA questionnaire and the data were analyzed using the SmartVA to determine the CoD at the individual and population level. The CoD were compared with description on the death notification forms by using t-test and Cohen's kappa coefficient. RESULTS: One thousand three hundred seventy-eight and 209 cases were included for persons aged 13 years and older (Adult) and those aged 1 month to 13 years old (Child), respectively. The top CoD for Adults were infectious diseases followed by non-communicable diseases and that for Child were infectious diseases, followed by accidents. The proportion of cases with a determined CoD was significantly higher when using the SmartVA (75% for Adult and 67% for Child) than the death notification form (61%). A proportion (42.7% for Adult and 46% for Child) of the CoD-determined cases matched in both sources, with a low concordance rate for Adult (kappa coefficient = 0.1385) and a good for Child(kappa coefficient = 0.635). CONCLUSIONS: The CoD of the BiD cases were successfully analyzed using the SmartVA for the first time in Zambia. While there many erroneous descriptions on the death notification form, the SmartVA could determine the CoD among more BiD cases. Since the information on the death notification form is reflected in the national vital statistics, more accurate and complete CoD data are required. In order to strengthen the death registration system with accurate CoD, it will be useful to embed the SmartVA in Zambia's health information system.

Genotype-phenotype correlations and effect of mutation location in Japanese CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by NOTCH3, and characterized by recurrent cerebral ischemic events without vascular risk factors, mood disturbance, and dementia. MRI testing shows cerebral white matter hyperintensities, especially in the external capsule and temporal pole. Typical mutations are cysteine-related missense ones located in one of 34 EGF-like repeats (EGFr) in the NOTCH3 receptor. To identify genotype-phenotype correlations, 179 Japanese CADASIL probands were recruited. Of the 68 mutations identified, p.Cys388Arg, p.Cys435Phe, p.Gly481Cys, p.Cys743Tyr, and p.Cys1009Phe were novel ones. The genotype-phenotype correlation was analyzed based on the three most common mutations: p.Arg75Pro, p.Arg141Cys, and p.Arg182Cys. p.Arg141Cys showed typical CADASIL phenotypes, whereas p.Arg75Pro showed mild and atypical phenotypes, a low frequency of stroke/TIA, high frequency of hypertension, and low frequency of temporal pole lesions. p.Arg182Cys showed various initial symptoms other than stroke/TIA. Subsequently, we analyzed the effect of the mutation location on the age at onset of stroke/TIA. We found that mutations in EGFr 1-6 excluding the cysteine-sparing mutation p.Arg75Pro were significantly correlated with a younger age at onset of stroke/TIA compared with those in EGFr 7-34. This was in agreement with a recent European report, suggesting that the effect of the mutation location is a consensus finding in CADASIL worldwide.

Quantification of Blood Caffeine Levels in Patients With Parkinson's Disease and Multiple System Atrophy by Caffeine ELISA.

Caffeine is considered to be a neuroprotective agent against Parkinson's disease (PD) and is expected to offer a blood-based biomarker for the disease. We herein investigated the ability of this biomarker to discriminate between PD and neurodegenerative diseases. To quantify caffeine concentrations in serum and plasma, we developed a specific competitive enzyme-linked immunosorbent assay (ELISA). To validate the diagnostic performance of the assay, we conducted a case control-study of two independent cohorts among controls and patients with PD and multiple system atrophy (MSA). Parallelism, recovery rate, and intra- and inter-assay precision of our assay were within the standard of acceptance. In the first cohort of 31 PD patients, 18 MSA patients and 33 age-matched controls, serum caffeine levels were significantly lower in PD patients than in Controls (p = 0.018). A similar trend was also observed in the MSA group, but did not reach the level of significance. In the second cohort of 50 PD patients, 50 MSA patients and 45 age-matched controls, plasma caffeine levels were significantly decreased in both PD and MSA groups compared to Controls (p < 0.001). This originally developed ELISA offered sufficient sensitivity to detect caffeine in human serum and plasma. We reproducibly confirmed decreased blood concentrations of caffeine in PD compared to controls using this ELISA. A similar trend was observed in the MSA group, despite a lack of consistent significant differences across cohorts.

Analysis of gut microbiota in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a major hereditary small vessel disease caused by mutations in NOTCH3. The variations in progression and severity among patients suggest that the CADASIL phenotype is modified by some genetic and environmental factors. Recent studies have shown the potential roles of gut microbiota in human diseases. We hypothesized that gut microbiota modifies the disease phenotype. We performed gut microbial meta 16S rRNA analysis of fecal samples from 15 CADASIL patients and 16 controls. The microbial α- and ß-diversities and taxonomy were compared between CADASIL patients and controls and between CADASIL patients with and without an ischemic stroke history. No significant difference in α- or ß-diversity was observed in either case-control or subgroup comparisons. In the taxonomic microbial analysis, there was a significant increase in abundance of 6 genera and significant decrease in 2 genera in CADASIL patients compared with controls. There was a significant decrease in abundance of 2 genera in CADASIL patients with compared with those without stroke. This is the first study on CADASIL focusing on gut microbiota. Our findings suggest that gut microbiota modifies the onset and progression of CADASIL.

Towards genomic database of Alexander disease to identify variations modifying disease phenotype.

Alexander disease (AxD) is an extremely rare neurodegenerative disorder caused by glial fibrillary acidic protein (GFAP) gene mutations. Compared with the cerebral type, which is characterized by infantile onset, the bulbospinal type and intermediate form are associated with a late onset, spanning from juveniles to the elderly, and more diverse clinical spectrum, suggesting the existence of factors contributing to phenotypic diversity. To build a foundation for future genetic studies of this rare disease, we obtained genomic data by whole exome-sequencing (WES) and DNA microarray derived from thirty-one AxD patients with the bulbospinal type and intermediate form. Using this data, we aimed to identify genetic variations determining the age at onset (AAO) of AxD. As a result, WES- or microarray-based association studies between younger (<45 years; n = 13)- and older (≥45 years; n = 18)-onset patients considering the predicted GFAP-mutation pathogenicity identified no genome-wide significant variant. The candidate gene approach identified several variants likely correlated with AAO (p < 0.05): GAN, SLC1A2, CASP3, HDACs, and PI3K. Although we need to replicate the results using an independent population, this is the first step towards constructing a database, which may serve as an important tool to advance our understanding of AxD.

The CADASIL Scale-J, A Modified Scale to Prioritize Access to Genetic Testing for Japanese CADASIL-Suspected Patients.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is definitely diagnosed by genetic testing. Such testing involves the analysis of exons 2-24 of NOTCH3, which encode the epidermal growth factor-like repeat domain, where CADASIL mutations are localized. We previously reported clinical diagnostic criteria for screening CADASIL-suspected Japanese patients prior to genetic testing. Because of its high sensitivity but low specificity, most patients need to undergo genetic testing. In this study, we aimed to develop the CADASIL scale-J, a modified scale to prioritize access to genetic testing for CADASIL-suspected Japanese patients. METHODS: We modified the CADASIL scale reported by Pescini et al based on clinical features of 126 CADASIL patients and 53 NOTCH3-negative CADASIL-like patients diagnosed up until March 2016 (Phase 1). For validation, we recruited 69 consecutive patients for genetic testing of NOTCH3 from April 2016 to March 2017 (Phase 2). RESULTS: We developed the CADASIL scale-J with a score ranging from 0 to 25 and the cut-off value of 16, using 8 items: hypertension, diabetes, young onset (≤50 years old), pseudobulbar palsy, stroke/TIA, family history, subcortical infarction, and temporal pole lesion. The sensitivity and specificity of the CADASIL scale-J were 78.9% and 85.7%, respectively. In Phase 2, we obtained a positive predictive value of 70.0% and a negative predictive value of 89.2%. In this study, we identified 54 mutations, 7 of which were novel. CONCLUSIONS: The CADASIL scale-J is helpful to prioritize access to genetic testing for CADASIL-suspected Japanese patients.

Cerebral Toxoplasmosis Diagnosed by Nested-polymerase Chain Reaction in a Patient with Rheumatoid Arthritis.

A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on brain magnetic resonance imaging. We discontinued methotrexate for RA and started a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was interrupted because of adverse reactions, her prognosis was favorable. The Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR) from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by nested-PCR is useful for the diagnosis and safer than a brain biopsy. In addition, the discontinuation of immunosuppressants may be recommended in patients compromised by those immunosuppressants.

Analysis of efficacy and safety of dulaglutide 0.75 mg stratified by sex in patients with type 2 diabetes in 2 randomized, controlled phase 3 studies in Japan.

We analyzed the efficacy and safety of once weekly dulaglutide 0.75 mg by sex in 2 randomized, controlled phase 3 studies in Japanese patients with type 2 diabetes (a 52-week monotherapy study [comparator liraglutide 0.9 mg] and a 26-week combination therapy study [comparator insulin glargine]). Females comprised 18% of patients in the monotherapy study and 29% of patients in the combination therapy study. Mean reductions from baseline in glycated hemoglobin (HbA1c) were similar between the sexes for dulaglutide- and liraglutide-treated patients (range -1.17% to -1.49%). Females had numerically greater weight loss or less weight gain than males across all treatment groups. The percentages of patients with reductions in both HbA1c and weight from baseline were also greater for females than for males in all treatment groups. In all treatment groups, the incidences of treatment-emergent adverse events tended to be greater among females than among males. No differences in the incidences of total or nocturnal hypoglycemia were observed between the sexes in any treatment group. Overall, in 2 studies in Japan, across all treatment groups it appeared that HbA1c lowering was unaffected by patient sex, while female patients had greater weight loss or less weight gain and greater incidence of adverse events, including nausea, compared to male patients. Incidences of patients discontinuing dulaglutide early due to adverse event were low (<10%) for both sexes, and no new safety concerns related to dulaglutide were identified for either sex. Therefore, the benefit/risk ratio for dulaglutide remains unchanged, positive for both sexes.

[A Case of Neuromyelitis Optica with Relapse Symptoms from Paroxysmal Pruritus].

We report the case of a 34-year-old woman who presented with neuromyelitis optica and paroxysmal pruritus. She noticed an itching sensation with no obvious rash in the right postauricular region. Seven days later, the pruritus changed to an abnormal, painful sensation. One month after the onset of the painful sensation, she was hospitalized due to abnormal sensations that extended along the right side of her body and extremities. A hyperintense area on T2-weighted imaging was accompanied by partial enhancement that extended from the lower medulla oblongata to the upper cervical spinal cord. The anti-aquaporin (AQP)-4 antibody was detected in serum. The patient had a history of optic neuritis. Therefore, neuromyelitis optica (NMO) was diagnosed. Her symptoms improved after intravenous and oral corticosteroid treatment. Itching attacks have been occasionally reported with multiple sclerosis, but many of these cases were described before the discovery of the anti-AQP4 antibody. Information on pruritus in serologically confirmed NMO is lacking. We should be aware that patients with NMO can experience recurrence that develops as pruritus.

Complete mineralization of propyzamide in aqueous solution containing TiO2 particles and H2O2 by the simultaneous irradiation of light and ultrasonic waves.

Environmental problems arise from the pollution of ground water and soil by propyzamide, 3,5-dichloro-N-(3-methyl-1-butyn-3-yl) benzamide, which is a popular herbicide. To decompose propyzamide, aqueous solutions containing propyzamide and TiO2 particles was irradiated by light. The photocatalytic decomposition was accelerated when the solution temperature and pH were high. The temperature dependence was due to the adsorption processes of propyzamide on the TiO2 particles. The decomposition was further promoted by addition of H2O2 because of its effective electron-trapping and generated *OH which was available to decompose propyzamide. Although no propyzamide was detected in the solution after the irradiation time of about 20 min, the decomposed intermediate compounds still remained. In order to mineralize completely propyzamide, simultaneous irradiation by light and ultrasonic waves was carried out. The hybrid effect of the irradiation by light and ultrasonic waves in conjunction with H2O2 was first confirmed to achieve the complete mineralization of propyzamide.