Anti-vascular endothelial growth factor biosimilars for neovascular age-related macular degeneration.

RATIONALE: Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss and disability worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is an effective treatment option that helps to prevent vision loss or to improve visual acuity in people with neovascular AMD, treatment imposes a significant financial burden on patients and healthcare systems. A biosimilar is a biological product that has been developed to be nearly identical to a previously approved biological product. The use of biosimilars may help reduce costs and so may increase patient access to effective biologic medicines with similar levels of safety to the drugs on which they are based. OBJECTIVES: To assess the benefits and harms of anti-VEGF biosimilar agents compared with their corresponding anti-VEGF agents (i.e. the reference products) that have obtained regulatory approval for intravitreal injections in people with neovascular AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was 2 June 2023. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) that compared approved anti-VEGF biosimilars with their reference products for treating the eyes of adult participants (≥ 50 years) who had an active primary or recurrent choroidal neovascularization lesion secondary to neovascular AMD. OUTCOMES: Our outcomes were: best-corrected visual acuity (BCVA), central subfield thickness (CST), vision-related quality of life, serious ocular and non-ocular adverse events (AE), treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADAs), and serum concentrations of biosimilars and reference drugs. RISK OF BIAS: We assessed the risk of bias (RoB) for seven outcomes reported in a summary of findings table by using the Cochrane RoB 2 tool. SYNTHESIS METHODS: We synthesized results for each outcome using meta-analysis, where possible, by calculating risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for dichotomous outcomes and continuous outcomes, respectively. Where this was not possible due to the nature of the data, we summarized the results narratively. We used GRADE to assess the certainty of evidence for prespecified outcomes. INCLUDED STUDIES: We included nine parallel-group multi-center RCTs that enrolled a total of 3814 participants (3814 participating eyes), with sample sizes that ranged from 160 to 705 participants per study. The mean age of the participants in these studies ranged from 67 to 76 years, and the proportion of women ranged from 26.5% to 58.7%. Ranibizumab (Lucentis) was the reference product in seven studies, and aflibercept (Eyelea) was the reference product in two others. All the included studies had been supported by industry. The follow-up periods ranged from 12 to 52 weeks (median 48 weeks). Five studies (56%) were conducted in multi-country settings across Europe, North America and Asia, two studies in India, and one each in Japan and the Republic of Korea. We judged all the included studies to have met high methodological standards. SYNTHESIS OF RESULTS: With regard to efficacy, our meta-analyses demonstrated that anti-VEGF biosimilars for neovascular AMD resulted in little to no difference compared with the reference products for BCVA change at 8 to 12 weeks (MD -0.55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% CI -1.17 to 0.07; 8 studies, 3603 participants; high-certainty evidence) and the proportion of participants who lost fewer than 15 letters in BCVA at 24 to 48 weeks (RR 0.99, 95% CI 0.98 to 1.01; 7 studies, 2658 participants; moderate-certainty evidence). Almost all participants (96.6% in the biosimilar group and 97.0% in the reference product group) lost fewer than 15 letters in BCVA. The evidence from two studies suggested that there was no evidence of difference between biosimilars and reference products in vision-related quality of life measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) summary scores at 24 to 48 weeks (MD 0.82, 95% CI -0.70 to 2.35; 2 studies, 894 participants; moderate-certainty evidence). With regard to the safety profile, meta-analyses also revealed little to no difference between anti-VEGF biosimilars and the reference products for the proportion of participants who experienced serious ocular AEs (RR 1.24, 95% CI 0.68 to 2.26; 7 studies, 3292 participants; moderate-certainty evidence), and for TEAEs leading to investigational product discontinuation or death (RR 0.96, 95% CI 0.63 to 1.46; 8 studies, 3497 participants; moderate-certainty evidence). Overall, 1.4% of participants in the biosimilar group and 1.2% in the reference product group experienced serious ocular adverse events. The most frequently documented serious ocular AEs were retinal hemorrhage and endophthalmitis. Although the evidence is of low certainty due to imprecision, meta-analysis suggested that anti-VEGF biosimilars led to no difference compared with the reference products for cumulative incidence of ADAs (RR 0.84, 95% CI 0.58 to 1.22; 8 studies, 3066 participants; low-certainty evidence) or mean maximum serum concentrations (MD 0.42 ng/mL, 95% CI -0.22 to 1.05; subgroup of 3 studies, 100 participants; low-certainty evidence). We judged the overall risk of bias to be low for all studies. AUTHORS' CONCLUSIONS: In our review, low to high certainty evidence suggests that there is little to no difference, to date, between the anti-VEGF biosimilars approved for treating neovascular AMD and their reference products in terms of benefits and harms. While anti-VEGF biosimilars may be a viable alternative to reference products, current evidence for their use is based on a limited number of studies - particularly for comparison with aflibercept - with sparse long-term safety data, and infrequent assessment of quality of life outcomes. Our effect estimates and conclusions may be modified once findings have been reported from studies that are currently ongoing, and studies of biosimilar agents that are currently in development. FUNDING: Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. Takeshi Hasegawa and Hisashi Noma were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239). REGISTRATION: Protocol available via doi.org/10.1002/14651858.CD015804.

Relationship between carbapenem use and major diagnostic category in curative care beds: Analysis of a 2020 Japanese national administrative database.

Excessive carbapenem use has contributed to the spread of carbapenem-resistant bacteria. In response, Japan's revised National Action Plan on Antimicrobial Resistance (AMR) 2023-2027 set the goal of a 20 % reduction in carbapenem use. The aim of this study is to reveal the circumstances associated with carbapenem use in diagnosis procedure combination (DPC) community hospitals and fee-for-service hospitals, which account for the majority of the hospitals in Japan. We analyzed publicly available data from the Survey of Discharged Patients conducted by the Ministry of Health, Labour and Welfare in 2020. We used multiple regression analysis to identify the factors associated with carbapenem use in small- to medium-sized hospitals. Considerable carbapenem use was observed in small- to medium-sized hospitals. There was a large difference in carbapenem use among curative care beds in both DPC community hospitals and non-DPC hospitals. Linear regression models showed the significant association of several major diagnostic categories (MDCs) with carbapenem use. In particular, rates of MDC No.02 (eye) and 05 (circulatory system) were potentially associated with excessive or inappropriate carbapenem use. A notable and novel study finding was that there was a large difference in carbapenem consumption as the number of curative care beds increased in both DPC community hospitals and non-DPC hospitals. This may contribute to the identification of carbapenem overuse and toward achieving the goal of the National Action Plan on AMR 2023-2027. Furthermore, identifying factors associated with carbapenem use helps in understanding disease-specific prescribing practices and detecting potential overuse.

Efficacy of carbapenems and alternative antimicrobials for treating complicated urinary tract infections caused by third-generation cephalosporin-resistant gram-negative bacteria: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking. OBJECTIVES: This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens. METHODS: In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov, were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95 % confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I2 statistics. RESULTS: Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95 % CI, 0.63-1.49; I2 = 21 %; low certainty of evidence). CONCLUSIONS: Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins.

An epidemiological evaluation of COVID-19 in La paz, Bolivia.

INTRODUCTION: The Plurinational State of Bolivia (Bolivia) has experienced four major waves of coronavirus disease 2019 (COVID-19) so far. Although the ministry of health has been tracking morbidity and mortality through each wave, epidemiology of COVID-19 in Bolivia is not well defined, despite a need for more accurate measurement of the number of cases and deaths to allow for forecasting of the pandemic. This study examined prevalence of COVID-19 at community level, determinants of its occurrence and vaccine effectiveness. METHODS: We conducted a cross-sectional study in La Paz city on 2,775 individuals between March 2020 and February 2022. A structured questionnaire was used to collect data on COVID-19 morbidity, mortality and vaccination status. RESULTS: Of the 2,775 participants, 1,586 (57.1%) were infected with COVID-19, and 187 (6.7%) were suspected cases. The mortality rate was 2.9%. Sinopharm, Johnson & Johnson, Gamaleya, Pfizer-BioNtech, Moderna and AstraZeneka vaccines are in use, and all vaccines have demonstrated effectiveness in reducing the risk of onset. Risk for mortality was significantly lower in the vaccinated group with an odds ratio of 0.037 (95％ confidential interval: 0.01-0.10, p-value: <0.001). CONCLUSIONS: Actual prevalence of COVID-19 in La Paz (the prevalence rate: 63.8%, including suspected case) was higher than that reported by the Ministry of Health and Sports in Bolivia (7.5%). In addition, vaccination has contributed significantly to the control of the COVID-19 epidemic in Bolivia. We believe that our report will be useful for COVID-19 prevention strategies in Bolivia for the future.

Evaluation of cortical superficial siderosis in patients with cognitive dysfunction using 3D FLAIR and 3D DIR.

OBJECTIVES: Our aim was to evaluate the detectability of cortical superficial siderosis (cSS) by 3D FLAIR and 3D DIR images in comparison with the SWI images in patients with cognitive dysfunction. METHODS: We studied 246 patients with cognitive dysfunction (144 women, 102 men; mean age: 75.5 ± 7.53 years) who visited a memory clinic at our hospital and underwent MR examinations at 3 T. Specifically, 16 patients with Alzheimer disease (AD) (n = 11) and AD with cerebrovascular disease (n = 5) manifested cSS based on SWI. Each set of MR images (3D FLAIR and 3D DIR) was reviewed by two reviewers separately for the detection of sulcal hyperintensity that suggested cSS. RESULTS: SWI detected a greater number of cSS sulci than 3D DIR and 3D FLAIR. The sensitivity and specificity for the detection of sulcal hyperintensity were the same between 3D FLAIR and 3D DIR (87.5%/100%). However, 3D DIR detected a greater number of cSS sulci than 3D FLAIR (p = .005). CONCLUSIONS: Our study showed that 3D DIR and 3D FLAIR can detect sulcal hyperintensity related to cSS although they are less sensitive to cSS lesions than SWI. KEY POINTS: • 3D FLAIR and 3D DIR can show sulcal signal abnormalities related to cSS in patients with cognitive dysfunction. • 3D FLAIR and 3D DIR detect sulcal hyperintensity of cSS, although they are less sensitive to cSS than SWI. • Signal alterations due to cSS are more detectable in 3D DIR than in 3D FLAIR.

Association between cortical microinfarcts and total small vessel disease burden in cerebral amyloid angiopathy on 3-Tesla magnetic resonance imaging.

BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are frequently found in the brains of patients with advanced cerebral amyloid angiopathy (CAA) at autopsy. The small vessel disease (SVD) score for CAA (i.e., the CAA-SVD score) has been proposed to evaluate the severity of CAA-associated vasculopathic changes by a combination of magnetic resonance imaging (MRI) markers. The aim of this study was to examine the association between total CAA-SVD score and features of CMIs on in vivo 3-Tesla MRI. METHODS: Eighty patients with probable CAA were retrospectively analyzed. Lobar cerebral microbleeds, cortical superficial siderosis, enlargement of perivascular space in the centrum semiovale and white matter hyperintensity were collectively assessed, and the total CAA-SVD score was calculated. The presence of CMI was also examined. RESULTS: Of the 80 patients, 13 (16.25%) had CMIs. CMIs were detected more frequently in the parietal and occipital lobes. A positive correlation was found between total CAA-SVD score and prevalence of CMI (ρ = 0.943; p = 0.005). Total CAA-SVD score was significantly higher in patients with CMIs than in those without (p = 0.009). In a multivariable logistic regression analysis, the presence of CMIs was significantly associated with total CAA-SVD score (odds ratio 2.318 [95% confidence interval 1.228-4.376]; p = 0.01, per each additional point). CONCLUSIONS: The presence of CMIs with a high CAA-SVD score could be an indicator of more severe amyloid-associated vasculopathic changes in patients with probable CAA.

Long-term MRI changes in a patient with Kelch-like protein 11-associated paraneoplastic neurological syndrome.

BACKGROUND AND PURPOSE: The aim of this study was to identify the long-term radiological changes, autoantibody specificities, and clinical course in a patient with kelch-like protein 11 (KLHL11)-associated paraneoplastic neurological syndrome (PNS). METHODS: Serial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage-display ImmunoPrecipitation and Sequencing (PhIP-Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue. RESULTS: A 42-year-old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a "hot-cross-bun sign", and low-signal intensity on susceptibility-weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP-Seq enriched for KLHL11-derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co-localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti-KLHL11 antibody-positive particles in cytoplasm. CONCLUSIONS: This study suggests that KLHL11-PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2-FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.

Determinants of clinic doctors' attitudes concerning antimicrobial prescription for patients with common colds or bronchitis: Additional analysis of a nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases.

BACKGROUND: In 2019, the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases reported nationwide, cross-sectional questionnaire survey data investigating the clinical status of clinic doctors' attitudes to antimicrobial stewardship. This study aimed to identify factors determining clinic doctors' attitudes concerning antimicrobial prescription for patients with a common cold or bronchitis. METHODS: In February 2018, 1500 randomly selected community-based medical clinics in Japan were sent a questionnaire. Primary and secondary endpoints were clinic doctors' attitudes concerning antimicrobial prescription, and antimicrobial medication types prescribed for patients with a common cold or bronchitis, respectively. We used multivariable linear regression analysis to identify factors associated with primary and secondary outcomes. RESULTS: We analyzed 269 of 274 responses (response rate, 18.3%). Linear regression analysis was used to identify determinants of proactive attitudes to antimicrobial prescription, including whether clinic doctors encountering patients with upper respiratory symptoms and no underlying illnesses, and diagnosed with a common cold would prescribe antimicrobial medication (ß = 0.283, t = 4.279, p = 0.000); whether clinic doctors frequently experienced requests from patients (or their families) with a common cold to prescribe antimicrobial medication (ß = 0.389, t = 6.133, p = 0.000), and; clinic doctors' awareness of antimicrobial stewardship in the past year (ß = -0.157, t = -2.456, p = 0.015). Determinants of proactive attitudes to prescribing broader-spectrum antimicrobials for patients with a common cold included clinic doctors' attitudes concerning antimicrobial prescription (ß = 0.165, t = 2.622, p = 0.009), whether the respondent was a pediatrician (ß = -0.288, t = -4.583, p = 0.000), and clinic doctors' attitudes to antimicrobial prescription (ß = 0.262, t = 4.075, p = 0.000) for patients with bronchitis. CONCLUSION: This study identified factors among clinic doctors that determined their attitudes to antimicrobial prescription concerning patients with a common cold or bronchitis. Identification and targeting of clinic doctors who unnecessarily prescribe antimicrobial medication is urgently required to promote antimicrobial stewardship in an outpatient setting.

Impact of the multidisciplinary antimicrobial stewardship team intervention focusing on carbapenem de-escalation: A single-centre and interrupted time series analysis.

BACKGROUND: As a result of the constant increase in carbapenem resistance amongst gram-negative bacteria in several countries, the inappropriate use of carbapenems must be reduced. Antimicrobial stewardship programmes (ASPs) aim to improve carbapenem usage by implementing interventions, including the promotion of the de-escalation (DE) strategy. Thus, this study aimed to evaluate the impact of this strategy on carbapenem use based on a clear definition of DE. METHODS: The post-prescription review and feedback (PPRF) strategy, which is used to optimise carbapenem use, was implemented by the antimicrobial stewardship team (AST). We compared the DE rate during the pre-AST intervention period (from April 2017 to March 2018) and post-AST intervention period (from April 2018 to March 2019). RESULT: A total of 1500 patients (n = 771 in the pre-AST intervention period and n = 729 in the intervention post-AST period) were admitted to the hospital. The average duration of antibiotic therapy decreased from 9.9 to 7.7 days. The DE rate significantly increased in the post-AST intervention period compared with the pre-AST intervention period (51.4% vs 40.3%; P < .001). CONCLUSION: The PPRF strategy implemented by the AST could improve the carbapenem usage by increasing the DE rate of carbapenem.

Cortical Microinfarcts Detected by 3-Tesla Magnetic Resonance Imaging: Differentiation Between Cerebral Amyloid Angiopathy and Embolism.

Background and Purpose- Cortical microinfarcts (CMIs) are small ischemic lesions found in cerebral amyloid angiopathy (CAA) and embolic stroke. This study aimed to differentiate CMIs caused by CAA from those caused by microembolisms, using 3-Tesla magnetic resonance imaging. Methods- We retrospectively investigated 70 patients with at least 1 cortical infarct <10 mm on 3-dimensional double inversion recovery imaging. Of the 70 patients, 43 had an embolic stroke history (Emboli-G) while 27 had CAA-group. We compared the size, number, location, and distribution of CMIs between groups and designed a radiological score for differentiation based on the comparisons. Results- CAA-group showed significantly more lesions <5 mm, which were restricted to the cortex (P<0.01). Cortical lesion number was significantly higher in Emboli-G than in CAA-group (4 versus 2; P<0.01). Lesions in CAA-group and Emboli-G were disproportionately located in the occipital lobe (P<0.01) and frontal or parietal lobe (P=0.04), respectively. In radiological scoring, ≥3 points strongly predicted microembolism (sensitivity, 63%; specificity, 92%) or CAA (sensitivity, 63%; specificity, 91%). The areas under the receiver operating characteristic curve were 0.85 and 0.87 for microembolism and CAA, respectively. Conclusions- Characteristics of CMIs on 3T-magnetic resonance imaging may differentiate CMIs due to CAA from those due to microembolisms.

A numerical approach for a discrete Markov model for progressing drug resistance of cancer.

The presence of treatment-resistant cells is an important factor that limits the efficacy of cancer therapy, and the prospect of resistance is considered the major cause of the treatment strategy. Several recent studies have employed mathematical models to elucidate the dynamics of generating resistant cancer cells and attempted to predict the probability of emerging resistant cells. The purpose of this paper is to present numerical approach to compute the number of resistant cells and the emerging probability of resistance. Stochastic model was designed and developed a method to approximately but efficiently compute the number of resistant cells and the probability of resistance. To model the progression of cancer, a discrete-state, two-dimensional Markov process whose states are the total number of cells and the number of resistant cells was employed. Then exact analysis and approximate aggregation approaches were proposed to calculate the number of resistant cells and the probability of resistance when the cell population reaches detection size. To confirm the accuracy of computed results of approximation, relative errors between exact analysis and approximation were computed. The numerical values of our approximation method were very close to those of exact analysis calculated in the range of small detection size M = 500, 100, and 1500. Then computer simulation was performed to confirm the accuracy of computed results of approximation when the detection size was M = 10000,30000,50000,100000 and 1000000. All the numerical results of approximation fell between the upper level and the lower level of 95% confidential intervals and our method took less time to compute over a broad range of cell size. The effects of parameter change on emerging probabilities of resistance were also investigated by computed values using approximation method. The results showed that the number of divisions until the cell population reached the detection size is important for emerging the probability of resistance. The next step of numerical approach is to compute the emerging probabilities of resistance under drug administration and with multiple mutation. Another effective approximation would be necessary for the analysis of the latter case.

Evaluation of Intradural Ecchordosis Physaliphora With Three-Dimensional Fluid-Attenuated Inversion Recovery.

OBJECTIVE: This study evaluated the efficacy of 3-dimensional fluid-attenuated inversion recovery (3D FLAIR) for detecting intradural ecchordosis physaliphora (EP). METHODS: We retrospectively determined the presence or absence of intradural EP on 3D FLAIR for 3888 consecutive patients, classifying the EP as "classical" or "possible" and analyzing the prevalence, size, and presence or absence of an intraosseous stalk. Where available, magnetic resonance cisternography images were compared with the 3D FLAIR images. RESULTS: Intradural EP was identified in 50 patients (1.3%): 36 (0.9%) classical and 14 (0.4%) possible. The classical EPs were significantly larger than the possible EPs (P < 0.01). Nine EPs (18.0%) showed an osseous stalk. Magnetic resonance cisternography was performed for 19 EPs (16 classical, 3 possible), detecting all 16 classical EPs but none of the possible EPs. CONCLUSIONS: Classical EPs were detected by 3D FLAIR as with magnetic resonance cisternography. The 3D FLAIR findings suggested a new type of possible EP variant previously unreported.

Development of the predicted and standardized carbapenem usage metric: Analysis of the Japanese Diagnosis Procedure Combination payment system data.

This study aimed to develop a metric for standardized and predicted carbapenem consumption using the Diagnosis Procedure Combination payment system database and patients' characteristics. Based on Diagnosis Procedure Combination data analysis, the developed metric will provide useful benchmarks that stewardship programs can use to help drive improvements.

A nationwide questionnaire survey of clinic doctors on antimicrobial stewardship in Japan.

BACKGROUND: Clinics are high prescribers of antimicrobials in Japan, but the present situation and the attitude of clinic doctors toward prescribing them remain unclear. OBJECTIVE: To investigate the present situation at clinics and clinic doctors' attitude toward antimicrobial stewardship. STUDY DESIGN: A questionnaire survey of clinic doctors. METHODS: A questionnaire targeting doctors was sent to 1500 clinics that were randomly selected from across the country. RESULTS: Among 274 respondents (response rate, 18.3%), 269 provided consent and their responses were analyzed. Awareness of the National Action Plan on Antimicrobial Resistance and the Manual of Antimicrobial Stewardship was low, but awareness of antimicrobial stewardship was high. A certain proportion of doctors prescribed antimicrobials for the common cold and acute bronchitis, and macrolides were the most commonly prescribed group of antimicrobials. Such prescription was not based solely on the doctors' knowledge but was also influenced by complex factors such as the doctor-patient relationship. CONCLUSION: Various measures such as improving doctor-patient communication and improving clinic doctors' knowledge are necessary to promote antimicrobial stewardship in the outpatient setting.

Evaluation of a high-signal lesion posterior to the intracranial vertebral artery using 3D balanced fast-field echo imaging.

Previous reports have identified a small, benign, high-signal lesion (HSL) posterior to the intracranial vertebral artery and associated with the ipsilateral spinal accessory nerve (SAN) using 3D fluid-attenuated inversion recovery (3D FLAIR) imaging as an emerging new entity. To elucidate the relationship between HSLs and SAN, 76 patients with 86 HSLs were evaluated using 3D FLAIR and 3D balanced fast-field echo (3D bFFE imaging). All HSLs showed contact with ipsilateral SAN on both the sequences. 3D bFFE imaging clearly distinguished between the two structures unlike 3D FLAIR. Moreover, SAN was surrounded by HSLs on 3D bFFE images, which may be a characteristic of this entity.

Essential human resources for antimicrobial stewardship teams in Japan: Estimates from a nationwide survey conducted by the Japanese Society of Chemotherapy.

Implementation of antimicrobial stewardship programs (ASPs) with multidisciplinary antimicrobial stewardship teams (ASTs) is critical for appropriate antimicrobial use at healthcare facilities. Although the Japanese medical reimbursement system was revised to allow fees for ASP implementation, several concerns remain, including understaffing and enforcement of the recommendations on ASTs and ASPs in practice. Furthermore, there are no recommendations on full-time equivalents (FTEs) of the core members in ASTs in Japan. This committee report presents our recommendations on ASTs based on an analysis of the nationwide survey on implemented ASPs and staff FTEs at 1358 healthcare facilities conducted by the Japanese Society of Chemotherapy. Our report provides a directive for structural and financial support of ASTs and should aid in planning for the enhancement of AST practices and the organization of new ASTs.

3D double inversion recovery MR imaging: Clinical applications and usefulness in a wide spectrum of central nervous system diseases.

Double inversion recovery (DIR) imaging provides two inversion pulses that attenuate signals from cerebrospinal fluid and normal white matter. This review was undertaken to describe the principle of the DIR sequence, the clinical applications of 3D DIR in various central nervous system diseases and the clinical benefits of the 3D DIR compared with those of other MR sequences. 3D DIR imaging provides better lesion conspicuity and topography than other MR techniques. It is particularly useful for diagnosing the following disease entities: cortical and subcortical abnormalities such as multiple sclerosis, cortical microinfarcts and cortical development anomalies; sulcal abnormalities such as meningitis and subacute/chronic subarachnoid hemorrhage; and optic neuritis caused by multiple sclerosis or neuromyelitis optica.

The Alere BinaxNOW Pneumococcal Urinary Antigen Test: Diagnostic Sensitivity for Adult Pneumococcal Pneumonia and Relationship to Specific Serotypes.

Little is known about the sensitivity of the BinaxNOW pneumococcal urinary antigen (PUA) test for adult pneumococcal pneumonia caused by different serotypes. In this study, we aimed to analyze the trends in the sensitivity of the PUA test over a 15-year period (2001 to 2015) and to analyze its sensitivity for pneumococcal pneumonia caused by different serotypes. In total, we analyzed 1,096 pneumococcal isolates from adults with pneumococcal pneumonia who had a PUA test performed at the onset of the episode. Three periods were analyzed: 2001 to 2005 (early use of the seven-valent pneumococcal conjugate vaccine [early PCV7]), 2006 to 2010 (late PCV7), and 2011 to 2015 (early PCV13). The sensitivity of the PUA test varied from 76.4% (95% confidence interval [CI], 70.5% to 82.4%) in the period from 2001 to 2005 to 77.9% in 2006 to 2010 (95% CI, 74.4% to 81.4%) and decreased to 60.5% (95% CI, 55.4% to 65.6%) in 2011 to 2015. This decrease was observed in 560 proven (83.2% in 2001 to 2005, 86.5% in 2006 to 2010, and 78.1%) and 536 probable (70.0% in 2001 to 2005, 68.7% in 2006 to 2010, and 41.5% in 2011 to 2015) episodes of pneumococcal pneumonia. Differences were observed in the sensitivity of the PUA test for diagnosing pneumonia caused by certain serotypes, being highest for the 9V (90.6%), 14 (86.8%), 18C (100%), and 20 (100%) serotypes and lowest for the 8 (55.2%), 9L/N (39.1%), 11A (48.8%), 23B (33.3%), and nontypeable (47.8%) serotypes. Comparing 2001 to 2005, 2006 to 2010, and 2011 to 2015, the prevalence of serotypes 9V (3.1%, 3.7%, and 1.7%, respectively) and 14 (7.2%, 5.1%, and 3.1%, respectively) decreased, while the prevalence of serotypes 23B (0%, 0.7%, and 1.4%, respectively), 9L/N (1.0%, 1.6%, and 3.4%, respectively), 11A (2.6%, 4.2%, and 3.7%, respectively), and 8 (1.5%, 1.5%, and 5.1%, respectively) increased. The PUA test sensitivity varied by pneumococcal pneumonia serotype, and these differences and the changes in serotype distribution were associated with an overall decrease in the sensitivity of the PUA test.

Small high-signal lesions posterior to the intracranial vertebral artery incidentally identified by 3D FLAIR: retrospective study of 127 patients.

PURPOSE: A small, benign high-signal lesion (HSL) posterior to the intracranial vertebral artery (VA) at the foramen magnum is a new entity revealed by a 3D FLAIR sequence. However, this entity has not been sufficiently investigated. We aimed to investigate the MR imaging findings of HSLs posterior to the intracranial VA that were incidentally detected by 3D FLAIR. METHODS: We retrospectively evaluated 3717 patients using a 3-T MR unit. HSLs on 3D FLAIR were assessed for prevalence, size, contact with the spinal accessory nerve (SAN), and size changes on follow-up images. RESULTS: Of 3717 patients, 127 (3.4%) (58 males and 69 females; age, 60.0 ± 18.9 years) showed 142 HSLs posterior to the intracranial VA. In total, 114 patients (89.8%) had a single lesion, whereas 13 patients (10.2%) had multiple lesions. The mean lesion size was 3.8 ± 1.6 mm. All HSLs showed contact with the ipsilateral SAN. Of 69 HSLs that were imaged during follow-up, the size was stable in 91.3% and increased in 8.7%. CONCLUSION: HSLs posterior to the intracranial VA were incidentally detected in 3.4% of patients by 3D FLAIR. Our results indicated a possible association between HSLs and SAN. These lesions appear to be benign in etiology and thus would not require any surgical intervention without continuous growth in a short period or relevant signs and symptoms.

Comparison of Premortem Magnetic Resonance Imaging and Postmortem Autopsy Findings of a Cortical Microinfarct.

An 85-year-old woman diagnosed with amyotrophic lateral sclerosis died of pneumonia and was autopsied. Magnetic resonance imaging (MRI) performed 16 days before death revealed an intracortical high-intensity lesion in her right temporal cortex on three-dimensional (3D)-double inversion recovery (DIR) and 3D-fluid-attenuated inversion recovery (FLAIR) images. Histopathological examination indicated a cortical microinfarct (CMI) juxtaposed to cerebral amyloid angiopathy. Recently, in vivo detection of CMIs using 3D-DIR and 3D-FLAIR on 3-tesla MRI has been reported, and postmortem MRI study confirmed the presence of CMIs. This is the first case study to compare CMI findings detected upon premortem MRI to the CMI itself discovered upon postmortem neuropathological examination.