The Similarities in Microbial and Chemical Patterns of Fermentation in Two Open Environments were Promoted by Using 150-Year-Old Nukadoko as Starters.

Nukadoko, a fermented rice bran employed in traditional Japanese pickling, uses lactic acid bacteria to ferment vegetables. Here, we report the microbial and chemical data of a mixture of matured 150-year-old nukadoko and commercially available rice bran placed in two open environments over 29 days. Across the two environments, Loigolactobacillus was identified as the dominant microbial genera in the later stages of fermentation in nukadoko. The period of increase in the relative abundance of Loigolactobacillus correlated with a decrease in pH and Oxidation-Reduction Potential (ORP) values. While the two environments showed a difference in the rate of change in microbial diversity, they shared the common process through which Loigolactobacillus outcompeted adventitious bacteria in nukadoko, as indicated by the alpha and beta diversity index. Thus, the similarities in microbial and chemical data across two open environments during fermentation using starters indicate that starters contribute to the stability of fermentation in open environments.

Comparative Efficacy and Acceptability of Treatment Strategies for Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-analysis.

BACKGROUND: Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear. DESIGN: We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA. RESULTS: We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights. CONCLUSIONS: Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.

Patterns of anti-vascular endothelial growth factor treatment for chorioretinal vascular diseases: Analysis of a nationwide claims database in Japan.

BACKGROUND: Although intravitreal anti-vascular endothelial growth factor therapy is currently considered the first-line treatment for chorioretinal vascular diseases in Japan, information regarding its treatment pattern is scarce. This study investigated the patterns of anti-vascular endothelial growth factor treatment for chorioretinal vascular diseases. METHODS: A health insurance claims database from acute care hospitals was used to estimate treatment intervals and continuation and drop-out rates regarding the anti-vascular endothelial growth factor. Patients aged ≥50 years diagnosed with neovascular age-related macular degeneration or aged ≥18 years diagnosed with diabetic macular edema or retinal vein occlusion were analyzed. RESULTS: Data were included for 76,535, 49,704, and 37,681 patients with neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively; exactly 8,111, 2,283, and 6,896 received the treatment, respectively. The mean and median interval ranges during the maintenance phase by treatment initiation year were 94-100 and 73-80, 111-120 and 98-102, and 97-103 and 87-93 days for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively, without any trend over time. A tendency to increase the treatment continuation rate was indicated in later years by Kaplan-Meier curves. The drop-out rate in the treatment initiation year (2016) was 32% from 63% (2009), 53% from 69% (2014), and 36% from 47% (2013) for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively. CONCLUSIONS: For all these diseases, the treatment intervals did not change remarkably, and a tendency toward improved treatment continuation was suggested.

Understanding the quality and safety of food production through the lens of The Microbiome of The Built Environment.

The Microbiome of the Built Environment (MoBE) is profoundly implicated in various sectors, including food science. The balance between beneficial and pathogenic microbes in these facilities directly influences product quality and public health. Maintaining a careful check on MoBE and external microbes is vital to the food industry to ensure quality control. There is also a risk of contamination in the meat processing facility as well. However, over-sanitization can increase drug-resistant microbes, highlighting the importance of balanced microbial management. Additionally, facility design, influenced by understanding MoBE, can optimize the growth of beneficial microbes and inhibit pathogenic microbes. Microbial mapping, an emerging practice, offers insights into microbial hotspots within facilities, resulting in targeted interventions. As the food industry evolves, the intricate understanding and management of MoBE will be pivotal to ensuring optimal food quality, safety, and innovation.

Effectiveness of Current Treatments for Wet Age-Related Macular Degeneration in Japan: A Systematic Review and Pooled Data Analysis.

PURPOSE: We conducted a systematic review to investigate the effectiveness of clinical treatments for wet age-related macular degeneration (wAMD) in Japanese patients in the decade since anti-vascular endothelial growth factor (VEGF) therapies were introduced. METHODS: PubMed was searched for articles published in English between 1 January 2008 and 30 September 2018 using a multistring search strategy. Reviews were scanned for additional relevant studies and select gray literature was evaluated. Mean and/or median for the logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), central retinal thickness (CRT), and the number of injections after 12 months of treatment were calculated using extracted data. Data were stratified by disease type and treatment modality. RESULTS: Of 335 studies identified, 94 were selected for data extraction (147 treatment arms; typical AMD, n = 25; polypoidal choroidal vasculopathy [PCV], n = 85). Mean (median) logMAR VA was 0.44 (0.32) for typical AMD and 0.34 (0.31) for PCV; the respective mean number of anti-VEGF injections was 5.6 and 4.6. The mean CRT was approximately 220 µm for both groups. For typical AMD, anti-VEGF monotherapy resulted in better VA outcomes than photodynamic therapy (PDT) alone. For PCV, anti-VEGF monotherapy or anti-VEGF plus PDT combination therapy resulted in better VA and CRT outcomes than PDT monotherapy. Combination therapy required fewer injections than anti-VEGF monotherapy (PCV, 3.2 versus 5.3). CONCLUSION: wAMD treatment has advanced dramatically in the years since anti-VEGF drugs were introduced in Japan. Discrete patient populations may benefit from differing management regimens, including the fewer injections required with combination therapy.

Factors of Anti-Vascular Endothelial Growth Factor Therapy Withdrawal in Patients with Neovascular Age-Related Macular Degeneration: Implications for Improving Patient Adherence.

We investigated the factors associated with the discontinuation of anti-vascular endothelial growth factor (VEGF) therapies in patients with neovascular age-related macular degeneration (AMD). Japanese patients with AMD aged ≥50 years, reporting at least one prior injection of an anti-VEGF drug, completed an online survey covering reasons for discontinuation or dissatisfaction with therapy, quality of life (EQ-5D-5L) and patient activation (PAM-13). The respondents were divided into two cohorts: Cohort 1-patients who discontinued anti-VEGF therapy (n = 207); Cohort 2-patients continuing anti-VEGF therapy (n = 65). The most common reason for discontinuing therapy was the "doctor's decision" in 89.4% (Cohort 1-1). In the other 22 (10.6%) patients in Cohort 1 (Cohort 1-2), reasons included "no deterioration in vision", "financial burden" and "ineffective treatment". Patients in Cohort 2 were dissatisfied with "long waiting times" (77%), "financial burden" and "ineffective treatment". Pain/discomfort posed the greatest impact on quality of life. Only 5% of patients in Cohorts 1-1 and 2 and none in Cohort 1-2 were considered advocates for their own health. In conclusion, most patients who discontinued anti-VEGF therapy did so at their doctor's decision. Addressing the reasons associated with discontinuation or dissatisfaction with anti-VEGF therapies might help improve their continuation.

Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan.

The chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009-2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

Relationship between diet/exercise and pharmacotherapy to enhance the GLP-1 levels in type 2 diabetes.

The rapid rise in the prevalence of type 2 diabetes mellitus (T2DM) poses a huge healthcare burden across the world. Although there are several antihyperglycaemic agents (AHAs) available including addition of new drug classes to the treatment algorithm, more than 50% of patients with T2DM do not achieve glycaemic targets, suggesting an urgent need for treatment strategies focusing on prevention and progression of T2DM and its long-term complications. Lifestyle changes including implementation of healthy diet and physical activity are cornerstones for the management of T2DM. The positive effects of diet and exercise on incretin hormones such as glucagon-like peptide-1 (GLP-1) have been reported. We hypothesize an IDEP concept (Interaction between Diet/Exercise and Pharmacotherapy) aimed at modifying the diet and lifestyle, along with pharmacotherapy to enhance the GLP-1 levels, would result in good glycaemic control in patients with T2DM. Consuming protein-rich food, avoiding saturated fatty acids and making small changes in eating habits such as eating slowly with longer mastication time can have a positive impact on the GLP-1 secretion and insulin levels. Further the type of physical activity (aerobic/resistance training), intensity of exercise, duration, time and frequency of exercise have shown to improve GLP-1 levels. Apart from AHAs, a few antihypertensive drugs and lipid-lowering drugs have also shown to increase endogenous GLP-1 levels, however, due to quick degradation of GLP-1 by dipeptidyl peptidase-4 (DPP-4) enzyme, treatment with DPP-4 inhibitors would protect GLP-1 from degradation and prolong its activity. Thus, IDEP concept can be a promising treatment strategy, which positively influences the GLP-1 levels and provide additive benefits in terms of improving metabolic parameters in patients with T2DM and slowing the progression of T2DM and its associated complications.

Choice of Treatment Regimen as Add-On to Insulin in Japanese Patients with Type 2 Diabetes Mellitus: Physicians' Perspective in a Real-World Setting, Insight from a Web Survey.

INTRODUCTION: The Japanese guidelines emphasize treatment individualization and intensification with oral anti-diabetes drugs and glucagon-like peptide-1 receptor agonists (OADGs) as add-on therapy to insulin in the management of type 2 diabetes mellitus (T2DM). However, a step-wise treatment algorithm is not clearly defined in the Japanese guidelines. This study explores the treatment factors and patient characteristics for selecting the OADGs as add-on therapy to insulin from physicians' perspectives in a real-world setting in Japan. METHODS: This web-based survey comprised a questionnaire designed for physicians (diabetologists with board certification and general physicians without board certification) across Japan. The primary endpoint was the proportion of treatment factors and patient characteristics influencing the selection of OADGs as add-on therapy to insulin by the physicians. RESULTS: In total, 549 physicians participated. The mean number of patients treated with insulin by diabetologists (102.2 ± 91.2) in the past 6 months was higher than the number by general physicians (35.1 ± 44.3). The dipeptidyl peptidase-4 (DPP-4) inhibitors were the most frequently prescribed OADGs as add-on therapy to insulin types among the physicians (75.4-88.2%), followed by metformin (65.2-76.3%). The treatment factors influencing the choice of a DPP-4 inhibitor were glycated hemoglobin (HbA1c) and postprandial glucose (PPG) lowering effect, frequency of administration, effect on glucagon, and ease of use in patients with renal or liver impairment. For metformin, cost-effectiveness was the key deciding factor. The patient characteristics for the choice of DPP-4 inhibitors among diabetologists were predominantly PPG, concern about hypoglycemia, diabetes complications, and adherence to diet and exercise. For metformin, it was age, body mass index (BMI), insulin resistance, renal and liver function, and economic status of the patients. CONCLUSION: DPP-4 inhibitors, followed by metformin, were the most frequently prescribed OADGs in combination with insulin in a real-world setting in Japan. The diabetologists considered more drug characteristics for DPP-4 inhibitor or metformin-insulin combinations. The treatment factors and patient characteristics for the choice of DPP-4 inhibitors and metformin were comparable across different insulin types. FUNDING: Novartis Pharma K.K.

Factors Influencing the Prescribing Preferences of Physicians for Drug-Naive Patients with Type 2 Diabetes Mellitus in the Real-World Setting in Japan: Insight from a Web Survey.

INTRODUCTION: The Japanese guidelines for type 2 diabetes mellitus (T2DM) emphasize individualization of treatment based on patient need and encourage physicians to select an appropriate oral antidiabetes drug (OAD). However, limited evidence is available on the factors influencing the selection by physicians (diabetes specialists and nonspecialists) of the first-line OAD to treat drug-naive patients with T2DM. A survey was designed to explore the treatment factors and patient characteristics that influence physicians when they choose an initial OAD to prescribe to a drug-naive patient with T2DM in a real-world setting in Japan. METHODS: The 25-min web-based online survey consisted of simple and focused multiple-choice questions, and was circulated to physicians across eight selected regions in Japan. The primary endpoints were the proportions of physicians who considered particular treatment factors and patient characteristics when selecting the appropriate treatment for drug-naive T2DM patients. RESULTS: A total of 491 physicians participated in the survey. Dipeptidyl peptidase-4 inhibitors (DPP-4is) were the most-preferred first-line OADs, followed by metformin, of both specialists (69% vs. 60%) and nonspecialists (73% vs. 47%). The most influential factors when a DPP-4i was selected were found to be glycated hemoglobin (HbA1c), postprandial glucose (PPG)-lowering effect, and a low risk of hypoglycemia, which were considered by > 80% of physicians, whereas the key factors when metformin was selected were improvement in insulin resistance, low cost, low risk of hypoglycemia, and PPG- and HbA1c-lowering effects, which were considered by > 85% of physicians. Regression analysis revealed that the dominant reason for choosing DPP-4is over metformin was their ease of use in patients with renal impairment, whereas the dominant reasons for choosing metformin over DPP-4is were improvement in insulin resistance and low cost. The key patient characteristics driving the choice of DPP-4is or metformin as the first-line OAD by physicians were similar to those that influenced the treatment intensification decision (DPP-4is: PPG and renal function; metformin: age, BMI, insulin resistance, and renal function). CONCLUSION: In Japan, DPP-4is are the preferred first-line OADs, followed by metformin. The key treatment factors and patient characteristics considered when selecting DPP-4is or metformin are similar for both specialists and nonspecialists. These results may prompt further discussion of the differences in T2DM treatment between Japan and other counties. FUNDING: Novartis.