Cross-sectional surveillance study of long COVID in Toyonaka city, Osaka prefecture, Japan.

BACKGROUND: As the COVID-19 epidemic continues, concerns about long-term health impacts, specifically long COVID, persist. While the prevalence and symptomatology of long COVID have been explored in various global contexts, large-scale cohort studies in Japan remain limited, especially after the advent of the Omicron variant. METHODS: In this observational study, 4,047 residents with a history of COVID-19 living in Toyonaka City, Osaka Prefecture, were assessed for long COVID symptoms using the VOICE mobile application and a paper survey. Respondents provided demographic and health information, as well as information regarding COVID-19 infection and subsequent symptoms. A Cox proportional hazard regression model was used to estimate the multivariable-adjusted hazard ratios and 95 % confidence intervals for overall morbidity of long COVID symptoms. RESULTS: The survey found that 5.2 % of participants reported the persistence of one or more symptoms at 30 days post-onset. Fatigue was the most commonly reported symptom (1.75 %), followed by hair loss (1.41 %), and cough (1.28 %). Factors associated with an increased risk of experiencing long COVID symptoms included BMI, severe illness during the acute phase, and infection with certain COVID-19 variant strains, including Alpha, Delta, and Omicron. However, the incidence rate of long COVID appears to be decreasing with the dominance of the Omicron variant. CONCLUSIONS: This large-scale study from Toyonaka City suggests a 5.2 % prevalence rate for persistent COVID-19 symptoms 4 weeks post-infection, potentially indicating a lower prevalence of long COVID in Japanese populations after the rise of the Omicron variant.

Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study.

OBJECTIVE: Nicotinamide adenine dinucleotide regulates various biological processes. Nicotinamide mononucleotide (NMN) increases its intracellular levels and counteracts age-associated changes in animal models. We investigated the safety and efficacy of oral nicotinamide mononucleotide supplementation in older patients with diabetes and impaired physical performance. METHOD: We carried out a 24-week placebo-controlled, double-blinded study of male patients with diabetes aged ≥65 years with reduced grip strength (<26 kg) or walking speed (<1.0 m/s). The primary end-points were to determine the safety of NMN oral administration (250 mg/day), and changes in grip strength and walking speed. The secondary end-points were to determine the changes in various exploratory indicators. RESULTS: We studied 14 participants aged 81.1 ± 6.4 years. NMN was tolerable without any severe adverse events. The changes in grip strength and walking speed showed no difference between the two groups: 1.25 kg (95% confidence interval -2.31 to 4.81) and 0.033 m/s (-0.021 to 0.087) in the NMN group, and -0.44 kg (-4.15 to 3.26) and 0.014 m/s (-0.16 to -0.13) in the placebo group, respectively. There were no significant differences in any exploratory indicators between the two groups. However, improved prevalence of frailty in the NMN group (P = 0.066) and different changes in central retinal thickness between the two groups (P = 0.051) was observed. CONCLUSION: In older male patients with diabetes and impaired physical performance, NMN supplementation for 24 weeks was safe, but did not improve grip strength and walking speed. Geriatr Gerontol Int 2023; 23: 38-43.

Botulinum Toxin Therapy: A Series of Clinical Studies on Patients with Spasmodic Dysphonia in Japan.

Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that adductor SD predominated (90-95% of all cases; 3.5-7.0/100,000), principally among young women in their 20s and 30s. To facilitate early diagnosis, we created diagnostic criteria for SD and a severity grading system. The diagnostic criteria include the principal and accompanying symptoms, clinical findings during phonation, the treatment response, and the differential diagnoses. The severity grade is determined using a combination of subjective and objective assessments. Botulinum toxin (BT) injection is the treatment of choice; however, there have been few high-quality clinical studies and BT has been used off-label. We conducted a placebo-controlled, randomized, double-blinded clinical trial of BT therapy; this was effective and safe. BT treatment is now funded by the Japanese medical insurance scheme. Studies thus far have facilitated early diagnosis and appropriate therapy; they have fostered patient awareness of SD.

Post-treatment clinical course following botulinum toxin injection therapy for adductor spasmodic dysphonia: Analysis of data from a placebo-controlled, randomized, double-blinded clinical trial in Japan.

OBJECTIVE: Botulinum toxin (BT) therapy is a first-line treatment for spasmodic dysphonia (SD). However, a detailed chronological course and clinical factors that affect the therapeutic effect have been vague. In this study, we analyzed the data from our placebo-controlled, randomized, double-blinded parallel-group comparison/open-label clinical trial of BT (Botox) to clarify these. METHODS: A total of 22 patients with abductor SD (ADSD) were enrolled. The female-to-male ratio was 20:2 with a mean age of 40.0 ± 10.3 years and a median duration of symptoms of 7.5 years. The therapeutic effect was evaluated based on the change in the number of aberrant morae (phonemes), GRBAS scale, Voice Handicap Index (VHI), and Visual Analogue Scale (VAS). RESULTS: The change in the number of aberrant morae peaked at 2 weeks and lasted for 12 weeks in the BT group with significance (P < .01) compared to the placebo group. Objective improvement (number of aberrant morae and [S] element in GRBAS) preceded subjective improvement (VHI and VAS). The change in number of aberrant morae and VHI showed a significant correlation (P < .01). The changes in the number of aberrant morae, VHI, and VAS in younger subjects were greater than in older subjects. Patients who presented with post-treatment breathy hoarseness or dysphagia showed better therapeutic effects. CONCLUSIONS: BT therapy was effective for ADSD based on both objective and subjective assessments. Improvements in subjective parameters were delayed compared to objective measures due to post-treatment breathy hoarseness. However, this adverse event was believed to reflect the treatment effect. LEVEL OF EVIDENCE: 1b.

Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial.

BACKGROUND AND PURPOSE: Botulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high-quality clinical studies have appeared, and BT is used off-label in most countries. METHODS: We performed a multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty-four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4 weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period. RESULTS: In the adductor SD group, the number of aberrant morae at 4 weeks after injection was reduced by 7.0 ± 2.30 (mean ± SE) in the BT group and 0.2 ± 0.46 in the placebo group (p = 0.0148). The improvement persisted for 12 weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2 weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4 weeks. CONCLUSIONS: Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.

The prevalence and clinical features of spasmodic dysphonia: A review of epidemiological surveys conducted in Japan.

OBJECTIVES: Spasmodic dysphonia (SD) is a rare disease and its epidemiological status is unclear. This review aimed to explore the current prevalence and clinical features of SD in Japan. METHODS: We reviewed Japanese surveys of SD and compared them to surveys reported from other countries. We focused on SD prevalence, clinical features (SD type, sex and age), and treatment modalities. RESULTS: The SD prevalence in Japan was 3.5-7.0/100,000, similar to that in Rochester (NY, USA) and Iceland. Adductor SD predominated (90-95%) and females were four-fold more likely to be affected than males. Mean age at onset was approximately 30 years in Japan. Several years elapsed from onset to diagnosis. The most frequent treatment was botulinum toxin injection, and surgical intervention, particularly type 2 thyroplasty is becoming more popular. CONCLUSIONS: Our review demonstrated some differences of clinical features of SD in Japan compared with other countries, such as a greater female predominance and younger age of onset. Many physicians and patients may be unfamiliar with the clinical features of SD leading to delayed of diagnosis. Therefore, we proposed diagnostic criteria to facilitate early diagnosis and an appropriate choice of treatment modalities.

Performance Index for Types of Clinical Research Support Service Providers for Academic Research Organizations in Japan: A Cross-Sectional Survey.

The purpose of this study was to conduct a factual survey to evaluate the type of clinical research support offered by service providers (supporters) in Japanese academic research organizations (AROs). From September to October 2018, we conducted an online questionnaire targeting researchers and supporters of AROs, including individuals supporting research and development (R&D) planning, as well as those involved in study management, biostatistics, coordination, data management, monitoring, and auditing. The number of responses was tabulated for each survey item. For items with written descriptions, we compiled summaries using the inductive regression method of qualitative research. Responses were obtained from 124 researchers, 258 supporters, and 40 AROs. None of the institutions responded that they had a performance index for all types of service providers, whereas 47% of institutions had an index for 1-3 types of service providers, and 40% of institutions had no index. Many institutions responded that they had a performance index for coordinators and data management, but few responded that there was a performance index for individuals engaged in R&D and study management. Furthermore, for all evaluations of AROs and researchers, the level of supporter satisfaction was low at only 20%. There was a discrepancy between the levels of researcher expectations and the actual contribution of R&D in the process of research planning. Our survey revealed that there is currently no performance index for services supporting clinical research. In future studies, we need to examine a performance index that accurately reflects the researcher attitudes revealed in this study.

Attenuation of metabolic heat production and cold-escape/warm-seeking behaviour during a cold exposure following systemic salt loading in rats.

The reduction of body core temperature (Tcore) after salt loading has been reported. In this study, we tested the hypothesis that, during a cold exposure in rats, (1) salt loading would decrease metabolic rate (MR), reducing Tcore, but (2) Tcore would be maintained when cold-escape/warm-seeking behaviour is available. In the first experiment (n = 7), MR and Tcore were measured by indirect calorimetry and telemetry, respectively, during 26, 20 and 10 degrees C exposure for 1 h each, in that order. In the second experiment (n = 7), each rat was placed in an operant system during the same exposure protocol as in the first experiment, where it could trigger a 40 degrees C air reward for 30 s at 20 and 10 degrees C by moving into specific areas (operant behaviour). In each experiment, rats repeated the same protocol twice with a subcutaneous injection (10 ml kg-1) of either isotonic saline (154 mM) or hypertonic saline (2500 mM). In the first experiment, MR in the isotonic-saline trial increased (P < 0.05) at 20 and 10 degrees C compared with that at 26 degrees C by 21 +/- 5 and 48 +/- 6 %, respectively (means +/- S.E.M.), with Tcore unchanged. However, values for MR and Tcore in the hypertonic-saline trial were lower (P < 0.05) than those in the isotonic-saline trial in any ambient temperature. In the second experiment, Tcore was also lower (P < 0.05) in the hypertonic-saline trial than in the isotonic-saline trial. The counts of the operant behaviour in the hypertonic-saline trial remained unchanged in each exposure period, but those in the isotonic-saline trial increased (P < 0.05) at 10 degrees C. These results may suggest that salt loading attenuates both metabolic and behavioural thermoregulatory responses to the cold.