Response to COVID-19 during the Tokyo Olympic Games: Did we properly assess the risk?

[Background] The number of coronavirus disease 2019 (COVID-19) cases was expected to increase during the Tokyo Olympic Games because of the increased physical contact within and between the domestic population and international participants of the Games. The rapid rise of the Delta variant (B.1.617) in Japan meant that hosting the Olympic Games without any restrictions was likely to lead to an increase in cases. We aimed to quantitatively assess possible COVID-19 response strategies for the Olympic Games, comparing the prevalence of severe cases and the cumulative number of COVID-19 deaths via scenario analysis. [Methods] We used a discrete-time deterministic compartmental model structured by age group. Parameters were calibrated using the age-stratified COVID-19 incidence data in Osaka. Numerical simulations incorporated the planned Olympics Games and nationwide COVID-19 vaccination into the proposed model, alongside various subjects and types of countermeasures. [Results] Our model-informed approach suggested that having spectators at the Tokyo Olympic Games could lead to a surge in both cases and hospitalization. Projections for the scenario that explicitly incorporated the spread of the Delta variant (i.e., time-dependent increase in the relative transmissibility) showed that imposing stringent social distancing measures (Rt=0.7) for more than 8 weeks from the end of the Olympic Games might be required to suppress the prevalence of severe cases of COVID-19 to avoid overwhelming the intensive care unit capacity in Tokyo. [Conclusions] Our modeling analyses guided an optimal choice of COVID-19 response during and after the Tokyo Olympic Games, allowing the epidemic to be brought under control despite such a large mass gathering

The impact of pneumococcal vaccination on pneumonia mortality among the elderly in Japan: a difference-in-difference study

Background It is plausible that the routine immunization among infants using pneumococcal conjugate vaccine 13 (PCV13) from 2013 and among the elderly using pneumococcal polysaccharide vaccine 23 (PPV23) from 2014 contributed to reducing the pneumonia mortality among the elderly in Japan. The present study aimed to estimate the causal effect of this vaccination on pneumonia mortality, using the available cause-of-death data and employing a difference-in-difference (DID) design. Methods Two types of mortality data, that is, prefecture-dependent and age- and gender-specific mortality data, from 2003 to 2017 were retrieved. We used mortality due to malignant neoplasm and heart disease as control groups and employed a DID design with an assumed parallel mortality trend between pneumonia and control group mortality since 2013 to estimate the causal effect of pneumococcal vaccination from 2014. Results Our estimation based on malignant neoplasm and heart disease as controls indicated that the reduced pneumonia mortality in 2017 owing to pneumococcal vaccination was as large as 41.9 (33.2, 50.6) and 31.2 (23.8, 38.6) per 100,000 individuals, respectively. The largest mortality reduction was observed for the oldest group (aged ≥90 years), especially among men. Discussion The pneumococcal vaccination program, perhaps mainly represented by high vaccination coverage of PCV13 among children and partly by PPV23 administration with low coverage among the elderly in Japan, was shown to have reduced the pneumonia mortality in the elderly at the population level

Epidemiology of coronavirus disease 2019 (COVID-19) in Japan during the first and second waves

Following the emergence and worldwide spread of coronavirus disease 2019 (COVID-19), each country has attempted to control the disease in different ways. The first patient with COVID-19 in Japan was diagnosed on 15 January 2020, and until 31 October 2020, the epidemic was characterized by two large waves. To prevent the first wave, the Japanese government imposed several control measures such as advising the public to avoid the 3Cs (closed spaces with poor ventilation, crowded places with many people nearby, and close-contact settings such as close-range conversations) and implementation of "cluster buster" strategies. After a major epidemic occurred in April 2020 (the first wave), Japan asked its citizens to limit their numbers of physical contacts and announced a non-legally binding state of emergency. Following a drop in the number of diagnosed cases, the state of emergency was gradually relaxed and then lifted in all prefectures of Japan by 25 May 2020. However, the development of another major epidemic (the second wave) could not be prevented because of continued chains of transmission, especially in urban locations. The present study aimed to descriptively examine propagation of the COVID-19 epidemic in Japan with respect to time, age, space, and interventions implemented during the first and second waves. Using publicly available data, we calculated the effective reproduction number and its associations with the timing of measures imposed to suppress transmission. Finally, we crudely calculated the proportions of severe and fatal COVID-19 cases during the first and second waves. Our analysis identified key characteristics of COVID-19, including density dependence and also the age dependence in the risk of severe outcomes. We also identified that the effective reproduction number during the state of emergency was maintained below the value of 1 during the first wave

Dose-Intensity of Bisphosphonates and the Risk of Osteonecrosis of the Jaw in Osteoporosis Patients

Objective: To examine the incidence rates and association between dose-intensity, stratified by exposure duration, of bisphosphonates and the risk of osteonecrosis of the jaw among Korean osteoporotic patients older than 50 years. Study Design and Setting: Using the population-based National Health Insurance Claims Data of Korea from January 1, 2006, through December 3, 2012, 13,730 new bisphosphonate users as of 2006 were identified. Truncated age-standardized incidence rate estimation and multivariate logistic regression analyses were conducted. Results: In this retrospective cohort study, increasing age-standardized incidence rates of ONJ attributed to bisphosphonate exposure were observed for individuals with less than 1 year, 1–2 years, over 2 years of defined daily dose (DDD) of bisphosphonate exposure (13.85, 16.19, and 38.20, respectively), using a truncated 2000 United States Standard Population. Also, over 2 years of bisphosphonate DDDs was associated with an increased risk of developing of ONJ with an adjusted odds ratio of 1.51 (95% confidence interval: 1.31–1.75), compared to individuals with less than 1 year of bisphosphonate exposure. Conclusion: Our data provided the evidence to support the association between risk of ONJ and duration of bisphosphonate exposure used in the treatment or prevention of osteoporosis

Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

<p>Abstract</p> <p>Background</p> <p>Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.</p> <p>Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.</p> <p>Methods</p> <p>A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.</p> <p>Results</p> <p>Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2^nd, 3^rdtertiles when compared with first tertile (p-value for trend = 0.022).</p> <p>Conclusions</p> <p>In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.</p

Projecting a second wave of COVID-19 in Japan with variable interventions in high-risk settings

An initial set of interventions, including the closure of host and hostess clubs and voluntary limitation of non-household contact, probably greatly contributed to reducing the disease incidence of coronavirus disease (COVID-19) in Japan, but this approach must eventually be replaced by a more sustainable strategy. To characterize such a possible exit strategy from the restrictive guidelines, we quantified the next-generation matrix, accounting for high- and low-risk transmission settings. This matrix was used to project the future incidence in Tokyo and Osaka after the state of emergency is lifted, presenting multiple 'post-emergency' scenarios with different levels of restriction. The effective reproduction numbers (R) for the increasing phase, the transition phase and the state-of-emergency phase in the first wave of the disease were estimated as 1.78 (95% credible interval (CrI): 1.73-1.82), 0.74 (95% CrI: 0.71-0.78) and 0.63 (95% CrI: 0.61-0.65), respectively, in Tokyo and as 1.58 (95% CrI: 1.51-1.64), 1.20 (95% CrI: 1.15-1.25) and 0.48 (95% CrI: 0.44-0.51), respectively, in Osaka. Projections showed that a 50% decrease in the high-risk transmission is required to keep R less than 1 in both locations-a level necessary to maintain control of the epidemic and minimize the risk of resurgence

Differential associations of central and brachial blood pressure with carotid atherosclerosis and microvascular complications in patients with type 2 diabetes

BACKGROUND: We examined the relationship between central blood pressure (BP), brachial BP with carotid atherosclerosis and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: We recruited 201 patients who were evaluated for central BP, brachial BP, carotid ultrasonography, brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI) and microvascular complications. Central BP were calculated using a radial automated tonometric system. RESULTS: Agreement between central BP and brachial BP was very strong (concordance correlation coefficient between central and brachial SBP = 0.889, between central and brachial PP = 0.816). Central pulse pressure (PP) was correlated with mean carotid intima-media thickness (CIMT), baPWV and ABI, whereas brachial PP was borderline significantly correlated with CIMT. The prevalence of nephropathy(DN) and retinopathy(DR) according to the brachial PP tertiles increased, the prevalences of microvascular complications were not different across central PP tertiles. In multivariate analysis, the relative risks (RRs) for the presence of DR were 1.2 and 4.6 for the brachial PP tertiles 2 and 3 when compared with the first tertile. Also, the RRs for the presence of DN were 1.02 and 3 for the brachial PP tertiles 2 and 3 when compared with the first tertile. CONCLUSIONS: Agreement of central BP and brachial BP was very strong. Nonetheless, this study showed that higher brachial PP levels are associated with increased probability for the presence of microvascular complications such as DR/DN. However, there are no associations with central SBP and central PP with microvascular complications. Central BP levels than brachial BP are correlated with surrogate marker of macrovascular complications

Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum field isolates from Myanmar

<p>Abstract</p> <p>Background</p> <p>Merozoite surface protein-1 (MSP-1) and MSP-2 of <it>Plasmodium falciparum </it>are potential vaccine candidate antigens for malaria vaccine development. However, extensive genetic polymorphism of the antigens in field isolates of <it>P. falciparum </it>represents a major obstacle for the development of an effective vaccine. In this study, genetic polymorphism of MSP-1 and MSP-2 among <it>P. falciparum </it>field isolates from Myanmar was analysed.</p> <p>Methods</p> <p>A total of 63 <it>P. falciparum </it>infected blood samples, which were collected from patients attending a regional hospital in Mandalay Division, Myanmar, were used in this study. The regions flanking the highly polymorphic characters, block 2 for MSP-1 and block 3 for MSP-2, were genotyped by allele-specific nested-PCR to analyse the population diversity of the parasite. Sequence analysis of the polymorphic regions of MSP-1 and MSP-2 was also conducted to identify allelic diversity in the parasite population.</p> <p>Results</p> <p>Diverse allelic polymorphism of MSP-1 and MSP-2 was identified in <it>P. falciparum </it>isolates from Myanmar and most of the infections were determined to be mixed infections. Sequence analysis of MSP-1 block 2 revealed that 14 different alleles for MSP-1 (5 for K1 type and 9 for MAD20 type) were identified. For MSP-2 block 3, a total of 22 alleles (7 for FC27 type and 15 for 3D7 type) were identified.</p> <p>Conclusion</p> <p>Extensive genetic polymorphism with diverse allele types was identified in MSP-1 and MSP-2 in <it>P. falciparum </it>field isolates from Myanmar. A high level of mixed infections was also observed, as was a high degree of multiplicity of infection.</p

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline with less than 1% of sexually active MSM population infected regardless of interventions or behavioural changes. Consistently, we found that many countries and US states experienced an epidemic peak with cumulative cases of around 0.1-0.5% of MSM population. The observed decline in cases may not necessarily be attributable to interventions or behavioural changes primarily

Comparison of the regeneration of cartilage and the clinical outcomes after the open wedge high tibial osteotomy with or without microfracture: a retrospective case control study

Background It is unclear whether postoperative outcomes are associated with the cartilage regeneration after open wedge high tibial osteotomy (OWHTO) combined with microfracture. The purpose of this study was to evaluate the regeneration of the articular cartilage, radiologic, and clinical outcomes after OWHTO with and without microfracture. Methods Eighty-seven patients who underwent OWHTO from 2014 to 2015 were retrospectively included in this study. Fifty-seven OWHTOs with microfracture on medial femoral condyle (MFC) (group 1) and 30 OWHTOs without microfracture (group 2) were compared at a mean 2-year follow-up. The regeneration of the articular cartilage was evaluated using International Cartilage Repair Society (ICRS) grade on the second-look arthroscopy and the magnetic resonance observation of cartilage repair tissue (MOCART) score on magnetic resonance imaging (MRI). The weight-bearing line (WBL) ratio, hip-knee-ankle (HKA) angle, joint line convergence angle (JLCA) and Ahlbäck grade were evaluated. The clinical outcomes were evaluated using the Western Ontario and McMaster University (WOMAC) scores and the Knee Society (KS). Results The articular cartilage in the MFC were regenerated in 67.8% of group 1 (43/57) and 58.6% of group 2 (16/30), respectively (p = 0.014). However, change of the ICRS grades of the medial tibial plateau, lateral and patellofemoral compartments showed no statistical difference between the groups. Total MOCART score in group 1 was superior to that in the group 2 at postoperative 2 years (41.8 ± 18.6 vs. 31.8 ± 19.8, p = 0.023). Regarding MOCART score, microfracture was only effective in the defect filling and integration to the border zone of the MFC (p < 0.001 and p = 0.035, respectively). Other radiologic and clinical outcomes showed no statistical differences between the groups. Conclusion Microfracture of the MFC during OWHTO only helped the filling of the degenerative cartilage defect and the integration of the cartilage with adjacent cartilage. However, the clinical and radiologic outcome could not be improved by mircrofracture in the OWHTO.This work was supported by Basic Science Research Program through the Ministry of Education of the Republic of Korea and National Research Foundation of Korea (NRF) (NRF-2017R1D1A1A09000509