Simple mathematical model for predicting COVID-19 outbreaks in Japan based on epidemic waves with a cyclical trend.

BACKGROUND: Several models have been used to predict outbreaks during the COVID-19 pandemic, with limited success. We developed a simple mathematical model to accurately predict future epidemic waves. METHODS: We used data from the Ministry of Health, Labour and Welfare of Japan for newly confirmed COVID-19 cases. COVID-19 case data were summarized as weekly data, and epidemic waves were visualized and identified. The periodicity of COVID-19 in each prefecture of Japan was confirmed using time-series analysis and the autocorrelation coefficient, which was used to investigate the longer-term pattern of COVID-19 cases. Outcomes using the autocorrelation coefficient were visualized via a correlogram to capture the periodicity of the data. An algorithm for a simple prediction model of the seventh COVID-19 wave in Japan comprised three steps. Step 1: machine learning techniques were used to depict the regression lines for each epidemic wave, denoting the "rising trend line"; Step 2: an exponential function with good fit was identified from data of rising straight lines up to the sixth wave, and the timing of the rise of the seventh wave and speed of its spread were calculated; Step 3: a logistic function was created using the values calculated in Step 2 as coefficients to predict the seventh wave. The accuracy of the model in predicting the seventh wave was confirmed using data up to the sixth wave. RESULTS: Up to March 31, 2023, the correlation coefficient value was approximately 0.5, indicating significant periodicity. The spread of COVID-19 in Japan was repeated in a cycle of approximately 140 days. Although there was a slight lag in the starting and peak times in our predicted seventh wave compared with the actual epidemic, our developed prediction model had a fairly high degree of accuracy. CONCLUSION: Our newly developed prediction model based on the rising trend line could predict COVID-19 outbreaks up to a few months in advance with high accuracy. The findings of the present study warrant further investigation regarding application to emerging infectious diseases other than COVID-19 in which the epidemic wave has high periodicity.

Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited. METHODS: We conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes. RESULTS: Among 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19-5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69-6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17-7.80) than on day 7 (OR = 1.60, 95% CI = 1.03-2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group. CONCLUSIONS: Favipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.

Spatiotemporal distribution of COVID-19 during the first 7 months of the epidemic in Vietnam.

BACKGROUND: Understanding the spatiotemporal distribution of emerging infectious diseases is crucial for implementation of control measures. In the first 7 months from the occurrence of COVID-19 pandemic, Vietnam has documented comparatively few cases of COVID-19. Understanding the spatiotemporal distribution of these cases may contribute to development of global countermeasures. METHODS: We assessed the spatiotemporal distribution of COVID-19 from 23 January to 31 July 2020 in Vietnam. Data were collected from reports of the World Health Organization, the Vietnam Ministry of Health, and related websites. Temporal distribution was assessed via the transmission classification (local or quarantined cases). Geographical distribution was assessed via the number of cases in each province along with their timelines. The most likely disease clusters with elevated incidence were assessed via calculation of the relative risk (RR). RESULTS: Among 544 observed cases of COVID-19, the median age was 35 years, 54.8% were men, and 50.9% were diagnosed during quarantine. During the observation period, there were four phases: Phase 1, COVID-19 cases occurred sporadically in January and February 2020; Phase 2, an epidemic wave occurred from the 1st week of March to the middle of April (Wave 1); Phase 3, only quarantining cases were involved; and Phase 4, a second epidemic wave began on July 25th, 2020 (Wave 2). A spatial cluster in Phase 1 was detected in Vinh Phuc Province (RR, 38.052). In Phase 2, primary spatial clusters were identified in the areas of Hanoi and Ha Nam Province (RR, 6.357). In Phase 4, a spatial cluster was detected in Da Nang, a popular coastal tourist destination (RR, 70.401). CONCLUSIONS: Spatial disease clustering of COVID-19 in Vietnam was associated with large cities, tourist destinations, people's mobility, and the occurrence of nosocomial infections. Past experiences with outbreaks of emerging infectious diseases led to quick implementation of governmental countermeasures against COVID-19 and a general acceptance of these measures by the population. The behaviors of the population and the government, as well as the country's age distribution, may have contributed to the low incidence and small number of severe COVID-19 cases.

Seasonality of newly notified pulmonary tuberculosis in Japan, 2007-2015.

BACKGROUND: The seasonality of pulmonary tuberculosis (TB) incidence may indicate season-specific risk factors that could be controlled if they were better understood. The aims of this study were to elucidate how the incidence of TB changes seasonally and to determine the factors influencing TB incidence, to reduce the TB burden in Japan. METHODS: We assessed the seasonality of newly notified TB cases in Japan using national surveillance data collected between 2007 and 2015. To investigate age and sex differences, seasonal variation was analyzed according to sex for all cases and then by stratified age groups (0-4, 5-14, 15-24, 25-44, 45-64, 65-74, and ≥ 75 years). We used Roger's test to analyze the cyclic monthly trends in seasonal variation of TB incidence. RESULTS: A total of 199,856 newly notified TB cases (male, 62.2%) were reported over the past 9-year period. Among them, 60.6% involved patients aged ≥65 years. Overall, the peak months of TB incidence occurred from April to October, excluding September. In the analysis stratified by age group, a significant seasonal variation in TB cases was observed for age groups ≥15 years, whereas no seasonal variation was observed for age groups ≤14 years. For female patients aged ≥25 years, the peak TB epidemic period was seen from June to December, excluding November. Male patients in the same age groups exhibited declining TB incidence from September to March. CONCLUSIONS: TB incidence exhibits seasonality in Japan for people aged > 15 years and peaks in summer to fall. Monthly trends differ according to age and sex. For age groups ≥25 years, cases in women showed longer peaks from June to December whereas cases in men declined from September to December. These results suggest that the seasonality of TB incidence in Japan might be influenced by health checkups in young adults, reactivation of latent TB infection with aging, and lifestyle habits in older adults. These findings can contribute to establishing the potential determinants of TB seasonality in Japan.

Difficulties in tuberculosis infection control in a general hospital of Vietnam: a knowledge, attitude, and practice survey and screening for latent tuberculosis infection among health professionals.

BACKGROUND: In Vietnam, a country with a high tuberculosis (TB) burden, health professionals in both TB-specialized and non-TB-specialized general hospitals have a high risk of acquiring TB. The aims of the present study were to clarify the difficulties in TB infection control at non-TB specialized hospitals and whether any associated risks of latent TB infection exist among health professionals in Vietnam. METHODS: We conducted a cross-sectional study in a national tertiary and general hospital of Hanoi, Vietnam. Participants were health professionals, including physicians, nurses, and other health professionals. We assessed difficulties in TB infection control by conducting a knowledge, attitude, and practice (KAP) survey. We also collected data on the results of tuberculin skin tests (TSTs) conducted during health check-ups for hospital staff to determine whether health professionals had latent TB infection or TB disease. KAP scores were compared among health professional groups (physicians vs. nurses vs. other health professionals). Factors influencing knowledge scores were evaluated using multiple regression analysis. RESULTS: A total 440 health professionals at the study site participated in the KAP survey, and we collected the results of TSTs from a total of 299 health professionals. We observed a high prevalence of latent TB infection (74.2%), especially among participants in the emergency department. Although participants had high KAP scores, some topics were less understood, such as symptoms and risks of TB, proper use of protective equipment such as N95 respirators, and preventing transmission by patients with confirmed or suspected TB. Factors influencing knowledge scores associated with TB were age, a belief that TB is the most important infectious disease, being a medical professional, having previously attended workshops or seminars, and knowing that Vietnam has a high burden of TB. CONCLUSION: In a non-TB specialized hospital of Vietnam, we observed a risk of TB infection among health professionals and difficulties in properly controlling TB infection. Early awareness regarding patients with suspected TB, to apply proper measures and prevent transmission, and education regarding obtaining updated knowledge through scientific information are crucial to enhancing TB infection control in general hospitals of Vietnam.

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

BACKGROUND: The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. METHOD: We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. RESULTS: The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. CONCLUSIONS: The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan.

Effectiveness of clarithromycin in patients with yellow nail syndrome.

BACKGROUND: Yellow nail syndrome (YNS) is a rare disease characterized by the triad of thickened, slow-growing yellow nails, lymphedema, and chronic respiratory manifestations. The cause of YNS is not known; however, it is suggested to be due to a congenital lymph abnormality. Since YNS is accompanied by chronic bronchial infection in more than half of patients, we hypothesized that treatment with clarithromycin (CAM) could be effective. We therefore evaluated the effectiveness of CAM against nail discoloration and respiratory manifestation in patients with YNS. METHODS: We conducted an observational study involving 5 patients with YNS who were treated at our institution between January 2005 and January 2016. CAM was prescribed for every patient. Patient demographic information, comorbidities, medications, chest radiographs, and clinical data such as nail color were extracted to evaluate clinical outcome. RESULTS: Mean patient age was 71.6 years, and 2 patients (40%) were male. Four patients had sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations, 4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail discoloration improved in every patient after CAM treatment. Four patients also experienced improvement in their respiratory manifestations. CONCLUSIONS: In patients with YNS, the anti-inflammatory activity of macrolides might improve their systemic inflammation. This improvement could help to reduce lymphedema and promote nail growth. TRIAL REGISTRATION: Ethical approval was provided by the institutional review board of the National Center of Global Health and Medicine (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for UMIN Clinical Trial Registry ( UMIN000028514 ) in August 4th, 2017.

Markers of Disease Severity in Patients with Spanish Influenza in the Japanese Armed Forces, 1919-1920.

We examined preserved medical charts of 470 Spanish influenza patients (8 with fatal cases) hospitalized at former army hospitals in Japan during 1919-1920. The following factors were associated with longer periods of hospitalization: adventitious discontinuous lung sounds, maximum respiration rate, continuation of high fever after hospital admission, and diphasic fever.

Chronological, geographical, and seasonal trends of human cases of avian influenza A (H5N1) in Vietnam, 2003-2014: a spatial analysis.

BACKGROUND: Human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to occur in Southeast Asia. The objective of this study was to identify when and where human H5N1 cases have occurred in Vietnam and how the situation has changed from the beginning of the H5N1 outbreaks in 2003 through 2014, to assist with implementing methods of targeted disease management. METHODS: We assessed the disease clustering and seasonal variation of human H5N1 cases in Vietnam to evaluate the geographical and monthly timing trends. The clustering of H5N1 cases and associated mortality were examined over three time periods: the outbreak period (2003-2005), the post-outbreak (2006-2009), and the recent period (2010-2014) using the flexibly shaped space-time scan statistic. The most likely cases to co-cluster and the elevated risks for incidence and mortality were assessed via calculation of the relative risk (RR). The H5N1 case seasonal variation was analysed as the cyclic trend in incidence data using Roger's statistical test. RESULTS: Between 2003 and 2005, H5N1 cases (RR: 2.15, p = 0.001) and mortality (RR: 2.49, p = 0.021) were significantly clustered in northern Vietnam. After 2010, H5N1 cases tended to occur on the border with Cambodia in the south, while H5N1 mortality clustered significantly in the Mekong delta area (RR: 6.62, p = 0.002). A significant seasonal variation was observed (p < 0.001), with a higher incidence of morbidity in December through April. CONCLUSIONS: These findings indicate that clinical preparedness for H5N1 in Vietnam needs to be strengthened in southern Vietnam in December-April.

Influence of pneumonia complications on the prognosis of patients with autopsy-confirmed Alzheimer's disease, dementia with Lewy bodies, and vascular dementia.

BACKGROUND: Pneumonia is a major, complicated disease in patients with dementia. However, the influence of pneumonia on the prognosis of patients with varying types of dementia has not been fully evaluated. METHODS: We retrospectively analyzed the data from medical and autopsy reports. All study patients had been hospitalized and underwent brain autopsy in a hospital in Toyohashi, Japan, between 2005 and 2014. The patients with subtypes of dementia, specifically Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or vascular dementia (VaD), were neuropathologically diagnosed and examined. Pneumonia incidence, cause of death, and the clinical time-course of dementia were compared among the dementia subtypes. The time to death from dementia onset (survival time) was compared by the Kaplan-Meier method among subtypes of dementia with or without pneumonia. Risk factors for survival time on all study patients were analyzed with the Cox proportional hazard model. RESULTS: Of the 157 eligible patients, 63 (40.1%) had AD, 42 (26.8%) had DLB, and 52 (33.1%) had VaD. Pneumonia complication was observed with high incidence in each subtype of dementia, especially in DLB (90.5%). The median total duration from dementia onset to death was 8 years in AD and DLB, and 5 years in VaD. The VaD subtype had more male patients than AD or DLB (P = 0.010), and age of death in this group was the youngest among the three groups (P = 0.018). A significant difference was observed in the survival time by the Kaplan-Meier method among the three groups (P < 0.001) and among the groups with pneumonia (P = 0.002). The factors associated with shorter survival time were male gender, pneumonia complications, diabetes mellitus, age of dementia onset ≥ 75 years, and VaD. CONCLUSIONS: Pneumonia complications shortened the survival time of patients with AD, DLB, and VaD.

Clinical characteristics and mortality risk among critically ill patients with COVID-19 owing to the B.1.617.2 (Delta) variant in Vietnam: A retrospective observational study.

BACKGROUND: SARS-CoV-2 Delta variant caused a large number of COVID-19 cases in many countries, including Vietnam. Understanding mortality risk factors is crucial for the clinical management of severe COVID-19. METHODS: We conducted a retrospective study at an intensive care center in Ho Chi Minh City that urgently built by Bach Mai Hospital during the COVID-19 outbreak in Vietnam, when the Delta variant predominated. Participants were laboratory-confirmed patients with SARS-CoV-2 infection, admitted in August 2021. Data on patients' demographic and clinical characteristics, radiographic and laboratory findings, treatment, and clinical time course were compared between survivors and non-survivors. Risk factors to mortality were assessed using logistic regression. RESULTS: Among 504 eligible COVID-19 patients, case fatality was 52.2%. Unvaccinated patients accounted for 61.2% of non-survivors and 43.6% of survivors (p < 0.001). The time from onset to hospital admission was 8 days in non-survivors and 7 days in survivors (p = 0.004). Among non-survivors, 90.2% developed acute respiratory distress syndrome (ARDS). Oxygen therapy was administered for all patients, but antiviral agent was given to 51.7% of non-survivors. 54.2% of non-survivors tested positive for the bacterial infection using blood culture. The risk factors for mortality were diabetes mellitus, respiration rate, oxygen saturation, vaccination status, time from onset to admission, and older age. CONCLUSIONS: Critical patients with COVID-19 owing to the Delta variant in Vietnam had delayed hospital admission, leading to ARDS and death. Early availability of vaccines and preventing bacterial infections are crucial for reducing mortality of COVID-19, especially in low- and middle-income countries.

Increased risk of nontuberculous mycobacterial infection in asthmatic patients using long-term inhaled corticosteroid therapy.

BACKGROUND AND OBJECTIVE: The risk of pneumonia is increased among COPD patients using inhaled corticosteroids (ICS). However, there is uncertainty regarding the association between long-term use of ICS and exacerbations of respiratory tract infections among asthmatic patients. METHODS: A case-control nested cohort study was performed to assess the association of asthma with nontuberculous mycobacterium (NTM) infection. RESULTS: Among this cohort of 464 asthmatic patients, 14 experienced complications due to NTM infections, of which eight were caused by Mycobacterium avium-intracellulare complex, three by M. kansasii, one by M.terrae and the remaining two by unclassifiable scotochromogens. Asthmatic patients with NTM infections were older (67.1 ± 8.6 vs 58.8 ± 12.3 years, P < 0.01) and had more severe airflow limitation (FEV(1) %, 60.6 ± 10.3 vs 72.3 ± 18.3, P < 0.03) than those without NTM infections. All except one had received ICS treatment for more than 5 years, and 12 of the 14 patients used inhaled fluticasone propionate daily (four patients at a dose of 400 µg/day and eight patients at a dose >800 µg/day). CONCLUSIONS: These findings suggest that the risk of NTM infection may be greater in asthmatic patients who are older, have more severe airflow limitation and receive higher doses of ICS therapy.

Superiority of nebulized corticosteroids over dry powder inhalers in certain patients with cough variant asthma or cough-predominant asthma.

BACKGROUND: The particle distribution might differ between nebulizer therapy and metered-dose inhaler (MDI) or dry powder inhaler (DPI) therapy because the particles repeatedly enter/re-enter the airways with the nebulizer. Inhaled corticosteroids (ICS) were administered with a nebulizer to assess the benefit of changes in the distribution of particles in patients with cough variant asthma (CVA) and cough-predominant asthma (CPA). METHODS: Patients whose symptoms were not controlled by their current therapy were enrolled. In patients receiving high-dose ICS by MDI or DPI (ICS-MDI/DPI), steroid therapy was switched to 1,320µg/day of nebulized dexamethasone (1,600µg as dexamethasone sodium phosphate) (chronic steroid-independent group). In patients receiving systemic steroids regardless of their ICS-MDI/DPI therapy, nebulized dexamethasone was added and any concurrent ICS-MDI/DPI therapy was halted to detect a steroid-sparing effect (chronic steroid-dependent group). In patients with acute exacerbation of CVA or CPA and persistent symptoms despite systemic corticosteroids, nebulized dexamethasone was added to assess its effect (acute group). RESULTS: Superior symptom control was achieved in 10 out of 12 steroid-independent patients, 3 out of 6 steroid-dependent patients, and all 7 acute patients. CONCLUSIONS: Delivery of ICS via a nebulizer has advantages over ICS-MDI/DPI in some patients with CVA or CPA.

[A case of an asthma patient receiving omalizumab during pregnancy].

We describe the first report in Japan of a woman who received omalizumab during pregnancy and delivery. Her asthma was so severe that she had been taking systemic corticosteroids since 22 years old, but asthma was poorly controlled. She had been pregnant seven times before, but almost every time asthma control had worsened and spontaneous abortion resulted, so she had only one child. She confirmed that she was not intending to become pregnant, and initiated use of omalizumab in August 2009. However, pregnancy was identified after she had taken the drug 3 times. We explained the risks in detail, but the patient wanted to keep taking omalizumab, as her asthma control was improved and she thought she could continue the pregnancy. We therefore decided to continue with omalizumab therapy. In October, she caught a cold and experienced asthma exacerbation. Despite the risk, she decided to suspend omalizumab therapy after taking the drug 7 times, as she was not feeling any benefit from therapy. Threat of abortion was identified in February 2010, so a 544-g female baby was delivered at 26 weeks gestation by Cesarean section. The baby had to be hospitalized in the neonatal intensive care unit because of low birth weight, but she has been developing and growing without handicap. We report this case as the first known case of pregnancy and delivery for a woman receiving omalizumab in Japan. Omalizumab may be safe to use in pregnant women with difficult-to-control asthma.

The pharmacokinetics and long-term therapeutic effects of gefitinib in patients with lung adenocarcinoma harboring the epidermal growth factor receptor(EGFR)mutation.

INTRODUCTION: The relationship between the pharmacokinetics and long-term antitumor activity of gefitinib in patients with epidermal growth factor receptor(EGFR)mutation-positive lung adenocarcinoma has not yet been clarified in clinical practice. The present study assessed the correlation between the pharmacokinetics and long-term therapeutic effects of gefitinib in patients with lung adenocarcinoma harboring the EGFR-activating mutation. METHODS: Fifteen patients with lung adenocarcinoma harboring the EGFR mutation were administered 250 mg of gefitinib daily. Blood samples were collected prior to the first administration of gefitinib and after 1, 4, 6, 8, and 24 h. Plasma concentrations of gefitinib were measured via liquid chromatography mass spectrometry, and the peak plasma concentration(Cmax)and area under the plasma concentration time curve from 0 to 24 h(AUC 0-24)of gefitinib were determined. The correlations between these pharmacokinetic variables and the objective responses, including progression-free survival(PFS)and overall survival(OS), were retrospectively analyzed. RESULTS: The Cmax of gefitinib in patients with a partial response(PR)was significantly lower than that of patients with stable disease(SD)(median Cmax: 278 vs 588 ng/mL, p<0.05 ). However, the Cmax of gefitinib did not correlate with longer PFS. Conversely, a significant negative correlation was found between the AUC 0-24 of gefitinib and longer survival(r=-0.545, p<0.05 ). CONCLUSIONS: It may be possible that a high concentration of gefitinib is not necessary to achieve long-term therapeutic effects in patients with lung adenocarcinoma harboring the EGFR mutation.

Effect of asthma, COPD, and ACO on COVID-19: A systematic review and meta-analysis.

INTRODUCTION: The prevalence of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with COVID-19 varies, as well as their risks of mortality. The present study aimed to assess the prevalence of asthma, COPD, and ACO as comorbidities, and to determine their risks of mortality in patients with COVID-19 using a systematic review and meta-analysis. METHODS: We systematically reviewed clinical studies that reported the comorbidities of asthma, COPD, and ACO in patients with COVID-19. We searched various databases including PubMed (from inception to 27 September 2021) for eligible studies written in English. A meta-analysis was performed using the random-effect model for measuring the prevalence of asthma, COPD, and ACO as comorbidities, and the mortality risk of asthma, COPD, and ACO in patients with COVID-19 was estimated. A stratified analysis was conducted according to country. RESULTS: One hundred one studies were eligible, and 1,229,434 patients with COVID-19 were identified. Among them, the estimated prevalence of asthma, COPD, and ACO using a meta-analysis was 10.04% (95% confidence interval [CI], 8.79-11.30), 8.18% (95% CI, 7.01-9.35), and 3.70% (95% CI, 2.40-5.00), respectively. The odds ratio for mortality of pre-existing asthma in COVID-19 patients was 0.89 (95% CI, 0.55-1.4; p = 0.630), while that in pre-existing COPD in COVID-19 patients was 3.79 (95% CI, 2.74-5.24; p<0.001). France showed the highest prevalence of asthma followed by the UK, while that of COPD was highest in the Netherlands followed by India. CONCLUSION: Pre-existing asthma and COPD are associated with the incidence of COVID-19. Having COPD significantly increases the risk of mortality in patients with COVID-19. These differences appear to be influenced by the difference of locations of disease pathophysiology and by the daily diagnosis and treatment policy of each country.

Clinical and radiological features of imported chikungunya fever in Japan: a study of six cases at the National Center for Global Health and Medicine.

Chikungunya fever (CHIKF) is currently distributed in Africa and in South and Southeast Asia; outbreaks have occurred periodically in the region over the past 50 years. After a large outbreak had occurred in countries in the western Indian Ocean region in 2005, several countries reported cases of CHIKF from travelers who had visited affected areas. In Japan, there have been only 15 cases of CHIKF patients so far, according to the National Institute of Infectious Diseases. Therefore, to evaluate the clinical and radiological features associated with the disease, we describe 6 imported cases of CHIKF. All of the patients had had prolonged arthralgia on admission to our hospital, and diagnosis was confirmed with specific antibodies by using an IgM-capture enzyme-linked immunoassay and a plaque reduction neutralizing antibody assay. Magnetic resonance imaging (MRI) of one patient revealed erosive arthritis and tenosynovitis during the convalescence stage. Clinicians should be aware of the late consequences of infection by the chikungunya virus (CHIKV) and recognize the possible association of subacute and chronic arthritis features. In addition, competent vectors of CHIKV, Aedes aegypti, can now be found in many temperate areas of the eastern and western hemispheres, including Japan. This fact raises concern that the virus could be introduced and become established in these areas. This necessitates an increased awareness of the disease, because imported cases are likely to contribute to the spread of CHIKV infection wherever the competent mosquito vectors are distributed.

An early intensive intervention for inducing inactive asthma in adults--a one-year follow-up observation study.

BACKGROUND: Treatment strategy that reduces dependence on long-term medication for chronic asthma is preferable. The purpose of the study is to investigate the efficacy of an early intensive intervention for inducing inactive asthma in adults and identify factors that affect the efficacy. METHODS: A prospective study was conducted on subjects who had asthma for two years or less. An intensive intervention consisting of systemic corticosteroid treatment for two weeks followed by inhaled corticosteroid for further 16 weeks with concomitant administration of bronchodilator(s) was administrated on 109 subjects. As a control group, 33 subjects were treated according to the current asthma treatment guidelines for 18 weeks. The primary outcome of the intervention was assessed with symptomatology and use of medication during 12 months after the cessation of treatment period. RESULTS: At one year after the intervention, significantly more patients in the intensive intervention group (41%) than in the control group (24%) had no respiratory symptoms and were medication-free or had experienced minor upper respiratory symptoms (inactive asthma) (P = 0.01). The intensive intervention maintained a significant factor associated with one-year inactive asthma (adjusted odds ratio: 3.61, 95% confidence interval: 1.20-10.84; P = 0.02). Infection as onset cause, asthma duration and pre-treatment %FEV(1.0) were also identified independently associated with inactive asthma. As the limitation, the study was not randomized trial. CONCLUSIONS: Intensive therapy in the early stage is very likely to contribute to increasing one-year asthma inactivity, which may reduce patients' dependence on long-term management by medical treatment.

[Clinical study concerning anti-inflammatory effect of fixed dose therapy by budesonide/formoterol combination inhaler for moderate persistent asthmatics].

BACKGROUND: The clinical usefulness of fixed dose maintenance therapy using a combination inhaler containing budesonide and formoterol (FBC) has already been established, still evidence concerning anti-inflammatory effect by maintenance therapy with fix-dosed FBC, in comparison with other ICS and LABA combination therapy including salmeterol/fluticasone combination inhaler, is lacking. METHODS: Moderate persistent adult asthmatics who has received combination therapy of ICS (200∼500 µg/day FP equivalent) and LABA (salmeterol 100 µg/day) for more than 6 months and under well-control conditions by asthma control test (ACT) have been recruited. FeNO, as a marker of airway inflammation, ACT score, and the results of spirometry have been evaluated after switching to maintenance therapy by FBC 640/18 µg/day for 8 weeks. RESULTS: The fixed dosed FBC therapy resulted in superior primary outcome, as compared with previous ICS/LABA combination therapy, as assessed by measuring FeNO, 44.0±26.5 to 31.3± 15.4 ppb (p<0.01, paired-t test). ACT score also improved significantly, 22.22±1.57 to 23.88±1.57 (p<0.01). The number of patients who used SABA more than once a week has decreased 13 to 0 with FBC treatment. CONCLUSION: The airway anti-inflammatory effect by 8 weeks maintenance therapy with fix-dosed FBC 640/18 µg/day (2 puffs twice a day) has been strongly suggested.

[Survival-related clinical factors of patients with advanced non-small cell lung cancer after 2000].

PURPOSE: To find new survival-related clinical factors in patients with non-small cell lung cancer (NSCLC) after 2000. PATIENTS AND METHOD: Two hundred one patients were registered with primary NSCLC from years 2000 to 2005. One hundred eighty-six patients were pathologically diagnosed with NSCLC (all patients in the group). These patients were reviewed after wards in order to find any new survival-related clinical factors. RESULTS: One hundred forty-nine patients had adenocarcinoma. Median age was 68 years old, and median performance status (PS) was 1. Fifty-nine patients were treated with gefitinib, which is an epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI). In initial treatment, 22 patients were given gefitinib, and 37 patients after secondary treatment. Sixteen patients were managed with the best supportive care, and 12 patients were not allowed to know their precise treatment. These 28 patients were excluded from the all patients group i. e., the treated patients group. In multivariate analysis of this group, the PS, the treatment by gefitinib, the number of metastasized organs, and the serum total bilirubin were independent survival-related clinical factors. The median survival time without use of gefitinib was 46 weeks, and the survival times in first-line or more than first-line were 40 or 105 weeks, respectively (p = 0. 01). CONCLUSION: In addition to PS, the number of metastasized organs, and serum total bilirubin, treatment by gefitinib was considered to be one of the survival-related clinical factors in unselected patients with NSCLC.