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.

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.

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.

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.

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.

Trends in clinical features of novel coronavirus disease (COVID-19): A systematic review and meta-analysis of studies published from December 2019 to February 2020.

BACKGROUND: Since novel coronavirus disease (COVID-19) emerged, various clinical features of COVID-19 have been reported. METHODS: We conducted a systematic review of published studies reporting the clinical features of COVID-19. Two investigators independently searched PubMed (December 2019-February 2020) for eligible articles. A meta-analysis was performed to measure the frequencies of clinical outcomes and symptoms of COVID-19. A stratified analysis was conducted according to the timeline of outbreak and exposure histories: Group I, most patients were exposed to the Hunan seafood wholesale market and lived in Wuhan, Hubei province; Group II, patients lived in Hubei province but were not directly exposed to the market; and Group III, patients lived outside Hubei. RESULTS: Thirteen studies, all from China, were eligible. The estimated mortality rate among all studies was 2.12%, but that in Group I was 8.66%. The incidence of acute respiratory distress syndrome in Group I was 20.00%. Both fever and cough were major symptoms, and their frequencies were higher in Group I than in Groups II and III, while the frequency of diarrhea in Group I was lower than that in Group III. The estimated frequency of dyspnea in Group I was 37.18%, while those in Groups II and III were 16.95% and 7.03%, respectively. CONCLUSIONS: The trends in the clinical features of COVID-19 changed from December 2019 to February 2020. During this observation period, as the infection continued to spread, the clinical conditions for majority of patients became less severe with the changes in the route of transmission.

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.

Clinical epidemiology and mortality on patients with acute respiratory distress syndrome (ARDS) in Vietnam.

BACKGROUND: The clinical epidemiology and disease prognosis in patients with acute respiratory distress syndrome (ARDS) have not yet been fully elucidated in Vietnam. METHODS: We conducted a retrospective observational study at a national tertiary hospital in Hanoi, Vietnam. Participants were adult patients (age ≥18 years) who were admitted and diagnosed with ARDS during 2015-2017. Data on patients' general and clinical conditions, radiographic findings, ventilator settings, gas exchange, and treatment methods were collected and compared between survivors and non-survivors. Risk factors for mortality were assessed using logistic regression analysis. RESULTS: Among 126 eligible patients with ARDS admitted to the central tertiary hospital in Vietnam, we observed high mortality (57.1%). Of the total patients, 91.3% were transferred from local hospitals with a diagnosis of severe pneumonia and then diagnosed with ARDS at the central hospital. At the time of admission, 53.2% of patients had severe ARDS, 37.3% had moderate ARDS, and 9.5% had mild ARDS. The mean (standard deviation) sequential organ failure assessment (SOFA) score was 9.5 (3.4) in non-survivors and 7.4 (3.4) in survivors (p = 0.002). Although there was no significant difference in PaO2/FiO2 on admission between non-survivors and survivors, that on day 3 after admission was significantly different (p = 0.002). Logistic regression revealed that PaO2/FiO2 on day 3 [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.003-1.017], length of stay in a local hospital before admission to the central hospital (OR, 1.122; 95% CI, 1.042-1.210) due to stable condition, and SOFA score on Day 1 (OR, 0.842; 95% CI, 0.708-1.002) were independent factors in patient survival. CONCLUSIONS: Patients with ARDS admitted the central tertiary hospital had severe illness and high mortality. Most patients were transferred from local hospitals. Improvements in human, medical, and sociological resources in local will contribute to reducing the mortality of ARDS in Vietnam.

Tuberculosis-induced acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation.

Tuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS) with a high mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) may be an alternative option for treating TB-induced ARDS. However, the literature on TB-induced ARDS treated with VV-ECMO is limited and the most of them were prolonged therapy. We report on a-48-year-old man with TB-induced ARDS who was successfully treated by short-term use of VV-ECMO (5 days). He was developed symptoms and hospitalized with severe dyspnea in a local hospital for 3 days before admission to our hospital. At the time when he was transferred to our hospital, his chest computed tomography showed bilateral, diffuse and consolidative shadows all over the lungs, the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) was 50 mmHg, and respiratory system compliance was 12.5 mL/cmH2O. Two days after admission, Mycobacterium tuberculosis was detected by a sputum smear examination and he was diagnosed with TB-induced ARDS. VV-ECMO support was then initiated with administration of anti-TB drugs and systemic corticosteroid treatment. On the 4thday of ECMO support, his PaO2/FiO2 increased to 400 mmHg and lung compliance increased to 45 mL/cmH2O. He was weaned from ECMO on the 5th day of ECMO support and was extubated at the 8th day. He was discharged from hospital on the 47th hospitalized day and continued anti-TB medication at home. VV-ECMO is effective for TB-induced ARDS even in short-term administration if progression of ARDS is rapid.

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.

Pneumonia-associated death in patients with dementia: A systematic review and meta-analysis.

BACKGROUND: Pneumonia is a serious disease associated with mortality among patients with dementia. However, the reported frequency of pneumonia as a cause of death in patients with dementia varies, the reason for which has not been fully elucidated. METHODS: We conducted a systematic search in PubMed and the Cochrane Database of Systematic Reviews (inception to December 2016). Two authors independently determined the suitability of studies and potential bias and extracted the data. The primary outcome was frequency of pneumonia-associated death in patients with dementia. Stratified subgroup analysis was conducted among studies grouped according to type of mortality cause (immediate or underlying), information source of mortality cause (autopsy or death certificate), and study setting (clinic, hospital, or nursing home). RESULTS: We included 7 studies reporting the cause of death among patients with dementia and 12 studies comparing the cause of death among patients with and without dementia. The frequency of pneumonia-associated death among 19 eligible studies was 29.69% (95% confidence interval [CI], 25.86-33.53). Those frequencies differed according to whether the source for information about cause of death was an autopsy confirmation (49.98%; 95% CI, 43.75-56.71) or death certificate (19.65%; 95% CI, 15.48-23.83) and according to whether the type of mortality cause was an indirect cause of death (13.96%; 95% CI, 9.42-18.51) or direct cause of death (44.45%; 95% CI, 29.81-50.10). The risk of pneumonia-associated death in patients with dementia was twice as high as among those without dementia (odds ratio, 2.15; 95% CI, 1.63-2.83; p < 0.001). CONCLUSION: The various frequencies of pneumonia-associated death in patients with dementia were associated with the information source, type of mortality cause, and study setting. Patients with dementia in the terminal stages urgently require careful clinical management of pneumonia, to maximize patient life expectancy and quality.

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.

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.

Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia.

Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia.

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.

Prognostic Factors Related to Dementia with Lewy Bodies Complicated with Pneumonia: An Autopsy Study.

Objective In patients demonstrating dementia with Lewy bodies (DLB), pneumonia is a common complication. However, the prognostic factors for the survival time in DLB with pneumonia have not been investigated by autopsy in patients with neuropathologically confirmed DLB. Methods We conducted a retrospective study of the medical and autopsy reports of 42 patients admitted to a Japanese hospital between 2005 and 2014. The patients were neuropathologically diagnosed as having DLB by post-mortem examinations. We analyzed the effects of various factors on the time from DLB onset to death. Results Thirty-nine of the 42 patients with DLB (92.9%) developed pneumonia during hospitalization. The median age at DLB onset was 78 years and the median time from DLB onset to death was 8 years. The Cox proportional hazard model demonstrated cerebral infarction [Hazard Ratio (HR), 2.36 (95% CI 1.12-4.96), p=0.023], muscle weakness [HR, 2.04 (0.95-4.39), p=0.067], male sex [HR, 2.84 (1.24-6.50), p=0.014], and age at onset (≥78 years.) [HR, 4.71 (1.82-12.18), p=0.001] to be prognostic factors for a shorter time from DLB onset to death. Conclusion Careful treatment of cerebral infarction and muscle weakness of the lower extremities is crucial for DLB patients with pneumonia, especially for those over 78 years of age, in order to maximize the patients' life expectancies.

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.

Polymyxin-B-immobilized-fiber column hemoperfusion with oseltamivir treatment for ARDS due to influenza H1N1/09.

Acute respiratory distress syndrome (ARDS) is one of the severe complications of influenza H1N1/09 infection, resulting in high mortality. Effective treatment strategies for ARDS are needed. This report presents two cases of ARDS due to influenza in Vietnam. Both cases were similar in terms of starting symptoms, the rapid progression to ARDS, and the treatment strategy, direct hemoperfusion with a polymyxin-B-immobilized fiber column (PMX-DHP) and oseltamivir. However, the clinical course of disease and the outcomes were different. For case 1, treatment was initiated on day 4 following the onset of hypoxemia due to ARDS. Symptoms improved rapidly after treatment and the patient was discharged on day 12. For case 2, treatment was initiated on day 9 after the onset of symptoms. Despite intensive therapy, the patient died on day 18. In conclusion, treatment with PMX-DHP and oseltamivir is effective on ARDS due to influenza but only if initiated early.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.