Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial.

BACKGROUND: Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19. METHODS: We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load. RESULTS: Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447). CONCLUSIONS: In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.

Prehospital shock index predicts 24-h mortality in trauma patients with a normal shock index upon emergency department arrival.

BACKGROUND: The shock index (heart rate divided by systolic blood pressure) of trauma patients upon emergency department arrival predicts blood loss and death. However, some patients with normal shock indices (0.4 < shock index <0.9) upon emergency department arrival also have poor prognoses. This study aimed to determine whether abnormal prehospital shock indices in trauma patients with normal shock indices upon emergency department arrival were predictors of a high risk of mortality. METHODS: We conducted a retrospective cohort study of emergency department-admitted trauma patients from 2004 to 2017. The study included 89,495 consecutive trauma patients aged ≥16 years, with Abbreviated Injury Scale score of ≥3, who were transported to the emergency department directly from the field and had a normal shock index upon emergency department arrival. According to the prehospital shock index scores, the patients were categorized into low shock index (≤ 0.4), normal shock index, and high shock index (≥0.9) groups. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. RESULTS: The 89,495 patients had a median age of 64 (interquartile range: 43-79) years, and 55,484 (62.0%) of the patients were male. There were 1350 (1.5%) 24-h deaths in total; 176/4263 (4.1%), 1017/78,901 (1.3%), and 157/6331 (2.5%) patients were in the low, normal, and high prehospital shock index groups, respectively. The adjusted odds ratios for 24-h mortality compared with the normal shock index group were 1.63 (95% confidence interval: 1.34-1.99) in the low shock index group and 1.62 (95% confidence interval: 1.31-1.99) in the high shock index group. CONCLUSION: Trauma patients with abnormal prehospital shock indices but normal shock indices upon emergency department arrival are at a higher risk of 24-h mortality. Identifying these indices could improve triage and targeted care for patients.

Two cases of pyelonephritis with bacteremia by Staphylococcus epidermidis in male patients with nephrolithiasis: Case reports and a literature review.

BACKGROUND: Staphylococcus epidermidis is a common cause of health care-associated bacteremia, especially in patients with an indwelling medical device. However, S. epidermidis is an uncommon causative organism in catheter-associated urinary tract infection, and rare pyelonephritis without any indwelling urinary device. To our knowledge, there are few cases reported of bacteremia secondary to urinary tract infection. We report two cases of pyelonephritis with bacteremia by S. epidermidis in male patients with unilateral nephrolithiasis and review prior case reports. CASE PRESENTATION: Case 1: 74-year-old man with a history of diabetes and overactive bladder had fever and pyuria with a right nephrolithiasis on abdominal CT scan. Case 2: 79-year-old man with a history of diabetes and post-myocardial infarction status had fever with a left nephrolithiasis on abdominal CT scan. In both cases, both the urine culture collected at ureteral stenting and blood culture were positive for S. epidermidis. We initiated intravenous antibiotics in these patients in addition to ureteral stenting. CONCLUSIONS: S. epidermidis is acknowledged as an uncommon pathogen that can cause bacteremia secondary to pyelonephritis without an indwelling urinary device. Clinicians should consider the possibility of pyelonephritis due to S. epidermidis if the pathogen is identified in blood and urine in patients with nephrolithiasis.

Changes in Quality of Life in Older Hemodialysis Patients: A Cohort Study on Dialysis Outcomes and Practice Patterns.

BACKGROUND: Despite improvements in dialysis treatment, mortality rates remain high, especially among older hemodialysis patients. Quality of life (QOL) among hemodialysis patients is strongly associated with higher risk of death. This study aimed to describe the health-related QOL and its change in older maintenance hemodialysis patients and to demonstrate characteristics associated with health-related QOL. METHODS: Data on 892 maintenance hemodialysis patients aged 60 years or older who were surveyed using the Kidney Disease Quality of Life Short Form at baseline and 2 years after study enrollment in phases 4 (2009-2011) and 5 (2012-2014) of the Japanese Dialysis Outcomes and Practice Patterns Study were analyzed. We categorized participants into 3 age groups (60-69, 70-79, and ≥80 years) and described baseline physical component summary (PCS) and mental component summary (MCS) scores, as well as their distribution of changes after 2 years across each category. RESULTS: Hemodialysis patients aged 70-79 years and ≥80 years had lower PCS scores than those aged 60-69 years (median: 70-79 years = 43.1; interquartile range [IQR], 35.2-49.4; ≥80 years = 38.8; IQR, 31.6-43.8; 60-69 years = 45.4; IQR, 37.5-51.4; p < 0.001). In contrast, MCS scores did not significantly differ by age category (70-79 years = 45.6; IQR, 38.4-53.7; ≥80 years = 45.4; IQR, 36.9-55.1; 60-69 years = 46.8; IQR, 39.5-55.7; p = 0.1). As dialysis vintage lengthened, the PCS score significantly became lower, whereas no association was found with change in the MCS score. The MCS score declined over time in older patients, especially among those aged 80 years and older after 2 years' follow-up. CONCLUSIONS: Physical QOL became worse as dialysis vintage lengthened. In contrast, mental QOL declined over time within a relatively short period among older maintenance hemodialysis patients.

Diagnostic test accuracy of jolt accentuation for headache in acute meningitis in the emergency setting.

BACKGROUND: Meningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of hours to several days. Delay in treatment can lead to serious outcomes. Inflammation of the meninges is assessed by analysing cerebrospinal fluid. Identifying the pathogen in cerebrospinal fluid is another way to diagnose meningitis. Cerebrospinal fluid is collected by doing a lumbar puncture, which is an invasive test, and can be avoided if a physical examination excludes the diagnosis of meningitis. However, most physical examinations, such as nuchal rigidity, Kernig's test, and Brudzinski's test, are not sufficiently sensitive to exclude meningitis completely. Jolt accentuation of headache is a new and less well-recognised physical examination, which assesses meningeal irritation. It is judged as positive if the headache is exacerbated by rotating the head horizontally two or three times per second. A 1991 observational study initially reported high sensitivity of this examination to predict pleocytosis. Pleocytosis, an abnormally high cerebrospinal fluid sample white cell count, is an accepted indicator of nervous system infection or inflammation. Jolt accentuation of headache may therefore accurately rule out meningitis without the use of lumbar puncture. However, more recent cross-sectional studies have reported variable diagnostic accuracy. OBJECTIVES: To estimate the diagnostic accuracy of jolt accentuation of headache for detecting acute meningitis in emergency settings. Secondary objectives: to investigate the sources of heterogeneity, including study population, patient condition, and types of meningitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Elsevier) to 27 April 2020. We searched ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web Version 5.0 to 28 April 2020. SELECTION CRITERIA: We included cross-sectional studies that assessed the diagnostic accuracy of jolt accentuation of headache for people with suspected meningitis in emergency settings. We included participants of any age and any severity of illness. Meningitis should be diagnosed with any reference standard, such as cerebrospinal fluid pleocytosis, proof of causative agents, or autopsy. DATA COLLECTION AND ANALYSIS: Two review authors independently collated study data. We assessed methodological quality of studies using QUADAS-2 criteria. We used a bivariate random-effects model to determine summary estimates of sensitivity and specificity where meta-analysis was possible. We performed sensitivity analyses to validate the robustness of outcomes. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included nine studies (1161 participants). Five studies included only adults. Four studies included both adults and children; however, the proportion was not reported in three of these studies. The youngest child reported in the studies was aged 13 years. There was no study including only children. The reference standard was pleocytosis in eight studies, and the combination of pleocytosis and increased protein in the cerebrospinal fluid in one study. Two studies also used smear or positive culture of cerebrospinal fluid. Risk of bias and concern about applicability was high in the participant selection domain for all included studies and the consciousness subgroup. Overall, pooled sensitivity was 65.3% (95% confidence interval (CI) 37.3 to 85.6), and pooled specificity was 70.4% (95% CI 47.7 to 86.1) (very low-certainty evidence). We established the possibility of heterogeneity from visual inspection of forest plots. However, we were unable to conduct further analysis for study population, types of meningitis, and participants' condition, other than disturbance of consciousness (a secondary outcome). Amongst participants whose consciousness was undisturbed (8 studies, 921 participants), pooled sensitivity and specificity were 75.2% (95% CI 54.3 to 88.6) and 60.8% (95% CI 43.4 to 75.9), respectively (very low-certainty evidence). AUTHORS' CONCLUSIONS: Jolt accentuation for headache may exclude diagnoses of meningitis in emergency settings, but high-quality evidence to support use of this test is lacking. Even where jolt accentuation of headache is negative, there is still the possibility of acute meningitis. This review identified the possibility of heterogeneity. However, factors that contribute to heterogeneity are incompletely understood, and should be considered in future research.

Imported and locally transmitted mild SARS-CoV-2 pneumonia cases in Japan.

Here, we describe two mild SARS-CoV-2 pneumonia cases. One was imported from Wuhan, and the other was locally transmitted in Japan without recent travel to China. In both cases, lower respiratory tract symptoms were observed first, and high fever progressed in about one week. The laboratory findings revealed normal WBC and CRP despite apparent lung infiltrations, and typical observations on CT imaging were important diagnostic clues. In the domestic endemic situation, a comprehensive evaluation of the clinical course, and laboratory and radiological findings was required for diagnosis.

Clinical and Molecular Characteristics of Klebsiella pneumoniae Isolates Causing Bloodstream Infections in Japan: Occurrence of Hypervirulent Infections in Health Care.

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae, respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan.

Body Mass Index Change and Hospitalization Risk in Elderly Hemodialysis Patients: Results from Japanese Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Short-term weight gains and losses are associated with a lower and higher mortality risk, respectively, in patients undergoing hemodialysis (HD). However, little is known about their association with the risk of subsequent hospitalization. METHODS: In a prospective cohort of 1,804 HD patients aged ≥65 years enrolled in the Japanese Dialysis Outcomes and Practice Patterns Study phases 3 (2005-2008) and 4 (2009-2011), we examined the associations between changes in body mass index (BMI) over a 4-month baseline period (<-3%, -3 to <-1%, -1 to <1% [reference], 1 to <3%, and ≥3%) and subsequent risk of all-cause, cardiovascular, and noncardiovascular hospitalization using Cox models with adjustment for potential confounders. RESULTS: During a median follow-up of 1.2 years, we noted 1,028 incident hospitalizations for any cause, including 275 and 753 hospitalizations for cardiovascular and noncardiovascular causes, respectively. An L-shaped association was observed between BMI change and all-cause hospitalization. The multivariable-adjusted hazard ratios (HRs; 95% CI) of all-cause hospitalization associated with BMI changes of <-3%, -3 to <-1%, 1 to <3%, and ≥3% (vs. -1 to <1%) were 1.29 (1.01-1.65), 1.22 (0.98-1.51), 1.04 (0.83-1.29), and 1.10 (0.83-1.45), respectively. Qualitatively similar associations were present for cardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.58 [1.06-2.37], 1.09 [0.75-1.58], 0.99 [0.72-1.36], and 0.91 [0.51-1.64], respectively) but not for noncardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.19 [0.90-1.57], 1.26 [0.99-1.59], 1.06 [0.84-1.35], and 1.18 [0.86-1.63], respectively). CONCLUSIONS: Decreases in BMI over a relatively short-term period were independently associated with higher risk of subsequent hospitalization, particularly cardiovascular-related hospitalization, among elderly HD patients.

Mycotic aneurysm caused by Edwardsiella tarda successfully treated with stenting and suppressive antibiotic therapy: a case report and systematic review.

BACKGROUND: Mycotic aneurysm is an uncommon disease which could be fatal without appropriate treatment. Although standard therapy for mycotic aneurysms consists of resection of the infected aorta and in situ graft replacement, some treat with endovascular stent-grafting because patients may not tolerate graft replacement due to underlying diseases. There are 6 more reported cases of mycotic aneurysm caused by Edwardsiella tarda. With the exception of our case, all underwent resection and debridement of the infected aorta or vascular prosthesis. Herein we report the first case ever of mycotic aneurysm caused by E. tarda, successfully treated with stenting and suppressive antibiotic therapy without resection of the infected aorta. CASE PRESENTATION: A 65-year-old Japanese woman with cirrhosis and hepatocellular carcinoma complained of fatigue. Her work up revealed a ruptured aneurysm of the descending aorta. She went through endovascular stent-graft placement. Edwardsiella tarda grew from blood cultures, which led to the diagnosis of mycotic aneurysm. Edwardsiella tarda is a Gram negative bacillus which rarely causes infections in humans. In the case of bacteremia, its mortality is reported to be very high and all reported cases with mycotic aneurysm caused by E. tarda ended up with resection of the infected aorta. CONCLUSION: Our case shows that in the case of mycotic aneurysm caused by E. tarda, endovascular stent-graft placement could be an alternative to in situ graft replacement.

Timing and prediction of secondary bacteremia in patients with COVID-19: A retrospective cohort study.

Background: We aimed to aid the appropriate use of antimicrobial agents by determining the timing of secondary bacteremia and validating and updating clinical prediction models for bacteremia in patients with COVID-19. Methods: We performed a retrospective cohort study on all hospitalized patients diagnosed with COVID-19 who underwent blood culture tests from January 1, 2020, and September 30, 2021, at an urban teaching hospital in Japan. The primary outcome measure was secondary bacteremia in patients with COVID-19. Results: Of the 507 patients hospitalized with COVID-19, 169 underwent blood culture tests. Eleven of them had secondary bacteremia. The majority of secondary bacteremia occurred on or later than the 9th day after symptom onset. Positive blood culture samples collected on day 9 or later after disease onset had an odds ratio of 22.4 (95% CI 2.76-181.2, p < 0.001) compared with those collected less than 9 days after onset. The area under the receiver operating characteristic curve of the modified Shapiro rule combined with blood culture collection on or after the 9th day from onset was 0.919 (95% CI, 0.843-0.995), and the net benefit was high according to the decision curve analysis. Conclusions: The timings of symptom onset and hospital admission may be valuable indicators for making a clinical decision to perform blood cultures in patients hospitalized with COVID-19.

Dose-response relationship between diarrhea quantity and mortality in critical care patients: A retrospective cohort study.

BACKGROUND: Previous studies have shown that diarrhea, defined as a dichotomized cutoff, is associated with increased mortality of patients in intensive care units (ICUs). This study aimed to examine the dose-response relationship between the quantity of diarrhea and mortality in ICU patients with newly developed diarrhea. METHODS: We conducted this single-center retrospective cohort study. We consecutively included all adult patients with newly developed diarrhea in the ICU between January 2017 and December 2018. Newly developed diarrhea was defined according to the World Health Organization definition. The consistency of diarrhea was evaluated by the Bristol stool chart scale, and the quantity of diarrhea was assessed on the day when patients newly developed diarrhea. The primary outcome was in-hospital mortality. The risk ratio (RR) and 95% confidence interval (CI) for the association between diarrhea quantity and mortality were estimated using multivariable modified Poisson regression models. RESULTS: Among the 231 participants, 68.4% were men; the median age was 72 years. The median diarrhea quantity was 401g (interquartile range [IQR] 230‒645g), and in-hospital mortality was 22.9%. More diarrhea at baseline was associated with higher in-hospital mortality; the adjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.20), p = 0.029. In sensitivity analyses with near quartile categories of diarrhea quantity (<250g, 250-399g, 400-649g, ≥650g), the adjusted RRs for each respective category were 1.00 (reference), 1.02 (0.51-2.04), 1.29 (0.69-2.43), and 1.77 (0.99-3.21), p for trend = 0.033. CONCLUSIONS: A greater quantity of diarrhea was an independent risk factor for in-hospital mortality. The diarrhea quantity may be an indicator of disease severity in ICU patients.

A case of amebic colitis and liver abscesses that occurred after treatment of coronavirus disease 2019 with dexamethasone.

Entamoeba histolytica infections, which can be asymptomatic, are endemic to developing countries; traveling to such countries is a risk factor for contracting these infections. A 65-year-old Japanese man was hospitalized for coronavirus disease 2019 (COVID-19)-associated respiratory distress, and was treated with remdesivir, dexamethasone, and oxygen supplementation. Although his respiratory condition improved and the oxygen support was discontinued, he developed a fever, severe abdominal pain, and diarrhea on day 13 of hospitalization. Fifteen years ago, he was hospitalized for diarrhea of an unknown origin in Suzhou, China, and had a history of passing loose stools for 1 year. Contrast-enhanced abdominal and pelvic computed tomography revealed liver abscesses in both lobes and intestinal edema from the ascending colon to the descending colon. The abscesses were suspected to be amebic based on the characteristics of the drained abscess fluid. The patient was treated with cefotaxime and metronidazole, and his temperature declined and abdominal pain improved. A culture analysis of abscess fluid yielded negative findings; however, polymerase chain reaction analyses of abscess and stool samples were positive for Entamoeba histolytica. We speculated that the patient was infected with Entamoeba histolytica while in China, and that the corticosteroid usage for COVID-19 had exacerbated the infection. Clinicians should be aware that corticosteroid treatments can lead to recurrent invasive amebiasis in asymptomatic amebic carriers.

Protocol for a Randomized, Open-Label Clinical Trial on the Effect of Mouthwash on Salivary SARS-CoV-2 Load.

Mouthwashes containing cetylpyridinium chloride (CPC) or on-demand aqueous chlorine dioxide (ACD) have potential to reduce the salivary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load in individuals with SARS-CoV-2 infection. This study will evaluate the effect of CPC and on-demand ACD mouthwashes on salivary SARS-CoV-2 levels in individuals with acute asymptomatic or mild SARS-CoV-2 infection (COVID-19) staying in a residential recuperation facility in Osaka, Japan. This randomized, open-label clinical trial will include three equal-sized groups (CPC mouthwash, on-demand ACD mouthwash, and placebo), with 30 participants per group. A stratified replacement block method will be used to ensure balanced allocation based on symptom presence and days since symptom onset. Participants will use mouthwash at set times for 7 days or until the end of recuperation. Saliva samples will be collected at multiple time points and tested for SARS-CoV-2 using quantitative reverse transcription polymerase chain reaction. The primary outcome will be changes in salivary SARS-CoV-2 viral load 2 h after the first mouthwash use compared with the pre-mouthwash level. Secondary outcomes will include changes in salivary viral load and clinical parameters at different time points. This study was registered with the Japan Registry of Clinical Trials on 18 October 2022 (jRCTs051220107).