Unveiling the viral escape: Quantification of microfloc-bound viruses in precoagulation and membrane filtration.

The implementation of precoagulation before the physical removal process is expected to achieve a high virus removal rate. However, viruses may form small flocs and subsequently escape into the effluent during physical removal processes. This study evaluated how viruses in the microflocs could be quantified using conventional virus quantification methods (plaque assay and quantitative polymerase chain reaction (qPCR)) to reveal the risk of underestimating virus concentration. In this study, the microfloc dissolution phenomenon in phosphate buffer solution was employed as a floc dissolution test. Viruses in microflocs formed under the experimental conditions. assuming water treatments, were quantified before and after floc dissolution. The findings revealed that virus concentrations increased by 1.0-3.9 log plaque-forming units/mL according to the plaque assay and by 1.7-4.0 log copies/mL according to the qPCR. This increase occurred after the dissolution of microflocs that were prepared in the humic acid test water. In the case of treated wastewater, virus concentrations increased in all samples according to the plaque assay and in seven of eight samples according to the qPCR. Our results indicate the necessity of careful consideration of virus quantification after precoagulation and physical removal systems.

Effects of surface hydrophobicity on the removal of F-specific RNA phages from reclaimed water by coagulation and ceramic membrane microfiltration.

Microfiltration (MF) has been widely adopted as an advanced treatment process to reduce suspended solids and turbidity in treated wastewater effluents designated for potable reuse. Although microfilter pores are much larger than viruses, the addition of a coagulant upstream of a microfilter system can achieve stable virus removal. Ceramic membranes have a narrow pore size distribution to achieve the high removal of contaminants. This study aims to evaluate virus log reduction using bench-scale coagulation and ceramic membrane MF. To investigate the effects of differences in net surface hydrophobicity, 18 sewage-derived F-specific RNA phages (FRNAPHs) were used for batch hydrophobicity and coagulation-MF tests. The capability of bench-scale coagulation and ceramic membrane MF under continuous automated long-term operation was tested to remove the lab reference strain MS2 and three selected FRNAPH isolates which varied by surface property. Median virus log reduction values (LRVs) exceeding 6.2 were obtained for all three isolates and MS2. Although coagulation and hydrophobicity were positively correlated, the virus isolate demonstrating the lowest level of hydrophobicity and coagulation (genogroup I) still exhibited a high LRV. Thus, coagulation and ceramic membrane MF systems may serve as viable options for virus removal during water reclamation and advanced treatment.

Applicability of pepper mild mottle virus and cucumber green mottle mosaic virus as process indicators of enteric virus removal by membrane processes at a potable reuse facility.

Treatment of wastewater for potable reuse is increasingly becoming a suitable alternative water source to meet the growing urban water needs worldwide. Potable reuse requires reduction of enteric viruses to levels at which they do not pose a risk to human health. Advanced water treatment trains (e.g., microfiltration (MF), ultrafiltration (UF), reverse osmosis (RO), and ultraviolet light and advanced oxidation process (UV/AOP)) provide significant protection and reduce virus loads in highly treated final product waters. Even though viruses are a principal concern, the performance of virus removal by membrane processes is not easily determined. The objective of this study was to evaluate the applicability of Aichi virus (AiV), pepper mild mottle virus (PMMoV), cucumber green mottle mosaic virus (CGMMV), and cross-assembly phage (crAssphage) removal as possible process indicators for MF, UF, and RO. Virus log reduction values (LRVs) based on gene copies measured using molecular methods were determined for MF and UF. The median LRVs of all viruses obtained after MF and UF were 2.9 and 3.1, respectively. The LRVs of the proposed indicators were lower than those of human enteric viruses. The morphological and physicochemical difference among indicators was not found to affect LRVs. Therefore, all proposed indicator viruses were determined to be suitable candidates as process indicators for MF and UF. Regarding RO, most of the viruses measured in this study were undetectable in permeate. Only PMMoV and CGMMV were detected showing median LRVs of 2.8 and 2.5, respectively. PMMoV and CGMMV are recommended as good process indicators of physical virus removal for the overall water treatment process.

Capsid integrity RT-qPCR for the selective detection of intact SARS-CoV-2 in wastewater.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes have been detected in wastewater worldwide. However, the assessment of SARS-CoV-2 infectivity in wastewater has been limited due to the stringent requirements of biosafety level 3. The main objective of this study is to investigate the applicability of capsid integrity RT-qPCR for the selective detection of intact SARS-CoV-2 in wastewater. Three capsid integrity reagents, namely ethidium monoazide (EMA, 0.1-100 µM), propidium monoazide (PMA, 0.1-100 µM), and cis-dichlorodiammineplatinum (CDDP, 0.1-1000 µM), were tested for their effects on different forms (including free genomes, intact and heat-inactivated) of murine hepatitis virus (MHV), which was used as a surrogate for SARS-CoV-2. CDDP at a concentration of 100 µM was identified as the most efficient reagent for the selective detection of infectious MHV by RT-qPCR (CDDP-RT-qPCR). Next, two common virus concentration methods including ultrafiltration (UF) and polyethylene glycol (PEG) precipitation were investigated for their compatibility with capsid integrity RT-qPCR. The UF method was more suitable than the PEG method since it recovered intact MHV (mean ± SD, 38% ± 29%) in wastewater much better than the PEG method did (0.013% ± 0.015%). Finally, CDDP-RT-qPCR was compared with RT-qPCR alone for the detection of SARS-CoV-2 in 16 raw wastewater samples collected in the Greater Tokyo Area. Five samples were positive for SARS-CoV-2 when evaluated by RT-qPCR alone. However, intact SARS-CoV-2 was detected in only three positive samples when determined by CDDP-RT-qPCR. Although CDDP-RT-qPCR was unable to determine the infectivity of SARS-CoV-2 in wastewater, this method could improve the interpretation of positive results of SARS-CoV-2 obtained by RT-qPCR.

Association between dipeptidyl peptidase-4 inhibitors and urinary tract infection in elderly patients: A retrospective cohort study.

PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. Although they have been reported to increase the risk of infection, the findings are controversial. Given that urinary tract infections (UTIs) are common in the elderly, we conducted a retrospective cohort study by using health care insurance claims data, to elucidate the association between the DPP-4 inhibitors and the incidence of UTI in latter-stage elderly patients. METHODS: We analyzed 25,111 Japanese patients aged 75 years and older between the fiscal years 2011 and 2016. Patients using DPP-4 inhibitors and sulfonylureas (SUs) were matched at a 1:1 ratio using propensity scoring. The Incidence rate ratio (IRR) of UTI was compared between users of SUs and users of DPP-4 inhibitors by Poisson regression. Moreover, subgroup analyses stratified by sex were conducted to evaluate whether the combination of prostatic hyperplasia and DPP-4 inhibitors is associated with the incidence of UTI in male patients. RESULTS: The use of DPP-4 inhibitors was associated with an increased risk of UTI (adjusted IRR 1.23, 95% CI [1.04-1.45]). After propensity score matching, the association remained significant (adjusted IRR 1.28, 95% CI [1.05-1.56]). Moreover, elderly male patients with prostatic hyperplasia who received DPP-4 inhibitors had a higher risk of UTI than SU users without prostatic hyperplasia (Matched: crude IRR 2.90, 95% CI [1.78-4.71]; adjusted IRR 2.32, 95% CI [1.40-3.84]). CONCLUSIONS: The long-term use of DPP-4 inhibitors by elderly patients, particularly male patients with prostatic hyperplasia, may increase the risk of UTI.

Investigation into the causes of indwelling urethral catheter implementation and its effects on clinical outcomes and health care resources among dementia patients with pneumonia: A retrospective cohort study.

There is a possibility that unnecessary treatments and low-quality medical care, such as inappropriate indwelling urethral catheter use, are being provided to older Japanese individuals.The aim of this study was to investigate contextual effects relating to indwelling urethral catheters in older people with dementia and to clarify the effects of indwelling urethral catheter use on patients' mortality, length of stay (LOS), and health care spending. This retrospective cohort study involved 4501 male and female Japanese participants. Those who were aged 75 or older with dementia and had a primary diagnosis of acute lower respiratory disease with antibiotics administered during hospitalization were eligible for inclusion. Patient mortality, LOS, and total charge during hospitalization were the main study outcomes. This study showed that indwelling urethral catheter use was significantly associated with higher mortality, longer LOS, and higher total charge for hospitalization. The pattern of indwelling urethral catheter use was clustered by care facility level. Physician density was significantly associated with indwelling urethral catheter use; the relationship was not linear but U-shaped, such that the approximate median had the lowest rate of urethral catheter use and this increased gradually toward both lower and higher physician densities. Our study found considerable variation in indwelling urethral catheter use between care facilities in older people with dementia. Additionally, indwelling urethral catheter use was related to poor outcomes. Based on these findings, we consider there to be an urgent need for constructing a framework to measure, report on, and promote the improvement of care quality for older individuals in Japan.

Investigation of the Existence of Supplier-Induced Demand in use of Gastrostomy Among Older Adults: A Retrospective Cohort Study.

The aim of this study is to clarify whether there is small area variation in the use of gastrostomy that is explained by hospital physician density, so as to detect the existence of supplier-induced demand (SID).The study design is a retrospective cohort using claim data of Fukuoka Late Elders' Health Insurance, submitted from 2010 to 2013. Study participants included 51,785 older adults who had been diagnosed with eating difficulties. We designated use of gastrostomy as an event. Multilevel logistic analyses were then used to investigate the existence of SID.After controlling for patient factors, we found significant regional level variance in gastrectomy use (median odds ratio [MOR]: 1.72, 1.37-2.51). Hospital physician density was significantly positively related with gastrostomy (adjusted OR of hospital physician density: 1.75, 1.25-2.45; P < 0.001). MORs were largely reduced for the input variable of hospital physician density.We found that the small area variation in use of gastrostomy among older adults could be explained by hospital physician density, which might indicate the existence of SID.

Quantification of adverse effects of regular use of triazolam on clinical outcomes for older people with insomnia: a retrospective cohort study.

OBJECTIVE: Older people are more likely to have insomnia. One of the most prescribed hypnotics in Japan is triazolam. Although some studies showed the possibility of adverse effects of triazolam in older people, there have been few studies investigating these effects in a clinical setting. The aim of this study was to determine whether patients who used triazolam regularly had increased risks of pneumonia, trauma, and pressure ulcers. METHODS: The research design was a retrospective cohort study using claim data. The subjects of the study were patients who were insured by Fukuoka Late Stage Elderly Healthcare Insurance. We defined patients who had received triazolam for 180 days or longer during fiscal year 2011 as the triazolam group, and those who had not received any hypnotics during the period as the non-triazolam group. Each patient in the triazolam group was then matched with a unique control from the non-triazolam group according to propensity score. Multivariate conditional logistic regression analyses were used to obtain adjusted odds ratios for pneumonia, trauma, and pressure ulcer in the triazolam group compared with the non-triazolam group. RESULTS: The number of patients in the triazolam and non-triazolam groups in the unmatched cohort was 13,015 and 411,610, respectively. Adjusted odds ratios show that the risks for pneumonia, trauma, and pressure ulcer in the matched cohort increased by approximately 40%, 30%, and slightly less than 30%, respectively (all statistically significant). CONCLUSIONS: Regular use of triazolam is a risk factor for pneumonia, trauma, and pressure ulcer in older people.

The Impact of Opportunistic Infections on Clinical Outcome and Healthcare Resource Uses for Adult T Cell Leukaemia.

We examined the impact of opportunistic infections on in-hospital mortality, hospital length of stay (LOS), and the total cost (TC) among adult T-cell leukaemia (ATL) patients. In this retrospective cohort study, we identified 3712 patients with ATL using national hospital administrative data. Analysed opportunistic infections included Aspergillus spp., Candida spp., cytomegalovirus (CMV), herpes simplex virus (HSV), pneumocystis pneumonia (PCP), tuberculosis, varicella zoster virus (VZV), Cryptococcus spp., nontuberculous mycobacteria, and Strongyloides spp. Multilevel logistic regression analysis for in-hospital mortality and a multilevel linear regression analysis for LOS and TC were employed to determine the impact of opportunistic infections on clinical outcomes and healthcare resources. We found ATL patients infected with CMV had significantly higher in-hospital mortality (adjusted odds ratio (AOR) 2.29 [1.50-3.49] p < 0.001), longer LOS (coefficient (B): 0.13 [0.06-0.20] p < 0.001) and higher TC (B: 0.25 [0.17-0.32] p < 0.001) than those without CMV. Those with CAN and PCP were associated with a lower in-hospital mortality rate (AOR 0.72 [0.53-0.98] p = 0.035 and 0.54[0.41-0.73] p < 0.001, respectively) than their infections. VZV was associated with longer LOS (B: 0.13 [0.06-0.19] p < 0.001), while aspergillosis, HSV, or VZV infections were associated with higher TC (B: 0.16 [0.07-0.24] p < 0.001, 0.12 [0.02-0.23] p = 0.025, and 0.17 [0.10-0.24] p < 0.001, respectively). Our findings reveal that CMV infection is a major determinant of poor prognosis in patients affected by ATL.