Association of demographics, HCV co-infection, HIV-1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV-1 Surveillance Network.

INTRODUCTION: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas. METHODS: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/µl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%. RESULTS: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/µl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07_BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis. CONCLUSIONS: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing.

Japanese antimicrobial consumption surveillance: First report on oral and parenteral antimicrobial consumption in Japan (2009-2013).

No reliable national antimicrobial consumption data have been available in Japan. The Japanese antimicrobial consumption surveillance (JACS) project started to collect data nationwide on antimicrobial consumption. This paper provides the first sales data from the JACS project on oral and parenteral antimicrobial consumption in Japan as well as the trends for the years from 2009 to 2013. The population-weighted total consumption was expressed as defined daily doses (DDDs) per 1000 inhabitants per day (DID). The value of DID increased from 14.7 in 2009 to 15.8 in 2013. Notably, oral antimicrobials accounted for 92.6% (mean of 2009, 2011 and 2013) of total consumption. Oral third-generation cephalosporins, macrolides and fluoroquinolones accounted for 77.1% (mean of 2009, 2011 and 2013) of oral consumption. Consumption of antimicrobials has increased during the years 2009 and 2013 regardless of the dosage form. This is the first report regarding the population-weighted consumption of oral and parenteral antimicrobials in Japan during the years 2009 and 2013. These results provide useful information for combating the menace of antimicrobial resistance in Japan.

Daily Review of Antimicrobial Use Facilitates the Early Optimization of Antimicrobial Therapy and Improves Clinical Outcomes of Patients with Bloodstream Infections.

Insufficient information is available to confirm the beneficial effects of implementing an antimicrobial stewardship program in reducing mortality of patients with bloodstream infections. A single institutional cohort study was conducted to evaluate clinical outcomes after implementation of a daily review of antimicrobials used to treat patients with bloodstream infections. Subjects were allocated to groups receiving either intervention or nonintervention. After implementation of an antimicrobial stewardship program, the day from the onset of infection required to administer effective intravenous antimicrobial treatment was significantly shortened (p=0.022), and the rate of de-escalation was significantly elevated (p<0.001) compared with the nonintervention group. Further, the rate of 30-d death associated with bloodstream infection was siginificantly reduced from 11.4 to 5.4% (p=0.030) compared with the nonintervention group. The incidence of adverse events was significantly lower in the intervention group than in the nonintervention group (7.7 vs. 28.0%, p<0.001). Our present findings suggest that daily review of the use of antimicrobials was highly effective for optimizing early antimicrobial therapy and improved clinical outcomes of patients with bloodstream infections.

[A retrospective study of the relationship between bacterial numbers from central venous catheter tip cultures and blood cultures for evaluating central line-associated bloodstream infections].

Catheter-related bloodstream infection (CRBSI) is an infectious disease requiring special attention. It is a common cause of nosocomial infections; catheter insertion into the central veins particularly increases the risk of infection (CLA-BSI: central line-associated bloodstream infection). We examined the relationship between the number of bacterial colonies cultured from shredded central venous catheter (CVC) tips and from blood cultures in our hospital from 2011 to 2012. Coagulase-negative staphylococci topped the list of microbe isolated from the CVC tip culture, followed by Pseudomonas aeruginosa, Staphylococcus aureus, and Candida spp. S. aureus and Candida spp., with growth of over 15 colony-forming units in the CVC tip culture, were also detected at high rates in the blood culture. However, gramnegative bacilli (Enterobacteriaceae and P. aeruginosa) did not show a similar increase in colony number in the CVC tip culture. Because microbes adhering to shredded catheter tips are readily detected by culture, this method is useful as a routine diagnostic test. In addition, prompt clinical reporting of the bacterial number of serious CLA-BSI-causing S. aureus and Candida spp. isolated from CVC tips could contribute to earlier CLA-BSI diagnosis.

Reduction of linezolid-associated thrombocytopenia by the dose adjustment based on the risk factors such as basal platelet count and body weight.

The aim of the present study was to evaluate the efficacy of dose modification based on the risk factor for linezolid-induced thrombocytopenia. A multivariate logistic regression analysis performed in the observational study showed that low body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16-510.1, P = 0.012) and the baseline platelet count of <200 × 10(3)/mm(3) (OR: 24.9, 95% CI: 1.53-404.7, P = 0.024) were found to be risk factors for linezolid-induced thrombocytopenia. In the subsequent intervention study, in which daily dose of linezolid was set to 20 mg/kg in patients with either one of the risk factors or 1200 mg in those without any risk factor, the onset of thrombocytopenia was significantly prolonged in the intervention study group (P = 0.043), without reducing clinical efficacy. These findings suggest that dose adjustment of linezolid is effective in preventing thrombocytopenia without reducing its clinical efficacy in patients having risk factors.

Effective recognition of HIV-1-infected cells by HIV-1 integrase-specific HLA-B∗4002-restricted T cells.

HLA-B∗4002 is one of the common HLA-B alleles in the world. All 7 reported HLA-B∗4002-restricted HIV epitopes are derived from Gag, Nef, and Vpr. In the present study we sought to identify novel HLA-B∗4002-restricted HIV epitopes by using overlapping 11-mer peptides of HIV-1 Nef, Gag, and Pol, and found that 6 of these 11-mer Pol peptides included HLA-B∗4002-restricted epitopes. Analysis using truncated peptides of these 6 peptides defined 4 optimal Pol (integrase) epitopes. All epitopes previously reported had Glu at position 2 (P2), suggesting that Glu at P2 is the anchor residue for HLA-B∗4002; whereas only 2 of the integrase epitopes that we here identified had Glu at P2. CTL clones specific for the 2 epitopes effectively recognized HIV-1-infected cells whereas those for other 2 epitopes only weakly recognized them. The antigen sensitivity of the former clones for the epitope peptide was much higher than that of the latter clones, suggesting 2 possibilities: 1) the former T cells have high-affinity TCRs and/or 2) the epitope peptides recognized by the former T cells are highly presented by HLA-B∗4002 in HIV-1-infected cells. These integrase-specific T cells with high antigen sensitivity may contribute to the suppression of HIV-1 replication in HIV-1-infected HLA-B∗4002+ individuals.

Serum (1-->3) beta-D-glucan as a noninvasive adjunct marker for the diagnosis of Pneumocystis pneumonia in patients with AIDS.

High serum (1-->3) beta-D-glucan levels are described in patients with Pneumocystis pneumonia (PCP). We evaluated the diagnostic value of beta-D-glucan in 111 patients with AIDS who had PCP and confirmed its usefulness. However, it does not correlate with disease severity and is not suitable for monitoring response to treatment.

Influence of polishing instruments on the surface texture of resin composites.

OBJECTIVE: There is a need for an ideal polishing system for resin composite restorations. The purpose of this study was to investigate the influence of polishing instruments on the surface texture of light-cured resin composites. METHODS AND MATERIALS: Four polishing systems-Compomaster (Shofu), Silicone Points C Type (Shofu), Super-Snap (Shofu), and Enhance Finishing and Polishing System (Dentsply/DeTrey)-were used to polish the flat surface of cylindrical blocks made of 3 different resin composites: Beautifil (Shofu), Clearfil AP-X (Kuraray Medical), and Lite-Fil II A (Shofu). The average surface roughness (Ra) and surface gloss (Gs60 degrees) were determined. Scanning electron microscopic observations of the polished specimens were made. The polished samples were immersed in a 0.3% acid rhodamine B solution for 1 week, and change in color was determined. RESULTS: The multiple-step systems, Enhance and Super-Snap, resulted in the best surface finishes. A new single-step point, Compomaster, ranked third in surface finish but was significantly better than the older point system, Silicone Points C. The color-staining experiments showed that there were no significant differences between the Compomaster system and the multiple-step systems, which were all significantly better than the older polishing point. CONCLUSION: The newly introduced 1-step polishing point has the ability to polish resin composites as effectively as multistep polishing systems.

Influence of polishing duration on surface roughness of resin composites.

There is a need for effective polishing instruments for resin composite restorations with highly polished surfaces. The purpose of this study was to investigate the influence of polishing duration on surface roughness of light-cured resin composites. Four polishing systems, Compomaster (Shofu), Silicone Points C Type (Shofu), Super Snap (Shofu) and Enhance Finishing and Polishing System (Dentsply/Caulk), were used to polish two commercially available resin composites, Clearfil AP-X (Kuraray Medical) and Lite-Fil II A (Shofu). Resin pastes were condensed into molds (10 mm in diameter, 5 mm in depth) and light irradiated for 40 s. Composite surfaces were ground with # 600 SiC paper followed by polishing with an instrument for 30 s, and the surface roughness was measured every 10 s during polishing procedures. The average surface roughnesses (Ra) were determined using a profilometer. Data were analyzed by Tukey HSD test (P = 0.05). After 30 s of polishing, mean Ra values ranged from 0.07 to 0.50 for Clearfil AP-X, and from 0.11 to 0.57 for Lite-Fil II A. Although the time required for polishing was longer, the surface finish produced by multiple-step polishing systems was superior to that obtained with one-step polishing systems.

Determination of elastic modulus of the components at dentin-resin interface using the ultrasonic device.

The purpose of this study was to determine the elastic moduli of the components at resin-dentin interface with the use of an ultrasonic device. Dentin plates were obtained from freshly extracted bovine incisors with a shape in rectangular form. Resin composites and bonding agents were polymerized and trimmed in the same shape as the dentin specimens. The ultrasonic equipment employed in this study was comprised of a Pulser-Receiver, transducers, and an oscilloscope. Each elastic modulus was determined by measuring the longitudinal and shear wave sound velocities. The mean elastic modulus of mineralized dentin was 17.4 GPa, while that of demineralized dentin was 1.4 GPa. When the demineralized dentin was immersed in bonding agents, the elastic modulus changed to 3.7-4.7 GPa, and these values were significantly higher than those of demineralized dentin. A gradient in elastic modulus was detected as the analysis shifted from the dentin side to the resin composite.