Association of non-steroidal anti-inflammatory drug use with encephalopathy development: An analysis using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Effect of participation in a surgical site infection surveillance programme on hospital performance in Japan: a retrospective study.

BACKGROUND: The effect of hospital participation in the Japan Nosocomial Infection Surveillance (JANIS) programme on surgical site infection (SSI) prevention is unknown. AIM: To determine if participation in the JANIS programme improved hospital performance in SSI prevention. METHODS: This retrospective before-after study analysed Japanese acute care hospitals that joined the SSI component of the JANIS programme in 2013 or 2014. The study participants comprised patients who had undergone surgeries targeted for SSI surveillance at JANIS hospitals between 2012 and 2017. Exposure was defined as the receipt of an annual feedback report 1 year after participation in the JANIS programme. The changes in standardized infection ratio (SIR) from 1 year before to 3 years after exposure were calculated for 12 operative procedures: appendectomy, liver resection, cardiac surgery, cholecystectomy, colon surgery, caesarean section, spinal fusion, open reduction of long bone fracture, distal gastrectomy, total gastrectomy, rectal surgery, and small bowel surgery. Logistic regression models were used to analyse the association of each post-exposure year with the occurrence of SSI. FINDINGS: In total, 157,343 surgeries at 319 hospitals were analysed. SIR values declined after participation in the JANIS programme for procedures such as liver resection and cardiac surgery. Participation in the JANIS programme was significantly associated with reduced SIR for several procedures, especially after 3 years. The odds ratios in the third post-exposure year (reference: pre-exposure year) were 0.86 [95% confidence interval (CI) 0.79-0.84] for colon surgery, 0.72 (95% CI 0.56-0.92) for distal gastrectomy, and 0.77 (95% CI 0.59-0.99) for total gastrectomy. CONCLUSION: Participation in the JANIS programme was associated with improved SSI prevention performance in several procedures in Japanese hospitals after 3 years.

Long-term outcomes of hemostatic therapy for variceal bleeding and the challenge pending in the post-direct-acting antivirals era.

Background and study aims: This study evaluated the longterm outcomes of mainly endoscopic hemostatic therapy for gastrointestinal variceal bleeding and of the transition of hemostatic therapy. Patients and methods: Among 1,163 patients treated for gastrointestinal varices between April 2006 and June 2020, a total of 125 patients who underwent emergency hemostatic therapy were enrolled. Survival rates and secondary evaluation points were analyzed. Additionally, patients were classified into two groups: the previous and latter term. Patients' background, therapeutic method, and treatment results were compared between the groups. Results: 94.4% had cirrhosis. The average Child-Pugh score was 8.90. Successful primary hemostasis rate was 98.4%, and 5.6% died within 2 weeks, all with a Child-Pugh score ≥9. The respective 1- and 5-year survival rates for Child-Pugh grade A/B were 81.3% and 55.4%, while those for Child-Pugh grade C were 58.1% and 17.8%. Child-Pugh grade C or hepatocellular carcinoma was significantly associated with poor prognosis. In total, 21.6% experienced variceal re-bleeding; 62.9% of these cases were triggered by continued alcohol consumption. There was no significant difference in survival between patients with and without variceal re-bleeding and in post-treatment survival between the previous and latter terms. In the latter term, the number of cases caused by continued alcohol consumption significantly increased. Conclusions: Multidisciplinary treatment and continuation of proper management after hemostatic therapy for variceal bleeding are crucial. Continued alcohol consumption leads to variceal bleeding and re-bleeding; its proper management, including alcohol abstinence, is one of the major challenges left in the post-directacting antivirals era.

A qualitative study of service engagement and unmet needs among unstably housed people who inject drugs in Massachusetts.

INTRODUCTION: People who inject drugs (PWID) are disproportionately affected by HIV in the United States, and HIV prevention and care services may be inaccessible to or underutilized by PWID. In 2018, the Massachusetts Department of Public Health (MDPH) and the Centers for Disease Control and Prevention (CDC) investigated an increase in HIV diagnoses primarily among unstably housed PWID in Lawrence and Lowell. METHODS: The response team interviewed 34 PWID in Lawrence and Lowell, with and without HIV, to inform effective response strategies. Qualitative interviews were recorded, transcribed, and coded. Interviews were transcribed verbatim and coded using a thematic analysis approach structured around pre-designated research questions related to service engagement (including harm reduction services, substance use disorder treatment, medical services, shelters, and other community services), unmet needs, and knowledge gaps regarding HIV prevention. RESULTS: Participants ranged in age from 20 to 54 years (median: 32); 21 of the 34 participants (62%) were male, and 21 were non-Hispanic white. Fifteen (44%) self-reported being HIV positive. All 34 participants had experienced homelessness in the past 12 months, and 29 (85%) had ever received services at syringe service programs (SSP). We identified five key themes: substance use as a barrier to accessing health and social services; experiences of trauma and mental illness as factors impacting substance use and utilization of services; unstable housing as a barrier to accessing services; negative perceptions of medication for opioid use disorder (MOUD); and the desire to be treated with dignity and respect by others. CONCLUSIONS: Findings highlight the need for well-resourced and integrated or linked service provision for PWID, which includes mental health services, housing, MOUD, harm reduction, and infectious disease prevention and care services. Co-locating and integrating low-barrier services at trusted community locations, such as SSPs, could increase service engagement and improve health outcomes for PWID. Further implementation science research may aid the development of effective strategies for services for PWID and build trusting relationships between service providers and PWID.

Partnering With State Health Departments to Address Injection-Related Infections During the Opioid Epidemic: Experience at a Safety Net Hospital.

Massachusetts is one of the epicenters of the opioid epidemic and has been severely impacted by injection-related viral and bacterial infections. A recent increase in newly diagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs in the state highlights the urgent need to address and bridge the overlapping epidemics of opioid use disorder (OUD) and injection-related infections. Building on an established relationship between the Massachusetts Department of Public Health and Boston Medical Center, the Infectious Diseases section has contributed to the development and implementation of a cohesive response involving ambulatory, inpatient, emergency department, and community-based services. We describe this comprehensive approach including the rapid delivery of antimicrobials for the prevention and treatment of HIV, sexually transmitted diseases, systemic infections such as endocarditis, bone and joint infections, as well as curative therapy for chronic hepatitis C virus in a manner that is accessible to patients on the addiction-recovery continuum. We also provide an overview of programs that provide access to medications for OUD, harm reduction services including overdose education, and distribution of naloxone. Finally, we outline lessons learned to inform initiatives in other settings.

Messenger RNA expression and localization of xenin in the gastrointestinal tract in sheep.

The present study aimed to determine the primary sequence of ovine xenin and clarify the mRNA expression and peptide localization of xenin in the gastrointestinal tract in sheep. The colocalization of xenin and glucose-dependent insulinotropic polypeptide was also compared in the antrum and duodenum. Analysis of the nucleotide sequence of ovine xenin revealed a high degree (97.9%) of sequence homology of the sequence between sheep and cattle, and the amino acids sequence determined for ovine xenin coincided (100%) with that of other mammalian species. Real-time quantitative PCR for ovine xenin did not show regional difference in the mRNA expression ratio of xenin. In contrast to the real-time quantitative PCR results, anti-xenin positive cells were abundantly localized in the abomasal antrum (P < 0.01) and at a lesser amount in the duodenum, but no antixenin positive cells were observed in the other regions. Anti-xenin single-positive cells were in a majority in the abomasal antrum, whereas anti-xenin single-positive cells, and anti-GIP single-positive cells, and double-positive cells were even colocalized in the duodenum. These results suggest that abomasal antrum is a major source of xenin in the ovine gastrointestinal tract.

Leveraging Health Department Capacities, Partnerships, and Health Insurance for Infectious Disease Response in Massachusetts, 2014-2018.

Policies facilitating integration of public health programs can improve the public health response, but the literature on approaches to integration across multiple system levels is limited. We describe the efforts of the Massachusetts Department of Public Health to integrate its HIV, viral hepatitis, sexually transmitted infection (STI), and tuberculosis response through policies that mandated contracted organizations to submit specimens for testing to the Massachusetts State Public Health Laboratory; co-test blood specimens for HIV, hepatitis C virus (HCV), and syphilis; integrate HIV, viral hepatitis, and STI disease surveillance and case management in a single data system; and implement an integrated infectious disease drug assistance program. From 2014 through 2018, the number of tests performed by the Massachusetts State Public Health Laboratory increased from 16 321 to 33 674 for HIV, from 11 054 to 33 670 for HCV, and from 19 169 to 30 830 for syphilis. Service contracts enabled rapid response to outbreaks of HIV, hepatitis A, and hepatitis B. Key challenges included lack of a billing infrastructure at the Massachusetts State Public Health Laboratory; the need to complete negotiations with insurers and to establish a retained revenue account to receive health insurance reimbursements for testing services; and time to train testing providers in phlebotomy for required testing. Investing in laboratory infrastructure; creating billing mechanisms to maximize health insurance reimbursement; proactively engaging providers, community members, and other stakeholders; and building capacity to transform practices are needed. Using multilevel policy approaches to integrate the public health response to HIV, STI, viral hepatitis, and tuberculosis is feasible and adaptable to other public health programs.

Opioid Use Fueling HIV Transmission in an Urban Setting: An Outbreak of HIV Infection Among People Who Inject Drugs-Massachusetts, 2015-2018.

Objectives. To describe and control an outbreak of HIV infection among people who inject drugs (PWID).Methods. The investigation included people diagnosed with HIV infection during 2015 to 2018 linked to 2 cities in northeastern Massachusetts epidemiologically or through molecular analysis. Field activities included qualitative interviews regarding service availability and HIV risk behaviors.Results. We identified 129 people meeting the case definition; 116 (90%) reported injection drug use. Molecular surveillance added 36 cases to the outbreak not otherwise linked. The 2 largest molecular groups contained 56 and 23 cases. Most interviewed PWID were homeless. Control measures, including enhanced field epidemiology, syringe services programming, and community outreach, resulted in a significant decline in new HIV diagnoses.Conclusions. We illustrate difficulties with identification and characterization of an outbreak of HIV infection among a population of PWID and the value of an intensive response.Public Health Implications. Responding to and preventing outbreaks requires ongoing surveillance, with timely detection of increases in HIV diagnoses, community partnerships, and coordinated services, all critical to achieving the goal of the national Ending the HIV Epidemic initiative.

A comparative analysis of treatment costs for home-based care and hospital-based care in enteral nutrition patients: A retrospective analysis of claims data.

OBJECTIVE: To explore the differences in mean treatment costs between home-based care and hospital-based care in enteral nutrition patients in Japan. METHODS: Using claims data from September 2013 to August 2014, we analyzed patients with recorded reimbursements for enteral nutrition at home or in a hospital. Treatment costs were compared using a panel data analysis with an individual fixed effects model that adjusted for the number of comorbidities and fiscal year. Costs were compared for all patients, as well as for specific diseases (pneumonia, sequelae of cerebrovascular disease, and dementia). RESULTS: The study sample comprised 7,783 patients with a cumulative total of 33,751 person-months of data. The mean patient age was 84.4 years for home-based care, 83.7 years for hospital-based care. The panel data analysis found that the cost estimates for hospital-based care were consistently higher than those for home-based care; the difference in adjusted treatment costs were $4,894 for all patients, $5,315 for pneumonia patients, $4,481 for sequelae of cerebrovascular disease patients, and $4,519 for dementia patients (all P < 0.001). Hospital-based care was still more expensive even when long-term care services were included in home-based care treatment cost estimates. CONCLUSION: Home-based care was consistently and substantially cheaper than hospital-based care in enteral nutrition patients in Japan.

Cost-effectiveness of implementing guidelines for the treatment of glucocorticoid-induced osteoporosis in Japan.

A model-based cost-effectiveness analysis was performed to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO). The treatment indication for GIO in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture. INTRODUCTION: The purpose of this study was to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO) from the perspective of the Japanese healthcare system. METHODS: A patient-level state transition model was developed to predict lifetime costs and quality-adjusted life years (QALYs) in postmenopausal Japanese women with osteopenia or osteoporosis using glucocorticoid (GC). An annual discount rate of 2% for both costs and QALYs was applied. The incremental cost-effectiveness ratio (ICER) of 5-year alendronate therapy compared with no therapy was estimated with different combinations of the risk factors such as starting age (45, 55, or 65), femoral neck BMD (% young adult mean (YAM) of 70%, 75%, or 80%), dose of GC (2.5, 5, or 10 mg per day), and the presence of previous fracture (yes or no). RESULTS: For 55-year-old women using GC with a BMD of 75% of YAM, the ICER ranged from $10,958 to $ 29,727 per QALY. Scenario analyses indicated that the lower age, the lower BMD, the higher dose of GC, and the presence of previous fracture associated with lower ICER. The best-case scenario was 45-year-old women with a BMD of 70% of YAM, GC dose of 10 mg per day, and previous fracture, and resulted in healthcare cost-savings. The worst-case scenario was 65-year-old women with a BMD of 80% of YAM, GC dose of 2.5 mg per day, and no previous fracture, and resulted in the ICER of $66,791 per QALY. Sensitivity analyses in the worst-case scenario showed that the annual discount rate for costs and health benefit had the strong influence on the estimated ICER. Although the ICER was influenced by other parameters such as disutility due to vertebral fracture, efficacy of alendronate, and so on, the ICERs remained more than $50,000 per QALY. CONCLUSIONS: The cost-effectiveness of preventive alendronate therapy for postmenopausal women with osteopenia or osteoporosis using GC is sensitive to age, BMD, GC dose, and the presence of previous fracture. Our analysis suggested that the treatment indication for postmenopausal women with osteopenia or osteoporosis using GC in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture.

Using HIV Surveillance Laboratory Data to Identify Out-of-Care Patients.

HIV-associated laboratory tests reported to public health surveillance have been used as a proxy measure of care engagement of HIV+ individuals. As part of a Health Resources and Services Administration (HRSA) Special Projects of National Significance (SPNS) Initiative, the Massachusetts Department of Public Health (MDPH) worked with three pilot clinical facilities to identify HIV+ patients whose last HIV laboratory test occurred at the participating facility but who then appeared to be out of care, defined as an absence of HIV laboratory test results reported to MDPH for at least 6 months. The clinical facilities then reviewed medical records to determine whether these patients were actually not in care, or if there was another reason that they did not have a laboratory test performed, and provided feedback to MDPH on each of the presumed out-of-care patients. In the first year of the pilot project, 37% of patients who appeared to be out of care based on laboratory data were confirmed to be out of care after review of clinical health records. Of those patients who were confirmed to be out of care, 55% had a subsequent laboratory test within 3 months, and 72% had a laboratory test within 6 months, indicating that they had re-engaged with a care provider. MDPH found that it was essential to have clinical staff confirm the care status of patients who were presumed to be out of care based on surveillance data.

Comparative Study on Variation of Quality of Life of Patients of Preemptive Kidney Transplantation and Nonpreemptive Kidney Transplantation.

BACKGROUND: There have been few studies that have reported the influence of kidney transplantation on the quality of life (QOL) of patients of preemptive kidney transplantation (PKT) and nonpreemptive kidney transplantation (NPKT). MATERIAL AND METHODS: Fifty patients of PKT and 49 patients of NPKT were employed as study subjects. A questionnaire survey using Short Form 36 and Kidney Disease QOL on patients' physical and psychological QOL was performed for these patients prior to transplantation and 1 month, 3 months, and 1 year after transplantation. RESULTS: The analysis of results has revealed that transplantation clearly has improved the physical and psychological QOL in patients with end-stage renal disease. For the items regarding physical burdens incurred by the transplantation, patient QOL deteriorated on a single occasion 1 month after the transplantation while it was improved 1 year after the transplantation. For the items regarding psychological burdens, the mental condition of the patients was improved overall without deterioration over time. Concerning the "Effect of Kidney Disease" and "Burden of Kidney Disease," QOL was significantly better in PKT than NPKT at baseline before transplantation, although the significant difference gradually decreased 1 month and 3 months after the transplantation and disappeared after 1 year. CONCLUSION: Transplantation certainly improved the QOL of patients with end-stage renal disease. Before transplantation, PKT was clearly better than NPKT in the QOL items associated with "Burden of Kidney Disease." This indicated that patients of PKT have improved QOL compared to patients of NPKT, and that the overall awareness of kidney disease is decreased. A postoperative gap in mental and bodies was observed especially in PKT, however, could be overcome by nursing interventions.

Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes.

OBJECTIVE: Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated, and the role of high ENO1 expression in keratinocytes was characterized. METHODS: ENO1 expression and morphological characteristics were examined in SC from the cheeks of 24 patients with AD. Additionally, the localization of ENO1 in the excised human epidermis was observed. Moreover, to analyse the role of ENO1 in cellular barrier function, tight junction proteins (TJs) and transepithelial electrical resistance (TEER) in keratinocytes with ENO1 overexpression were evaluated. Furthermore, the localization of ENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA). RESULTS: ENO1 expression was substantially correlated with the rate of nucleated corneocytes in AD. In addition, ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy human SC. ENO1 overexpression in human epidermal keratinocytes reduced the expression of TJs (claudin-4, E-cadherin, tricellulin, and occludin) and TEER, and treatment with anti-ENO1 IgG reversed these effects. ENO1 colocalized with plasminogen in keratinocytes. Treatment with TXA rescued the ENO1-induced reductions in TJ and TEER expression. CONCLUSION: We found a substantial correlation between ENO1 expression and the rate of nucleated corneocytes in AD and decreased ENO1 expression with nuclear disappearance. These results suggest that high ENO1 expression in the SC of AD is caused by deficient keratinization, which is an AD characteristic. Moreover, ENO1 overexpression in keratinocytes promoted dysfunction of TJ dynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose that ENO1 is a useful indicator of parakeratosis and might have a potential role in cellular TJ barrier function in the epidermis.

Factors Associated with Pre-exposure Prophylaxis in a Highly Insured Population of Urban Men Who Have Sex with Men, 2014.

In the United States, an estimated 25% of men who have sex with men (MSM) have indications for receiving pre-exposure prophylaxis to prevent HIV infection (PrEP), but <4% reported PrEP use in the past 12 months. We evaluate factors associated with having heard of, willingness to use, and use of PrEP in a venue-based, time-spaced sample of 316 urban, highly insured Boston MSM in the 2014 NHBS. We found that 53.7% of respondents reported receiving usual medical care from a doctor's office or health maintenance organization, 57.6% had an indication for PrEP, 66.6% had heard of PrEP, 53.6% reported willingness to use PrEP, and 5.8% reported use of PrEP in the past 12 months. In multivariable analyses, an indication for PrEP was statistically associated with having heard of, willingness to use and use of PrEP in the past 12 months. Findings guide statewide efforts to evaluate and promote PrEP.

Sequence analysis of ABO and its homologues is valid for species identification.

BACKGROUND: ABO and its paralogues, such as A3GALT2 and GGTA1, encoding α1,3-Gal(NAc) transferases, belong to the glycosyltransferase 6 (GT6) gene family. We have developed an alternative method for the identification of species based on sequence variations within the GT6 gene family, which is applicable to degraded DNA. METHODS/MATERIALS: DNA samples prepared from control mammalian species, together with an unknown sample, were polymerase chain reaction (PCR)-amplified using one universal primer pair targeting the sequences in the last coding exons of the GT6 gene family, yielding 141-bp products derived from those multiple loci. After cloning, sequence determination and Basic Local Alignment Search Tool analysis, phylogenetic trees were constructed. RESULTS: Comparison of the sequences obtained with those references showed good concordance with each of the starting species of mammals. This system was able to identify 'mouse' or 'rodent' as the origin of the unknown sample. CONCLUSION: For the identification of species, genotyping of ABO and its homologues would be applicable for the analysis of degraded DNA samples. Although the method employed in this study is likely valid for mammals, it would not be suitable for birds, fish and reptiles. It may be possible to improve the present method for use with other species by employing an alternative universal primer set.

Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis.

BACKGROUND: There have been no reports evaluating progression-free survival (PFS) as a surrogate endpoint in resectable esophageal cancer. This study was conducted to evaluate the trial level correlations between PFS and overall survival (OS) in resectable esophageal cancer with preoperative therapy and to explore the potential benefit of PFS as a surrogate endpoint for OS. METHODS: A systematic literature search of randomized trials with preoperative chemotherapy or preoperative chemoradiotherapy for esophageal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane Library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R2) within PFS and OS. The primary analysis included trials in which the HR for both PFS and OS was reported. The sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. RESULTS: Of 614 articles, 10 trials were selected for the primary analysis and 15 for the sensitivity analysis. The primary analysis did not show a correlation between treatment effects on PFS and OS (R2 0.283, 95% CI [0.00-0.90]). The sensitivity analysis did not show an association between PFS and OS (R2 0.084, 95% CI [0.00-0.70]). CONCLUSION: Although the number of randomized controlled trials evaluating preoperative therapy for esophageal cancer is limited at the moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS.

Sustained Reduction in HIV Diagnoses in Massachusetts, 2000-2014.

OBJECTIVES: To describe secular trends in reported HIV diagnoses in Massachusetts concurrent with treatment access expansion. METHODS: We characterized cases of HIV infection reported to the Massachusetts HIV/AIDS Surveillance Program between 2000 and 2014 by sex, age, race/ethnicity, and exposure mode. We used Poisson regression to test the statistical significance of trends in diagnoses. RESULTS: Between 2000 and 2014, annual new HIV infections diagnosed in Massachusetts decreased by 47% (P < .001 for trend). We observed significant reductions in diagnoses among women (58% when comparing 2000 with 2014), men (42%), Whites (54%), Blacks (51%), and Hispanics (35%; P < .001 for trend). New diagnoses decreased significantly among men who have sex with men (19%), persons who inject drugs (91%), and heterosexuals (86%; P < .001 for trend). We saw statistically significant downward trends among all men by race/ethnicity, but the trend among Black men who have sex with men was nonsignificant. CONCLUSIONS: Sustained reduction in new HIV diagnoses was concurrent with Massachusetts's Medicaid expansion, state health care reform, and public health strategies to improve care access. A contributory effect of expanded HIV treatment and population-level viral suppression is hypothesized for future research.

Susceptibility of isogeneic ginbuna Carassius auratus langsdorfii Temminck et Schlegel to cyprinid herpesvirus-2 (CyHV-2) as a model species.

Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus-2 (CyHV-2), has affected the commercial production of the goldfish Carassius auratus and gibelio carp Carassius auratus gibelio. High water temperature treatments are reported to reduce the mortality rate of infected goldfish and elicit immunity in the survivors. To define the mechanism by which this intervention induces resistance, clonal ginbuna Carassius auratus langsdorfii, which is closely related to both species and has been used in fish immunology, may represent a promising model species. In this study, we investigated the susceptibility of clonal ginbuna strains to CyHV-2 and the effect of high water temperature treatment on infected ginbuna and goldfish. Experimental intraperitoneal infection with CyHV-2 at 25 °C caused 100% mortality in ginbuna strains, which was accompanied by histopathological changes typical of HVHN. Both infected ginbuna S3n strain and goldfish, exposed to high temperature for 6 days [shifting from 25 °C (permissive) to 34 °C (non-permissive)], showed reduced mortalities after the 1st inoculation, and subsequent 2nd virus challenge to 0%, indicating induction of immunity. It was concluded that ginbuna showed a similar susceptibility and disease development in CyHV-2 infection compared to goldfish, suggesting that ginbuna can be a useful fish model for the study of CyHV-2 infection and immunity.

Inter-institutional heterogeneity in outcomes of chemotherapy for metastatic gastric cancer: correlative study in the JCOG9912 phase III trial.

BACKGROUND: The standard chemotherapy regimen for gastric cancer has been established by several phase III trials. However, few studies have evaluated inter-institutional heterogeneity in randomised trials; such research may assure the generalisability of the results and also the reliability of the study group itself. PATIENTS AND METHODS: The Japan Clinical Oncology Group (JCOG)9912 phase III trial compared irinotecan plus cisplatin and S-1 alone with fluorouracil alone for metastatic gastric cancer, and finally demonstrated the non-inferiority of S-1 alone with respect to overall survival (OS). Mixed effects models were used to evaluate outcomes of 658 patients from 22 hospitals. After adjustment for nine background factors, the heterogeneity in OS, progression-free survival (PFS), and incidences of grade 3-4 adverse events among hospitals was estimated. We also estimated the correlation between outcomes and either hospital volume or medical oncology clinical experience. RESULTS: A large degree of heterogeneity in median OS was observed for fluorouracil alone (range, 8.3-13.3 months), while the difference in median PFS between hospitals was small (range, 2.4-3.4 months). Although some heterogeneity in the treatment effect of irinotecan plus cisplatin or S-1 alone was observed in OS and PFS, the HRs did not exceed 1.00 in any hospital for either regimen. There was minimal heterogeneity in the incidences of grade 3-4 adverse events. There was a trend towards correlation between greater medical oncology clinical experience and both better OS after fluorouracil alone and a lower HR for OS after irinotecan plus cisplatin, but it was not statistically significant. CONCLUSIONS: Large inter-institutional heterogeneity was observed in OS, but not in PFS, after the standard regimen, but there was little heterogeneity in the treatment effects of irinotecan plus cisplatin or S-1 alone, indicating that the final results of the JCOG9912 trial can be generalised to the target population. TRIAL REGISTRATION NUMBER: NCT00142350.