RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm

Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 minute injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 minute unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury blood flow was decreased in the inner cortex of wild type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 hours after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMC) to secrete the macrophage chemoattractant, RANTES; a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared to transgenic and non-transgenic mice after the 10 minute injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation

Getting a grippe on severity: a retrospective comparison of influenza-related hospitalizations and deaths captured in reportable disease and administrative data sources in Ontario, Canada

Abstract Background Since 2009, in Ontario, reportable disease surveillance data has been used for timely in-season estimates of influenza severity (i.e., hospitalizations and deaths). Due to changes in reporting requirements influenza reporting no longer captures these indicators of severity, necessitating exploration of other potential sources of data. The purpose of this study was to complete a retrospective analysis to assess the comparability of influenza-related hospitalizations and deaths captured in the Ontario reportable disease information system to those captured in Ontario’s hospital-based discharge database. Methods Hospitalizations and deaths of laboratory-confirmed influenza cases reported during the 2010–11 to 2013–14 influenza seasons were analyzed. Information on hospitalizations and deaths for laboratory-confirmed influenza cases were obtained from two databases; the integrated Public Health Information System, which is the provincial reportable disease database, and the Discharge Abstract Database, which contains information on all in-patient hospital visits using the International Classification of Diseases, 10th Revision, Canada (ICD-10-CA) coding standards. Analyses were completed using the ICD-10 J09 and J10 diagnosis codes as an indicator for laboratory-confirmed influenza, and a secondary analysis included the physician-diagnosed influenza J11 diagnosis code. Results For each season, reported hospitalizations for laboratory-confirmed influenza cases in the reportable disease data were higher compared to hospitalizations with J09 and J10 diagnoses codes, but lower when J11 codes were included. The number of deaths was higher in the reportable disease data, whether or not J11 codes were included. For all four seasons, the weekly trends in the number of hospitalizations and deaths were similar for the reportable disease and hospital data (with and without J11), with seasonal peaks occurring during the same week or within 1 week of each other. Conclusion In our retrospective analyses we found that hospital data provided a reliable estimate of the trends of influenza-related hospitalizations and deaths compared to the reportable disease data for the 2010–11 to 2013–14 influenza seasons in Ontario, but may under-estimate the total seasonal number of deaths. Hospital data could be used for retrospective end-of-season assessments of severity, but due to delays in data availability are unlikely to be timely estimates of severity during in-season surveillance

Impact of the 2012 extreme drought conditions on private well owners in the United States, a qualitative analysis

Abstract Background Extreme hot and dry weather during summer 2012 resulted in some of the most devastating drought conditions in the last half-century in the United States (U.S.). While public drinking water systems have contingency plans and access to alternative resources to maintain supply for their customers during drought, little is known about the impacts of drought on private well owners, who are responsible for maintaining their own water supply. The purpose of this investigation was to explore the public health impacts of the 2012 drought on private well owners’ water quality and quantity, identify their needs for planning and preparing for drought, and to explore their knowledge, attitudes, and well maintenance behaviors during drought. Methods In the spring of 2013, we conducted six focus group discussions with private well owners in Arkansas, Indiana, and Oklahoma. Results There were a total of 41 participants, two-thirds of whom were men aged 55 years or older. While participants agreed that 2012 was the worst drought in memory, few experienced direct impacts on their water quantity or quality. However, all groups had heard of areas or individuals whose wells had run dry. Participants conserved water by reducing their indoor and outdoor consumption, but they had few suggestions on additional ways to conserve, and they raised concerns about limiting water use too much. Participants wanted information on how to test their well and any water quality issues in their area. Conclusions This investigation identified information needs regarding drought preparedness and well management for well owners

Beyond flu: Trends in respiratory infection outbreaks in Ontario healthcare settings from 2007 to 2017, and implications for non-influenza outbreak management

Background: Outbreaks cause significant morbidity and mortality in healthcare settings. Current testing methods can identify specific viral respiratory pathogens, yet the approach to outbreak management remains general. Objectives: Our aim was to examine pathogen-specific trends in respiratory outbreaks, including how attack rates, case fatality rates and outbreak duration differ by pathogen between hospitals and long-term care (LTC) and retirement homes (RH) in Ontario. Methods: Confirmed respiratory outbreaks in Ontario hospitals and LTC/RH reported between September 1, 2007, and August 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Median attack rates and outbreak duration and overall case fatality rates of pathogen-specific outbreaks were compared in both settings. Results: Over the 10-year surveillance period, 9,870 confirmed respiratory outbreaks were reported in Ontario hospitals and LTC/RH. Influenza was responsible for most outbreaks (32% in LTC/RH, 51% in hospitals), but these outbreaks were shorter and had lower attack rates than most non-influenza outbreaks in either setting. Human metapneumovirus, while uncommon (<4% of outbreaks) had high case fatality rates in both settings. Conclusion: Attack rates and case fatality rates varied by pathogen, as did outbreak duration. Development of specific outbreak management guidance that takes into account pathogen and healthcare setting may be useful to limit the burden of respiratory outbreaks

Parental Attitudes and Perceptions of Support after Brief Clinician Intervention Predict Intentions to Accept the Adjuvanted Seasonal Influenza Vaccination: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)–I

Adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against seasonal influenza in children compared with nonadjuvanted trivalent influenza vaccine (TIV). This prospective cohort study assessed parental attitudes, beliefs, and intentions to vaccinate their infants aged 6–23 months with aTIV. Parents were surveyed before and after routine healthy baby visits, and post clinician interaction results were analyzed using multivariable logistic regression. Physicians at 15 community practice clinics and nurses at 3 public health clinics participated; 207 parents were surveyed. After clinician consultation, most parents considered immunization with aTIV to be safe (72.9%), effective (69.6%), and important (69.0%); most perceived support for vaccination from significant others (62.8%) and clinicians (81.6%); and 66.6% intended to vaccinate their infant with aTIV. Parental attitudes toward vaccinating their infant with aTIV were strongly correlated with perceptions of vaccine safety, efficacy, and importance, and these represented the strongest influence on intentions to vaccinate (odds ratio (OR) 79.25; 95% confidence interval (CI) 6.05–1037.50). Parental intentions were further influenced by perceived strength of clinician recommendation (OR 4.55, 95% CI 1.38–15.06) and social support for vaccination (OR 3.46, 95% CI 0.50–24.13). These findings may inform clinician approaches to parental education to ensure optimal seasonal pediatric influenza vaccination

Validation of a clinical prediction rule to predict asymptomatic chlamydia and gonorrhea infections among internet-based testers

Background Clinical prediction rules (CPRs) can be used in sexually transmitted infection (STI) testing environments to prioritize individuals at the highest risk of infection and optimize resource allocation. We previously derived a CPR to predict asymptomatic chlamydia and/or gonorrhea (CT/NG) infection among women and heterosexual men at in-person STI clinics based on 5 predictors. Population differences between clinic-based and Internet-based testers may limit the tool's application across settings. The primary objective of this study was to assess the validity, sensitivity, and overall performance of this CPR within an Internet-based testing environment (GetCheckedOnline.com). Methods We analyzed GetCheckedOnline online risk assessment and laboratory data from October 2015 to June 2019. We compared the STI clinic population used for CPR derivation (data previously published) and the GetCheckedOnline validation population using χ2 tests. Calibration and discrimination were assessed using the Hosmer-Lemeshow goodness-of-fit test and the area under the receiver operating curve, respectively. Sensitivity and the fraction of total screening tests offered were quantified for CPR-predicted risk scores. Results Asymptomatic CT/NG infection prevalence in the GetCheckedOnline population (n = 5478) was higher than in the STI clinic population (n = 10,437; 2.4% vs. 1.8%, P = 0.007). When applied to GetCheckedOnline, the CPR had reasonable calibration (Hosmer-Lemeshow, P = 0.90) and discrimination (area under the receiver operating characteristic, 0.64). By screening only individuals with total risk scores ≥4, we would detect 97% of infections and reduce screening by 14%. Conclusions The application of an existing CPR to detect asymptomatic CT/NG infection is valid within an Internet-based STI testing environment. Clinical prediction rules applied online can reduce unnecessary STI testing and optimize resource allocation within publicly funded health systems

Clinicians Are Not Able to Infer Parental Intentions to Vaccinate Infants with a Seasonal Influenza Vaccine, and Perhaps They Should Not Try: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)–IV

This prospective cohort survey evaluated the concordance of clinicians’ perceptions of parental intentions and parents’ actual intentions to vaccinate their infants against influenza. During a routine healthy baby visit, clinicians provided parents with information about influenza, children’s vulnerability to influenza, and nonadjuvanted and adjuvanted trivalent influenza vaccines (TIV and aTIV, respectively). Before and after the clinician–parent interaction, parents were surveyed about their attitudes, their perceptions of support from significant others, and the intention to vaccinate their infant with aTIV. Clinicians were asked about their perception of parents’ intentions to choose aTIV for their children. These assessments included 24 clinicians at 15 community practices and nine public health clinics, and 207 parents. The correlation coefficients of the clinicians’ assessment of parents’ intention to vaccinate were 0.483 (p p p = 0.036) if the cost was $50, accounting for 23%, 7%, and 2% of the variance in parental intentions, respectively. The clinicians were poor at predicting parental intentions to immunize, particularly when cost was involved. Information on vaccine options and influenza infection should be provided for every eligible patient to allow parents to determine if the vaccine is appropriate for their child