The Impact of Sociodemographic Factors, Comorbidities, and Physiologic Responses on 30-Day Mortality in Coronavirus Disease 2019 (COVID-19) Patients in Metropolitan Detroit.

BACKGROUND: The relationship of health disparities and comorbidities in coronavirus disease 2019 (COVID-19)-related outcomes are an ongoing area of interest. This report assesses risk factors associated with mortality in patients presenting with COVID-19 infection and healthcare disparities. METHODS: We conducted a retrospective cohort study of consecutive patients presenting to emergency departments within an integrated health system who tested positive for COVID-19 between 7 March and 30 April 2020 in metropolitan Detroit. The primary outcomes were hospitalization and 30-day mortality. RESULTS: A total of 3633 patients with a mean age of 58 years were included. The majority were female and Black non-Hispanic. Hospitalization was required for 64% of patients, 56% of whom were Black. Hospitalized patients were older, more likely to reside in a low-income area, and had a higher burden of comorbidities. By 30 days, 433 (18.7%) hospitalized patients died. In adjusted analyses, the presence of comorbidities, an age >60 years, and more severe physiological disturbance were associated with 30-day mortality. Residence in low-income areas (odds ratio [OR], 1.02; 95% confidence interval [CI], .76-1.36) and public insurance (OR, 1.24; 95% CI, .76-2.01) were not independently associated with a higher risk of mortality. Black female patients had a lower adjusted risk of mortality (OR, 0.46; 95% CI, .27-.78). CONCLUSIONS: In this large cohort of COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Disparities in income or source of health insurance were not associated with outcomes. Black women had a lower risk of dying.

Improving Primary Care Delivery for Patients Receiving Maintenance Hemodialysis.

The beneficial impact of primary care, focused on all aspects of a patient's health (rather than a disease-specific focus) is well established. Recognized benefits include greater receipt of preventive care and counseling, lower use of emergency care and hospitalization for ambulatory care-sensitive conditions, and decreased early mortality. Although the importance of primary care and care coordination at the primary care/specialty interface is well recognized, the role of primary care within traditional and emerging care models for patients receiving in-center maintenance hemodialysis remains ill-defined. In this perspective article, we will describe: (1) the role of primary care for patients receiving maintenance hemodialysis and the current evidence regarding the receipt of primary care among these patients; (2) the key challenges to delivery of primary care in these complex cases, including suboptimal care coordination between nephrology and primary care providers, the intensity of dialysis care, and the limited capacity of nephrologists and primary care providers to meet the broad health needs of hemodialysis patients; (3) potential strategies for improving the delivery of primary care for patients receiving hemodialysis; and (4) future research requirements to improve primary care delivery for this high-risk population.

Burnout and Emotional Well-Being among Nephrology Fellows: A National Online Survey.

BACKGROUND: Physician burnout and emotional distress are associated with work dissatisfaction and provision of suboptimal patient care. Little is known about burnout among nephrology fellows. METHODS: Validated items on burnout, depressive symptoms, and well being were included in the American Society of Nephrology annual survey emailed to US nephrology fellows in May to June 2018. Burnout was defined as an affirmative response to two single-item questions of experiencing emotional exhaustion or depersonalization. RESULTS: Responses from 347 of 808 eligible first- and second-year adult nephrology fellows were examined (response rate=42.9%). Most fellows were aged 30-34 years (56.8%), male (62.0%), married or partnered (72.6%), international medical graduates (62.5%), and pursuing a clinical nephrology fellowship (87.0%). Emotional exhaustion and depersonalization were reported by 28.0% and 14.4% of the fellows, respectively, with an overall burnout prevalence of 30.0%. Most fellows indicated having strong program leadership (75.2%), positive work-life balance (69.2%), presence of social support (89.3%), and career satisfaction (73.2%); 44.7% reported a disruptive work environment and 35.4% reported depressive symptoms. Multivariable logistic regression revealed a statistically significant association between female gender (odds ratio [OR], 1.90; 95% confidence interval [95% CI], 1.09 to 3.32), poor work-life balance (OR, 3.97; 95% CI, 2.22 to 7.07), or a disruptive work environment (OR, 2.63; 95% CI, 1.48 to 4.66) and burnout. CONCLUSIONS: About one third of US nephrology fellows surveyed reported experiencing burnout and depressive symptoms. Further exploration of burnout-especially that reported by female physicians, as well as burnout associated with poor work-life balance or a disruptive work environment-is warranted to develop targeted efforts that may enhance the educational experience and emotional well being of nephrology fellows.

Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection.

Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.

Primary Care Physicians' Perceived Barriers to Nephrology Referral and Co-management of Patients with CKD: a Qualitative Study.

BACKGROUND: Effective co-management of patients with chronic kidney disease (CKD) between primary care physicians (PCPs) and nephrologists is increasingly recognized as a key strategy to ensure the delivery of efficient and high-quality CKD care. However, the co-management of patients with CKD remains suboptimal. OBJECTIVE: We aimed to identify PCPs' perceptions of key barriers and facilitators to effective co-management of patients with CKD at the PCP-nephrology interface. STUDY DESIGN: Qualitative study SETTING AND PARTICIPANTS: Community-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC; and San Francisco, CA APPROACH: We conducted four focus groups of PCPs. Two members of the research team coded transcribed audio-recorded interviews and identified major themes. KEY RESULTS: Most of the 32 PCPs (59% internists and 41% family physicians) had been in practice for > 10 years (97%), spent ≥ 80% of their time in clinical care (94%), and practiced in private (69%) or multispecialty group practice (16%) settings. PCPs most commonly identified barriers to effective co-management of patients with CKD focused on difficulty developing working partnerships with nephrologists, including (1) lack of timely adequate information exchange (e.g., consult note not received or CKD care plan unclear); (2) unclear roles and responsibilities between PCPs and nephrologists; and (3) limited access to nephrologists (e.g., unable to obtain timely consultations or easily contact nephrologists with concerns). PCPs expressed a desire for "better communication tools" (e.g., shared electronic medical record) and clear CKD care plans to facilitate improved PCP-nephrology collaboration. CONCLUSIONS: Interventions facilitating timely adequate information exchange, clear delineation of roles and responsibilities between PCPs and nephrologists, and greater access to specialist advice may improve the co-management of patients with CKD.

Alterations in circulating concentrations of IL-17, IL-31 and total IgE in dogs with atopic dermatitis.

BACKGROUND: The pathogenesis of canine atopic dermatitis (AD) is complex. Dysregulation of the cutaneous immune system is considered an important regulator of the allergic response. Exploration of association of interleukin-17 (IL-17), IL-31, IgE and leukogram attributes with canine AD could provide novel insights into its immunopathology. HYPOTHESIS/OBJECTIVES: To investigate possible associations of IL-17, IL-3, IgE and leukogram attributes of canine AD. ANIMALS: 17 dogs diagnosed with AD and six healthy dogs. METHODS AND MATERIALS: Circulating concentrations of IL-17, IL-31 and total IgE from sera samples were determined using commercial canine-specific quantitative immunoassay kits. Complete blood cell counts were analysed by an automated haematology analyser. Statistical differences between the two groups were determined using an unpaired t-test. The degree of relationship between the IL-17, IL-31, IgE, total leukocyte count (TLC) values and clinical signs scores (Canine Atopic Dermatitis Lesion Index and pruritus Visual Analog Scale pVAS) was determined by Pearson's r correlation statistic. RESULTS: Dogs with AD had significantly (P < 0.0001) higher circulating concentrations of IL-17, IL-31 and total IgE compared with healthy dogs. Dogs with AD also had significantly higher TLC (P < 0.0002), absolute neutrophils (P < 0.0001) and absolute eosinophils (P < 0.0001) counts, and percentage of neutrophils (P < 0.03) and eosinophils (P < 0.0001) compared with healthy controls. A significant positive correlation (r2  = 0.396; P < 0.007) between the pVAS and IL-31 was observed in dogs with AD. CONCLUSIONS AND CLINICAL IMPORTANCE: Marked elevation in circulating IL-17, IL-31 and total IgE along with the abnormalities in leukogram may be associated with canine AD and could be possible targets in the therapeutic management of canine AD.

Indicators of Cognitive Impairment From a Medical Record Review: Correlations With Early (30-d) Readmissions Among Hospitalized Patients in a Nephrology Unit.

BACKGROUND: Patients with end-stage renal disease have the highest 30-day hospital readmission rates of any medical condition. Previous research suggests that cognitive impairment contributes to readmission. It is important to identify patients at risk for early readmission, and this might be accomplished efficiently using medical record data. METHOD: We reviewed the medical records of 100 patients with kidney disease (57 women, mean age = 61.2) who were hospitalized in the nephrology unit at an urban U.S. hospital. For each patient, we recorded easily available indicators of cognitive impairment along with other potential risk factors, and also recorded the number of 30-day readmissions over the past year. RESULTS: Half of the sample (n = 50) had at least 1 readmission (median = 0.5, range: 0-20). A lifetime history of delirium, which is a known marker of chronic cognitive impairment, was significantly related to readmissions, and several other impairment indicators (positive head imaging, history of seizures, and history of hypoxia) showed similar trends. A "cognitive impairment index" (positive for one or more variables possibly reflecting impaired central nervous system) was significantly related to the presence of a 30-day readmission, beyond the effects of a number of behavioral and medical covariates. CONCLUSIONS: Easily accessible cognitive impairment markers, especially a known history of delirium, may be useful to identify patients in nephrology units who are at increased risk for early hospital readmissions. Interventions can be targeted to these patients with the goal of reducing the likelihood of readmissions and improving health care outcomes.

Underestimated and unreported prolonged QTc by automated ECG analysis in patients on methadone: can we rely on computer reading?

BACKGROUND: Recognition of prolonged corrected QT (QTc) interval is of particular importance, especially when using medications known to prolong QTc interval. Methadone can prolong the QTc interval and has the potential to induce torsades de pointes. OBJECTIVE: The objective of this study is to investigate the accuracy of computerized ECG analysis in correctly identifying and reporting QTc interval in patients on methadone. METHODS: We conducted a retrospective review of ECGs in the Muse electronic database of patients on methadone who are above 18 years old between January 2012 and December 2013 at an urban community hospital. ECGs were analyzed by the Marquette 12SL ECG Analysis Program (GE'Healthcare) reviewed by a cardiologist. RESULTS: A total of 826 ECGs of patients on methadone were examined manually for the QTc interval, of which 625 (75.7%) had QTc less than 470 ms, 149 (18%) had QTc between 470-499 ms and 52 (6.3%) had QTc more than 499 ms. QTc between 470-499 ms was underestimated by machine in 19 (12.8%) ECGs and QTc more than 499 ms was underestimated in 10 (19.6%) when compared to manually calculated QTc. QTc prolongation was underreported in 63 ECGs (48.5%) of those whose QTc between 470-499 ms and in 1 ECG (2.4%) of those whose QTc was more than 499 ms. CONCLUSIONS: QTc can be underestimated or unreported by the computer analysis. Physicians not only should calculate QTc manually but also examine the actual QTc value displayed on the report before concluding that this parameter is normal, especially in patients who are at risk of QTc prolongation.

Comparative cost-effectiveness of two-tiered testing strategies for serodiagnosis of lyme disease with noncutaneous manifestations.

The mainstay of laboratory diagnosis for Lyme disease is two-tiered serological testing, in which a reactive first-tier enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay is supplemented by separate IgM and IgG immunoblots. Recent data suggest that the C6 ELISA can be substituted for immunoblots without a reduction in either sensitivity or specificity. In this study, the costs of 4 different two-tiered testing strategies for Lyme disease were compared using the median charges for these tests at 6 commercial diagnostic laboratories in 2012. The study found that a whole-cell sonicate ELISA followed by the C6 ELISA was the most cost-effective two-tiered testing strategy for Lyme disease with acute-phase serum samples. We conclude that the C6 ELISA can substitute for immunoblots in the two-tiered testing protocol for Lyme disease without a loss of sensitivity or specificity and is less expensive.

Perceptions and use of the national kidney foundation KDOQI guidelines: a survey of U.S. renal healthcare providers.

BACKGROUND: The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) developed guidelines to care for patients with chronic kidney disease (CKD). While these are disseminated through the NKF's website and publications, the guidelines' usage remains suboptimal. The KDOQI Educational Committee was formed to identify barriers to guideline implementation, determine provider and patient educational needs and develop tools to improve care of patients with CKD. METHODS: An online survey was conducted from May to September 2010 to evaluate renal providers' familiarity, current use of and attitudes toward the guidelines and tools to implement the guidelines. RESULTS: Most responders reported using the guidelines often and felt that they could be easily implemented into clinical practice; however, approximately one-half identified at least one barrier. Physicians and physician extenders most commonly cited the lack of evidence supporting KDOQI guidelines while allied health professionals most commonly listed patient non-adherence, unrealistic guideline goals and provider time-constraints. Providers thought that the guidelines included too much detail and identified the lack of a quick resource as a barrier to clinical implementation. Most were unaware of the Clinical Action Plans. CONCLUSIONS: Perceived barriers differed between renal clinicians and allied health professionals; educational and implementation tools tailored for different providers are needed.

Concordance between clinical outcomes in the Systolic Blood Pressure Intervention Trial and in the electronic health record.

BACKGROUND: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied. METHODS: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data. RESULTS: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment. CONCLUSIONS: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Management of Hospitalized Kidney Transplant Recipients for Hospitalists and Internists.

The number of kidney transplant recipients has grown incrementally over the years. These patients have a high comorbidity index and require special attention to immunosuppression management. In addition, this population has an increased risk for cardiovascular events, electrolyte abnormalities, allograft dysfunction, and infectious complications. It is vital for hospitalists and internists to understand the risks and nuances in the care of this increasingly prevalent, but also high-risk, population.

Burnout Among Nephrologists in the United States: A Survey Study.

Rationale & Objective: Burnout decreases job satisfaction and leads to poor patient outcomes but remains underinvestigated in nephrology. We explored the prevalence and determinants of burnout among a sample of nephrologists. Study Design: Cross-sectional. Setting & Participants: The nephrologists were approached via the American Medical Association Physicians Masterfile, National Kidney Foundation listserv, email, and social media between April and August 2019. The predictors were demographics and practice characteristics. The outcome was burnout, defined as responding "once a week" or more on either 1 of the 2 validated measures of emotional exhaustion and depersonalization or both. Analytical Approach: Participant characteristics were tabulated. Responses were compared using χ2 tests. Multivariable logistic regression was used to estimate the odds ratios (ORs) of burnout for risk factors. Free text responses were thematically analyzed. Results: About half of 457 respondents were 40-59 years old (n=225; 49.2%), and the respondents were more predominantly men (n=296; 64.8%), US medical graduates (n=285; 62.4%), and in academic practice (n=286; 62.6%). Overall, 106 (23.2%) reported burnout. The most commonly reported primary drivers of burnout were the number of hours worked (n=27; 25.5%) and electronic health record requirements (n=26; 24.5%). Caring for ≤25 versus 26-75 patients per week (OR, 0.34; 95% confidence interval [95% CI], 0.15-0.77), practicing in academic versus nonacademic settings (OR, 0.33; 95% CI, 0.21-0.54), and spending time on other responsibilities versus patient care (OR, 0.32; 95% CI, 0.17-0.61) were each independently associated with nearly 70% lower odds of burnout after adjusting for age, sex, race, and international medical graduate status. The free text responses emphasized disinterested health care systems and dissatisfaction with remuneration as the drivers of burnout. Limitations: Inability to precisely capture response rate. Conclusions: Nearly one-quarter of the nephrologists in our sample reported burnout. Future studies should qualitatively investigate how the care setting, time spent on electronic medical records, and hours of clinical care drive burnout and explore other system-level drivers of burnout in nephrology.

Differences in ejection fraction as inclusion criterion in randomized controlled trials among patients with heart failure with reduced ejection fraction: a systematic review.

INTRODUCTION: Heart failure (HF) with reduced ejection fraction (HFrEF) has been defined by varying ejection fraction (EF) criteria in clinical trials, leading to differences in quantifying treatment effects. AREAS COVERED: The definitions of HFrEF in randomized controlled trials from 2010 until 2020 were collected. The EF ranges were clustered into very low (<30%), low (30-39%) and mildly reduced (40-49%) stratified by intervention. A time series regression analysis was performed. A total of 3052 articles were screened and 706 were included. Interventions included were pharmacologic (37%), device therapy (10%), and a combination of programs, procedural, and laboratory testing (53%). Regarding EF cutoffs, 41% of the studies utilized <40% while 26% used <35%. About 31% did not have a clearly defined EF. Between 2010 and 2020, studies with HFrEF ranges 30-39% have significantly decreased (p value < 0.001 for trend), but those which included very low EF (<30%) and mildly reduced EF (40-49%) have remained the same. EXPERT OPINION: EF definitions across clinical trials in HFrEF varied widely. Defining the specific target HF population phenotype when designing trials or in patient treatment is important as various beneficial effects of different heart failure treatment modalities can be modified or even attenuated across the spectrum of EF.

Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study.

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.

Expression of barrier proteins in the skin lesions and inflammatory cytokines in peripheral blood mononuclear cells of atopic dogs.

Atopic dermatitis (AD) is one of the most common skin diseases of dogs. Defects in the skin barrier and overproduction of inflammatory cytokines may be the pathogenesis of canine AD. Therefore, the present study was aimed to quantify the gene expression of certain skin barrier proteins and inflammatory cytokines in dogs with AD. Eleven dogs with AD and three healthy dogs were included in the present study. The skin barrier proteins, namely Filaggrin (FLG) and Involucrin (IVL), gene expression was quantified by Real-time PCR in the lesional skin tissues of the atopic dogs and normal skin of the healthy dogs. In addition to the skin proteins, the gene expressions of the interleukin (IL)-13, IL-31, and tumour necrosis factor (TNF)-α were also quantified in the peripheral blood mononuclear cells (PBMCs) of these dogs. Compared to the healthy dogs, significantly higher (P ≤ 0.01) FLG gene expression and significantly (P ≤ 0.05) lower expression of the IVL gene were quantified in the skin of atopic dogs. Further, the dogs with AD revealed significantly higher expression of TNF-α (P ≤ 0.01), IL-31 (P ≤ 0.05), and IL-13 (P ≤ 0.05) as compared to the healthy dogs. The findings of our present study evidently suggest significantly increased and decreased expressions of FLG and IVL genes, respectively, which may be responsible for disruption of the skin barrier in dogs with AD. While, the over-expressions of TNF-α, IL-31, and IL-13 genes might be attributed to the clinical pathology and manifestations of AD in dogs. However, further studies are warranted to substantiate our hypothesis about pathogenesis and clinical manifestation of AD in dogs by including a large number of animals.

Quantification of immuno-regulatory cytokine and toll-like receptors gene expression in dogs with generalized demodicosis.

The proliferation of Demodex mites is mainly controlled by host immunity; however, the precised mechanism of host-mite interplay and host immune response in the cutaneous microenvironment of dogs with generalized demodicosis (GD) are not yet established. In the present study, we envisaged the alterations in the expression of toll-like receptors (TLRs) and immuno-regulatory cytokine gene in the skin lesions and peripheral blood mononuclear cells (PBMCs) of dogs with GD. The expression of TLR2, TLR6, IFN-γ, TGF-ß and IL-10 genes in the skin lesions and PBMCs of 15 dogs with GD was quantified by qRT-PCR. Compared to healthy dogs, significantly elevated expression of TLR2 (P = 0.048), TGF-ß (P = 0.04) and IL-10 (P = 0.012) were found in the PBMCs of dogs with GD. Conversely, there was significantly reduced expression of TLR6 gene (P = 0.021) in the PBMCs of these dogs. The infested dogs also revealed significantly elevated expression of TLR2 gene (P = 0.034) in the skin lesions, while, the expression of the TLR6 gene was found to be significantly (P = 0.004) reduced. Interestingly, significant alterations in TGF-ß (P = 0.105) and IL-10 (P = 0.162) genes expression were not observed in the skin lesions of diseased dogs. Our findings suggest that Demodex mites contribute to a different systemic and cutaneous immune response in dogs for their proliferation, and consequently the development of GD. Therefore, Demodex mites might be inducing the immunosuppression through activating the systemic over-expression of immunosuppressive cytokines; however, in the cutaneous lesions, the expression of immunosuppressive cytokines remained unaltered. Both systemic and local over-expression of TLR2 and reduced expression of TLR6 genes might be responsible for the inflammatory signs of canine demodicosis and helping to the mite to escape the host immunity.

Concordance Between Blood Pressure in the Systolic Blood Pressure Intervention Trial and in Routine Clinical Practice.

Importance: There are concerns with translating results from the Systolic Blood Pressure Intervention Trial (SPRINT) into clinical practice because the standardized protocol used to measure blood pressure (BP) may not be consistently applied in routine clinical practice. Objectives: To evaluate the concordance between BPs obtained in routine clinical practice and those obtained using the SPRINT protocol and whether concordance varied by target trial BP. Design, Setting, and Participants: This observational prognostic study linking outpatient vital sign information from electronic health records (EHRs) with data from 49 of the 102 SPRINT sites was conducted from November 8, 2010, to August 20, 2015, among 3074 adults 50 years or older with hypertension without diabetes or a history of stroke. Statistical analysis was performed from May 21, 2019, to March 20, 2020. Main Outcomes and Measures: Blood pressures measured in routine clinical practice and SPRINT. Results: Participant-level EHR data was obtained for 3074 participants (2482 men [80.7%]; mean [SD] age, 68.5 [9.1] years) with 3 or more outpatient and trial BP measurements. In the period from the 6-month study visit to the end of the study intervention, the mean systolic BP (SBP) in the intensive treatment group from outpatient BP recorded in the EHR was 7.3 mm Hg higher (95% CI, 7.0-7.6 mm Hg) than BP measured at trial visits; the mean difference between BP recorded in the outpatient EHR and trial SBP was smaller for participants in the standard treatment group (4.6 mm Hg [95% CI, 4.4-4.9 mm Hg]). Bland-Altman analyses demonstrated low agreement between outpatient BP recorded in the EHR and trial BP, with wide agreement intervals ranging from approximately -30 mm Hg to 45 mm Hg in both treatment groups. In addition, the difference between BP recorded in the EHR and trial BP varied widely by site. Conclusions and Relevance: Outpatient BPs measured in routine clinical practice were generally higher than BP measurements taken in SPRINT, with greater mean SBP differences apparent in the intensive treatment group. There was a consistent high degree of heterogeneity between the BPs recorded in the EHR and trial BPs, with significant variability over time, between and within the participants, and across clinic sites. These results highlight the importance of proper BP measurement technique and an inability to apply 1 common correction factor (ie, approximately 10 mm Hg) to approximate research-quality BP estimates when BP is not measured appropriately in routine clinical practice. Trial Registration: SPRINT ClinicalTrials.gov Identifier: NCT01206062.