o Patient and primary care physician characteristics associated with billing incentives for chronic diseases in British Columbia: a retrospective cohort study By www.cmajopen.ca Published On :: 2020-05-05T05:00:14-07:00 Background: Incentive payments for chronic diseases in British Columbia were intended to support primary care physicians in providing more comprehensive care, but research shows that not all physicians bill incentives and not all eligible patients have them billed on their behalf. We investigated patient and physician characteristics associated with billing incentives for chronic diseases in BC. Methods: We conducted a retrospective cohort analysis using linked administrative health data to examine community-based primary care physicians and patients with eligible chronic conditions in BC during 2010–2013. Descriptive analyses of patients and physicians compared 3 groups: no incentives in any of the 4 years, incentives in all 4 years, and incentives in any of the study years. We used hierarchical logistic regression models to identify the patient- and physician-level characteristics associated with billing incentives. Results: Of 428 770 eligible patients, 142 475 (33.2%) had an incentive billed on their behalf in all 4 years, and 152 686 (35.6%) never did. Of 3936 physicians, 2625 (66.7%) billed at least 1 incentive in each of the 4 years, and 740 (18.8%) billed no incentives during the study period. The strongest predictors of having an incentive billed were the number of physician contacts a patient had (odds ratio [OR] for > 48 contacts 134.77, 95% confidence interval [CI] 112.27–161.78) and whether a physician had a large number of patients in his or her practice for whom incentives were billed (OR 42.38 [95% CI 34.55–52.00] for quartile 4 v. quartile 1). Interpretation: The findings suggest that primary care physicians bill incentives for patients based on whom they see most often rather than using a population health management approach to their practice. Full Article
o Use of the health care system by Ontario First Nations people with diabetes: a population-based study By www.cmajopen.ca Published On :: 2020-05-05T05:00:14-07:00 Background: First Nations people in Ontario have an increased prevalence of diabetes compared to other people in the province. This study examined use of health care services by First Nations people with diabetes and other people with diabetes in Ontario. Methods: Using linked health administrative databases, we identified all people in Ontario with diabetes as of Apr. 1, 2014. We identified First Nations people using the Indian Register. We looked at outcomes from Apr. 1, 2014, to Mar. 31, 2015. We determined the proportion of people with a regular family physician and their continuity of care with that physician. We also examined visits with specialists for diabetes care, hospital admissions for ambulatory-care–sensitive conditions, and emergency department visits for hypo- or hyperglycemia. Results: There were 1 380 529 people diagnosed with diabetes in Ontario as of Apr. 1, 2014, of whom 22 952 (1.7%) were First Nations people. First Nations people were less likely to have a regular family physician (85.3% v. 97.7%) and had lower continuity of care with that physician (mean score for continuity of care 74.6 v. 77.7) than other people in Ontario. They were also less likely to see specialists. First Nations people were more likely to be admitted to hospital for ambulatory-care–sensitive conditions (2.4% v. 1.2%) and to have an emergency department visit for hypo- or hyperglycemia (1.5% v. 0.8%). Disparities were particularly marked for those living in First Nations communities. Interpretation: First Nations people with diabetes in Ontario had poorer access to and use of primary care than other people with diabetes in the province. These findings may help explain continued disparities in the rates of complications related to diabetes. Full Article
o Emergency department use by pregnant women in Ontario: a retrospective population-based cohort study By www.cmajopen.ca Published On :: 2020-04-28T01:30:11-07:00 Background: Peripregnancy emergency department use may be common, but data specific to health care systems like that in Canada are lacking. As prior research was limited to livebirths, omitting pregnancies ending in miscarriage or induced abortion, the current study quantified and characterized emergency department use among women in Ontario with a recognized pregnancy. Methods: This retrospective population-based cohort study included all recognized pregnancies among Ontario residents aged 10–55 years with an estimated date of conception between Apr. 1, 2002, and Mar. 31, 2017. We defined peripregnancy emergency department use as any emergency department visit during pregnancy or within 42 days after pregnancy. We used modified Poisson regression with a robust error variance to generate relative risks (RRs) and 95% confidence intervals (CIs) for the outcome of any peripregnancy emergency department use in association with maternal age, parity, residential income quintile, location of residence, immigrant status, antenatal care provider and number of comorbidities within 120 days before the clinical start of the pregnancy (expressed as total number of Aggregated Diagnosis Groups [ADGs] obtained with the Johns Hopkins Adjusted Clinical Group System). All RRs, except for number of comorbidities, were further adjusted for number of ADGs. Results: Peripregnancy emergency department use occurred in 1 075 991 (39.4%) of 2 728 236 recognized pregnancies, including 35.8% of livebirths, 47.3% of stillbirths, 73.7% of miscarriages and 84.8% of threatened abortions. A peripregnancy emergency department visit was more likely among women who were less than 25 years of age (adjusted RR 1.16, 95% CI 1.16–1.17), were nulliparous (adjusted RR 1.13, 95% CI 1.13–1.13), resided in the lowest income quintile area (adjusted RR 1.16, 95% CI 1.15–1.16) or in a rural area (adjusted RR 1.50, 95% CI 1.50–1.51), were Canadian-born (adjusted RR 1.22, 95% CI 1.22–1.23), were not seen by an obstetrician (adjusted RR 1.66, 95% CI 1.54–1.80) or had a greater number of ADGs. Emergency department use peaked in the first trimester and in the first week postpartum. Compared to women residing in urban areas, those residing in rural areas had an odds ratio (OR) of 3.44 (95% CI 3.39–3.49) for 3 or more emergency department visits. Women with 3–4 (OR 1.99, 95% CI 1.97–2.01), 5–6 (OR 3.55, 95% CI 3.49–3.61), or 7 or more (OR 7.59, 95% CI 7.39–7.78) prepregnancy comorbidities were more likely to have 3 or more peripregnancy emergency department visits than were those with 2 or fewer comorbidities. Interpretation: Peripregnancy emergency department use occurred in nearly 40% of pregnancies, notably in the first trimester and early in the postpartum period. Efforts are needed to streamline rapid access to ambulatory obstetric care during these peak periods, when women are susceptible to miscarriage or a complication after a livebirth. Full Article
o Characteristics of high-drug-cost beneficiaries of public drug plans in 9 Canadian provinces: a cross-sectional analysis By www.cmajopen.ca Published On :: 2020-04-28T01:30:11-07:00 Background: Drugs are the fastest growing cost in the Canadian health care system, owing to the increasing number of high-cost drugs. The objective of this study was to examine the characteristics of high–drug-cost beneficiaries of public drug plans across Canada relative to other beneficiaries. Methods: We conducted a cross-sectional study among public drug plan beneficiaries residing in all provinces except Quebec. We used the Canadian Institute for Health Information’s National Prescription Drug Utilization Information System to identify all drugs dispensed to beneficiaries of public drug programs in 2016/17. We stratified the cohort into 2 groups: high–drug-cost beneficiaries (top 5% of beneficiaries based on annual costs) and other beneficiaries (remaining 95%). For each group, we reported total drug costs, prevalence of high-cost claims (> $1000), median number of drugs, proportion of beneficiaries aged 65 or more, the 10 most costly reimbursed medications and the 10 medications most commonly reimbursed. We reported estimates overall and by province. Results: High–drug-cost beneficiaries accounted for nearly half (46.5%) of annual spending, with an average annual spend of $14 610 per beneficiary, compared to $1570 among other beneficiaries. The median number of drugs dispensed was higher among high–drug-cost beneficiaries than among other beneficiaries (13 [interquartile range (IQR) 7–19] v. 8 [IQR 4–13]), and a much larger proportion of high–drug-cost beneficiaries than other beneficiaries received at least 1 high-cost claim (40.9% v. 0.6%). Long-term medications were the most commonly used medications for both groups, whereas biologics and antivirals were the most costly medications for high–drug-cost beneficiaries. Interpretation: High–drug-cost beneficiaries were characterized by the use of expensive medications and polypharmacy relative to other beneficiaries. Interventions and policies to help reduce spending need to consider both of these factors. Full Article
o A novel decision aid to help plan for serious illness: a multisite randomized trial By www.cmajopen.ca Published On :: 2020-04-28T01:30:11-07:00 Background: Recent studies have shown substantial deficiencies in the quality or quantity (or both) of communication and decision-making during serious illness. We evaluated the efficacy of a novel decision support intervention, the Plan Well Guide, in increasing completion of a standard medical order form for advance medical care planning and improving decisional outcomes in nonacademic primary care settings. Methods: We conducted a randomized trial in 3 primary care practices in Lethbridge, Alberta in 2017–2018. We recruited "patients at high risk" referred by the primary care doctor who required establishment or review of their Goals of Care Designation (GCD). Enrolled patients were randomly allocated to receive the Plan Well Guide, delivered by a trained facilitator, or usual care. Eight to 12 weeks after the intervention, a research assistant blinded to intervention assignment contacted the patients in both groups by telephone to do a final outcome assessment. The primary outcome was completion of GCD forms; secondary outcomes included decisional conflict scores and ratings of satisfaction. Results: A total of 123 patients (59 women [48.0%]; mean age 73.9 yr) were enrolled, 66 in the intervention arm and 57 in the usualcare arm; 119 patients completed the trial. After the intervention, GCD completion rates in the intervention and usual-care groups were 95.3% and 90.9%, respectively (risk difference [RD] 4%, 95% confidence interval [CI] –14% to 22%), and the rate of concordance between medical orders and expressed preferences on follow-up was 78% and 66%, respectively (RD 12%, 95% CI –7% to 30%). Significantly fewer patients in the intervention group than in the usual-care group had written medical orders for intensive care unit care and cardiopulmonary resuscitation (22 [34%] v. 33 [60%], RD –26%, 95% CI –42% to –8%). Patients in the intervention group had lower decisional conflict scores than those in the usual-care group (mean 30.9 v. 43.1, adjusted mean difference –12.0, 95% CI –23.2 to –0.8). Physicians considered patients in the intervention group to have lower decisional conflict than those in the usual-care group, although not significantly so (mean score 10.4 v. 14.9, adjusted mean difference –4.7, 95% CI –9.9 to 0.4) and spent less time with the former (mean 9.7 v. 13.2 min, adjusted mean difference –3.5, 95% CI –5.5 to –1.5 min). Interpretation: The decision-support intervention did not increase GCD completion rates but did seem to improve some aspects of decisional quality while reducing the physician’s time to accomplish GCD decisions. Trial registration: ClinicalTrials.gov, no. NCT01297946 Full Article
o Diabetes-induced eye disease among First Nations people in Ontario: a longitudinal, population-based cohort study By www.cmajopen.ca Published On :: 2020-04-17T08:42:26-07:00 Background: In Canada, First Nations populations experience a higher incidence of diabetes and diabetes-related complications than other people. Given the paucity of information on use of preventive eye examinations and the need for interventional care for severe retinopathy among First Nations people, we carried out a population-based study to compare rates of eye examinations and interventional therapies to treat vision-threatening stages of diabetic retinopathy among First Nations people and other people with diabetes in Ontario. Methods: In collaboration with the Chiefs of Ontario, we carried out a population-based study to identify cohorts of First Nations people and other people with diabetes in Ontario from 1995/96 to 2014/15. We used linked health administrative databases to evaluate rates of eye examination (2005/06–2014/15) and severe diabetic retinopathy treatment and compared them between the 2 populations, and between First Nations people living in and outside of First Nations communities. Results: We identified 23 013 First Nations people and 1 364 222 other people diagnosed with diabetes from 1995/96 to 2014/15, of whom 49.8% (95% confidence interval [CI] 48.9%–50.7%) and 53.8% (95% CI 53.7%–54.0%), respectively, received an eye examination in 2014/15. Eye examination rates were similar for First Nations people regardless of whether they lived in or outside a First Nations community. First Nations people developed severe diabetic retinopathy at a faster rate than other people (hazard ratio 1.19, 95% CI 1.02–1.38). The gap between First Nations people and other people in the proportion requiring therapy for severe diabetic retinopathy was especially prominent among younger people. There were no significant differences in rates of diabetic retinopathy treatment in First Nations people stratified by place of residence. Interpretation: Eye examination rates remain suboptimal among people with diabetes in Ontario and were lower among First Nations people. This is particularly concerning in light of our other findings showing an increased risk of requiring treatment for advanced diabetic retinopathy and the accelerated rate of diabetic retinopathy progression among First Nations people with diabetes. Full Article
o Deprivation and mortality related to pediatric respiratory tract infection: a cohort study in 3 high-income jurisdictions By www.cmajopen.ca Published On :: 2020-04-28T01:30:11-07:00 Background: Deaths from respiratory tract infections (RTIs) in children are preventable through timely access to public health and medical interventions. We aimed to assess whether socioeconomic disparities in mortality related to pediatric RTI persisted after accounting for health status at birth. Methods: We compared the prevalence of and risk factors for RTI-related death in singletons aged 28 days to 4 years across Ontario (Canada), Scotland and England (jurisdictions with universal health care) using linked administrative data for 2003–2013. We estimated rates of RTI-related mortality for children living in deprived areas and those born to teenage girls; we estimated both crude rates and those adjusted for health status at birth. Results: A total of 1 299 240 (Ontario), 547 556 (Scotland) and 3 910 401 (England) children were included in the study. Across all jurisdictions, children born in the most deprived areas experienced the highest rates of RTI-related mortality. After adjustment for high-risk chronic conditions and prematurity, we observed differences in mortality according to area-level deprivation in Ontario and England but not in Scotland. In Ontario, teenage motherhood was also an independent risk factor for RTI-related mortality. Interpretation: Socioeconomic disparities played a substantial role in child mortality related to RTI in all 3 jurisdictions. Context-specific investigations around the mechanisms of this increased risk and development of programs to address socioeconomic disparities are needed. Full Article
o Codesigning care improvements for women living with HIV: a patient-oriented deliberative dialogue workshop in Montreal, Quebec By www.cmajopen.ca Published On :: 2020-04-17T08:42:26-07:00 Background: Care services have not been sufficiently adapted to meet the comprehensive care needs of women living with HIV. Our study objective was to engage patients and providers in codesigning care recommendations to improve care for this population in the province of Quebec. Methods: We conducted a 5-hour deliberative dialogue workshop in April 2019 in Montréal as the final phase of a mixed-methods study investigating comprehensive care for women living with HIV. The study drew on data from the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS). Recruitment was guided by a purposive maximum-variation sampling strategy to ensure an appropriate mix of participants and was facilitated by our existing CHIWOS networks. Participants included patients (women living with HIV) and HIV care providers (doctors, nurses, pharmacists). The workshop was facilitated professionally and included a synthesis of the evidence, small- and large-group deliberations, and voting on care improvements. Results: Eight patients and 8 HIV care providers participated. Drawing on identified care priorities, the participants identified 4 relatively rapid care improvements and 3 longer-term improvements. The rapid care improvements included delegating medical acts to members of multidisciplinary care teams; greater involvement of HIV community members within care settings and health care decision-making; creating a women’s health information booklet; and increasing HIV education among all health care providers and raising awareness of women’s care needs beyond HIV-specific care among HIV care providers. The longer-term care improvements included advocating for complete financial coverage of antiretroviral therapy within the government-sponsored Medicare program, facilitating access to allied care providers (e.g., physiotherapists and psychologists) and launching a population-wide campaign to increase awareness about the Undetectable = Untransmittable (U=U) initiative and other HIV advances. Interpretation: The deliberative dialogue workshop yielded evidence-based, stakeholder-driven recommendations to improve the comprehensive care of women living with HIV in Quebec. Full Article
o Palliative care clinical rotations among undergraduate and postgraduate medical trainees in Canada: a descriptive study By www.cmajopen.ca Published On :: 2020-04-14T05:09:06-07:00 Background: The number of medical undergraduate and postgraduate students completing palliative care clinical rotations in Canadian medical schools is currently unknown. The aim of this study was to assess the proportion of Canadian medical trainees completing clinical rotations in palliative care and to determine whether changes took place between 2008 and 2018. Methods: In this descriptive study, all Canadian medical schools (n = 17) were invited to provide data at the undergraduate and postgraduate levels (2007/08–2015/16 and 2007/08–2017/18, respectively). Information collected included the number, type and length of palliative care clinical rotations offered and the total number of medical trainees or residents enrolled at each school. Results: All 17 Canadian medical schools responded to the request for information. At the undergraduate level, palliative care clinical rotations were not offered in 2 schools, mandatory in 2 and optional in 13. Three schools that offered optional rotations were unable to provide complete data and were therefore excluded from further analyses. In 2015/16, only 29.7% of undergraduate medical students completed palliative care clinical rotations, yet this was a significant improvement compared to 2011/12 (13.6%, p = 0.02). At the postgraduate level, on average, 57.9% of family medicine trainees completed such rotations between 2007/08 and 2016/17. During the same period, palliative care clinical rotations were completed by trainees in specialty or subspecialty programs in anesthesiology (34.2%), geriatric medicine (64.4%), internal medicine (30.9%), neurology (28.2%) and psychiatry (64.5%). Interpretation: Between 2008 and 2018, a large proportion of Canadian medical trainees graduated without the benefit of a clinical rotation in palliative care. Without dedicated clinical exposure to palliative care, many physicians will enter practice without vital palliative care competencies. Full Article
o Perspectives of specialists and family physicians in interprofessional teams in caring for patients with multimorbidity: a qualitative study By www.cmajopen.ca Published On :: 2020-04-06T05:19:07-07:00 Background: Patients with multimorbidity often require services across different health care settings, yet team processes among settings are rarely implemented. We explored perceptions of specialists and family physicians collaborating in a telemedicine interprofessional consultation for patients with multimorbidity to better understand the value of bringing physicians together across the boundaries of health care settings. Methods: This was a descriptive qualitative, interview-based study. Physicians who had previously participated in the Telemedicine Interprofessional Model of Practice for Aging and Complex Treatments (Telemedicine IMPACT Plus [TIP] Program) were invited to participate and asked to describe their experience of being a member of the program. Interviews were conducted from March to May 2016. We conducted an iterative and interpretive process using both individual and team analysis to identify themes. Results: There were 15 participants, 9 specialists and 6 family physicians. Three themes emerged in the analysis: creating new perspectives on care for patients with multimorbidity by sharing knowledge, skills and attitudes; the shift from a consultant model to an interprofessional team model (allowing a window into the community, extending discussions beyond the medical model and focusing on the patient’s health in context); and opportunities for learners, including learning about interprofessional collaboration and gaining exposure to a real-world model for caring for people with multimorbidity in outpatient settings. Interpretation: Family physicians and specialists participating in a TIP Program believed the program improved their knowledge and skills, while also serving as an effective care delivery strategy. The findings also support that learners require more exposure to nontraditional consultant models in order to care for patients with multimorbidity effectively. Full Article
o Proportion of female recipients of resident-selected awards across Canada from 2000 to 2018: a retrospective observational study By www.cmajopen.ca Published On :: 2020-04-06T05:19:07-07:00 Background: Female physicians have been shown to receive fewer awards from medical societies than their male colleagues. We examined the sex distribution of recipients of Canadian residency association awards. Methods: We conducted a retrospective observational study of the sex of staff and resident physician recipients of resident-selected awards from provincial and national residency associations using data from 2000–2018. We classified awards into professionalism, advocacy and wellness awards, and education and teaching awards based on award names and descriptions, and compared the proportion of male and female recipients in these categories. Results: We identified 314 recipients of staff physician awards and 129 recipients of resident physician awards. Male staff and resident physicians had higher odds of receiving awards than their female counterparts (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.13–1.89 and OR 1.70, 95% CI 1.18–2.46, respectively). There was a reduction in the odds of male residents’ receiving an award over the study period (OR 0.94, 95% CI 0.90–0.98). Male physicians had higher odds of receiving education and teaching awards than female physicians as staff but not as residents (OR 3.21, 95% CI 1.72–5.95 and OR 1.96, 95% CI 0.84–4.60, respectively). Interpretation: Male staff and resident physicians in Canada had higher odds of receiving awards from provincial and national residency associations between 2000 and 2018 than their female counterparts. Given this disparity, it would be prudent for organizations that distribute awards to physicians, residents and medical students to examine their nomination criteria and processes for potential bias. Full Article
o Digging Deep in the Microbiome to Diagnose Clostridioides difficile Infection By academic.oup.com Published On :: Thu, 13 Feb 2020 00:00:00 GMT Clostridioides difficileDiagnosticsMetabolomicsMicrobiome Full Article
o The SARS-CoV-2 Outbreak: Diagnosis, Infection Prevention, and Public Perception By academic.oup.com Published On :: Wed, 26 Feb 2020 00:00:00 GMT At the end of 2019 and early 2020, an outbreak of pneumonia of unknown etiology emerged in the city of Wuhan in China. The cases were found to be caused by a novel beta coronavirus, which was subsequently named SARS-CoV-2 by the World Health Organization (WHO). The virus has since spread further in China and to other regions of the world, having infected more than 88 K people, and causing close to 3000 deaths as of March 1, 2020. More than 50 million people remain in quarantine at this time. Scientists and clinicians globally are working swiftly to combat COVID-19, the respiratory disease caused by the virus. Notably, diagnostic assays have been developed rapidly in many countries, and have played significant roles in diagnosis, monitoring, surveillance, and infection control. Starting February 29, 2020, the development and performance of molecular testing for SARS-CoV-2 in high complexity Clinical Laboratory Improvement Amendments (CLIA) laboratories prior to emergency use authorization was allowed by the US FDA. Although the epidemic is evolving rapidly, many valuable lessons have been learned and many questions remain to be answered. Here we invited multiple experts across the globe from clinical laboratories, public health laboratories, infection control, and diagnostic industry to share their views on the diagnosis, infection control, and public perception of SARS-CoV-2. Full Article
o Emergence of a Novel Coronavirus Disease (COVID-19) and the Importance of Diagnostic Testing: Why Partnership between Clinical Laboratories, Public Health Agencies, and Industry Is Essential to Control the Outbreak By academic.oup.com Published On :: Thu, 12 Mar 2020 00:00:00 GMT Full Article
o 25-Hydroxyvitamin D and Risk of Osteoporotic Fractures: Mendelian Randomization Analysis in 2 Large Population-Based Cohorts By academic.oup.com Published On :: Tue, 07 Apr 2020 00:00:00 GMT AbstractBackgroundWhether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis.MethodsWe genotyped 116 335 randomly chosen white Danish persons aged 20–100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries.ResultsDuring up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97–1.09) for individuals with 25–49.9 nmol/L, 1.19 (1.10–1.28) for individuals with 12.5–24.9 nmol/L, and 1.39 (1.21–1.60) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00–1.15), 1.25 (1.13–1.37), and 1.49 (1.25–1.77) for osteoporotic fractures and 1.09 (0.98–1.22), 1.37 (1.18–1.57), and 1.41 (1.09–1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98–1.00) for total fractures, 0.99 (0.97–1.00) for osteoporotic fractures, and 0.98 (0.95–1.00) for fractures of hip or femur.ConclusionsLow plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures. Full Article
o Analytical Performance Specifications for Lipoprotein(a), Apolipoprotein B-100, and Apolipoprotein A-I Using the Biological Variation Model in the EuBIVAS Population By academic.oup.com Published On :: Wed, 08 Apr 2020 00:00:00 GMT AbstractBackgroundWith increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population.MethodSerum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles.ResultsWithin-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB.ConclusionUsing a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)–compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable. Full Article
o Associations of Cardiac, Kidney, and Diabetes Biomarkers With Peripheral Neuropathy among Older Adults in the Atherosclerosis Risk in Communities (ARIC) Study By academic.oup.com Published On :: Wed, 08 Apr 2020 00:00:00 GMT AbstractBackgroundThe aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population.MethodsWe conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro–B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [Hb A1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016–2017; age 71–94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adults with and without diabetes after adjusting for traditional risk factors.ResultsIn total, 33.5% of participants had PN (37.3% with diabetes and 31.9% without diabetes). There was an independent association of hs-cTnT with PN regardless of diabetes status (diabetes T3 vs. T1: odds ratio [OR], 2.15 [95% CI, 1.44–3.22]; no diabetes: OR, 2.31 [95%CI, 1.76–3.03]; P = 0.72 for interaction). Among participants without diabetes, there were also significant associations of NT-proBNP (OR, 1.40 [95% CI, 1.08–1.81]) and urine albumin-to-creatinine ratio (OR, 1.55 [95% CI, 1.22–1.97]) with PN. Associations of hyperglycemia biomarkers including Hb A1c (OR, 1.76 [95% CI, 1.22–2.54]), fructosamine (OR, 1.71 [95% CI, 1.19–2.46]), and glycated albumin (OR, 1.45 [95% CI, 1.03–2.03]) with PN were significant only among participants with diabetes.ConclusionsOverall, hs-cTnT appears to be a global marker of end organ damage, including PN. Laboratory biomarkers may be able to help us identify those individuals with PN. Full Article
o Detection of ctDNA from Dried Blood Spots after DNA Size Selection By academic.oup.com Published On :: Wed, 08 Apr 2020 00:00:00 GMT AbstractBackgroundRecent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole-genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes. Dried blood spots have practical advantages for sample collection, may facilitate serial sampling, and could support novel study designs in humans and animal models.MethodsWe developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots using filter paper cards and bead-based size selection. DNA extracted and size-selected from dried spots was analyzed using sWGS and polymerase chain reaction (PCR).ResultsAnalyzing a 50 μL dried blood spot from frozen whole blood of a patient with melanoma, we identified ctDNA based on the presence of tumor-specific somatic copy-number alterations, and found a fragment-size profile similar to that observed in plasma DNA. We found alterations in different chromosomes in blood spots from 2 patients with high-grade serous ovarian carcinoma. Extending this approach to serial dried blood spots from mouse xenograft models, we detect tumor-derived cell-free DNA and identified ctDNA from the originally grafted ascites.ConclusionOur data suggest that ctDNA can be detected and monitored in dried blood spots from archived and fresh blood samples, enabling new approaches for sample collection and novel study/trial designs for both patients and in vivo models. Full Article
o Is the Sun Setting on Vitamin D? By academic.oup.com Published On :: Wed, 08 Apr 2020 00:00:00 GMT Osteoporotic fractures and low vitamin D concentrations are prevalent, especially among older adults. One in 2 women and 1 in 5 men in the United States aged ≥50 years will have an osteoporotic fracture (1). According to the National Health and Nutrition Examination Survey (NHANES) 2011–2014, 24% of women, 23% of men, and 15% of adults aged ≥60 years in the United States have low 25-hydroxy vitamin D (25-OHD) concentrations (i.e., 25-OHD < 20 ng/mL [50 nmol/L]) (2). Several observational studies, including the Cardiovascular Health Study and NHANES III, have found an association between low serum 25-OHD concentrations and higher risk of fractures, at least in these predominantly white populations (3, 4). These observational studies raise the possibility that low 25-OHD concentrations may be a risk factor for fracture but, given the potential for uncontrolled confounding, cannot prove a cause–effect relationship. Full Article
o Plasma S100A8/A9 Concentrations and Clinical Outcomes of Ischemic Stroke in 2 Independent Multicenter Cohorts By academic.oup.com Published On :: Tue, 14 Apr 2020 00:00:00 GMT AbstractBackgroundS100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts.MethodsPlasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events.ResultsAmong the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66–2.68) for the primary outcome and 1.62 (95% CI, 1.27–2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10–8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38–3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%–39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations.ConclusionsHigh plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke. Full Article
o Peripheral Neuropathy—Time for Better Biomarkers? By academic.oup.com Published On :: Thu, 16 Apr 2020 00:00:00 GMT Peripheral neuropathy (PN) is a condition affecting up to 20% of the general population. The symptoms range from mild to disabling, depending on the types of nerve fiber affected and the type and severity of damage. Full Article
o Salivary AMY1 Copy Number Variation Modifies Age-Related Type 2 Diabetes Risk By academic.oup.com Published On :: Sun, 26 Apr 2020 00:00:00 GMT AbstractBackgroundCopy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain.MethodsWe measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk.ResultsWe found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR.ConclusionsWe found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age. Full Article
o Correction By academic.oup.com Published On :: Sun, 26 Apr 2020 00:00:00 GMT The article “Effect of Lipoprotein(a) on the Diagnosis of Familial Hypercholesterolemia: Does It Make a Difference in the Clinic?” (Clin Chem 2019;65:1258–66) contained several descriptive errors in the laboratory methods reported on page 1259. Full Article
o Commentary on Cryptogenic Cushing Syndrome Due to a White Lie By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Cushing syndrome results from chronic excessive exposure to glucocorticoids, impacting virtually every organ system with the most dominant effects on fat metabolism, immune function, and musculoskeletal systems. Endogenous Cushing syndrome is rare, most usually due to excess ACTH secretion from pituitary, and less frequently from ectopic tumors. Other cases result from ACTH-independent adrenal overproduction of cortisol. Full Article
o A Yellow-Green Cerebrospinal Fluid Sample By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT body fluidsCSF Full Article
o Persistent Hyponatremia in an Elderly Patient By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Hyponatremiahyposmolarreset osmostatsyndrome of inappropriate antidiuresiselderly Full Article
o Commentary on Persistent Hyponatremia in an Elderly Patient By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Lai et al. report the case of an elderly gentleman who presented with resolving neurologic findings from a transient ischemic attack and who was found to have hyponatremia with a serum sodium concentration of 123 mmol/L. Hypoosmolality was confirmed, and a diluting defect identified with a urine osmolality that ranged between 167 and 285 mOsm/kg. As the urine osmolality rose to > 400 mOsm/kg with water deprivation, a diagnosis of syndrome of inappropriate antidiuresis (SIAD) from reset osmostat was entertained. Full Article
o Commentary on Cryptogenic Cushing Syndrome Due to a White Lie By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT This interesting case report from South Africa focuses on a difficult diagnostic challenge: apparent Cushing syndrome with inconsistent laboratory findings. Full Article
o Sailing through the Three Gorges in China By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT At about 6300 km, Chang Jiang or Long River (长江) is the longest river in Asia and third longest in the world. It is the longest in the world to flow entirely within one country and plays a large role in the history, culture, and economy of China. For thousands of years, the river has been used for water, irrigation, sanitation, transportation, industry, boundary-marking, and war. Passing through 10 provinces, it commences its flow from the Tanggula Mountains (唐古拉山) in ethnic Tibetan Qinghai (青海) Province in northwest China and ends at the East China Sea in Shanghai (上海). Along the middle reaches of the river, between the western upstream Baidi City (白帝城) of Chongqing (重庆) Municipality and Yichang (宜昌) city of Hubei (湖北) Province downstream, the river passes through 3 adjacent gorges, known as the Three Gorges (三峡): Qutang, Wuxia, and Xiling gorge (瞿塘, 巫峡, 西陵峡) cutting through the Wu Mountains (巫山). Spanning a distance of about 120 km, these gorges are noted for their natural beauty: unusual-looking mountain peaks ranging from 800 m to 2000 m, precipitous valleys, dense forest, and spectacular landscape. Many ancient government officials, scholars, poets, and painters visited the Three Gorges and left their impressions and praises in writings. Archeological discoveries in recent years have shown for the first time that the Three Gorges area should be recognized as the birthplace of Chinese civilization. Full Article
o Measurement of Serum Neuron-Specific Enolase in Neuroblastoma: Is There a Clinical Role? By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT AbstractBACKGROUNDThe measurement of neuron-specific enolase (NSE) in serum is frequently requested for diagnosis, risk stratification, and treatment monitoring of neuroblastoma (NB) in the pediatric population. However, authoritative clinical practice guidelines advise about the poor diagnostic performance of NSE.ContentWe critically appraised the available literature evaluating the diagnostic and prognostic value of NSE in the management of NB, paying special attention to the definition of appropriate threshold levels. In addition, we discuss the interfering conditions causing artifactual increases of NSE concentrations in serum and potentially influencing the clinical evaluation of patients with suspected NB.SummaryNo definitive evidence supports the use of serum NSE for diagnosis and monitoring of NB. The risk of obtaining false-positive NSE results associated with confounders (e.g., sample hemolysis) and other pathophysiologic conditions (e.g., inflammation) is remarkable and hampers the diagnostic value of this test. NSE may be helpful to define the risk of death of patients with NB, mainly in the advanced stages of disease. However, further studies validating currently marketed immunoassays and defining threshold values useful for this scope are warranted. Full Article
o Commentary on Persistent Hyponatremia in an Elderly Patient By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Hyponatremia, the most common electrolyte disorder, is present in 2%–4% of ambulatory patients and up to 22% of geriatric inpatients (1). Clinicians classify hyponatremia into three main categories: hypovolemic (decreased intravascular volume from salt and water loss with inadequate replacement), euvolemic (normal intravascular volume, but increased water dilutes sodium), and hypervolemic (total body water is increased, usually causing edema, while intravascular volume is often decreased). Less frequent causes are pseudohyponatremia (due to decreased water in a fixed volume of plasma, usually due to increased lipids or protein) and water shifting due to increased osmolality (most commonly due to glucose). While the most extreme examples of hypovolemic and hypervolemic states can be determined by physical examination, in many cases the patient is euvolemic clinically. Full Article
o Metabolic Acidosis and Hypoglycemia in a Child with Leigh-Like Phenotype By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Full Article
o Can We Improve Current Cancer Screening Programs? By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Cancer continues to be one of the leading causes of morbidity and mortality in the US. Although the treatment of cancer has evolved over the past decades with the use of targeted therapies and immunotherapy, many of these new treatments are expensive and are not readily available to everyone. Moreover, the recent success with treatment advances are not generalized to all cancer types, as some cancers continue to be devastating without significant progress in treatment options. Hence, early detection through population screening remains a critical armament against cancer. Full Article
o Lactic Acidosis after Drinking Mysterious Beverage By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT ethylene glycol poisoninglactateanalytical interference Full Article
o Cryptogenic Cushing Syndrome Due to a White Lie By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Cushing syndromeExogenousDexamethasoneSkinWhiteningCream Full Article
o Chinese Health Care Workers and COVID-19: For Whom the Bell Tolls By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Full Article
o JACC: Basic to Translational Science 2019 Young Author Award Winner By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Full Article
o JACC: Basic to Translational Science 2019 Young Author Award Winner By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Full Article
o Targeting Vascular Calcification in Chronic Kidney Disease By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Cardiovascular (CV) disease remains an important cause of morbidity and mortality for patients with chronic kidney disease (CKD). Although clustering of traditional risk factors with CKD is well recognized, kidney-specific mechanisms are believed to drive the disproportionate burden of CV disease. One perturbation that is frequently observed at high rates in patients with CKD is vascular calcification, which may be a central mediator for an array of CV sequelae. This review summarizes the pathophysiological bases of intimal and medial vascular calcification in CKD, current strategies for diagnosis and management, and posits vascular calcification as a risk marker and therapeutic target. Full Article
o Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Part 2: Potential Alternatives to the Use of Animals in Preclinical Trials By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Dramatically rising costs in drug development are in large part because of the high failure rates in clinical phase trials. The poor correlation of animal studies to human toxicity and efficacy have led many developers to question the value of requiring animal studies in determining which drugs should enter in-human trials. Part 1 of this 2-part series examined some of the data regarding the lack of concordance between animal toxicity studies and human trials, as well as some of the potential reasons behind it. This second part of the series focuses on some alternatives to animal trials (hereafter referred to as animal research) as well as current regulatory discussions and developments regarding such alternatives. Full Article
o Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development. Full Article
o Targeting Phosphorylcholine in Established Atherosclerosis? By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Full Article
o Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular 18F-FDG Uptake in Atherosclerotic Mice By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of 18F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies. Full Article
o Shining a Light on Venous Thromboembolism By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Full Article
o In Vivo Imaging of Venous Thrombus and Pulmonary Embolism Using Novel Murine Venous Thromboembolism Model By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology. Full Article
o Immune Cell Profiling and Risk Stratification: Cast a Wider Net By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Full Article
o In Situ Immune Profiling of Heart Transplant Biopsies Improves Diagnostic Accuracy and Rejection Risk Stratification By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Recognizing that guideline-directed histologic grading of endomyocardial biopsy tissue samples for rejection surveillance has limited diagnostic accuracy, quantitative, in situ characterization was performed of several important immune cell types in a retrospective cohort of clinical endomyocardial tissue samples. Differences between cases were identified and were grouped by histologic grade versus clinical rejection trajectory, with significantly increased programmed death ligand 1+, forkhead box P3+, and cluster of differentiation 68+ cells suppressed in clinically evident rejections, especially cases with marked clinical-histologic discordance. Programmed death ligand 1+, forkhead box P3+, and cluster of differentiation 68+ cell proportions are also significantly higher in "never-rejection" when compared with "future-rejection." These findings suggest that in situ immune modulators regulate the severity of cardiac allograft rejection. Full Article
o Design of the {beta}3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (β3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available β3AR agonist) in patients with CpcPH due to HF. The effect of β3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539) Full Article
o Insight into the structure and tasks of the Early Career Members Committee of the European Respiratory Society By breathe.ersjournals.com Published On :: 2020-03-18T06:44:39-07:00 The Early Career Members Committee (ECMC) of the European Respiratory Society (ERS) consists of 14 members, one Early Career Member (ECM) representative per assembly. In September 2019, seven recently elected representatives joined the ECMC. An overview is given of the tasks performed by each representative within the ECMC (table 1). In addition, a short summary about the content of these tasks is provided. Full Article