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The ability to reliably and reproducibly measure any protein of the human proteome in any tissue or cell type would be transformative for understanding systems-level properties as well as specific pathways in physiology and disease. Here, we describe the generation and verification of a compendium of highly specific assays that enable quantification of 99.7% of the 20,277 annotated human proteins by the widely accessible, sensitive, and robust targeted mass spectrometric method selected reaction monitoring, SRM. This human SRMAtlas provides definitive coordinates that conclusively identify the respective peptide in biological samples. We report data on 166,174 proteotypic peptides providing multiple, independent assays to quantify any human protein and numerous spliced variants, non-synonymous mutations, and post-translational modifications. The data are freely accessible as a resource at http://www.srmatlas.org/, and we demonstrate its utility by examining the network response to inhibition of cholesterol synthesis in liver cells and to docetaxel in prostate cancer lines.
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Bases de Datos de Proteínas , Proteoma , Acceso a la Información , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Colesterol/biosíntesis , Docetaxel , Femenino , Humanos , Internet , Hígado/efectos de los fármacos , Masculino , Mutación , Neoplasias de la Próstata/tratamiento farmacológico , Empalme del ARN , Taxoides/uso terapéuticoRESUMEN
BACKGROUND: Self-management education and support (SMES) interventions have modest effects on intermediate outcomes for those at risk of cardiovascular disease, but few studies have measured or demonstrated an effect on clinical end points. Advertising for commercial products is known to influence behavior, but advertising principles are not typically incorporated into SMES design. METHODS: This randomized trial studied the effect of a novel tailored SMES program designed by an advertising firm among a population of older adults with low income at high cardiovascular risk in Alberta, Canada. The intervention included health promotion messaging from a fictitious "peer" and facilitated relay of clinical information to patients' primary care provider and pharmacist. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and hospitalizations for cardiovascular-related ambulatory care-sensitive conditions. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (EQ-5D [EuroQoL 5-dimension] index score), medication adherence, and overall health care costs. RESULTS: We randomized 4761 individuals, with a mean age of 74.4 years, of whom 46.8% were female. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. Over a median follow-up time of 36 months, the rate of the primary outcome was lower in the group that received SMES compared with the control group (incidence rate ratio, 0.78 [95% CI, 0.61 to 1.00]; P=0.047). No significant between-group changes in quality of life over time were observed (mean difference, 0.0001 [95% CI, -0.018 to 0.018]; P=0.99). The proportion of participants who were adherent to medications was not different between the 2 groups (P=0.199 for statins and P=0.754 for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Overall adjusted health care costs did not differ between those receiving SMES and the control group ($2015 [95% CI, -$1953 to $5985]; P=0.320). CONCLUSIONS: For older adults with low income, a tailored SMES program using advertising principles reduced the rate of clinical outcomes compared with usual care. The mechanisms of improvement are unclear and further studies are required. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.
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Enfermedades Cardiovasculares , Automanejo , Humanos , Femenino , Anciano , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Calidad de Vida , Publicidad , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , AlbertaRESUMEN
BACKGROUND: One in eight people with heart disease has poor medication adherence that, in part, is related to copayment costs. This study tested whether eliminating copayments for high-value medications among low-income older adults at high cardiovascular risk would improve clinical outcomes. METHODS: This randomized 2×2 factorial trial studied 2 distinct interventions in Alberta, Canada: eliminating copayments for high-value preventive medications and a self-management education and support program (reported separately). The findings for the first intervention, which waived the usual 30% copayment on 15 medication classes commonly used to reduce cardiovascular events, compared with usual copayment, is reported here. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and cardiovascular-related hospitalizations over a 3-year follow-up. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (Euroqol 5-dimension index score), medication adherence, and overall health care costs. RESULTS: A total of 4761 individuals were randomized and followed for a median of 36 months. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. The rate of the primary outcome was not reduced by copayment elimination, (521 versus 533 events, incidence rate ratio 0.84 [95% CI, 0.66-1.07], P=0.162). The incidence rate ratio for nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (0.97 [95% CI, 0.67-1.39]), death (0.94 [95% CI, 0.80 to 1.11]), and cardiovascular-related hospitalizations (0.78 [95% CI, 0.57 to 1.06]) did not differ between groups. No significant between-group changes in quality of life over time were observed (mean difference, 0.012 [95% CI, -0.006 to 0.030], P=0.19). The proportion of participants who were adherent to statins was 0.72 versus 0.69 for the copayment elimination versus usual copayment groups, respectively (mean difference, 0.03 [95% CI, 0.006-0.06], P=0.016). Overall adjusted health care costs did not differ ($3575 [95% CI, -605 to 7168], P=0.098). CONCLUSIONS: In low-income adults at high cardiovascular risk, eliminating copayments (average, $35/mo) did not improve clinical outcomes or reduce health care costs, despite a modest improvement in adherence to medications. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.
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Enfermedades Cardiovasculares , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Anciano , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Calidad de Vida , Factores de Riesgo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , AlbertaRESUMEN
BACKGROUND AND AIMS: Plant water status is important for fruit development, because many fleshy fruits contain large amounts of water. However, there is no information on vascular flows of Persea americana 'Hass' avocado. The aims of this research were to explore the impact of drought stress on the water relationships of the 'Hass' avocado plant and its fruit growth. METHODS: Well-watered and water-stressed 'Hass' avocado plants were compared. Over 4 weeks, water flows through the shoot and fruit pedicel were monitored using external sap flow gauges. Fruit diameter was monitored using linear transducers, and stomatal conductance (gs), photosynthesis (A) and leaf and stem water potentials (Ñ°leaf and Ñ°stem) were measured to assess the response of the plants to water supply. KEY RESULTS: In well-watered conditions, the average water inflow to the shoot was 72 g day-1. Fruit water inflow was 2.72 g day-1, but there was water loss of 0.37 g day-1 caused by the outflow (loss back into the tree) through the vascular tissues and 1.06 g day-1 from the fruit skin. Overall, fruit volume increased by 1.4 cm3 day-1. In contrast, water flow into fruit of water-stressed plants decreased to 1.88 g day-1, with the outflow increasing to 0.61 g day-1. As a result, increases in fruit volume were reduced to 0.4 cm3 day-1. The values of A, gs and sap flow to shoots were also reduced during drought conditions. Changes in the hourly time-courses of pedicel sap flow, fruit volume and stem water potential during drought suggest that the stomatal response prevented larger increases in outflow from the fruit. Following re-watering, a substantial recovery in growth rate was observed. CONCLUSIONS: In summary, a reduction in growth of avocado fruit was observed with induced water deficit, but the isohydric stomatal behaviour of the leaves helped to minimize negative changes in water balance. Also, there was substantial recovery after re-watering, hence the short-term water stress did not decrease avocado fruit size. Negative impacts might appear if the drought treatment were prolonged.
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Sequías , Frutas , Persea , Fotosíntesis , Estomas de Plantas , Agua , Persea/fisiología , Persea/crecimiento & desarrollo , Estomas de Plantas/fisiología , Frutas/fisiología , Frutas/crecimiento & desarrollo , Agua/fisiología , Agua/metabolismo , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Hojas de la Planta/crecimiento & desarrollo , Transpiración de Plantas/fisiología , Tallos de la Planta/fisiología , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/anatomía & histología , Brotes de la Planta/fisiología , Brotes de la Planta/crecimiento & desarrollo , Estrés Fisiológico/fisiología , DeshidrataciónRESUMEN
AIM: Canadian guidelines recommend metformin as first-line therapy for incident uncomplicated type 2 diabetes and the vast majority of patients are treated accordingly. However, only 54% 65% remain on treatment after 1 year, with the highest discontinuation rates within the first 3 months. The purpose of this study was: (a) to identify individual and clinical factors associated with metformin discontinuation among patients with newly diagnosed uncomplicated type 2 diabetes in Alberta, Canada, and (b) describe glycated haemoglobin (HbA1c) trajectories in the first 12 months after initiation of pharmacotherapy, stratified by metformin usage pattern. MATERIALS AND METHODS: We conducted a retrospective cohort study using linked administrative datasets from 2012 to 2017 to define a cohort of individuals with uncomplicated incident type 2 diabetes. Using logistic regression, we determined individual and clinical characteristics associated with metformin discontinuation. We categorized individuals based on patterns of metformin use and then used mean HbA1c measurements over a 12-month follow-up period to determine glycaemic trajectories for each pattern. RESULTS: Characteristics associated with metformin discontinuation were younger age, lower baseline HbA1c and having fewer comorbidities. Sex, income and location (urban/rural) were not significantly associated with metformin discontinuation. Individuals who continued metformin with higher adherence and individuals who discontinued metformin entirely had lowest HbA1c values at 12 months from treatment initiation. Those who changed therapy or had additional therapies added had higher HbA1c values at 12 months. CONCLUSION: Identifying characteristics associated with discontinuation of metformin and individuals' medication usage patterns provide an opportunity for targeted interventions to support patients' glycaemic management.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/inducido químicamente , Hemoglobina Glucada , Hipoglucemiantes/efectos adversos , Estudios Retrospectivos , Alberta/epidemiología , Quimioterapia CombinadaRESUMEN
AIM: To estimate the real-world effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) at reducing loss of kidney function and adverse kidney events in adults with varying levels of albuminuria. MATERIALS AND METHODS: In this retrospective cohort study using administrative data, we matched new SGLT2i users 1:2 to DPP4i users on diabetes therapy, chronic kidney disease (CKD) stage, albuminuria and time-conditional propensity score. Albuminuria was defined by spot urine albumin or equivalent as mild, moderate or severe. Linear regression was used to model the estimated glomerular filtration rate (eGFR), and Poisson regression for a composite kidney outcome (> 40% loss of eGFR, kidney replacement therapy or death from kidney causes) and all-cause mortality. RESULTS: SGLT2i users (n = 19 238, median age 57.9 years, female 40.9%) had mostly nil/mild albuminuria (70.7%). SGLT2is were associated with a 1.36 (95% CI 0.98-1.74) mL/min/1.73m2 (P < .001) acute (≤ 60 days) decline in eGFR, relative to DPP4is. Thereafter, SGLT2is were associated with 1.04 (95% CI 0.93-1.15) mL/min/1.73m2 (P < .001) less annual eGFR loss. SGLT2i users had fewer adverse kidney outcomes (incidence rate ratio [IRR] 0.58 [0.47-0.71]; P < .001), but not all-cause mortality (IRR 0.82 [0.66-1.01]; P = .06). Outcomes were similar considering only those with nil/mild albuminuria. CONCLUSIONS: SGLT2is may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes and nil or non-severe albuminuria.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Inhibidores de la Dipeptidil-Peptidasa IV , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Femenino , Humanos , Persona de Mediana Edad , Albuminuria/tratamiento farmacológico , Albuminuria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Riñón , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Estudios Retrospectivos , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversosRESUMEN
AIMS: Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. METHODS AND RESULTS: We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. CONCLUSION: Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.
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Fibrilación Atrial , Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Insuficiencia Cardíaca , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Accidente Cerebrovascular , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Estudios de Cohortes , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Insuficiencia Cardíaca/epidemiología , Glucosa , Sodio , Hipoglucemiantes , Estudios RetrospectivosRESUMEN
BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.
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Estenosis Carotídea , Endarterectomía Carotidea , Médicos , Accidente Cerebrovascular , Humanos , Estenosis Carotídea/complicaciones , Estenosis Carotídea/tratamiento farmacológico , Estenosis Carotídea/cirugía , Fibrinolíticos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Stents , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVE: FoodRx is a 12-month healthy food prescription incentive program for people with type 2 diabetes (T2DM) and experiences of household food insecurity. In this study, we aimed to explore potential users' prospective acceptability (acceptability prior to program use) of the design and delivery of the FoodRx incentive and identify factors influencing prospective acceptability. DESIGN: We used a qualitative descriptive approach and purposive sampling to recruit individuals who were interested or uninterested in using the FoodRx incentive. Semi-structured interviews were guided by the theoretical framework of acceptability, and corresponding interview transcripts were analysed using differential qualitative analysis guided by the socioecological model. SETTING: Individuals living in Alberta, Canada. PARTICIPANTS: In total, fifteen adults with T2DM and experiences of household food insecurity. RESULTS: People who were interested in using the FoodRx incentive (n 10) perceived it to be more acceptable than those who were uninterested (n 5). We identified four themes that captured factors that influenced users' prospective acceptability: (i) participants' confidence, views and beliefs of FoodRx design and delivery and its future use (intrapersonal), (ii) the shopping routines and roles of individuals in participants' social networks (interpersonal), (iii) access to and experience with food retail outlets (community), and (iv) income and food access support to cope with the cost of living (policy). CONCLUSION: Future healthy food prescription programs should consider how factors at all levels of the socioecological model influence program acceptability and use these data to inform program design and delivery.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Alberta , Motivación , Estudios Prospectivos , Abastecimiento de Alimentos , Inseguridad AlimentariaRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) describes a spectrum of chronic fattening of liver that can lead to fibrosis and cirrhosis. Diabetes has been identified as a major comorbidity that contributes to NAFLD progression. Health systems around the world make use of administrative data to conduct population-based prevalence studies. To that end, we sought to assess the accuracy of diabetes International Classification of Diseases (ICD) coding in administrative databases among a cohort of confirmed NAFLD patients in Calgary, Alberta, Canada. METHODS: The Calgary NAFLD Pathway Database was linked to the following databases: Physician Claims, Discharge Abstract Database, National Ambulatory Care Reporting System, Pharmaceutical Information Network database, Laboratory, and Electronic Medical Records. Hemoglobin A1c and diabetes medication details were used to classify diabetes groups into absent, prediabetes, meeting glycemic targets, and not meeting glycemic targets. The performance of ICD codes among these groups was compared to this standard. Within each group, the total numbers of true positives, false positives, false negatives, and true negatives were calculated. Descriptive statistics and bivariate analysis were conducted on identified covariates, including demographics and types of interacted physicians. RESULTS: A total of 12,012 NAFLD patients were registered through the Calgary NAFLD Pathway Database and 100% were successfully linked to the administrative databases. Overall, diabetes coding showed a sensitivity of 0.81 and a positive predictive value of 0.87. False negative rates in the absent and not meeting glycemic control groups were 4.5% and 6.4%, respectively, whereas the meeting glycemic control group had a 42.2% coding error. Visits to primary and outpatient services were associated with most encounters. CONCLUSION: Diabetes ICD coding in administrative databases can accurately detect true diabetic cases. However, patients with diabetes who meets glycemic control targets are less likely to be coded in administrative databases. A detailed understanding of the clinical context will require additional data linkage from primary care settings.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Comorbilidad , Alta del Paciente , Alberta/epidemiologíaRESUMEN
BACKGROUND: Lower doses of irradiation (≤ 5 Mrad) during the manufacture of highly crosslinked polyethylene acetabular liners may result in less crosslinking and an increased wear rate. Radiostereometric analysis (RSA) studies have found that wear of more highly irradiated highly crosslinked polyethylene liners (7 to 10 Mrad) decreases at longer-term follow-up compared with earlier reports of the same cohorts. Although wear of 5-Mrad irradiated liners appears to increase at midterm follow-up, it is unclear whether that remains true at longer follow-up. QUESTIONS/PURPOSES: We asked: (1) In patients who underwent THA with a 5-Mrad highly crosslinked polyethylene liner, what is the wear rate evaluated with RSA during the first 14 years? (2) Does the wear rate decrease after 6 years in situ? METHODS: This is a brief follow-up of prior RSA studies performed at 2 and 6 years. We prospectively reviewed the longer-term wear rate in 13 patients who underwent primary THAs with the same design of a 5-MRad irradiated crosslinked acetabular liner and a 28-mm cobalt-chromium articulation. Of the initial 30 patients who were enrolled, 13 (43%) were available at the 14-year timepoint; nine patients had died, 1 patient had withdrawn, 1 had an intraoperative fracture, 3 patients were too infirm to have radiographs, 2 had no baseline RSA radiographs, and 1 had poor-quality RSA images. Tantalum markers were inserted during surgery, and all patients had RSA radiographic examinations at 1 week, 6 months, and 1, 2, 6, and 14 years postoperatively. RESULTS: The mean ± standard deviation proximal, 2D, and 3D wear rates calculated between 1 year and 14 years were 0.019 ± 0.013 mm, 0.022 ± 0.015 mm, and 0.025 ± 0.019 mm per year, respectively. No patient had proximal 2D or 3D wear rates exceeding 0.06 mm per year. An increasing wear rate over time was measured for proximal and 2D wear rates between 6 and 14 years (0.024 and 0.030 mm per year) compared with that between 1 and 6 years (0.008 and 0.010 mm per year; p = 0.03). CONCLUSION: The proximal, 2D, and 3D wear of a highly crosslinked polyethylene liner produced using 5-Mrad radiation remains low in the longer-term. With the small numbers available in a long-term RSA study such as this, we confirmed that the wear rate did not decrease at longer-term follow-up, unlike previous RSA studies of more highly irradiated highly crosslinked polyethylene liners. Nevertheless, the wear rate remains very low and below the threshold typically associated with the development of osteolysis (0.1 mm/year of wear). This should provide assurance to orthopaedic surgeons monitoring patients with this 5-Mrad irradiated liner in situ, while providing useful information to manufacturers of future highly crosslinked polyethylene liners. LEVEL OF EVIDENCE: Level IV therapeutic study.
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ABO-incompatible (ABOi) heart transplantation (HT) has increased organ availability for infants with end-stage heart failure. Despite increasing adoption of ABOi listing for HT, data remain limited regarding pre- and post-HT immunologic profiles to guide listing practices and post-HT follow-up. Thus, the purpose of this study was to evaluate post-HT outcomes at a single center employing inclusive ABOi listing irrespective of pre-HT isohemagglutinin titers. All HT recipients listed at less than 24 months of age at our institution from 2010-2020 were included. Pre- and post-operative variables were compared for ABOi and ABO-compatible (ABOc) recipients. Separate iso-IgG and iso-IgM titers were monitored pre- and post-HT. Primary outcomes were compared between ABOi versus ABOc groups at mid-term follow-up. 51 HTs were performed on 50 patients from 2010-2020 (ABOi, N = 13; ABOc, N = 38). Six ABOi recipients received intra-operative plasma exchange for elevated titers (greater than 1:8 for IgG or IgM or reverse type greater than 2 +). Treated rejection, DSA, CAV, primary graft failure, need for re-HT, and survival were comparable between ABOi and ABOc groups at mid-term follow-up. An inclusive approach to ABOi HT listing for infants less than 24 months of age results in comparable post-transplant rejection-free survival, CAV, and prevalence of DSA at mid-term follow-up. These data define a potential role for specific IgM and IgG testing to promote understanding of risk stratification in pediatric ABOi listing, and support an inclusive strategy irrespective of high pre-HT titers to expand the number of available donor hearts for infants and older children awaiting HT.
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We present the coupled oscillator: A new mechanism for signal amplification with widespread application in metrology. We introduce the mechanical theory of this framework and support it by way of simulations. We present a particular implementation of coupled oscillators: A microelectromechanical system (MEMS) that uses one large (â¼100mm) N52 magnet coupled magnetically to a small (â¼0.25mm), oscillating N52 magnet, providing a force resolution of 200zN measured over 1s in a noiseless environment. We show that the same system is able to resolve magnetic gradients of 130aT/cm at a single point (within 500µm). This technology, therefore, has the potential to revolutionize force and magnetic gradient sensing, including high-impact areas such cardiac and brain imaging.
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PURPOSE: To determine the occult nodal disease rate and whether elective regional lymph node dissection (RLND) confers any 10-year overall survival (OS) in cN0 intermediate-grade mucoepidermoid carcinoma (MEC) of the parotid gland. MATERIALS & METHODS: The National Cancer Database was reviewed from 2004 to 2016 on adults with cT1-4aN0M0 intermediate-grade parotid MEC undergoing resection with/without RLND. Comparisons between patients with and without RLND were made. Occult nodal rate and 10-year overall survival (OS) were determined. RESULTS: Out of 898 included patients with cN0 intermediate grade parotid MEC undergoing elective RLND, the occult nodal rate was 7.6%. This was significantly different from low-grade (3.9%) and high-grade (25.7%) cN0 disease. When stratified by pT-classification, marginal differences were identified between low-grade and intermediate-grade tumors, whereas high-grade tumors demonstrated increased occult nodal disease with low T-stage (pT1-pT2, 20.4% vs. 5.1%) and high T-stage (pT3-pT4a, 32.1% vs. 17.6%). Patients undergoing elective RLND were more often treated at an academic facility (53.8% vs. 41.2%), had higher pT3-pT4 tumors (19.2% vs. 10.4%), and more frequently underwent total/radical parotidectomy (46.0% vs. 29.9%) with adjuvant radiation therapy (53.8% vs. 41.0%) Cox-proportional hazard modeling did not identify RLND, regardless if stratified by nodal yield or pT-classification, nor nodal positivity as significant predictors of 10-year OS. CONCLUSIONS: The occult nodal disease in intermediate-grade parotid MEC is low and similar to low-grade. Elective RLND may have a limited impact on OS, though its effect on locoregional control remains unknown. LEVEL OF EVIDENCE: III.
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Carcinoma Mucoepidermoide , Procedimientos Quirúrgicos Electivos , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Neoplasias de la Parótida , Humanos , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/cirugía , Carcinoma Mucoepidermoide/mortalidad , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/cirugía , Neoplasias de la Parótida/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Clasificación del Tumor , Anciano , Tasa de Supervivencia , Metástasis Linfática , Glándula Parótida/cirugía , Glándula Parótida/patología , Estudios Retrospectivos , Bases de Datos FactualesRESUMEN
Mobile cardiovascular prevention interventions are still uncommon in Switzerland. Mobile clinics improve access to prevention and enable new diagnoses of hypertension or hypercholesterolemia to be identified in a cost-effective way and has shown benefits in health behaviors such as physical activity, smoking cessation and medication compliance. The Unisanté Bus Santé is a mobile clinic run by nurses that offers screening for cardiovascular risk factors, health advice and, if necessary, referral to medical care. Mobile health initiatives such as the Bus Santé could play a more important role in the Swiss healthcare system, bringing personalized preventive care closer to the population.
Les interventions mobiles de promotion de la santé et de prévention sont encore peu fréquentes en Suisse. Elles permettent pourtant, par exemple, l'identification de nouveaux diagnostics d'hypertension ou d'hypercholestérolémie avec un rapport coût-efficacité favorable et ont également montré des bénéfices sur les comportements de santé comme l'activité physique, le sevrage tabagique et l'observance médicamenteuse. Le Bus santé d'Unisanté est une clinique mobile gérée par des infirmières proposant un dépistage des facteurs de risque cardiovasculaire, des conseils de santé et, si nécessaire, une orientation vers des soins médicaux. Ces interventions mobiles pourraient jouer un rôle plus important dans le système de santé suisse en amenant une offre de prévention personnalisée au plus proche de la population.
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Hipertensión , Humanos , Suiza , Hipertensión/diagnóstico , Hipertensión/epidemiología , Etnicidad , Ejercicio Físico , Conductas Relacionadas con la SaludRESUMEN
BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.
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Leucemia Linfocítica Crónica de Células B , Leucemia , Neoplasias Inducidas por Radiación , Exposición a la Radiación , Humanos , Factores de Riesgo , Leucemia/epidemiología , Exposición a la Radiación/efectos adversos , Incidencia , Radiación Ionizante , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Dosis de RadiaciónRESUMEN
OBJECTIVES: To develop a transferable process, CATALYST (challenging antibiotic allergystatus), to assess and challenge penicillin allergy status of inpatients within an NHS Foundation Hospital. METHODS: A multidisciplinary team (MDT) steering group reviewed existing literature and protocols enabling penicillin allergy assessment, challenge and de-labelling. Using this, they identified five key steps forming the basis of CATALYST: clinical assessment of the nature of allergy; inclusion/exclusion criteria; consent; direct oral penicillin challenge; and removal of allergy label. A pharmacist-led pilot was conducted to assess the process, during which a continuous PDSA (plan-do-study-act) cycle was observed. This included formally auditing endpoint data such as accuracy of allergy status in medical records post-intervention. RESULTS: CATALYST was successfully developed with key resources produced to support clinicians. It was piloted in 304 patients, with 172 patients excluded and 132 successful allergy challenges. There was one incident of an adverse event (acute kidney injury) in the 132 successful patients, which occurred as a delayed reaction following 22 days of penicillin therapy. Only 64% of permanent records (held by GP) were appropriately updated when audited at the end of the pilot. CONCLUSIONS: CATALYST is a transferable process to facilitate safe assessment, challenge and removal of spurious penicillin allergy labels. Handover between care sectors forms a key element of allergy removal to ensure all records are updated and work is needed to ensure this process is done effectively.
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Hipersensibilidad a las Drogas , Hipersensibilidad , Humanos , Antibacterianos/efectos adversos , Penicilinas/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Registros MédicosRESUMEN
RATIONALE & OBJECTIVE: Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies. STUDY DESIGN: A modified Delphi process following guidelines for conducting and reporting Delphi studies. SETTING & PARTICIPANTS: An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by 3 sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow the participants to provide their input and rapidly prioritize and refine ideas. OUTCOME: Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as >75% agreement. ANALYTICAL APPROACH: Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants. RESULTS: The final panel included 26 clinician participants from 4 countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: 5 regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; 6 regarding signs that should prompt urgent contact with a health care provider (including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever); and 14 related to scenarios and strategies for patient self-management (including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent hypoglycemia). There was consensus that renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, sodium/glucose cotransporter 2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10%-20% if blood glucose was elevated. There was consensus on 6 recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking. LIMITATIONS: Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings. CONCLUSIONS: A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Hipoglucemia , Insulinas , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Glucemia , Consenso , Automonitorización de la Glucosa Sanguínea , Ausencia por Enfermedad , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipovolemia , Riñón , Técnica DelphiRESUMEN
This study examined the individual and joint effects of modifiable risk factors mediating the associations between socioeconomic position (SEP) and morbidity and mortality from cardiovascular diseases (CVD) in a nationally representative sample of adults in Canada. Participants in the Canadian Community Health Survey (n = 289,800) were followed longitudinally for CVD morbidity and mortality using administrative health and mortality data. SEP was measured as a latent variable consisting of household income and individual educational attainment. Mediators included smoking, physical inactivity, obesity, diabetes and hypertension. The primary outcome was CVD morbidity and mortality, defined as the first fatal/nonfatal CVD event during follow-up (median 6.2 years). Generalized structural equation modeling tested the mediating effects of modifiable risk factors in associations between SEP and CVD in the total population and stratified by sex. Lower SEP was associated with 2.5 times increased odds of CVD morbidity and mortality (OR: 2.52, 95% CI: 2.28, 2.76). Modifiable risk factors mediated 74% of associations between SEP and CVD morbidity and mortality in the total population and were more important mediators of associations in females (83%) than males (62%). Smoking mediated these associations independently and jointly with other mediators. The mediating effects of physical inactivity were through joint mediating effects with obesity, diabetes or hypertension. There were additional joint mediating effects of obesity through diabetes or hypertension in females. Findings point to modifiable risk factors as important targets for interventions along with interventions that target structural determinants of health to reduce socioeconomic inequities in CVD.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Hipertensión , Adulto , Masculino , Femenino , Humanos , Factores Socioeconómicos , Estudios de Cohortes , Canadá/epidemiología , Factores de Riesgo , Hipertensión/epidemiología , Obesidad/epidemiología , Obesidad/complicaciones , Diabetes Mellitus/epidemiología , MorbilidadRESUMEN
BACKGROUND: The challenges presented by multimorbidity continue to rise in the United States. Little is known about how the relative contribution of individual chronic conditions to multimorbidity has changed over time, and how this varies by race/ethnicity. The objective of this study was to describe trends in multimorbidity by race/ethnicity, as well as to determine the differential contribution of individual chronic conditions to multimorbidity in hospitalized populations over a 20-year period within the United States. METHODS: This is a serial cross-sectional study using the Nationwide Inpatient Sample (NIS) from 1993 to 2012. We identified all hospitalized patients aged ≥ 18 years old with available data on race/ethnicity. Multimorbidity was defined as the presence of 3 or more conditions based on the Elixhauser comorbidity index. The relative change in the proportion of hospitalized patients with multimorbidity, overall and by race/ethnicity (Black, White, Hispanic, Asian/Pacific Islander, Native American) were tabulated and presented graphically. Population attributable fractions were estimated from modified Poisson regression models adjusted for sex, age, and insurance type. These fractions were used to describe the relative contribution of individual chronic conditions to multimorbidity over time and across racial/ethnic groups. RESULTS: There were 123,613,970 hospitalizations captured within the NIS between 1993 and 2012. The prevalence of multimorbidity increased in all race/ethnic groups over the 20-year period, most notably among White, Black, and Native American populations (+ 29.4%, + 29.7%, and + 32.0%, respectively). In both 1993 and 2012, Black hospitalized patients had a higher prevalence of multimorbidity (25.1% and 54.8%, respectively) compared to all other race/ethnic groups. Native American populations exhibited the largest overall increase in multimorbidity (+ 32.0%). Furthermore, the contribution of metabolic diseases to multimorbidity increased, particularly among Hispanic patients who had the highest population attributable fraction values for diabetes without complications (15.0%), diabetes with complications (5.1%), and obesity (5.8%). CONCLUSIONS: From 1993 to 2012, the secular increases in the prevalence of multimorbidity as well as changes in the differential contribution of individual chronic conditions has varied substantially by race/ethnicity. These findings further elucidate the racial/ethnic gaps prevalent in multimorbidity within the United States. PRIOR PRESENTATIONS: Preliminary finding of this study were presented at the Society of General Internal Medicine (SGIM) Annual Conference, Washington, DC, April 21, 2017.