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The combined use of immune checkpoint inhibitors and tyrosine kinase inhibitors (ICI/TKI) is an effective treatment strategy for some cancers. A better understanding of the potential additive toxicity for ICI/TKI combinations is needed to inform patient and provider treatment decisions. We aim to evaluate the safety of ICI/TKI combinations for individuals with renal cell or endometrial carcinoma. This rapid systematic review (SR) protocol follows PRISMA guidelines. A systematic search will be designed, peer reviewed and executed by experienced information specialists (Cochrane Central, MEDLINE, Embase) to identify published SRs and primary studies published since the most recent SR search. Randomized, quasi- or non-randomized controlled trials and comparative cohort studies are eligible if they compare ICI/TKI combinations to monotherapy or standard of care in participants with renal cell or endometrial carcinoma. The primary outcome is grade ≥ 3 treatment-related adverse-effects. Studies will be screened, selected, extracted and assessed for risk of bias by a single reviewer and checked completely by a second. Where feasible and appropriate, we will pool studies separately by design and indication using meta-analysis and test robustness of effects using prespecified subgroup and sensitivity analyses. Results will be summarized descriptively and presented in tables and figures. (PROSPERO ID: CRD42023416388).â¢This will be a comprehensive systematic review of the additive toxicity arising from the combined use of ICI/TKIs in patients with renal-cell or endometrial carcinoma.â¢We will consider treatment-related, treatment-emergent adverse events (Grade 3 or higher).â¢Identified safety profile may be used to inform patient or provider treatment decisions.
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The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).
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Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Ticagrelor/uso terapêutico , Aspirina/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Ponte de Artéria Coronária/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: Positron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. OBJECTIVES: The authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. METHODS: Adults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. RESULTS: A total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: -6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = -0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. CONCLUSIONS: The 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786).
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BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.
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Arterite , Aterosclerose , Diabetes Mellitus Tipo 2 , Ataque Isquêmico Transitório , Estado Pré-Diabético , Acidente Vascular Cerebral , Humanos , Fluordesoxiglucose F18 , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Compostos Radiofarmacêuticos , Proteína C-Reativa , Estudos Prospectivos , Interleucina-6 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Canadá , Aterosclerose/tratamento farmacológico , Tomografia Computadorizada por Raios X , Inflamação/tratamento farmacológico , Biomarcadores , Anti-Inflamatórios/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Frailty has emerged as an important prognostic marker of increased mortality after cardiac surgery, but its association with quality of life (QoL) and patient-centered outcomes is not fully understood. We sought to evaluate the association between frailty and such outcomes in older patients undergoing cardiac surgery. METHODS: This systematic review included studies evaluating the effect of preoperative frailty on QoL outcomes after cardiac surgery amongst patients 65 years and older. The primary outcome was patient's perceived change in QoL following cardiac surgery. Secondary outcomes included residing in a long-term care facility for 1 year, readmission in the year following the intervention, and discharge destination. Screening, inclusion, data extraction, and quality assessment were performed independently by two reviewers. Meta-analyses based on the random-effects model were conducted. The evidential quality of findings was assessed with the GRADE profiler. RESULTS: After the identification of 3105 studies, 10 observational studies were included (1580 patients) in the analysis. Two studies reported on the change in QoL following cardiac surgery, which was higher for patients with frailty than for patients without. Preoperative frailty was associated with both hospital readmission (pooled odds ratio [OR] 1.48 [0.80-2.74], low GRADE level) as well as non-home discharge (pooled OR 3.02 [1.57-5.82], moderate GRADE level). CONCLUSION: While evidence in this field is limited by heterogeneity of frailty assessment and non-randomized data, we demonstrated that baseline frailty may possibly be associated with improved QoL, but with increased readmission as well as discharge to a non-home destination following cardiac surgery. These patient-centered outcomes are important factors when considering interventional options for older patients. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).
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Procedimentos Cirúrgicos Cardíacos , Fragilidade , Humanos , Idoso , Fragilidade/diagnóstico , Qualidade de Vida , Readmissão do Paciente , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Background For patients with atrial fibrillation seen in the emergency department (ED) following a transient ischemic attack (TIA) or minor stroke, the impact of initiating oral anticoagulation immediately rather than deferring the decision to outpatient follow-up is unknown. Methods and Results We conducted a planned secondary data analysis of a prospective cohort of 11 507 adults in 13 Canadian EDs between 2006 and 2018. Patients were eligible if they were aged 18 years or older, with a final diagnosis of TIA or minor stroke with previously documented or newly diagnosed atrial fibrillation. The primary outcome was subsequent stroke, recurrent TIA, or all-cause mortality within 90 days of the index TIA diagnosis. Secondary outcomes included stroke, recurrent TIA, or death and rates of major bleeding. Of 11 507 subjects with TIA/minor stroke, atrial fibrillation was identified in 11.2% (1286, mean age, 77.3 [SD 11.1] years, 52.4% male). Over half (699; 54.4%) were already taking anticoagulation, 89 (6.9%) were newly prescribed anticoagulation in the ED. By 90 days, 4.0% of the atrial fibrillation cohort had experienced a subsequent stroke, 6.5% subsequent TIA, and 2.6% died. Results of a multivariable logistic regression indicate no association between prescribed anticoagulation in the ED and these 90-day outcomes (composite odds ratio, 1.37 [95% CI, 0.74-2.52]). Major bleeding was found in 5 patients, none of whom were in the ED-initiated anticoagulation group. Conclusions Initiating oral anticoagulation in the ED following new TIA was not associated with lower recurrence rates of neurovascular events or all-cause mortality in patients with atrial fibrillation.
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Fibrilação Atrial , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Masculino , Idoso , Feminino , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/prevenção & controle , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Estudos Prospectivos , Canadá/epidemiologia , Recidiva Local de Neoplasia/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Anticoagulantes/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: Computed tomography (CT) findings of acute and chronic ischemia are associated with subsequent stroke risk in patients with transient ischemic attack. We sought to validate these associations in a large prospective cohort of patients with transient ischemic attack or minor stroke. METHODS: This prospective cohort study enrolled emergency department patients from 13 hospitals with transient ischemic attack who had CT imaging. Primary outcome was stroke within 90 days. Secondary outcomes were stroke within 2 or 7 days. CT findings were abstracted from radiology reports and classified for the presence of acute ischemia, chronic ischemia, or microangiopathy. Multivariable logistic regression was used to test associations with primary and secondary end points. RESULTS: From 8670 prospectively enrolled patients between May 2010 and May 2017, 8382 had a CT within 24 hours. From this total population, 4547 (54%) patients had evidence of acute ischemia, chronic ischemia, or microangiopathy on CT, of whom 175 had a subsequent stroke within 90 days (3.8% subsequent stroke rate; adjusted odds ratio [aOR], 2.33 [95% CI, 1.62-3.36]). This was in comparison to those with CT imaging without ischemia. Findings associated with an increased risk of stroke at 90 days were isolated acute ischemia (6.0%; aOR, 2.42 [95% CI, 1.03-5.66]), acute ischemia with microangiopathy (10.7%; aOR, 3.34 [95% CI, 1.57-7.14]), chronic ischemia with microangiopathy (5.2%; aOR, 1.83 [95% CI, 1.34-2.50]), and acute ischemia with chronic ischemia and microangiopathy (10.9%; aOR, 3.49 [95% CI, 1.54-7.91]). Acute ischemia with chronic ischemia and microangiopathy were most strongly associated with subsequent stroke within 2 days (aOR, 4.36 [95% CI, 1.31-14.54]) and 7 days (aOR, 4.50 [95% CI, 1.73-11.69]). CONCLUSIONS: In patients with transient ischemic attack or minor stroke, CT evidence of acute ischemia with chronic ischemia or microangiopathy significantly increases the risk of subsequent stroke within 90 days of index visit. The combination of all 3 findings results in the greatest early risk.
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Isquemia Encefálica , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/complicações , Estudos Prospectivos , Recidiva Local de Neoplasia/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/complicações , Tomografia Computadorizada por Raios X/efeitos adversos , Isquemia/complicaçõesRESUMO
AIM: The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). METHODS AND RESULTS: Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: - .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. CONCLUSION: In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Fluordesoxiglucose F18/uso terapêutico , Estudos Prospectivos , Tomografia por Emissão de Pósitrons , Psoríase/diagnóstico por imagem , Psoríase/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Inflamação/diagnóstico por imagem , Anti-Inflamatórios/uso terapêuticoRESUMO
Anammox-based nitrogen removal and enhanced biological phosphorus removal (EBPR) are increasingly applied for nutrient removal from wastewater, but are typically operated in separate reactors. Here, a novel process for integrated partial nitritation/anammox (PN/A) and EBPR in a single reactor employing integrated fixed film activated sludge was tested. The reactor was fed with mainstream municipal wastewater (5.4 ± 1.3 g COD/g N) at 20 °C for 243 days. Robust ammonium, total inorganic nitrogen, and orthophosphate removal efficiencies of 94 ± 4 %, 87 ± 7 % and 92 ± 7 % were achieved. Nitrite-oxidizing organisms suppression and ammonia-oxidizing organisms retention were achieved via solids retention time control, intermittent aeration, and suspended versus attached biomass population segregation. The contribution of anammox to nitrogen removal increased from 24 % to 74 %. In parallel, a substantial enrichment of Tetrasphaera polyphosphate accumulating organisms was observed. This work demonstrates a novel intensified bioprocess coupling PN/A and EBPR in the same reactor for efficient nutrient removal from wastewater.
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Compostos de Amônio , Águas Residuárias , Fósforo , Oxidação Anaeróbia da Amônia , Oxirredução , Esgotos , Reatores Biológicos , Nitrogênio , DesnitrificaçãoRESUMO
BACKGROUND: Dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, optimal duration remains uncertain in some situations. We assessed the benefits and harms of extending DAPT beyond 1 year after PCI in clinically important patient subgroups. METHODS: We conducted a systematic review and meta-analysis. We searched electronic databases (Embase, MEDLINE, PubMed, Cochrane Library) and grey literature (from inception to Nov. 5, 2021) and included randomized controlled trials (RCTs) of extended DAPT (> 12 mo) compared with DAPT for 6-12 months following PCI with stenting. The primary outcome was death (all cause, cardiovascular, noncardiovascular); secondary outcomes included major adverse cardiovascular and cerebrovascular events, myocardial infarction (MI), stroke, stent thrombosis and bleeding. Subgroups were based on prespecified patient characteristics (prior MI, acute coronary syndrome [ACS], diabetes mellitus, age, smoking status). Data were analyzed by random-effects pairwise meta-analysis. RESULTS: We identified 9 RCTs that provided subgroup data. We found that extended DAPT reduced the risk of MI and stent thrombosis but increased the risk of bleeding, compared with standard DAPT, with no difference in the risk of all-cause death (relative risk [RR] 1.07, 95% confidence interval [CI] 0.80-1.42) or cardiovascular death (RR 0.98, 95% CI 0.74-1.30). We found that patients with a prior MI, with ACS at presentation, without diabetes or aged younger than 75 years may derive the most benefit from extended DAPT. Among patients who received extended DAPT, the risk of all-cause death was significantly increased among those with no prior MI (RR 1.64, 95% CI 1.08-2.24), whereas there was no significant difference in the risk of all-cause death between standard and extended DAPT for patients with ACS (RR 1.20, 95% CI 0.51-2.83), with diabetes (RR 1.27, 95% CI 0.86-1.89), aged older than 75 years (RR 1.32, 95% CI 0.39-4.54) or who smoked (RR 0.90, 95% CI 0.42-1.92). Similar results were found for cardiovascular death, where data were available. INTERPRETATION: Patients with a previous MI with ACS at presentation, without diabetes, or aged younger than 75 years may derive the most benefit from extended DAPT. These findings support the need for careful selection of patients who may benefit most from extended DAPT. STUDY REGISTRATION: PROSPERO no. CRD42018082587.
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Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombose , Humanos , Idoso , Inibidores da Agregação Plaquetária/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Hemorragia/induzido quimicamente , Trombose/induzido quimicamente , Intervenção Coronária Percutânea/métodosRESUMO
BACKGROUND: Arm restriction after cardiac implantable electronic device (CIED) placement is common practice despite minimal supporting evidence. Patients receive a range of restriction recommendations of variable durations with the goal of reducing complications such as wound dehiscence, infection, lead dislodgement, or hematoma formation. These movement limitations can lead to emotional stress and anxiety, complications such as frozen shoulder, and upper extremity venous thrombosis due to immobilization. There are no published clinical trials assessing the benefits and risks of arm restrictions post-CIED implant. OBJECTIVES: The randomized trial of lenient vs strict arm and activity instruction post-CIED surgery (LENIENT trial; NCT04915261) is a single center nonblinded randomized prospective study designed to evaluate lenient compared to restrictive post-CIED care instructions. We hypothesize that there will be no significant difference in complications between the arms. METHODS/DESIGN: All patients receiving a de novo CIED or those with upgrades and revisions requiring a new lead implant will be enrolled. Subjects are enrolled in a nonblinded randomized prospective trial with 6 randomly assigned 8-month periods, during which either a lenient or restrictive postoperative activity instructions will be given to all patients. Postoperative instructions are given at the time of discharge and further reinforced by recurrent interactive voice recognition (IVR) phone calls, text messages and emails. The requirement for individual consent has been waived. The primary end point is a composite of (1) lead dislodgement, (2) frozen shoulder, (3) upper extremity venous thrombosis, (4) clinically significant hematoma, and (5) infection occurring within 52 weeks of index surgery. The study is a noninferiority trial with a sample size of 1,250 per group. DISCUSSION: This is the first large randomized clinical trial designed to establish an evidence-based postoperative standard of care for patients undergoing CIED implantation. This will improve the quality of care provided to patients and help guide implanting physicians providing postoperative care instructions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915261.
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Desfibriladores Implantáveis , Trombose Venosa , Humanos , Estudos Prospectivos , Braço , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
Water resource recovery facilities are faced with stringent effluent phosphorus limits to reduce nutrient pollution. Enhanced biological phosphorus removal (EBPR) is the most common biological route to remove phosphorus; however, many facilities struggle to achieve consistent performance due to limited carbon availability in the influent wastewater. A promising process to improve carbon availability is through return activated sludge (RAS) fermentation via sidestream EBPR (S2EBPR). In this study, a full-scale S2EBPR pilot was operated with a sidestream plus carbon configuration (SSRC) at a carbon-limited facility. A model based on the pilot test was developed and calibrated in the SUMO platform and used to explore routes for improving orthophosphate (OP) effluent compliance. Modeling results showed that RAS diversion by itself was not sufficient to drive OP removal to permit limits of 1 mg L-1, therefore, other strategies were evaluated. Supplemental carbon addition of MicroC® at 1.90 L min-1 and controlling the phosphorus concentration below 3.5 mgP L-1 in the primary effluent (PE) proved to be valid supplemental strategies to achieve OP removal below 1 mg L-1 most of the time. In particular, the proposed supplemental carbon flow rate would result in an improvement of the rbCOD:P ratio from 17:1 to 26:1. The synergistic approach of RAS diversion and supplemental carbon addition increased the polyphosphate accumulating organisms (PAO) population while minimizing the supplemental carbon needed to achieve consistent phosphorus removal. Overall, this pilot and modeling study shows that joint strategies, including RAS diversion, carbon addition and PE control, can be effective to achieve optimal control of OP effluent.
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Fósforo , Águas Residuárias , Carbono , Reatores Biológicos , EsgotosRESUMO
BACKGROUND: Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation. METHODS: We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilization, and safety were collected. RESULTS: A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group. CONCLUSIONS: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).
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Antiarrítmicos , Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Humanos , Antiarrítmicos/efeitos adversos , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Criocirurgia/efeitos adversos , Criocirurgia/métodos , Recidiva , Taquicardia/etiologia , Resultado do Tratamento , Progressão da Doença , SeguimentosRESUMO
BACKGROUND: Transseptal puncture to achieve left atrial access is necessary for many cardiac procedures, including atrial fibrillation ablation. More recently, there has been an increasing need for left atrial access using large caliber sheaths, which increases risk of perforation associated with the initial advancement into the left atrium. We compared the effectiveness of a radiofrequency needle-based transseptal system versus conventional needle for transseptal access. METHODS: This prospective controlled trial randomized 161 patients with symptomatic paroxysmal atrial fibrillation undergoing cryoballoon pulmonary vein isolation to transseptal access with a commercially available transseptal system (radiofrequency needle plus stiff pigtail wire; RF + Pigtail group) versus conventional transseptal access (standard group). The primary outcome was time required for left atrial access. Secondary outcomes included failure of the assigned transseptal system, radiation exposure, and complications. RESULTS: The median transseptal puncture time was significantly shorter using the radiofrequency needle plus stiff pigtail wire transseptal system compared with conventional transseptal (840 ± 323 vs. 956 ± 407 s, P = 0.0489). Compared to conventional transseptal puncture, fewer transseptal attempts were required (1.0 ± 0.5 RF applications vs. 1.3 ± 0.8 mechanical punctures, P = 0.0123) and the fluoroscopy time was significantly shorter (72.0 [IQR 48.0, 129.0] vs. 93.0 [IQR 60.0, 171.0] s, P = 0.0490) with the radiofrequency needle plus stiff pigtail wire transseptal system. Failure to achieve transseptal LA access with the assigned system was rarely observed (1.3% vs. 5.7%, P = 0.2192). There were no procedural complications observed with either system. CONCLUSIONS: The use of a radiofrequency needle plus stiff pigtail wire resulted in shorter time to left atrial access and reduced fluoroscopy time compared to left atrial access using conventional transseptal equipment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03199703.
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Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Estudos Prospectivos , Punções , Resultado do TratamentoRESUMO
INTRODUCTION: There is emerging evidence supporting the use of the radial artery (RA) as a preferred secondary conduit for coronary artery bypass grafting (CABG) as it is associated with higher rates of graft patency at 5 years when compared with saphenous vein grafts (SVG). The modified Allen's test (MAT) is traditionally regarded as the standard of care in the assessment of ulnar artery (UA) patency prior to RA harvesting. Unfortunately, due to high false-positive rates, a substantial number of pre-CABG patients are found to have an abnormal MAT despite normal UA patency, resulting in inappropriate exclusion from RA harvesting. The SVG is generally used in its place when this occurs, resulting in potentially lower rates of long-term graft patency. METHODS AND ANALYSIS: The CAPITAL iRADIAL-CABG trial is currently enrolling participants 18 years of age or older undergoing CABG for whom the treating physician is considering the use of an RA conduit. Eligible patients will be randomised in a 1:1 fashion to MAT or smartphone-based photoplethysmography application assessment to assess collateral palmar circulation prior to RA harvesting. The primary outcome of the trial is the use of the RA as a conduit during CABG. The primary safety outcome is postoperative palmar ischaemia as determined by clinical assessment or requirement of vascular intervention. Secondary outcomes include vascular complications, early graft failure, need for rescue percutaneous coronary intervention during the index hospitalisation and a composite cardiovascular outcome of myocardial infarction, stroke and cardiovascular death prior to discharge from hospital. A total of 236 participants are planned to be recruited. ETHICS AND DISSEMINATION: The study was approved by the Ottawa Heart Science Network Research Ethics Board (approval number 20180865-01H). The study results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03810729.
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Artéria Radial , Smartphone , Adolescente , Adulto , Ponte de Artéria Coronária/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Frailty has emerged as an important prognostic marker of adverse outcomes after cardiac surgery, but evidence regarding its ability to predict quality of life after cardiac surgery is currently lacking. Whether frail patients derive the same quality of life benefit after cardiac surgery as patients without frailty remains unclear. METHODS: This systematic review will include interventional studies (RCT and others) and observational studies evaluating the effect of preoperative frailty on quality-of-life outcomes after cardiac surgery amongst patients 65 years and older. Studies will be retrieved from major databases including the Cochrane Central Register of Controlled Trials, Embase, and Medline. The primary exposure will be frailty status, independent of the tool used. The primary outcome will be change in quality of life, independent of the tool used. Secondary outcomes will include readmission during the year following the index intervention, discharge to a long-term care facility and living in a long-term care facility at one year. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Meta-analysis based on the random-effects model will be conducted to compare the outcomes between frail and non-frail patients. The evidential quality of the findings will be assessed with the GRADE profiler. CONCLUSION: The findings of this systematic review will be important to clinicians, patients and health policy-makers regarding the use of preoperative frailty as a screening and assessment tool before cardiac surgery. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).
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Qualidade de VidaRESUMO
Introduction: Immigrants to Western countries tend to have darker skin than native-born populations. We examined the relationship between skin melanin and serum vitamin D (vitD) [S-25(OH)D] levels and explored whether melanin levels explained S-25(OH)D variations between immigrants and native-born Canadians. This study offers novel findings as no such study has been conducted. Methods: We used a national cross-sectional population-based design with data from the Canadian Health Measures Survey (CHMS). Skin melanin levels among first-generation immigrants based on their ethnicity and origin/country of birth were compared with white and native-born populations. We assessed the association between S-25(OH)D and melanin after adjusting for independent variables related to S-25(OH)D, melanin level, and immigration status. Results: Of 11,579 participants, 21.9% were immigrants aged 3-79 years (mean age 39.23 years). Compared with non-immigrants, immigrants had lower S-25(OH)D levels (mean: 51.23 vs. 62.72; 95% CI: 8.37, 14.62; P < 0.001) but higher melanin levels (mean [SE]: 17.08 [0.25] vs. 16.29 [0.29]; 95% CI: -1.29, -0.281; P = 0.004). Melanin did not differ by length of stay in Canada but was weakly positively correlated (r = 0.088, P < 0.001) with S-25(OH)D. Sex (male), age (≥18 years), summer/fall seasons, sunlight exposure, sunscreen non-use, smoking, and alcohol consumption were associated with higher melanin levels, whereas indoor tanning use was not. Conclusion: Skin melanin levels were associated with sociodemographic and behavioral characteristics. Immigrants had higher melanin levels, but melanin did not differ by length of stay in Canada. The weak positive correlation between melanin and S-25(OH)D suggested confounding factors may impact the relationship between melanin levels, S-25(OH)D, and immigration status.
RESUMO
OBJECTIVES: Double arterial conduit use during coronary artery bypass grafting is associated with improved clinical outcomes compared with single arterial conduits in the general population. However, the sex-specific outcomes of this strategy remain unknown and are needed to inform sex-specific revascularization guidelines. METHODS: We conducted a population-based, retrospective cohort study of all Ontarians who underwent primary isolated coronary artery bypass grafting with single arterial conduits or double arterial conduits between October 2008 and September 2017. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events, defined as a composite of myocardial infarction, heart failure hospitalization, repeat revascularization, and stroke. We used inverse probability of treatment weighting to account for group imbalances. RESULTS: A total of 9135 women and 36,748 men underwent coronary artery bypass grafting. At 30 days, there was no between-group difference in mortality or major adverse cardiac and cerebrovascular events in men. However, among women, a double arterial conduit was associated with an increased rate of 30-day death (hazard ratio, 1.48; 95% confidence interval, 1.23-1.79) and major adverse cardiac and cerebrovascular events (hazard ratio, 1.32; 95% confidence interval, 1.14-1.51). The risk of medium-term mortality with double arterial conduits was less in men (hazard ratio, 0.88; 95% confidence interval, 0.84-0.92) and women (hazard ratio, 0.87; 95% confidence interval, 0.81-0.94), as was the medium-term risk of major adverse cardiac and cerebrovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87-0.94) [men]; hazard ratio, 0.91; 95% confidence interval, 0.86-0.97) [women]). The incremental improvement in 9-year survival was 4.0% in women with a double arterial conduit and 0.9% in men. CONCLUSIONS: Double arterial conduit is associated with better medium-term survival and cardiovascular outcomes in both sexes. Double arterial conduits are associated with increased perioperative risk in women, but the medium-term benefit is greater than in men.
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Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Idoso , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Systematic reviews are the cornerstone of evidence-based medicine. However, systematic reviews are time consuming and there is growing demand to produce evidence more quickly, while maintaining robust methods. In recent years, artificial intelligence and active-machine learning (AML) have been implemented into several SR software applications. As some of the barriers to adoption of new technologies are the challenges in set-up and how best to use these technologies, we have provided different situations and considerations for knowledge synthesis teams to consider when using artificial intelligence and AML for title and abstract screening. METHODS: We retrospectively evaluated the implementation and performance of AML across a set of ten historically completed systematic reviews. Based upon the findings from this work and in consideration of the barriers we have encountered and navigated during the past 24 months in using these tools prospectively in our research, we discussed and developed a series of practical recommendations for research teams to consider in seeking to implement AML tools for citation screening into their workflow. RESULTS: We developed a seven-step framework and provide guidance for when and how to integrate artificial intelligence and AML into the title and abstract screening process. Steps include: (1) Consulting with Knowledge user/Expert Panel; (2) Developing the search strategy; (3) Preparing your review team; (4) Preparing your database; (5) Building the initial training set; (6) Ongoing screening; and (7) Truncating screening. During Step 6 and/or 7, you may also choose to optimize your team, by shifting some members to other review stages (e.g., full-text screening, data extraction). CONCLUSION: Artificial intelligence and, more specifically, AML are well-developed tools for title and abstract screening and can be integrated into the screening process in several ways. Regardless of the method chosen, transparent reporting of these methods is critical for future studies evaluating artificial intelligence and AML.