Transcatheter aortic valve implantation (TAVI) has emerged as an important treatment for patients with severe symptomatic aortic stenosis who are at high operative risk, but accurate estimates of ...serious adverse effects in contemporary practice are not available.
To quantify the adverse effects associated with TAVI, and to evaluate whether the type of transcatheter valve and the route of valve implantation are associated with differences in adverse outcomes.
PubMed to 5 May 2012.
All studies that included at least 100 patients who had TAVI and reported at least 1 outcome of interest.
Two reviewers abstracted the data independently. A random-effects model was used to combine data on adverse outcomes and conduct stratified analyses.
A total of 49 studies enrolling 16 063 patients met the inclusion criteria. Overall 30-day and 1-year survival after TAVI were 91.9% (95% CI, 91.1% to 92.8%) and 79.2% (CI, 76.9% to 81.4%), respectively. Heart block requiring permanent pacemaker implantation was the most common adverse outcome (13.1%) and was 5 times more common with the CoreValve (Medtronic, Minneapolis, Minnesota) than the Sapien valve (Edwards Lifesciences, Irving, California) implanted using the transarterial route (25.2% vs. 5.0%, respectively). The overall rate of vascular complications was 10.4% and was highest with transarterial implantation of the Sapien valve (22.3%). Acute renal failure requiring renal replacement therapy was the third most common complication, occurring in 4.9% of patients.
Rates of major vascular complications may be overestimated owing to rapidly evolving TAVI technology.
The most common adverse effects associated with TAVI are heart block, vascular complications, and renal failure. The type of transcatheter valve and the route of implantation are associated with observed variations in the risks for some adverse effects.
Heart and Stroke Foundation of Canada.
Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to ...method of cancer detection is unknown.
We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age.
As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval CI, 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram.
Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.
Background
Although increasing evidence has suggested that an efficacy‐effectiveness gap exists between clinical trial (CT) and real‐world evidence (RWE), to the authors' knowledge, the magnitude of ...this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies.
Methods
Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population‐based databases. The efficacy‐effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1‐year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan‐Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates.
Results
Twenty‐nine indications from 20 systemic therapies were included. Twenty‐eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0‐12.1 months). Lower effectiveness in RWE also was demonstrated through a meta‐analysis of an OS hazard ratio of 1.58 (95% CI, 1.39‐1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%‐22%).
Conclusions
An efficacy‐effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2‐month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real‐world decision making regarding the use of cancer systemic therapies.
Through a review of clinical trial and real‐world evidence for contemporary cancer systemic therapies, an efficacy‐effectiveness gap has been demonstrated. Thus, supportive evidence is provided in the current study for the further investigation of real‐world outcomes of patients to inform real‐world decision making.
Objectives The study assessed the appropriateness of coronary revascularization in Ontario, Canada, and examined its association with longer-term outcomes. Background Although appropriate use ...criteria for coronary revascularization have been developed to improve the rational use of cardiac invasive procedures, it is unknown whether greater adherence to appropriateness guidelines is associated with improved clinical outcomes in stable coronary artery disease. Methods A population-based cohort of stable patients undergoing cardiac catheterization was assembled from April 1, 2006, to March 31, 2007. The appropriateness for coronary revascularization at the time of coronary angiography was retrospectively adjudicated using the appropriate use criteria. Clinical outcomes between coronary revascularization and medical treatment without revascularization, stratified by appropriateness categories, were compared. Results In 1,625 patients with stable coronary artery disease, percutaneous coronary intervention or coronary artery bypass grafting was only performed in 69% who had an appropriate indication for coronary revascularization. Coronary revascularization was associated with a lower adjusted hazard of death or acute coronary syndrome (hazard ratio HR: 0.61; 95% confidence interval CI: 0.42 to 0.88) at 3 years compared with medical therapy in appropriate patients. The rate of coronary revascularization was 54% in the uncertain category and 45% in the inappropriate category. No significant difference in death or acute coronary syndrome between coronary revascularization and no revascularization in the uncertain category (HR: 0.57; 95% CI: 0.28 to 1.16) and the inappropriate category (HR: 0.99; 95% CI: 0.48 to 2.02) was observed. Conclusions Using the appropriateness use criteria, we identified substantial underutilization and overutilization of coronary revascularization in contemporary clinical practice. Underutilization of coronary revascularization is associated with significantly increased risks of adverse outcomes in patients with appropriate indications.
Heart failure is a leading cause of admission to hospital, but whether the incidence of heart failure is increasing or decreasing is uncertain. We examined temporal trends in the incidence and ...outcomes of heart failure in Ontario, Canada.
Using population-based administrative databases of hospital discharge abstracts and physician health insurance claims, we identified 419 551 incident cases of heart failure in Ontario between Apr. 1, 1997, and Mar. 31, 2008. All patients were classified as either inpatients or outpatients based on the patient's location at the time of the initial diagnosis. We tracked subsequent outcomes through linked administrative databases.
The age- and sex-standardized incidence of heart failure decreased 32.7% from 454.7 per 100 000 people in 1997 to 306.1 per 100 000 people in 2007 (p < 0.001). A comparable decrease in incidence occurred in both inpatient and outpatient settings. The greatest relative decrease occurred in patients aged 85 and over. Over the study period, 1-year risk-adjusted mortality decreased from 17.7% in 1997 to 16.2% in 2007 (p = 0.02) for outpatients, with a nonsignificant decrease from 35.7% in 1997 to 33.8% in 2007 (p = 0.1) for inpatients.
The incidence of heart failure decreased substantially during the study period. Nevertheless, the prognosis for patients with heart failure remains poor and is associated with high mortality.
Due to the unprecedented public health crisis caused by COVID-19, our first contribution to the newly launching journal, Advances in Biomarker Sciences and Technology, has abruptly diverted to focus ...on the current pandemic. As the number of new COVID-19 cases and deaths continue to rise steadily around the world, the common goal of healthcare providers, scientists, and government officials worldwide has been to identify the best way to detect the novel coronavirus, named SARS-CoV-2, and to treat the viral infection – COVID-19. Accurate detection, timely diagnosis, effective treatment, and future prevention are the vital keys to management of COVID-19, and can help curb the viral spread. Traditionally, biomarkers play a pivotal role in the early detection of disease etiology, diagnosis, treatment and prognosis. To assist myriad ongoing investigations and innovations, we developed this current article to overview known and emerging biomarkers for SARS-CoV-2 detection, COVID-19 diagnostics, treatment and prognosis, and ongoing work to identify and develop more biomarkers for new drugs and vaccines. Moreover, biomarkers of socio-psychological stress, the high-technology quest for new virtual drug screening, and digital applications are described.
Abstract Objective With the increasing use of electronic medical records (EMRs) comes the potential to efficiently evaluate and improve quality of care. We set out to determine if diabetics could be ...accurately identified using structured data contained within an EMR. Study Design and Setting We used a 5% random sample of adult patients (969 patients) within a convenience sample of 17 primary care physicians using Practices Solutions EMR in Ontario. A reference standard of diabetes status was manually confirmed by reviewing each patient's record. Accuracy for identifying people with diabetes was assessed using various combinations of laboratory tests and prescriptions. EMR data was also compared with administrative data. Results A rule of one elevated blood sugar or a prescription for an antidiabetic medication had a 83.1% sensitivity, 98.2% specificity, 80.0% positive predictive value (PPV) and 98.5% negative predictive value (NPV) compared with the reference standard of diabetes status. Conclusion We found that the use of structured data within an EMR could be used to identify patients with diabetes. Our results have positive implications for policy makers, researchers, and clinicians as they develop registries of diabetic patients to examine quality of care using EMR data.
Greater weight and body mass index (BMI) are negatively correlated with mammographic density, a strong risk factor for breast cancer, and are associated with an increased risk of breast cancer in ...postmenopausal women, but with a reduced risk in premenopausal women. We have examined the associations of body size and mammographic density on breast cancer risk.
We examined the associations of body size and the percentage of mammographic density at baseline with subsequent risk of breast cancer among 1,114 matched case-control pairs identified from three screening programs. The effect of each factor on risk of breast cancer was examined before and after adjustment for the other, using logistic regression.
In all subjects, before adjustment for mammographic density, breast cancer risk in the highest quintile of BMI, compared with the lowest, was 1.04 95% confidence interval (CI), 0.8-1.4. BMI was associated positively with breast cancer risk in postmenopausal women, and negatively in premenopausal women. After adjustment for density, the risk associated with BMI in all subjects increased to 1.60 (95% CI, 1.2-2.2), and was positive in both menopausal groups. Adjustment for BMI increased breast cancer risk in women with 75% or greater density, compared with 0%, increased from 4.25 (95% CI, 1.6-11.1) to 5.86 (95% CI, 2.2-15.6).
BMI and mammographic density are independent risk factors for breast cancer, and likely to operate through different pathways. The strong negative correlated between them will lead to underestimation of the effects on risk of either pathway if confounding is not controlled.
Background
In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab‐paclitaxel (GnP) have been publicly funded for first‐line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic ...pancreatic cancer (mPC) since April 2015. We examined the real‐world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC.
Methods
Patients receiving first‐line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population‐based databases. Overall survival (OS) was assessed using Kaplan‐Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models.
Results
For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70‐0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia‐related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia‐related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar.
Conclusion
In the real world, FFX had longer OS, less frequent all‐cause EDV and all‐cause hospitalization, but more febrile neutropenia‐related hospitalization compared to GnP.
In the real world, implementation of universal public funding of FOLFIRINOX for metastatic pancreatic cancer was associated with improved overall survival, less frequent all‐cause emergency department visits, less frequent all‐cause hospitalization, but increased febrile neutropenia‐related hospitalization compared to patients treated with gemcitabine + nab‐paclitaxel. Expanding funding to include unresectable locally advanced pancreatic cancer was associated with a similar trend in benefits, but with improved absolute survival.
Abstract Background Few longitudinal studies have delineated the association between traditional cardiovascular risk factors and development of aortic stenosis (AS). Objectives The authors examined ...the association between traditional cardiovascular risk factors and incident severe AS in a large, unselected elderly population. Methods This observational cohort study used multiple linked health care population-based databases of individuals older than 65 years on April 1, 2002, without prior valvular disease, coronary artery disease, heart failure, cardiac arrhythmia, cerebrovascular disease, congenital heart disease, or admissions with cardiac symptoms. The relationship between hypertension (HTN), diabetes, dyslipidemia, and incident severe AS requiring hospitalization or surgical or interventional treatment was examined. Results Among 1.12 million individuals followed for a median of 13 years, 20,995 subjects developed severe AS. Overall absolute incidence was 144 per 100,000 person-years (169 and 127 per 100,000 person-years in men and women, respectively). In cause-specific hazard models, HTN (adjusted hazard ratio HR: 1.71; 95% confidence interval CI: 1.66 to 1.76), diabetes (HR: 1.49; 95% CI: 1.44 to 1.54), and dyslipidemia (HR: 1.17; 95% CI: 1.14 to 1.21) were all significantly associated with increased risk of developing severe AS (all p < 0.001). There was a positive dose-response relationship between the number and duration of cardiac risk factors and risk of AS. In the Fine-Gray model, all 3 risk factors were independently associated with a higher incidence of AS. The population-attributable risk of AS associated with 3 cardiac risk factors was 34.4% (95% CI: 32.8 to 36.0). Conclusions HTN, diabetes, and dyslipidemia have independent and dose-response associations with incident AS in an unselected population of older individuals, and together accounted for approximately one-third of the incidence of severe AS.
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