This trial compared coronary-artery bypass grafting alone with CABG plus mitral-valve repair in patients with coronary artery disease and moderate ischemic mitral regurgitation. Mitral-valve repair ...provided no apparent benefit and was associated with more neurologic complications.
Each year, approximately 1 million Americans have a myocardial infarction, and nearly 8 million Americans have a history of myocardial infarction.
1
Ischemic mitral regurgitation, which results from functional-valve incompetence due to myocardial injury and adverse left ventricular remodeling, develops in approximately 50% of patients after an infarction, and moderate regurgitation occurs in more than 10% of patients.
2
–
4
Ischemic mitral regurgitation is associated with excess mortality regardless of management.
5
,
6
The valve leaflets and chordal structures in affected patients are “innocent bystanders”; mitral regurgitation results from papillary muscle displacement, leaflet tethering, reduced closing forces, and annular dilatation.
7
–
10
Many patients . . .
Objective
Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow‐up. Unfortunately, ...the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three‐dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image‐based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE.
Methods
This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively.
Results
Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic‐clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome.
Significance
LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.
IMPORTANCE: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. OBJECTIVE: To determine whether ...catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. DESIGN, SETTING, AND PARTICIPANTS: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. INTERVENTIONS: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. RESULTS: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio HR, 0.86 95% CI, 0.65-1.15; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 95% CI, 0.60-1.21; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 95% CI, 0.74-0.93; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 95% CI, 0.45-0.60; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00911508
We present an overview of state-of-the-art chemistry-climate and chemistry transport models that are used within phase 1 of the Chemistry-Climate Model Initiative (CCMI-1). The CCMI aims to conduct a ...detailed evaluation of participating models using process-oriented diagnostics derived from observations in order to gain confidence in the models' projections of the stratospheric ozone layer, tropospheric composition, air quality, where applicable global climate change, and the interactions between them. Interpretation of these diagnostics requires detailed knowledge of the radiative, chemical, dynamical, and physical processes incorporated in the models. Also an understanding of the degree to which CCMI-1 recommendations for simulations have been followed is necessary to understand model responses to anthropogenic and natural forcing and also to explain inter-model differences. This becomes even more important given the ongoing development and the ever-growing complexity of these models. This paper also provides an overview of the available CCMI-1 simulations with the aim of informing CCMI data users.
We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is ...transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.
A fundamental goal of the Earth Science community is to understand how perturbations on Earth's surface are preserved in the stratigraphic record. Recent Source to Sink (S2S) studies of the Waipaoa ...Sedimentary System (WSS), New Zealand, are synthesized herein to provide a holistic perspective of the processes that generate, transport and preserve sedimentary strata and organic carbon on the Waipaoa margin in the late Quaternary. Rapid uplift associated with subduction processes and weak sedimentary units have conspired to generate rapid rates of incision and erosion in the Waipaoa catchment since the Last Glacial Maximum (LGM). We show that although much of the sediment exported offshore during this time interval originated from valley excavation, a substantial portion emanated from hillslopes, mostly through deep-seated landslide and earthflow processes that were vigorous during periods of rapid fluvial incision just prior to the Pleistocene–Holocene transition. Lacustrine sediments deposited in naturally-dammed 7-ky-old Lake Tutira provide a record of Holocene environmental controls on upper catchment sedimentation in the WSS, with 1400 storms identified. Storm frequency is modulated by the waxing and waning of atmospheric teleconnections between the tropics and Antarctica. Furthermore, clear long-term changes in sediment yield are evident from the Lake Tutira record following human settlement as conversion to pasture is accompanied by a 3-fold increase in the long-term lake sediment accumulation rate.
Whereas there is ample evidence that Waipaoa River flood deposits are routinely deposited offshore in the sheltered confines of Poverty Bay, over the longer term, waves and currents subsequently resuspend and transport these deposits both landward (sandy fraction) and seaward (finer fraction). Thus, the timing of sediment supply to areas of net sediment accumulation is more often driven by wave events that are not associated with river flooding. Therefore, we conclude that asynchronicity of river-sediment delivery and of wave resuspension in most instances precludes the direct preservation of flood events in the stratigraphic record of the Waipaoa Shelf. Over the longer term, the sediment package preserved on the shelf and slope since the LGM can be explained in large measure by sequence-stratigraphic models forced by varying sea level and ongoing tectonic deformation of the margin. As sea level rose, sediment supply to the slope was reduced by about a factor of 5 due to shelf trapping. Despite this reduction, turbidites are found at similar frequency throughout the LGM–Present, as the dominant trigger appears to be subduction earthquakes, with large ones having a return interval of about 200±100years. Sediment-budget exercises that consider both modern (river discharge versus centennial accumulation rates) and post-LGM (terrestrial production versus offshore isopachs) mass balances indicate that about half of the total sediment production from the Waipaoa escapes the study area. Moreover, a coupled sediment transport-hydrodynamic model and observations of textural trends on the shelf indicate that a large fraction of the sediment is carried outside the study area along the shelf to the northeast by the river plume or by combined current/wave activity. Therefore, we conclude that the WSS is an open system with sediment escape from the present day through the LGM.
The organic matter associated with sediment as it moves from upland source to marine sink is a product of particle history, and provides a record of materials that have cycled over timescales of days to millions of years. The ubiquity of fossil Organic Carbon (OC) in both the terrestrial and marine realms of the Waipaoa attests both to the chronic nature of its source, crumbling mudstones further destabilized by land use, and its biogeochemical recalcitrance. Modern OC persists by virtue of its continual production along the S2S transit, and is buried and preserved within the adjacent marine depocenters. The Waipaoa contrasts with dispersal systems on wide, energetic shelves (e.g., the Amazon and Fly Rivers) where sediment is extensively refluxed in oxygenated overlying water resulting in the biogeochemical incineration of particulate OC. The Waipaoa, like other small mountainous rivers on active margins, exhibits a high riverine OC preservation efficiency (>50%) in its marine depocenters because of the relatively rapid, event-driven accumulation of sediment.
Hypertension and hypercholesterolemia are recognized complications of liver transplantation, but whether they contribute to the development of cardiovascular disease is uncertain. We aimed first to ...determine the prevalence of risk factors for coronary heart disease (CHD) after liver transplantation and second to study the effect of liver transplantation on the predicted 10-year risk of developing CHD and the incidence of cardiovascular events in comparison with a matched local population.
Data on blood pressure, serum lipids, weight, diabetes mellitus, smoking, and incidence of myocardial infarction (MI) and stroke were obtained retrospectively from the case notes of 181 consecutive adult liver transplant recipients (median follow-up 54 months). The Framingham coronary risk equations were used to calculate the 10-year probability of developing CHD.
The prevalences of hypertension and hypercholesterolemia after transplantation were 77% and 62%, respectively. The predicted 10-year risk of CHD increased from 6.9% before transplantation to 11.5% at 1 year after transplantation, whereas that of a matched local population was 7%. Compared with a matched nontransplant population, the incidence ratios for MI and stroke were 0.55 (95% confidence interval, 0.01-3.06 ) and 1.45 (95% confidence interval, 0.18-5.22), respectively. No patients died from MI or stroke.
Liver transplant recipients have a high prevalence of risk factors for cardiovascular disease, exceeding that of the general population, and have a higher predicted risk of developing CHD. Despite this, there were no deaths from CHD or stroke during the study period.
Malaria endemic countries have scaled-up community health worker (CHW) interventions, to diagnose and treat malaria in communities with limited access to public health systems. The evaluations of ...these programmes have centred on CHW's compliance to guidelines, but the broader changes at public health centres including utilisation and diagnoses made, has received limited attention.
This analysis was conducted during a CHW-intervention for malaria in Rukungiri District, Western Uganda. Outpatient department (OPD) visit data were collected for children under-5 attending three health centres one year before the CHW-intervention started (pre-intervention period) and for 20 months during the intervention (intervention-period). An interrupted time series analysis with segmented regression models was used to compare the trends in malaria, non-malaria and overall OPD visits during the pre-intervention and intervention-period.
The introduction of a CHW-intervention suggested the frequency of diagnoses of diarrhoeal diseases, pneumonia and helminths increased, whilst the frequency of malaria diagnoses declined at health centres. In May 2010 when the intervention began, overall health centre utilisation decreased by 63% compared to the pre-intervention period and the health centres saw 32 fewer overall visits per month compared to the pre-intervention period (p<0.001). Malaria visits also declined shortly after the intervention began and there were 27 fewer visits per month during the intervention-period compared with the pre-intervention period (p<0.05). The declines in overall and malaria visits were sustained for the entire intervention-period. In contrast, there were no observable changes in trends of non-malarial visits between the pre-intervention and intervention-period.
This analysis suggests introducing a CHW-intervention can reduce the number of child malaria visits and change the profile of cases presenting at health centres. The reduction in workload of health workers may allow them to spend more time with patients or undertake additional curative or preventative roles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that ...delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer.
In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849.
Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3–4 study drug-related adverse event (two 1% of 157 patients, both grade 3), and there were no treatment-related deaths.
Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state.
FKD Therapies Oy.