Abstract Background Despite increasing interest in advance care planning (ACP) and prior ACP descriptions, a consensus definition does not yet exist to guide clinical, research, and policy ...initiatives. Objective To develop a consensus definition of ACP for adults. Design Delphi Panel Setting/Participants Participants included a multidisciplinary panel of international ACP experts consisting of 52 clinicians, researchers, and policy leaders from 4 countries, and a patient/surrogate advisory committee. Measurements We conducted 10 rounds of a modified Delphi method and qualitatively analyzed panelists’ input. Panelists identified several themes lacking consensus, and iteratively discussed and developed a final consensus definition. Results Panelists identified several tensions concerning ACP concepts such as whether the definition should focus on conversations vs. written advance directives; patients’ values vs. treatment preferences; current shared decision making vs. future medical decisions; and who should be included in the process. The panel achieved a final consensus one-sentence definition and accompanying goals statement: “Advance care planning is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences regarding future medical care. The goal of advance care planning is to help ensure that people receive medical care that is consistent with their values, goals and preferences during serious and chronic illness.” The panel also described strategies to best support adults in ACP. Conclusions A multidisciplinary Delphi panel developed a consensus definition for ACP for adults that can be used to inform implementation and measurement of ACP clinical, research, and policy initiatives.
Abstract Objectives Routine device surveillance after successful left atrial appendage closure is recommended to evaluate for intermediate to late complications. The aim of this study was to assess ...the incidence and clinical impact of these complications on cardiovascular events. Methods Centers participating in the Amplatzer Cardiac Plug multicenter study were requested to submit their post-procedural transesophageal echocardiograms for independent adjudication. Thirteen of 22 centers contributed all their post-procedural echocardiograms, which included 344 from 605 consecutive patients. These images were submitted to a core laboratory and reviewed by 2 independent experts for peri-device leak, device-associated thrombus, device embolization, device migration, left atrial appendage thrombus, and left atrial thrombus. Clinical events were prospectively collected by each center. Results Of the 344 transesophageal echocardiograms, 339 were deemed analyzable. Patients’ mean age was 74.4 ± 7.5 years, and 67.3% were men. The mean CHADS2 score was 2.7 ± 1.3, the mean CHA2 DS2 -VASc score was 4.3 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.2. Amplatzer Cardiac Plug implantation was successful in all patients. Periprocedural major adverse events occurred in 2.4%. Median clinical follow-up duration was 355 days (range 179 to 622 days). Follow-up transesophageal echocardiography was performed after a median of 134 days (range 88 to 227 days). Device-associated thrombus was observed in 3.2% and peri-device leak in 12.5% (5.5% minimal, 5.8% mild, 0.6% moderate, 0.6% severe). Neither device-associated thrombus nor peri-device leak was associated with an increased risk for cardiovascular events. Independent predictors of device-associated thrombus were smoking (odds ratio: 5.79; p = 0.017) and female sex (odds ratio: 4.22; p = 0.027). Conclusions Following successful left atrial appendage closure with the Amplatzer Cardiac Plug, the presence of peri-device leak was relatively low, and device-associated thrombus was infrequent. Neither was associated with increased risk for thromboembolism.
Purpose Intraoperative performance assessment of residents is of growing interest to trainees, faculty, and accreditors. Current approaches to collect such assessments are limited by low ...participation rates and long delays between procedure and evaluation. We deployed an innovative, smartphone-based tool, SIMPL (System for Improving and Measuring Procedural Learning), to make real-time intraoperative performance assessment feasible for every case in which surgical trainees participate, and hypothesized that SIMPL could be feasibly integrated into surgical training programs. Methods Between September 1, 2015 and February 29, 2016, 15 U.S. general surgery residency programs were enrolled in an institutional review board-approved trial. SIMPL was made available after 70% of faculty and residents completed a 1-hour training session. Descriptive and univariate statistics analyzed multiple dimensions of feasibility, including training rates, volume of assessments, response rates/times, and dictation rates. The 20 most active residents and attendings were evaluated in greater detail. Results A total of 90% of eligible users (1267/1412) completed training. Further, 13/15 programs began using SIMPL. Totally, 6024 assessments were completed by 254 categorical general surgery residents ( n = 3555 assessments) and 259 attendings ( n = 2469 assessments), and 3762 unique operations were assessed. There was significant heterogeneity in participation within and between programs. Mean percentage (range) of users who completed ≥1, 5, and 20 assessments were 62% (21%-96%), 34% (5%-75%), and 10% (0%-32%) across all programs, and 96%, 75%, and 32% in the most active program. Overall, response rate was 70%, dictation rate was 24%, and mean response time was 12 hours. Assessments increased from 357 (September 2015) to 1146 (February 2016). The 20 most active residents each received mean 46 assessments by 10 attendings for 20 different procedures. Conclusions SIMPL can be feasibly integrated into surgical training programs to enhance the frequency and timeliness of intraoperative performance assessment. We believe SIMPL could help facilitate a national competency-based surgical training system, although local and systemic challenges still need to be addressed.
Objectives This study aimed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ...ST-segment elevation myocardial infarction (STEMI). Background Myocardial edema is a reperfusion injury with potentially severe consequences. Post-conditioning is a cardioprotective therapy that reduces infarct size after reperfusion, but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans. Methods Fifty patients with STEMI were randomly assigned to either a control or post-conditioned group. Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission. Myocardial edema was measured by T2-weighted sequences, and infarct size was determined by late gadolinium enhancement sequences and creatine kinase release. Results The post-conditioned and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before percutaneous coronary intervention. As expected, post-conditioning was associated with smaller infarct size (13 ± 7 g/m2 vs. 21 ± 14 g/m2 ; p = 0.01) and creatine kinase peak serum level (median interquartile range: 1,695 1,118 to 3,692 IU/l vs. 3,505 2,307 to 4,929 IU/l; p = 0.003). At reperfusion, the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group (23 ± 16 g/m2 vs. 34 ± 18 g/m2 ; p = 0.03); the relative increase in T2W signal intensity was also significantly lower (p = 0.02). This protective effect was confirmed after adjustment for the size of the area at risk. Conclusions This randomized study demonstrated that post-conditioning reduced infarct size and edema in patients with reperfused STEMI. (Post Cond No Reflow; NCT01208727 )
Left atrial appendage occlusion (LAAO) is emerging as a promising alternative to oral anticoagulation. Because aged patients present a greater risk of not only cardioembolic events but also major ...bleeding, LAAO might represent a valid alternative as this would allow oral anticoagulation cessation while keeping cardioembolic protection. The objective of the study was to explore the safety and efficacy of LAAO in elderly patients. Data from the AMPLATZER Cardiac Plug multicenter registry were analyzed. The cohort was categorized in 2 groups (<75 vs ≥75 years). A total of 1,053 subjects were included in the registry. Of them, 219 were excluded because of combined procedures. As a result, 828 subjects were included (54.6% ≥75 years). Procedural success was high and similar in both groups (97.3%). Acute procedural major adverse events were not statistically different among groups (3.2% in <75 years vs 5.1%; p = 0.17) although stratified analysis showed a higher incidence of cardiac tamponade in elderly patients (0.5% vs 2.2%; p = 0.04). With a median follow-up of 16.8 months, no significant differences in stroke/TIA (1.9% vs 2.3%; p = 0.89) and major bleeding (1.7% vs 2.6%; p = 0.54) were observed. In conclusion, LAAO was associated with similar procedural success in patients aged <75 and ≥75 years although older patients had a higher incidence of cardiac tamponade. At follow-up, stroke and major bleeding rates were similar among groups.
Objectives This study sought to assess the impact of permanent pacemaker (PPM) implantation on clinical outcomes among patients undergoing transfemoral transcatheter aortic valve implantation (TAVI). ...Background TAVI is associated with atrioventricular-conduction abnormalities requiring PPM implantation in up to 40% among patients treated with self-expanding prostheses. Methods Between 2007 and 2010, 353 consecutive patients (mean age: 82.6 ± 6.1 years, log EuroSCORE: 25.0 ± 15.0%) with severe aortic stenosis underwent transfemoral TAVI at 2 institutions. Clinical outcomes were compared among 3 groups: (1) patients requiring PPM implantation after TAVI (PPM after TAVI), (2) patients without PPM before or after TAVI (no PPM), and (3) patients with PPM before TAVI (PPM before TAVI). The primary endpoint was all-cause mortality at 12 months, and an age-, sex-, and origin-matched standardized population served as controls. Results Of 353 patients, 98 patients (27.8%) belonged to the PPM after TAVI group, 48 patients (13.6%) belonged to the PPM before TAVI group, and 207 patients (58.6%) belonged to the no PPM group. The PPM before TAVI patients had a significantly higher baseline risk compared with the PPM after TAVI and no PPM patients (coronary artery disease: 77.1% vs. 52.7% and 58.2%, respectively, p = 0.009; atrial fibrillation: 43.8% vs. 22.7% and 20.4%, respectively, p = 0.005). At 12 months of follow-up, all-cause mortality was similar in all 3 groups (PPM after TAVI group: 19.4%, PPM before TAVI group: 22.9%, no PPM group: 18.0%) in unadjusted analyses (p = 0.77) and adjusted analyses (p = 0.90). Compared with the standardized population, adjusted hazard ratios for death were 2.37 (95% confidence interval CI: 1.51 to 3.72) for the PPM after TAVI group, 2.75 (95% CI: 1.52 to 4.97) for the PPM before TAVI group, and 2.24 (95% CI: 1.62 to 3.09) for the no PPM group. Conclusions Although prognosis remains impaired compared with an age-, sex-, and origin-matched standardized population, periprocedural PPM implantation does not seem to affect clinical outcomes adversely among patients undergoing transfemoral TAVI.
Objective To evaluate the health benefits of an exclusively human milk–based diet compared with a diet of both human milk and bovine milk–based products in extremely premature infants. Study design ...Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk–based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk–based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. Results The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention ( P = .007). Conclusions For extremely premature infants, an exclusively human milk–based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk–based diet that also includes bovine milk–based products.
Summary Background One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether ...the addition of neoadjuvant radiotherapy improves outcomes. Methods We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m2 cisplatin and 85 mg/m2 docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00030771. Findings From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7–22·9) in the chemoradiotherapy group and 11·6 months (8·4–15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6–50·0) with radiotherapy, compared with 26·2 months (19·9–52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. Interpretation Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. Funding Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi.
Abstract Background The significance of periconceptional nutrition for optimizing offspring and maternal health and reducing social inequalities warrants greater understanding of diet quality among ...US women. Objective Our objective was to evaluate racial or ethnic and education inequalities in periconceptional diet quality and sources of energy and micronutrients. Design Cross-sectional analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort. Participants and setting Nulliparous women (N=7,511) were enrolled across eight US medical centers from 2010 to 2013. Main outcome measures A semiquantitative food frequency questionnaire assessing usual dietary intake during the 3 months around conception was self-administered during the first trimester. Diet quality, measured using the Healthy Eating Index-2010 (HEI-2010), and sources of energy and micronutrients were the outcomes. Statistical analyses Differences in diet quality were tested across maternal racial or ethnic and education groups using F tests associated with analysis of variance and χ2 tests. Results HEI-2010 score increased with higher education, but the increase among non-Hispanic black women was smaller than among non-Hispanic whites and Hispanics (interaction P value <0.0001). For all groups, average scores for HEI-2010 components were below recommendations. Top sources of energy were sugar-sweetened beverages, pasta dishes, and grain desserts, but sources varied by race or ethnicity and education. Approximately 34% of energy consumed was from empty calories (the sum of energy from added sugars, solid fats, and alcohol beyond moderate levels). The primary sources of iron, folate, and vitamin C were juices and enriched breads. Conclusions Diet quality is suboptimal around conception, particularly among women who are non-Hispanic black, Hispanic, or who had less than a college degree. Diet quality could be improved by substituting intakes of refined grains and foods empty in calories with vegetables, peas and beans (legumes), seafood, and whole grains.
Summary Background We aimed to assess the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with metastatic breast cancer by undertaking a pooled ...analysis of individual patient data. Methods We contacted 51 European centres and asked them to provide reported and unreported anonymised data for individual patients with metastatic breast cancer who participated in studies between January, 2003, and July, 2012. Eligible studies had participants starting a new line of therapy, data for progression-free survival or overall survival, or both, and CTC quantification by the CellSearch method at baseline (before start of new treatment). We used Cox regression models, stratified by study, to establish the association between CTC count and progression-free survival and overall survival. We used the landmark method to assess the prognostic value of CTC and serum marker changes during treatment. We assessed the added value of CTCs or serum markers to prognostic clinicopathological models in a resampling procedure using likelihood ratio (LR) χ2 statistics. Findings 17 centres provided data for 1944 eligible patients from 20 studies. 911 patients (46·9%) had a CTC count of 5 per 7·5 mL or higher at baseline, which was associated with decreased progression-free survival (hazard ratio HR 1·92, 95% CI 1·73–2·14, p<0·0001) and overall survival (HR 2·78, 95% CI 2·42–3·19, p<0·0001) compared with patients with a CTC count of less than 5 per 7·5 mL at baseline. Increased CTC counts 3–5 weeks after start of treatment, adjusted for CTC count at baseline, were associated with shortened progression-free survival (HR 1·85, 95% CI 1·48–2·32, p<0·0001) and overall survival (HR 2·26, 95% CI 1·68–3·03) as were increased CTC counts after 6–8 weeks (progression-free survival HR 2·20, 95% CI 1·66–2·90, p<0·0001; overall survival HR 2·91, 95% CI 2·01–4·23, p<0·0001). Survival prediction was significantly improved by addition of baseline CTC count to the clinicopathological models (progression-free survival LR 38·4, 95% CI 21·9–60·3, p<0·0001; overall survival LR 64·9, 95% CI 41·3–93·4, p<0·0001). This model was further improved by addition of CTC change at 3–5 weeks (progression-free survival LR 8·2, 95% CI 0·78–20·4, p=0·004; overall survival LR 11·5, 95% CI 2·6–25·1, p=0·0007) and at 6–8 weeks (progression-free survival LR 15·3, 95% CI 5·2–28·3; overall survival LR 14·6, 95% CI 4·0–30·6; both p<0·0001). Carcinoembryonic antigen and cancer antigen 15-3 concentrations at baseline and during therapy did not add significant information to the best baseline model. Interpretation These data confirm the independent prognostic effect of CTC count on progression-free survival and overall survival. CTC count also improves the prognostication of metastatic breast cancer when added to full clinicopathological predictive models, whereas serum tumour markers do not. Funding Janssen Diagnostics, the Nuovo-Soldati foundation for cancer research.
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