Absolute Mortality Reduction Research Articles

The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption

ObjectivesCoupled Plasma Filtration and Adsorption (CPFA) use in septic shock remains controversial. The objective is to clarify whether the application of high doses of CPFA in addition to the current...

Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae bacteremia and pneumonia.

Background: Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown.Methods: We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY.Results: In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively.Conclusion: CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.

Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study

BackgroundRoutine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status.MethodsThe CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results.DiscussionThe CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results.Trial registrationClinicalTrials.gov, NCT03382730. Registered on December 26, 2017.

Economic and Societal Impact of a Systems-of-Care Approach for STEMI Management in Low and Middle-Income Countries: Insights from the TN STEMI Program.

The TN STEMI Program was a multicenter, prospective, observational study conducted in Tamil Nadu, India, that assessed the effects of implementing the STEMI India Model for the management of STEMI. We discuss the economic and societal impact in this article. Given that the intervention resulted in an absolute mortality reduction of 3.4%, we calculated a number needed to treat of 30 patients. At an annualized project cost of INR 15.11 million, this approximately calculates to INR 193,749 (USD 3,311) per life saved. The utility of the TN-STEMI Program can be estimated to be 1,108 life-years. This calculates to approximately INR 13,643 (USD 233) per life-year saved. Our estimates will likely be of particular interest to policy makers in low and middle-income countries, where financial and resource constraints pose a perennial public health challenge.

Residual inflammatory risk after contemporary lipid lowering therapy.

Recently, there has been an increasing interest in targeting inflammation to reduce major adverse cardiovascular events (MACE) in patients with cardiovascular risk. Statins, PCSK9 inhibitors, and ezetimibe have been shown to reduce MACE owing to reduction in low-density lipoproteins cholesterol (LDL-c). Herein, we investigate whether the intensity of these agents is associated with (i) discernible reduction in inflammation measured by the levels of high-sensitivity C-reactive protein (hsCRP); (ii) reduction in MACE; (iii) if there is an association between the baseline hsCRP and MACE. Electronic databases were searched for randomized controlled trials (RCTs) that compared statins, ezetimibe, PCSK9 inhibitors with placebos/active controls and reported MACEs and hsCRP (mg/L). Studies were stratified based on baseline hsCRP (<2, 2-3, >3) with subgroup analysis conducted across each stratum. Fourteen RCTs including 133109 patients randomized into more intensive therapy (MIT) and less intensive therapy were selected. Meta-analysis did not demonstrate any significant differences between use of MIT and hsCRP levels (mean difference, -0.02; CI, -0.06, 0.02; P = 0.31). The MIT significantly reduced the risk of MACE (RR, 0.82; CI, 0.75, 0.91; P < 0.001). The relative risk and absolute risk remained consistent across the strata. However, there was a 0.5% statistically significant absolute risk reduction in all-cause mortality in patients with higher hsCRP (RD, -0.005; CI, -0.009, -0.001; P = 0.01). Overall, LDL-c lowering therapies reduce relative risk of MACEs particularly in patients with higher baseline hsCRP. However, there appears to be a residual inflammatory risk despite the use of contemporary lipid lowering agents.

Interfacility Transfer of Medicare Beneficiaries With Acute Type A Aortic Dissection and Regionalization of Care in the United States.

The feasibility and effectiveness of delaying surgery to transfer patients with acute type A aortic dissection-a catastrophic disease that requires prompt intervention-to higher-volume aortic surgery hospitals is unknown. We investigated the hypothesis that regionalizing care at high-volume hospitals for acute type A aortic dissections will lower mortality. We further decomposed this hypothesis into subparts, investigating the isolated effect of transfer and the isolated effect of receiving care at a high-volume versus a low-volume facility. We compared the operative mortality and long-term survival between 16 886 Medicare beneficiaries diagnosed with an acute type A aortic dissection between 1999 and 2014 who (1) were transferred versus not transferred, (2) underwent surgery at high-volume versus low-volume hospitals, and (3) were rerouted versus not rerouted to a high-volume hospital for treatment. We used a preference-based instrumental variable design to address unmeasured confounding and matching to separate the effect of transfer from volume. Between 1999 and 2014, 40.5% of patients with an acute type A aortic dissection were transferred, and 51.9% received surgery at a high-volume hospital. Interfacility transfer was not associated with a change in operative mortality (risk difference, -0.69%; 95% CI, -2.7% to 1.35%) or long-term mortality. Despite delaying surgery, a regionalization policy that transfers patients to high-volume hospitals was associated with a 7.2% (95% CI, 4.1%-10.3%) absolute risk reduction in operative mortality; this association persisted in the long term (hazard ratio, 0.81; 95% CI, 0.75-0.87). The median distance needed to reroute each patient to a high-volume hospital was 50.1 miles (interquartile range, 12.4-105.4 miles). Operative and long-term mortality were substantially reduced in patients with acute type A aortic dissection who were rerouted to high-volume hospitals. Policy makers should evaluate the feasibility and benefits of regionalizing the surgical treatment of acute type A aortic dissection in the United States.

Centralization of High-Risk Cancer Surgery Within Existing Hospital Systems.

Centralization is often proposed as a strategy to improve the quality of certain high-risk health care services. We evaluated the extent to which existing hospital systems centralize high-risk cancer surgery and whether centralization is associated with short-term clinical outcomes. We merged data from the American Hospital Association's annual survey on hospital system affiliation with Medicare claims to identify patients undergoing surgery for pancreatic, esophageal, colon, lung, or rectal cancer between 2005 and 2014. We calculated the degree to which systems centralized each procedure by calculating the annual proportion of surgeries performed at the highest-volume hospital within each system. We then estimated the independent effect of centralization on the incidence of postoperative complications, death, and readmissions after accounting for patient, hospital, and system characteristics. The average degree of centralization varied from 25.2% (range, 6.6% to 100%) for colectomy to 71.2% (range, 8.3% to 100%) for pancreatectomy. Greater centralization was associated with lower rates of postoperative complications and death for lung resection, esophagectomy, and pancreatectomy. For example, there was a 1.1% (95% CI, 0.8% to 1.4%) absolute reduction in 30-day mortality after pancreatectomy for each 20% increase in the degree of centralization within systems. Independent of volume and hospital quality, postoperative mortality for pancreatectomy was two times higher in the least centralized systems than in the most centralized systems (8.9% v 3.7%, P < .01). Centralization was not associated with better outcomes for colectomy or proctectomy. Greater centralization of complex cancer surgery within existing hospital systems was associated with better outcomes. As hospitals affiliate in response to broader financial and organization pressures, these systems may also present unique opportunities to improve the quality of high-risk cancer care.

Efficacy and Safety of Meropenem-Vaborbactam Versus Best Available Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Without Prior Antimicrobial Failure: A Post Hoc Analysis.

IntroductionInfections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased morbidity and high mortality. Meropenem–vaborbactam (MV) is a novel β-lactam/β-lactamase inhibitor combination active against KPC-producing Enterobacteriaceae. The aim of this post hoc analysis of the TANGO-II randomized controlled trial was to assess the efficacy of MV versus best available therapy (BAT) in the subgroup of patients without prior antimicrobial failure.MethodsThe primary outcome measure was clinical cure at the test of cure (TOC). Secondary outcome measures included (1) clinical cure at the end of therapy (EOT), (2) microbiological cure at TOC, (3) microbiological cure at EOT, and (4) 28-day all-cause mortality.ResultsFirst-line MV was associated with a 42.9% absolute increase in clinical cure rate at TOC (95% confidence intervals [CI] 13.7–72.1) in comparison with first-line BAT. A 49.3% absolute increase in clinical cure rate at EOT (95% CI 20.8–77.7), a 42.6% absolute increase in microbiological cure rate at EOT (95% CI 13.4–71.8), and a 36.2% absolute increase in microbiologic cure rate at TOC (95% CI 5.9–66.6) were also observed, in addition to a 29.0% absolute reduction in mortality (95% CI − 54.3 to − 3.7). Overall, fewer adverse events were observed in the MV group than in the BAT group.ConclusionMV was superior to BAT in the subgroup of patients with serious carbapenem-resistant Enterobacteriaceae (CRE) infections and no prior antimicrobial failure, with very high rates of clinical success, and was well tolerated. Post approval and real-world studies remain essential to clearly define the most appropriate population for early, empirical MV coverage, in accordance with antimicrobial stewardship principles.FundingThe Medicines Company.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-00981-y) contains supplementary material, which is available to authorized users.

Lung-protective Ventilation for Acute Respiratory Distress Syndrome.

Lung-protective Ventilation for Acute Respiratory Distress Syndrome.

Association of Medicaid Expansion With 1-Year Mortality Among Patients With End-Stage Renal Disease

The Affordable Care Act Medicaid expansion may be associated with reduced mortality, but evidence to date is limited. Patients with end-stage renal disease (ESRD) are a high-risk group that may be particularly affected by Medicaid expansion. To examine the association of Medicaid expansion with 1-year mortality among nonelderly patients with ESRD initiating dialysis. Difference-in-differences analysis of nonelderly patients initiating dialysis in Medicaid expansion and nonexpansion states from January 2011 to March 2017. Living in a Medicaid expansion state. The primary outcome was 1-year mortality. Secondary outcomes were insurance, predialysis nephrology care, and type of vascular access for hemodialysis. A total of 142 724 patients in expansion states (mean age, 50.2 years; 40.2% women) and 93 522 patients in nonexpansion states (mean age, 49.7; 42.4% women) were included. In Medicaid expansion states, 1-year mortality following dialysis initiation declined from 6.9% in the preexpansion period to 6.1% after expansion (change, -0.8 percentage points; 95% CI, -1.1 to -0.5). In nonexpansion states, mortality rates were 7.0% before expansion and 6.8% after expansion (change, -0.2 percentage points; 95% CI, -0.5 to 0.2), yielding an adjusted absolute reduction in mortality in expansion states of -0.6 percentage points (95% CI, -1.0 to -0.2). Mortality reductions were largest for black patients (-1.4 percentage points; 95% CI, -2.2, -0.7; P=.04 for interaction) and patients aged 19 to 44 years (-1.1 percentage points; 95% CI, -2.1 to -0.3; P=.01 for interaction). Expansion was associated with a 10.5-percentage-point (95% CI, 7.7-13.2) increase in Medicaid coverage at dialysis initiation, a -4.2-percentage-point (95% CI, -6.0 to -2.3) decrease in being uninsured, and a 2.3-percentage-point (95% CI, 0.6-4.1) increase in the presence of an arteriovenous fistula or graft. Changes in predialysis nephrology care were not significant. Among patients with ESRD initiating dialysis, living in a state that expanded Medicaid under the Affordable Care Act was associated with lower 1-year mortality. If this association is causal, further research is needed to understand what factors may have contributed to this finding.

Antibiotics has more impact on mortality than other early goal-directed therapy components in patients with sepsis: An instrumental variable analysis

PurposeTo estimate the effect of each of the EGDT components, as well as of the antibiotics, on length-of-stay and mortality. MethodsProspective cohort in three hospitals. Adult patients admitted by the Emergency Rooms (ER) with infection and any of systolic blood pressure < 90 mmHg or lactate >4 mmol/L. An instrumental analysis with hospital of admission as the instrumental variable was performed to estimate the effect of each intervention on hospital mortality and secondary outcomes. ResultsAmong 2587 patients evaluated 884 met inclusion criteria, with a hospital mortality rate of 17% (n = 150). In the instrumental analysis, the only intervention associated with an absolute reduction in mortality (21%) was the use of antibiotics in the first 3 h. In patients with lactate values ≥4 mmol/L in the ER, a non-decrease of at least 10% at six hours was independently associated with mortality (OR = 3.1; 95%CI = 1.5–6.2). ConclusionsAmong patients entering ER with infection and shock or hypoperfusion criteria, the use of appropriate antibiotics in the first 3 h is the measure that has the greatest impact on survival. In addition, among patients with hyperlactatemia >4 mmol/L, the clearance of >10% of lactate during resuscitation is associated with better outcomes.

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor-recipient combination.

The impact of donor quality on post-kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post-KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n=120818) and waitlisted candidates (n=376272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5-year post-KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTSscore of80, 5-year waitlist survival was 47.6%, and 5-year post-KT survival was 78.9% after receiving kidneys with a KDPIof20 and was 70.7% after receiving kidneys with a KDPIof80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPIof100 (>16 percentage points). Our prediction tool (www.transplantmodels.com/kdpi-epts) can support individualized decision-making on kidney offers in clinical practice.

Impact of declining exposure to secondhand tobacco smoke in public places to decreasing smoking-related cancer mortality in the US population

BackgroundThe major decrease in exposure to secondhand smoke (SHS) in public places in recent decades could have contributed to the decline in smoking-related cancer mortality observed in the US population. MethodsProspective study among 11,856 non-smoking adults aged ≥40 years who participated in NHANES 1988–1994 or 1999–2004 and were followed for mortality through 2006. We estimated the amount of change in cancer mortality over time attributed to the intermediate pathway of changes in SHS exposure in public places, after adjustment for risk factors and SHS exposure at home. ResultsThe adjusted smoking-related cancer mortality rate ratios (95% CI) for a two-fold increase in serum cotinine and a 1-hour increase in occupational SHS exposure time were 1.10 (1.03, 1.17) and 1.14 (1.06, 1.24) for all-cancer, and 1.13 (1.03, 1.24) and 1.14 (1.02, 1.26) for smoking-related cancer, respectively. The absolute reduction in mortality comparing 1999–2004 to 1988–1994 was 75.8 (−25.5, 177.0) and 77.0 (2.6, 151.4) deaths/100,000 person-years, for all-cancer and smoking-related cancer, respectively. Among these avoided all-cancer deaths, 45.8 (2.8, 89.5) and 18.1 (−1.2, 39.6)/100,000 person-year were attributable to changes in serum cotinine concentrations and occupational SHS exposure time, respectively. The corresponding numbers of smoking-related cancer avoided deaths were 36.4 (0.7, 72.8) and 9.9 (−3.8, 24.9)/100,000 person-year. ConclusionsDeclines in SHS exposure were associated with reductions in all-cancer and smoking-related cancer mortality, supporting that smoking bans in public places may have reduced cancer mortality among non-smoking adults.

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK\u2014a randomized controlled trial

BackgroundSeptic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study.MethodsANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle.ConclusionsIf peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources.Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017)

Explaining trends in coronary heart disease mortality in different socioeconomic groups in Denmark 1991-2007 using the IMPACTSEC model.

AimTo quantify the contribution of changes in different risk factors population levels and treatment uptake on the decline in CHD mortality in Denmark from 1991 to 2007 in different socioeconomic groups.DesignWe used IMPACTSEC, a previously validated policy model using data from different population registries.ParticipantsAll adults aged 25–84 years living in Denmark in 1991 and 2007.Main outcome measureDeaths prevented or postponed (DPP).ResultsThere were approximately 11,000 fewer CHD deaths in Denmark in 2007 than would be expected if the 1991 mortality rates had persisted. Higher mortality rates were observed in the lowest socioeconomic quintile. The highest absolute reduction in CHD mortality was seen in this group but the highest relative reduction was in the most affluent socioeconomic quintile. Overall, the IMPACTSEC model explained nearly two thirds of the decline in. Improved treatments accounted for approximately 25% with the least relative mortality reduction in the most deprived quintile. Risk factor improvements accounted for approximately 40% of the mortality decrease with similar gains across all socio-economic groups. The 36% gap in explaining all DPPs may reflect inaccurate data or risk factors not quantified in the current model.ConclusionsAccording to the IMPACTSEC model, the largest contribution to the CHD mortality decline in Denmark from 1991 to 2007 was from improvements in risk factors, with similar gains across all socio-economic groups. However, we found a clear socioeconomic trend for the treatment contribution favouring the most affluent groups.

2018 ACC/AHA Clinical Performance and Quality Measures for Cardiac Rehabilitation: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures.

The American College of Cardiology (ACC)/American Heart Association (AHA) performance measurement sets serve as vehicles to accelerate translation of scientific evidence into clinical practice. Measure sets developed by the ACC/AHA are intended to provide practitioners and institutions that deliver cardiovascular services with tools to measure the quality of care provided and identify opportunities for improvement. Writing committees are instructed to consider the methodology of performance measure development1 and to ensure that the measures developed are aligned with ACC/AHA clinical guidelines. The writing committees also are charged with constructing measures that maximally capture important aspects of care quality, including …

Abstract P4-15-02: Impact of radiotherapy and endocrine therapy on further events: Final multivariate analysis of a prospective, national cohort study of screen detected ductal carcinoma in situ (DCIS) of the breast

Abstract Key words: DCIS, radiotherapy, endocrine therapy, survival, surgical margins Background: The benefits and risks of breast screening remain controversial, with particular concern that ductal carcinoma in situ (DCIS) may be over-diagnosed and over-treated. There is little prospective data on treatment or outcomes for screen detected DCIS. Methods: A prospective cohort of non-invasive lesions diagnosed through the United Kingdom National Health Service Breast Screening Programme (NHSBSP) (1 April 2003 to 31 March 2012) was linked to national databases and case note review to analyse patterns of care, recurrence and mortality. Results: Screen-detected DCIS in 9938 women was analysed, 33% (9938/30041) of women with a final diagnosis of non-invasive breast neoplasia diagnosed through the NHSBSP over the same time. The patients (mean age was 60 years: range 46-87 years) were treated by breast conservation surgery (BCS; 7007; 70.5%) or mastectomy (2931). At 64 months median follow up, 697 (6.8%) had further DCIS or invasive breast cancer after BCS (7.8%) or mastectomy (4.5%) (p&amp;lt;0.001) and 228 women (2.3%) developed contralateral malignancy. Breast radiotherapy (RT) after BCS (4363/7007; 62%) was associated with a 3.1% absolute reduction in any ipsilateral DCIS or invasive cancer (No RT: 7.2% vs RT: 4.1% (p&amp;lt;0.001) and a 1.9% absolute reduction for ipsilateral invasive breast recurrence (No RT: 3.8% vs RT: 1.9% (p&amp;lt;0.001), independent of excision margin width or size of DCIS. Women who did not receive RT after BCS had more ipsilateral events (p=0.008) when the radial excision margin was &amp;lt;2mm. RT was rarely used after mastectomy for DCIS (33 women). Adjuvant endocrine therapy (prescribed for 1208/9938; 12.2%) was associated with a reduction in any ipsilateral recurrence, independent of whether women did (HR 0.57: 95% CI 0.41 - 0.80) or did not (HR 0.68: 95% CI 0.51 - 0.91) receive RT after BCS. Among 321 (3.2%) women who died, 46 deaths (0.5%; 14.3% of all deaths) were attributed to invasive breast cancer. Death from breast cancer was uncommon and outnumbered 5:1 by death due to other causes. RT after BCS was associated with a non-significant 0.2% absolute reduction in breast cancer mortality. However, women who developed invasive breast cancer had a worse survival than those with further DCIS (p&amp;lt;0.001). Conclusions: Recurrent DCIS or invasive cancer is uncommon following screen detected DCIS treated by surgery and adjuvant therapy. Both RT and endocrine therapy following surgery were associated with a significant reduction in further DCIS and invasive disease, but not breast cancer mortality, within 5 years of diagnosis. This study quantifies the benefits of radiotherapy and endocrine therapy to inform decision making in the management of screen detected DCIS. Citation Format: Thompson AM, Clements K, Cheung S, Pinder SE, Lawrence G, Sawyer E, Kearins O, Ball GR, Tomlinson I, Hanby AM, Thomas J, Maxwell AJ, Wallis MG, Dodwell DJ. Impact of radiotherapy and endocrine therapy on further events: Final multivariate analysis of a prospective, national cohort study of screen detected ductal carcinoma in situ (DCIS) of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-02.

New mechanical ventilation strategies in acute respiratory distress syndrome

Objective The purpose of this paper was to assess the new mechanical ventilation strategies in acute respiratory distress syndrome (ARDS). Data sources Data sources includes Medline databases (PubMed, Medscape, ScienceDirect, and EMF-Portal) and all materials available on the internet from 2003 to 2016. Study selection The search presented articles that met the inclusion criteria involving the definition, pathophysiology, medical treatment, mechanical ventilation strategies, and prognosis of ARDS. Data extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Data synthesis Comparisons were made by different lines of treatment and new mechanical ventilation strategies of ARDS. Results The studies show that mechanical ventilation is the hallmark of ARDS treatment and a lifesaving intervention for severe hypoxemia that characterizes it. Despite it being used in this setting for several decades, our knowledge about its benefits and potential harm has evolved widely over time. Early ventilation strategies involved volume-controlled ventilation with tidal volume (Vt) of 10–15 ml/kg to achieve “normal” arterial blood gases. However, ventilation itself can cause lung injury. A landmark trial conducted by the ARDS Network compared conventional Vtof 12 ml/kg with low Vtof 6 ml/kg and permissive hypercapnia. A 9% absolute mortality reduction was found in the low Vtventilation group along with reduced pulmonary and circulating inflammatory cytokines. The aim of positive end-expiratory pressures (PEEP) in ARDS is to recruit (or maintain recruitment) of atelectatic or flooded lung. Initial studies looking at the effects of PEEP described adverse hemodynamic effects at high levels, leading to a reduction in cardiac output and oxygen delivery. Recruitment maneuvers are used to open areas of atelectasis improving lung compliance and oxygenation. The prognosis of ARDS has improved over the past 20 years. Overall, 60–70% of patients survive. Patients with poor prognostic factors include those older than 65 years and those with sepsis as the underlying cause. The adverse effect of age may be related to underlying health status. Conclusion We found that mechanical ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (Vt), and higher PEEPs can improve survival in patients with ARDS, but the relative importance of each of these components is uncertain. The ARDS Network trial showed that a ventilation strategy with a lower tidal volume (4–8 ml/kg of predicted body weight) was associated with lower mortality and shorter length of mechanical ventilation. This trial used a combination of volume and pressure limitation.

Transcatheter Aortic Valve Replacement: OPTIMIZING OUTCOMES FOR HEALTHY RECOVERY.

Transcatheter aortic valve replacement (TAVR) has been approved in the United States for intermediate and high-risk patients with severe symptomatic aortic stenosis. More than 80 000 TAVR procedures have been performed in the United States and the number is growing every year. Two valve designs are approved in the United States including the balloon expandable Edwards Sapien prosthesis and self-expanding CoreValve prosthesis. The PARTNER trial of the Sapien valve, involving patients who were considered inoperable, reported a 19% absolute risk reduction in mortality compared with medical therapy, with a number needed to treat of 5. Randomized controlled trials in patients with high and intermediate risk of inhospital mortality based on the Society of Thoracic Surgeons score showed noninferiority of TAVR compared with surgical aortic valve replacement. Major complications associated with TAVR include a 2% to 3% risk of stroke at 30 d, 8% to 25% risk of permanent pacemaker implantation depending on valve design, and 6% risk of major vascular complications. There are some concerns regarding valve durability as this technology is extended to younger patients with lower risk. Five-year follow-up data from the initial PARTNER trials noted appropriate valve performance and hemodynamics in survivors; however, longer follow-up is required to assess the true incidence of structural deterioration. Approximately one-third of TAVR patients are transferred to a transitional care facility after TAVR, and more than 50% of the patients are frail. Cardiac rehabilitation has been reported to be safe in post-TAVR patients and was associated with significant improvements in exercise capacity, functional independence, and frailty.

Indications for extracorporeal support: why do we need the results of the EOLIA trial?

Acute respiratory distress syndrome (ARDS) is asevere lung disease, with an associated mortality rate exceeding 60% for the most severe forms of the disease. In these situations, establishing an extracorporeal circuit, combining acentrifugal pump and amembrane oxygenator (extra-corporeal membrane oxygenation, ECMO), can ensure total pulmonary assistance and allow the lungs to rest under ultraprotective mechanical ventilation. Unfortunately, former trials of ECMO in ARDS were negative or highly criticized due to many technical and methodological shortcomings. Prior to the widespread use of venovenous ECMO for severe ARDS, new trials are needed to test the efficacy of early initiation of the technique with tight control of mechanical ventilation in the control group, initiation of ECMO prior to transportation to ECMO centers, and the use of ECMO in all patients randomly assigned to receive this treatment. Therefore, the international multicenter randomized EOLIA (ECMO to rescue Lung Injury in severe ARDS) trial was designed to test the benefit of systematic and early installation of the latest-generation ECMO circuits in patients with very severe ARDS. Patients randomized to the control group were managed with tight control of mechanical ventilation and recourse to paralyzing agents and prone positioning, while an ethical crossover option to ECMO was permitted only if refractory hypoxemia (SaO2< 80%) lasted for >6 h despite all possible conventional emergency interventions. The primary endpoint of the study was the 60-day mortality rate, with an expected 20% absolute mortality reduction with ECMO.