Meaningful Improvements In Clinical Outcomes Research Articles

Triple therapy boosts survival in NSCLC patients with brain metastases: a retrospective cohort study of chemotherapy, ICIs, and antiangiogenic agents

BackgroundTreatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) patients, especially those with non-sensitive genetic mutations, is hindered by limited drug delivery through the blood–brain barrier (BBB). This retrospective study explores the efficacy of systemic treatments during brain metastasis to radiotherapy evaluation window in improving patient survival.MethodsIn this retrospective cohort study, we evaluated 209 NSCLC patients with non-sensitive mutations and BMs, treated between 2016 and 2023 at two tertiary medical centers (Chongqing University Cancer Hospital and Guangxi Medical University Cancer Hospital). The patients were divided into three groups, namely chemotherapy alone (C; n = 95), chemotherapy plus immune checkpoint inhibitors (ICIs) (C + I; n = 62), and chemotherapy with ICIs and antiangiogenic therapy (A) (C + I + A; n = 52). Statistical analyses were performed using R software, version 4.3.3. Categorical variables were compared using Fisher’s exact test, and survival curves were estimated with the Kaplan–Meier method and compared via the log-rank test. Univariate and multivariate Cox regression models were used to assess factors associated with overall survival (OS). Bayesian model averaging (BMA) was employed to address model uncertainty and improve result robustness. Subgroup analyses evaluated treatment-related mortality risk.ResultsFrom an initial cohort of 658 NSCLC patients with BMs, 209 were analyzed with a median age of 59; the majority were male (80.9%) and diagnosed with adenocarcinoma (78.9%). Univariate analysis identified significant variables influencing outcomes, including BMs radiotherapy EQD2, BMs count, local thoracic treatment, BMs radiotherapy field, intracranial response, and systemic treatment post-BMs diagnosis. The C + I + A regimen significantly improved median OS to 23.6 months compared to 11.4 months with C and 16.2 months with C + I, with a hazard ratio (HR) of 0.60 (95% CI: 0.43–0.82; P < 0.0001). The two-year OS rate was highest in the C + I + A group at 38.5%, versus 10.5% in C and 20.4% in C + I (P < 0.001). Cox regression and BMA analyses confirmed the stability of BMA in providing HR estimates, yielding area under the curve (AUC) values of 0.785 for BMA and 0.793 for the Cox model, with no significant difference in predictive performance. Subgroup analysis revealed a 71% mortality risk reduction with C + I + A (HR: 0.29; 95% CI: 0.18–0.47; P < 0.0001), showing consistent benefits regardless of patient sex, BMs count, extracranial metastases presence, and local thoracic treatments. Treatment sequence analysis indicated a median OS of 33.4 months for patients starting with A, though not statistically significant (HR: 0.59; P = 0.36). The overall incidence of radiation-induced brain injury was low at 3.3%, with rates in the C, C + I, and C + I + A groups being 3.2%, 4.8%, and 1.9%, respectively (P = 0.683).ConclusionOur study demonstrates the significant benefit of the C + I + A combination therapy in improving OS and reducing mortality risk in NSCLC patients with non-sensitive gene-mutated BMs. The sequential administration of A followed by ICIs shows a promising synergistic effect with cranial radiotherapy, highlighting the potential for optimized treatment sequencing. These findings emphasize the efficacy of tailored combination therapies in complex oncological care and suggest that our approach could lead to meaningful improvements in clinical outcomes for this challenging patient population.

2-Year Clinical and Echocardiography Follow-Up of Transcatheter Mitral Valve Replacement With the Transapical Intrepid System

BackgroundThirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. ObjectivesThe authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. MethodsPatient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. ResultsThe cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. ConclusionsThis analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.

Background for the introduction of enhanced recovery after surgery and patient outcomes

Background: To facilitate early postoperative recovery of surgical patients, various efforts have been made to develop effective treatment methods since 1990; moreover, these efforts have not been limited to surgical techniques and include multiple aspects of the entire treatment process. Enhanced recovery after surgery (ERAS) is a surgical quality improvement project that has advanced substantially since it was first introduced in 1995 and has now been firmly established in the field of perioperative care.Current Concepts: ERAS consists of many components that cover each stage before, during, and after surgery, and its clinical application changes according to the results of evidence-based research for each item. To date, more than 20 ERAS guidelines have been created for each disease, and more guidelines are expected in the future. Many studies have reported that ERAS is associated with meaningful improvements in clinical outcomes and reductions of medical costs in many surgical fields.Discussion and Conclusion: ERAS remains a work in progress, and continuous research and improvement is needed in relation to the components, areas of application, audit of compliance and results, education, and a multidisciplinary approach.

Improvement of clinical and radiological outcomes of root repair patients with advanced articular cartilage degeneration and osteoarthritis

PurposeThe main purpose of this study was to investigate clinical and radiological outcomes of medial meniscus posterior root tear (MMPRT) repair in knees with advanced articular cartilage degeneration and osteoarthritis compared to those with minimal degenerative change.MethodsThirty-three knees underwent MMPRT repair using an arthroscopic pullout repair tibial tunnel technique. Clinical scores including Lysholm Score, International Knee Documentation Committee (IKDC) Score and Knee injury and Osteoarthritis Outcome (KOOS) Score were collected preoperatively and sequentially at 6 months, 12 months and mean final follow-up of 39.4 months. Kellgren-Lawrence (K-L) osteoarthritis grade, Outerbridge classification of cartilage degeneration and the presence of bone marrow oedema on MRI were also evaluated.ResultsAll clinical scores improved at final follow-up for knees with K-L grade ≥ 2 osteoarthritis (p < 0.001), with no significant difference compared to K-L 0/1. Patients with Outerbridge class 3/4 cartilage degeneration also reported improvements in clinical scores, albeit lower than those with class 2 degeneration (p < 0.05). During recovery, the majority of patients reported clinical improvements by 6 months, and six patients further improved by at least 15 points in IKDC score between 6 and 12 months. Osteoarthritis progressed in 10 of 31 knees (32%), with an overall mean pre-operative K-L grade of 1.6 ± 0.9 compared to 2.0 ± 0.9 at final follow-up (n.s.). No knees progressed to K-L 4 or underwent re-operation. Pre-operative bone marrow oedema was present in 17 knees (52%), all of which had signal localised to the medial tibia or femur. Oedema had resolved in all but 5 knees post-operatively (p < 0.01).ConclusionArthroscopic repair of medial meniscus posterior root tears is associated with improved outcomes in knees with advanced cartilage degeneration and osteoarthritis. Meaningful improvements in clinical outcomes can be achieved beyond 6 months, thus success of the operation is best determined at the 12-month mark. Oedema signal significantly improved post-operatively, however a relatively high proportion of knees had K-L progression.Level of evidenceIV – Case Series.

Catheter Ablation in Persistent AF, the Evolution towards a More Pragmatic Strategy.

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and represents a heterogeneous disorder with a complex pathological basis. While significant technological advances have taken place over the last decade in the field of catheter ablation of AF, response to ablation varies and long-term success rates in those with persistent AF remain modest. Mechanistic studies have highlighted potentially different sustaining factors for AF in the persistent AF population with substrate-driven focal and re-entrant sources in the body of the atria identified on invasive and non-invasive mapping studies. Translation to clinical practice, however, remains challenging and the application of such mapping techniques to clinical ablation has yet to demonstrate a significant benefit beyond pulmonary vein isolation (PVI) alone in the persistent AF cohort. Recent advances in catheter and ablation technology have centered on improving the durability of ablation lesions at index procedure and although encouraging results have been demonstrated with early studies, large-scale trials are awaited. Further meaningful improvement in clinical outcomes in the persistent AF population requires ongoing advancement in the understanding of AF mechanisms, coupled with continuing progress in catheter technology capable of delivering durable transmural lesions.

Acute changes of left ventricular function during surgical revascularization by 3D speckle tracking.

Detecting early impact of coronary artery bypass grafting (CABG) on left ventricular (LV) function is important because such measures may contribute to meaningful improvement in clinical outcomes. We aimed to gain knowledge about acute changes of LV performance during surgical revascularization using three-dimensional speckle tracking echocardiography (3D STE). Thirty-five patients scheduled for CABG surgery who underwent intraoperative transesophageal echocardiography (TEE) were enrolled (mean age 68.9±7.3years). TEE was performed before and after surgery, as well as before and after grafting. 3D LV ejection fraction (LVEF), tissue motion annular displacement (TMAD) of the mitral valves, 3D global longitudinal strain (GLS), global circumferential strain (GCS), twist, and torsion were quantified. Regional longitudinal strain (LS) was calculated based on coronary perfusion territories in a 16-segment LV model. Despite the absence of change in TMAD and 3D LVEF, 3D GLS (-18.6±4.3% at baseline vs -16.0±4.0% after surgery, P=.01) was significantly decreased, followed with no significant effect on GCS, twist, and torsion during surgery. 3D GLS correlated significantly with 3D LVEF (r between -0.34 and -0.51, P<.05 for all) under the whole operation. Territorial LS did not increase immediately after surgery. 3D speckle tracking imaging allows for detailed and direct evaluation of myocardial deformation, though impaired LV longitudinal function is still apparent immediately after surgery. GLS is more sensitive to an acute reduction in LV function than conventional parameters, which can be potentially useful for serial monitoring of functional recovery.

Abstract PS10-17: Palbociclib (P) in combination with fulvestrant (F) or letrozole (L) in endocrine-sensitive patients (pts) with hormone receptor (HR)[+]/HER2[-] metastatic breast cancer (MBC): detailed safety analysis from a multicenter, randomized, open-label, phase II trial (PARSIFAL)

Abstract Background: P led to a meaningful improvement in clinical outcomes when used in combination with endocrine therapy for first- or later-line regimen in HR[+]/HER2[-] MBC. Grade 3-4 neutropenia was the most common adverse event (AE) in the P-containing regimens. Although venous thromboembolic events (VTE) have been rarely reported in registrational trials, a systematic review and meta-analysis of randomized controlled trials demonstrated a higher rate of these AEs. Moreover, rare but severe cases of interstitial lung disease (ILD)/pneumonitis have been observed during post-approval use of P. Here, we present a comprehensive toxicity profile of pts included in the PARSIFAL study, with particular emphasis given to AEs of special interest of the overall safety population. Methods: A total of 486 pts with HR[+]/HER2[-] MBC with no prior therapy in the advanced setting and endocrine sensitive criteria (relapse &amp;gt;12 months [mo] after the end of adjuvant endocrine therapy or diagnosed with de novo metastatic disease) were randomly assigned 1:1 to receive P (oral 125 mg/day [d]; 3 weeks on/1 week off) plus either F (intramuscular injection 500 mg/d; d 0, 14, 28, and then every 28 ds) or L (oral 2.5 mg/d). Pts were stratified by visceral involvement and type of disease presentation (de novo/recurrent). Safety assessments included blood analysis and collection of vital signs at screening, d1 of each cycle, and end of treatment/withdrawal. Severity was graded as per the NCI Common Terminology Criteria for Adverse Events v.4.03. Results: The incidence rate of any grade, grade 3-4, and serious AEs was 99.6%, 80.9%, and 29.9%, respectively, in the FP arm, and 99.2%, 78.5%, and 21.1% in the LP arm. Discontinuations due to AEs were 5.4% in the FP arm and 2.1% in the LP arm. Neutropenia, leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most frequent AEs in both arms. Febrile neutropenia was reported in 1.2% (3 pts) and 0.4% (1 patient) in the FP and LP arms, respectively. The rate of VTE of any grade was 5.8% (14 pts) in the FP arm and 4.5% (11 pts) in the LP arm (p = 0.531). Among 18 pts who had grade ≥ 3 pulmonary embolism (PE), the incidence reported in the FP and LP arms was 5% (12 pts) vs 2.5% (6 pts), respectively, and many of them (n=16, 88.9%) were unrelated PE. Asymptomatic grade 3 PE was reported in 10 pts of the entire study population on every 3-mo CT scan. Further, in 5 pts PE was detected in the context of progressive disease. Median time from the first dose of study drugs to occurrence of PE was 4.1 mo (range 1.4-32.0 mo) in the FP arm and 7 mo (range 1.8-19.3 mo) in the LP arm. Analysis of baseline characteristics in the whole population revealed that older pts had a significantly increased risk for developing PE (69.5 years [range 47-84 years]; p &amp;lt; 0.01). ECOG performance status, menopausal status, metastatic disease, visceral involvement, number of disease sites, and prior therapies including antithrombotic agents did not significantly increase the risk for developing PE. Grade 3 ILD/pneumonitis was rarely observed in the FP and LP arms (0.8% vs 1.2%, respectively) with no grade 4 AE. Conclusions: First-line treatment with FP and LP for HR[+]/HER2[-] MBC in the PARSIFAL study confirmed the favorable safety profile, with neutropenia representing the most common AE. Although rare, ILD/pneumonitis can be a side effect of P-based regimens. VTE and PE incidence rates were low and consistent with age-specific analyses from PALOMA trials and breast cancer population. Early detection of these AEs may assist in optimizing their management. Citation Format: José Manuel Pérez-García, Antonio Llombart-Cussac, Meritxell Bellet, Florence Dalenc, Miguel J. Gil Gil, Manuel Ruiz Borrego, Joaquín Gavilá, Miguel Sampayo-Cordero, Elena Aguirre, Peter Schmid, Frederik Marmé, Serena Di Cosimo, Joseph Gligorov, Andreas Schneeweiss, Joan Albanell, Pilar Zamora, Duncan Wheatley, Eduardo Martínez-De Dueñas, Vicente Carañana, Kepa Amillano, Andrea Malfettone, Javier Cortés. Palbociclib (P) in combination with fulvestrant (F) or letrozole (L) in endocrine-sensitive patients (pts) with hormone receptor (HR)[+]/HER2[-] metastatic breast cancer (MBC): detailed safety analysis from a multicenter, randomized, open-label, phase II trial (PARSIFAL) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-17.

Radiotherapy and Immunotherapy Combinations for Lung Cancer.

Positive results from recent immunotherapy trials of non-small cell lung cancer (NSCLC) have coincided with a greater appreciation for the impact of radiation therapy (RT) on tumor immunity. Here, we summarize key clinical findings and ongoing efforts to combine immunotherapy and RT for the treatment of NSCLC. The role of immunotherapy for NSCLC has expanded significantly following the pivotal approvals of nivolumab and pembrolizumab for metastatic NSCLC, maintenance durvalumab in unresectable stage III NSCLC, and atezolizumab for metastatic NSCLC. Several small early-phase trials have demonstrated the ability of RT to elicit clinically significant tumor immunity. These positive findings support current trial efforts combining RT with immunotherapy for NSCLC. Recently initiated trials of RT and immunotherapy hold significant promise in expanding the therapeutic options for NSCLC. Optimization of therapy will require careful patient selection to yield meaningful improvements in clinical outcomes.

Demonstrating the Clinical Impact of Continuous Glucose Monitoring Within an Integrated Healthcare Delivery System.

Approximately 30 million Americans currently suffer from diabetes, and nearly 55 million people will be impacted by 2030. Continuous glucose monitoring (CGM) systems help patients manage their care with real-time data. Although approximately 95% of those with diabetes suffer from type 2, few studies have measured CGM's clinical impact for this segment within an integrated healthcare system. A parallel randomized, multisite prospective trial was conducted using a new CGM device (Dexcom G6) compared to a standard of care finger stick glucometer (FSG) (Contour Next One). All participants received usual care in primary care clinics for six consecutive months while using these devices. Data were collected via electronic medical records, device outputs, exit surveys, and insurance company (SelectHealth) claims in accordance with institutional review board approval. Ninety-nine patients were randomized for analysis (n = 50 CGM and n = 49 FSG). CGM patients significantly decreased hemoglobin A1c (p = .001), total visits (p = .009), emergency department encounters (p = .018), and labs ordered (p = .001). Among SelectHealth non-Medicare Advantage patients, per member per month savings were $417 for CGM compared to FSG, but $9 more for Medicare Advantage. Seventy percent of CGM users reported that the technology helped them better understand daily activity and diet compared to only 16% for FSG. Participants using CGM devices had meaningful improvements in clinical outcomes, costs, and self-reported measures compared to the FSG group. Although a larger study is necessary to confirm these results, CGM devices appear to improve patient outcomes while making treatment more affordable.

Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease

While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients does not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involves assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post-challenge analysis identified a novel expression-based risk marker, PHF19, which has recently been found to have an important biological role in multiple myeloma. Lastly, we show that a simple four feature predictor composed of age, ISS, and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.

239 Setting Bones and Getting Home: The Impact of a New Orthogeriatric Service

Abstract Background Orthogeriatric services have been shown to improve quality of care for older patients post hip fracture and have an impact on length of stay (LOS), both acutely and in the rehab setting(1) but other key performance indicators (KPIs) have not been examined in detail. Methods Data was prospectively collected on all hip fracture patients seen by the Orthogeriatric service from Aug 2018-Feb 2019 and was retrospectively compared with patients admitted with hip fractures from Aug 2017-Feb 2018. We examined KPIs including LOS on the orthopaedic ward, rehab admissions, rehab LOS, new nursing home (NH) admissions. We compared the proportions discharged directly home instead of to convalescence, and conducted a preliminary cost benefit analysis. Results Similar numbers of patients were seen in each time period (n=146 v n=139). Mean reduction in LOS on the orthopedic ward was 3.5 days (15.5 days vs 19 days). The proportion of patients admitted to rehabilitation increased from 8.8% to 17.5% (p = 0.02). Patients got to rehabilitation faster and for those patients who availed of rehabilitation they had significantly shorter total length of stays (51.1 days vs 71.6 days, p=0.029). Fewer patients went to convalescence. Although not statistically significant there was a trend towards an increased proportion of patients discharged directly home (32.7% to 43.6%) and less new nursing home admissions (6.8% vs 8.4%). A cost benefit analysis incorporating shortened acute and rehab LOS and a reduction in spending on convalescence resulted in a projected saving of €480,390 over a six month period. Conclusion Introduction of OrthoGeriatric services has improved care for older people with hip fractures and has resulted in positive improvements to KPIs, resulting in meaningful improvements in clinical outcomes for patients in a cost effective manner. Monies saved should be redirected into further developing orthogeriatric services.

Key Service Improvements After the Introduction of an Integrated Orthogeriatric Service.

Introduction:Models of orthogeriatric care have been shown to improve functional outcomes for patients after hip fractures and can improve compliance with best practice guidelines for hip fracture care.Methods:We evaluated improvements to key performance indicators in hip fracture care after implementation of a formal orthogeriatric service. Compliance with Irish Hip Fracture standards of care was reviewed, and additional outcomes such as length of stay, access to rehabilitation, and discharge destination were evaluated.Results:Improvements were observed in all of the hip fracture standards of care. Mean length of stay decreased from 19 to 15.5 days (mean difference 3.5 days; P < .05). A higher proportion of patients were admitted to rehabilitation (16.7% vs 7.9%, P < .05), and this happened in a timelier fashion (17.8 vs 24.8 days, P < .05). We found that less patients required convalescence post-hip fracture.Discussion:A standardized approach to integrated post-hip fracture care with orthogeriatrics has improved standards of care for patients.Conclusion:Introduction of orthogeriatric services has resulted in meaningful improvements in clinical outcomes for older people with hip fractures.

Teasing Apart Heart Failure With Preserved Ejection Fraction Phenotypes With Echocardiographic Imaging: Potential Approach to Research and Clinical Practice.

Phenotyping heart failure represents a major challenge for both research studies and clinical practice. Large-scale clinical trials have failed to achieve meaningful improvement in clinical outcomes with different pharmacological agents in patients with heart failure and preserved left ventricular ejection fraction. Therefore, an alternative scheme for phenotyping heart failure is needed, which is both pathophysiologically distinct and practical for routine clinical application. Heart failure is a syndromic diagnosis broadly based on clinical features, physical findings, and serum biomarkers. Although the assessment of exercise hemodynamics and invasive estimation of filling pressures may be necessary, it is typically confirmed and phenotyped by the imaging data. Phenotyping heart failure represents a major challenge despite decades of ongoing research, vast clinical experience in the field, and multiple iterations of published guidelines. Left ventricular ejection fraction (LVEF) remains the major phenotyping tool endorsed by multiple cardiology societies. However, it has multiple limitations especially in patients with heart failure with preserved LVEF (HFpEF), and many have questioned the current approach to phenotyping of heart failure but no alternative, widely accepted, scheme (which is both clinically relevant and practical) has been offered.1 The existing phenotyping approach to heart failure is based on the premise of LVEF as a surrogate marker for left ventricular systolic performance and, in turn, prognosis. Heart failure patients with reduced LVEF (HFrEF) are assumed to have systolic heart failure, whereas many heart failure patients have preservation of LVEF and are commonly labeled as HFpEF. This assumption makes LVEF the primary marker of heart failure and excludes other important abnormalities that can create the heart failure syndrome. Furthermore, LVEF is an imperfect marker even for assessment of systolic function: it has high interobserver variability, it mainly reflects radial shortening, it is load dependent, and it does not reflect the remodeling pattern of the …

A prospective study examining the influence of cardiac rehabilitation on the sedentary time of highly sedentary, physically inactive patients

ObjectivesProlonged sedentary time is recognized as a distinct health risk, and mortality risks are expected to be greatest for individuals with low exercise levels. It is unknown whether participation in exercise-based cardiac rehabilitation (CR) programs influences sedentary behaviour particularly among those patients expected to be at greatest mortality risk. This study examined the influence of CR participation on sedentary behaviour and identified the proportion and characteristics (socio-demographic and clinical) of patients who do not meet exercise recommendations and have prolonged sedentary times. MethodsA prospective study was conducted among patients of an exercise-based CR program and assessments performed at baseline and 3 months. Physical activity and sedentary behaviour information were collected by self-report, and convergent validity was examined on an accelerometer-wearing subsample. ResultsOf 468 CR patients approached, 130 participants were recruited with an average sedentary time of 8hours/day. Sedentary behaviour remained consistent at follow-up (relative change= −2.4%, P=0.07) notwithstanding a greater proportion meeting exercise recommendations (relative change= 57.4%). 19.2% of participants were classified to have prolonged sedentary time and not meet exercise recommendations at baseline. No significant differences were found between the characteristics of high-risk individuals and lower risk subgroups. Findings were consistent among the accelerometer-derived subgroup and the overall sample despite poor to moderate convergent validity. ConclusionsThese results suggest that the exercise-focus of CR may not reduce sedentary behaviours. Future studies are needed to determine whether sedentary behaviour-specific reduction strategies are more effective than traditional exercise-based strategies and lead to meaningful improvements in clinical outcomes.

Emerging uses of biomarkers in lung cancer management

Over the past decade, non-small cell lung cancer (NSCLC) has witnessed unprecedented scientific advances that have translated into meaningful improvements in clinical outcomes. Much of these gains have been predicated on a better understanding of tumor biology including the identification of driver mutations that allow patients to receive novel, genotype-driven therapies. Multiple studies have now demonstrated improvements in outcomes in advanced stage patients EGFR mutations and ALK rearrangements treated with tyrosine kinase inhibitors (TKIs) when compared to chemotherapy. While the precision therapy paradigm was initially restricted to these aforementioned genotypes, a broader genomic characterization of lung cancer via next generation sequencing (NGS) approaches has identified BRAF, MET exon 14 skipping mutations as well as ROS-rearrangements as actionable mutations. Aiding this effort has been the development of novel diagnostic platforms like plasma genotyping (i.e., liquid biopsies) that can identify relevant, genetic alterations in blood when tissue is inadequate. These important diagnostic and therapeutic advances in lung cancer have converged to increase the number of patients eligible for targeted therapies and improved outcomes for these patients.

Exploring the Effectiveness of Smart Technologies in the Management of Type 2 Diabetes Mellitus.

The global epidemic of diabetes, with increasing prevalence of type 2 diabetes (T2D), is placing a huge burden on health care management and financial systems. Unless new strategic solutions are developed, the increasing prevalence of T2D will result in a significant rise in morbidity, health care costs, and complications associated with diabetes. The introduction of smart devices in diabetes management may provide meaningful improvements in clinical outcomes, patient engagement, as well as potential cost reductions for the health care system. Future research may be capable of providing new smart and interactive solutions to the growing multidisciplinary diabetes team and, most important, to reduce the morbidity associated with T2D.

Navigation and Robotics in Total Hip Arthroplasty.

➢ Navigation provides information about patient anatomy and the relative positioning of the implants to guide the surgeon.➢ Some systems use a robotic arm that assists with specific parts of the procedure on the basis of anatomical information provided to the navigation system. Currently, all total hip arthroplasty robotic systems require preoperative imaging.➢ Imageless systems rely only on intraoperative landmarks identified by the surgeon and provide feedback about limb alignment and component positioning.➢ The primary benefits of navigation are a reduction in outliers during acetabular cup positioning and improved accuracy when quantifying limb-length and offset measurements. It remains to be seen whether these benefits translate into meaningful improvements in clinical outcomes.

Evolving role for mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction.

The majority of randomized clinical trials in heart failure with preserved ejection fraction (HFpEF) have failed to show meaningful improvements in clinical outcomes. Recent randomized trials have shown benefits from mineralocorticoid receptor antagonists (MRAs) in the management of HFpEF. This review will focus on new evidence for MRA therapy in patients with HFpEF. Three randomized trials were reviewed: the Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial; the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial; and its echocardiography substudy. The Aldo-DHF trial showed improvements in echocardiographic measures of diastolic function. In the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial, hospitalization for heart failure was significantly reduced with MRA therapy with no difference in the primary outcome of cardiovascular death or hospitalization. In patients with high risk, however, there may be a reduction in cardiovascular mortality. We will also briefly discuss finerenone, a new generation MRA associated with a lower incidence of hyperkalemia. New evidence shows that MRA therapy decreases left ventricular mass and left atrial size, reduces hospitalization, and may reduce cardiovascular mortality in patients with high risk.

Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial

Adenoid cystic carcinomas (ACCs) are malignant salivary gland tumors noteworthy for high rates of late failure with limited salvage therapy options. We have previously shown increased Akt signaling is common in ACC and the human immunodeficiency virus (HIV) protease inhibitor nelfinavir (NFV) inhibits in vitro tumor growth by suppressing Akt signaling. This phase II trial was conducted to determine progression-free survival in response to NFV in patients with recurrent/endstage ACC who have failed standard therapies. Eligible patients had recurrent or end-stage ACC and measureable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. NFV was provided at 1250 mg twice daily. Among 15 trial participants, median progression-free survival was 5.5 months (lower 95% bound 4.4 months). No patient achieved a RECIST partial or complete response to therapy. NFV monotherapy does not result in a meaningful improvement in clinical outcomes among patients with recurrent ACC.

Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study

IntroductionColonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD.MethodsWe included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use.ResultsAmong 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups.ConclusionsNebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.