Real-world relationship of early end points to survival end points in patients with resectable non-small-cell lung cancer.

Aim: Pathologic response has been shown to be a promising surrogate for survival in non-small-cell lung cancer. We examined the real-world relationship between these end  points in patients with resectable stage IB-IIIA non-small-cell lung cancer receiving neoadjuvant chemotherapy/chemoradiotherapy (CT/CRT). Methods: Electronic health records/medical charts were analyzed. Overall and event-free survival (OS/EFS) were assessed by Kaplan-Meier stratified by pathologic response. Associations between the end  points were assessed by Cox analyses. Results: A total of 425 patients were selected for the study; 147 and 278 received CT and CRT, respectively. Pathologic complete response (pCR) was associated with longer OS (adjusted HR = 0.50; 95% CI: 0.29-0.85) and EFS (adjusted HR = 0.44; 95% CI: 0.28-0.68) versus no pCR, and EFS was associated with OS (HR = 0.51, 95% CI: 0.38, 0.69). Conclusion: In patients receiving neoadjuvant CT/CRT, pCR and EFS were associated with improved survival in this real-world dataset.

Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017.

BACKGROUND: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. METHODS: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013-2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. RESULTS: Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45-59) for IIV4 versus 45% (95% CI, 34-54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. CONCLUSIONS: The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

First and recurrent events after percutaneous coronary intervention: implications for survival analyses.

Objectives. Using composite endpoints and/or only first events in clinical research result in information loss and alternative statistical methods which incorporate recurrent event data exist. We compared information-loss under traditional analyses to alternative models. Design. We conducted a retrospective analysis of patients who underwent percutaneous coronary intervention (Jan2010-Dec2014) and constructed Cox models for a composite endpoint (readmission/death), a shared frailty model for recurrent events, and a joint frailty (JF) model to simultaneously account for recurrent and terminal events and evaluated the impact of heart failure (HF) on the outcome. Results. Among 4901 patients, 2047(41.8%) experienced a readmission or death within 1 year. Of those with recurrent events, 60% had ≥1 readmission and 6% had >4; a total of 121(2.5%) patients died during follow-up. The presence of HF conferred an adjusted Hazard ratio (HR) of 1.32 (95% CI: 1.18-1.47, p < .001) for the risk of composite endpoint (Cox model), 1.44 (95% CI: 1.36-1.52, p < .001) in the frailty model, and 1.34 (95% CI:1.22-1.46, p < .001) in the JF model. However, HF was not associated with death (HR 0.87, 95% CI: 0.52-1.48, p = .61) in the JF model. Conclusions. Using a composite endpoint and/or only the first event yields substantial loss of information, as many individuals endure >1 event. JF models reduce bias by simultaneously providing event-specific HRs for recurrent and terminal events.

Prognostic value of urinary 11-dehydro-thromboxane B2 for mortality: A cohort study of stable coronary artery disease patients treated with aspirin.

AIM: There is a variable cardiovascular risk reduction attributable to aspirin because of individual differences in the suppression of thromboxane A2 and its downstream metabolite 11-dehydro-thromboxane B2 (11dhTxB2 ). The aim of this study is to evaluate the optimal cut point of urinary 11dhTxB2 for the risk of mortality in aspirin-treated coronary artery disease (CAD) patients. METHODS AND RESULTS: This was a prospective cohort study including stable CAD patients who visited the Baylor Heart and Vascular Hospital in Dallas or the Texas Heart Hospital Baylor Plano, TX between 2010 and 2013. The outcome of all-cause mortality was ascertained from chart review and automated sources. The 449 patients included in this analysis had a mean age of 66.1 ± 10.1 years. 67 (14.9%) patients died within 5 years; 56 (87.5%) of the 64 patients with known cause of death suffered a cardiovascular related mortality. Baseline ln(urinary 11dhTxB2 /creatinine) ranged between 5.8 and 11.1 (median = 7.2) with the higher concentrations among those who died (median: 7.6) than those who survived (median = 7.2, P < 0.001). Using baseline ln(11dhTxB2 ) to predict all-cause mortality, the area under the curve was 0.70 (95% CI: 0.64-0.76). The optimal cut point was found to be ln(7.38) = 1597.8 pg/mg, which had the following decision statistics: sensitivity = 0.67, specificity = 0.62, positive predictive value = 0.24, negative predictive value = 0.92, and accuracy = 0.63. CONCLUSION: Our data indicate the optimal cut point for urine 11dhTxB2 is 1597.8 (pg/mg) for the risk prediction of mortality over five years in stable patients with CAD patients treated with aspirin.

Renal Function and Scaled Troponin in Patients Presenting to the Emergency Department with Symptoms of Myocardial Infarction.

BACKGROUND: Cardiac troponins are often found to be elevated in patients with renal dysfunction, even in the absence of acute myocardial injury. The objective of this report was to characterize the scaled troponin values and proportion of adjudicated acute myocardial infarction (AMI) among patients with and without renal dysfunction. METHODS: The data was from a multicenter prospective study including patients presenting to the emergency department with symptoms of AMI. Troponin measurements were standardized across various assays by calculating the observed results as multiples of the assay-specific 99th percentile upper limit of normal. Patients with an estimated glomerular filtration rate (eGFR; calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) <60 mL/min/1.73 m2 were considered to have renal dysfunction. RESULTS: Of 430 included patients, 249 (58%) were male and 181 (42%) were female, with a mean age of 55.9 ± 12.3 and 57.3 ± 12.8 years, respectively. Eighty-seven (20.2%) had renal dysfunction. The proportions of patients with at least one scaled troponin value above the 99th percentile cut-off point among patients with and without renal dysfunction were 40 (45.9%) and 81 (23.6%) respectively (p < 0.001). The proportions of patients with an adjudicated diagnosis of AMI among those with and without renal dysfunction were 20.7 and 18.7%, respectively (p = 0.67). Using scaled troponins, by the second test there was >5X and by the third test >15X separation in the excursion of troponin among those with AMI compared to those without. CONCLUSIONS: One or more elevated troponin values are common in those with renal dysfunction. Scaled troponins for eGFR groups were similar, indicating that the use of this interpretative technique is applicable in discerning AMI for those with and without renal dysfunction.

A prediction tool for nosocomial multi-drug Resistant Gram-Negative Bacilli infections in critically ill patients - prospective observational study.

BACKGROUND: The widespread use of empiric broad spectrum antibiotics has contributed to the global increase of Resistant Gram-Negative Bacilli (RGNB) infections in intensive care units (ICU). The aim of this study was to develop a tool to predict nosocomial RGNB infections among ICU patients for targeted therapy. METHODS: We conducted a prospective observational study from August'07 to December'11. All adult patients who were admitted and stayed for more than 24 hours at the medical and surgical ICU's were included. All patients who developed nosocomial RGNB infections 48 hours after ICU admission were identified. A prediction score was formulated by using independent risk factors obtained from logistic regression analysis. This was prospectively validated with a subsequent cohort of patients admitted to the ICUs during the following time period of January-September 2012. RESULTS: Seventy-six patients with nosocomial RGNB Infection (31bacteremia) were compared with 1398 patients with Systemic Inflammatory Response Syndrome (SIRS) without any gram negative bacterial infection/colonization admitted to the ICUs during the study period. The following independent risk factors were obtained by a multivariable logistic regression analysis - prior isolation of Gram negative organism (coeff: 1.1, 95% CI 0.5-1.7); Surgery during current admission (coeff: 0.69, 95% CI 0.2-1.2); prior Dialysis with end stage renal disease (coeff: 0.7, 95% CI 0.1-1.1); prior use of Carbapenems (coeff: 1.3, 95% CI 0.3-2.3) and Stay in the ICU for more than 5 days (coeff: 2.4, 95% CI 1.6-3.2). It was validated prospectively in a subsequent cohort (n = 408) and the area-under-the-curve (AUC) of the GSDCS score for predicting nosocomial ICU acquired RGNB infection and bacteremia was 0.77 (95% CI 0.68-0.89 and 0.78 (95% CI 0.69-0.89) respectively. The GSDCS (0-4.3) score clearly differentiated the low (0-1.3), medium (1.4-2.3) and high (2.4-4.3) risk patients, both for RGNB infection (p:0.003) and bacteremia (p:0.009). CONCLUSION: GSDCS is a simple bedside clinical score which predicts RGNB infection and bacteremia with high predictive value and differentiates low versus high risk patients. This score will help clinicians to choose appropriate, timely targeted antibiotic therapy and avoid exposure to unnecessary treatment for patients at low risk of nosocomial RGNB infection. This will reduce the selection pressure and help to contain antibiotic resistance in ICUs.

Treatment Patterns and Clinical Outcomes Among Patients with Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations Previously Treated with Platinum-Based Chemotherapy and Immunotherapy.

BACKGROUND: For patients with metastatic non-small cell lung cancer, timely molecular testing is essential to determine the appropriate course of therapy. Initial treatment with platinum chemotherapy and/or an immune checkpoint inhibitor (ICI) is the standard of care for patients without actionable genomic alterations. OBJECTIVE: We aimed to assess treatment patterns and clinical outcomes among patients with metastatic non-small cell lung cancer, no actionable genomic alterations, and with prior ICI and platinum-based chemotherapy in a community oncology setting. METHODS: This retrospective observational study examined electronic health records from adult patients with an initial metastatic non-small cell lung cancer diagnosis without actionable genomic alterations from 2017 to 2019. Patients had received a subsequent line of therapy (LOT) [index] after discontinuing platinum-based chemotherapy plus an ICI in the previous one or two LOTs. Patient demographics and clinical characteristics were analyzed descriptively. Clinical outcomes were evaluated using Kaplan-Meier analyses. RESULTS: Among the study population (n = 961), the most common index LOT regimens were non-platinum-based chemotherapies (57.3%), platinum-based chemotherapies (12.9%), ICI-based chemotherapies (12.7%), platinum + ICI-based chemotherapies (9.4%), and other (7.7%). The most common post-index LOT regimens were non-platinum based (61.2%), ICI based (15.3%), platinum based (10.7%), platinum + ICI based (3.2%), and other (2.5%). Median time to treatment discontinuation, time to next treatment, and overall survival were numerically longest with index LOT ICI-based regimens (6.5, 9.9, and 18.9 months, respectively) and shortest with platinum-based regimens (2.8, 5.3, and 8.0 months, respectively) and non-platinum-based regimens (2.6, 5.0, and 7.8 months, respectively). CONCLUSIONS: Among patients with metastatic non-small cell lung cancer without actionable genomic alterations previously treated with platinum + ICIs, non-platinum chemotherapy agents were most commonly prescribed in the index LOT. Clinical outcomes including time to treatment discontinuation, time to next treatment, and overall survival were short, highlighting the unmet need for more effective later-line treatments.

Compromised Outcomes in Stage IV Non-Small-Cell Lung Cancer With Actionable Mutations Initially Treated Without Tyrosine Kinase Inhibitors: A Retrospective Analysis of Real-World Data.

PURPOSE: Identification and targeting of actionable oncogenic drivers (AODs) in advanced non-small-cell lung cancer (NSCLC) has dramatically improved outcomes. However, genomic testing uptake is variable and hampered by factors including slow turnaround time, frequently resulting in initial non-tyrosine kinase inhibitor (TKI) treatment. We investigate how this behavior affects outcomes. METHODS: This retrospective analysis of real-world, deidentified data from the Integra Connect Database included adults with stage IV NSCLC newly diagnosed from January 1, 2018, to December 31, 2020, with mutations of EGFR, ALK, ROS1, BRAF, MET, RET, ERBB2, or NTRK. Outcomes were reported as time to next treatment or death (TTNT) and overall survival (OS). RESULTS: Five hundred ten patients harboring AODs were identified and grouped as follows: group A (n = 379) were treated after the AOD was reported and served as the comparator. One hundred thirty-one patients treated before their AOD report were divided into group B (n = 47) who were initially started on chemotherapy and/or checkpoint inhibitor but switched to appropriate TKI within 35 days and group C (n = 84) who were also started empirically on non-TKI and did not switch within 35 days. Survival (OS) was significantly superior in group A compared with group C; TTNT was significantly superior in group A compared with groups B and C. CONCLUSION: For patients harboring AODs in advanced NSCLC, initial treatment before receipt of genomic test results yields significantly inferior outcomes and should be avoided. Molecular profiling panels with rapid turnaround times are essential to optimize patient outcomes and should be standard of care.

Risk factors for infection/colonization caused by resistant Gram negative bacilli in critically ill patients (an observational study of 1633 critically ill patients).

OBJECTIVE: The objective of this study is to identify risk factors associated with multi-resistant Gram negative (RGNB) infection and colonization among critically ill patients. METHODS: A prospective cohort study of all patients aged 21-90 admitted for more than 24 hours in Medical and Surgical intensive care units (ICU) at a large teaching hospital in Singapore for the period of Aug '07-Dec '09 was conducted. Patient demographics, comorbidities, antibiotics, invasive devices, and culture results were collected. Forward stepwise logistic regression analyses were done to identify risk factors associated with RGNB infection and colonization. RESULTS: Of the 1373 patients included in the analysis, 13.5% developed RGNB infection. A logistic regression analysis including variables with a p value of <0.2 in the univariate analysis showed that recent surgery (OR 2.1, 95% CI 1.2-3.6), renal impairment (OR 2.9, 95% CI 1.5-5.4), liver disease (OR: 3.8, 95% CI 1.7-8.8), central line (OR 1.8, 95% CI 1.01-3.4) were independently associated with RGNB infection in the ICU. Surgery (OR 3.9, 95% CI 2.7-5.7), third-line antibiotics (carbapenem, vancomycin, linezolid) (OR 1.8, 95% CI 1.2-2.9) were independently associated with RGNB infection during their hospitalization. CONCLUSION: The major risk factors identified for RGNB infection and colonization in the ICU were mainly patient dependent. However, broad spectrum initial antibiotic treatment remains an important independent modifiable risk factor. Interventions aimed at reducing initial broad spectrum antibiotics are clearly needed to help control the spread of these difficult to treat infections.

Neutralizing and protective murine monoclonal antibodies to the hemagglutinin of influenza H5 clades 2.3.2.1 and 2.3.4.4.

BACKGROUND: Highly pathogenic avian H5 influenza viruses have spread and diversified genetically and antigenically into multiple clades and subclades. Most isolates of currently circulating H5 viruses are in clade 2.3.2.1 or 2.3.4.4. METHODS: Panels of murine monoclonal antibodies (mAbs) were generated to the influenza hemagglutinin (HA) of H5 viruses from the clade 2.3.2.1 H5N1 vaccine virus A/duck/Bangladesh/19097/2013 and the clade 2.3.4.4 H5N8 vaccine virus A/gyrfalcon/Washington/41088-6/2014. Antibodies were selected and characterized for binding, neutralization, epitope recognition, cross-reactivity with other H5 viruses, and the ability to provide protection in passive transfer experiments. RESULTS: All mAbs bound homologous HA in an ELISA format; mAbs 5C2 and 6H6 were broadly binding for other H5 HAs. Potently neutralizing mAbs were identified in each panel, and all neutralizing mAbs provided protection in passive transfer experiments in mice challenged with a homologous clade influenza virus. Cross-reacting mAb 5C2 neutralized a wide variety of clade 2.3.2.1 viruses, as well as H5 viruses from other clades, and also provided protection against heterologous H5 clade influenza virus challenge. Epitope analysis indicated that the majority of mAbs recognized epitopes in the globular head of the HA. The mAb 5C2 appeared to recognize an epitope below the globular head but above the stalk region of HA. CONCLUSIONS: The results suggested that these H5 mAbs would be useful for virus and vaccine characterization. The results confirmed the functional cross-reactivity of mAb 5C2, which appears to bind a novel epitope, and suggest the therapeutic potential for H5 infections in humans with further development.

Real-world patterns of biomarker testing and targeted therapy in de novo metastatic non-small cell lung cancer patients in the US oncology network.

BACKGROUND: This study investigated biomarker testing and biomarker-guided treatment among patients with metastatic NSCLC in a real-world setting. METHODS: This retrospective study examined adult patients diagnosed with de novo mNSCLC between 01-Jan-2016 and 30-Sep-2019, with follow-up through 31-Dec-2019 using The US Oncology Network structured electronic health records data, with chart review for a subset. RESULTS: Of 2257 patients, 76.3% had results for ≥1 driver mutation (DM) or programmed death ligand-1 (PD-L1) during the study observation period. The proportion with results for all 4 DM before 1L initiation increased from 2017 to 2019. Over 40% had results for anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and c-ros oncogene 1 (ROS1) and 22% for B-Raf proto-oncogene (BRAF) before 1L initiation by structured data. In the chart review subset (n = 197), >70% had results for ALK, EGFR, or ROS1 with 44% for BRAF. Of the 42 ALK+ patients, 5 had results before 1L treatment and 3 received 1L ALK inhibitors. Similar, for the other biomarkers, not all who tested positive for a DM received 1L targeted therapy. The proportion of biomarker-positive patients receiving 1L targeted therapy was higher in chart review versus structured data. However, in both analyses, a substantial proportion did not have results for all 4 DM plus PD-L1 tests for appropriate biomarker-directed 1L treatment selection. CONCLUSIONS: Despite increasing biomarker testing rates, reduced turnaround times, and availability of promising biomarker-based therapies, inadequate testing in the community oncology setting means that not all eligible patients are receiving the most effective therapies up front.

Risk factors predisposing to acute stroke in India: a prospective study.

BACKGROUND: Stroke is an important neurological disorder with significant morbidity and mortality. In India, the risk factors for stroke (obesity, diabetes mellitus, alcoholism, hypertension, and sedentary lifestyle) are mounting with economic growth and increasing the disease burden. OBJECTIVE: To assess the severity and risk factors of stroke in India and identify any new predisposing factors. METHODS: A multicentric (six tertiary care hospitals across India) prospective observational study (from September 2016 to July 2017) was conducted on 526 stroke patients, presenting within the first 24 h to examine the risk factors for ischemic and hemorrhagic strokes. Severity was determined using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Predominantly male (72.3%), 75% of the sample was >50 years old, with a mean body mass index (BMI) of 25.8 ±â€Š4.3 kg/m2 and 14.6% obese patients. Hypertension and diabetes mellitus were the commonest comorbidities, followed by a history of ischemic heart disease and familial history of stroke. 20.5% of patients had mild strokes, 57.4% had moderate, 8.4% experienced moderate-severe strokes, whereas 7.2% had severe strokes. Regarding the admission diagnoses, 56.8% were ischemic, 18.6% were hemorrhagic, 1.1% had a transient ischemic attack, 6.6% suffered recurrent strokes, and 17% were other forms. CONCLUSION: The foremost risk factors for stroke in India, hypertension and diabetes, need to be controlled and treated like other global high-risk populations for stroke prevention. The NIHSS scores highlight the relationship between risk factors and stroke severity.

Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case-control study.

BACKGROUND: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. METHOD: A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. RESULTS: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting. CONCLUSION: A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.

Hybrid intervention approach to coronary artery and valvular heart disease.

Coronary angiography is used to assess the burden of coronary artery disease prior to surgical valve repair/replacement and often leads to concomitant bypass and valve surgery. We sought to evaluate outcomes of an alternative, hybrid approach involving percutaneous coronary intervention (PCI) and valve surgery, assessing the rate of stent thrombosis as a primary outcome. We reviewed charts of consecutive patients who underwent planned PCI prior to surgical valve repair/replacement by a single surgeon from January 2008 to December 2016. We calculated rates of surgical complication, duration of dual antiplatelet therapy (DAPT) prior to surgery, and rates of stent thrombosis and in-stent restenosis. Twenty-four patients were included in this study. Surgery was performed a median of 52.5 days following PCI. DAPT was withheld an average of 8 days before and resumed an average of 4 days after surgery. Ninety-two percent of surgeries were minimally invasive. There were no bleeding complications, stent thromboses, or restenosis events. All patients survived the 1-year follow-up. For patients with mixed coronary and valvular heart disease, a heart team approach involving preoperative PCI followed by staged minimally invasive valvular surgery appears to be safe and warrants further exploration.

Comparison of the Bentall procedure versus valve-sparing aortic root replacement.

Bentall and valve-sparing root replacement (VSRR) procedures are established treatments for aortic root disease. We present a single-center retrospective analysis comparing outcomes of bioprosthetic Bentall (BB), mechanical Bentall (MB), and VSRR patients from November 2007 to October 2016. Survival analysis was performed to evaluate the composite endpoint of freedom from recurrent aortic insufficiency, reoperation, or death. Of the 170 patients, BB was performed in 36 patients, MB in 63 patients, and VSRR in 71 patients. For BB, MB, and VSRR, the mean age was 63.8, 45.5, and 49.2 years (P < 0.001), respectively. Additionally, significantly more patients in the MB group (n = 32, 50.8%, P < 0.001) than in the BB and VSRR groups had prior cardiac surgeries. Cardiopulmonary bypass time and cross-clamp time were significantly longer in the VSRR group (P = 0.04 and 0.0005, respectively). Despite the complexity of the procedure, VSRR patients had higher combined freedom from death and reoperation than patients in the BB or MB groups. Elective Bentall root replacement is an excellent option for patients with root disease. Patients undergoing Bentall tend to have more severe or emergent cases, making them unlikely candidates for VSRR. VSRR in experienced centers carries equivalent morbidity and mortality and improved survival.

Limitations of transoesophageal echocardiogram in acute ischaemic stroke.

Objective: The role of transoesophageal echocardiography (TOE) in identifying ischaemic stroke aetiology is debated. In 2018, the American Heart Association/American Stroke Association (AHA/ASA) issued class IIa recommendation for echocardiography, with the qualifying statement of use in cases where it will alter management. Hence, we sought to determine the rate at which TOE findings altered management in cases of confirmed ischaemic stroke. Methods: We retrospectively analysed TOE cases with confirmed ischaemic stroke at our centre between April 2015 and February 2017. We defined a change in management as the initiation of anticoagulation therapy, antibiotic therapy or patent foramen ovale closure as a direct result of TOE findings. Results: There were 185 patients included in this analysis; 19 (10%) experienced a change in management. However, only 7 of the 19 (4% of all subjects) experienced a change in management due to TOE findings. The remaining 12 were initiated on oral antigoagulation as a result of discoveries during routine workup, mainly atrial fibrillation on telemetry monitoring. Conclusions: This work suggests an overuse of TOE and provides support for the 2018 AHA/ASA stroke guidelines, which recommend against the routine use of echocardiography in the work up of cerebrovascular accident due to a cardioembolic source.

Comparison of Frequency of Vascular Complications With Ultrasound-Guided Versus Fluroscopic Roadmap-Guided Femoral Arterial Access in Patients Who Underwent Transcatheter Aortic Valve Implantation.

To compare outcomes of ultrasound guidance (USG) versus fluoroscopy roadmap guidance (FG) angiography for femoral artery access in patients who underwent transfemoral (TF) transcatheter aortic valve implantation (TAVI) to determine whether routine USG use was associated with fewer vascular complications. Vascular complications are the most frequent procedural adverse events associated with TAVI. USG may provide a decreased rate of access site complications during vascular access compared with FG. Patients who underwent TF TAVI between July 2012 and July 2017 were reviewed and outcomes were compared. Vascular complications were categorized by Valve Academic Research Consortium-2 criteria and analyzed by a multivariable logistic regression adjusting for potential confounding risk factors including age, gender, body mass index, peripheral vascular disease, Society of Thoracic Surgeons score and sheath to femoral artery ratio. Of the 612 TAVI patients treated, 380 (63.1%) were performed using USG for access. Routine use of USG began in March 2015 and increased over time. Vascular complications occurred in 63 (10.3%) patients and decreased from 20% to 3.9% during the study period. There were fewer vascular complications with USG versus FG (7.9% vs 14.2%, p = 0.014). After adjusting for potential confounding risk factors that included newer valve systems, smaller sheath sizes and lower risk patients, there was still a 49% reduction in vascular complications with USG (odds ratio 0.51, 95% confidence interval 0.29 to 0.88, p = 0.02). In conclusion, USG for TF TAVI was associated with reduced vascular access site complications compared with FG access even after accounting for potential confounding risk factors and should be considered for routine use for TF TAVI.

Association between irritable bowel syndrome and asthma: a meta-analysis and systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder often seen in outpatient clinics. Diagnosing IBS is often challenging, as it frequently presents with other complicated rheumatological and psychiatric conditions. Asthma has often been associated with gastrointestinal conditions such as gastroesophageal reflux disease and eosinophilic esophagitis. This review and meta-analysis aimed at a better understanding of the association between the conditions. METHODS: A comprehensive literature review was completed using MEDLINE and EMBASE databases through January 2019. Case-control, cross-sectional and cohort studies that evaluated the association between asthma and IBS were divided into 2 groups: the first included studies that identified patients with asthma first and then looked for the presence of IBS. The second group included studies that identified IBS patients first and then looked for the presence of asthma. Random effects meta-analysis was conducted using STATA 15. RESULTS: The search strategy generated a total of 634 studies and 10 eligible studies (8 case-control and 2 cross-sectional) were selected for meta-analysis. Analysis showed that asthmatics have twice the risk of having IBS (pooled odds ratio [OR] 2.0, 95% confidence interval [CI] 1.5-2.8), and patients with IBS have twice the risk of having asthma (pooled OR 2.2, 95%CI 1.3-3.9). CONCLUSIONS: This study highlights that the risk of asthma is considerably higher in IBS patients and vice versa. Physicians should look out for pulmonary symptoms in IBS patients and consider evaluation with spirometry when necessary. Likewise, asthmatics presenting with gastrointestinal symptoms may need consultation and evaluation for IBS.

Frequency of abnormal fractional flow reserve measurements among major coronary arteries.

BACKGROUND: Fractional flow reserve(FFR) is a validated tool for evaluating functional severity and guiding the revascularization of angiographically moderate coronary artery lesions. OBJECTIVE: To study if there is a higher frequency of positive FFR measurements in the left anterior descending(LAD) versus other major coronary arteries and also evaluate the differences in the total length of the stent placed. METHODS: A retrospective cohort study including all subjects (January 2011 to December 2015) who had fractional flow reserve (FFR) measured during coronary catheterization was conducted. Coronary catheterizations with FFR at a single tertiary care center were reviewed and FFR ≤ 0.80 post adenosine was deemed positive. The differences in the baseline characteristics and the degree of stenosis were compared between the different vessel groups. RESULTS: Of the 758 vessels included in the analysis, the majority were LAD(51.3%) followed by right coronary artery(RCA)(22.8%), Circumflex(22.2%), Left main(2.2%), and Ramus intermedius(1.5%). 25.1% of 758 vessels were FFR positive. The proportion of positive FFR were higher among LAD versus other vessels(33.2%vs.16.5%,p < 0.001), while no differences were noted between RCA and circumflex(p = 0.87) or other vessels excluding LAD(p = 0.69). Of 175 patients who received stents, no statistical difference was noted in the median[range] total length of the stent between LAD(22[9-64]) and the other coronary arteries (18[8-42])(p = 0.19). In patients with an FFR <0.75, we found that the stent length(median [range]) was significantly longer in LAD(28[9-42]) than the other coronary arteries(18[8-42])(p = 0.03). CONCLUSION: In our study, FFR was almost twice as likely to be positive in the LAD when compared to other major coronary arteries. Furthermore, there was a trend towards FFR positive LAD lesions needing longer stents than other coronary arteries. This data should encourage operators to evaluate moderate, long lesions in the LAD with FFR, as they have a higher probability of functional significance.

Event dependence in the analysis of cardiovascular readmissions postpercutaneous coronary intervention.

Recurrent hospitalizations are common in longitudinal studies; however, many forms of cumulative event analyses assume recurrent events are independent. We explore the presence of event dependence when readmissions are spaced apart by at least 30 and 60 days. We set up a comparative framework with the assumption that patients with emergency percutaneous coronary intervention (PCI) will be at higher risk for recurrent cardiovascular readmissions than those with elective procedures. A retrospective study of patients who underwent PCI (January 2008-December 2012) with their follow-up information obtained from a regional database for hospitalization was conducted. Conditional gap time (CG), frailty gamma (FG) and conditional frailty models (CFM) were constructed to evaluate the dependence of events. Relative bias (%RB) in point estimates using CFM as the reference was calculated for comparison of the models. Among 4380 patients, emergent cases were at higher risk as compared with elective cases for recurrent events in different statistical models and time-spaced data sets, but the magnitude of HRs varied across the models (adjusted HR [95% CI]: all readmissions [unstructured data]-CG 1.16 [1.09 to 1.22], FG 1.45 [1.33 to 1.57], CFM 1.24 [1.16 to 1.32]; 30-day spaced-CG1.14 [1.08 to 1.21], FG 1.28 [1.17 to 1.39], CFM 1.17 [1.10 to 1.26]; and 60-day spaced-CG 1.14 [1.07 to 1.22], FG 1.23 [1.13 to 1.34] CFM 1.18 [1.09 to 1.26]). For all of the time-spaced readmissions, we found that the values of %RB were closer to the conditional models, suggesting that event dependence dominated the data despite attempts to create independence by increasing the space in time between admissions. Our analysis showed that independent of the intercurrent event duration, prior events have an influence on future events. Hence, event dependence should be accounted for when analyzing recurrent events and challenges contemporary methods for such analysis.