Elevated Risk Of Adverse Events Research Articles

Comparison of physiological and clinical reactions to COVID-19 and influenza vaccination

BackgroundPublic reluctance to receive COVID-19 vaccination is associated with safety concerns. By contrast, the seasonal influenza vaccine has been administered for decades with a solid safety record and a high level of public acceptance. We compare the safety profile of the BNT162b2 COVID-19 booster vaccine to that of the seasonal influenza vaccine.MethodsWe study a prospective cohort of 5079 participants in Israel and a retrospective cohort of 250,000 members of MHS selected randomly. We examine reactions to BNT162b2 mRNA COVID-19 booster and to influenza vaccinations. All prospective cohort participants wore a smartwatch and completed a daily digital questionnaire. We compare pre-vaccination and post-vaccination smartwatch heart-rate data, and a stress measure based on heart-rate variability. We also examine adverse events from electronic health records.ResultsIn the prospective cohort, 1905 participants receive the COVID-19 booster vaccine; 899 receive influenza vaccination. Focusing on those who receive both vaccines yields a total of 689 participants in the prospective cohort and 31,297 members in the retrospective cohort. Individuals reporting a more severe reaction after influenza vaccination tend to likewise report a more severe reaction after COVID-19 vaccination. In paired analysis, the increase in both heart rate and stress measure for each participant is higher for COVID-19 than for influenza in the first 2 days after vaccination. No elevated risk of hospitalization due to adverse events is found following either vaccine. Except for Bell’s palsy after influenza vaccination, no elevated risk of adverse events is found.ConclusionsThe more pronounced side effects after COVID-19 vaccination may explain the greater concern associated with it. Nevertheless, our comprehensive analysis supports the safety profile of both vaccines.

Transition mentorship for spina bifida patients with the JUMP program: a pilot study.

The transition from pediatric to adult care is challenging for patients and families with spina bifida (SB). Lifelong care relationships yield to new care environments that are typically larger, less personal, and less engaged with the nuances of SB care. Adolescence and young adulthood are often characterized by personal and psychological stresses due to factors independent of illness or chronic medical complexity. Surveys have demonstrated that transition is associated with uncertainty, anxiety, and elevated risk of adverse events for many SB patients. To help mitigate this, the authors developed a trial mentorship program between teen patients with SB and undergraduate/medical students. This study analyzes and presents the initial outcomes from this program. The authors created the Join, Unite, Motivate, and Prepare (JUMP) program to improve readiness for the transition process. The mentee target population was patients aged 13-19 years receiving care at the authors' SB clinic. Mentors were screened/approved undergraduate/medical students who volunteered to participate and successfully completed online training in mentorship. Upon enrollment, each patient set a combination of clinical, self, and parent/guardian goals using the individualized transition plan. These goals were shared with the mentor, mentee, parent/guardian, and physician. To monitor success, the SB program director routinely met with each mentor to discuss progress made and areas of growth. These included continuous quantitative and qualitative goal setting and failures that needed to be addressed for each agenda. Thirteen mentor-mentee matches were created over 9 months. Of the 13 matches, 6 had more than 5 communications after the initial meeting, and 1 mentor-mentee match is still in contact today. Noted success in the program has been through mentees gaining employment, applying for scholarships, starting college, and connecting with others who are going through similar circumstances. Challenges have arisen through failure to follow-up after the initial office visit, risk with using the virtual platform, and wide geographic dispersion of both mentors and mentees across the authors' state. Transition from pediatric to adult care for adolescents with SB has proven to be a large hurdle. Easing this process through well-thought-out, interactive processes has the potential to improve readiness, increase patient autonomy, and provide exposure to the adult healthcare community. However, the mentorship model, in the SB setting, has not proven to be the remedy.

Discontinuing disease-modifying therapies in multiple sclerosis

Aging in multiple sclerosis (MS) leads to altered clinical manifestations, where the pathophysiology shifts towards compartmentalized inflammation that drives clinical progression independent of relapse activity. Consequently, the effectiveness of disease-modifying therapies (DMTs) diminishes in older patients, coinciding with an elevated risk of adverse events. This raises the question of whether MS therapies should be discontinued after a certain age, which is often proposed for patients over 55 years. Studies on treatment discontinuation have shown a slight increase in disease activity, yet without significant disability progression. This suggests that the decision to stop DMTs should be discussed with older patients, considering existing comorbidities. Following the cessation of therapy, meticulous monitoring is essential.

NSAID: Current limits to prescription

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to alleviate pain and inflammation in conditions like arthritis, migraines, and post-operative recovery. Their mechanism involves inhibiting prostaglandins that contribute to inflammation. NSAIDs are categorized based on their structure, selectivity for COX-1 and COX-2 enzymes, and plasma half-life. They are effective in treating osteoarthritis, spondyloarthritis, and rheumatoid arthritis but might carry an elevated risk of adverse events. Despite their effectiveness, NSAIDs have limitations and risks that warrant cautious consideration. Extensive research has investigated their side effects, and this review aims to examine the current limitations of oral NSAID therapy, including safety profiles, specific scenarios where their use may not be appropriate, and gaps in knowledge. By critically evaluating these aspects, healthcare practitioners can make informed decisions about prescribing NSAIDs, optimizing patient outcomes while minimizing potential risks. This narrative review summarizes existing knowledge and underscores the importance of risk-benefit assessments in NSAID prescribing. Ultimately, the goal is to enhance the rational use of NSAIDs, maximizing benefits while mitigating adverse effects.

Clinical phenotypes of cardiogenic shock survivors: insights into late host responses and long-term outcomes.

An elevated risk of adverse events persists for years in cardiogenic shock (CS) survivors with high mortality rate and physical/mental disability. This study aims to link clinical CS-survivor phenotypes with distinct late host-response patterns at intensive care unit (ICU) discharge and long-term outcomes using model-based clustering. In the original prospective, observational, international French and European Outcome Registry in Intensive Care Units (FROG-ICU) study, ICU patients with CS on admission were identified (N=228). Among them, 173 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct CS-survivor phenotypes at ICU discharge using 15 readily available clinical and laboratory variables. The primary endpoint was 1year of mortality after ICU discharge. Secondary endpoints were readmission and physical/mental disability [short form-36 questionnaire (SF-36) score] within 1year after ICU discharge. Two distinct phenotypes at ICU discharge were identified (A and B). Patients in Phenotype B (38%) were more anaemic and had higher circulating levels of lactate, sustained kidney injury, and persistent elevation in plasma markers of inflammation, myocardial fibrosis, and endothelial dysfunction compared with Phenotype A. They had also a higher rate of non-ischaemic origin of CS and right ventricular dysfunction on admission. CS survivors in Phenotype B had higher 1year of mortality compared with Phenotype A (P=0.045, Kaplan-Meier analysis). When adjusted for traditional risk factors (i.e. age, severity of illness, and duration of ICU stay), Phenotype B was independently associated with 1year of mortality [adjusted hazard ratio=2.83 (95% confidence interval 1.21-6.60); P=0.016]. There was a significantly lower physical quality of life in Phenotype B patients at 3months (i.e. SF-36 physical component score). A phenotype with sustained inflammation, myocardial fibrosis, and endothelial dysfunction at ICU discharge was identified from readily available data and was independently associated with poor long-term outcomes in CS survivors.

Impact of Age on Antiplatelet Monotherapy in the Chronic Maintenance Period After Percutaneous Coronary Intervention: A Post Hoc Analysis From the HOST-EXAM Extended Study

BackgroundsThe HOST-EXAM Extended study reported the benefit of clopidogrel monotherapy over aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI). This age-specific subgroup analysis of the study aimed to assess the impact of age on antiplatelet monotherapy after PCI. MethodsWe analysed data from the per-protocol population (4717 patients) with a median follow-up of 5.8 years. The old age group comprised 2033 patients (43.1%), defined as those 65 years of age or older. The primary end point was the composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome (ACS), and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. The secondary end points were thrombotic composite outcomes and any bleeding. ResultsAge correlated with an elevated risk of adverse events, particularly from age 65. Clopidogrel monotherapy was associated with a reduction of the primary end point in both the old age group (19.4% vs 23.1%, hazard ratio [HR] 0.802, 95% confidence interval [CI] 0.664-0.968; P = 0.022) and the young age group (7.8% vs 11.7%, HR 0.646, 95% CI 0.506-0.825; P < 0.001), without significant interaction (interaction P = 0.167). These findings were consistent for the secondary composite thrombotic end point and any bleeding events (interaction P value of secondary thrombotic end point: 0.786; interaction P value of any bleeding end point: 0.565). Consistent results were observed in analyses with a 75-year age cutoff and in subgroup analyses by 10-year age intervals. ConclusionsIn patients requiring antiplatelet monotherapy after PCI, occurrence of both ischemic and bleeding events dramatically increased from age 65. The beneficial impact of clopidogrel over aspirin monotherapy was consistent regardless of age. Clinical Trial Registration InformationClinicalTrials.gov Identifier: NCT02044250.

Cap-assisted endoscopic mucosal resection as a salvage technique for challenging colorectal laterally spreading tumors.

Cap-assisted endoscopic mucosal resection (EMR-c) has emerged as a potential alternative to standard piecemeal wide-field EMR (WF-EMR) for the resection of laterally spreading tumors (LSTs). However, clear indications for this technique are still lacking. Our objective was to investigate the performance of salvage EMR-c after WF-EMR failure in the resection of large colorectal LSTs. The data of consecutive patients undergoing WF-EMR for large colorectal LSTs (2015-2021) were analyzed in this single-center, retrospective, observational study. In the event of a WF-EMR failure, the procedure was switched to EMR-c in the same session. The efficacy of the two techniques was evaluated in terms of complete endoscopic resection, R0 resection, and recurrence rate. Safety was also assessed. Overall,the data from 81 WF-EMRs were collected. Eighteen cases of WF-EMR failure were switched to EMR-c in the same session and complete endoscopic resection was achieved in 17/18 patients (94.4%). No statistically significant difference was observed between WF-EMR and salvage EMR-c in terms of macroscopic radicality (P = 0.40) and R0 resection (P = 0.12). However, recurrence was more common with EMR-c (44.4% vs. 23.5%; P = 0.05), as were adverse events, particularly intraprocedural bleeding (27.8% vs. 7.9%; P = 0.04). EMR-c is an effective salvage technique for challenging colorectal LSTs following WF-EMR failure. Due to the elevated risk of adverse events associated with this procedure, careful patient selection, endoscopic expertise, and close follow-up are strongly recommended.

HTA83 Investigating the Net Benefit of a Clinical Algorithm Detecting Chemotherapy Patients’ Risk of Emergency Care and Inpatient Hospitalization

For chemotherapy patients, unplanned emergency department (ED) visits and inpatient hospitalization (IP) stays are common and costly. Recent evidence suggests a deep learning algorithm (the Reverse Time Attention (RETAIN) model) can identify patients at elevated risk of adverse events to guide more efficient patient services. This study aims to investigate the intrinsic net benefit of a deep learning algorithm (i.e., RETAIN model) and the economic costs for a given threshold selected by the clinician.

Impact of Frailty on the Development of Proximal Junctional Failure: Does Frailty Supersede Achieving Optimal Realignment?

Patients undergoing surgery for adult spinal deformity (ASD) are often elderly, frail, and at elevated risk of adverse events perioperatively, with proximal junctional failure (PJF) occurring relatively frequently. Currently, the specific role of frailty in potentiating this outcome is poorly defined. To determine if the benefits of optimal realignment in ASD, with respect to the development of PJF, can be offset by increasing frailty. Retrospective cohort. Operative ASD patients (scoliosis >20°, SVA>5cm, pelvic tilt>25°, or TK>60°) fused to the pelvis or below with available baseline and 2-year (2Y) radiographic and HRQL data were included. The Miller Frailty Index (FI) was used to stratify patients into 2 categories: Not Frail (FI <3) and Frail (>3). Proximal Junctional Failure (PJF) was defined using the Lafage criteria. "Matched" and "unmatched" refers to ideal age-adjusted alignment postoperatively. Multivariable regression determined the impact of frailty on the development of PJF. Two hundred eighty-four ASD patients met inclusion criteria [62.2yrs±9.9, 81%F, BMI: 27.5kg/m 2 ±5.3, ASD-FI: 3.4±1.5, Charlson Comorbidity Index (CCI): 1.7±1.6]. Forty-three percent of patients were characterized as Not Frail (NF) and 57% were characterized as Frail (F). PJF development was lower in the NF group compared with the F group (7% vs . 18%; P =0.002). F patients had 3.2 × higher risk of PJF development compared to NF patients (OR: 3.2, 95% CI: 1.3-7.3, P =0.009). Controlling for baseline factors, F unmatched patients had a higher degree of PJF (OR: 1.4, 95% CI:1.02-1.8, P =0.03); however, with prophylaxis, there was no increased risk. Adjusted analysis shows F patients, when matched postoperatively in PI-LL, had no significantly higher risk of PJF. An increasingly frail state is significantly associated with the development of PJF after corrective surgery for ASD. Optimal realignment may mitigate the impact of frailty on eventual PJF. Prophylaxis should be considered in frail patients who do not reach ideal alignment goals.

Long-term follow-up of contemporarydrug-eluting stent implantation in diabetic patients: Subanalysis of a randomized controlled trial.

The elevated risk of adverse events following percutaneous coronary intervention in diabetic patients persists with newer-generation DES. The polymer-free amphilimus-eluting stent (PF-AES) possesses characteristics with a potentially enhanced performance in patients with diabetes. Data from the 1-year follow-up period has been previously published. The aim of this subanalysis was to assess long-term performance of two contemporary drug-eluting stents (DES) in a diabetic population. In the ReCre8 trial, patients were stratified for diabetes and troponin status, and randomized to implantation of a permanent polymer zotarolimus-eluting stent (PP-ZES) or PF-AES. The primary endpoint was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Clinical outcomes between discharge and 3 years follow-up were assessed. A total of 302 patients with diabetes were included in this analysis. After 3 years, TLF occurred in 12.5% of PP-ZES patients versus 10.0% in PF-AES patients (p = 0.46). Similarly, the separate components of TLF were comparable between the two study arms. The secondary composite endpoint of NACE was higher in the PP-ZES arm with 45 cases (29.6%) versus 30 cases (20.0%) in the PF-AES arm (p = 0.036). In the insulin-dependent diabetic population, TLF occurred in 19.1% of PP-ZES patients versus 10.4% of PF-AES patients (p = 0.21). NACE occurred in 40.4% of PP-ZES patients versus 27.1% of PF-AES patients (p = 0.10). This subanalysis shows that the use of PF-AES results in similar clinical outcomes as compared to PP-ZES, yet some benefits of use of PF-AES in diabetic patients may prevail. Future dedicated trials should confirm these findings.

PERFORMANCE 1 study: Novel carotid stent system with integrated post-dilation balloon and embolic protection device.

The PERFORMANCE I study was designed to evaluate the safety and feasibility of the Neuroguard IEP® System, a novel carotid stent system with an integrated embolic filter and post-dilatation balloon, to treat clinically significant carotid artery stenosis. The risk of major adverse events during carotid artery stenting is comparable to carotid endarterectomy, however, the risk of minor stroke remains higher with stenting. In total, 67 patients undergoing carotid artery stenting were enrolled at nine centers in Europe. Follow-up assessments included neurological exams, duplex ultrasound, 12-lead electrocardiogram, and cardiac enzyme analysis. The primary endpoint was the 30-day composite rate of stroke, death, and myocardial infarctions versus a prespecified performance goal. Secondary endpoints included procedure success, device success, and target lesion revascularization. The study population was predominantly male (74.6%) with a mean age of 69.3 ± 8.9 years and 67% of subjects met at least one criterion placing them at an elevated risk for adverse events following carotid endarterectomy. All patients were treated successfully with the study device. There were no deaths or strokes within 30 days of the index procedure. One subject (1.5%) experienced a non-ST elevation myocardial infarction at day 17. The primary endpoint was met with a 30-day major adverse events rate of 1.5% (1/67). Through 12-month follow-up, there were no strokes, neurological deaths, target lesion revascularizations, or instances of in-stent-restenosis. Results from this study demonstrate the Neuroguard IEP system is safe and feasible with a stroke/death rate of 0% at 30 days. A large pivotal study is currently underway.

A Qualitative Exploration of the Functional, Social, and Emotional Impacts of the COVID-19 Pandemic on People Who Use Drugs.

Since 2020, people who use drugs (PWUD) experienced heightened risks related to drug supply disruptions, contamination, overdose, social isolation, and increased stress. This study explored how the lives of PWUD changed in Philadelphia over a one-year period. Using semi-structured interviews with 20 participants in a Housing First, low-barrier medication for opioid use (MOUD) program in Philadelphia, the effects of the first year of the COVID-19 pandemic on the daily lives, resources, functioning, substance use, and treatment of PWUD were explored. Interviews were analyzed using a combination of directed and conventional content analysis. Six overarching themes emerged during data analysis: (1) response to the pandemic; (2) access to MOUD and support services; (3) substance use; (4) impacts on mental health, physical health, and daily functioning; (5) social network impacts; and (6) fulfillment of basic needs. Participants reported disruptions in every domain of life, challenges meeting their basic needs, and elevated risk for adverse events. MOUD service providers offset some risks and provided material supports, treatment, social interaction, and emotional support. These results highlight how there were significant disruptions to the lives of PWUD during the first year of the COVID-19 pandemic and identified critical areas for future intervention and policies.

Declining utilization of potentially inappropriate medications in older adults by dermatologists: A cross-sectional Medicare analysis

To the Editor: The American Geriatrics Society Beers Criteria lists medications that are potentially inappropriate for use in older adults due to an elevated risk of adverse events.1 The evidence-based list was created by an expert panel and is updated regularly and often consulted by clinicians and health care administrators.1 We sought to compare annual trends in dermatologist prescriptions among the Medicare population for medications meeting the Beers Criteria. This is important to understand, given the aging dermatology patient population.

Association of High Density Cholesterol With Hyperemic Epicardial Flow and Frame Count Reserve in Patients With Moderate Coronary Lesions and Slow Coronary Flow.

BackgroundPatients with microvascular angina and non-obstructive coronary atherosclerotic disease have an elevated risk of adverse events and all-cause mortality compared with individuals without ischaemic heart disease. The diagnosis coronary microvascular dysfunction in this setting relies on the detection of impaired coronary flow at rest or on calculation of coronary flow reserve. Previous studies demonstrate that the coronary flow reserve assessed by the corrected thrombolysis in myocardial infarction method - the frame count reserve is an objective quantitative alternative to other widely used invasive methods for microvascular status evaluation.PurposeWe assessed the significance of clinical, hemodynamic, angiographic variables and therapy with reference to FCR in a small group of patients with up to moderate atherosclerotic coronary lesions and slow coronary flow. Materials and methods: Frame count reserve was evaluated in 15 patients without flow-limiting (>50%) coronary stenoses admitted with unstable angina. Frame count reserve was calculated by dividing the baseline corrected thrombolysis in myocardial infarction frame count (cTFC) by the cTFC assessed after intracoronary infusion of 100 µg of the calcium channel blocker - verapamil.ResultsThe values of frame count reserve correlate positively with the levels of high density cholesterol (r= 0.900, p=0.001), inversely coronary flow after the application of verapamil - cTFCv (r= - 0.534, p=0.049). cTFCv was positively related with the levels of high density lipoproteins (r = - 0.645; p= 0.044) and was negatively influenced by the presence of atherosclerotic lesions at quantitative angiography (42.8±19.1 (n=8) vs 23±5.4 (n=7), p=0.029).The therapy with β-blocker and long-acting nitrate was associated with insignificantly higher frame count reserves after intracoronary verapamil compared to the continuous intake only of β-blocker or β-blocker and verapamil (2.1±0.78 vs 1.34±0.14 vs 1.70±0.70, p=NS).ConclusionsHigher high-density lipoproteins relate to higher frame count reserves evaluated using verapamil. The improved blood flow after this microvascular vasodilator is consistently positively related to high-density cholesterol and the lack of atherosclerosis at conventional coronary angiography. The combined intake of micro- and macrovascular vasodilator could be associated with higher frame count reserves compared to therapy with β-blocker and one vasodilating drug.

Impact of variability in estimated glomerular filtration rate on major clinical outcomes: A nationwide population-based study.

BackgroundThe estimated glomerular filtration rate (eGFR), commonly estimated using the serum creatinine value, often fluctuates throughout the serial measurement. The clinical significance of GFR variation among the general population with normal renal function has not yet been demonstrated. Thus, we explored the impact of GFR variability on adverse clinical outcomes.MethodsA nationwide retrospective cohort study using the Korean National Health Insurance System database was performed. National health screening examinees who underwent creatinine measurement ≥3 times between 2012 and 2016 were considered. Those with eGFR under 60 mL/min/m2 were excluded. The fluctuation of eGFR was represented with variability independent of the mean (VIM) index; which was calculated by the standard deviation divided by the exponent of the regression coefficient of the mean. Then, the risks of myocardial infarction (MI), stroke and death were assessed according to the quartiles of the VIMResultsOf total 3,538,500 participants, 0.29% of myocardial infarction (MI), 0.14% of stroke, 0.36% of deaths were observed during the median follow up of 3.27 years. Participants with the highest VIM index, which represents the highest eGFR variability, were significantly associated with an increased risk of MI (hazard ratio [HR]; 1.10, 95% confidence interval [95% CI]; 1.04–1.16), stroke (HR: 1.16; 95% CI 1.09–1.23), and death (HR: 1.18; 95% CI 1.12–1.24). The elevated risk of adverse events was consistent after the multivariate adjustment with potential confounding factors, except the risk of MI (HR 1.06; 95% 1.00–1.06).ConclusionsIncreased eGFR variability exhibited an association with major clinical outcomes, indicating that monitoring eGFR variability might be a useful parameter for predicting the adverse outcomes.

Identifying patients with symptoms suspicious for COVID-19 at elevated risk of adverse events: The COVAS score.

ObjectiveDevelop and validate a risk score using variables available during an Emergency Department (ED) encounter to predict adverse events among patients with suspected COVID-19.MethodsA retrospective cohort study of adult visits for suspected COVID-19 between March 1 – April 30, 2020 at 15 EDs in Southern California. The primary outcomes were death or respiratory decompensation within 7-days. We used least absolute shrinkage and selection operator (LASSO) models and logistic regression to derive a risk score. We report metrics for derivation and validation cohorts, and subgroups with pneumonia or COVID-19 diagnoses.Results26,600 ED encounters were included and 1079 experienced an adverse event. Five categories (comorbidities, obesity/BMI ≥ 40, vital signs, age and sex) were included in the final score. The area under the curve (AUC) in the derivation cohort was 0.891 (95% CI, 0.880–0.901); similar performance was observed in the validation cohort (AUC = 0.895, 95% CI, 0.874–0.916). Sensitivity ranging from 100% (Score 0) to 41.7% (Score of ≥15) and specificity from 13.9% (score 0) to 96.8% (score ≥ 15). In the subgroups with pneumonia (n = 3252) the AUCs were 0.780 (derivation, 95% CI 0.759–0.801) and 0.832 (validation, 95% CI 0.794–0.870), while for COVID-19 diagnoses (n = 2059) the AUCs were 0.867 (95% CI 0.843–0.892) and 0.837 (95% CI 0.774–0.899) respectively.ConclusionPhysicians evaluating ED patients with pneumonia, COVID-19, or symptoms suspicious for COVID-19 can apply the COVAS score to assist with decisions to hospitalize or discharge patients during the SARS CoV-2 pandemic.

Cardiovascular Safety and Benefits of Noninsulin Antihyperglycemic Drugs for the Treatment of Type 2 Diabetes Mellitus: Part 2.

Ideal drugs to improve outcomes in type 2 diabetes mellitus (T2DM) are those with antiglycemic efficacy, as well as cardiovascular safety that has to be determined in appropriately designed cardiovascular outcome trials as mandated by regulatory agencies. The more recent antihyperglycemic medications have shown promise with regards to cardiovascular disease (CVD) risk reduction in T2DM patients at a high cardiovascular risk. Sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists are associated with better cardiovascular outcomes and mortality in T2DM patients than are dipeptidylpeptidase-4 inhibitors, leading to the Food and Drug Administration's approval of empagliflozin to reduce mortality, and of liraglutide to reduce CVD risk in high-risk T2DM patients. For heart failure outcomes, sodium glucose cotransporter-2 inhibitors are beneficial, while glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are neutral. Ongoing and planned randomized controlled trials of these newer drugs should clarify the possibility of class effects and of CVD risk reduction benefits in low-moderate cardiovascular risk patients. While we eagerly await the results on ongoing studies, these medications should be appropriately prescribed in T2DM patients with baseline CVD or those at a high CVD risk after carefully evaluating the elevated risk for adverse events like gastrointestinal disturbances, bladder cancer, genital infections, and amputations. Studies to understand the pleotropic and novel pathophysiological mechanisms demonstrated by the sodium glucose cotransporter-2 inhibitors will shed light on the effects of the modulation of microvascular, inflammatory, and thrombotic milieu for improving the CVD risk in T2DM patients. This is part 2 of the series on noninsulin antihyperglycemic drugs for the treatment of T2DM.

One-Year Outcomes of Percutaneous Coronary Intervention in Patients with End-Stage Liver Disease.

Background:Patients with cirrhosis and coronary artery disease (CAD) are at high risk for morbidity during surgical revascularization so they are often referred for complex percutaneous coronary intervention (PCI). Percutaneous coronary intervention in the cirrhotic population also has inherent risks; however, quantifiable data on long-term outcomes are lacking.Methods:Patients with angiographically significant CAD and cirrhosis were identified from the catheterization lab databases of the University of Pennsylvania Health System between 2007 and 2015. Outcomes were obtained from the medical record and telephonic contact with patients/families.Results:Percutaneous coronary intervention was successfully performed in 42 patients (51 PCIs). Twenty-nine patients with significant CAD were managed medically (36 angiograms). The primary outcome (a composite of mortality, subsequent revascularization, and myocardial infarction) was not significantly different between the 2 groups during a follow-up period at 1 year (PCI: 50%, Control: 40%, P = .383). In the PCI group, a composite adverse outcome rate that included acute kidney injury (AKI), severe bleed, and peri-procedural stroke was elevated (40%), with severe bleeding occurring after 23% of PCI events and post-procedural AKI occurring after 26% of events. The medical management group had significantly fewer total matched adverse outcomes (17% vs 40% in the PCI group, P = .03), with severe bleeding occurring after 11% of events and AKI occurring after 6% of events. Increased risk of adverse events following PCI was associated with severity of liver disease by Child-Pugh class.Conclusions:Percutaneous coronary intervention in patients with cirrhosis is associated with an elevated risk of adverse events, including severe bleeding and AKI.

Long-term comparison of everolimus- vs. novolimus-eluting bioresorbable vascular scaffolds in real world patients.

IntroductionElevated risk of adverse events in comparison to metallic stents resulted in withdrawal of everolimus-eluting bioresorbable scaffolds (eBVS), known as the most intensively studied BVS. There is a paucity of data comparing the two different BVS.AimTo evaluate the long-term clinical outcomes of the novolimus-eluting bioresorbable vascular scaffold (nBVS) compared with eBVS.Material and methodsConsecutive patients treated with nBVS or eBVS in our center were screened. The primary outcome was the 3-year rate of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, target vessel myocardial infarction (TV-MI), and target-lesion revascularization (TLR).ResultsAfter matching, 98 patients treated with 135 eBVS were compared with 98 patients treated with 136 nBVS. Baseline characteristics, clinical presentation, and lesion characteristics were comparable in both groups. The 3-year MACE rate was higher in the eBVS group (17.3% vs. 6.1%; p log-rank = 0.02). The occurrence of TLR (16.3% vs. 5.1%; p log-rank = 0.02) and TV-MI (8.2% vs. 0 %; p log-rank = 0.004) was also higher in the eBVS group except for cardiac deaths (1% vs. 2%; p log-rank = 0.98, eBVS vs. nBVS, respectively). Of note, definite device thrombosis rate was markedly increased in the eBVS group (5.1% vs. 0%; p log-rank = 0.03).ConclusionsThe present study revealed that the 3-year event risk was lower for nBVS compared to eBVS. More evidence is needed to evaluate long-term performance of novolimus-eluting biovascular platforms.

Multicomponent hospital-led interventions to reduce hospital stay for older adults following elective surgery: a systematic review

BackgroundElective older adult inpatient admissions are increasingly common. Older adults are at an elevated risk of adverse events in hospital, potentially increasing with lengthier hospital stay. Hospital-led organisational strategies may optimise hospital stay for elective older adult inpatients.ObjectivesTo evaluate the effectiveness and cost-effectiveness of hospital-led multicomponent interventions to reduce hospital stay for older adults undergoing elective hospital admissions.Data sourcesSeven bibliographic databases (MEDLINE, MEDLINE In-Process &amp; Other Non-Indexed Citations, EMBASE, Health Management Information Consortium, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine Database) were searched from inception to date of search (August 2017), alongside carrying out of web searches, citation searching, inspecting relevant reviews, consulting stakeholders and contacting authors. This search was duplicated, with an additional cost-filter, to identify cost-effectiveness evidence.Review methodsComparative studies were sought that evaluated the effectiveness or cost-effectiveness of relevant interventions in elective inpatients with a mean or median age of ≥ 60 years. Study selection, data extraction and quality assessment were completed independently by two reviewers. The main outcome was length of stay, but all outcomes were considered. Studies were sorted by procedure, intervention and outcome categories. Where possible, standardised mean differences or odds ratios were calculated. Meta-analysis was performed when multiple randomised controlled trials had the same intervention, treatment procedure, comparator and outcome. Findings were explored using narrative synthesis.FindingsA total of 218 articles were included, with 80 articles from 73 effectiveness studies (n = 26,365 patients) prioritised for synthesis, including 34 randomised controlled trials conducted outside the UK and 39 studies from the UK, of which 12 were randomised controlled trials. Fifteen studies included cost-effectiveness data. The evidence was dominated by enhanced recovery protocols and prehabilitation, implemented to improve recovery from either colorectal surgery or lower limb arthroplasty. Six other surgical categories and four other intervention types were identified. Meta-analysis found that enhanced recovery protocols were associated with 1.5 days’ reduction in hospital stay among patients undergoing colorectal surgery (Cohen’sd = –0.51, 95% confidence interval –0.78 to –0.24;p &lt; 0.001) and with 5 days’ reduction among those undergoing upper abdominal surgery (Cohen’sd = –1.04, 95% confidence interval –1.55 to –0.53;p &lt; 0.001). Evidence from the UK was not pooled (owing to mixed study designs), but it echoed findings from the international literature. Length of stay usually was reduced with intervention or was no different. Other clinical outcomes also improved or were no worse with intervention. Patient-reported outcomes were not frequently reported. Cost and cost-effectiveness evidence came from 15 highly heterogeneous studies and was less conclusive.LimitationsStudies were usually of moderate or weak quality. Some intervention or treatment types were under-reported or absent. The reporting of variance data often precluded secondary analysis.ConclusionsEnhanced recovery and prehabilitation interventions were associated with reduced hospital stay without detriment to other clinical outcomes, particularly for patients undergoing colorectal surgery, lower limb arthroplasty or upper abdominal surgery. The impacts on patient-reported outcomes, health-care costs or additional service use are not well known.Future workFurther studies evaluating of the effectiveness of new enhanced recovery pathways are not required in colorectal surgery or lower limb arthroplasty. However, the applicability of these pathways to other procedures is uncertain. Future studies should evaluate the implementation of interventions to reduce service variation, in-hospital patient-reported outcomes, impacts on health and social care service use, and longer-term patient-reported outcomes.Study registrationThis study is registered as PROSPERO CRD42017080637.FundingThe National Institute for Health Research Health Services and Delivery Research programme.