Search

A new group of hypoglycemic drugs has been used to treat diabetes type 2. This group is active sodium glucose co-transporter (SGLT2) or SGLT2 inhibitors. It has been shown that besides the treatment of diabetes, this drug class is responsible for the mildness of the cardiovascular events shown in patients with diabetes type 2. However, there is an intriguing question regarding the range of SGLT2 inhibitors and if there is a difference between them or if there is a class effect among their results. EMPA-REG OUTCOME trial and the CVD-study are used to answer this question. Additional information from the DECLARE-TIMI 58 and Dapa-HF trials is studied.

The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) are transforming the care of CKD. An inherent challenge of practice-changing advances on this scale is how to best incorporate them into daily practice. In this vein, although there are four SGLT2is commercially available in the United States, the question remains whether these SGLT2is may be viewed as interchangeable or if specific agents offer unique benefits or harms in specific clinical settings. The more similarities between the agents within a pharmacologic class ( e.g. , chemical structure, pharmacodynamics, and pharmacokinetics), the greater the likelihood of shared class effects. Preclinical data, starting with largely comparable chemical structures, provide a foundation where class effects might be anticipated. Nevertheless, on- and off-target effects may be expected to modify the response to any drug—an area of particular interest when considering the potential for drug, rather than class-specific, effects (1). Although translational, toxicologic, and pharmacologic investigations carried out in model systems may shed light into class- versus drug-specific effects, the ultimate adjudicator of this question is data from sufficiently powered, rigorously controlled, human, randomized clinical trials (RCTs). Before delving into the trial data, it may be helpful to briefly review the preclinical data regarding SGLT2is to explore the a priori bio-plausibility of class- versus drug-specific effects. The origins of SGLT2is can be linked to two earlier tracks of research: familial renal glucosuria (FRG) and phlorizin rodent studies (2). The presence of patients with a familiar tendency to produce elevated levels of glucose in the urine, despite normal blood glucose, had been identified for some time and, as early as the 1920s, work had begun to identify the pattern of inheritance (2,3). The precise molecular mechanism for this clinical finding would take considerably longer to come to light (4). One observation from these patients that …

Objectives Statins have proved to reduce cardiovascular morbidity and mortality in high-risk population and are generally well tolerated, although adverse events can occur. Up to 3% of patients develop aminotransferases elevation, which usually normalizes with continued treatment and hardly is associated with clinical symptoms. Serious statin-related liver injury is exceedingly rare. Furthermore, literature regarding rechallenge with a second statin is extremely poor. Some authors caution that re-exposure to these drugs is associated with a more serious liver injury but safe switching to a second statin after drug-induced liver injury (DILI) is also reported. Case presentation We describe a case of a middle-aged woman who developed hepatocellular liver injury after simvastatin dose escalation; a rechallenge with low dose rosuvastatin caused rapid recurrence of DILI. Conclusions In our opinion, clinicians should be very cautious upon rechallenge and closely follow-up patients who experienced statin-induced liver injury when trying re-exposure to another statin.

Renal protection is likely to be a class effect of SGLT‐2 inhibitors and GLP‐1RA. When used simultaneously, there may be a synergistic effect. Both agents are also safe to use in high renal risk patients (eGFR between 21 and 30 mL/min/1.73m2), Renal protection is likely to be a class effect of SGLT‐2 inhibitors and GLP‐1RA. When used simultaneously, there may be a synergistic effect. Both agents are also safe to use in high renal risk patients (eGFR between 21 and 30 mL/min/1.73 m2)

Purpose: To determine if fluorescein angiographic (FA) findings after intravitreal ranibizumab (IVR) for retinopathy of prematurity (ROP) conform to a class effect previously described with bevacizumab. Methods: Single-center retrospective case series of all infants treated with 0.2 mg (0.02 mL) IVR for Type 1 ROP from July 2016 to November 2018. FA were obtained at 40, 52, 62, and 72 weeks of postmenstrual age (PMA) using wide-angle photography. FA images were analyzed and the peripheral avascular areas measured with ImageJ using a reference disc diameter (DD). Based on the extent of the avascular area and tortuosity of the retinal vessels all eyes were classified into four categories: complete vascular maturity (vascularization within 2 DD of the ora serrata), VAA (avascular area >2 DD of the ora serrata), VAT (avascular area >2 DD of the ora serrata and posterior tortuosity), and reactivation (recurrence of stage disease). Results: About 13 infants were enrolled and 24 eyes were available in this study. None of the eyes reached complete vascular maturity at an average PMA of 60 weeks, 7 (29%) eyes presented with VAA, 8 (33%) with VAT, and 9 (37.5%) reactivated. The reactivated eyes presented with the largest area of peripheral ischemia, followed by the VAT and then the VAA groups ( p = 0.02). Conclusion: IVR conforms to the previously described regression patterns following intravitreal bevacizumab for ROP indicative of a class effect. Follow-up using FA might help to optimize the management of these infants after injection of the drug.

Bradykinin-mediated angioedema is a rare but potentially fatal adverse event. Angioedema induced by angiotensin-converting enzyme (ACE) inhibitors is generally attributed to an inhibition of bradykinin degradation following ACE inhibition. Clinical studies on ACE inhibitors mainly focus on their efficacy. Few examine their potential to generate undesirable adverse effects, particularly with regard to angioedema.We report here a case of angioedema occurring after ramipril initiation in a patient chronically treated with quinapril. Angioedema subsided spontaneously after ramipril discontinuation and quinapril reintroduction.Our clinical case suggests that despite similar pharmacodynamic properties, quinapril and ramipril do not have the same potential to generate angioedema. To explain this difference, we suggest a potentiation of the effect of bradykinin at the B2 receptor level by ramipril, which does not occur with quinapril. Consequently, angioedema may not always be a class effect of ACE inhibitors.

English teaching includes several parts such as self-study instruction, cooperative inquiry, intensive lecture and after class practice. In this paper, the role of extracurricular application on the effectiveness of college English teaching is explored through questionnaires, teaching experiments and interviews. The experimental design and study of college English teaching in the first year of Nanning University, using R language to analyze the experimental data. The conclusion is that extracurricular application has positive effect on college English teaching. Moreover, it is found that although students have different attitudes and opinions, some of them also affirm the positive effect of after class application. At the same time, in the process of teaching implementation, we should pay attention to the difficulty of practice content and the variety of practice methods, but we should not excessively occupy after class time of students. The most importance is to provide students with feedback and summary of after class practice in time. The research shows that after class application can improve the effectiveness of classroom teaching when it is well integrated with classroom teaching.

Purpose: To provide a comprehensive review to determine whether there is a class effect among angiotensin receptor blockers (ARBs) in relation to serum uric acid. Summary: A literature search was conducted and 8 articles were identified for inclusion in this review. In the studies reviewed, candesartan and valsartan were shown to have either a neutral or negative effect on serum uric acid. Azilsartan was shown to have a negative impact on serum uric acid while eprosartan appeared to have no impact on serum uric acid levels. Irbesartan demonstrated either a neutral or positive effect on serum uric acid while losartan exhibited a positive effect. Conclusion: The available data indicate that the reduction of serum uric acid is not a class effect of ARBs. Of the available agents, only losartan has clear evidence of its ability to lower serum uric acid. For patients with high blood pressure and elevated serum uric acid, losartan should be considered as a first-line agent with irbesartan as an alternative when appropriate.

The Absorb bioresorbable scaffold (BRS), the most studied device among all BRS, suffered a major setback following the negative results of the ABSORB trials. However, approximately 34 BRSs from 22 companies are currently under development. The potential device-specific factors related to the increased event rate in Absorb were: 1) weak mechanical properties, 2) larger strut thickness (less embedment and larger protrusion) and width (larger footprint) predisposing to underexpansion/protrusion of struts, eventually resulting in increased thrombogenicity, and 3) longer bioresorption time combined with failure of encapsulation of struts before the dismantling process ensues. Given the diversity of bioresorbable materials (even amongst PLLA), and the different mechanical properties and bioresorption profiles of each new BRS, one could expect considerable difference in early and late clinical outcomes. As a matter of fact, data from first-in-man (FIM) and pivotal trials have demonstrated variable clinical results. Indeed, early clinical evidence from FIM trials does not support a class effect. However, the absence of a comparator precludes us from drawing definitive conclusions. Further clinical evidence should confirm the absence (or presence) of a class effect.

Aims In 2008, the US Food and Drug Administration (FDA) issued a guidance requiring that cardiovascular outcome trials (CVOTs) be conducted for newer hypoglycaemic drugs for type 2 diabetes (T2D). We aimed to examine the decisions by 3 regulatory authorities in response to identical CVOT data. Methods We surveyed ClinicalTrials.gov to identify CVOTs and examined the revision histories of drug labels in databases from the FDA, the European Medicines Agency, and the Pharmaceuticals and Medical Devices Agency in Japan. Results We selected 14 drugs and corresponding CVOTs, 12 of which were conducted as postmarketing trials. In the USA and the EU, the pre-CVOT indication on all 14 labels was "improvement in glycaemic control". Six drugs showed significant cardiovascular risk reduction, which led to an additional indication regarding reduction of cardiovascular adverse events in the USA, and a change to the EU indication to specify treatment of adults with T2D. The initial indication in Japan, T2D, remained unchanged. Regarding safety, significant increases in heart failure were observed only in the saxagliptin trial. A warning was added to the saxagliptin labels in the EU and Japan, whereas the FDA required a class effect warning to be added to the labels of all 4 dipeptidyl peptidase-4 inhibitors. Conclusions Regulatory authorities using identical trial data made substantially different decisions regarding both safety and efficacy of hypoglycaemic drugs. The differences in initial indication wording between Japan and the other authorities suggest that trial data and T2D are interpreted differently in these regions.

Hospitalization for major diabetes complications, including myocardial infarction, stroke, lower-extremity amputation, and end-stage kidney disease, is on the rise and represents a great health burden for patients with type 2 diabetes (T2D), in particular for older people. Newer glucose-lowering medications have generated some optimism on the possibility to influence the natural history of cardiorenal complications of T2D. This review summarizes work in the area of sodium–glucose cotransporter 2 inhibitors (SGLT-2i) treatment and prevention of cardiorenal complications in patients with T2D (major adverse cardiovascular events, hospitalization for heart failure, kidney outcomes), with a particular emphasis on the effect of age, the role of primary versus secondary prevention and the possible extension of their cardiorenal benefits to the entire class of SGLT-2i.

Objective The aim of this study was to assess the causality of anti-TNFα agents-associated pleuropericarditis in VigiBase with a focus on its diverse types. Methods All variables contained in the pleuropericarditis reports were reviewed. Well-documented reports, vigiGrade completeness score ≥ 0.80 or with an informative narrative, were analyzed and with a focus on the clinical features of the cases. Bradford-Hill criteria were used in the case series assessment of causality. Results From 1968 up to 18 December 2019, there were 94 unique cases from 18 countries reporting pleuropericarditis with anti-TNFα agents as a suspected or interacting medicine. Among the 94 reports, 42 were identified as well-documented and further assessed for clinical features. Of the 42 cases, 39 were serious, including three fatal and seven life-threatening. In 35 cases, an anti-TNFα agent was the only suspected drug. Positive de- and re-challenge were reported in 95% and 17% of the 42 cases, respectively. The times to onset (TTO) varied greatly among individual cases, ranging from one month to 75 months (mean = 24 months). The most commonly involved anti-TNFα agents were adalimumab, infliximab and etanercept; and the mostly reported pleuropericarditis types were classified as autoimmune-related with (n = 17) or without (n = 15) co-reported drug-induced lupus (DIL), or infection-related (n = 8). While adalimumab was the most reported in the infection-related cases (7/8), infliximab was the most frequent in the autoimmune-related cases, in particular co-reported with DIL (9/17). There were four cases where the reaction occurred one to two months after the anti-TNFα agents (infliximab and adalimumab) were stopped. Based on the review of the case series using Bradford-Hill criteria the anti-TNFα agents associated pleuropericarditis are considered as a class effect. Conclusions To clinically recognize and manage these potentially life-threatening serious cardiopulmonary complications, health care professionals should be aware of this possible risk. Meanwhile, attention should be paid to the clinical features of pleuropericarditis cases, since they may cause diagnostic and therapeutic difficulties. Considering the long elimination time, clinicians need to be reminded to remain vigilant for the adverse reactions even after discontinuing anti-TNFα therapy.

In recent years, successive reports have been made on large-scale cardiovascular outcome trials using novel hypoglycemic drugs. Their results have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors are hypoglycemic drugs that could potentially greatly improve the heart failure-related outcomes in type 2 diabetes patients with a high cardiovascular risk. Further analyses have subsequently been performed from various perspectives, and SGLT2 inhibitors with their class effect have been indicated to be potentially useful for heart failure in type 2 diabetes patients with extensive clinical background. As a result, a clear concept has globally emerged with SGLT2 inhibitors as drugs of choice in clinical practice to prevent heart failure in type 2 diabetes patients. Further studies are needed to examine the next research topics on heart failure prevention using SGLT2 inhibitors, including their detailed pharmacological mechanism of action and their effectiveness and safety against heart failure in patients regardless of diabetes status. This paper outlines (1) the current evidence of heart failure prevention by SGLT2 inhibitors based on the results of recent large-scale cardiovascular outcome trials and (2) future research topics on their further applications in clinical practice.

Mammalian target of rapamycin inhibitors (mTORi) are used to treat a variety of malignancies and have an established role in organ transplantation. Interstitial lung disease (ILD) is one of the complications of mTORi and is believed to be a class effect. More cases of ILD have been reported with sirolimus than with everolimus in the literature, possibly due to earlier introduction and wider use of sirolimus. We report the case of a kidney transplant recipient who developed ILD secondary to sirolimus and improved rapidly after switching to everolimus.

Objectives There are increasing concerns regarding proton pump inhibitor (PPI) use and the risk of fractures in adults. Few studies have evaluated this risk among pediatric patients. This study examined fractures and fracture location among pediatric patients exposed to PPI compared with those without documented exposure. Study design Encounters for patients 6 months to 15.5 years were identified between July 1, 2011 to December 31, 2015 in the Pediatric Hospital Information System database. Exclusion criteria was applied for chronic illnesses, conditions or medications predisposing to fracture. Encounters were classified as PPI encounters if a charge for PPI was documented. PPI encounters were propensity matched to non-PPI encounters. Following initial encounter, patients were evaluated over a 2-year period for hospitalizations resulting from fracture. Results There was a statistically significant higher rate of fractures among the PPI-exposed group (1.4% vs 1.2%, P = 0.019). Adjusting for remaining differences in sex, race, encounter type, payer, and resource intensity after matching, the difference remained statistically significant (P = 0.017) with an adjusted odds ratio (95% CI) of 1.2 (1.0--1.4). Upper extremity was the most common location for fracture; however, the PPI cohort was more likely to suffer from lower extremity, rib, and spinal fractures (P = 0.01). Conclusions This study suggests an increased risk of fracture among pediatric patients taking PPI. Among patients hospitalized with a fracture, those with PPI exposure had a higher rate of lower extremity, rib, and spine fractures compared with controls. This appeared to be a class effect not related to individual PPI agent.

Maternal immunization with reduced antigen content tetanus-diphtheria-acellular pertussis (Tdap)-containing vaccines has been recommended to prevent infant pertussis. However, maternal antibodies may interfere with infant responses to routine immunization with diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccines, raising concerns of suboptimal protection after infant vaccination. We performed a narrative literature review to assess whether blunting occurs regardless of the manufacturer of maternal and infant vaccines. Because internationally agreed correlates of protection are lacking, the clinical significance of blunting is not yet fully understood. We have reviewed the evidence available to date.Thirteen studies that evaluated blunting after maternal immunization and infant primary/booster series were identified. Blunting was observed with various combinations of Tdap- and DTaP-containing vaccines for maternal and pediatric immunization. Studies assessing the effectiveness of maternal Tdap immunization beyond the primary infant immunization series in England and in the United States suggested no evidence of a clinically relevant blunting effect so far.This review indicates that the phenomenon of blunting does not depend on the manufacturer/brand of the pertussis-containing vaccines used for immunizing mothers or children. Currently, there is no epidemiological evidence that children whose mothers received Tdap are at increased risk of pertussis after pediatric vaccinations, although longer follow-up is required.

International audience; We thank Brož et al. for their interest in our study aiming to determine if drug-induced hypoglycemia could be a class effect for opioids [1] and for their useful comments.The French PharmacoVigilance Database (FPVD) contains a narrative description of cases provided by the declarant, which we examined for this study. The description of the report’s narrative in pharmacovigilance study is a complement to disproportionality analysis that may identify potential mechanisms underlying the associations found between drugs and adverse drug reactions. We are glad that they shared our interest in finding such mechanisms to further investigate the link between hypoglycemia and opioids. As they accurately mentioned, 45 of the 93 tramadol-associated hypoglycemia cases included in our descriptive study in the FPVD were related to diabetic patients. Indeed, hypoglycemia in these patients could have been favored by the antihyperglycemic treatment they received. We agree with them that sleepiness, one of the common side effect of opioids, combined to the use of those antihyperglycemic treatments could have been one of the factors leading to the onset of hypoglycemia in those patients. However, not all the reports mentioned sleepiness and the prescription of opioids appeared to be the trigger factor causing the hypoglycemia even in diabetic patients, regardless of the underlying mechanism.

Drug-induced liver injury is a common cause of acute liver failure. β-blockers are a widely prescribed class of medications; however, hepatotoxicity is a rare adverse effect of this medication of which clinicians must be aware. This case suggests that hepatotoxicity may be a class effect of β-blockers.

The paper discusses the effects of drugs from different pharmacological groups on cognitive functions. It details the impact of drugs used to treat nervous system, cardiovascular, gastrointestinal, respiratory, and endocrine diseases on cognitive functions. It is emphasized that many drugs exert both negative and (less frequently) positive effect on cognitive functions, but it is especially pronounced in drugs used to treat nervous system diseases. There is evidence suggesting that different representatives of a number of pharmacological groups have no class effect on cognitive functions.

Background:The atypical antipsychotics (AAPs) are associated with a recognized class effect of glucose and lipid dysregulation. The use of these medications is rapidly increasing in elderly patients with, and without, dementia. However, the metabolic risks specific to elderly remain poorly studied.Methods:Design: A case-control study.Setting: Psychogeriatric service in Auckland, New Zealand.Participants: Elderly patients either receiving AAP treatment (cases) or not (controls) between 1 Jan 2008 and 1 Jan 2014.Main outcome measures: metabolic data of glucose, HbA1c, lipids, and cardiovascular events and death. The data were analyzed usingt-tests and linear regression models for each metabolic outcome.Results:There were 330 eligible cases and 301 controls from a total study population of 5,307. There was a statistically significant change in the HbA1c over time, within the cases group of −1.14 mmol/mol (p = 0.018, 95% CI −0.19 to −2.09). Also statistically significant was the reduction in total cholesterol of −0.13 mmol/L (p = 0.036, 95% CI −0.008 to −0.245). The only significant difference found between cases and controls was in the change in cholesterol ratio of 0.16 mmol/L between groups (95%CI 0.01–0.31, p = 0.036).Conclusions:AAP use was not associated with any clinically significant change in metabolic outcomes in this study population.

The Food and Drug Administration (FDA) is advising health care practitioners that lamotrigine (Lamictal), used in managing seizures and bipolar disorder, may increase the risk of serious and potentially lethal arrythmias.The risk is greater if the patient has underlying cardiac disease or is taking medications that affect heart conduction.The FDA is requiring in vitro studies of other sodium channel blockers to determine if this risk is a class effect or unique to lamotrigine.

Zusammenfassung Zielsetzung Die perkutane transluminale Angioplastie (PTA) ist ein anerkanntes Verfahren zur Gefäßrekanalisierung. Ein mögliches Werkzeug zur Ergebnisoptimierung sind Paclitaxel-beschichtete Ballonkatheter (drug coated balloon, DCB). Ziel dieses systematischen Reviews ist, herauszufinden, ob zwischen den unterschiedlichen DCB ein Klasseneffekt besteht. Material und Methoden Primärer Endpunkt war die Freiheit von Re-Intervention (FfTLR) nach 1 Jahr. Eine systematische Literatursuche bei PubMed wurde durchgeführt, das Verzerrungsrisiko der eingeschlossenen Studien wurde erhoben. Die Effektivität von DCB gegenüber unbeschichteten Ballonkathetern (POBA) wurde für binäre Endpunkte durch Bestimmung des relativen Risikos und Anzahl der notwendigen Behandlungen (number needed to treat, NNT) untersucht. Ergebnisse Zehn Studien mit 1835 Patienten wurden identifiziert – diese untersuchten 6 verschiedene DCB – es zeigte sich ein hohes Verzerrungsrisiko. Es wurde ein geringerer Late Lumen Loss (DCB: − 0,01 – 0,51 mm; POBA: 1,0 – 1,7 mm) nach DCB-Behandlung nach 6 Monaten und eine höhere FfTLR (DCB: 71 – 98%; POBA: 52 – 85%) sowie höhere primäre Offenheit (DCB: 65 – 84%; POBA: 34 – 61%) nach DCB-Behandlung nach 1 Jahr beobachtet – insbesondere bei der FfTLR zeigten sich große Unterschiede in der DCB-Effektivität zwischen den Studien. Die NNT variierte zwischen 3 und 33. In Summe zeigten sich keine Vorteile nach DCB-Behandlung in Bezug auf ABI- und Rutherford-Outcome nach 1 Jahr; nach DCB-Behandlung traten keine vermehrten Komplikationen auf. Schlussfolgerungen Die getesteten DCB konnten das PTA-Ergebnis nach 1 Jahr verbessern. Es zeigen sich jedoch deutliche Unterschiede in der Effektivität zwischen den unterschiedlichen DCB. Ein Klasseneffekt kann daher aktuell nicht bestätigt werden. Bedingt durch das hohe Verzerrungsrisiko in den Studien ist zu befürchten, dass der Effekt der DCB-Behandlung überschätzt wird.

With the addition of sodium–glucose cotransporter-2 inhibitors to the current arsenal of oral antidiabetics (OAD), a lot has changed. From questioning their glucouretic mechanism to understanding their pleiotropic effects, it has been an eventful journey. In 2008, after the rosiglitazone fiasco, the US Food and Drug Administration (FDA) mandate was passed to ensure the safety of the OAD. Up to the gliptins, there was an era of cardiovascular (CV) safety which progressed to CV protection with the EMPA-REG OUTCOME trial. It came with a lot of questions regarding the probable mechanism and the doubts of whether it will translate into a class effect or not. After the Canagliflozin CV Assessment Study results, a lot of things have come into light regarding the overall benefits with these molecules. This review highlights the similarities and dissimilarities in the two trial results.

A direct comparison of the effects of febuxostat and allopurinol on flow-mediated dilatation (FMD) will help to clarify which agent provides a better reduction of cardiovascular risk in hypertensive patients. Hypertensive patients with hyperuricemia were randomized into a febuxostat (10-40 mg, n = 33) or allopurinol (100-200 mg, n = 31) group and followed up for 6 months. Both the febuxostat (7.9 ± 1.3 mg/dL vs 5.6 ± 1.0 mg/dL, P < .001) and allopurinol (8.2 ± 1.3 mg/dL vs 6.1 ± 1.0 mg/dL, P < .001) groups exhibited significant reductions in uric acid after treatment. There was no significant difference in the change in FMD between the two treatment groups (0.6 ± 2.6% vs 0.2 ± 2.3%, P = .504). However, stratified analysis showed that febuxostat achieved a significantly greater change in FMD compared to allopurinol in the elderly group (1.3 ± 2.9% vs -0.7%±1.8%, P = .047). There was no difference in the improvement of FMD between febuxostat and allopurinol, but febuxostat may provide an improvement of FMD in elderly people.

We read with interest the review article by Chretien et al, “Comparative study of hypoglycemia induced by opioids. Is it a class effect?” published online in this journal [1]. The authors performed...

There has been a great deal of excitement regarding the potential benefits of statins beyond their lipid-lowering effect, and repurposing them for other indications. In this commentary, we evaluate the role of statins in protecting the kidneys, with a focus on three areas: cardiac surgery, contrast-induced nephropathy, and aminoglycoside-induced nephrotoxicity.

Very late stent thrombosis (VLST) has been recognized as a class effect of 1st generation drug eluting stents (DES) implantation. Although rare, VLST has been reported between 1 and 4 years after DES implantation. Very very late stent thrombosis (VVLST) occurring more than 5 years after DES implantation is extremely rare. We report the first case of a VVLST from India occurring 3465 days (9.5 years) after DES implantation with a brief discussion on its pathogenesis and prevention.

The importance of industry-specific factors for a firm's performance has often attracted the attention of researchers, managers, and investment analysts. This research uses random-effect variance component analysis to examine the relevance of structure-conduct-performance (SCP) paradigm in the context of restaurant and petroleum/natural gas firms. The study further investigates class-effect in firm performance by analyzing whether the relative importance of industry-and-firm-level effects varies across different performance groups. Results suggest a direct relevance of the SCP paradigm and industry-specific factors for firm performance, and a distinct dominance of industry-effect over firm-effect regardless of the choice of accounting or value based performance measures. Results further reveal varying roles of industry and firm-level factors (corporate or strategic) across middle-of-the road and non-average (exceptional) performance groups. As such the importance of SCP paradigm and the strategic role of both industry-and-firm effect factors for value creation in US based restaurant firms is better understood.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called “incretin-based therapies” (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clinical practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored. A summary of the main findings from CVOTs performed to-date with particular emphasis on various outcomes and inconsistencies observed in the trials is provided. Overall, available data is favourable to the early deployment of GLP-1RAs in clinical practice, fully in line with recommendations from international scientific guidelines, and based on their effects on glucose metabolism parameters, body weight reduction and CV outcomes. Evidence further suggest that the CV benefits of GLP-1RAs may not be a class effect, with GLP-1 analogues having a greater benefit rather than exendin-based agents.

SGLT2i, empagliflozin and canagliflozin, have been shown to reduce the incidence of major adverse CV events (MACE), all-cause mortality (ACM) and renal events in CV outcomes trials (CVOTs), with robust real-world evidence (RWE) suggesting class effect benefits. In the exenatide CVOT EXSCEL, ∼10% of patients took an SGLT2i with ∼5% use of dapagliflozin (DAPA). Effects of all SGLT2i, and DAPA alone, on MACE, ACM, and eGFR were analyzed in EXSCEL participants randomized to placebo. Propensity-matched cohorts (including by study visit) of SGLT2i users and non-users (n=709 per group) were generated, based on their last measured characteristics before SGLT2i initiation. Subsequent time-to-first adjudicated MACE and ACM were compared using a Cox regression. Decline in eGFR over time (slope) was quantified in the matched cohorts using a mixed model repeated measurement (MMRM) analysis. SGLT2i overall, and DAPA alone, numerically decreased the MACE hazard ratio, and SGLT2i significantly reduced the ACM risk (Table). The eGFR slope was improved significantly for SGLT2i overall and DAPA alone (Table). This post-hoc EXSCEL analysis supports a beneficial class effect for SGLT2i on MACE, ACM, and renal function, consistent with published CVOTs, Real-World data, and for DAPA alone. DECLARE, the ongoing DAPA CVOT, will complete in 2018.Time-to-First Adjudicated EventPropensity-matched cohortnEventsSubject-years of follow-upCrude rate (events/100 subject-years)Unadjusted hazard ratio (95% CI)Adjusted hazard ratio (95% CI)MACEaNo SGLT2i709449904.45SGLT2i709288223.410.78 (0.48–1.27)0.79 (0.49–1.28)No DAPA354224844.54DAPA354114082.690.59 (0.28–1.24)0.55 (0.26–1.15)All-cause mortalityNo SGLT2i7093711083.34SGLT2i709148711.610.48 (0.26–0.89)0.50 (0.27–0.95)No DAPA354135382.42DAPA35474321.620.66 (0.25–1.69)0.66 (0.25–1.72)MMRM analysisPropensity matched cohorteGFR slope (standard error)Treatment effect (95% CI)p-valueeGFR slope (mL/min/1.73m2/year) No SGLT2i−0.91 (0.26)SGLT2i+0.87 (0.37)+1.78 (0.87–2.69)0.00013No DAPA−1.04 (0.37)DAPA+1.24 (0.54)+2.28 (1.01–3.54)0.0004aMACE: a composite endpoint of CV death, non-fatal myocardial infarction or non-fatal stroke Disclosure L. Clegg: Employee; Self; AstraZeneca. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Consultant; Self; Janssen Research & Development, Fresenius SE & Co. KGaA. Advisory Panel; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. R.C. Penland: Employee; Self; AstraZeneca. Stock/Shareholder; Self; Novartis Pharmaceuticals Corporation. W. Tang: Employee; Self; AstraZeneca. D.W. Boulton: Employee; Self; AstraZeneca. Stock/Shareholder; Self; Bristol-Myers Squibb Company. S. Bachina: Employee; Self; AstraZeneca. R.D. Fox: None. P. Fenici: Employee; Self; AstraZeneca. M. Thuresson: Consultant; Self; AstraZeneca. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.

Background Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). Results We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Conclusions Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of drugs and their associated ADRs. Furthermore, our analysis of drug class effects identified 3 benzimidazole drugs sharing 43 ADRs, leading to new hypothesis generation and possible mechanism understanding of drug-induced peripheral neuropathy.

Kontext: Je prokazano, že prasugrel a ticagrelor, dva nove peroralni inhibitory P2Y12, jsou v lecbě akutnich koronarnich syndromů (AKS) obecně výhodnějsi než clopidogrel. Miru sniženi mortality pozorovanou konkretně v připadě ticagreloru lze těžko posoudit pouhým pohledem na celkove výsledky studii, protože hodnocene populace zahrnovaly různe kohorty s podstatně odlisným rizikem umrti.Metody: Byla provedena regresni metaanalýza udajů 12 různých kohort pacientů, přicemž sest kohort uživalo prasugrel a dalsich sest ticagrelor; cilem metaanalýzy bylo zkoumat ucinky uvedených inhibitorů P2Y12 na mortalitu.Výsledky: Udaje pro analýzu kohort (celkem 37 372 pacientů) byly ziskany z publikaci a zahrnuji z mnoha hledisek srovnatelne spektrum různých typů pacientů, definovane typem AKS a strategii lecby. Linky mortality z kardiovaskularnich přicin vynesene pomoci udajů z regresni metaanalýzy výsledků lecby prasugrelem nebo ticagrelorem samostatně, připadně souhrnných výsledků lecby těmito latkami (vždy ve srovnani s clopidogrelem), ukazuji na linearni vztah mezi zvysujicim se přinosem a zvysujicim se zakladnim rizikem (p = 0,007; 0,021 a 0,003 a R2 = 0,87; resp. 0,77 a 0,62).Zavěry: U hodnocených pacientů s AKS jsme zaznamenali přinos podani dvou nových peroralnich inhibitorů P2Y12 ve srovnani s clopidogrelem; přinos se postupně zvětsuje se zvysujicim se zakladnim rizikem umrti. Zda se, že se jedna o ucinek inhibitorů P2Y12 jako lekove skupiny.

A new era in antiembolic therapy has been initiated by the growing numbers of device-based therapies. Early concerns surrounding eliminating this enigmatic structure have not proven true. Other benefits are being further evaluated. Many other questions remain, such as whether there is a device-specific outcome effect or whether it is a class effect. Other questions include other devices, what head-to-head studies will show, and the impact of residual leak. Left atrial appendage using the Watchman ablation strategy can reduce cardioembolic stroke, with comparable or fewer adverse effects by device technology than obtained by long-term anticoagulation with its attendant bleeding risks.