Reduction In Clinical Outcomes Research Articles

Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania.

We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania. This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18. We estimated incidence rate ratios adjusted for timing of HIV-detection (aIRR) and reported viral suppression <1000 copies/mL. Among 6602 neonates enrolled October 2019-September 2021, 125 were diagnosed HIV-positive by week 12. In the intervention arm, 38/69 (55.1%) were diagnosed at birth with 35 initiating ART within two days. In the control arm, 27/56 (48.2%) were retrospectively detected HIV-positive at birth, of whom 6/56 (10.7%) died or were lost to follow-up before testing. Median age at ART initiation was 6 (intervention) versus 33 days (control). Birth test-and-treat was not associated with a significant reduction in clinical outcomes up to month-18 [53 (76.8%) versus 48 (85.7%); aIRR 0.857; 95% CI 0.505-1.492], but showed a 68% relative reduction in 6-month mortality. Viral suppression was poor overall, but improved in the intervention group at month 18 (65.7% versus 29.6%; p=0.005). PoC test-and-treat at birth is feasible in resource-poor settings and resulted in clinically-relevant reduction of early infant mortality, though improved clinical outcomes were not sustained to month-18. Poor viral suppression may undermine early survival benefits, calling for better paediatric treatments and tailored adherence interventions.

Screening strategy to advance HCV elimination in Italy: a cost-consequence analysis.

Italy has the greatest burden of hepatitis C virus (HCV) infection in Western Europe. The screening strategy represents a crucial prevention tool to achieve HCV elimination in Italy. We evaluated the cost-consequences of different screening strategies for the diagnosis of HCV active infection in the birth cohort 1948-1968 to achieve the HCV elimination goal. We designed a probabilistic model to estimate the clinical, and economic outcomes of different screening coverage uptakes, considering the direct costs of HCV management according to eachliverfibrosis stage, in the Italian context. A decision probabilistic tree simulates 4years of HCV testing of the 1948-1968 general population birth cohort, (15,485,565 individuals to be tested) considering different coverage rates. A No-screening scenario was compared with two alternative screening scenarios that represented different coverage rates each year: (1) Incremental approach (coverage rates equal to 5%, 10%, 30%, and 50% at years 1, 2, 3, and 4, respectively) and (2) Fast approach (50% coverage rate at years 1, 2, 3 and 4). Overall 106,200 cases were previouslyestimated to have an HCV active infection. A liver disease progression Markov model was considered for an additional 6years (horizon-time 10 years). The highest increased number of deaths and clinical events are reported for the No-screening scenario (21,719 cumulative deaths at the end of ten years; 10,148 cases with HCC and/or 7618 cases with Decompensated Cirrhosis). Following the Fast-screening scenario, the reductions in clinical outcomes and deaths were higher compared with No-screening and Incremental-screening. At ten years time horizon, less than 5696 liver deaths (PSA CI95%: -3873 to 7519), 3,549 HCC (PSA CI95%: -2413 to 4684) and less than 3005 liver decompensations (PSA CI 95%: -2104 to 3907) were estimated compared with the Incremental-scenario. The overall costs of the Fast-screening, including the costs of the DAA and liver disease management of the infected patients for 10years, are estimated to be € 43,107,543 more than no-investment in screening and € 62,289,549 less compared with the overall costs estimated by the Incremental-scenario. It is necessary to guarantee dedicated funds and efficiency of the system for the cost-efficacious screening of the 1948-1968 birth cohort in Italy. A delay in HCV diagnosis and treatment in the general population, yet not addressed for the HCV free-of-charge screening, will have important clinical and economic consequences in Italy.

Pretreatment with P2Y12 inhibitors and relationship with clinical outcomes in NSTEMI: Analysis of 2 Argentinian registries

Abstract Introduction Pretreatment with P2Y12 inhibitors has been widely studied in the context of NSTEMI patients, with varying results. General consensus is that this strategy should be avoided, unless a long wait time is expected before angiography can be performed. However, it is unclear whether this strategy is associated with a reduction in clinical outcomes, or an increase in bleeding events. Purpose To analyze frequency of pretreatment in NSTEMI in our medium, and association with clinical outcomes. Methods We analyzed the results of two Argentinian acute coronary syndrome registries from 2017 and 2022. We explored incidence of pretreatment, and drug used. We evaluated first through univariate analysis the relationship between pretreatment use and a clinical composite outcome of in hospital events: Myocardial infarction + Mortality + In stent thrombosis + post MI angina + Stroke/TIA. We also explored the relationship of pretreatment with bleeding events (BARC 2 or higher). We later conducted a logistic regression with other clinical variables: Age, gender, diabetes, previous bleeding events, previous MI, aspirin use, anticoagulation, killip-kimball scale and ejection fraction. Results 1297 patients were included in the analysis, after excluding STEMI patients, patients with current use of P2Y12 inhibitors at time of event, and patients who did not undergo angiography. 75.6% were men, 25.6% diabetic, 27,1% smokers, 70.3% hypertensive, and 23.1% had a previous acute coronary syndrome. Mean age was 55.3 years old. Mean GRACE score was 113,5 and CRUSADE 23,8. 44% of patients recieved pretreatment, mostly with clopidogrel (93.5%). Patients that recieved pretreatment were more frequently hypertensive (73.8% vs 67%, p=0.01) and had a higher incidence of previous MI (27% vs 19%, p=0.002). GRACE score was significantly lower in patients that were pretreated (111,5 vs 115, p=0.04). Pretreatment use was significantly associated with a higher incidence of the composite clinical outcome, occuring in 10.1% of patients pretreated and in 6.9% of patients not pretreated (OR 1.56 (1.06-2.3) p=0.02. Bleeding events were numerically more frequent with pretreatment (8.7% vs 5.9%), though did not reach statistical significance (OR 1.51 (0.99-2.3) p=0.054). In multivariate analysis, after adjusting for multiple clinical variables, pretreatment was no longer associated with a higher incidence of clinical outcomes, though also not with a lower incidence (OR 1.4 (0.89-2.3) p=0.13). Discussion Pretreatment, mostly with clopidogrel, did not show a relationship with either benefit or harm with regard to ischemic and bleeding outcomes in NSTEMI patients.

#5621 BENEFICIAL EFFECTS OF CHRONIC INTRADIALYTIC EXERCISE TRAINING ON HEMODIALYSIS-INDUCED-MYOCARDIAL STUNNING

Abstract Background and Aims Hemodialysis (HD) induces left ventricular (LV) segmental regional wall motion abnormalities (RWMAs) due to hypoperfusion, leading to acute LV transient dysfunction, well known as myocardial stunning. Repeated episodes of HD-related myocardial stunning contribute directly to the development of heart failure and increased mortality in patients receiving HD (Burton et al., 2009). Exercise training exert pleiotropic favorable effects on the cardiovascular system. No study has however investigated its impact on the kinetics of regional myocardial function during HD. This study aims to evaluate the effect of intradialytic exercise (IDE) on RWMAs compared with standard care. Method This was a prospective, open-label, two-center trial (clinicaltrials.gov NCT04697459) with two parallel groups: 31 patients (ENT) undergoing a 4-month IDE program (30min of cycling + 30min of resistance training starting 30 min after HD onset) and 21 patients continuing usual care (CTRL). Untrained adults, aged 20-79 years, undertaking maintenance HD for &amp;gt;3 months were eligible to participate. Exclusion criteria were poor echogenicity, contraindication to exercise, orthopedic complications, severe heart (ischemic, valvular, ...), vascular or respiratory diseases, ejection fraction &amp;lt;45% and body mass index &amp;gt;35. Longitudinal strain (LS) using speckle-tracking echocardiography were measured during a standard HD session, just before HD onset (HDT0) and at peak stress of HD (30 min before HD-ending, HDPeak). The same procedure was used before and after 4-months of IDE or usual care. LS from a 18 LV segment model were used to assess the presence of HD-induced RWMAs, defined as a ≥20% reduction in LS at peak stress compared to baseline. A generalized linear mixed model (Poisson model) was used to analyze the effect of IDE on RWMAs. Results After 4 months of IDE, we observed a significant reduction of RWMAs at HDPeak (mean before: 6.03±3.19 vs after: 4.55±2.26; point estimate: -1.48, 95% confident interval CI: -0.39/-2.57, p = 0.03), whereas its occurrence remained unchanged in CTRL (mean before: 6.14±3.51 vs after: 6.09±3.16; point estimate: -0.05; 95% CI: 1.45/-1.54, p = 0.96). There was also evidence that IDE program significantly attenuated the decline of global LS observed during HD (before: 2.11±2.39% vs after: 1.10±1.95%; point estimate: -1.01%; 95% CI: -1.86/-0.13, p = 0.02) compared to the similar impairment in CTRL (before: 1.60±2.30% vs after: 1.79±2.08%; point estimate: +0.18%; 95% CI: +1.20/-0.85 p = 0.72). Conclusion There is clear evidence that chronic IDE is cardioprotective. Identifying the underlying mechanisms responsible for exercise-induced cardioprotection was beyond the scope of our study, but we can reasonably assume that structural and/or functional changes in the coronary arteries, especially in microcirculatory territories (i.e. increased collateral circulation due to angiogenesis/arteriogenesis, improved endothelial function, reduced blood viscosity) and/or intrinsic changes in the cardiac myocyte (reduced fibrosis, enhanced calcium handling/sensitivity, altered mitochondrial turnover and phenotype), related among others to reduced oxidative stress and/or inflammation, might play a role (Powers et al 2014). Whether our results translate to longer-term reduction in clinical outcomes and cardiovascular mortality in end-stage renal disease patients require further studies.

Mental Health Outcomes for Youths With Public Versus Private Health Insurance Attending a Telehealth Intensive Outpatient Program: Quality Improvement Analysis.

COVID-19 exacerbated a growing mental health crisis among youths and young adults, worsened by a lack of existing in-person options for high-acuity care. The emergence and growth of remote intensive outpatient programs (IOPs) is a solution to overcome geographic limitations to care. However, it remains unclear whether remote IOPs engender equivalent clinical outcomes among youths with public insurance (eg, Medicaid) versus private insurance (eg, commercial) given the disparities found in previous research on place-based treatment in both clinical and engagement outcomes. This analysis sought to establish, as part of ongoing quality improvement efforts, whether engagement and clinical outcomes among adolescents and young adults attending remote IOP treatment differed between youths with public and those with private insurance. The identification of disparities by payer type was used to inform programmatic decisions within the remote IOP system for which this quality improvement analysis was conducted. Pearson chi-square analyses and independent 2-tailed t tests were used to establish that the 2 groups defined by insurance type were equivalent on clinical outcomes (depression, suicidal ideation, and nonsuicidal self-injury [NSSI]) at intake and compare changes in clinical outcomes. McNemar chi-square analyses and repeated-measure 2-tailed t tests were used to assess changes in clinical outcomes between intake and discharge in the sample overall. In total, 495 clients who attended the remote IOP for youths and young adults in 14 states participated in ≥7 treatment sessions, and completed intake and discharge surveys between July 2021 and April 2022 were included in the analysis. Overall, the youths and young adults in the remote IOP attended a median of 91% of their scheduled group sessions (mean 85.9%, SD 16.48%) and reported significantly fewer depressive symptoms at discharge (t447=12.51; P<.001). McNemar chi-square tests of change indicated significant reductions from intake to discharge in suicidal ideation (N=470, χ21=104.4; P<.001), with nearly three-quarters of youths who reported active suicidal ideation at intake (200/468, 42.7%) no longer reporting it at discharge (142/200, 71%), and in NSSI (N=430, χ21=40.7; P<.001), with more than half of youths who reported NSSI at intake (205/428, 47.9%) reporting lower self-harm at discharge (119/205, 58%). No significant differences emerged by insurance type in attendance (median public 89%, median private 92%; P=.10), length of stay (t416=-0.35; P=.73), or reductions in clinical outcomes (depressive symptom severity: t444=-0.87 and P=.38; active suicidal ideation: N=200, χ21=0.6 and P=.49; NSSI frequency: t426=-0.98 and P=.33). Our findings suggest that youths and young adults who participated in remote IOP had significant reductions in depression, suicidal ideation, and NSSI. Given access to the same remote high-acuity care, youths and young adults on both public and private insurance engaged in programming at comparable rates and achieved similar improvements in clinical outcomes.

Sodium-glucose co-transporter-2 inhibitors in heart failure with reduced ejection fraction: Current evidence and future perspectives.

The sodium-glucose co-transporter-2 (SGLT2) inhibitors were developed as glucose-lowering drugs to treat type 2 diabetes (T2D). However, significant reductions in clinical outcomes have now been demonstrated in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of T2D. Multiple hypotheses have been proposed for the underlying mechanisms, and the data to support these proposals are emerging. To review the clinical outcome data with SGLT2 inhibitors in HFrEF and the data to support the mechanisms for these clinical effects. Literature review was supported by a PubMed search for relevant articles up to 19 April 2022. Current data support increased diuresis and reverse cardiac remodelling as important mechanisms for the reductions in heart failure hospitalizations and mortality observed with SGLT2 inhibitors (empagliflozin or dapagliflozin) in patients with HFrEF. Alteration in intrarenal haemodynamic is likely contributing to the observed renoprotective effect of SGLT2 inhibitors. Solid clinical data support the current recommendations to use empagliflozin or dapagliflozin in HFrEF. The underlying mechanisms likely include changes in cardiac and intrarenal haemodynamic. Yet, these mechanisms do not seem to solely explain the observed magnitude of clinical effect with SGLT2 inhibitors in HFrEF, and other mechanisms may contribute.

A Pharmacological Review of Siddha Classical Preparations for the Management of COVID-19 at TPEC COVID Care Centre, Vellore

Despite the threat of coronavirus infection, the Siddha system of medicine, India's traditional medicine, plays an important role in southern India, particularly in Tamilnadu. It contributed considerably not only in the first wave of Covid-19, but also in the second wave. The Government of Tamilnadu developed Siddha COVID-19 treatment centers for asymptomatic, mild, and moderate COVID-19 positive patients in 2020. The TPEC COVID Care Centre initiated at Vellore also one of the Centers that can be managed by Siddha medicines and Siddhar’s Yogam. As of July 14, 2021, about 4525 COVID positive patients had been treated with Siddha integrated treatment at Vellore alone in the first and second waves. Kaba Sura Kudineer, Thalisathy Vadagam, Amukkara Chooranam Mathirai, Bramanandha Bairavam Mathirai, and Adathodai Manapagu are indeed the five Siddha classical preparations used to manage the symptoms of COVID-19 positive patients at TPEC COVID Care Centre in Vellore. This Siddha medical practice is effective in conditions of symptoms and helps in the reduction of clinical outcomes. A pilot study at the same site confirmed the Siddha classical preparation's safety and effectiveness. A feedback analysis study performed at the same center also revealed that the above-mentioned Siddha classical preparations are beneficial in symptomatic treatment without causing any side effects. The medicines utilized in this study are typically proposed in other COVID care centers also in Tamilnadu. This review attempted to analyze the preclinical and clinical efficacy of Siddha Classical medicines used at that Centre for the management of COVID-19.

Differing effects of beta-blockers on long-term clinical outcomes following percutaneous coronary intervention between patients with mid-range and reduced left ventricular ejection fraction

BackgroundThe aim of this study was to determine the difference in effects of beta-blockers on long-term clinical outcomes between ischemic heart disease (IHD) patients with mid-range ejection fraction (mrEF) and those with reduced ejection fraction (rEF).MethodsData were assessed of 3508 consecutive IHD patients who underwent percutaneous coronary intervention (PCI) between 1997 and 2011. Among them, 316 patients with mrEF (EF = 40–49%) and 201 patients with rEF (EF < 40%) were identified. They were assigned to groups according to users and non-users of beta-blockers and effects of beta-blockers were assessed between mrEF and rEF patients, separately. The primary outcome was a composite of all-cause death and non-fatal acute coronary syndrome.ResultsThe median follow-up period was 5.5 years in mrEF patients and 4.3 years in rEF patients. Cumulative event-free survival was significantly lower in the group with beta-blockers than in the group without beta-blockers in rEF (p = 0.003), whereas no difference was observed in mrEF (p = 0.137) between those with and without beta-blockers. In the multivariate analysis, use of beta-blockers was associated with reduction in clinical outcomes in patients with rEF (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36–0.97; p = 0.036), whereas no association was observed among those with mrEF (HR 0.74; 95% CI 0.49–1.10; p = 0.137).ConclusionsOur observational study showed that use of beta-blockers was not associated with long-term clinical outcomes in IHD patients with mrEF, whereas a significant association was observed in those with rEF.

Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis

Background and aimsThere is limited data on clinical outcomes in high risk groups such as patients with diabetes mellitus (DM) with atrial fibrillation (AF) on direct-acting oral anticoagulants (DOACs). Using a systematic review and meta-analysis of published studies, we aimed to determine the risk of stroke and other clinical outcomes in patients with AF on DOACs, with or without DM. MethodsObservational cohort studies reporting clinical outcomes in patients with AF on DOACs, with or without DM were identified from MEDLINE, Embase, Web of Science, the Cochrane Library, and search of bibliographies to April 2020. Summary measures of effect were relative risks with 95% confidence intervals (CIs). ResultsEight studies comprising of 4 observational cohorts (n = 76,260 participants) and 4 randomised controlled trials (RCTs) (n = 71,683 participants) were included. In RCTs, DOACs compared with warfarin reduced the risk of the composite outcome of stroke and systemic embolism, CVD death and intracranial bleeding in patients with DM: RRs (95% CIs) of 0.75 (0.62–0.90), 0.84 (0.72–0.97), and 0.57 (0.40–0.81) respectively. The corresponding estimates for patients without DM were 0.81 (0.68–0.96), 0.93 (0.80–1.08), and 0.47 (0.31–0.70) respectively. There was no evidence of interactions between DM status and effects of DOACs. The absolute reduction in clinical outcomes with DOACs compared to warfarin was greater in DM than without DM. Regardless of treatment strategy, interventional and observational evidence indicate that patients with DM had higher rates of stroke or systemic embolism, mortality and major bleeding compared to patients without DM. ConclusionsPatients with AF and DM have increased risk of vascular events, which is reduced with the use of DOACs. The use of DOACs should be considered as an option in reducing the risk of stroke in these populations. Systematic review registrationPROSPERO 2020: CRD42020157196.

N-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials.

BackgroundCardiac surgeries are complex procedures aiming to re-establish coronary flow and correct valvular defects. Oxidative stress, caused by inflammation and ischemia-reperfusion injury, is associated with these procedures, increasing the risk of adverse outcomes. N-acetylcysteine (NAC) acts as an antioxidant by replenishing the glutathione stores, and emerging evidence suggests that NAC may reduce the risk of adverse perioperative outcomes. We conducted a systematic review and meta-analysis to investigate the addition of NAC to a standard of care among adult patients undergoing cardiac surgery.MethodsWe searched four databases (PubMed, EMBASE, CENTRAL, LILACS) from inception to October 2018 and the grey literaure for randomized controlled trials (RCTs) investigating the effect of NAC on pre-defined outcomes including mortality, acute renal insufficiency (ARI), acute cardiac insufficiency (ACI), hospital length of stay (HLoS), intensive care unit length of stay (ICULoS), arrhythmia and acute myocardial infarction (AMI). Reviewers independently screened potentially eligible articles, extracted data and assessed the risk of bias among eligible articles. We used the GRADE approach to rate the overall certainty of evidence for each outcome.ResultsTwenty-nine RCTs including 2,486 participants proved eligible. Low to moderate certainty evidence demonstrated that the addition of NAC resulted in a non-statistically significant reduction in mortality (Risk Ratio (RR) 0.71; 95% Confidence Interval (CI) 0.40 to 1.25), ARI (RR 0.92; 95% CI 0.79 to 1.09), ACI (RR 0.77; 95% CI 0.44 to 1.38), HLoS (Mean Difference (MD) 0.21; 95% CI -0.64 to 0.23), ICULoS (MD -0.04; 95% CI -0.29 to 0.20), arrhythmia (RR 0.79; 95% CI 0.52 to 1.20), and AMI (RR 0.84; 95% CI 0.48 to 1.48).LimitationsAmong eligible trials, we observed heterogeneity in the population and interventions including patients with and without kidney dysfunction and interventions that differed in route of administration, dosage, and duration of treatment. This observed heterogeneity was not explained by our subgroup analyses.ConclusionsThe addition of NAC during cardiac surgery did not result in a statistically significant reduction in clinical outcomes. A large randomized placebo-controlled multi-centre trial is needed to determine whether NAC reduces mortality.RegistrationPROSPERO CRD42018091191.

Managing Acinetobacter baumannii infections.

We reviewed recent data about epidemiology of Acinetobacter baumannii, resistance mechanisms, and therapeutic options for severe infections caused by multidrug-resistant strains. A. baumannii is a major cause of nosocomial infections affecting mainly to debilitating patients in the ICU, although the spread to regular wards and to long-term care facilities is increasing. It is characterized by its great persistence in the environment and to have an extraordinary capability to develop resistance to all antimicrobials.Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are the antimicrobials with the greatest level of in-vitro activity against A. baumannii. Colistin is the most widely used in clinical practice although polymyxin B seems to be associated with less renal toxicity. Colistin is administered intravenously as its inactive prodrug colistimethate. A loading dose of 9 million IU and subsequently high, extended-interval maintenance doses (4.5 million IU/12 h) are recommended. Combination therapy instead of monotherapy increases the rates of microbiological eradication although no clinical study has demonstrated a reduction in clinical outcomes (mortality or length of stay). The optimal treatment for multidrug-resistant A. baumannii nosocomial infections has not been established. There are no compelling data to recommend combination therapy for severe A. baumannii infections.

Loss of job-related right to healthcare is associated with reduced quality and clinical outcomes of diabetic patients in Mexico.

The Mexican Institute of Social Security (IMSS) provides a package of health, economic and social benefits to workers employed in private firms within the formal labour market and to their economic dependants. Affiliates have a right to these benefits only while they remain contracted, thus posing a risk for the continuity of healthcare. This study evaluates the association between the time (in days) without the right to healthcare due to job loss in the formal labour market and the quality of healthcare and clinical outcomes among IMSS affiliates with Type 2 diabetes mellitus (T2DM). Retrospective cohort study 2013-2015. Six IMSS family medicine clinics (FMC) in Mexico City. T2DM patients (n = 27 217) affiliated with job-related health insurance and at least one consultation with a family doctor during 2013. IMSS affiliation department database and electronic health records and clinical laboratory databases. Quality of the processes (eight indicators) and outcomes (three indicators) of healthcare. The results indicated that losing IMSS right to healthcare is frequent, occurring to one-third of T2DM patients during the follow-up period. The time without the right to healthcare in the observed period was of 120 days on average and was associated with a 43.2% loss of quality of care and a 19.2% reduction in clinical outcomes of T2DM. Policies aimed at ensuring access and continuity of care, regardless of job status, are critical for improving the quality of processes and outcomes of healthcare for diabetic patients.

Role of inflammation versus hypercholesterolemia in the development of atherosclerosis in male albino rats

Background Atherosclerosis (AS) is a chronic condition in which dyslipidemia had been contributed to its development, along with evidence proving an inflammatory cause. Objective The aim was to determine the relation between dietary hypercholesterolemia and AS with a trial to evaluate the role of inflammation in development of AS in male albino rats. Materials and methods A total of 30 adult male albino rats were divided into two main groups: control group (n=6) and high-cholesterol diet (HCD)-fed group (n=24), which was subdivided into four subgroups (n=6): HCD-fed, HCD-fed with methotrexate, HCD-fed with cholestyramine, and HCD-fed with statin groups. Serum total cholesterol (TC), triglycerides, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, low-density lipoprotein (LDL)-cholesterol, very LDL-cholesterol, atherogenic index, LDL/HDL ratio, and inflammatory markers such as inerlukin-6, tumor necrotic factor-α, and highly sensitive C-reactive protein were estimated. Carotid artery histopathology was done. Results HCD produced marked disturbance in lipid profile and increased inflammatory markers and atherosclerotic changes in carotid artery. Administration of statin and cholestyramine significantly improved this dyslipidemia. Elevated inflammatory markers were significantly decreased by administration of methotrexate and statin. Atherosclerotic changes in carotid artery decreased significantly in rats pretreated with methotrexate and statin. Conclusion Atherosclerotic condition is closely associated with excessive intake of cholesterol-rich diet; however, inflammation has a central role in the pathogenesis of the atherosclerotic process, as atherosclerotic changes could be reduced despite disturbed lipid profile by anti-inflammatory medication. Further studies are recommended for more evaluation of the role of anti-inflammatory drugs in reduction of clinical outcomes in atherosclerotic conditions.

Impact of cigarette smoking on clinical outcomes of periodontal flap surgical procedures: a systematic review and meta-analysis.

Periodontal flap surgery is frequently used to remove subgingival deposits, yielding consequential reductions in gingival inflammation and probing depth (PD) with a gain in clinical attachment level (CAL) to treat advanced periodontal disease. However, clinical studies have reported diminished periodontal healing in smokers compared with non-smokers. The aim of the present systematic review and meta-analysis was to assess the impact of cigarette smoking on clinical outcomes following periodontal flap surgical procedures. A systematic electronic review of articles relevant to periodontal flap surgical procedures in smokers was conducted from 1977 to March 2014 inclusive, using predefined, optimized search strategies. Meta-analyses were done separately for changes in the two primary outcomes of PD and CAL. The initial search yielded 390 titles and abstracts. After screening, eight controlled clinical studies were finally selected. Three studies were assessed as having a low risk of bias, two as having moderate risk of bias, and three as having a high risk of bias. Qualitative assessment of the articles consistently showed an improved treatment effect among non-smokers versus smokers. The reduction in PD in smokers and non-smokers ranged from 0.76 to 2.05 mm and 1.27 to 2.40 mm, respectively. For CAL, the gain in non-smokers versus smokers ranged from 0.29 to 1.6 mm and 0.09 to 1.2 mm, respectively. Meta-analysis on eight studies reporting on 363 study participants demonstrated an increased reduction in mean (95% confidence interval) PD of 0.39 (0.33 to 0.45) mm. Similar results were found for mean gain in CAL (0.35 [0.30 to 0.40] mm, n = 4 studies). Considering the relatively homogenous information available, the authors conclude that active smokers could be candidates for periodontal flap surgical procedures. However, the magnitude of the therapeutic effect is compromised in smokers compared with non-smokers. Therefore, cigarette smokers should be: 1) encouraged to abstain from smoking; and 2) thoroughly informed preoperatively of substantial reduction in clinical outcomes compared with non-smokers.

Ezetimibe: rescued by randomization (clinical and mendelian).

Since its market launch in the early 2000s, ezetimibe has had a stormy history of acceptance and use by the clinical community. Ezetimibe’s initial approval by regulatory bodies was based primarily on its low side effect profile together with its ability to consistently reduce low-density lipoprotein (LDL) cholesterol by ≈20% either as monotherapy or as an additive to statin therapy. Notably, approval was granted despite the absence from ezetimibe’s portfolio of studies, demonstrating reductions in hard clinical cardiovascular outcomes, such as myocardial infarction or stroke. By 2006, ezetimibe accounted for >15% of all prescriptions for lipid-lowering medications in the United States,1 reflecting that era’s stout faith in the reliability of LDL cholesterol as a surrogate marker for clinical end points, together with practitioners’ positive real-world experiences with ezetimibe’s biochemical efficacy and good tolerability. It was tacitly anticipated that the pending cardiovascular outcome studies would be positive, eventually vindicating the early confidence that clinicians placed in the drug. However, the waters grew rough for ezetimibe in 2008. First, the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial conducted for 24 months in 720 patients with familial hypercholesterolemia showed that combined therapy with ezetimibe and simvastatin did not significantly change carotid intima–media thickness when compared with simvastatin alone, despite decreased levels of LDL cholesterol.2 Next, the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial conducted for 52 months in 1873 elderly nondiabetic patients with aortic stenosis showed that ezetimibe plus simvastatin did not reduce the composite outcome of combined aortic valve events and ischemic events.3 To add insult to injury, the 2009 Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol-6-HDL and LDL Treatment Strategies in Atherosclerosis (ARBITER 6-HALTS) study demonstrated that when combined with a statin, extended-release niacin caused a significant …

Untangling the relationship between medication adherence and post–myocardial infarction outcomes: Medication adherence and clinical outcomes

Patients who adhere to medications experience better outcomes than their nonadherent counterparts. However, these observations may be confounded by patient behaviors. The level of adherence necessary for patients to derive benefit and whether adherence to all agents is important for diseases that require multiple drugs remain unclear. This study quantifies the relationship between medication adherence and post-myocardial infarction (MI) adverse coronary events. This is a secondary analysis of the randomized MI FREEE trial. Patients who received full prescription coverage were classified as adherent (proportion of days covered ≥80%) or not based upon achieved adherence in the 6 months after randomization. First major vascular event or revascularization rates were compared using multivariable Cox models adjusting for comorbidity and health-seeking behavior. Compared with patients randomized to usual care, full coverage patients adherent to statin, β-blocker, or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were significantly less likely to experience the study's primary outcome (hazard ratio [HR] range 0.64-0.81). In contrast, nonadherent patients derived no benefit (HR range 0.98-1.04, P ≤ .01 for the difference in HRs between adherent and nonadherent patients). Partially adherent patients had no reduction in clinical outcomes for any of the drugs evaluated, although their achieved adherence was higher than that among controls. Achieving high levels of adherence to each and all guideline-recommended post-MI secondary prevention medication is associated with improved event-free survival. Lower levels of adherence appear less protective.

Trombectomia adjunta em intervenção percutânea primária para infarto agudo do miocárdio

Primary percutaneous coronary intervention (PCI) has become the favored reperfusion strategy in acute ST-segment elevation myocardial infarction. Lower post-PCI myocardial perfusion grade, no-reflow and even drug-eluting stent thrombosis have been related to the presence of intracoronary thrombus. Adjunctive thrombectomy refers to procedures and devices that remove thrombotic material from the infarction-related artery, in theory, before distal embolization can occur. There is substantial variability between randomized controlled trials of thrombectomy in primary PCI with regards to tested devices, procedural characteristics, adjuvant medical regimen and examined outcomes. As a general statement, improvements in myocardial perfusion endpoints do not translate into reductions in clinical outcomes. Yet, an increasing number of trials with a longer follow-up reported benefits arising late after the index myocardial infarction. Simple aspiration catheters may also produce better outcomes than devices that fragment the thrombus before aspirating debris. Clinical or angiographic variables which best predict benefits from the use of thrombectomy remain to be defined. The aim of this review is to provide perspective on the conclusions of available trials and meta-analysis of adjunctive thrombectomy in acute myocardial infarction. Targets for future studies are discussed.

The Number of Useable Embryos per Oocyte Retrieved is Reduced in Cycles Where More than Twenty Oocytes are Retrieved in Anonymous Egg Donors

BACKGROUND AND SIGNIFICANCE: The reduction of clinical outcomes in cycles where high numbers of oocytes are retrieved has been debated in the literature. The hypothesis that extremely super physiological estrogen concentrations may impair implantation has been discussed as has the direct effect on embryo viability. In order to be able to study the effect of high numbers of oocytes retrieved independent of the many variables infertility type brings, this study was performed on anonymous oocyte donors only.

Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial

The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 microg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. During the lead-in, >or=4-log(10) decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by >or=4 log(10) during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Viral suppression by >or=4 log(10) with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.

Treatment disparities in patients with acute coronary syndromes and kidney disease

Management of acute coronary syndromes (ACS) has been considerably refined over the past several decades, with the advances in diagnostics including prompt electrocardiography, use of cardiac biomarkers including cardiac troponin, antiplatelet and antithrombotic agents, b-adrenergic blockers, statins, and targeted utilization of invasive management with coronary angiography and revascularization with percutaneous coronary intervention (PCI) in the majority, with amenable anatomy and coronary artery bypass surgery in a minority of patients with multivessel disease and critical stenoses in one or more vessels. In the optimal care of a patient with ACS, each of these advances has contributed to relative risk reductions in clinical outcomes including recurrent myocardial infarction (MI), rehospitalization for ACS, and cardiac death. Because the use of early invasive management depends on hospital facilities, the willingness of the physician, and consent from the patient, this component of treatment is particularly susceptible to treatment bias. Therefore, a previous meta-analysis of seven randomized trials (n ¼ 9212 ACS patients) is important as it demonstrated that death or MI was reduced from 14.4 to 12.2% in the routine invasive group (relative 18% risk reduction) with a non-significant trend toward fewer deaths (6.0% vs. 5.5%). 1 If a subgroup could be identified where this 8% relative mortality reduction was amplified 4-fold, most would agree this subset should be considered a priority for invasive management. In the analysis by Wong et al., patients with stage 4 and higher chronic kidney disease (CKD) denoted by an estimated glomerular filtration rate (eGFR) ,30 mL/min/1.73 m 2 who were selected for an early invasive management approach for ACS enjoyed a 33.7% relative risk reduction in mortality compared with those managed conservatively who ultimately had a 41.5% all-cause mortality. 2 The propensity analysis supported these findings with an adjusted 47% risk reduction, suggesting that much more than selection bias accounts for the disparities in outcomes. How can disparities in the use of invasive management account for such a large differential in mortality? The answer lies in a careful look at those patients who had the worst health in the three registries summarized. In the 639 (5.6%) with an eGFR ,30 mL/min/1.73 m 2 [serum creatinine (Cr) 2.7 mg/dL (238 mmol/L)] the median age was 76 years (interquartile range 68‐84), 50% had diabetes, 75% demonstrated positive biomarkers indicating acute MI, 55% had a history of previous MI, and 36% suffered from prior heart failure. Hence, the eGFR ,30 mL/min/1.73 m 2 or Cr 2.7 mg/dL (238 mmol/L) served as a proxy for a clinical ‘package’ containing elderly patients with the highest risk for mortality in ACS. So why was an invasive approach used in fewer than a third of patients in this group despite low rates of patient/family refusal? The answer appears to be in the response of ‘not high enough risk or not supported by evidence’ which is frankly disturbing. The evidence-based risk predictors in the eGFR ,30 mL/min/1.73 m 2 suggest clinicians are failing to recognize risk. 3 While this trend is slowly improving over the time course of these registries, these data point to much room for improvement in estimation of mortality risk in elderly ACS patients. The indicators from treating physicians highlight for the first time that concern over contrast-induced acute kidney injury,bleeding, and co-morbidities does not account for intentional ‘therapeutic nihilism’ in patients with CKD. In summary, there appears to be a perceived risk mismatch between the clinical impression and the real mortality risk of ACS in patients with eGFR ,30 mL/min/1.73 m 2 . Educational efforts should be directed towards understanding how traditional risk predictors including positive biomarkers, age, diabetes, and histories of MI and heart failure aggregate in patients with significant CKD. 4 If managed conservatively, the study of Wong et al. 2 and a study by Keeley et al. 5 suggest this ACS population has disastrous outcomes with a nearly 50% case fatality rate at 1 year. This rate can be cut in half with an invasive management approach in appropriate patients. Giving the ageing population structures of developed countries, we can and should expect considerable improvement in treatment outcomes for this important group of ACS patients. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.