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Background. We defined clinically relevant benchmark values in deceased donor kidney transplantation (KT), to assess the best achievable results in low-risk patient cohorts from experienced centers. Methods. We identified the “ideal” cases from the United Network for Organ Sharing Standard Transplant Analysis and Research files from centers performing ≥50 KT per year between 2010 and 2018. Cases have been selected based on the kidney donor profile index values (

BackgroundMany European Health Systems are implementing or increasing levels of cost-sharing for medicine in response to the growing constrains on public spending on health despite their negative impact on population health due to delay in seeking care.ObjectiveThis study aims to examine the relationships between multimorbidity (two or more coexisting chronic diseases, CDs), complex multimorbidity (three or more CDs impacting at least three different body systems), and out-of-pocket expenditure (OOPE) for medicine across European nations.MethodsThis study utilized data on participants aged 50 years and above from two recent waves of the Survey of Health, Aging, and Retirement in Europe conducted in 2013 (n = 55,806) and 2015 (n = 51,237). Pooled cross-sectional and longitudinal study designs were used, as well as a two-part model, to analyse the association between multimorbidity and OOPE for medicine.ResultsThe prevalence of multimorbidity was 50.4% in 2013 and 48.2% in 2015. Nearly half of those with multimorbidity had complex multimorbidity. Each additional CD was associated with a 34% greater likelihood of incurring any OOPE for medicine (Odds ratio = 1.34, 95% CI = 1.31–1.36). The average incremental OOPE for medicine was 26.4 euros for each additional CD (95% CI = 25.1–27·7), and 32.1 euros for each additional body system affected (95% CI 30.6–33.7). In stratified analyses for country-specific quartiles of household income the average incremental OOPE for medicine was not significantly different across groups.ConclusionBetween 2013 and 2015 in 13 European Health Systems increased prevalence of CDs was associated with greater likelihood of having OOPE on medication and an increase in the average amount spent when one occurred. Monitoring this indicator is important considering the negative association with treatment adherence and subsequent effects on health.

Familial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism that causes an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Although early diagnosis and treatment of FH can significantly improve the cardiovascular prognosis, this disorder is underdiagnosed and undertreated. For these reasons the Italian Society for the Study of Atherosclerosis (SISA) assembled a Consensus Panel with the task to provide guidelines for FH diagnosis and treatment. Our guidelines include: i) an overview of the genetic complexity of FH and the role of candidate genes involved in LDL metabolism; ii) the prevalence of FH in the population; iii) the clinical criteria adopted for the diagnosis of FH; iv) the screening for ASCVD and the role of cardiovascular imaging techniques; v) the role of molecular diagnosis in establishing the genetic bases of the disorder; vi) the current therapeutic options in both heterozygous and homozygous FH. Treatment strategies and targets are currently based on low-density lipoprotein cholesterol (LDL-C) levels, as the prognosis of FH largely depends on the magnitude of LDL-C reduction achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment. Addition of novel medications like PCSK9 inhibitors, ANGPTL3 inhibitors or lomitapide in homozygous FH results in a further reduction of LDL-C levels. LDL apheresis is indicated in FH patients with inadequate response to cholesterol-lowering therapies. FH is a common, treatable genetic disorder and, although our understanding of this disease has improved, many challenges still remain with regard to its identification and management. [ABSTRACT FROM AUTHOR]

Background and Objective: Arterial stiffness (AS) is an independent cardiovascular risk factor. A number of studies have reported a beneficial role of statins on AS albeit with controversial results, in addition to their effects on lipid profile. Therefore, we carried out a meta-analysis of the available randomized controlled trials assessing the effects of statin therapy on AS, in the attempt to reach more definitive conclusions. Methods: A systematic search of the on-line databases available up to March 2017 was conducted, including intervention studies reporting AS expressed by carotid-femoral pulse wave velocity (PWV), as difference between the effects of treatment with or without statins. For each study, mean difference (MD) and 95% confidence intervals (CI) were pooled using a random effect model. Results: Eleven studies met the pre-defined inclusion criteria, for a total of 573 participants and 2–144 weeks’ intervention time. In the pooled analysis, statin therapy was associated with a −6.8% (95% C.I.: −11.7 to −1.8) reduction in PWV. There was significant heterogeneity among studies (I2 = 96%); none of the study characteristics seems to have influenced the effect of statin use on PWV. Conclusions: The results of this meta-analysis suggest that statin therapy reduces AS. This effect appears to be at least in part independent of the changes in blood pressure and lipid profile.

OBJECTIVE: Peginterferon β-1a (PEG-IFN-β-1a) is the most recent interferon beta formulation approved for treating relapsing-remitting multiple sclerosis (RRMS). We aim to describe the real-world utilization of PEG-IFN-β-1a in RRMS and compare it with other injectable disease-modifying therapies (DMTs). PATIENTS AND METHODS: In this population-based study, we used 2015-2019 routinely collected healthcare data of the Campania region of Italy from National Healthcare System DMT prescriptions, inpatient and outpatient clinical records of hospitals in Campania, and the Federico II University MS clinical registry for a subset of patients. We included individuals with RRMS receiving new prescriptions of PEG-IFN-β-1a [n=281; age = 38.8±12.3 years; females=70.5%; disease duration = 8 .4±8.3 years; Expanded Disability S tatus Scale (EDSS) at baseline=2.0 (1.0-6.5)], glatiramer acetate [n=751; age = 46.0±11.4 years; females= 67.1%; disease duration = 9.8±8.2 years; EDSS=4.0 (1.5-8.5)], and subcutaneous (SC) IFN-β-1a [n=1,226; a ge = 3 9.7±11.7 y ears; f emales= 66.5%; disease duration = 8.2±6.5 years; EDSS 2.5 (1.5-6.5)]. Adherence [medication possession ratio (MPR)], escalation to more effective DMTs, hospitalization rates and costs were measured. We used mixed-effect linear regression models (for adherence, hospitalization rates and costs) and Cox regression models (for escalation) to assess differences between PEGIFN-β-1a (statistical reference), glatiramer acetate, and SC IFN-β-1a. All models included age, sex, previous treatment/untreated, year of treatment initiation, treatment duration, and adherence as covariates. RESULTS: Adherence was lower in glatiramer acetate (MPR = 0.91±0.1; Coeff=-0.11; p<0.01), and IFN-β-1a (MPR = 0.92±0.1; Coeff=-0.08; p<0.01), compared with PEG-IFN-β-1a (MPR = 1.01±0.1). The probability of escalating to more effective DMTs was higher for glatiramer acetate (14.9%; HR=4.09; p<0.01) and IFN-β-1a (9.1%; HR=3.35; p=0.01), compared with PEG-IFN-β-1a (4.9%). No differences in annualized hospitalization rates were identified between glatiramer acetate [annualized hospitalization rates (AHR) = 0.05±0.30; Coeff=0.02; p=0.31), IFN-β-1a (AHR = 0.02±0.21; Coeff=0.01; p=0.97], and P EG-IFN-β-1a (AHR = 0 .02±0.24); h owever, monthly costs for MS admissions were higher for glatiramer acetate (€49.45±€195.27; Coeff=-29.89; p=0.03), compared with IFN-β-1a (€29.42±€47.83; Coeff=6.79; p=0.61), and PEGIFN-β-1a (€23.91±€43.90). CONCLUSIONS: SC PEG-IFN-β-1a and IFN-β-1a were used in relatively similar populations, while glatiramer acetate was preferred in older and more disabled patients. PEG-IFN-β-1a was associated with higher adherence and lower escalation rates toward more effective (and costly) DMTs. [ABSTRACT FROM AUTHOR]

Carotid artery plaques are considered a measure of atherosclerosis and are associated with an increased risk of atherosclerotic cardiovascular disease, particularly ischemic strokes. Monitoring of patients with an elevated risk of stroke is critical in developing better prevention strategies. Non-invasive imaging allows us to directly see atherosclerosis in vessels and many features that are related to plaque vulnerability. A large body of evidence has demonstrated a strong correlation between some lipid parameters and carotid atherosclerosis. In this article, we review the relationship between lipids and atherosclerosis with a focus on carotid ultrasound, the most common method to estimate atherosclerotic load.

Maria Triassi,1 Elena Giancotti,2 Antonio Nardone,1 Giulia Mancini,3 Fabiana Rubba1 1Public, Preventive and Social Medicine School, University Federico II of Naples, Naples, Italy; 2Procurement and Transplantation Coordination, Naples, Italy; 3Sociology Unit, G D'annunzio University, Chieti-Pescara, Italy Introduction: The growing disparity between organ availability for transplantation and the number of patients in need has challenged the donation and transplantation community to develop innovative processes, ideas, and techniques to bridge this gap. Advances in the sharing of best practices in the donation community have contributed greatly to this aim over the past 5 years. Studies published during the past five years (2010–2014) were analyzed to gain insight on the evolving organizational areas and tools that the procurement and transplantation pathways have been focused on. The hypothesis assessed is that networking and efficacious handling of this complex path may be ameliorated by an adaptive organizational toolbox. Methods: A thorough search has been conducted using various databases, ie, Cochrane library, PubMed, EMBASE, Federico II University Open Archive. The evidence was considered following the Effective Practice and Organization of Care Group checklist. Prevalent organizational attitudes and areas were assessed, and various scenarios were analyzed. Initially, all titles and abstracts were screened. In the next phase, the full text of all abstracts considered potentially relevant by at least one of the reviewers was evaluated. Inconsistencies in decision-making within this second phase were solved based on consensus between both reviewers. In this phase, for every study we defined whether the organization was considered relevant and what the scenario was. The information was extracted from each study based on bibliographic details (author, journal, year of publication, and language). As many as 1,071 studies were analyzed, and 81 were selected as potentially relevant. Results: We found three prevalent areas of interest focused on organizational elements: global organizational strategies scenario, clinical hospital organization, and citizenship and social scenario. Conclusion: We reached the conclusion that organization has a central role in different scenarios of procurement and transplantation in a continuum from government to hospital (the core of the system) and finally among citizens. A standardized hospital pathway definitely remains the essential step in order to ameliorate either procurement or transplantation. Keywords: transplant procurement, management, organizational tool, network

Scores student-constructed concept maps (n=17) that emerged from post-instructional interviews about chlorofluorocarbons against a teacher-expert map using a scheme weighted for relationships. Supports the recommendations of others to use expert referents and emphasize concept relationships in assessing concept maps. (Author/MM)

Describes the West Virginia K-12 RuralNet project which provides inservice teacher training to public school teachers on the use of Internet resources and presents a summary of quantitative and qualitative evaluation. Explains the validation of two instruments, the Level of Use of Internet and the Personal Internet Teaching Efficacy Beliefs Scale. (Author/LRW)

The main causes of familial hypercholesterolemia (FH) are mutations in LDL receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR function impairment caused by mutations and would be useful as a diagnostic tool if they allow discrimination between FH patients and controls. In order to identify the best method to detect LDLR activity, we compared continuous Epstein-Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes. In addition, we characterized both novel and known mutations in the LDLR gene. T-lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood of 24 FH patients and 24 control subjects. Functional assays were performed by incubation with fluorescent LDL followed by flow cytometry analysis. Residual LDLR activity was calculated normalizing fluorescence for the mean fluorescence of controls. With stimulated T-lymphocytes we obtained a better discrimination capacity between controls and FH patients compared with EBV-transformed B-lymphocytes as demonstrated by receiver operating characteristic (ROC) curve analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001 both). The characterization of LDLR activity through T-lymphocytes is more simple and faster than the use of EBV-transformed B-lymphocytes and allows a complete discrimination between controls and FH patients. Therefore the evaluation of residual LDLR activity could be helpful not only for mutation characterization but also for diagnostic purposes.

Reports on a study of seventh-grade life science students who received Science-Technology-Society (STS) instruction in their life science classes (n=264) versus students who received only instruction in life science content (n=136). Finds that the model of STS instruction employed significantly increased students' participation in citizenship issues on STS issues. Contains 22 references. (Author/WRM)

Paolo Rubba, Gennaro Marotta, Marco GentileDepartment of Clinical and Experimental Medicine, Federico II University of Naples, ItalyAbstract: Rosuvastatin is a synthetic statin that represents an advance in the pharmacologic and clinical properties of statins. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. As with other statins, serious adverse effects with rosuvastatin therapy are uncommon and primarily involve effects on the liver and skeletal muscle. The risk increases with increasing dosages and coadministration with other drugs interacting with the same metabolic pathway. The degree of LDL reduction is important to achieve the treatment goals suggested by international guidelines. Among the most potent statins, rosuvastatin is capable of getting the majority of patients to their LDL cholesterol goals. In addition, rosuvastatin has been found effective in reducing small-dense LDL, C-reactive protein and in increasing HDL cholesterol levels. Controlled clinical trials using vascular end-points have been performed. In particular, a study demonstrated that rosuvastatin therapy could slow progression and/or cause regression of carotid intima-media thickness over 2 years in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis. A primary prevention study (JUPITER) was stopped before the programmed end of the study, because of excess benefit for high-risk individuals receiving rosuvastatin treatment. It is suggested that pronounced LDL reduction, in association with significant HDL cholesterol increase, are the bases of a marked preventive action of rosuvastatin. The results from JUPITER support the use of rosuvastatin for primary cardiovascular prevention, in overweight men and women, with near to normal LDL cholesterol and high CRP. There is now evidence of benefit from rosuvastatin treatment for a wide segment of the general population at intermediate cardiovascular risk. In absolute numbers, this segment represents the main source of cardiovascular events: on the basis of JUPITER results, it is expected that treatment target and potential candidates to statin therapy will be revaluated and redefined.Keywords: cardiovascular prevention, cholesterol, high-density lipoprotein, C-reactive protein, vascular end-point, overweight

Investigates the effectiveness of two different types of interviews: one that embeds a concept map, and one that does not embed a concept map in order to elicit post-instructional understandings. Focuses on students' understandings of chlorofluorocarbons and their role in global atmospheric change. Contains 71 references. (DDR)

Four upper elementary teachers involved in Science, Technology and Society (STS) instruction through participation in a Leadership Institute in STS Education were examined for their views on teachers serving as models of responsible citizenship action. The teachers appeared to operate under the belief that teachers must practice what they preach in order to inspire students to responsible citizenship action. Contains 27 references. (Author/PVD)

Describes a leadership institute in Science-Technology-Society (STS) education which was established to develop middle-school science teacher/leaders in STS education across rural areas of central Pennsylvania and northern West Virginia. The program was comprised of professional-development activities and complementary research that used STS curriculum, development, and implementation as the means toward that end. Contains 34 references. (PVD)

This study compares inservice (n=30) and preservice (n=30) earth and space science teachers on general mental abilities, content knowledge, Gagnean levels of content knowledge, and procedural knowledge in solving earth and space science problems. Results support Norman's theory of learning that inservice teachers function at the tuning mode of learning while preservice teachers function in a structuring mode. (MVL)

Proposes the use of procedural task analysis as a tool to assess a person's mental processes during problem solving in science education research. Uses transcriptions of videotape or audiotape problem-solving sessions to identify students' knowledge structures and misconceptions. (MDH)

The effectiveness of using a set of models in two protein synthesis laboratory exercises accompanied by a series of two lectures on the topic was assessed. The purpose, procedure, example test items, the findings, and a discussion are included. (KR)

Discusses students' awareness of science/technology/society (STS) issues, the importance students assign to STS issues, and students' achievement in a genetics unit after infusing STS vignettes into class discussions. Recommendations are made on the use of STS vignettes by science teachers. (KR)

Background and Aims: ODYSSEY APPRISE trial evaluated efficacy and safety of alirocumab in 994 patients with hypercholesterolemia and high CV risk in a real-life setting. The aim of the present report is to detail on the Italian cohort enrolled and treated in the trial.Methods and Results: The methodology of the of the multinational, single-arm, Phase 3b open-label ODYSSEY APPRISE (Clinicaltrials.gov: NCT02476006) has been previously reported. 255 Italian patients were enrolled and treated according to the trial protocol. Overall mean exposure to alirocumab was 83.3 ± 27.7 weeks. At week 12, LDL-C decreased by 51.3 ± 23.1% and this reduction was overall maintained for the duration of the study. A similar reduction was observed in patients with and without heterozygous familial hypercholesterolemia (HeFH 50.7% ± 23.9 vs. non-FH, 53.6% ± 19.6). LDL-C was reduced below 1.8 mmol/L and/or by ≥ 50% reduction from baseline in 62% of patients overall (61% in HeFH and 67% in non-FH). Alirocumab was similarly well tolerated in the Italian cohort as in the entire study population and the more common treatment emergent adverse events (TEAEs) were influenza, myalgia and nasopharyngitis. The incidence LDL-C levels <25 mg/dl and <15 mg/dl, was 8.2% and 2.9% respectively.Conclusion: The efficacy and safety of alirocumab in a real-life setting, in the Italian subgroup of patients are consistent with findings in the entire study population and confirm that alirocumab is a beneficial approach to further reduce LDL-C levels in patients at high CV risk on maximally tolerated conventional lipid lowering treatment.Clinicaltrials: Gov Identifier: NCT02476006. [ABSTRACT FROM AUTHOR]

Background and Aims: Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy.Methods and Results: We evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54 ± 13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygous (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p = 1.00) and T36w (p = 0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p = 0.069), whereas none of compound-He/Ho-FH achieved LDL-C target.Conclusions: After 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations. Registration number for clinical trials: NCT04313270 extension. [ABSTRACT FROM AUTHOR]

Discusses studies done on science/technology/society (STS) education and lessons that may be drawn for teachers. Maintains that issue investigation and action-based units focusing on locally relevant and student-relevant issues are clearly supported and encouraged by STS research. (DB)

Validates a Personal Internet Teaching Efficacy Beliefs Scale (PITEBS) using a sample of 389 inservice teachers who were participants in an Internet-based professional development project. The scale was then used to assess changes in self-efficacy beliefs among 155 participants in summer workshops. The PITEBS appears ready to be utilized for future research and evaluation studies. (Author/NB)

Background and Aim: Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. We evaluated changes in lipid profile and carotid stiffness in patients with familial hypercholesterolemia during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®.Methods and Results: Patients with familial hypercholesterolemia starting a treatment with Evolocumab® were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), small dense LDL (assessed by LDL score) and carotid stiffness were evaluated before starting treatment with Evolocumab® and during 12 weeks of treatment. Twenty-five subjects were enrolled (52% males, mean age 51.5 years). TC and LDL-C were reduced of 38% and 52%, respectively during treatment, with LDL score reduced of 46.1%. In parallel, carotid stiffness changed from 8.8 (IQR: 7.0-10.4) m/sec to 6.6 (IQR: 5.4-7.5) m/sec, corresponding to a median change of 21.4% (p < 0.001), with a significant increase in carotid distensibility (from 12.1, IQR: 8.73-19.3 kPA-1 × 10-3 at T0 to 21.8, IQR: 16.6-31.8 kPA-1 × 10-3 at T12w) corresponding to a median change of 62.8% (p < 0.001). A multivariate analysis showed that changes in LDL score were independently associated with changes in carotid stiffness (β = 0.429, p = 0.041).Conclusion: Small dense LDL reduction, as assessed by LDL score, is associated with changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®. [ABSTRACT FROM AUTHOR]

Reports on the development and validation of an inventory designed to identify the needs of science teachers in developing nations, particularly the Arab countries. The instrument, Science Teacher Inventory of Need, consists of 83 items arranged under seven categories. (JN)

Illinois principals (N=228) were surveyed to determine the qualities they examine when hiring mathematics and science teachers. Content area knowledge, area of certification, and personality characteristics were of higher priority than sponsoring extracurricular activities, references, and minor areas of certification. (DH)

To verify its factor structure and construct validity, the Science Teacher Inventory of Need was administered to Malaysian secondary school teachers, using English-language and Bahasa Malaysia versions. Validity and reliability were adequate. The resulting six factors involved instruction, updating knowledge and teaching skills, diagnosing students, and specifying objectives. (GDC)