Sex Differences in Low-Density Lipoprotein Cholesterol Reduction With PCSK9 Inhibitors in Real-world Patients: The LIPID-REAL Registry.

BACKGROUND: Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%-65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors. METHODS: This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded. RESULTS: Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115-166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38-84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects. CONCLUSIONS: This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.

Effectiveness of a community intervention to reduce social isolation among older people in low-income neighbourhoods.

BACKGROUND: Social and demographic trends show a global increase of proportion of older people at risk of social isolation. This study aimed to evaluate the effectiveness of an intervention conducted in low-income neighbourhoods to reduce social isolation and its negative effects on health in older persons. METHODS: A quasi-experimental study with a comparison group was performed. The 'School of Health for Older People' is a weekly community intervention that promotes resources among individuals and communities to enhance their ability to identify problems and activate solutions, encouraging community participation. Data were collected at the beginning and at the end of the intervention. Social support, psychological morbidity and health-related quality of life were measured through questionnaires information on visits to the primary care centre was obtained from the electronic medical records of primary care centres. Multivariate regression models were conducted to assess changes after the intervention. RESULTS: A total of 135 participants were included in the study. The intervention helped to improve participants' mental health (aPR = 0.46; 95% CI: 0.23-0.90) comparing with the comparison group. Also, the intervention helped to maintain quality of life and social support, which were worsened or maintained respectively in the case of comparison group. CONCLUSIONS: Our results provide evidence on how a community intervention can improve quality of life, mental health and social support in older people. The evidence can help to fill the knowledge gap in this area and might be especially useful for the design of social and public health policies and programmes for older people in disadvantaged neighbourhoods in urban areas. TRIAL REGISTRATION: NCT03142048.

Effect of composition and coating on the interparticle interactions and magnetic hardness of MFe2O4 (M = Fe, Co, Zn) nanoparticles.

Single domain superparamagnetic ferrite nanoparticles with the composition MFe2O4 (M = Fe, Co, Zn) have been prepared by thermal decomposition of metal acetylacetonates in diphenyl ether or dibenzyl ether, using oleic acid in the presence of oleylamine as a stabilizing agent. The Fe, Co and Zn ferrite nanoparticles are monodisperse with diameters of 4.9, 4.4 and 4.7 nm, respectively. The TG and IR results indicate that four or six carboxylate groups per nm2 are bonded at the surface of the particles acting as chelating and/or bridging bidentate ligands depending on the composition. The oleate groups minimize the interparticle interactions in Fe and Zn ferrite samples, while in the Co ferrite sample dipolar interactions produce broad maxima in the ZFC and energy barriers distribution curves. The inversion degree has been estimated from the Raman spectra and the obtained x values have been used to calculate the saturation magnetization and compare them with the experimental MS values. Compared to bulk materials, the magnetization value is higher for the Zn ferrite sample due to its mixed spinel cation distribution. For the Co ferrite sample, and probably for the Fe one, the low value of saturation magnetization seems to be due to the surface disordered layer of canted spins. Compared to non-coated nanoparticles with the same composition and similar size, the oleate groups, covalently bonded to the superficial cations, increase the anisotropy field and decrease the magnetization.

Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes.

Hyperosmotic stress response involves the adaptative mechanisms needed for cell survival. Under high osmolarity conditions, many stress response genes are activated by several unrelated transcription factors that are controlled by the Hog1 kinase. Osmostress transcription factor Hot1 regulates the expression of several genes involved in glycerol biosynthesis, and the presence of this transcription factor in their promoters is essential for RNApol II recruitment. The physical association between Hog1 and Hot1 activates this transcription factor and directs the RNA polymerase II localization at these promoters. We, herein, demonstrate that physical and genetic interactions exist between Hot1 and several proteins involved in transcriptional and posttranscriptional processes: for example, transcription co-activator Sub1 and elongation complex Spt4/5. The results presented in this work demonstrate that Hot1 enrichment is not detected through the coding regions of its target genes and rule out a direct role in transcription elongation. Instead, other data presented herein indicate a key function of the Hot1 transcription factor in the recruitment of these proteins to the promoter or the 5'-coding region of the genes under its control.

Development of new tolerant strains to hydrophilic and hydrophobic organic solvents by the yeast surface display methodology.

Yeast surface display is a research methodology based on anchoring functional proteins and peptides onto the surface of the cells of this eukaryotic organism. Its development has resulted in the construction of a good number of new whole-cell biocatalysts with diverse applications in biotechnology, pharmacy, and medicine. In this work, we describe the design of new yeast strains in which several proteins and peptides have been introduced at the N-terminal position of protein agglutinin Aga2p. In all cases, proteins were correctly expressed and displayed on the cell surface according to the western blot, fluorescence microscopy, and fluorescence-activated cell sorting (FACS) analyses. The introduction of a glycosylable, Ser/Thr-rich protein (S1) resulted in improved resistance to ethanol, nonane, and dimethyl sulfoxide (DMSO) stress. The protein with a very high hydrophobic content (S2d) proved to confer tolerance to acetonitrile, ethanol, nonane, salt, and sodium dodecyl sulfate (SDS). The introduction of five leucine residues at the N-terminal position of S1 and S2 resulted in similar or increased resistance to the above-mentioned stress conditions. The adverse effects described in a previous work, when these residues were introduced into the N-terminus of Aga2p, with no other protein acting as a spacer, were not observed. Indeed, these strains grew better in the presence of hydrophilic solvents such as acetonitrile and ethanol. The new strains reported in this work have biotechnological potentiality given their behavior under adverse conditions of interest for biocatalytic and industrial processes.

The impact of dental appearance and anxiety on self-esteem in adult orthodontic patients.

OBJECTIVES: To analyse the relationship between different dimensions of dental appearance impact and self-esteem in adult patients undergoing orthodontic treatment, with special attention to the possible mediating role of anxiety. SETTING AND SAMPLE POPULATION: A quasi-experimental design was used with a matched control group (without orthodontic treatment). In each group (experimental and control), there were 85 patients. MATERIAL AND METHODS: The impact of dental appearance was measured using the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). State anxiety was assessed with the State Anxiety Inventory (STAI-S) and self-esteem with Rosenberg's self-esteem scale. RESULTS: In both groups (experimental and control), self-esteem correlates negatively, ranging between 0.26 and 0.43, with all dimensions of dental appearance impact (except for the positive dental self-confidence dimension, where all correlations were positive). Anxiety correlates positively, ranges between 0.35 and 0.44, with social impact, psychological impact and aesthetic concern, although it maintains no significant correlations with dental self-confidence. Nevertheless, in patients undergoing orthodontic treatment, anxiety plays a mediating role between dental impact dimensions and self-esteem, whilst for the control group anxiety only plays a mediator role between psychological impact and self-esteem. CONCLUSION: Anxiety plays a fundamental role in the effect of perceived dental impact on self-esteem in adult patients undergoing orthodontic treatment. These results have important practical implications for the design of bio-psycho-social intervention programs that contemplate cognitive-affective variables as an essential part of orthodontic treatment in adults.

Outcomes of off-label drug uses in hospitals: a multicentric prospective study.

PURPOSE: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. METHODS: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. RESULTS: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.9-5,872.54). CONCLUSIONS: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

Yeast arming by the Aga2p system: effect of growth conditions in galactose on the efficiency of the display and influence of expressing leucine-containing peptides.

The amino or carboxy-terminal regions of certain cell wall proteins are capable of anchoring foreign proteins or peptides on the cell wall of the yeast Saccharomyces cerevisiae. This possibility has resulted in the development of a methodology known as yeast display which has powerful applications in biotechnology, pharmacy, and medicine. This work describes the results of experiments in which the agglutinin Aga2p protein is used as an anchor and several leucine-based peptides have been introduced into its N-terminal or C-terminal position. We found that the sequence of these peptides can affect plasmid stability, growth kinetics, and levels of the fusion protein displayed, and we analyzed how the incubation conditions influence these parameters. Besides, we show that the introduction of these small peptides can modify the properties of cell cover; in particular, fusing five or ten leucine residues to the Aga2p protein results in greater hydrophobicity of the cell wall and also in increased resistance to the presence of the organic solvents acetonitrile and ethanol and to high salt concentrations. The introduction of the RLRLL sequence also results in higher resistance to the exposure of yeast cells to NaCl stress.

Isometric knee extensor fatigue following a Wingate test: peripheral and central mechanisms.

Central and peripheral fatigue have been explored during and after running or cycling exercises. However, the fatigue mechanisms associated with a short maximal cycling exercise (30 s Wingate test) have not been investigated. In this study, 10 volunteer subjects performed several isometric voluntary contractions using the leg muscle extensors before and after two bouts of cycling at 25% of maximal power output and two bouts of Wingate tests. Transcranial magnetic stimulation (TMS) and electrical motor nerve stimulation (NM) were applied at rest and during the voluntary contractions. Maximal voluntary contraction (MVC), voluntary activation (VA), twitch amplitude evoked by electrical nerve stimulation, M wave and motor potential evoked by TMS (MEP) were recorded. MVC, VA and twitch amplitude evoked at rest by NM decreased significantly after the first and second Wingate tests, indicating central and peripheral fatigue. MVC and VA, but not the twitch amplitude evoked by NM, recovered before the second Wingate test. These results suggest that the Wingate test results in a decrease in MVC associated with peripheral and central fatigue. While the peripheral fatigue is associated with an intramuscular impairment, the central fatigue seems to be the main reason for the Wingate test-induced impairment of MVC.

Evolution of socio-economic inequalities in mortality in small geographical areas of the two largest cities in Spain (Barcelona and Madrid), 1996-2007.

OBJECTIVES: To describe the evolution of socio-economic inequalities in mortality in small areas of two Spanish cities (Barcelona and Madrid) from 1996 to 2001 and from 2002 to 2007. STUDY DESIGN: A small-area ecological study of trends was performed, in which the units of analysis were census tracts. METHODS: The association between mortality and socio-economic deprivation was assessed through Poisson regression analysis. Models were stratified by sex, age group and period of study. The trend in inequalities in mortality was assessed by introducing an interaction term between deprivation and the period of study. RESULTS: Mortality in the most-deprived areas was significantly higher than mortality in the less-deprived areas in both periods and most age groups. However, inequalities seemed to diminish in young people and elderly women, especially in Barcelona. CONCLUSIONS: There is a need to monitor inequalities in mortality in the near future because the current financial crisis could change this situation.

The Saccharomyces cerevisiae Hot1p regulated gene YHR087W (HGI1) has a role in translation upon high glucose concentration stress.

BACKGROUND: While growing in natural environments yeasts can be affected by osmotic stress provoked by high glucose concentrations. The response to this adverse condition requires the HOG pathway and involves transcriptional and posttranscriptional mechanisms initiated by the phosphorylation of this protein, its translocation to the nucleus and activation of transcription factors. One of the genes induced to respond to this injury is YHR087W. It encodes for a protein structurally similar to the N-terminal region of human SBDS whose expression is also induced under other forms of stress and whose deletion determines growth defects at high glucose concentrations. RESULTS: In this work we show that YHR087W expression is regulated by several transcription factors depending on the particular stress condition, and Hot1p is particularly relevant for the induction at high glucose concentrations. In this situation, Hot1p, together to Sko1p, binds to YHR087W promoter in a Hog1p-dependent manner. Several evidences obtained indicate Yhr087wp's role in translation. Firstly, and according to TAP purification experiments, it interacts with proteins involved in translation initiation. Besides, its deletion mutant shows growth defects in the presence of translation inhibitors and displays a slightly slower translation recovery after applying high glucose stress than the wild type strain. Analyses of the association of mRNAs to polysome fractions reveals a lower translation in the mutant strain of the mRNAs corresponding to genes GPD1, HSP78 and HSP104. CONCLUSIONS: The data demonstrates that expression of Yhr087wp under high glucose concentration is controlled by Hot1p and Sko1p transcription factors, which bind to its promoter. Yhr087wp has a role in translation, maybe in the control of the synthesis of several stress response proteins, which could explain the lower levels of some of these proteins found in previous proteomic analyses and the growth defects of the deletion strain.

Impact of antiretroviral therapy interruption on plasma biomarkers of cardiovascular risk and lipids: 144-week final data from the STOPAR study.

OBJECTIVE: The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study. METHODS: This was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay. Total cholesterol (total-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined using standard methods. RESULTS: Fifty-four patients were included in the study [34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm]. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP-1, which was higher in the TC arm (P = 0.039). MCP-1 and sVCAM-1 were increased relative to baseline at the three study time-points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P = 0.02). t-PA was increased in both arms at the three time-points. Total-c, HDL-c and low-density lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time-points, with no changes in the total-c/HDL-c ratio. HIV viral load positively correlated with MCP-1 at months 12 and 24. Regression analysis showed a significant negative association of HDL-c with MCP-1 and sVCAM-1. CONCLUSIONS: A significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.

Detection of glucose abnormalities in patients with acute coronary heart disease: study of reliable tools in clinical practice.

AIM: To investigate the prevalence of glucose abnormalities in patients with acute coronary syndrome and to assess the reliability of certain clinical or analytical variables to predict a pathologic result of oral glucose tolerance test (OGTT) at 3 months from discharge. SUBJECTS AND METHODS: Prospective study of 102 patients admitted to the coronary care units. Patients were classified according to the American Diabetes Association criteria. Three months after discharge, an OGTT was performed to non-diabetic patients. RESULTS: Forty-six (45.1%) patients were identified as diabetic (5 previously undiagnosed) and 56 (54.9%) as non-diabetic. OGTT identified 22% of diabetes, 33% of impaired glucose tolerance, and 45% of normal glucose tolerance. Fasting glucose (r=0.55, p<0.001), glycated hemoglobin (HbA1c) (r=0.46, p<0.001), low HDL cholesterol (HDLc) levels (r=-0.34, p<0.02), waist-hip ratio (r=0.45, p<0.01), high systolic blood pressure (r=0.5, p<0.01), and presence of acute myocardial infarction (r=0.46, p<0.001) at admission resulted significant to predict a pathologic result of OGTT. CONCLUSIONS: Glucose abnormalities are frequent in acute coronary syndrome patients. Certain clinical and analytical markers at admission such as fasting glucose, HbA1c, HDL-c<40 mg/dl, waist-hip ratio, and systolic blood pressure, are useful to recognize patients with a higher predisposition to present a pathologic result in OGTT at 3 months from discharge.

The effects of aerobic exercise and transcranial direct current stimulation on cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Aerobic exercise (AE) may slow age-related cognitive decline. However, such cognition-sparing effects are not uniform across cognitive domains and studies. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation and is also emerging as a potential alternative to pharmaceutical therapies. Like AE, the effectiveness of tDCS is also inconsistent for reducing cognitive impairment in ageing. The unexplored possibility exists that pairing AE and tDCS could produce synergistic effects and reciprocally augment cognition-improving effects in older individuals with and without cognitive impairments. Previous research found such synergistic effects on cognition when cognitive training is paired with tDCS in older individuals with and without mild cognitive impairment (MCI) or dementia. AIM: The purpose of this systematic review with meta-analysis was to explore if pairing AE with tDCS could augment singular effects of AE and tDCS on global cognition (GC), working memory (WM) and executive function (EF) in older individuals with or without MCI and dementia. METHODS: Using a PRISMA-based systematic review, we compiled studies that examined the effects of AE alone, tDCS alone, and AE and tDCS combined on cognitive function in older individuals with and without mild cognitive impairment (MCI) or dementia. Using a PICOS approach, we systematically searched PubMed, Scopus and Web of Science searches up to December 2021, we focused on 'MoCA', 'MMSE', 'Mini-Cog' (measures) and 'cognition', 'cognitive function', 'cognitive', 'cognitive performance', 'executive function', 'executive process', 'attention', 'memory', 'memory performance' (outcome terms). We included only randomized controlled trials (RTC) in humans if available in English full text over the past 20 years, with participants' age over 60. We assessed the methodological quality of the included studies (RTC) by the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Overall, 68 studies were included in the meta-analyses. AE (ES = 0.56 [95% CI: 0.28-0.83], p = 0.01) and tDCS (ES = 0.69 [95% CI: 0.12-1.26], p = 0.02) improved GC in all three groups of older adults combined (healthy, MCI, demented). In healthy population, AE improved GC (ES = 0.46 [95% CI: 0.22-0.69], p = 0.01) and EF (ES = 0.27 [95% CI: 0.05-0.49], p = 0.02). AE improved GC in older adults with MCI (ES = 0.76 [95% CI: 0.21-1.32], p = 0.01). tDCS improved GC (ES = 0.69 [90% CI: 0.12-1.26], p = 0.02), all three cognitive function (GC, WM and EF) combined in older adults with dementia (ES = 1.12 [95% CI: 0.04-2.19], p = 0.04) and improved cognitive function in older adults overall (ES = 0.69 [95% CI: 0.20-1,18], p = 0.01). CONCLUSION: Our systematic review with meta-analysis provided evidence that beyond the cardiovascular and fitness benefits of AE, pairing AE with tDCS may have the potential to slow symptom progression of cognitive decline in MCI and dementia. Future studies will examine the hypothesis of this present review that a potentiating effect would incrementally improve cognition with increasing severity of cognitive impairment.

Crystallinity assessment and in vitro cytotoxicity of polylactide scaffolds for biomedical applications.

Bioresorbable polylactides are one of the most important materials for tissue engineering applications. In this work we have prepared scaffolds based on the two optically pure stereoisomers: poly(L: -lactide) (PLLA) and poly(D: -lactide) (PDLA). The crystalline structure and morphology were evaluated by DSC, AFM and X-ray diffraction. PLLA and PDLA crystallized in the α form and the equimolar PLLA/PDLA blend, crystallized in the stereocomplex form, were analyzed by a proliferation assay in contact with mouse L-929 and human fibroblasts and neonatal keratinocytes for in vitro cytotoxicity evaluation. SEM analysis was conducted to determine the cell morphology, spreading and adhesion when in contact with the different polymer surfaces. The preserved proliferation rate showed in MTT tests and the high colonization on the surface of polylactides observed by SEM denote that PLLA, PDLA and the equimolar PLLA/PDLA are useful biodegradable materials in which the crystalline characteristics can be tuned for specific biomedical applications.

Management by objectives and its impact on specialist prescription quality at discharge and in external consultations.

OBJECTIVE: To verify that implementing a policy of management by objectives, based on collaboration between hospital pharmacy, primary care and specialised medical managers, improves prescription quality indicators in specialised care and reduces unwanted "induced" prescriptions (i.e. those issued by specialists, hospital doctors or the patients themselves) in primary care. METHOD: A four year quasi-experimental controlled intervention study on prescription at discharge and in outpatient hospital consultations was conducted. In hospital A, a quality cycle was applied: assessment, identifying improvement opportunities, implementing corrective actions and re-assessment. However, it was not applied in control hospital B. The indicators chosen were the percentage of generic medicines prescribed, the percentage of prescriptions for new therapies with no added value and the percentage of prescriptions for ACE inhibitors recommended. RESULTS: In hospital A, an increase in indicators 1 and 3 has been observed, both being statistically significant, between the last year of intervention and the year previous to intervention. Hospital A managed to reduce indicator 2 to 4.5%, while this indicator increased in hospital B to 8.8%. Furthermore, a statistically significant difference in indicators between the two hospitals has been registered. CONCLUSION: Pay-for-Performance programs in prescription practices of hospital physicians are effective actions to improve quality indicators of medication use.

Effect of a smartphone application (Perx) on medication adherence and clinical outcomes: a 12-month randomised controlled trial.

OBJECTIVE: To determine whether the Perx app improves medication adherence and clinical outcomes over 12 months compared with standard care in patients requiring polypharmacy. DESIGN: Randomised controlled trial with 12-month follow-up. SETTING: Outpatient clinics in three tertiary hospitals in Sydney, Australia. PARTICIPANTS: Eligible participants were aged 18-75 years, with at least one chronic condition, taking ≥3 different medications (oral medications or injections), with smartphone accessibility. Participants were randomised in a 1:1 ratio. INTERVENTIONS: The intervention group used the Perx app that contained customised reminders and gamified interactions to reward verified medication adherence. MAIN OUTCOME MEASURES: The primary outcome was medication adherence over 12 months measured using pill counts. Secondary outcomes included clinical outcomes (haemoglobin A1c (HbA1c), cholesterol, blood glucose, triglycerides, creatinine, thyroid function, blood pressure and weight). RESULTS: Of 1412 participants screened for eligibility, 124 participants were randomised; 45 in the Perx arm and 40 in the control arm completed the study. The average age was 59.5, 58.9% were women, chronic conditions were cardiovascular disease (78%), type 2 diabetes (75%), obesity (65%) or other endocrine disorders (18%). On average, participants were taking six medications daily. The Perx group had greater improvements in adherence at month 2 (Coef. 8%; 95% CI 0.01 to 0.15), month 3 (Coef. 7%; 95% CI 0.00 to 0.14) and month 12 (Coef. 7%; 95% CI 0.00 to 0.13). The probability of HbA1c ≤6.5% was greater in the Perx group at months 9 and 12 and cholesterol (total and low-density lipoprotein cholesterol) was lower in the Perx group at month 3. The intervention was particularly effective for those with obesity, taking medications for diabetes and taking ≤4 medications. CONCLUSIONS: This study provides evidence that app-based behavioural change interventions can increase medication adherence and produce longer-term improvements in some clinical outcomes in adults managing multimorbidity. More trials are needed to build the evidence base. TRIAL REGISTRATION NUMBER: ACTRN12617001285347.

[Variability in the neuropsychological performance of patients with acute coronary syndrome]. / Variabilidad en el rendimiento neuropsicológico en pacientes con síndrome coronario agudo.

INTRODUCTION: There is a growing interest in the study of the relationship between heart disease, including acute coronary syndrome (ACS) and cognitive impairment, and although the factors mediating ACS and cognitive impairment are not well understood, the debate revolves around the role of the left ventricular ejection fraction (LVEF). AIMS: To determine the presence of cognitive impairment in patients with ACS and explore its association with various factors, including sociodemographic, medication use and performance on cardiac function tests (in particular LVEF). PATIENTS AND METHODS: Sociodemographic, medical and neuropsychological variables were collected in 80 patients with ACS participating in a cardiac rehabilitation programme. Their scores on the neuropsychological battery were compared with normative population data to determine which subjects showed deficient performance. Regression analyses were conducted to determine which factors are associated with performance on neuropsychological tests. RESULTS: Compared to their normative group, 37.5% of the subjects had low scores on three or more neuropsychological tests. Age, low educational level and low LVEF explained up to 51% of the variability in neuropsychological test results. CONCLUSIONS: Patients with ACS are more likely to have impaired cognitive functions, such as attention, memory and executive functions, along with a slower information processing speed. An LVEF below 50% could be a major explanatory factor for such cognitive impairment.

TITLE: Variabilidad en el rendimiento neuropsicológico en pacientes con síndrome coronario agudo.Introducción. Existe un interés creciente por el estudio de la relación entre las cardiopatías, incluido el síndrome coronario agudo (SCA) y el deterioro cognitivo, y, aunque no se conocen con concreción los factores que median entre el SCA y el deterioro cognitivo, en el centro de este debate se encuentra el papel de la fracción de eyección del ventrículo izquierdo (FEVI). Objetivos. Determinar la presencia de deterioro cognitivo en pacientes con SCA y explorar su asociación con diversos factores ­sociodemográficos, consumo de fármacos, rendimiento en pruebas funcionales cardíacas (en particular, la FEVI)­. Pacientes y métodos. Se recogieron variables sociodemográficas, médicas y neuropsicológicas en 80 pacientes con SCA que participaban en un programa de rehabilitación cardíaca. Se compararon sus puntuaciones en la batería neuropsicológica con los datos normativos poblacionales para determinar qué sujetos mostraban un rendimiento deficitario. Se realizaron análisis de regresión para determinar qué factores se asocian con el rendimiento en las pruebas neuropsicológicas. Resultados. En comparación con su grupo normativo, el 37,5% de los sujetos presentó una baja puntuación en tres o más test neuropsicológicos. La edad, un bajo nivel educativo y una FEVI baja explicaron hasta el 51% de la variabilidad en los resultados de las pruebas neuropsicológicas. Conclusiones. Los pacientes con SCA tienen más posibilidades de presentar un deterioro de funciones cognitivas, como la atención, la memoria y las funciones ejecutivas, junto con un enlentecimiento en la velocidad de procesamiento de la información. Una FEVI inferior al 50% podría ser un factor explicativo destacado de dicho deterioro cognitivo.

Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials.

PURPOSE: Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors treatment induce large reductions in low-density lipoprotein cholesterol (LDLc) and major cardiovascular events. Clinical trials might have been underpowered to test the effect of PSCK9 inhibitors treatment on myocardial infarction and stroke, two of the most relevant cardiovascular events, since all analyzed a combined endpoint. METHODS: we performed a meta-analysis, with currently available studies involving PCSK9 inhibitors and event rate adjudication, with the aim of assessing treatment effects on myocardial infarction and stroke. RESULTS: We included 81,700 patients, 41,979 treated with a PSCK9 inhibitors: 17,244 with evolocumab; 13,720 with bococizumab and 11,015 with alirocumab. A total of 1,319 cases of myocardial infarctions were registered in the treatment group vs. 1,608 in controls, resulting in 19.0% reduction associated with PCSK9 treatment (RR: 0.81, 95% CI 0.76-0.87). Similarly, PCSK9 inhibitors treatment resulted in a 25% reduction of stroke (RR: 0.75, 95% CI 0.65-0.85) when all studies were analyzed together and the statistically significant heterogeneity was not observed in the analysis restricted to end-point based clinical trials. PCSK9 inhibitors treatment had no effect on mortality (RR: 0.95, 95% CI 0.86-1.04). CONCLUSIONS: PCSK9 inhibitors reduce the incidence of myocardial infarction by 19% and stroke by 25%.