Effects of working from home on lifestyle behaviors and mental health during the COVID-19 pandemic: A survey study.

The COVID-19 outbreak has led to relevant changes in everyday life worldwide. One of these changes has been a rapid transition to and an increasing implementation of working from home (WH) modality. This study aimed to evaluate the impact of mandatory WH during the COVID-19 pandemic on lifestyle behaviors, Mediterranean diet adherence, body weight, and depression. An online cross-sectional survey was conducted in the early 2022 at the National Research Council of Italy using ad hoc questions and validated scales collecting information on physical activity, sedentary behavior, hobbies/pastimes, dietary habits including adherence to the Mediterranean diet, body weight, and depression during WH compared with before WH. 748 respondents were included in the study. An increased sedentary lifetime was reported by 48% of respondents; however, the subsample of workers who previously performed moderate physical activity intensified this activity. Body weight gain during WH was self-reported in 39.9% of respondents. Mediterranean diet adherence increased (p≪0.001) during WH compared with before WH. The average level of mental health did not record an overall variation; however, the proportion of subjects with mild and moderate depression increased (p = 0.006), while workers who reported values indicative of depression before the transition declared an improvement. These findings highlight health-related impact of WH during the COVID-19 pandemic that may inform future strategies and policies to improve employees' health and well-being.

Association Between Physical Activity and the Risk of Burnout in Health Care Workers: Systematic Review.

BACKGROUND: Burnout is a multidimensional psychological syndrome that arises from chronic workplace stress. Health care workers (HCWs), who operate in physically and emotionally exhausting work contexts, constitute a vulnerable group. This, coupled with its subsequent impact on patients and public economic resources, makes burnout a significant public health concern. Various self-care practices have been suggested to have a positive effect on burnout among HCWs. Of these, physical activity stands out for its ability to combine psychological, physiological, and biochemical mechanisms. In fact, it promotes psychological detachment from work and increases self-efficacy by inhibiting neurotransmitters and neuromodulators, increasing endorphin levels, enhancing mitochondrial function, and attenuating the hypothalamic pituitary-adrenal axis response to stress. OBJECTIVE: Our objective was to conduct a systematic review of the evidence on the association between physical activity and burnout among HCWs. METHODS: We considered HCWs, physical activity, and burnout, framing them as population, exposure, and outcome, respectively. We searched APA PsycArticles, MEDLINE, and Scopus until July 2022. We extracted relevant data on study design, methods to measure exposure and outcome, and statistical approaches. RESULTS: Our analysis encompassed 21 independent studies. Although 10% (2/21) of the studies explicitly focused on physical activity, the remaining investigations were exploratory in nature and examined various predictors, including physical activity. The most commonly used questionnaire was the Maslach Burnout Inventory. Owing to the heterogeneity in definitions and cutoffs used, the reported prevalence of burnout varied widely, ranging from 7% to 83%. Heterogeneity was also observed in the measurement tools used to assess physical activity, with objective measures rarely used. In total, 14% (3/21) of the studies used structured questionnaires to assess different types of exercise, whereas most studies (18/21, 86%) only recorded the attainment of a benchmark or reported the frequency, intensity, or duration of exercise. The reported prevalence of physically active HCWs ranged from 44% to 87%. The analyses, through a variety of inferential approaches, indicated that physical activity is often associated with a reduced risk of burnout, particularly in the domains of emotional exhaustion and depersonalization. Furthermore, we compiled and classified a list of factors associated with burnout. CONCLUSIONS: Our comprehensive overview of studies investigating the association between physical activity and burnout in HCWs revealed significant heterogeneity in definitions, measurements, and analyses adopted in the literature. To address this issue, it is crucial to adopt a clear definition of physical activity and make thoughtful choices regarding measurement tools and methodologies for data analysis. Our considerations regarding the measurement of burnout and the comprehensive list of associated factors have the potential to improve future studies aimed at informing decision-makers, thus laying the foundation for more effective management measures to address burnout.

Corrigendum: The medium-term perceived impact of work from home on life and work domains of knowledge workers during COVID-19 pandemic: a survey at the National Research Council of Italy.

[This corrects the article DOI: 10.3389/fpubh.2023.1151009.].

miRNAs as biomarkers of musculoskeletal pain in long-distance runners: the MiMuS study protocol.

miRNAs are involved in the generation and progression of musculoskeletal pain, a condition that causes significant clinical, economic and social burden. In runners, the presence of musculoskeletal pain related to an inflammatory state or ongoing underlying tissue damage may result in poor training ability and performance. This study aims to evaluate the association between circulating and salivary miRNAs and pain in runners with and without musculoskeletal pain and to observe whether dysregulated miRNAs can distinguish between responders and nonresponders to a kinesiological intervention. The possible correlation between these miRNAs and inflammatory molecules, stress parameters and individual or behavioral characteristics will be evaluated. Finally, in silico analysis will be used to characterize miRNAs function. Ethics approval was obtained.

The medium-term perceived impact of work from home on life and work domains of knowledge workers during COVID-19 pandemic: A survey at the National Research Council of Italy.

Objective: The study aimed to investigate perceptions and determinants of the overall impact on life and work domains among a community of knowledge workers after 18 months of forced work from home due to the pandemic. Methods: A cross-sectional study with a retrospective assessment was conducted early in 2022 at the National Research Council of Italy. Five single-item questions explored the perceived impact on life domain while a 7-item scale the impact on the work domain. Bivariate analyses and multivariate regressions were used to evaluate the associations between impacts and some key factors defined by 29 ad hoc closed questions. Results: More than 95% of the 748 respondents reported a perceived change in at least one item of the life domain. For each of these items, although a large group of subjects has reported that working from home had no impact (from 27 to 55%), in the rest of the sample the positive evaluation (from 30 to 60%) clearly prevailed over the negative one. Overall, most of the subjects (64%) rated the impact on the work experience positively. Relationship with colleagues and participation in the work context were the items where the greatest number of negative rates was concentrated (27 and 25%, respectively). On the other hand, positive perceptions prevailed over both negative perceptions and lack of impact perceptions on the subjects of organizational flexibility and quality of work. The frequency of work-room sharing, home-work commute time and changes in sedentary lifestyle, have been identified as common explanatory factors of perceived impacts on both domains. Conclusion: Overall, respondents reported positive rather than negative perceived impacts of forced work from home in both their lives and work. The obtained results suggest that policies to promote the physical and mental health of employees, strengthen inclusion and maintain a sense of community are necessary to improve workers' health and prevent the effects of perceived isolation on research activities.

Economic Evaluations of Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A Systematic Review.

OBJECTIVES: This review systematically summarizes the evidence on the economic impact of magnetic resonance image-guided RT (MRIgRT). METHODS: We systematically searched INAHTA, MEDLINE, and Scopus up to March 2022 to retrieve health economic studies. Relevant data were extracted on study type, model inputs, modeling methods and economic results. RESULTS: Five studies were included. Two studies performed a full economic assessment to compare the cost-effectiveness of MRIgRT with other forms of image-guided radiation therapy. One study performed a cost minimization analysis and two studies performed an activity-based costing, all comparing MRIgRT with X-ray computed tomography image-guided radiation therapy (CTIgRT). Prostate cancer was the target condition in four studies and hepatocellular carcinoma in one. Considering the studies with a full economic assessment, MR-guided stereotactic body radiation therapy was found to be cost effective with respect to CTIgRT or conventional or moderate hypofractionated RT, even with a low reduction in toxicity. Conversely, a greater reduction in toxicity is required to compete with extreme hypofractionated RT without MR guidance. CONCLUSIONS: This review highlights the great potential of MRIgRT but also the need for further evidence, especially for late toxicity, whose reduction is expected to be the real added value of this technology.

A postural program to reduce dynamic knee valgus during single-limb squatting in young athletes: a preliminary study.

BACKGROUND: Dynamic knee valgus (DKV) is an undesirable multi-joint movement pattern associated with anterior cruciate ligament injury and patellofemoral pain syndrome, especially in sport activities. We assessed DKV in young athletes who followed a postural program to reduce a posterior rigidity mostly attributable to the tightness of hamstring muscles. METHODS: We considered 12- to 18-year-old athletes that followed a six-week program simply based on hamstring stretching and abdominal muscle activation/strengthening. DKV was assessed during a single-limb squat and the frontal plane projection angle (FPPA) between the femur and tibia was considered. RESULTS: Sixty-six athletes with a significant DKV (FPPA≥10°) were identified. Twenty-one subjects exhibited the considered rigidity profile and completed the intervention program. The mean reduction of the FPPA after the intervention was 8.1±7.9°, significantly asymmetric by about 3° (P<0.005) and skewed towards larger negative differences. The average change from the initial condition of -37±25% was statistically significant (P=1.7 x10-6). CONCLUSIONS: This preliminary result suggests that working on enhancing posterior muscle chain flexibility could be effective in reducing DKV in young athletes with a marked tightness of hamstring muscles. Moreover, this simple postural program can be a candidate for inclusion in sport training as a protective strategy against knee injuries.

Health Technology Assessment for In Silico Medicine: Social, Ethical and Legal Aspects.

The application of in silico medicine is constantly growing in the prevention, diagnosis, and treatment of diseases. These technologies allow us to support medical decisions and self-management and reduce, refine, and partially replace real studies of medical technologies. In silico medicine may challenge some key principles: transparency and fairness of data usage; data privacy and protection across platforms and systems; data availability and quality; data integration and interoperability; intellectual property; data sharing; equal accessibility for persons and populations. Several social, ethical, and legal issues may consequently arise from its adoption. In this work, we provide an overview of these issues along with some practical suggestions for their assessment from a health technology assessment perspective. We performed a narrative review with a search on MEDLINE/Pubmed, ISI Web of Knowledge, Scopus, and Google Scholar. The following key aspects emerge as general reflections with an impact on the operational level: cultural resistance, level of expertise of users, degree of patient involvement, infrastructural requirements, risks for health, respect of several patients' rights, potential discriminations for access and use of the technology, and intellectual property of innovations. Our analysis shows that several challenges still need to be debated to allow in silico medicine to express all its potential in healthcare processes.

Underdetection in a stochastic SIR model for the analysis of the COVID-19 Italian epidemic.

We propose a way to model the underdetection of infected and removed individuals in a compartmental model for estimating the COVID-19 epidemic. The proposed approach is demonstrated on a stochastic SIR model, specified as a system of stochastic differential equations, to analyse data from the Italian COVID-19 epidemic. We find that a correct assessment of the amount of underdetection is important to obtain reliable estimates of the critical model parameters. The adaptation of the model in each time interval between relevant government decrees implementing contagion mitigation measures provides short-term predictions and a continuously updated assessment of the basic reproduction number.

Burnout Among Healthcare Workers in the COVID 19 Era: A Review of the Existing Literature.

In the current period of global public health crisis due to the COVID-19, healthcare workers are more exposed to physical and mental exhaustion - burnout - for the torment of difficult decisions, the pain of losing patients and colleagues, and the risk of infection, for themselves and their families. The very high number of cases and deaths, and the probable future "waves" raise awareness of these challenging working conditions and the need to address burnout by identifying possible solutions. Measures have been suggested to prevent or reduce burnout at individual level (physical activity, balanced diet, good sleep hygiene, family support, meaningful relationships, reflective practices and small group discussions), organizational level (blame-free environments for sharing experiences and advices, broad involvement in management decisions, multi-disciplinary psychosocial support teams, safe areas to withdraw quickly from stressful situations, adequate time planning, social support), and cultural level (involvement of healthcare workers in the development, implementation, testing, and evaluation of measures against burnout). Although some progress has been made in removing the barrier to psychological support to cope with work-related stress, a cultural change is still needed for the stigma associated with mental illness. The key recommendation is to address the challenges that the emergency poses and to aggregate health, well-being and behavioral science expertise through long term researches with rigorous planning and reporting to drive the necessary cultural change and the improvement of public health systems.

Predictive Added Value of Selected Plasma Lipids to a Re-estimated Minimal Risk Tool.

Background: Lipidomics is emerging for biomarker discovery in cardiovascular disease, and circulating lipids are increasingly incorporated in risk models to predict cardiovascular events. Moreover, specific classes of lipids, such as sphingomyelins, ceramides, and triglycerides, have been related to coronary artery disease (CAD) severity and plaque characteristics. To avoid unnecessary testing, it is important to identify individuals at low CAD risk. The only pretest model available so far to rule out the presence of coronary atherosclerosis in patients with chest pain, but normal coronary arteries, is the minimal risk tool (MRT). Aim: Using state-of-the-art statistical methods, we aim to verify the additive predictive value of a set of lipids, derived from targeted plasma lipidomics of suspected CAD patients, to a re-estimated version of the MRT for ruling out the presence of coronary atherosclerosis assessed by coronary CT angiography (CCTA). Methods: Two hundred and fifty-six subjects with suspected stable CAD recruited from five European countries within H2020-SMARTool, undergoing CCTA and blood sampling for clinical biochemistry and lipidomics, were selected. The MRT was validated by regression methods and then re-estimated (reMRT). The reMRT was used as a baseline model in a likelihood ratio test approach to assess the added predictive value of each lipid from 13 among ceramides, triglycerides, and sphingomyelins. Except for one lipid, the analysis was carried out on more than 240 subjects for each lipid. A sensitivity analysis was carried out by considering two alternative models developed on the cohort as baseline models. Results: In 205 subjects, coronary atherosclerosis ranged from minimal lesions to overt obstructive CAD, while in 51 subjects (19.9%) the coronary arteries were intact. Four triglycerides and seven sphingomyelins were significantly (p < 0.05) and differentially expressed in the two groups and, at a lesser extent, one ceramide (p = 0.067). The probability of being at minimal risk was significantly better estimated by adding either Cer(d18:1/16:0) (p = 0.01), SM(40:2) (p = 0.04), or SM(41:1) at a lesser extent (p = 0.052) to reMRT than by applying the reMRT alone. The sensitivity analysis confirmed the relevance of these lipids. Furthermore, the addition of SM(34:1), SM(38:2), SM(41:2), and SM(42:4) improved the predictive performance of at least one of the other baseline models. None of the selected triglycerides was found to provide an added value. Conclusions: Plasma lipidomics can be a promising source of diagnostic and prognostic biomarkers in cardiovascular disease, exploitable not only to assess the risk of adverse events but also to identify subjects without coronary atherosclerosis, thus reducing unnecessary further testing in normal subjects.

Discrimination capability of pretest probability of stable coronary artery disease: a systematic review and meta-analysis suggesting how to improve validation procedures.

OBJECTIVE: Externally validated pretest probability models for risk stratification of subjects with chest pain and suspected stable coronary artery disease (CAD), determined through invasive coronary angiography or coronary CT angiography, are analysed to characterise the best validation procedures in terms of discriminatory ability, predictive variables and method completeness. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Global Health (Ovid), Healthstar (Ovid) and MEDLINE (Ovid) searched on 22 April 2020. ELIGIBILITY CRITERIA: We included studies validating pretest models for the first-line assessment of patients with chest pain and suspected stable CAD. Reasons for exclusion: acute coronary syndrome, unstable chest pain, a history of myocardial infarction or previous revascularisation; models referring to diagnostic procedures different from the usual practices of the first-line assessment; univariable models; lack of quantitative discrimination capability. METHODS: Eligibility screening and review were performed independently by all the authors. Disagreements were resolved by consensus among all the authors. The quality assessment of studies conforms to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A random effects meta-analysis of area under the receiver operating characteristic curve (AUC) values for each validated model was performed. RESULTS: 27 studies were included for a total of 15 models. Besides age, sex and symptom typicality, other risk factors are smoking, hypertension, diabetes mellitus and dyslipidaemia. Only one model considers genetic profile. AUC values range from 0.51 to 0.81. Significant heterogeneity (p<0.003) was found in all but two cases (p>0.12). Values of I2 >90% for most analyses and not significant meta-regression results undermined relevant interpretations. A detailed discussion of individual results was then carried out. CONCLUSIONS: We recommend a clearer statement of endpoints, their consistent measurement both in the derivation and validation phases, more comprehensive validation analyses and the enhancement of threshold validations to assess the effects of pretest models on clinical management. PROSPERO REGISTRATION NUMBER: CRD42019139388.

Simulated versus physical bench tests: The economic evaluation of the InSilc platform for designing, developing, and assessing vascular scaffolds.

BACKGROUND: In silico medicine allows for pre-clinical and clinical simulated assessment of medical technologies and the building of patient-specific models to support medical decisions and forecast personal health status. While there is increasing trust in the potential central role of in silico medicine, there is a need to recognize its degree of reliability and evaluate its economic impact. An in silico platform has been developed within a Horizon 2020-funded project (In-Silc) for simulations functional to designing, developing, and assessing drug-eluting bioresorbable vascular scaffolds.The main purpose of this study was to compare the costs of 2 alternative strategies: the adoption of In-Silc platform versus the performance of only physical bench tests. METHODS: A case study was provided by a medical device company. The values of the model parameters were principally set by the project partners, with use of interviews and semi-structured questionnaires, and, when not available, through literature searches or derived by statistical techniques. An economic model was built to represent the 2 scenarios. RESULTS: The InSilc strategy is superior to the adoption of physical bench tests only. Ceteris paribus, the costs are 424,355€ for the former versus 857,811€ for the latter. CONCLUSIONS: In silico medicine tools can decrease the cost of the research and development of medical devices such as bioresorbable vascular scaffolds. Further studies are needed to explore the impact of such solutions on the innovation capacity of companies and the consequent potential advantages for target patients and the healthcare system.

The effect of a postural exercise program on muscle power in Italian high school students.

[Purpose] The present study aimed to investigate the effect of an innovative postural program (the Canali Postural Method, CPM) on muscle power in Italian high school students. It is note that deficits in posture control may, in long term, generate posture weakness as early as childhood and adolescence. Postural programs based on stretching and strengthening exercises can remove these deficits and can be framed in general physical or sport activities. [Participants and Methods] Thirty-four students completed a 8-week postural program. The intervention, consisting of stretching and muscle activation exercises, was integrated in physical education lessons. For the evaluation of the effect of CPM program, we have used the countermovement jump (CMJ), a simple and versatile test that measures muscle power. [Results] The CPM program resulted in significantly increased vertical jump height of the students. The average difference between Initial and Final CMJ was 2.1 cm. [Conclusion] This finding indicates the benefic effect of this new postural program on physical performance in the youth. Further randomized control trials should be conducted to evaluate CPM long-term implications in the prevention of posture weaknesses and its inclusion in the regular school curriculum.

Basal astrocyte and microglia activation in the central nervous system of Familial Hemiplegic Migraine Type I mice.

BACKGROUND: Gain-of-function missense mutations in the α1A subunit of neuronal CaV2.1 channels, which define Familial Hemiplegic Migraine Type 1 (FHM1), result in enhanced cortical glutamatergic transmission and a higher susceptibility to cortical spreading depolarization. It is now well established that neurons signal to surrounding glial cells, namely astrocytes and microglia, in the central nervous system, which in turn become activated and in pathological conditions can sustain neuroinflammation. We and others previously demonstrated an increased activation of pro-algogenic pathways, paralleled by augmented macrophage infiltration, in both isolated trigeminal ganglia and mixed trigeminal ganglion neuron-satellite glial cell cultures of FHM1 mutant mice. Hence, we hypothesize that astrocyte and microglia activation may occur in parallel in the central nervous system. METHODS: We have evaluated signs of reactive glia in brains from naïve FHM1 mutant mice in comparison with wild type animals by immunohistochemistry and Western blotting. RESULTS: Here we show for the first time signs of reactive astrogliosis and microglia activation in the naïve FHM1 mutant mouse brain. CONCLUSIONS: Our data reinforce the involvement of glial cells in migraine, and suggest that modulating such activation may represent an innovative approach to reduce pathology.

Obstructive sleep apnoea: Improving healthcare services by combining process modelling and population analysis.

CONTEXT: Disease management broke through in the early 1990s to counterbalance hyper-specialization with a more comprehensive approach. Its role became immediately relevant in chronic conditions and, consequently, in Obstructive Sleep Apnoea (OSA). This is a common chronic condition for which is important to organise services at the local level, taking into account organisational factors and the characteristics of the assisted population. OBJECTIVES: The aim of this work is to propose and apply, coherently with a disease management approach, a combination of healthcare process modelling and population analysis as a way to identify critical issues and explore shared solutions. METHODS: A multidisciplinary working group was created with scholars who are skilled in process analysis, statistics and medicine. Through semi-structured interviews and on-site meetings, healthcare processes were represented with a standard graphical language: Unified Modeling Language™. Population analysis was based on statistical analysis performed on a 5-year retrospective cohort assisted by a Community Pulmonary Service. RESULTS: A shared graphic presentation of the current healthcare process and the results of the statistical analyses constituted the knowledge base to identify critical issues and recommend corresponding solutions, which include: a) refine the local patient database with additional details on comorbidities and risk factors; b) support a greater involvement of "gate-keepers" in the screening phase; c) provide practical tools for the definition of strategies to increment the adherence to therapy; d) include recommendations for physical exercise and interdisciplinary cooperation; and e) define process indicators for measuring the quality of the screening and therapeutic phases. CONCLUSION: The concomitant analyses of formalised processes and critical risk factors represent a useful approach for systematically identifying areas of improvement in healthcare processes and allow us to discuss solutions. Moreover, the specific adoption of UML® for graphical modelling and representation of patient care processes allows us to formalise them by adopting a standard language that can be taken as the basis for implementing web services to support the execution of the modelled processes.

Calcitonin gene-related peptide decreases IL-1beta, IL-6 as well as Ym1, Arg1, CD163 expression in a brain tissue context-dependent manner while ameliorating experimental autoimmune encephalomyelitis.

Activation states of immune cells (among them, the so-called pro- or anti-inflammatory states) influence the pathogenesis of multiple sclerosis (MS). The neuropeptide calcitonin gene-related peptide (CGRP) can exert a pro- or anti-inflammatory role in a context-dependent manner. In mice CGRP was found to attenuate the development of experimental autoimmune encephalomyelitis (EAE, a common MS animal model). We analyzed CGRP effects on the expression of cytokines and markers of activation states, as well as its intracellular cascade, following intrathecal administration during EAE immunization. Real Time quantitative-PCR (RT-PCR) showed that IL-1beta and IL-6 (associated to a pro-inflammatory state in EAE), but also Ym1 (also known as Chil3), Arg1 and CD163 (associated to an anti-inflammatory state in EAE) were decreased in the encephalon (devoid of cerebellum). In the cerebellum itself, IL-1beta and Ym1 were decreased. TNF-alpha (associated to a pro-inflammatory state in EAE), but also IL-10 (associated to another type of anti-inflammatory state) and BDNF were unchanged in these two regions. No changes were detected in the spinal cord. Additional tendencies toward a change (as revealed by RT-PCR) were again decreases: IL-10 in the encephalon and Arg1 in the spinal cord. CGRP decreased percentage of Ym1+/CD68+ immunoreactive cells and cell density of infiltrates in the cervical spinal cord pia mater. Instead, Ym1 in the underlying parenchyma and at thoracic and lumbar levels, as well as Arg1, were unchanged. In cultured microglia the neuropeptide decreased Ym1, but not Arg1, immunoreactivity. Inducible NOS (iNOS) was unchanged in spinal cord microglia and astrocytes. The neuropeptide increased the activation of ERK1/2 in the astrocytes of the spinal cord and in culture, but did not influence the activation of ERK1/2 or p38 in the spinal cord microglia. Finally, in areas adjacent to infiltration sites CGRP-treated microglia showed a larger ramification radius. In conclusion, CGRP-induced EAE amelioration was associated to a concomitant, context-dependent decrease in the expression of markers belonging to both pro- or anti-inflammatory activation states of immune cells. It can be hypothesized that CGRP-induced EAE attenuation is obtained through a novel mechanism that promotes down-regulation of immune cell activation that facilitates the establishment of a beneficial environment in EAE provided possibly also by other factors.

Aspirin resistance determined with PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease.

OBJECTIVE: Evidence is growing that some patients are not responsive to the antithrombotic action of aspirin. We prospectively evaluated the ability of aspirin resistance status, determined by PFA-100, to predict new thrombotic events in patients with stable ischemic cerebrovascular disease. METHODS: We studied 129 consecutive patients with stroke, transient ischemic attack (TIA) or vascular cognitive impairment. We assessed relationships between aspirin resistance, risk factors for ischemic cerebrovascular disease, and occurrence of new thrombotic events (composite of stroke, TIA, myocardial infarction, and cardiovascular death). RESULTS: Aspirin resistance, found in 26 (20.1%) cases, was unrelated to any of the examined vascular risk factors. During mean follow-up of 56 months, new thrombotic events occurred in 19 patients (14.7%), four with aspirin resistance (15.4%) and 15 (14.6%) without aspirin resistance (p=1.00). CONCLUSION: Aspirin resistance determined by PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease.

An effect of the PAI-1 4G/5G polymorphism on cholesterol levels may explain conflicting associations with myocardial infarction and stroke.

BACKGROUND AND PURPOSE: The gene-encoding plasminogen activator inhibitor type 1 (PAI-1) has a common 4G/5G 'functional' polymorphism, and people homozygous for the 4G allele have higher PAI-1 plasma concentrations. The 4G/4G genotype is associated with increased risk of myocardial infarction but paradoxically protects against stroke. We hypothesized that this paradox may be explained via an effect of the PAI-1 polymorphism on plasma lipids. METHODS: We studied 71 consecutive Italian patients referred to our Institute for first stroke or vascular cognitive impairment. PAI-1 gene 4G/5G polymorphism, total plasma cholesterol, plasma triglycerides, sex, age, smoking, oral contraceptive use, statin therapy, hypertension, diabetes, and history of myocardial infarction were examined. RESULTS: The 4G/4G genotype was significantly associated with high cholesterol (p = 0.003) but not with triglycerides (p = 0.39). Adjusted odds ratios were: 5.8 for 4G/4G vs. 4G/5G (95% CI, 3.1-23.0), and 15.9 for 4G/4G vs. 5G/5G (95% CI, 2.4-105.0). CONCLUSIONS: This finding may explain the involvement of the PAI-1 polymorphism in the clustering of atherothrombotic risk factors, and why people with the 4G/4G genotype are at increased risk for myocardial infarction. Stroke is not so clearly related to hypercholesterolemia and other effects of the 4G/4G genotype (perhaps increased PAI-1 expression) may protect against stroke.