[2022 Practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension]. / Guía práctica sobre el diagnóstico y tratamiento de la hipertensión arterial en España, 2022. Sociedad Española de Hipertensión - Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA).

Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients.

Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa inhibitor fondaparinux does not. In the lethal SARS-CoV-2 K18-hACE2 model, FXa prolongs survival yet its combination with rivaroxaban but not fondaparinux abrogates that protection. These results identify both a previously unknown function for FXa and an associated antiviral host defense mechanism against SARS-CoV-2 and suggest caution in considering direct FXa inhibitors for preventing or treating thrombotic complications in COVID-19 patients.

Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants.

We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 µM, 8.5 µM, 24.1 µM, 8.2 µM and 13.6 µM, respectively. A separate experiment focusing on a combination of 10 µM stenoparib and 0.5 µM remdesivir, an antiviral drug, resulted in over 80% inhibition of the alpha variant, which is substantially greater than the effect achieved with either drug alone, suggesting at least additive effects from combining the different mechanisms of activity of stenoparib and remdesivir.

Detection of SARS-CoV-2 and its S and N proteins using surface enhanced Raman spectroscopy† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra03481b

The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection. This need has generated a high number of new testing methods aimed at replacing RT-PCR, which is the golden standard for testing. Most of the testing techniques are based on biochemistry methods and require chemicals that are often expensive and the supply might become scarce in a large crisis. In the present paper we suggest the use of methods based on physics that leverage novel nanomaterials. We demonstrate that using Surface Enhanced Raman Spectroscopy (SERS) of virion particles a very distinct spectroscopic signature of the SARS-CoV-2 virus can be obtained. We demonstrate that the spectra are mainly composed by signals from the spike (S) and nucleocapsid (N) proteins. It is believed that a clinical test using SERS can be developed. The test will be fast, inexpensive, and reliable. It is also clear that SERS can be used for analysis of structural changes on the S and N proteins. This will be an example of application of nanotechnology and properties of nanoparticles for health and social related matters. The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection.

Assessing law enforcement websites: a comparative analysis exploring types, quantity and quality of information available

Purpose>The purpose of this study is to explore the availability of information on law enforcement websites in the state of Wisconsin.Design/methodology/approach>The study conducted a content analysis of all 179 county and municipal local law enforcement agency websites within Wisconsin. The authors then implemented a comparative analysis that explored whether the quantity and quality of information available on law enforcement websites are similar to those of local governments and school districts. The authors then estimated models to test whether there is a relationship between the population size served and gender distribution of law enforcement departments to the availability of information on law enforcement websites.Findings>Law enforcement websites contain a noticeable lack of information. The finding is even more apparent when comparing law enforcement websites to the websites of local governments and school districts. Finally, the authors show a positive link between information sharing on law enforcement websites and the proportion of the civilian staff at an agency that are women.Originality/value>Past studies that reviewed the make-up of law enforcement websites analyzed large law enforcement departments rather than local law enforcement departments, which notably represent the majority of most law enforcement departments. The authors also explicitly demonstrate that the commitment to information sharing is lagging within law enforcement websites compared to local-level governments. Future scholarship and law enforcement departments may benefit from exploring the employment of female civilians.

[Evaluation of contingency plans in the care of patients in intensive care units in the COVID-19 pandemic]. / Evaluación de los planes de contingencia en la atención a pacientes en Unidades de Cuidados Intensivos en la pandemia por COVID-19.

BACKGROUND: The expansion of intensive care areas has been one of the most significant measures in this forced adaptation to the evolution of the different phases of the COVID-19 pandemic. The objective is to evaluate the deployment of contingency plans in the care of patients admitted to intensive care units during the period from March 19 to April 20, 2020, in a public hospital, reference for 300,000 inhabitants belonging to the Galician Health Service. MATERIALS AND METHODS: Qualitative research from focus groups, with systematic sampling. Based on the adaptation to the health environment of the 10 measures recommended by Deloitte to face a pandemic, an evaluation was carried out by the quality unit of the Health Area. As outcome indicators, the number of COVID-19 patients, % of patients admitted to hospital, % patients admitted to intensive care units, as well as the number of deaths from COVID-19, were evaluated in seven health areas in the period March 19 to April 20, 2020. RESULTS: The qualitative evaluation identified 2 areas for improvement (communication and risk assessment) of the 10 recommended measures. The Health Area has the lowest relative (2.6%) and absolute (16) rate of deceased patients, as well as the lowest relative (7.9%) and absolute (24) rate of patients admitted to intensive services for COVID-19. The infection rate in professionals has been 4.4%. CONCLUSIONS: The simplicity and identification of areas for improvement added to the low consumption of resources are strengths of this proposal. This self-assessment can be helpful in identifying areas for improvement.

Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants (preprint)

We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Stenoparib is an inhibitor of mammalian poly (ADP-ribose) polymerases (PARPs). Here we show that stenoparib effectively inhibits additional SARS-CoV-2 variants, including an additional wild-type strain (Germany/BavPat1/2020), and the variants alpha (B.1.1.7), beta (B.1.351) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 M, 8.5 M, 24.2 M and 13.6 M, respectively. A second study focusing on a combination of 10 M stenoparib and 0.5 {micro}M remdesivir resulted in over 90% inhibition of the alpha (B.1.1.7) variant, which is substantially greater than what was achieved with stenoparib or remdesivir alone at these concentrations.

Detection of SARS-CoV-2 and its S and N proteins using surface enhanced Raman spectroscopy.

The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection. This need has generated a high number of new testing methods aimed at replacing RT-PCR, which is the golden standard for testing. Most of the testing techniques are based on biochemistry methods and require chemicals that are often expensive and the supply might become scarce in a large crisis. In the present paper we suggest the use of methods based on physics that leverage novel nanomaterials. We demonstrate that using Surface Enhanced Raman Spectroscopy (SERS) of virion particles a very distinct spectroscopic signature of the SARS-CoV-2 virus can be obtained. We demonstrate that the spectra are mainly composed by signals from the spike (S) and nucleocapsid (N) proteins. It is believed that a clinical test using SERS can be developed. The test will be fast, inexpensive, and reliable. It is also clear that SERS can be used for analysis of structural changes on the S and N proteins. This will be an example of application of nanotechnology and properties of nanoparticles for health and social related matters.

COVID-19 Mortality Risk Prediction Using X-Ray Images

The pandemic caused by coronavirus COVID-19 has already had a massive impact in our societies in terms of health, economy, and social distress. One of the most common symptoms caused by COVID-19 are lung problems like pneumonia, which can be detected using X-ray images. On the other hand, the popularity of Machine Learning models has grown exponentially in recent years and Deep Learning techniques have become the state-of-the-art for image classification tasks and is widely used in the healthcare sector nowadays as support for clinical decisions. This research aims to build a prediction model based on Machine Learning, including Deep Learning, techniques to predict the mortality risk of a particular patient given an X-ray and some basic demographic data. Keeping this in mind, this paper has three goals. First, we use Deep Learning models to predict the mortality risk of a patient based on this patient X-ray images. For this purpose, we apply Convolutional Neural Networks as well as Transfer Learning techniques to mitigate the effect of the reduced amount of COVID19 data available. Second, we propose to combine the prediction of this Convolutional Neural Network with other patient data, like gender and age, as input features of a final Machine Learning model, that will act as second and final layer. This second model layer will aim to improve the goodness of fit and prediction power of our first layer. Finally, and in accordance with the principle of reproducible research, the data used for the experiments is publicly available and we make the implementations developed easily accessible via public repositories. Experiments over a real dataset of COVID-19 patients yield high AUROC values and show our two-layer framework to obtain better results than a single Convolutional Neural Network (CNN) model, achieving close to perfect classification.

Telemedicine in the management of patients with headache: current situation and recommendations of the Spanish Society of Neurology's Headache Study Group. / Aplicación de la telemedicina en la asistencia a pacientes con cefaleas: situación actual y recomendaciones del Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: The COVID-19 pandemic has caused an unexpected boost to telemedicine. We analyse the impact of the pandemic on telemedicine applied in Spanish headache consultations, review the literature, and issue recommendations for the implementation of telemedicine in consultations. METHOD: The study comprised 3 phases: 1) review of the MEDLINE database since 1958 (first reported experience with telemedicine); 2) Google Forms survey sent to all members of the Spanish Society of Neurology's Headache Study Group (GECSEN); and 3) online consensus of GECSEN experts to issue recommendations for the implementation of telemedicine in Spain. RESULTS: COVID-19 has increased waiting times for face-to-face consultations, increasing the use of all telemedicine modalities: landline telephone (from 75% before April 2020 to 97% after), mobile telephone (from 9% to 27%), e-mail (from 30% to 36%), and video consultation (from 3% to 21%). Neurologists are aware of the need to expand the availability of video consultations, which are clearly growing, and other e-health and m-health tools. CONCLUSIONS: The GECSEN recommends and encourages all neurologists who assist patients with headaches to implement telemedicine resources, with the optimal objective of offering video consultation to patients under 60-65 years of age and telephone calls to older patients, although each case must be considered on an individual basis. Prior approval and advice must be sought from legal and IT services and the centre's management. Most patients with stable headache and/or neuralgia are eligible for telemedicine follow-up, after a first consultation that must always be held in person.

Clinical characterization of headache attributed to COVID-19: A series of 457 cases

Introduction: Headache is one of the most frequent symptoms of coronavirus disease 2019 (Covid-19). Most of the published series and cases described hospitalized patients, which could bias the results because of a more severe Covid-19. Objectives: In the present study we aim to describe the clinical phenotype of headache attributed to Covid-19 (HAC-19) including the full spectrum of patients, including cases managed both in primary care and hospital care. Methods:We screened the presence of headache all consecutive patients with a confirmed diagnosis of Covid-19, since the first hospitalized patient (March 8th, 2020) until April 11th. Patients with headache and capability to describe the headache phenotype were invited to participate. Diagnosis was confirmed by polymerase chain reaction test in all patients. A physician conducted a structured interview including demographic and clinical variables. Local ethics review board approved the study (PI 20- 1738). Results: A total of 138/576 (26.0%) hospitalized patients and 408/1690 (24.1%) primary care patients described headache, being.8 included in the study 105 and 352 of them. Mean age was 52.1±15.6 years, being 329 (72.0%) female, and 151 (33.0%) had pneumonia. Prior history of headache was described by 223 (48%) of patients, being migraine in 83 (18.2%). Headache was the first Covid-19 symptom in 126 (27.6%) patients and the mean duration of headache was 12.8 (16.1) days. The most frequent concomitant symptoms were olfactory disorders in 268 (58.6%) cases, followed by asthenia 335 (73.3%), cough 296 (64.8%), fever 259 (56.7%), and myalgia 223 (48.8%). Headache was the most bothersome Covid- 19 symptom in 69 (15.1%) cases, being the mean intensity 6.9±1.7. Patients estimated that headache allowed them to do 49.1±32.6% of their planned activities because of it. The headache was holocranial in 335 (73.3%), with frontal topography in 244 (53.4%), followed by temporal (121 (26.5%) and periocular in 97 (21.2%). Quality of pain was oppressive in 323 (70.7%) and throbbing in 66 (14.1%). Patients described avoidance of routine physical activity in 288 (63.0%) cases, photophobia in 150 (32.8%) cases, phonophobia in 146 (31.9%), and nausea in 69 (15.1%). The most frequently used symptomatic medication was paracetamol in 379 (82.9%), followed by ibuprofen in 70 (15.3%) and metamizole in 48 (10.5%). Conclusion: Headache is a frequent symptom in Covid- 19 disease. The clinical phenotype combines features from both tension-type headache and migraine, with moderate intensity and significant disability. A quarter of patients described headache as the first Covid-19 symptom.

Stenoparib, an Inhibitor of Cellular Poly(ADP-Ribose) Polymerase, Blocks Replication of the SARS-CoV-2 and HCoV-NL63 Human Coronaviruses In Vitro.

By late 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused tens of millions of infections and over 1 million deaths worldwide. A protective vaccine and more effective therapeutics are urgently needed. We evaluated a new poly(ADP-ribose) polymerase (PARP) inhibitor, stenoparib, that recently advanced to phase II clinical trials for treatment of ovarian cancer, for activity against human respiratory coronaviruses, including SARS-CoV-2, in vitro Stenoparib exhibits dose-dependent suppression of SARS-CoV-2 multiplication and spread in Vero E6 monkey kidney and Calu-3 human lung adenocarcinoma cells. Stenoparib was also strongly inhibitory to the human seasonal respiratory coronavirus HCoV-NL63. Compared to remdesivir, which inhibits viral replication downstream of cell entry, stenoparib impedes entry and postentry processes, as determined by time-of-addition (TOA) experiments. Moreover, a 10 µM dosage of stenoparib-below the approximated 25.5 µM half-maximally effective concentration (EC50)-combined with 0.5 µM remdesivir suppressed coronavirus growth by more than 90%, indicating a potentially synergistic effect for this drug combination. Stenoparib as a stand-alone or as part of combinatorial therapy with remdesivir should be a valuable addition to the arsenal against COVID-19.IMPORTANCE New therapeutics are urgently needed in the fight against COVID-19. Repurposing drugs that are either already approved for human use or are in advanced stages of the approval process can facilitate more rapid advances toward this goal. The PARP inhibitor stenoparib may be such a drug, as it is currently in phase II clinical trials for the treatment of ovarian cancer and its safety and dosage in humans have already been established. Our results indicate that stenoparib possesses strong antiviral activity against SARS-CoV-2 and other coronaviruses in vitro. This activity appears to be based on multiple modes of action, where both pre-entry and postentry viral replication processes are impeded. This may provide a therapeutic advantage over many current options that have a narrower target range. Moreover, our results suggest that stenoparib and remdesivir in combination may be especially potent against coronavirus infection.