Single-pill combination for treatment of hypertension: Just a matter of practicality or is there a real clinical benefit?

Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician's inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP ''per se'' and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin-angiotensin-aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide-like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control.

[Ambulatory blood pressure monitoring, adult and pediatric population. A narrative review]. / Monitorización ambulatoria de la presión arterial en adultos y población pediátrica. Una revisión narrativa.

Hypertension has become a central risk factor for the development of cardiovascular disease, underscoring the importance of its accurate diagnosis. Numerous studies have established a close relationship between elevated systolic (SBP) and diastolic (DBP) blood pressure and an increased risk of cardiovascular event (CVE). Traditionally, blood pressure (BP) measurements performed in clinical settings have been the main method for diagnosing and assessing hypertension. However, in recent years, it has been recognized that BP measurements obtained outside the clinical setting, using self-monitoring blood pressure (SMBP) and ambulatory blood pressure monitoring (ABPM), offer a more realistic perspective of patients' daily lives and therefore provide more reliable results. Given the evolution of medical devices, diagnostic criteria, and the increasing relevance of certain components of ABPM in the prediction of adverse cardiovascular outcomes, a comprehensive update that is practical for daily clinical practice is required. The main objective of this article is to provide an updated review of ABPM, focusing on its importance in the evaluation of hypertension and its impact on public health in Colombia. In addition, it will discuss the implications of changes in diagnostic thresholds and provide concrete recommendations for the effective implementation of ABPM in clinical practice, allowing health professionals to make informed decisions and improve the care of their patients.

Mediastinitis secondary to invasive infection by group A Streptococcus in Spain.

This study describes 5 mediastinitis cases secondary to invasive group A Streptococcus (iGAS) disease in a recent outbreak in Spain. Among 398 iGAS cases between January 2019-March 2023, 5 (1.3%) were mediastinitis, 4 occurring in December 2022, all secondary to pneumonia or deep neck infection. We outline the clinical outcome with a review of the scarce pediatric literature.  Conclusion: mediastinistis is a rare but severe complication of iGAS and a high level of suspicion is required to diagnose it. What is Known: • Group A Streptococcus can cause invasive and severe infections in children. • Mediastinitis is a severe complication from some bacterial infections, mainly secondary due to deep-neck abscesses. What is New: • Mediastinitis is an unrecognized complication due to an invasive group A Streptococcus (iGAS) infection. • In cases of a deep-neck abscess or complicated pneumonia a high clinical suspicion of iGAS mediastinitis is required, especially when the clinical course is not favorable.

Perspectives on improving blood pressure control to reduce the clinical and economic burden of hypertension.

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long-term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient-, physician- and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single-pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient-focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long-term improvements in population health and cost-efficiency for healthcare systems.

How low should blood pressure be in patients with chronic coronary and cerebrovascular diseases.

Over the last three decades, there are an increasing number of investigators and meta-analyses focusing on the fact that lowering blood pressure levels below a critical point is no longer beneficial and possibly even deleterious. In recent years, several trials and meta-analyses assessing intensive blood pressure (BP) lowering found that intensive treatment and lower blood pressure levels are associated with a reduction in CV events and mortality. However, a careful examination of the results shows that current data are not easily applicable to the general hypertensive population. In addition, recommendations of different guidelines since 2017 so far suggest different BP levels regarding the systolic and diastolic thresholds to be achieved and maintained, particularly in specific clinical situations such as patients with coronary artery disease and stroke. The challenge is to better define the limits of intervention and to define phenotypes of patients who are particularly vulnerable to over-aggressive lowering of blood pressure. This article reviews the evidence, controversies and current state of knowledge regarding intensive BP lowering and the lower thresholds of BP to be achieved in patients with chronic coronary or cerebrovascular diseases.

[Comprehensive Therapeutic Approach to Hypertension. Recommendations for Central America and the Caribbean]. / Abordaje terapéutico integral de la hipertensión arterial. Recomendaciones para Centroamérica y el Caribe.

Latin American hypertension guidelines, tailored to the needs of countries of Central and South America, should be applied and known by most Latin American physicians. The knowledge and implementation of the Guidelines is one of the greatest challenges of hypertension societies in Latin America such as the Central American and Caribbean Society of Arterial Hypertension (SCCH), the Latin American Society of Hypertension (LASH) and the Inter-American Society of Cardiology (SIAC). In 2020, the Inter-American Society of Cardiology (SIAC) published its position on the current Guidelines for Arterial Hypertension due to the need to standardize the evaluation, diagnosis, treatment and control of hypertension, establishing recommendations that should be adopted in all Latin American countries, aimed at optimizing the management of cardiovascular risk and achieving a substantial improvement in the reduction of cardiovascular events and mortality. This document intends to reinforce all proposals by the LASH guidelines and the position of the SIAC in relation to the therapeutic approach and pharmacological recommendations for patients with hypertension (HT), in order to achieve better HT control in the Central American and Caribbean area, and the consequently prognosis improvement of cardiovascular disease in the area.

[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.

Latin-American Ambulatory Blood Pressure Registry (MAPA-LATAM): An urgent need.

Hypertension (HT) is one of the main risk factors for cardiovascular disease (CVD). Although it is a global problem, independently of economic situation, region, race or culture, the data available on Latin America are limited. Clinical guidelines emphasise the importance of obtaining reliable blood pressure readings. For this reason, the use of ambulatory blood pressure monitoring (ABPM) is recommended. This improves precision and reproducibility, resulting in better diagnosing and therapeutic decision-making, and constitutes a better estimation of prognosis than office measurements. Unfortunately, there is no global prospective ABPM registry for all of Latin America that analyses HT prevalence, the level of knowledge about it, treatment percentage and the degree of control. Consequently, the authors of this article consider its implementation a priority.

In vivo pharmacokinetic evaluation of carprofen delivery from intra-articular nanoparticles in rabbits: A population modelling approach.

Osteoarthritis is treated with COX or fosfolipase A2 inhibitors such as carprofen, a propionic acid NSAID. The enhancement of its action over the articular cartilage is mandatory to facilitate its therapeutic application. Drug uptake into the cartilage requires high synovial fluid concentrations, anticipating its rapid distribution towards bloodstream. Thus, intraarticular administration improves local targeting of the drug, lining with the site of action. A pharmacokinetic study in rabbits has been performed to evaluate carprofen nanoparticles after intraarticular administration. Pharmacokinetic analysis of plasma profiles through a modelling approach, has demonstrated the rapid distribution of drug outside of synovial chamber but mainly remaining in plasma. The data modelling has demonstrated the existence of two release-absorption processes when the nanoparticles are administered in the synovial space. Additionally, results are predictive of the PK profile of some other species such as cat, dogs or humans.

Signaling pathway deregulation and molecular alterations across pediatric medulloblastomas.

Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs). This stratification moved forward recently to better define these groups and their correlation to outcome. This new stratification into 7 novel subgroups was helpful to lay foundations and complementary data on the understanding regarding molecular pathways and gene mutations underlying medulloblastoma biology. This review was aimed at answering the recent key questions on MB genomics and go further in the relevance of those genes in MB development as well as in their targeted therapies.

[Choice optimisation of radiation therapy technique for central neurocytomas from literature data]. / Optimisation du choix de la technique d'irradiation des neurocytomes centraux à partir des données de la littérature.

Neurocytomas represent 0,25 to 0,5 of brain tumours. These tumours have neuronal differentiation. It's a young adult disease. The main treatment is neurosurgery. The place of other therapies is still unclear, noticeably with regards to radiotherapy. This review aim is to determine the place and the modalities of radiotherapy in the management of neurocytomas. A literature search using PubMed allowed to select the most relevant studies. Finally, 22 studies were selected according to pre-established criteria to answer the problem. All studies were retrospective studies except one. The analysis conclusion defined radiotherapy as a treatment of choice in selected patients, when surgical resection was incomplete or when tumour was atypical.

[Impact of cognitive biases in therapeutic inertia in arterial hypertension: Not everything is as it seems]. / Impacto de los sesgos cognitivos en la inercia terapéutica en hipertensión arterial: no todo es lo que parece.

Therapeutic inertia is defined as the failure to take therapeutic decisions, such as initiating, adding or increasing the dose of a drug during patient follow-up, despite there being an indication to do so. It is currently considered that therapeutic inertia is a considerable impediment to achieving adequate control of hypertension, and this has implications for the prognosis of the disease. Therapeutic inertia might be due to various factors involving physicians, patients and the health system. Many studies have attempted to find determinants for therapeutic inertia in hypertension and to explain the reasons why health professionals in charge of treatment are failing to make the appropriate modifications to therapy. The many reasons for therapeutic inertia on the part of physicians include the various cognitive and affective biases that influence clinical reasoning and decision-making during healthcare activity in doctors' surgeries. Identifying and recognising these cognitive and affective biases could be important for planning educational strategies for health professionals. This requires a multi-dimensional approach, including knowledge beyond that observed in terms of insufficient information and updating on the disease, and starting to analyse and consider other reasons. Preventing therapeutic inertia should be made a priority along with other important measures to control hypertension and minimise its consequences.

The Grisel's syndrome: A non-traumatic subluxation of the atlantoaxial joint.

INTRODUCTION: Grisel's syndrome consists in rotational subluxation of C1-C2 following ENT infection or surgery. There is no consensus on management. We present 2 cases requiring surgical treatment in our center. CASE REPORTS: Two 10-year-old patients presented torticollis with cervical pain resistant to medical treatment, with onset a few months after tonsillectomy. In both cases, radiological assessment, comprising CT scan and MRI, showed Fielding-Hawkins type-3 C1-C2 rotational subluxation, without ligament lesion. After failure of conservative treatment, posterior reaming, realignment, C1-C2 arthrodesis using lateral masses and pars interarticularis screws and bone graft achieved good fusion and immediate spinal stability in all planes of the atlantoaxial complex. DISCUSSION: Grisel's syndrome consists in non-traumatic subluxation of the atlantoaxial joint with intact atlantoaxial ligaments. Initial pharyngeal inflammation spreads to the prevertebral fascia via direct connections between the periodontoidal venous plexus and pharyngovertebral veins, inducing fasciitis that leads to abnormal relaxation of the atlantoaxial ligaments and reactional muscle contraction with ankylosis. This phenomenon, appearing gradually and insidiously over a period of a few weeks, creates a frozen joint with ankylosis. Medical treatment with NSAIDs, muscle relaxants, and immobilization is usually sufficient; cervical traction may be needed. Surgical treatment by C1-C2 arthrodesis is indicated in case of failure of medical management or onset of neurologic signs. CONCLUSION: Close collaboration between pediatricians, ENT surgeons and neurosurgeons is essential for early diagnosis and management, which is the main prognostic factor for successful medical treatment, avoiding surgery.

[Spanish Society of Hypertension position statement on the 2017 ACC/AHA hypertension guidelines]. / Documento de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) sobre las guías ACC/AHA 2017 de hipertensión arterial.

The American College of Cardiology (ACC) and the American Heart Association (AHA) have recently published their guidelines for the prevention, detection, evaluation, and management of hypertension in adults. The most controversial issue is the classification threshold at 130/80mmHg, which will allow a large number of patients to be diagnosed as hypertensive who were previously considered normotensive. Blood pressure (BP) is considered normal (<120mmHg systolic and <80mmHg diastolic), elevated (120-129 and <80mmHg), stage 1 (130-139 or 80-89mmHg), and stage 2 (≥140 or ≥90mmHg). Out-of-office BP measurements are recommended to confirm the diagnosis of hypertension and for titration of BP-lowering medication. In management, cardiovascular risk would be determinant since those with grade 1 hypertension and an estimated 10-year risk of atherosclerotic cardiovascular disease ≥10%, and those with cardiovascular disease, chronic kidney disease and/or diabetes will require pharmacological treatment, the rest being susceptible to non-pharmacological treatment up to the 140/90mmHg threshold. These recommendations would allow patients with level 1 hypertension and high atherosclerotic cardiovascular disease to benefit from pharmacological therapies and all patients could also benefit from improved non-pharmacological therapies. However, this approach should be cautious because inadequate BP measurement and/or lack of systematic atherosclerotic cardiovascular disease calculation could lead to overestimation in diagnosing hypertension and to overtreatment. Guidelines are recommendations, not impositions, and the management of hypertension should be individualized, based on clinical decisions, preferences of the patients, and an adequate balance between benefits and risks.

Waist-to-height ratio and sedentary lifestyle as predictors of metabolic syndrome in children in Ecuador.

OBJECTIVE: To determine the predictors and prevalence of metabolic syndrome (MS) and the presence of vascular inflammation in apparently-normal children (10-15 years) of both sexes in Guayaquil, Ecuador. STUDY DESIGN AND METHODS: We included 395 apparently-healthy students from a middle-income school in a cross-sectional survey. Informed consent was obtained from students and parents. Anthropometric measurements including blood pressure (BP), body mass index (BMI) and waist-to-height ratio (WHtR), and blood tests were recorded. Vascular inflammation parameters were assessed. Percentiles of the different parameters were used, and MS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP-ATPIII). Waist circumference>P 75, blood pressure>P 90, glucose>100mg/dl, triglycerides>100mg/dl, HDL<45mg/dl. If 3 of the 5 criteria were present, this was considered MS. RESULTS: The mean age was 12 years (186 boys, 209 girls). The overall prevalence of MS was 9.37% (6.33% in girls, 3.04% in boys). Sustained hypertension was detected in 6.6% of children and pre-hypertension in 7.1%. Obesity was found in 1.8% of subjects, and overweight in 15.2%. Triglycerides has a RR 2.34 (1.97-2.76); HOMA index has a RR 1.97(1.62-2.40); HDL cholesterol has a RR 1.84(1.58-2.13); Insulin level has a RR 1.53(1.40-1.67) and interleukin 6 has RR 1.83(1.20-2.79). Serum glucose, total cholesterol and LDL-Cholesterol had no association with the metabolic syndrome. HDL-Cholesterol<45mg/dl and triglyceride>100mg/dl were present in 70% of subjects with MS. The WHtR threshold≥0.5 was 100% sensitive in both sexes (67% specificity in boys and 69% in girls). There were significant associations between the WHtR and pre-hypertension and sedentary lifestyle (P<0.001 and P<0.003 respectively). A WHtR value of ≥0.50 indicated a 2.2-fold increased risk of MS compared with normal WHtR, and normal weight. CONCLUSIONS: A WHtR≥0.5 was 100% sensitive in detecting MS in 10-15 year-old boys and girls in the normal or overweight range of the BMI. This assessment is a simple and practical tool for use in population-based studies of cardiovascular risk. When combined with pre-hypertension and a sedentary lifestyle, the WHtR is highly sensitive in predicting MS.