Showing papers by "Gdańsk Medical University published in 2021"

Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer

Abstract: Background Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduc...

Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors.

Abstract: Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors-in-chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.

The legal extension of the role of pharmacists in light of the COVID-19 global pandemic.

Abstract: Background The COVID-19 epidemic has affected every area of life. The greatest challenge has been to adapt the functioning of the health service to prevent the spread of the epidemic and to help infected patients. This has required the involvement of not only doctors and nurses, but also pharmacists. In the face of this pandemic, governments in many countries have granted pharmacists greater authority. Objectives The purpose of this paper is to review the legal extension of the role of pharmacists in light of the COVID-19 pandemic. The review considers recent changes in European countries, Canada, and the United States. Methods A literature review was performed to summarise knowledge about the extension of the role of pharmacists during the pandemic period. Key articles were retrieved mainly from PubMed and Google Scholar, using the terms “COVID‐19”, “2019‐nCoV”, “coronavirus”, and “pandemic” in combination with “pharmacist” as keywords for our search. We included scientific publications from February 1, 2019 to May 15, 2020. Results Pharmacists have been given numerous opportunities so that they can actively join in the fight against the virus. Some of the novel legal extensions aimed at aiding overloaded healthcare systems are as follows: authorisation to prepare hand and surface disinfectants, eligibility to renew chronic treatment prescriptions, as well as filling pro auctore and pro familia prescriptions by pharmacists, performing COVID-19, influenza, and Group A Streptococcus screening tests, and vaccine administration. Moreover, many countries have facilitated Internet services, such as virtual medical consultations, e-prescriptions, and home drug delivery – to promote social distancing among patients. To mitigate drug shortages, the following strategies have been implemented: alternative sourcing, strength, generic, or therapeutic substitution, and preparing compounded formulations at the pharmacy. Conclusions Novel legal extensions have allowed exploitation of the full potential ofpharmacists worldwide, aiding the limited resources of overloaded healthcare systems.

Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls.

Abstract: Background Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and def...

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.

European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage

Abstract: The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provi...

The incidence and clinical analysis of non-melanoma skin cancer.

Abstract: Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.

Molecular Mechanisms of Atopic Dermatitis Pathogenesis.

Abstract: Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature is persistent itching of the skin. The chronic, relapsing course of the disease, economic burden, and the whole family's involvement in the treatment process immensely reduce the quality of life of patients and their families. The disease emerges as a social problem by increasing indirect costs, such as visiting a doctor, absenteeism from work and school, and avoiding social interactions. Thepathophysiology of atopic dermatitis is complex and multifactorial. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, anddisruption of the skin's microbial balance. The numerous complex changes at thegenetic level and innate and adaptive immunity provide the basis for characterizing the various phenotypes and endotypes of atopic dermatitis. Emerging therapies rely on the action of specific molecules involved in the disease's pathogenesis. It may be the starting point for the individualization of atopic dermatitis treatment. This paper will try to present some molecular mechanisms of atopic dermatitis and their clinical implications.

Obesity and Cardiometabolic Risk Factors: From Childhood to Adulthood.

Abstract: Obesity has become a major epidemic in the 21st century. It increases the risk of dyslipidemia, hypertension, and type 2 diabetes, which are known cardiometabolic risk factors and components of the metabolic syndrome. Although overt cardiovascular (CV) diseases such as stroke or myocardial infarction are the domain of adulthood, it is evident that the CV continuum begins very early in life. Recognition of risk factors and early stages of CV damage, at a time when these processes are still reversible, and the development of prevention strategies are major pillars in reducing CV morbidity and mortality in the general population. In this review, we will discuss the role of well-known but also novel risk factors linking obesity and increased CV risk from prenatal age to adulthood, including the role of perinatal factors, diet, nutrigenomics, and nutri-epigenetics, hyperuricemia, dyslipidemia, hypertension, and cardiorespiratory fitness. The importance of ‘tracking’ of these risk factors on adult CV health is highlighted and the economic impact of childhood obesity as well as preventive strategies are discussed.

Physical activity, screen time and the COVID-19 school closures in Europe - An observational study in 10 countries.

Abstract: To date, few data on how the COVID-19 pandemic and restrictions affected children's physical activity in Europe have been published. This study examined the prevalence and correlates of physical activity and screen time from a large sample of European children during the COVID-19 pandemic to inform strategies and provide adequate mitigation measures. An online survey was conducted using convenience sampling from 15 May to 22 June, 2020. Parents were eligible if they resided in one of the survey countries and their children aged 6-18 years. 8395 children were included (median age [IQR], 13 [10-15] years; 47% boys; 57.6% urban residents; 15.5% in self-isolation). Approximately two-thirds followed structured routines (66.4% [95%CI, 65.4-67.4]), and more than half were active during online P.E. (56.6% [95%CI, 55.5-57.6]). 19.0% (95%CI, 18.2-19.9) met the WHO Global physical activity recommendation. Total screen time in excess of 2 h/day was highly prevalent (weekdays: 69.5% [95%CI, 68.5-70.5]; weekend: 63.8% [95%CI, 62.7-64.8]). Playing outdoors more than 2 h/day, following a daily routine and being active in online P.E. increased the odds of healthy levels of physical activity and screen time, particularly in mildly affected countries. In severely affected countries, online P.E. contributed most to meet screen time recommendation, whereas outdoor play was most important for adequate physical activity. Promoting safe and responsible outdoor activities, safeguarding P.E. lessons during distance learning and setting pre-planned, consistent daily routines are important in helping children maintain healthy active lifestyle in pandemic situation. These factors should be prioritised by policymakers, schools and parents.Highlights To our knowledge, our data provide the first multi-national estimates on physical activity and total screen time in European children roughly two months after COVID-19 was declared a global pandemic.Only 1 in 5 children met the WHO Global physical activity recommendations.Under pandemic conditions, parents should set pre-planned, consistent daily routines and integrate at least 2-hours outdoor activities into the daily schedule, preferable on each day. Schools should make P.E. lessons a priority. Decision makers should mandate online P.E. be delivered by schools during distance learning. Closing outdoor facilities for PA should be considered only as the last resort during lockdowns.

Immunology of Aging: the Birth of Inflammaging.

Abstract: The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.

Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists as of March 31, 2020.

Abstract: 352 symptoms, the signs of acute respiratory failure develop, which leads to multiorgan failure and death of the patient. Mortality rates ranging from 0% to 8% vary from country to country and depend on the quality of health care, in particular the equipment and the availability of intensive care units, but perhaps also on many unknown human genetic factors and / or virus genetic mutability. Etiotropic treatment confirmed in clinical trials is not available. There are attempts to use drugs registered so far for other indications, but their effectiveness has not been confirmed either. Work on developing vaccines has begun, and it can bring results no earlier than in 2021.

Dietary Habits before and during the COVID-19 Epidemic in Selected European Countries

Abstract: During the so-called “second wave of the pandemic” in Europe, the authors conducted a cross-sectional online survey that aimed to examine changes in dietary habits and associated practices, as well as physical activity during the COVID-19 pandemic and before the onset of lockdowns in three European countries: Poland, Austria and the United Kingdom. Methods: The online observational study, both prospective and retrospective, conducted with the use of social media for the distribution of an anonymous online questionnaire, was completed from 1 October to 30 October 2020, during the second wave of the pandemic in Europe. The study encompassed a total of 1071 adults from Poland (n = 407), Austria (n = 353) and the United Kingdom (n = 311). Results: The results of this study indicate that the COVID-19 confinement period influenced eating behavior and the level of physical activity in a group of adult residents of Poland, Austria and the United Kingdom. The general shopping frequency decreased, regardless of the place and manner. However, there was an increased interest in online grocery shopping. The resulting data revealed an increased frequency of the daily consumption of food products such as dairy, grains, fats, vegetables and sweets (p < 0.05). A rise in the frequency of purchasing frozen goods and food with long shelf life has also been observed. The changed workplace and working conditions or unemployment probably affected a perceptible rise in alcohol consumption (p = 0.02). In turn, physical activity levels markedly decreased, which reflected the body mass changes. Conclusion: The dietary habits in the studied countries have changed as a result of the pandemic situation. They contribute to the aggravation of the problem of excess body weight and its health consequences.

Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer

Abstract: PURPOSEGenetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 (ROS1) are oncogenic drivers in non-small-cell lung cancer (NSCLC). We report the results of an updated integrated...

Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis.

Abstract: © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)

Comparison of physical activity levels in Spanish adults with chronic conditions before and during COVID-19 quarantine.

Abstract: Background: This is the first study analysing levels of physical activity in a sample of quarantined adults with chronic conditions. The aim of this study was to compare moderate-intensity and vigorous-intensity physical activity levels in Spanish adults with chronic conditions before and during COVID-19 quarantine. Methods: A cross-sectional online survey was administered during the COVID-19 quarantine in Spain. A total of 163 participants with chronic conditions (113 females and 47 males; age range 18-64 years) completed the survey. A total of 26 chronic conditions were included. Participants self-reported average minutes/day of moderate and vigorous physical activity before and during quarantine. Differences in moderate-intensity physical activity and vigorous-intensity physical activity levels before and during COVID-19 quarantine (overall, by gender, by age, by number of chronic conditions and by each chronic condition) were assessed by Wilcoxon signed-rank test. Results: During COVID-19 quarantine, there was a significant decrease of moderate-intensity physical activity in Spanish people with chronic conditions (in both males and females, in those aged 18-24, 25-34, 35-44 and 55-64 years, in those with multimorbidity, in those with one/two chronic condition/s, and in those diagnosed with asthma/hypercholesterolemia/chronic skin disease/hemorrhoids). Also, there was a significant decrease of vigorous-intensity physical activity in Spanish males with chronic conditions and in those with multimorbidity. Conclusions: These results should be considered to develop effective strategies of physical activity promotion targeting these specific groups when new quarantine or restriction measures are implemented, in order to avoid new significant decreases of physical activity in these vulnerable populations.

Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria.

Abstract: The recent Chandos House meeting of the Alport Variant Collaborative extended the indications for screening for pathogenic variants in the COL4A5, COL4A3 and COL4A4 genes beyond the classical Alport phenotype (haematuria, renal failure; family history of haematuria or renal failure) to include persistent proteinuria, steroid-resistant nephrotic syndrome, focal and segmental glomerulosclerosis (FSGS), familial IgA glomerulonephritis and end-stage kidney failure without an obvious cause. The meeting refined the ACMG criteria for variant assessment for the Alport genes (COL4A3-5). It identified 'mutational hotspots' (PM1) in the collagen IV α5, α3 and α4 chains including position 1 Glycine residues in the Gly-X-Y repeats in the intermediate collagenous domains; and Cysteine residues in the carboxy non-collagenous domain (PP3). It considered that 'well-established' functional assays (PS3, BS3) were still mainly research tools but sequencing and minigene assays were commonly used to confirm splicing variants. It was not possible to define the Minor Allele Frequency (MAF) threshold above which variants were considered Benign (BA1, BS1), because of the different modes of inheritances of Alport syndrome, and the occurrence of hypomorphic variants (often Glycine adjacent to a non-collagenous interruption) and local founder effects. Heterozygous COL4A3 and COL4A4 variants were common 'incidental' findings also present in normal reference databases. The recognition and interpretation of hypomorphic variants in the COL4A3-COL4A5 genes remains a challenge.

Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions.

Abstract: Bone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment.

Abstract: We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70-75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70-80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.

Environmental Phage-Based Cocktail and Antibiotic Combination Effects on Acinetobacter baumannii Biofilm in a Human Urine Model.

Abstract: The emergence of multidrug-resistant (MDR) bacterial infections poses a catastrophic threat to medicine. The development of phage-based therapy combined with antibiotics might be an advantageous weapon in the arms race between human and MDR bacteria. A cocktail composed of the MDR Acinetobacter baumannii infecting bacteriophages with high lytic activity was used in combination with antibiotics to destroy a bacterial biofilm in human urine. A. baumannii exhibited varying susceptibility to the host range of bacteriophages used in this study, ranging from 56% to 84%. This study demonstrated that bacteriophages could reduce biofilm biomass in a human urine model, and some of the antibiotics commonly used in the treatment of urinary tract infection (UTI) act synergistically with phage cocktails. Additionally, the combined treatment showed a significantly greater reduction of biofilm biomass and clearance of persister cells.

The Mechanism of Drug Nephrotoxicity and the Methods for Preventing Kidney Damage

Abstract: Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19–26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed.

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Abstract: Diabetes mellitus (DM) has become a vital societal problem as epidemiological studies demonstrate the increasing incidence of type 1 and type 2 diabetes. Lesions observed in the retina in the course of diabetes, referred to as diabetic retinopathy (DR), are caused by vascular abnormalities and are ischemic in nature. Vascular lesions in diabetes pertain to small vessels (microangiopathy) and involve precapillary arterioles, capillaries and small veins. Pericyte loss, thickening of the basement membrane, and damage and proliferation of endothelial cells are observed. Endothelial cells (monolayer squamous epithelium) form the smooth internal vascular lining indispensable for normal blood flow. Breaking its continuity initiates blood coagulation at that site. The endothelium controls the process of exchange of chemical substances (nutritional, regulatory, waste products) between blood and the retina, and blood cell passing through the vascular wall. Endothelial cells produce biologically active substances involved in blood coagulation, regulating vascular wall tension and stimulating neoangiogenesis. On the other hand, recent studies have demonstrated that diabetic retinopathy may be not only a microvascular disease, but is a result of neuroretinal degeneration. Neuroretinal degeneration appears structurally, as neural apoptosis of amacrine and Muller cells, reactive gliosis, ganglion cell layer/inner plexiform (GCL) thickness, retinal thickness, and retinal nerve fiber layer thickness, and a reduction of the neuroretinal rim in minimum rim width (MRW) and functionally as an abnormal electroretinogram (ERG), dark adaptation, contrast sensitivity, color vision, and microperimetric test. The findings in early stages of diabetic retinopathy may precede microvascular changes of this disease. Furthermore, the article's objective is to characterize the factors and mechanisms conducive to microvascular changes and neuroretinal apoptosis in diabetic retinopathy. Only when all the measures preventing vascular dysfunction are determined will the risk of complications in the course of diabetes be minimized.

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Abstract: Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

SPARTE Study: Normalization of Arterial Stiffness and Cardiovascular Events in Patients With Hypertension at Medium to Very High Risk.

Abstract: The SPARTE study (Strategy for Preventing cardiovascular and renal events based on ARTErial stiffness; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02617238) is a multicenter open-label randomized controlled trial with blinded end point evaluation, undertaken at 25 French research centers in university hospitals. Patients with primary hypertension were randomly assigned (1:1) to a therapeutic strategy targeting the normalization of carotid-femoral pulse wave velocity (PWV) measured every 6 months (PWV group, n=264) versus a classical therapeutic strategy only implementing the European Guidelines for Hypertension Treatment (conventional group, n=272). In the PWV group, the therapeutic strategy used preferably a combination of ACE (angiotensin-converting enzyme) inhibitor or angiotensin receptor blocker and calcium channel blockers, as well as maximal recommended doses of ACE inhibitors and angiotensin receptor blockers. The primary outcome was a combined end point including particularly stroke and coronary events. Secondary outcomes included the time-course changes in brachial office blood pressure (BP), ambulatory BP, PWV, and treatments. After a median follow-up of 48.3 months, there was no significant between-group difference in primary outcome (hazard ratio, 0.74 [95% CI, 0.40-1.38], P=0.35). In the PWV group, combinations of renin-angiotensin-system blockers and calcium channel blockers were prescribed at higher dosage (P=0.028), office and ambulatory systolic blood pressure and diastolic blood pressure decreased more (P<0.001 and P<0.01, respectively), and PWV increased less (P=0.0003) than in the conventional group. The SPARTE study lacked sufficient statistical power to demonstrate its primary outcome. However, it demonstrated that a PWV-driven treatment for hypertension enables to further reduce office and ambulatory systolic blood pressure and diastolic blood pressure and prevent vascular aging in patients with hypertension at medium-to-very-high risk, compared with strict application of guidelines.