bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PHARMACISTS’ AND MOBILE APPLICATIONS’ ROLE IN THE TREATMENT OF HYPERTENSION
Authors: Tarnovski Lorka , Frkanec Stjepan , Frkanec Stjepan , Katic Luka , Strbac Tea , Lovakovic Josip , Susnjara Petar , Rasic Fran , Sekulic Mislav , Josipovic Josipa , Begic Zvonimir , Barisic Klara , Prelevic Vladimir , Radunovic Danilo , Jelakovic Ana , Gellineo Lana , Domislovic Marija , Velkovski Olgica , Dapic Kresimir , Jelakovic Bojan 
Published: June 2022

Objective:
Poor adherence is the main reason for inadequate blood pressure control. Pharmacists are highly accessible healthcare professionals, and it has been reported that community pharmacist-led interventions improved patients’ BP control and outcomes. Some authors reported on the beneficial effects of mobile applications on better drug adherence. The aim of this study was to identify subjects in the general population who may benefit from such interventions.

Design and method:
A total of 1228 subjects enrolled in the EHUH 2 study (a random sample, nationwide survey) and 424 participants of the Hunt on the Silent Killer (HSK) (opportunistic screening on islands) were included in this analyses. The same questionnaire was applied containing questions about health issues, therapy, habits, and opinion on pharmacists’ and mobile applications’ (MA) role in hypertension treatment.

Results:
The binomial logistic regression analysis showed a significant model when comparing positive and negative answers for the following: the participants were more likely to be in favour of pharmacists’ role if they had a positive history of angina pectoris ( = 1.333, p = 0.016), diabetes mellitus ( = 1.125, p < 0.001), dyslipidemia ( = 1.326, p < 0.001), or being treated for hypertension ( = 1.326, p < 0.001) in the HSK, and in the EHUH 2 study if they suffered a stroke (100%). Socio-demographic factors had no impact on the pharmacists’ role in the general population. However, at islands significantly enhanced negative responses in case of lower household income (35%), married state (29%) and employed subjects (17%) were observed. The participants were more likely to be in favour of MA if they had a positive history of hypertension, have higher income and were married. Interestingly, the history of cardiovascular diseases indicated more negative responses.

Conclusions:
The participants were generally in favour of MA, which may confirm the need to digitalise the healthcare system, but it was more enhanced in participants with a higher socio-demographic status. Pharmacists-led interventions (lifestyle support and adherence increasing programs) have to be individualized.
ATHERO: AN OBSERVATIONAL CROSS-SECTIONAL EVALUATION OF ATHEROSCLEROTIC RISK CONTROL IN THE BELGIAN POPULATION TREATED WITH AT LEAST ONE ANTIHYPERTENSIVE AND ONE LIPID-LOWERING DRUG
Authors: Rietzschel Ernst , Descamps Olivier , De Sutter Johan , Philips Jean-Christophe , van de Borne Philippe , Mertens Ann , Verhaegen Ann , Wallemacq Caroline , Demeure Fabian , De Buyzere Marc 
Published: June 2022

Objective:
To evaluate real-life lipid and blood pressure (BP) control in a contemporary Belgian population sample treated with at least one lipid-lowering and one antihypertensive drug.

Design and method:
Data was collected through GP questionnaires on 2337 subjects (ATHERO STUDY).

Results:
A complete set of relevant clinical variables was available for 1706 subjects (61.5% men; mean age 67.9 ± 10.9 years; mean BMI 28.4 ± 4.9 kg/m2), in which CVD, CAD, DM and renal insufficiency were reported respectively in 34.0%; 22.2%, 37.5% and 6.6% of cases. Based on the 2016 EAS/ESC guidelines for the management of dyslipidemias, 68.8% of subjects were classified as very high risk (VHR) and 10.9% as high-risk (HR). Despite the majority (almost 70%) taking > 1 antihypertensive drug, BP was uncontrolled in 44.0% (using the 140/90 mmHg threshold), without clear differences in control across risk strata. Treatment targets from the 2016 LDL-cholesterol guidelines were met in only 24.4% of VHR and 45.7% of HR subjects. For the new LDL-cholesterol targets 2019 ESC/EAS guidelines for the management of dyslipidemias (which came after the data collection) this would be 10.1% and 11.7%% respectively. GP’s estimated adequate BP control in 69.2% and LDL-cholesterol control in 63.4% of cases. Combined BP and LDL-cholesterol control was achieved in 16.1% of VHR and 26.9% of HR subjects. In the VHR group there was a clear gender disparity (11.7% of women compared to 18.6% of men) in achieving adequate combined control. More striking, combined control in those VHR subjects with a clinical condition (1040/1174 subjects) was 17.9% whilst in those with VHR due to risk factor combinations this was only 2.2%. Use of combination lipid-lowering and antihypertensive drug combinations was low (1.8%) whilst 66.5% of subjects were potential candidates.

Conclusions:
In GP practices, target achievement was very low for BP and even more so for LDL-cholesterol prevention targets amongst VHR patients, especially in those associated to risk factor combinations rather than more easily recognizable clinical conditions. There was a clear disparity between GPs’ estimates of risk factor control/target achievement and real-life figures in GP practices.
MAIN FACTORS THAT DETERMINE ADHERENCE TO PHARMACOLOGICAL TREATMENT IN HYPERTENSIVE PATIENTS. SYSTEMATIC REVIEW
Authors: Montealegre Leslie , Amador Eulalia , Pulido Tammy , Cabrera Carlos , Rivera Alma , Rebolledo Roberto 
Published: June 2022

Objective:
To determine through the systematic review which are the factors that determine adherence to pharmacological treatment in hypertensive patients.

Design and method:
Systematic review with the terms DeCS and MeSH: Medication adherence, treatment adherence, medication compliance, hypertension, hypertensive patients, factors associated, in different databases. We included cohort studies and systematic review studies. Articles were assessed at risk of bias, with the help of critical and methodological guidelines STROBE and Prism, and level of evidence (CEBM)

Results:
The factors associated with pharmacological adherence were: age greater than 45 years, greater knowledge of the disease, treatment and therapeutic adherence, high levels of self-efficacy and / or recognize low level of barriers, the factors associated with pharmacological non-adherence were: lower economic income, age less than 35 years, difficulty accessing health care, not having adequate follow-up of the disease, prescription of more than two types of antihypertensive drugs, diagnosis of hypertension less than 5 years, deficiency of knowledge of the disease, treatment and adherence, not trusting in the treatment or using alternative, complementary or traditional medicine.

Conclusions:
High blood pressure is a global public health problem associated with an increased risk of developing cardiovascular disease, which requires lifelong treatment. The main consequence of suffering from hypertension is the development of complications that deteriorate the patient’s quality of life and inevitably cause death. Therefore, adherence to pharmacological treatment is essential in the treatment of chronic diseases, particularly hypertension, the identification and understanding of the factors that modify adherence to treatment is key to adapt a better control of hypertensive patients. The findings of existing studies should be interpreted with caution due to their methodological limitations. The results of this study confirm that pharmacological adherence to the treatment of hypertension is due to a multiplicity of factors, such as: socioeconomic factors, related to access to health systems, therapy, related to the condition and the patient. Since some of these factors are modifiable, they may be the focus of interventions to increase medication adherence.
RESISTANT HYPERTENSION PATIENTS’ PERSPECTIVES ABOUT AN AEROBIC EXERCISE PROGRAM: INSIGHTS FROM THE ENRICH TRIAL
Authors: Lopes Susana , Diniz Filipa , Oliveira José , Mesquita-Bastos José , Polónia Jorge , Alves Alberto J. , Ribeiro Fernando , Figueiredo Daniela 
Published: June 2022

Objective:
Aerobic exercise training programs decrease blood pressure in patients with resistant hypertension. However, patients’ experiences regarding exercise training participation are often undervalued. The aim of this study is to explore the lived experiences of patients with resistant hypertension who participated in a 12-week moderate intensity aerobic exercise training program.

Design and method:
An exploratory qualitative study was conducted with twenty patients (11 males and 9 females) with resistant hypertension, after the exercise program. Participants’ mean age was 58.9 ± 8.9 years and were taking an average of 4.7 ± 0.9 antihypertensive medications. Focus group interviews were performed to explore participants’ perspectives. The interviews were video-recorded, transcribed verbatim, and submitted to thematic analysis.

Results:
Five main themes have emerged from interviews’ analyses: 1) impacts of participating in the exercise program; 2) facilitators of adherence to exercise; 3) perceived barriers; 4) perception of the program structure; and 5) global satisfaction with the exercise training program.
Overall positive benefits were reported regarding emotional and physical well-being, associated with a decrease in daily life stress and irritability alongside a decrease in blood pressure. Adherence to the physical activity program was facilitated by the commitment to attend the training sessions, different schedule options and the professional and individualized supervision. Participants referred to lack of motivation, absence of company, physical health limitations and difficulty in conciliating schedules as barriers to the maintenance of exercise training.

Conclusions:
The perceived benefits by the participants are important indicators of adherence and maintenance of exercise training, despite the perceived barriers. This study has an innovative approach by focusing on the participants’ perception analysis, going beyond quantitative clinical data, and providing important insights to increase future participants’ adherence to exercise training programs.
GLOBAL BURDEN, REGIONAL DIFFERENCES, TRENDS, AND HEALTH CONSEQUENCES OF MEDICATION NON-ADHERENCE IN PATIENTS WITH HYPERTENSION DURING 2010-2020: A SYSTEMATIC REVIEW AND META-ANALYS
Authors: Lee Eric Kam-Pui , Poon Paul , Bo Yacong , Zhu Meng-Ting , Yu Chun-Pong , Ngai Alfonse Ch , Wong Martin Cs , Wong Samuel Ys 
Published: June 2022

Objective:
Non-adherence to anti-hypertensive medications (anti-HT non-adherence) is the leading cause of poor blood pressure (BP) control, and thereby cardiovascular diseases and mortality worldwide. This study aims to investigate the global epidemiology of anti-HT non-adherence.

Design and method:
This study comprises a systematic review and meta-analysis investigating global prevalence, regional differences, and trends of anti-HT non-adherence in 2010–2020. Multiple medical databases and clinicaltrial.gov were searched for articles with a cut-off of December 2020. Observational studies reporting the proportion of patients with anti-HT non-adherence were included. The proportion of non-adherence, publication year, year of first recruitment (for trend analysis), country, and health outcomes due to anti-HT non-adherence were extracted. Two independent reviewers conducted abstract and full text screening, classified countries according to levels of income and locations and extracted data. Meta-analyses were conducted using a random effect model and trends of prevalence were analysed using meta-regression.

Results:
A total of 161 studies, including more than 27 million participants were included. The global prevalence of anti-HT non-adherence was 43% (95%CI: 40–45%, I2: 99·98%, p < 0·001). Non-adherence was more prevalent in low-to-middle-income countries than in high-income countries (47% vs. 38%, meta-regression p = 0·002), and in non-Western countries than in Western countries (46% vs. 36%, p = 0·002). No significant trend in prevalence was detected during 2010–2020. Patients with anti-HT non-adherence had suboptimal BP control (OR 2·15, 95%CI: 1·84–2·5, I2: 97·4%, p < 0·001), complications from HT (OR 2·08, 95%CI: 0·99–4.35, I2: 94·2%, p < 0.001), all-cause hospitalisation (OR 1·38, 95%CI: 1·35–1·41, I2: 0, p = 0·64), and all-cause mortality (OR 1·38, 95%CI: 1·35–1·41, I2: 0, p = 0·509).

Conclusions:
While a high prevalence of anti-HT non-adherence was detected worldwide, a higher prevalence was detected in low-to-middle-income and non-Western countries. Interventions are urgently required, especially in these regions. Current evidence is limited by high heterogeneity.
IMPLICATIONS OF CYP2D6 POLYMORPHISMS FOR THERAPEUTIC DRUG MONITORING IN PATIENTS WITH HYPERTENSION
Authors: Halvorsen Lene Vernås , Gognstad Stine , Søraas Camilla Lund , Ågnes Camilla , Hjørnholm Ulla , Kjær Vibeke Norheim , Svarstad Anja Camilla , Bergland Ola Undrum , Brobak Karl Marius , Aune Arleen , Olsen Eirik , Solbu Marit D. , Gerdts Eva , Mo Rune , Fadl Elmula Fadl Elmula M. , Rostrup Morten , Kjeldsen Sverre E. , Tuv Silja Skogstad , Høieggen Aud , Larstorp Anne Cecilie K. , Opdal Mimi Stokke 
Published: June 2022

Objective:
When using therapeutic drug monitoring for evaluating non-adherence, serum concentrations of drugs are related to the actual intake, but also to pharmacokinetic variability. We aimed to map CYP2D6 polymorphisms in treated hypertensive patients and assess implications for a previous classification of adherence.
Metoprolol is predominantly metabolized by CYP2D6, and is the most commonly prescribed beta-blocker in our population. Reduced metabolism can lead to increased concentrations of this drug, potentially causing more side effects and erroneous evaluation of adherence.

Design and method:
In a multicenter study we mapped CYP2D6 polymorphisms retrospectively in 331 patients being prescribed at least 2 antihypertensive agents, already reported as adherent or non-adherent based on serum concentrations of antihypertensive drugs by mass-spectrometry (UPLC-MS/MS).
The CYP2D6 panel included the non-functional variants (null) 2D6*3, 2D6*4, 2D6*5, 2D6*6, 2D6*13 and 2D6*68, and the reduced-functional variants (red) 2D6*9, 2D6*10 and 2D6*41. 2D6*2 or absence of the assayed variant alleles was interpreted as 2D6*1 (wild-type).
Patients with *null/*null and absent enzyme activity were classified as poor metabolizers, and patients with *null/*wild-type or *null/*red and varied degree of reduced enzyme activity as intermediate metabolizers. Normal metabolizers included homozygote wildtype and *wildtype/*red. Patients with duplications of functional alleles, leading to increased enzyme activity, were classified as ultra-rapid metabolizers.

Results:
Based on genotype, 117 patients (35.3%) were intermediate-, 21 (6.3%) were poor- and 3 (0.9%) were ultra-rapid metabolizers, comparable to the European reference population. The low frequency of ultra-rapid metabolizers did not affect the classification of non-adherence. Serum concentrations of metoprolol were related to the CYP2D6 genotype. Some (perhaps 5–10%) non-adherent patients with absent or severely reduced enzyme activity may have been misclassified as adherent; with a higher serum concentration of metoprolol due to poor metabolism rather than excellent adherence.

Conclusions: In 331 hypertensive patients with a normal distribution of CYP2D6 polymorphisms, the genotype seemed to influence the serum concentration of metoprolol, but did not affect the classification of non-adherence. However, perhaps 5–10% of the non-adherent patients with reduced metabolism may have been misclassified as adherent.
SYSTOLIC BLOOD PRESSURE, FRAILTY, AND ALL-CAUSE MORTALITY IN COMMUNITY-DWELLING OLDER ADULTS: FINDINGS FROM THE CHINESE LONGITUDINAL HEALTHY LONGEVITY SURVEY 2002-2014
Authors: Chaolei Chen , Liu Lin , Huang Yuqing , Feng Yingqing 
Published: June 2022

Objective:
Although convincing evidence on blood pressure (BP) targets in older adults is increasing, data of individual BP management in this group is lacking, especially in frail subjects. We aimed to investigate whether frailty modifies the association between systolic blood pressure (SBP) and all-cause mortality in community-dwelling older adults.

Design and method:
This study included participants aged 65 years or older from the Chinese Longitudinal Healthy Longevity Survey 2002–2014 and followed up to 2018. They were divided into two groups according to a frailty index based on the accumulation of 44-items deficits. The association between SBP and mortality was analyzed using Cox proportional hazards models adjusted for age, sex, marital status, education, residence, economic income, current smoking, current alcohol consumption, BMI, DBP, cognitive impairment, hypertension, diabetes, cardiovascular disease, stroke and other cerebrovascular diseases, respiratory disease, and cancer.

Results:
Among 18,503 participants included, 75.2% of them were 80y or older, and 42.2% were frail. The median follow-up time was 42.7 months, detecting 15,901 (85.9%) deaths. We identified 7808 (42.2%, 7533 deaths) frail participants (mean frailty index = 0.33). Effect modification by frailty was detected. Among frail participants, a U-shaped association was found with hazard ratios of 1.16 (95% CI, 1.02–1.32) for SBP < 100 mmHg, and 1.11 (95% CI, 1.00–1.24) for SBP 150 mmHg or higher compared with SBP 120–130 mmHg. For non-frail older adults, a tendency toward higher risk among those with SBP 130 mmHg or higher was observed.

Conclusions:
Our results suggest the presence of effect modification by frailty indicating a possible negative effect for elevated SBP in non-frail older adults and a U-shaped relationship of SBP in frail older adults with respect to all-cause mortality even after adjusting for diastolic blood pressure.
EFFECTIVENESS AND TOLERABILITY OF BISOPROLOL/PERINDOPRIL SINGLE-PILL COMBINATION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE AND CONCOMITANT HYPERTENSION WHO HAD A HISTORY OF MIOCARDIAL INFARCTION
Authors: Burtsev Yuriy , Boytsov Sergey , Karpov Yuriy , Khomitskaya Yunona 
Published: June 2022

Objective:
To evaluate effectiveness and tolerability of bisoprolol/perindopril single-pill combination (Bis/Per SPC) in the subgroup with stable coronary artery disease (CAD) and concomitant hypertension (HTN) and a history of myocardial infarction (MI)

Design and method:
STYLE (NCT03730116) was a 3-month, multicenter, open-label, uncontrolled observational study conducted in Russia. Stable CAD patients (n = 1892) comorbid with HTN and treated with Bis/Per SPC were included from November 2018 to January 2019. Data were collected at 3 visits: V1 (inclusion visit), V2, V3 (1, 3 months). In this post-hoc analysis, the antihypertensive effectiveness of Bis/ Per SPC in the subgroup with a history of MI was assessed by mean change in systolic (SBP) and diastolic blood pressure (DBP) and antianginal effectiveness - by mean changes in number of angina attacks and short acting nitrates (SAN) intake. Treatment tolerability was assessed by investigators as excellent, good, or acceptable.

Results:
Subanalisis included 495 patients (26.2%) with a history of MI. At baseline (BL), mean age was 62.9 ± 8.5 years, 39.0% (n = 193) were women, mean SBP and DBP were 155.5 ± 16.2 mmHg and 92.1 ± 10.3 mmHg, respectively and mean heart rate (HR) was 80.2 ± 10.3 bpm.
By V3, mean SBP/DBP significantly decreased by 29.6 ± 15.2/15.5 ± 10.0 mmHg respectively (p < 0.0001 for both) and 86.9% (n = 430) of patients achieved target BP < 140/90 mmHg. Mean HR decreased by 12.1 ± 8.5 bpm after 1 month and by 16.1 ± 9.6 bpm after 3 months (p < 0.0001 for both) and 27.3% (n = 135) of patients reached target level of HR (55–60 bpm). The proportion of patients who achieved target BP (<140/90 mmHg) with HR < 60 bpm at V3 was 27,5 % (131 of 476). The number of angina attacks per week and intake of SAN decreased from 5.2 ± 14.5 and 5.0 ± 4.9 (at V1) to 0.8 ± 1.7 and 1.3 ± 1.7 (at V3), respectively (p < 0.0001 for both). 97% of investigators rated tolerability of SPC as excellent or good at V3.

Conclusions:
In stable CAD patients with HTN and a history of MI treated with Bis/Per SPC for 3 months, significant improvement in BP and HR control, reduced angina attacks and SAN intake were observed, and treatment was well tolerated.
Exploring Surgeons’, Nurses’, and Patients’ Information Seeking Behavior on Medical Innovations
Authors: Whyte Stephen , Bray Laura , Chan Ho Fai , Chan Raymond J. , Hunt Jeremy , Peltz Tim S. , Dulleck Uwe , Hutmacher Dietmar W. 
Published: June 2022

Objectives:
To explore information seeking behavior on medical innovations.

Background:
While autologous and alloplastic options for breast reconstruction are well established, it is the advent of the combination of 3D printing technology and the biocompatible nature of a highly porous biodegradable implants that offers new treatment options for the future. While this type of prosthesis is not yet clinically available understanding how patients, surgeons, and nurses take up new medical innovations is of critical importance for efficient healthcare provision.

Materials and Methods:
Using the largest ever combined sample of breast cancer patients (n = 689), specialist surgeons (n = 53), and breast care nurses (n = 101), we explore participants preference for a new surgical treatment concept rooted in 3D printed and biodegradable implant technologies in the context of breast reconstruction.

Results:
We find that patients overwhelmingly favor information from a successful patient of the proposed new technology when considering transitioning. Surgeons and nurses instead favor regulatory body advice, peer-reviewed journals, and witnessing the procedure performed (either in person or online). But while 1 in 4 nurses nominated talking to a successful patient as an information source, not a single surgeon chose the same. Our multinomial logit analysis exploring patient preference (controlling for individual differences) showed statistically significant results for both the type of surgical treatment and choice to undergo reconstruction. Women who underwent a type of mastectomy procedure (compared with lumpectomy patients) were more likely to choose a former patient than a surgeon for seeking information relating to a new breast implant technology. Further, women who chose to undergo a reconstruction procedure, compared with those who did not, where more likely to prefer a surgeon for information relating to a new breast implant technology, rather than a successful patient. For medical professionals, we find no statistically significant relationship between medical professionals’ preference and their age, nor the number of other medical professionals they work with daily, nor the average number of breast procedures performed in their practice on a weekly basis.

Conclusions:
As our findings show large variation exists (both within our patient group and compared with medical professionals) in where individuals favor information on new medical innovations, future behavioral research is warranted.