Non-adherence to antihypertensive medication is the most important cause of uncontrolled blood pressure and is influenced by multiple interrelating factors. Understanding the complexity of medication ...non-adherence and its associated factors is important to determine intervention strategies. Therefore, a systematic review was performed aimed to identify factors associated with antihypertensive medication non-adherence. Different databases were searched for observational studies reporting on factors associated with non-adherence to antihypertensive medication. Titles, abstracts and full texts were reviewed by three researchers. Subsequently, the methodological quality of each study was assessed. Factors that were extracted from the included studies were categorised as factors with consistent or inconsistent evidence to put their potential importance into perspective. Forty-four studies were included. Higher co-payment, side effects and a poor patient-provider relationship were identified as factors with consistent evidence since consistent significant relationships were found for these factors whenever studied. The relationships between non-adherence and multiple other factors were inconsistent among the reviewed studies. However, some of these factors deserve some consideration. Since multiple potentially relevant factors were identified, patient-tailored interventions focussing on identifying and addressing patients' specific barriers to adherence are needed. Further research should clarify the influence of inconsistent factors on adherence and their potential to be addressed in interventions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The ...mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (
ApoE
−/−
Svep1
+/−
) compared to Svep1 wild-type mice
(ApoE
−/−
Svep1
+/+
) and
ApoE
−/−
Svep1
+/−
mice displayed elevated plaque neutrophil, Ly6C
high
monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in
ApoE
−/−
Svep1
+/−
mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (
CXCL1
) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in
ApoE
−/−
Svep1
+/−
mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial
CXCL1
expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
RATIONALE:Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise ...molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes.
OBJECTIVE:To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs.
METHODS AND RESULTS:We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors MIA3. The G allele of the lead risk single nucleotide polymorphism (SNP) rs67180937 was associated with lower VSMC MIA3 expression and lower proliferation. Lentivirus-mediated silencing of MIA3 (melanoma inhibitory activity protein 3) in VSMCs resulted in lower proliferation, consistent with human genetics findings. Furthermore, we observed a significant reduction of MIA3 protein in VSMCs in thin fibrous caps of late-stage atherosclerotic plaques compared to early fibroatheroma with thick and protective fibrous caps in mice and humans.
CONCLUSIONS:Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high MIA3 expression may promote atheroprotective VSMC phenotypic transitions, including increased proliferation, which is essential in the formation or maintenance of a protective fibrous cap.
Magnetic skyrmions in chiral magnets are nanoscale, topologically protected magnetization swirls that are promising candidates for spintronics memory carriers. Therefore, observing and manipulating ...the skyrmion state on the surface level of the materials are of great importance for future applications. Here, we report a controlled way of creating a multidomain skyrmion state near the surface of a Cu2OSeO3 single crystal, observed by soft resonant elastic X-ray scattering. This technique is an ideal tool to probe the magnetic order at the L 3 edge of 3d metal compounds giving an average depth sensitivity of ∼50 nm. The single-domain 6-fold-symmetric skyrmion lattice can be broken up into domains, overcoming the propagation directions imposed by the cubic anisotropy by applying the magnetic field in directions deviating from the major cubic axes. Our findings open the door to a new way to manipulate and engineer the skyrmion state locally on the surface or on the level of individual skyrmions, which will enable applications in the future.
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IJS, KILJ, NUK, PNG, UL, UM
Surgical site infections (SSI) are a serious complication in vascular surgery which may lead to severe morbidity and mortality. Staphylococcus aureus nasal carriage is associated with increased risk ...for development of SSIs in central vascular surgery. The risk for SSI can be reduced by perioperative eradication of S. aureus carriage in cardiothoracic and orthopedic surgery. This study analyzes the relation between S. aureus eradication therapy and SSI in a vascular surgery population.
A prospective cohort study was performed, including all patients undergoing vascular surgery between February 2013 and April 2015. Patients were screened for S. aureus nasal carriage and, when tested positive, were subsequently treated with eradication therapy. The presence of SSI was recorded based on criteria of the CDC. The control group consisted of a cohort of vascular surgery patients in 2010, who were screened, but received no treatment.
A total of 444 patients were screened. 104 nasal swabs were positive for S. aureus, these patients were included in the intervention group. 204 patients were screened in the 2010 cohort. 51 tested positive and were included in the control group. The incidence of S. aureus infection was 5 out of 51 (9.8%) in the control group versus 3 out of 104 in the eradication group (2.2%; 95% confidence interval 0.02-1.39; P = 0.13). A subgroup analysis showed that the incidence of S. aureus infection was 3 out of 23 (13.0%) in the control group in central reconstructive surgery versus 0 out of 44 in the intervention group (P = 0.074). The reduction of infection pressure by S. aureus was stronger than the reduction of infection pressure by other pathogens (exact maximum likelihood estimation; OR = 0.0724; 95% CI: 0.001-0.98; p = 0.0475).
S. aureus eradication therapy reduces the infection pressure of S. aureus, resulting in a reduction of SSIs caused by S. aureus.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Prevention of alloreactivity by rabbit anti-thymocyte globulins (rATG) may not only result from immunodepletion but also from the induction of T cells that control allogeneic immune ...responses. In the present prospective and controlled study, we investigated the effect of rATG on the frequency, function and phenotype of peripheral immunoregulatory CD4+ T cells in kidney transplant (KTx) patients. Methods. After transplantation, 16 patients received ATG-induction therapy and triple therapy consisting of tacrolimus, MMF and steroids. The control group (n = 18) received triple therapy only. By flow cytometry, T cells were analysed for CD25, FoxP3, CD127, CD45RO and CCR7. To study their suppressive capacities, CD25bright T cells were co-cultured with CD25−/dim effector T cells (Teff) in mixed lymphocyte reactions (MLR), stimulated with donor and third party (3P) antigens. Results. Pre-transplant levels of FoxP3+CD127−/low T cells were 6% of CD4+ T cells. One week post-ATG treatment, no measurable numbers of regulatory T cells were present (P < 0.01). After 4 weeks, the cell numbers of CD4+FoxP3+CD127−/low T cells slowly reappeared and thereafter remained low (P < 0.01). At 14 weeks, a significant shift towards the CD45RO+CCR7+ (central memory) phenotype within CD4+FoxP3+ T cells was observed (P < 0.01). At 26 weeks, the proliferative alloresponses of the PBMC and CD25−/dim Teff profoundly decreased compared to pre-transplant (P = 0.01 and P = 0.02 respectively), while the regulatory capacity of the CD25bright T cells, of which 90% consisted of FoxP3+CD127−/low T cells, remained unaffected. The CD25bright T cells suppressed the anti-donor (94%) and 3P responses (93%). Conclusion. Our findings show that rATG therapy does not spare peripheral immunoregulatory T cells in vivo, but after regeneration preserves their suppressive activity.
Sex and gender influence health and disease outcomes, therefore, doctors should be able to deliver gender-sensitive care. To train gender-sensitive doctors, relevant sex and gender differences have ...to be included in medical education. In order to develop appealing, relevant, and effective education for undergraduate medical students, education should be tailored to students' level and anticipated on their ideas and assumptions. Therefore, we wanted to answer the following research questions: 1. What do aspiring medical students want to learn about gender medicine?; 2. How would they like to learn about gender medicine?; and 3. What are their ideas and assumptions about sex and gender differences in health and disease?
We performed an explorative thematic document analysis of educational assignments made by successful applicants (n = 50) during the selection procedure of their entry into medical school. To test aspirants' capacity for self-directed learning, students were asked to formulate their own study plan after they watched a video that resembled a future practical experience (a consultation with a patient). As the content of this video was gender-sensitive, the assignments of the successful applicants gave us the unique opportunity to examine aspiring medical students' views about gender medicine.
Aspiring medical students were eager to start their training to become gender-sensitive doctors. They believed in better care for all patients and thought doctors should obtain gender competences during their medical training. Students preferred to start with acquiring basic biomedical knowledge about differences between men and women and continue their training by developing gender-sensitive communication skills in (simulated) practical settings. Students differed in their interpretation of the gender-sensitive video, some generalized potential differences to all men and all women. Teachers were considered as important role models in learning about gender medicine.
We advise medical schools to teach gender medicine from the beginning of medical school, by focusing on sex differences first and adding gender related themes later on in the curriculum. As students may interpret gender-sensitive information differently, structurally embedding reflection on gender medicine with gender competent teachers is necessary.
Background. Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Methods. Data were obtained from an observational cohort ...of 245 human immunodeficiency virus (HIV)–infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Results. Pillbox organizer use was estimated to improve adherence by 4.1%–4.5% and was associated with a decrease in viral load of 0.34–0.37 log10 copies/mL and a 14.2%–15.7% higher probability of achieving a viral load ⩽400 copies/mL (odds ratio, 1.8–1.9). All effect estimates were statistically significant. Conclusion. Pillbox organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of ∼$19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.
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BFBNIB, NUK, PNG, UL, UM, UPUK
To investigate the influence of age on the effectiveness and tolerance of antitumour necrosis factor alpha (TNFalpha) therapy in rheumatoid arthritis (RA).
730 patients of the Dutch Rheumatoid ...Arthritis Monitoring (DREAM) register were categorised into three groups according to their age at initiation of anti-TNFalpha therapy (<45, 45-65 and >65 years). Effectiveness of anti-TNFalpha therapy was primarily assessed by longitudinal analysis of the DAS28 during the first 12 months of treatment.
Improvement in disease activity and physical functioning was significantly less in elderly patients, correcting for relevant confounders. Elderly patients reached the EULAR categories of good responders and remission less often than younger patients. Drug survival, co-medication use and tolerance were comparable between the three age groups.
Anti-TNFalpha therapy significantly reduced disease activity in all age groups of patients; however, it appeared less effective in elderly compared with younger RA patients.
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