Abstract Background Tacrolimus is an established immunosuppressant used for the prevention and treatment of allograft rejection in solid organ transplantation. An immediate-release oral formulation ...of tacrolimus has been commercially available since 1994 that is administered orally BID. To improve the compliance and quality of life of transplant patients, a once-daily modified release (MR) formulation is an attractive option. However, to be successful, the drug of interest must be sufficiently well absorbed from the distal region of the gastrointestinal tract. Objective To facilitate the development of an MR formulation, we investigated the absorption of tacrolimus from different regions of the human gastrointestinal tract, proximal and distal small bowels, and ascending colon. Methods The study was performed as an open-label, randomized, 4-way crossover design in 6 healthy white male subjects. For each subject, 1 mg (2 mg/mL) of tacrolimus solution in polyethylene glycol 400 was administered to each location in the gastrointestinal tract via a site-specific radiolabeled delivery capsule, which can release tacrolimus solution at specific sites of the gastrointestinal tract. Real-time visualization of capsule location and tacrolimus release at each target site was performed by using γ-scintigraphy. Blood samples were collected to determine tacrolimus levels in the blood. The pharmacokinetic parameters Cmax , Tmax after the capsule activation, AUC0–24 , and mean residence time were determined from the concentration–time profiles. Results Ten healthy male subjects underwent dosing. Six subjects completed all 4 treatments. Three adverse events (mild headache n = 1, small amount of blood in stool n = 1, and mild syncopal episode n = 1) that were possibly study drug related were reported in 3 different subjects. Tacrolimus was absorbed from not only the small intestine but also from the colonic region of the gastrointestinal tract. Although AUC0–24 values revealed some site-specific absorption tendencies, the mean AUC0–24 values obtained were similar regardless of the location of tacrolimus release from the capsule. Conclusions Tacrolimus was absorbed from the duodenum to the colon in these male subjects, although differences were observed in the value of AUC0–24 , possibly due to variation in cytochrome P450 3A4 activity in the intestine. Although this study was conducted in small group of healthy fasting men, the present results indicate that tacrolimus is suitable for MR formulation development due to a wide absorption window throughout the intestine in humans.
To assess and compare the prevalence of medication nonadherence (MNA) (implementation and persistence) to immunosuppressants and co-medications in heart transplant recipients.
MNA prevalence was ...assessed using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (self-report) and compared using logistic regression in a 4-continent sample of 1397 heart transplant recipients from 36 heart transplant centers in 11 countries.
MNA was significantly (α = 0.05) higher to co-medications than to immunosuppressants (taking nonadherence: 23.9% vs 17.3%; odds ratio OR = 1.5; 95% CI, 1.30–1.73; drug holiday: 5.7% vs 1.9%; OR = 3.17; 95% CI, 2.13–4.73; dose alteration: 3.8% vs 1.6%; OR = 2.46; 95% CI, 1.49–4.06; and discontinuation: 2.6% vs 0.5%; OR = 5.15; 95% CI, 2.36–11.20).
The observed MNA necessitates adherence-enhancing interventions encompassing the entire post–heart transplant medication regimen. ClinicalTrials.gov identifier: NCT01608477.
A trustful relationship between transplant patients and their transplant team (interpersonal trust) is essential in order to achieve positive health outcomes and behaviors. We aimed to 1) explore ...variability of trust in transplant teams; 2) explore the association between the level of chronic illness management and trust; 3) investigate the relationship of trust on behavioral outcomes. A secondary data analysis of the BRIGHT study (ID: NCT01608477; https://clinicaltrials.gov/ct2/show/NCT01608477?id=NCT01608477&rank=1) was conducted, including multicenter data from 36 heart transplant centers from 11 countries across four different continents. A total of 1,397 heart transplant recipients and 100 clinicians were enrolled. Trust significantly varied among the transplant centers. Higher levels of chronic illness management were significantly associated with greater trust in the transplant team (patients: AOR= 1.85, 95% CI = 1.47-2.33,
< 0.001; clinicians: AOR = 1.35, 95% CI = 1.07-1.71,
= 0.012). Consultation time significantly moderated the relationship between chronic illness management levels and trust only when clinicians spent ≥30 min with patients. Trust was significantly associated with better diet adherence (OR = 1.34, 95%CI = 1.01-1.77,
= 0.040). Findings indicate the relevance of trust and chronic illness management in the transplant ecosystem to achieve improved transplant outcomes. Thus, further investment in re-engineering of transplant follow-up toward chronic illness management, and sufficient time for consultations is required.
Transplant recipients are chronically ill patients, who require lifelong follow-up to manage co-morbidities and prevent graft loss. This necessitates a system of care that is congruent with the ...Chronic Care Model. The eleven-item self-report Patient Assessment of Chronic Illness Care (PACIC) scale assesses whether chronic care is congruent with the Chronic Care Model, yet its validity for heart transplant patients has not been tested.
We tested the validity of the English version of the PACIC, and compared the similarity of the internal structure of the PACIC across English-speaking countries (USA, Canada, Australia and United Kingdom) and across six languages (French, German, Dutch, Spanish, Italian and Portuguese). This was done using data from the cross-sectional international BRIGHT study that included 1378 heart transplant patients from eleven countries across 4 continents. To test the validity of the instrument, confirmatory factor analyses to check the expected unidimensional internal structure, and relations to other variables, were performed.
Main analyses confirmed the validity of the English PACIC version for heart transplant patients. Exploratory analyses across English-speaking countries and languages also confirmed the single factorial dimension, except in Italian and Spanish.
This scale could help healthcare providers monitor level of chronic illness management and improve transplantation care.
Clinicaltrials.gov ID: NCT01608477, first patient enrolled in March 2012, registered retrospectively: May 30, 2012.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Health literacy (HL) is a major determinant of health outcomes; however, there are few studies exploring the role of HL among heart transplant recipients. The objectives of this study were to: (1) ...explore and compare the prevalence of inadequate HL among heart transplant recipients internationally; (2) determine the correlates of HL; and (3) assess the relationship between HL and health-related behaviors.
A secondary analysis was conducted using data of the 1,365 adult patients from the BRIGHT study, an international multicenter, cross-sectional study that surveyed heart transplant recipients across 11 countries and 4 continents. Using the Subjective Health Literacy Screener, inadequate HL was operationalized as being confident in filling out medical forms none/a little/some of the time (HL score of 0 to 2). Correlates of HL were determined using backward stepwise logistic regression. The relationship between HL and the health-related behaviors were examined using hierarchical logistic regression.
Overall, 33.1% of the heart transplant recipients had inadequate HL. Lower education level (adjusted odds ratio AOR 0.24, p < 0.001), unemployment (AOR 0.69, p = 0.012) and country (residing in Brazil, AOR 0.25, p < 0.001) were shown to be associated with inadequate HL. Heart transplant recipients with adequate HL had higher odds of engaging in sufficient physical activity (AOR 1.6, p = 0.016). HL was not significantly associated with the other health behaviors.
Clinicians should recognize that almost one third of heart transplant participants have inadequate health literacy. Furthermore, they should adopt communication strategies that could mitigate the potential negative impact of inadequate HL.
Introduction
Heart transplant (HTx) recipients need to follow a complex therapeutic regimen. We assessed the international prevalence and variability in nonadherence to six nonpharmacologic treatment ...components (physical activity, sun protection, diet, alcohol use, nonsmoking, and outpatient follow‐up visits).
Methods
We used self‐report data of 1397 adult HTx recipients from the 36‐HTx‐center, 11‐country, 4‐continent, cross‐sectional BRIGHT study (ClinicalTrials.gov ID: NCT01608477). The nonadherence definitions used were as follows: Physical activity: <3 times/wk 20 minutes’ vigorous activity, <5 times/wk 30 minutes’ moderate activity, or <5 times/wk a combination of either intensity; Sun protection: not “always” applying any sun protection; Diet: not “often” or “always” following recommended diet(s); Alcohol use: >1 alcoholic drink/d (women) or >2 drinks/d (men); Smoking: current smokers or stopped <1 year before; Follow‐up visits: missing ≥1 of the last 5 outpatient follow‐up visits. Overall prevalence figures were adjusted to avoid over‐ or underrepresentation of countries. Between‐country variability was assessed within each treatment component via chi‐square testing.
Results
The adjusted study‐wide nonadherence prevalence figures were as follows: 47.8% for physical activity (95% CI 45.2‐50.5), 39.9% for sun protection (95% CI 37.3‐42.5), 38.2% for diet recommendations (95% CI 35.1‐41.3), 22.9% for alcohol consumption (95% CI 20.8‐25.1), 7.4% for smoking cessation (95% CI 6.1‐8.7), and 5.7% for follow‐up visits (95% CI 4.6‐6.9). Significant variability was observed between countries in all treatment components except follow‐up visits.
Conclusion
Nonadherence to the post‐HTx nonpharmacologic treatment regimen is prevalent and shows significant variability internationally, suggesting a need for tailored adherence‐enhancing interventions.
Background:
As medication non-adherence is a major risk factor for poor post-transplant outcomes, we explored how adherence is assessed, enhanced and integrated across the transplant continuum.
Aim:
...The aim of this study was to study practice patterns regarding pre- and post-transplant medication adherence assessment and interventions in international heart transplant centres.
Methods:
We used data from the Building Research Initiative Group: chronic illness management and adherence in heart transplantation (BRIGHT) study, a cross-sectional study conducted in 36 heart transplant centres in 11 countries. On a 27-item questionnaire, 100 clinicians (range one to five per centre) reported their practice patterns regarding adherence assessment and intervention strategies pre-transplant, immediately post-transplant, less than one year, and one or more year post-transplant. Educational/cognitive, counselling/behavioural and psychosocial/affective strategies were assessed. Clinicians’ responses (intervention present vs. absent; or incongruence in reporting intervention) were aggregated at the centre level.
Results:
The adherence assessment method most commonly used along the transplant continuum was questioning patients (range 75–88.9%). Pre-transplant, all three categories of intervention strategy were applied. Providing reading materials (82.9%) or instructions (68.6%), involving family or support persons in education (91.4%), and establishing partnership (91.4%) were used most frequently. Post-transplant, strategies closely resembled those employed pre-transplant. Training patients (during recovery) and cueing were more often applied during hospitalisation (74.3%). After the first year post-transplant, except for motivational interviewing (25.7–28.6%), the number of strategies decreased.
Conclusions:
Across the transplant continuum, diverse adherence interventions are implemented; however, post-transplant, the frequency of adherence interventions decreases. Therefore, increased investment is necessary in long-term adherence interventions.
Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 ...loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P=0.04), Arg735Trp (OR=17.4, 95% CI=2.2-136; P=0.0003), and Ser1619Arg (OR=5.2, 95% CI=1.0-25; P=0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cet article examine les spécificités de la politique antillaise néerlandaise ainsi que le niveau d’éducation des femmes et leur insertion dans la société civile, en lien avec l’émergence de ...mouvements de femmes à Aruba et Curaçao. Plusieurs de ces mouvements (1940-début des années 1990) sont ici analysés dans le but de comprendre ce qui rend les stratégies militantes féminines efficaces. Cet article avance l’hypothèse que leur réussite dépend des multiples ajustements qui sont faits à un environnement particulier. Bien que la réussite de tels mouvements puisse être attribuée à des forces intellectuelles actives et à une compréhension approfondie des changements politiques, en fin de compte, c’est moins la connaissance, l’idéologie et la stratégie qui comptent que la capacité à agir au bon moment, à s’organiser et à coopérer, dans le but de surfer sur la vague du progrès.
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