Implementation of an innovative health service a "real-world" diffusion study

BACKGROUND: Although reporting on the healthcare-setting level of continuance or discontinuance of an intervention once a trial is completed has been recommended, such "real-world" diffusion studies are rare. The present example was made possible by funding to explore opportunities for post-trial implementation of an innovative health counseling intervention for cardiovascular prevention in The Netherlands. METHODS: Between 2001 and 2004, in a longitudinal case study, we compared two healthcare settings: a cardiology outpatient clinic and general practices. Rogers' diffusion of innovations theory served as the theoretical background. Information was extracted from minutes of meetings and informal conversations with health counselors, and checked by the project manager. Additional data were collected from physicians with a short questionnaire. RESULTS: Implementation of the health counseling intervention was successful in the cardiology outpatient clinic, but was unsuccessful in the general practices. Success was related to a centralized diffusion system, stronger "change agent" efforts, avoidance of post-trial interruption of service delivery, easily achievable "reinventions," and positive physician perceptions of the service (i.e., not complex and compatible with current practice routines). Support came from changes in the organization of care that created opportunities for, instead of competition with, the innovative service. However, coincidental events may also have played a part. CONCLUSIONS: Our findings confirm the importance of most theoretically predicted individual and organizational diffusion variables. This implies that the implementation of innovative healthcare services requires attention at both levels.     

Preoperative supplementation with a carbohydrate mixture decreases organ dysfunction-associated risk factors

BACKGROUND & AIMS: Recently, both asymmetrical dimethylarginine and IL-6 have been suggested to be associated with the induction and severity of single and multiple organ dysfunction. The aims of the present study were to elucidate if these factors were increased in an ischemia reperfusion (IR) model and whether pre-operative carbohydrate supplementation can reduce the risk factors along with the IR injury. METHODS: One group of male Wistar rats was fasted for 16 h (water ad libitum) prior to clamping the superior mesenteric artery (IR fasted n=14). A second group had ad libitum access to a carbohydrate solution prior to clamping (IR fasted CHO group n=11). Sham-fasted animals, which only received laparotomy and no clamping, served as controls (n=4). RESULTS: Plasma urea and ALAT activity were both increased in the IR fasted animals when compared to the sham rats (P=0.007 and P<0.02, respectively). Furthermore, it was shown that IR fasted rats had increased ADMA and IL-6 concentration in plasma when compared to sham animals (P<0.02). Moreover, the GSH level in lung was significantly decreased in the IR fasted animals (P=0.014). IR CHO supplemented showed no significant increase of ALAT activity and decrease of lung GSH. Furthermore, significantly lower plasma urea, ADMA and IL-6 concentration was seen in the IR CHO supplemented group when compared to the IR fasted rats (P=0.028, P<0.01 and P<0.02, respectively). The liver glycogen concentration in IR fasted rats was 48% of that IR rats supplemented the carbohydrate mixture. CONCLUSION: The present rat intestinal ischemia reperfusion model not only induces organ injury indicated by the classical parameters such as plasma urea and ALAT activity, but also increased plasma IL-6 and ADMA and decreased lung GSH concentration in IR fasted rats. Pre-operative supplementation with the carbohydrate mixture significantly lowered the plasma urea, IL-6 and ADMA concentrations and maintained lung GSH concentration. This indicates that pre-operative carbohydrate supplementation reduces post-operative organ injury.     

Broad phenotypic variability in a single pedigree with a novel 1410delC mutation in the PST domain of the PAX6 gene

The PAX6 mutation present in an individual with aniridia was determined and phenotypic features of immediate relatives carrying the same mutation investigated. Mutation analysis revealed a novel single base deletion 1410delC in the PAX6 gene in ten affected individuals. Clinical features ranged from total aniridia to very mild anterior segment findings. Other findings included partial aniridia, iris stromal hypoplasia, keratitis, cataract, glaucoma, optic disc anomalies and foveal hypoplasia. It appears that independent modifying factors may underlie the variability of the different phenotypic features of the PAX6 mutation.     

Phox2B mutations and the Delta-Notch pathway in neuroblastoma

We recently identified six neuroblastoma patients with constitutional or tumor-specific mutations in the homeobox gene Phox2B. Phox2B controls part of the differentiation program of the sympathetic nervous system (SNS). Mice with a homozygous inactivation of Phox2B fail in the proper differentiation of the chromaffin lineage of the SNS. Phox2B regulates HASH1 which can control expression of genes of the Delta-Notch pathway. We previously showed that a subset of neuroblastoma cell lines highly expresses Delta-like 1 (Dlk1), which is a marker for the chromaffin lineage of the SNS. Notch3 is expressed in another subset of neuroblastoma cell lines and marks tumors from an alternative differentiation lineage. Phox2B is also related to the TrkA differentiation pathway in neuroblastoma. Here we will review the role of Phox2B in differentiation programs of the SNS and in neuroblastoma pathogenesis.     

Biological effects of TrkA and TrkB receptor signaling in neuroblastoma

The Trk family consists of three receptor tyrosine kinases, each of which can be activated by one or more of four neurotrophins-NGF, BDNF, NT3 and NT4. Neurotrophins mediate their multiple effects through a number of distinct intracellular signaling cascades regulating such diverse biological responses as cell survival, proliferation and differentiation in normal and neoplastic neuronal cells. Expression of Trk receptors also plays an important role in the biology and clinical behavior of neuroblastomas. High expression of TrkA is present in neuroblastomas with favorable biological features and highly correlated with patient survival, whereas TrkB is mainly expressed on unfavorable, aggressive neuroblastomas. This short review discusses recent data on the biological roles of TrkA and TrkB signaling in neuroblastoma.     

Carbohydrate supplementation before operation retains intestinal barrier function and lowers bacterial translocation in a rat model of major abdominal surgery

BACKGROUND: Overnight fasting of rats augments the susceptibility of the small intestine to ischemia-reperfusion damage. Feeding before surgery may improve injuries to distant organs that were induced by ischemia-reperfusion. The present study tested the hypothesis that one of the food constituents, namely carbohydrates, may be responsible for the protective effect of preoperative feeding on postoperative organ dysfunction. METHODS: Male Wistar rats were fed ad libitum for 5 d and had either free access to water or free access to a carbohydrate drink and water. Then they were fasted for 16 h and access remained to either water or a carbohydrate drink and water. Following this, the arteria mesenterica superior was clamped for 60 min followed by 180 min of reperfusion. Subsequently, the intestinal permeability of stripped ileum was determined by measuring the mucosal to serosal flux in Ussing chambers. For assessment of bacterial content, organs were aseptically removed and assessed for bacterial content by culture under anaerobic conditions. RESULTS: Preoperative supplementation with carbohydrates resulted in a better maintenance of intestinal barrier function when compared with water supplemented animals. Moreover, carbohydrate supplementation resulted in a reduction in the ischemiareperfusion-induced increase in bacterial content of the liver, kidney, and mesenteric lymph nodes. CONCLUSIONS: Preoperative intake of carbohydrates by rats retains both the intestinal barrier function and prevents translocation of bacteria to distant organs.     

Antibody Avidity and Immunoglobulin G Isotype Distribution following Immunization with a Monovalent Meningococcal B Outer Membrane Vesicle Vaccine

The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.     

Effects of a brief cardiovascular prevention program by a health advisor in primary care; the 'Hartslag Limburg' project, a cluster randomized trial

Objective

To determine in primary care patients at high risk for a cardiovascular event, the effects on biomedical risk factors for and incidence of cardiovascular events, of a brief cardiovascular prevention program executed by a health advisor.

Method

Design: cluster randomized controlled trial with 1275 patients (24 general practices) in and around Maastricht, the Netherlands (1999–2004).Intervention: health advisors were to complete computerized cardiovascular risk profiles, provide multi-factorial tailored health education and advice, and communicate with GP's to optimize treatment.Outcome: differences in changes in risk factors between baseline and follow up at 6, 18, and 36 months and incidence of cardiovascular events at 36 months.

Results

Process: Because of logistic reasons risk profiles were put on paper instead of in the computerized patient files. On average patients attended 2.3 counseling sessions. Interaction with GPs was less productive than expected. Outcome: Effect after six months on BMI (− 0.20 kg/m² (95% CI − 0.38 to − 0.01, p = 0.039), Cohen's d: −0.18), and after 18 months on HDL-cholesterol (+ 0.05 mmol/l (95% CI + 0.01 to + 0.09, p = 0.014), Cohen's d: 0.14). No other (subgroup) effects were found.

Conclusion

Given the lack of clinically meaningful effects, implementation of this intervention in its present form is not justified.     

Pseudomonas bronchopulmonary infections in a palliative care setting

Blood stream infections and pneumonia caused by Pseudomonas aeruginosa is associated with high mortality, especially in an immunocompromised host. A large section of the palliative care patient population has varied forms of compromised immunity due to advanced cancer or cancer treatment, organ failures, chronic autoimmune disorders, degenerative conditions, and acquired immunodeficiency syndrome. The lung is one of the most frequently involved organs in a variety of complications in an immunocompromised host and infection is the most common complication. P. aeruginosa is one of the most common pathogens associated with bronchopulmonary infections in an immunocompromised host. Routine radiological tests like chest X-ray may often be unyielding and an early and a prompt initiation of treatment reduces mortality and morbidity risk.