Development of a Complex Intervention for Secondary Prevention of Coronary Heart Disease in Primary Care Using the UK Medical Research Council Framework

Objective: To apply the UK Medical Research Council (MRC) framework for development and evaluation of trials of complex interventions to a primary healthcare intervention to promote secondary prevention of coronary heart disease. Study Design: Case report of intervention development. Methods: First, literature relating to secondary prevention and lifestyle change was reviewed. Second, a preliminary intervention was modeled, based on literature findings and focus group interviews with patients (n = 23) and staff (n = 29) from 4 general practices. Participants’ experiences of and attitudes toward key intervention components were explored. Third, the preliminary intervention was pilot-tested in 4 general practices. After delivery of the pilot intervention, practitioners evaluated the training sessions, and qualitative data relating to experiences of the intervention were collected using semistructured interviews with staff (n = 10) and patient focus groups (n = 17). Results: Literature review identified 3 intervention components: a structured recall system, practitioner training, and patient information. Initial qualitative data identified variations in recall system design, training requirements (medication prescribing, facilitating behavior change), and information appropriate to the prospective study participants. Identifying detailed structures within intervention components clarified how the intervention could be tailored to individual practice, practitioner, and patient needs while preserving the theoretical functions of the components. Findings from the pilot phase informed further modeling of the intervention, reducing administrative time, increasing practical content of training, and omitting unhelpful patient information. Conclusion: Application of the MRC framework helped to determine the feasibility and development of a complex intervention for primary care research.

Interrelationship between two variants of the Circulifer tenellus complex and Spiroplasma citri: the causal agent of stubborn disease

Tese de Doutoramento, Ciências Naturais, Unidade de Ciências e Tecnologias Agrárias, Universidade do Algarve, 1992

Phylogenetic analysis of beak and feather disease virus across a host ring-species complex

Pathogens have been hypothesized to play a major role in host diversity and speciation. Susceptibility of hybrid hosts to pathogens is thought to be a common phenomenon that could promote host population divergence and subsequently speciation. However, few studies have tested for pathogen infection across animal hybrid zones while testing for codivergence of the pathogens in the hybridizing host complex. Over 8 y, we studied natural infection by a rapidly evolving single-strand DNA virus, beak and feather diseases virus (BFDV), which infects parrots, exploiting a host-ring species complex (Platycercus elegans) in Australia. We found that host subspecies and their hybrids varied strikingly in both BFDV prevalence and load: both hybrid and phenotypically intermediate subspecies had lower prevalence and load compared with parental subspecies, while controlling for host age, sex, longitude and latitude, as well as temporal effects. We sequenced viral isolates throughout the range, which revealed patterns of genomic variation analogous to Mayr's ring-species hypothesis, to our knowledge for the first time in any host-pathogen system. Viral phylogeny, geographic location, intraspecific host density, and parrot community diversity and composition did not explain the differences in BFDV prevalence or load between subpopulations. Overall, our analyses suggest that functional host responses to infection, or force of infection, differ between subspecies and hybrids. Our findings highlight the role of host hybridization and clines in altering host-pathogen interactions, dynamics that can have important implications for models of speciation with gene flow, and offer insights into how pathogens may adapt to diverging host populations.

Occurrence of socransky red complex in pregnant women with and without periodontal disease

Purpose: To verify the presence of Socransky Red Complex (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) and P. intermedia using polymerase chain reaction (PCR) in periodontally healthy pregnant women and pregnant women with periodontal disease, as well as its relation to arterial blood pressure and capillary glycaemia.Materials and Methods: This case control study included 86 pregnant women, including 50 pregnant women with healthy periodontium, 27 with gingivitis and 9 with periodontitis. Arterial blood pressure and glycaemia were evaluated and recorded. Clinical specimens from the gingival crevice or periodontal pockets were gathered with sterile absorbent paper cones. DNA extraction was accomplished using the Easy-DNA Kit test and the presence of bacteria was detected by PCR with primers and specific probes for each microorganism.Results: The arterial pressure of all pregnant women was found to be within normal levels and 51% presented with hyperglycaemia, these two variables were not associated with periodontal conditions and/or presence of microorganisms. Socransky Red Complex was not present in pregnant women with healthy periodontium; however, it was present in pregnant women with gingivitis (3.7%) and in a higher percentage of pregnant women with periodontitis (33.3%).Conclusion: Socransky Red Complex was found only in cases of periodontal diseases and is not related to blood pressure and/or high levels of blood glucose.

Right ventricular absolute myocardial blood flow in complex congenital heart disease

A consequence in patients with d-transposition of the great arteries (d-TGA) and tetralogy of Fallot (TOF) is right ventricular hypertrophy (RVH) and right ventricular failure. Myocardial contrast echocardiography (MCE) permits the determination of the myocardial microvascular density reflected by the relative myocardial blood volume (rBV; ml/ml). This study was conducted to elucidate the relationship between RVH and myocardial microvascular changes by quantitative MCE in patients with d-TGA and TOF.

Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: complex congenital cardiac lesions

With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death. Medical aspects that need to be considered relate to the long-term and multisystemic effects of single ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part III of the guidelines includes recommendations for the care of patients with complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Fontan operations and single ventricles, Eisenmenger's syndrome, and cyanotic heart disease. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.

Specific attentional impairments and complex visual hallucinations in eye disease

OBJECTIVE: To test the prediction by the Perception and Attention Deficit (PAD) model of complex visual hallucinations that cognitive impairment, specifically in visual attention, is a key risk factor for complex hallucinations in eye disease. METHODS: Two studies of elderly patients with acquired eye disease investigated the relationship between complex visual hallucinations (CVH) and impairments in general cognition and verbal attention (Study 1) and between CVH, selective visual attention and visual object perception (Study 2). The North East Visual Hallucinations Inventory was used to classify CVH. RESULTS: In Study 1, there was no relationship between CVH (n=10/39) and performance on cognitive screening or verbal attention tasks. In Study 2, participants with CVH (n=11/31) showed poorer performance on a modified Stroop task (p<0.05), a novel imagery-based attentional task (p<0.05) and picture (p<0.05) but not silhouette naming (p=0.13) tasks. Performance on these tasks correctly classified 83% of the participants as hallucinators or non-hallucinators. CONCLUSIONS: The results suggest that, consistent with the PAD model, complex visual hallucinations in people with acquired eye disease are associated with visual attention impairment.

Complex interaction between proliferative kidney disease, water temperature and concurrent nematode infection in brown trout

Proliferative kidney disease (PKD) is a temperature-dependent disease caused by the myxozoan Tetracapsuloides bryosalmonae. It is an emerging threat to wild brown trout Salmo trutta fario populations in Switzerland. Here we examined (1) how PKD prevalence and pathology in young-of-the-year (YOY) brown trout relate to water temperature, (2) whether wild brown trout can completely recover from T. bryosalmonae-induced renal lesions and eliminate T. bryo - salmonae over the winter months, and (3) whether this rate and/or extent of the recovery is influenced by concurrent infection. A longitudinal field study on a wild brown trout cohort was conducted over 16 mo. YOY and age 1+ fish were sampled from 7 different field sites with various temperature regimes, and monitored for infection with T. bryosalmonae and the nematode Raphidascaris acus. T. bryosamonae was detectable in brown trout YOY from all sampling sites, with similar renal pathology, independent of water temperature. During winter months, recovery was mainly influenced by the presence or absence of concurrent infection with R. acus larvae. While brown trout without R. acus regenerated completely, concurrently infected brown trout showed incomplete recovery, with chronic renal lesions and incomplete translocation of T. bryosalmonae from the renal interstitium into the tubular lumen. Water temperature seemed to influence complete excretion of T. bryosalmonae, with spores remaining in trout from summer-warm rivers, but absent in trout from summer-cool rivers. In the following summer months, we found PKD infections in 1+ brown trout from all investigated river sites. The pathological lesions indicated a reinfection rather than a proliferation of remaining T. bryosalmonae. However, disease prevalence in 1+ trout was lower than in YOY.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Thoracic aortic disease in tuberous sclerosis complex: molecular pathogenesis and potential therapies in Tsc2+/- mice.

Tuberous sclerosis complex (TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are characterized on pathologic examination by smooth muscle cell (SMC) proliferation in the aortic media. SMCs were explanted from Tsc2(+/-) mice to investigate the pathogenesis of aortic aneurysms caused by TSC2 mutations. Tsc2(+/-) SMCs demonstrated increased phosphorylation of mammalian target of rapamycin (mTOR), S6 and p70S6K and increased proliferation rates compared with wild-type (WT) SMCs. Tsc2(+/-) SMCs also had reduced expression of SMC contractile proteins compared with WT SMCs. An inhibitor of mTOR signaling, rapamycin, decreased SMC proliferation and increased contractile protein expression in the Tsc2(+/-) SMCs to levels similar to WT SMCs. Exposure to alpha-elastin fragments also decreased proliferation of Tsc2(+/-) SMCs and increased levels of p27(kip1), but failed to increase expression of contractile proteins. In response to artery injury using a carotid artery ligation model, Tsc2(+/-) mice significantly increased neointima formation compared with the control mice, and the neointima formation was inhibited by treatment with rapamycin. These results demonstrate that Tsc2 haploinsufficiency in SMCs increases proliferation and decreases contractile protein expression and suggest that the increased proliferative potential of the mutant cells may be suppressed in vivo by interaction with elastin. These findings provide insights into the molecular pathogenesis of aortic disease in TSC patients and identify a potential therapeutic target for treatment of this complication of the disease.

High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial

OBJECTIVES This study sought to determine the effect of rotational atherectomy (RA) on drug-eluting stent (DES) effectiveness. BACKGROUND DES are frequently used in complex lesions, including calcified stenoses, which may challenge DES delivery, expansion, and effectiveness. RA can adequately modify calcified plaques and facilitate stent delivery and expansion. Its impact on DES effectiveness is widely unknown. METHODS The ROTAXUS (Rotational Atherectomy Prior to TAXUS Stent Treatment for Complex Native Coronary Artery Disease) study randomly assigned 240 patients with complex calcified native coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120, standard therapy group). Stenting was performed using a polymer-based slow-release paclitaxel-eluting stent. The primary endpoint was in-stent late lumen loss at 9 months. Secondary endpoints included angiographic and strategy success, binary restenosis, definite stent thrombosis, and major adverse cardiac events at 9 months. RESULTS Despite similar baseline characteristics, significantly more patients in the standard therapy group were crossed over (12.5% vs. 4.2%, p = 0.02), resulting in higher strategy success in the rotablation group (92.5% vs. 83.3%, p = 0.03). At 9 months, in-stent late lumen loss was higher in the rotablation group (0.44 ± 0.58 vs. 0.31 ± 0.52, p = 0.04), despite an initially higher acute lumen gain (1.56 ± 0.43 vs. 1.44 ± 0.49 mm, p = 0.01). In-stent binary restenosis (11.4% vs. 10.6%, p = 0.71), target lesion revascularization (11.7% vs. 12.5%, p = 0.84), definite stent thrombosis (0.8% vs. 0%, p = 1.0), and major adverse cardiac events (24.2% vs. 28.3%, p = 0.46) were similar in both groups. CONCLUSIONS Routine lesion preparation using RA did not reduce late lumen loss of DES at 9 months. Balloon dilation with only provisional rotablation remains the default strategy for complex calcified lesions before DES implantation.