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1.  Supplemental plant sterols and stanols for serum cholesterol and cardiovascular disease 
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effects of phytosterols, phytostanols or their esters, ingested in supplemented foods, on blood cholesterol concentrations and cardiovascular disease;To look for adverse effects e.g. on nutritional status or physiological function;To study/comment on, possible effects of cost.
doi:10.1002/14651858.CD004814.pub2
PMCID: PMC4178528  PMID: 25278808
2.  Statins for the primary prevention of cardiovascular disease 
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search methods
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.84, 95% CI 0.73 to 0.96) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors’ conclusions
Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of cancers or muscle pain among people without evidence of cardiovascular disease treated with statins. Other potential adverse events were not reported and some trials included people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
doi:10.1002/14651858.CD004816.pub4
PMCID: PMC4164175  PMID: 21249663
Cardiovascular Diseases [blood; *prevention & control]; Cause of Death; Cholesterol, HDL [blood]; Cholesterol, LDL [blood]; Hydroxymethylglutaryl-CoA Reductase Inhibitors [adverse effects; *therapeutic use]; Primary Prevention; Randomized Controlled Trials as Topic; Adult; Humans
3.  Multiple risk factor interventions for primary prevention of coronary heart disease 
Background
Primary prevention programmes in many countries attempt to reduce mortality and morbidity due to coronary heart disease (CHD) through risk factor modification. It is widely believed that multiple risk factor intervention using counselling and educational methods is efficacious and cost-effective and should be expanded. Recent trials examining risk factor changes have cast considerable doubt on the effectiveness of these multiple risk factor interventions.
Objectives
To assess the effects of multiple risk factor intervention for reducing cardiovascular risk factors, total mortality, and mortality from CHD among adults without clinical evidence of established cardiovascular disease.
Search strategy
MEDLINE was searched for the original review to 1995. This was updated by searching the Cochrane Central Register of Controlled Trials on The Cochrane Library Issue 3 2001, MEDLINE(2000 to September 2001) and EMBASE (1998 to September 2001).
Selection criteria
Intervention studies using counselling or education to modify more than one cardiovascular risk factor in adults from general populations, occupational groups, or high risk groups. Trials of less than 6 months duration were excluded.
Data collection and analysis
Data were extracted by two reviewers independently. Investigators were contacted to obtain missing information.
Main results
A total of 39 trials were found of which ten reported clinical event data. In the ten trials with clinical event end-points, the pooled odds ratios for total and CHD mortality were 0.96 (95% confidence intervals (CI) 0.92 to 1.01) and 0.96 (95% CI 0.89 to 1.04) respectively. Net changes in systolic and diastolic blood pressure, and blood cholesterol were (weighted mean differences) −3.6 mmHg (95% CI −3.9 to −3.3 mmHg), −2.8 mmHg (95% CI −2.9 to −2.6 mmHg) and −0.07 mMol/l (95% CI −0.8 to −0.06 mMol/l) respectively. Odds of reduction in smoking prevalence was 20% (95% CI 8% to 31%). Statistical heterogeneity between the studies with respect to mortality and risk factor changes was due to trials focusing on hypertensive participants and those using considerable amounts of drug treatment.
Authors’ conclusions
The pooled effects suggest multiple risk factor intervention has no effect on mortality. However, a small, but potentially important, benefit of treatment (about a 10% reduction in CHD mortality) may have been missed. Risk factor changes were relatively modest, were related to the amount of pharmacological treatment used, and in some cases may have been over-estimated because of regression to the mean effects, lack of intention to treat analyses, habituation to blood pressure measurement, and use of self-reports of smoking. Interventions using personal or family counselling and education with or without pharmacological treatments appear to be more effective at achieving risk factor reduction and consequent reductions in mortality in high risk hypertensive populations. The evidence suggests that such interventions have limited utility in the general population.
doi:10.1002/14651858.CD001561.pub2
PMCID: PMC4160097  PMID: 17054138
Coronary Disease [mortality; *prevention & control]; Patient Education as Topic; Randomized Controlled Trials as Topic; Risk Factors; Humans
4.  Report from a consensus conference on antibody-mediated rejection in heart transplantation 
BACKGROUND
The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation.
METHODS
The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus.
RESULTS
A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided.
CONCLUSIONS
The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues.
doi:10.1016/j.healun.2010.11.003
PMCID: PMC3829685  PMID: 21300295
heart transplant; antibody; rejection; treatment; outcomes
5.  Expanding Colorectal Cancer Screening among Minority Women 
Cancer  2010;117(1):70-76.
Background
Colorectal cancer screening (CRCS) in the United States is inadequate in minority communities and particularly among those who lack insurance; finding ways to increase screenings among African Americans and Hispanics, presents a major healthcare challenge.
Methods
This study was offered to women attending the Breast Examination Center of Harlem, a community outreach program of Memorial Sloan-Kettering serving the primarily black and Hispanic Harlem Community. Screening was explained, medical fitness was determined, and colonoscopies were performed. Barriers to screening and ways to overcome them were ascertained. Participation was offered to eligible women seen at BECH from July 2003 through October 2005. Participants had to be at least 50 years of age without history of colorectal cancer or screening within the last 10 years.
Results
There were 2616 women who were eligible for CRCS, and of these women 2005 (77%) refused to participate in the study, and 611 (23%) women were enrolled. There was a high interest in CRCS including among those who declined to participate in the study. The major barrier was lack of medical insurance which was overcome by alternative funding. Of the 611 women enrolled, 337 (55%) went on to have screening colonoscopy. Forty-nine women (15%) had adenomatous polyps.
Conclusions
Offering CRCS to poor minority women at the time of mammography and without a doctor's referral is an effective way to expand screening. Screening colonoscopy findings are similar to those in the general population. Alternatives to traditional medical insurance are needed for the uninsured.
doi:10.1002/cncr.25566
PMCID: PMC3782747  PMID: 21170901
Colorectal cancer screening; colonoscopy; underserved population; uninsured
6.  The multifaceted responses of primary human astrocytes and brain microvascular endothelial cells to the Lyme disease spirochete, Borrelia burgdorferi 
ASN NEURO  2013;5(3):e00119.
The vector-borne pathogen, Borrelia burgdorferi, causes a multi-system disorder including neurological complications. These neurological disorders, collectively termed neuroborreliosis, can occur in up to 15% of untreated patients. The neurological symptoms are probably a result of a glial-driven, host inflammatory response to the bacterium. However, the specific contributions of individual glial and other support cell types to the pathogenesis of neuroborreliosis are relatively unexplored. The goal of this project was to characterize specific astrocyte and endothelial cell responses to B. burgdorferi. Primary human astrocytes and primary HBMEC (human brain microvascular endothelial cells) were incubated with B. burgdorferi over a 72-h period and the transcriptional responses to the bacterium were analyzed by real-time PCR arrays. There was a robust increase in several surveyed chemokine and related genes, including IL (interleukin)-8, for both primary astrocytes and HBMEC. Array results were confirmed with individual sets of PCR primers. The production of specific chemokines by both astrocytes and HBMEC in response to B. burgdorferi, including IL-8, CXCL-1, and CXCL-10, were confirmed by ELISA. These results demonstrate that primary astrocytes and HBMEC respond to virulent B. burgdorferi by producing a number of chemokines. These data suggest that infiltrating phagocytic cells, particularly neutrophils, attracted by chemokines expressed at the BBB (blood–brain barrier) may be important contributors to the early inflammatory events associated with neuroborreliosis.
doi:10.1042/AN20130010
PMCID: PMC3745032  PMID: 23883071
astrocyte; blood–brain barrier; Borrelia burgdorferi; chemokine; endothelium; neuroborreliosis.; BBB, blood–brain barrier; CCL, CC chemokine ligand; CNS, central nervous system; CSF, cerebrospinal fluid; CXCR, CXC chemokine receptor; ECM, endothelial cell medium; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HBMEC, human brain microvascular endothelial cells; IL, interleukin; MOI, multiplicity of infection; QPCR, quantitative PCR; TNFα, tumor necrosis factor α
7.  Is MRI better than CT for detecting a vascular component to dementia? A systematic review and meta-analysis 
BMC Neurology  2012;12:33.
Background
Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD (“mixed dementia”), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question.
Methods
We searched eight databases and screened reference lists to identify studies addressing the review question. We assessed study quality using QUADAS. We estimated summary diagnostic accuracy according to imaging finding, and ratios of diagnostic odds ratios (RDORs) for MRI versus CT and high versus low risk of bias.
Results
We included 7 autopsy and 31 non-autopsy studies. There was little evidence that selective patient enrolment and risk of incorporation bias impacted on diagnostic accuracy (p = 0.12 to 0.95). The most widely reported imaging finding was white matter hyperintensities. For CT (11 studies) summary sensitivity and specificity were 71% (95% CI 53%-85%) and 55% (44%-66%). Corresponding figures for MRI (6 studies) were 95% (87%-98%) and 26% (12%-50%). General infarcts was the most specific imaging finding on MRI (96%; 95% CI 94%-97%) and CT (96%; 93%-98%). However, sensitivity was low for both MRI (53%; 36%-70%) and CT (52%; 22% to 80%). No imaging finding had consistently high sensitivity. Based on non-autopsy studies, MRI was more accurate than CT for six of seven imaging findings, but confidence intervals were wide.
Conclusion
There is insufficient evidence to suggest that MRI is superior to CT with respect to identifying cerebrovascular changes in autopsy-confirmed and clinical cohorts of VaD, AD, and ‘mixed dementia’.
doi:10.1186/1471-2377-12-33
PMCID: PMC3403932  PMID: 22672344
Dementia; CT; MRI; Diagnosis; Systematic review
9.  Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under‐recognised spectrum of disease 
Thorax  2006;62(3):248-252.
Aims and Methods
A review was undertaken of 19 patients diagnosed with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) between 1992 and 2006.
Results
Most patients were women (n = 15) and non‐smokers (n = 16). Clinical presentation was either with symptomatic pulmonary disease (group 1; n = 9) or as an incidental finding during investigation for another disorder, most frequently malignant disease (group 2; n = 10). In group 1, cough and dyspnoea were the most frequent symptoms, with an average duration of 8.6 years before diagnosis. Both groups showed mainly stable disease without treatment, although one patient progressed to severe airflow obstruction and one was diagnosed at single lung transplantation. Mosaicism with nodule(s) was the typical pattern of DIPNECH on high‐resolution computed tomography, but one case had normal imaging despite airflow obstruction. Lung function tests showed obstructive (n = 8), mixed (n = 3) or normal (n = 5, all group 2) physiology. Two patients underwent a bronchoalveolar lavage and showed a lymphocytosis (30%) with mild chronic bronchiolitis being seen in all biopsies. Tumourlets and associated typical carcinoids (n = 9) showed weak positivity for thyroid transcription factor‐1. Three patients had atypical carcinoids, one with multiple endocrine neoplasia type 1 syndrome.
Conclusions
DIPNECH is being increasingly recognised, probably because of an increase in the usage and accuracy of investigative imaging and increased awareness of the entity. Most cases remain stable over many years independent of the mode of presentation, although a few patients progress to severe airflow obstruction.
doi:10.1136/thx.2006.063065
PMCID: PMC2117154  PMID: 17099078
10.  A Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels Is Amenable to Exon 51 Skipping 
PLoS ONE  2010;5(1):e8647.
Background
Duchenne muscular dystrophy (DMD), which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products. For these patients, restoration of the reading frame via antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach. The major DMD deletion “hot spot” is found between exons 45 and 53, and skipping exon 51 in particular is predicted to ameliorate the dystrophic phenotype in the greatest number of patients. Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials. The Golden Retriever muscular dystrophy (GRMD) model has a severe phenotype, but due to its large size, is expensive to use. Both these models have mutations in regions of the dystrophin gene distant from the commonly mutated DMD “hot spot”.
Methodology/Principal Findings
Here we describe the severe phenotype, histopathological findings, and molecular analysis of Cavalier King Charles Spaniels with dystrophin-deficient muscular dystrophy (CKCS-MD). The dogs harbour a missense mutation in the 5′ donor splice site of exon 50 that results in deletion of exon 50 in mRNA transcripts and a predicted premature truncation of the translated protein. Antisense oligonucleotide-mediated skipping of exon 51 in cultured myoblasts from an affected dog restored the reading frame and protein expression.
Conclusions/Significance
Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD.
doi:10.1371/journal.pone.0008647
PMCID: PMC2800183  PMID: 20072625
12.  Amyloidosis presenting as bilateral transudative pleural effusions with normal cardiac investigations: a case report 
Cases Journal  2009;2:6963.
A 66-year-old man with a diagnosis of monoclonal gammopathy of unknown significance was referred for investigation of bilateral transudative pleural effusions by the cardiology team. Echocardiography, myocardial perfusion scanning and left heart catheterisation were all normal or non diagnostic. Given significant occupational asbestos exposure in his twenties he underwent thoracoscopic pleural biopsy. This showed fibrous inflammation only. He subsequently developed proteinuria and peripheral oedema. Reanalysis of the pleural biopsy specimen for amyloidosis was positive. Pleural disease is an uncommon presentation of systemic amyloidosis. The aetiology of the pleural effusions is unclear and is not simply a consequence of cardiac or renal impairment.
doi:10.4076/1757-1626-2-6963
PMCID: PMC2740277  PMID: 19829885

Results 1-14 (14)