Analysis of F9 point mutations and their correlation to severity of haemophilia B disease.

Haemophilia B is an X-linked recessive disorder caused by deficiency of functional coagulation factor IX, which results almost exclusively from mutations in the F9 gene. We sought to determine features, which could distinguish between mutations that cause severe disease symptoms from those that cause non-severe disease symptoms. Towards this objective, we have performed a statistical analysis of reported point mutations in F9. These include: potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location of the mutation with regard to protein secondary structure and functional domain and amino acids' evolutionary conservation scores. Wilcoxon signed-rank tests showed highly significant differences between severe and non-severe disease causing mutations in their effect on free energy of small mRNA fragments and evolutionarily conserved amino acids. Our results suggest that information at the mRNA level as well as conservation of the amino acid correlate well with disease severity. This study demonstrates that computational tools may be used to characterize the severity of haemophilia B associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins.

Premature coronary artery disease and early stage chronic kidney disease.

A 30 year old asymptomatic male with stage 3 chronic kidney disease (CKD) secondary to Focal Segmental Glomerulosclerosis was found to have features of CKD associated cardiomyopathy including left ventricular hypertrophy (LVH) and focal sub-endocardial scarring on cardiac magnetic resonance imaging. There was also a significantly raised CT coronary calcium score and evidence of non-flow limiting coronary artery disease (CAD) on a CT coronary angiogram. Early stage CKD is a major risk factor for cardiovascular risk causing myocardial hypertrophy and fibrosis and coronary artery atheroma. Cardiovascular risk begins to increase from an eGFR of around 75ml/min/1.73m2. The pathophysiology of cardiovascular disease in CKD is under investigation but to date, treatment options are limited. Blood pressure control and statins have the strongest supportive evidence.

The treatment of coronary artery disease in patients with chronic kidney disease.

Premature cardiovascular disease is the largest cause of mortality, and a major cause of morbidity, in patients with chronic kidney disease (CKD). Patients with end-stage kidney disease (ESKD) are at extreme risk, but cardiovascular event rates are increased even in early CKD. There is little controlled trial evidence on which to base treatment, as most therapeutic trials have excluded CKD patients. Current treatment strategies are therefore based upon small prospective studies or retrospective analyses of controlled trials and registry data. It is thus unclear whether CKD patients benefit from modern secondary preventive treatments in the same manner as patients with normal renal function. There is a need for randomized trials to identify effective drugs to prevent and treat coronary artery disease in CKD. Revascularization by CABG in CKD has been widely reported in registry data to provide better results than medical treatment or angioplasty. Recent angioplasty data in patients with CKD, however, show improving results, and the risks of CABG in CKD remain high. It is not clear which revascularization technique has a better outcome in patients 'equally suitable' on angiographic criteria for either procedure. The high rate of late adverse cardiovascular events after both CABG and angioplasty accentuates the need for effective secondary preventive therapy disease in these high-risk patients.

Effect of Valvular Surgery in Carcinoid Heart Disease: An Observational Cohort Study.

CONTEXT: Carcinoid heart disease (NET-CHD) is associated with the development of symptom-limited exercise capacity and high rates of morbidity and mortality. OBJECTIVE: This study sought to determine the survival, cardiac function, and functional class following surgery. DESIGN AND SETTING, AND PATIENTS: This was a retrospective observational cohort study between 2005 and 2015 at a European Centre of Excellence for Neuroendocrine Tumours, Queen Elizabeth Hospital Birmingham. England consisting of 62 consecutive patients referred to the NET-Cardiology Service. INTERVENTIONS: Subjects were assessed at referral using transthoracic echocardiography (with saline contrast) and transesophageal echocardiography, and 77% with confirmed NET-CHD underwent cardiovascular magnetic resonance imaging. Symptomatic patients with concomitant severe valvular dysfunction were referred for surgery with stable NET disease. MAIN OUTCOME MEASURE: Survival of patients with proven NET-CHD following medical and surgical treatments was measure. RESULTS: In total, 47/62 patients were diagnosed with NET-CHD. Thirty-two patients (68%) underwent surgery with bioprosthetic valve replacements in all subjects; tricuspid, n = 31; pulmonary, n = 30; mitral, n = 3; and aortic, n = 3. Four patients underwent concomitant coronary artery bypass grafting. There were 4 (13%) early post-operative deaths. One- and 2-y survival rates after surgery were 75 and 69% compared with 45 and 15% in un-operated patients. Post-operatively, functional class was improved (pre-New York Heart Association Classification [NYHA], 2.6 [0.5] vs post-NYHA, 1.7 [1.1]), P < .05, right-ventricular (RV) size was reduced (136 ml/m(2) [25] vs 71 ml/m(2) [7]; P < .01) with preserved RV ejection fraction (61% ± 9 vs 55% ± 10; P = .26). CONCLUSION: Valve surgery improved functional class and resulted in RV reverse remodelling with improved survival rates at 2 y compared with those not proceeding to operation. These data highlight the importance of close collaboration between NET clinicians, cardiology, and cardiothoracic surgery teams. Early referral can improve functional capacity but more research is needed to define the selection of appropriate candidates and randomized data are needed to define the effect of surgery on prognosis.

Variability in cardiac MR measurement of left ventricular ejection fraction, volumes and mass in healthy adults: defining a significant change at 1 year.

OBJECTIVE: Variability in the measurement of left ventricular (LV) parameters in cardiovascular imaging has typically been assessed over a short time interval, but clinicians most commonly compare results from studies performed a year apart. To account for variation in technical, procedural and biological factors over this time frame, we quantified the within-subject changes in LV volumes, LV mass (LVM) and LV ejection fraction (EF) in a well-defined cohort of healthy adults at 12 months. METHODS: Cardiac MR (CMR) was performed in 42 healthy control subjects at baseline and at 1 year (1.5 T Magnetom® Avanto; Siemens Healthcare, Erlangen, Germany). Analysis of steady-state free precession images was performed manually offline (Argus software; Siemens Healthcare) for assessment of LV volumes, LVM and EF by a single blinded observer. A random subset of 10 participants also underwent repeat imaging within 7 days to determine short-term interstudy reproducibility. RESULTS: There were no significant changes in any LV parameter on repeat CMR at 12 months. The short-term interstudy biases were not significantly different from the long-term changes observed at 1 year. The smallest detectable change (SDC) for LVEF, end-diastolic volume, end-systolic volume and LVM that could be recognized with 95% confidence were 6%, 13 ml, 7 ml and 6 g, respectively. CONCLUSION: The variability in CMR-derived LV measures arising from technical, procedural and biological factors remains minimal at 12 months. Thus, for patients undergoing repeat annual assessment by CMR, even small differences in LV function, size and LVM (which are greater than the SDC) may be attributed to disease-related factors. ADVANCES IN KNOWLEDGE: The reproducibility and reliability of CMR data at 12 months is excellent allowing clinicians to be confident that even small changes in LV structure and function over this time frame are real.

Important considerations in the use of ethnicity as a study variable.

Ethnicity is widely used as a study variable by community health researchers. However, there is little consistency in the definition of ethnicity and the process by which ethnicity is assigned. Potential problems in the use of ethnicity as a study variable are discussed as well as suggestions for improvements.

Translating written material for community health research and service delivery: guidelines to enhance the process.

Translating health promotion and research material for cross-cultural use is costly and time-consuming. Methods to enhance the translation process are reviewed. The concept of equivalence and non-statistical approaches to achieve equivalence are presented. Utilization of these approaches may help strengthen the development of health promotion material and community health research instruments for use with ethnically diverse populations.

Tobacco use and ethnicity: the existing data gap.

Tobacco use contributes substantially to the burden of illness throughout the world. Significant efforts have been made to design health promotion programs for the prevention and cessation of tobacco use in North America. However, most of these programs have been planned and implemented on the basis of needs assessments conducted among the dominant cultural group. Evidence exists that lifestyle modification and tobacco cessation programs must be culturally relevant to ensure successful outcomes. A review of the literature from nursing, anthropological and epidemiological perspectives suggests that there is a paucity of data available on the largely culture-dependent values which influence the decision to use tobacco in those groups which comprise the Canadian multicultural mosaic. The interpretation of results from existing studies is limited by a number of recurrent methodological flaws. The implications of this review for future research and public health planning are discussed. The development of culturally appropriate programs directed at the prevention and cessation of tobacco use remains a significant challenge for health professionals.

A randomized controlled trial of alternative approaches to community follow-up for postpartum women.

This three-group randomized controlled trial assessed the effectiveness of a postpartum public health nurse telephone visit on infant-care behaviours of primiparous women in Ottawa-Carleton. The impact of a clerk call on recruiting mothers to parent-baby groups was also described. Low risk primiparas were randomized into telephone visit, clerk call and control groups. At three months postpartum, there were no significant differences in infant-care behaviour scores among the study groups. Women who received the telephone visit had the highest parent-baby group attendance rates and among attenders, the highest rates of smoking during pregnancy, the least education, and lowest incomes. Analysis of variance revealed a significant interaction term between attendance at parent-baby groups and assigned study group. This effect disappeared after adjusting for age and education. The telephone visit was no more effective in producing the desired infant-care behaviour changes than a mailed out information package with or without a clerk phone call. However, the intervention did increase the utilization of parent-baby support groups by women who were more socioeconomically disadvantaged.

The hospital liaison process: identifying risk factors in postnatal multiparas.

Postnatal home visiting has been a routine part of the public health nurse's role in Canada for decades. Resource limitations in recent years have required Health Units to justify programming choices and in some cases have dictated a shift toward more intensive service provision to high risk clients. This study examined the screening accuracy of a tool developed for use by hospital liaison nurses to identify multiparas in need of home visiting. Results showed poor agreement between client information collected by the hospital liaison nurse and the assessment done by the PHN in the clients' home, even when explicit referral criteria were used. Changes are required in the referral process to effectively screen postnatal clients in need of further services.

The provision of public health nursing follow-up services for postnatal clients in Ontario: a cross-sectional survey.

We did a cross-sectional survey of official health agencies in Ontario in 1990 to assess methods of providing postnatal services. The response rate was 78.6%. We found that diverse methods of postnatal follow-up are offered although home visits remain a primary mode of service delivery. There are significant differences in the timing of home and telephone visits and postnatal group sessions.

Central pulse pressure in patients with chronic kidney disease and in renal transplant recipients.

Patients with chronic kidney disease (CKD) and renal transplant recipients (RTR) have increased cardiovascular risk. The value of measuring central pulse pressure (cPP) over brachial pulse pressure (pPP) is not known. Central PP was measured in 597 patients (364 CKD:233 RTR). In multivariate analysis, age and female gender positively correlated with cPP; heart rate and estimated glomerular filtration rate negatively correlated with cPP. Associations for age, heart rate and gender persisted after additional adjustment for pPP and aortic wave reflection. This model accounted for 91% of the variability in cPP, with pPP alone accounting for 74%. Results were similar when both patient groups were analysed separately. A subset of patients with CKD had aortic pulse wave velocity (PWV) and left ventricular mass index (LVMI) measured. There were no differences in the univariate correlations between PWV (r=0.368 vs 0.315; P=0.4) or LVMI (r=0.125 vs 0.163; P=0.7); nor in the multivariate models created for PWV (P=0.1) or LVMI (P=0.1) when either cPP or pPP were used. This study demonstrates that in these patients most of the variability in cPP can be explained by pPP. Additionally, cPP does not appear to provide additional information beyond pPP in determining PWV and LVMI.

Understanding the effects of chronic kidney disease on cardiovascular risk: are there lessons to be learnt from healthy kidney donors?

Chronic kidney disease (CKD) is now a recognized global public health problem. It is highly prevalent and strongly associated with hypertension and cardiovascular disease (CVD); far more patients with a glomerular filtration rate below 60 ml min(-1) per 1.73 m(2) will die from cardiovascular causes than progress to end-stage renal disease. A better understanding of the complex mechanisms underlying the development of CVD among CKD patients is required if we are to begin devising therapy to prevent or reverse this process. Observational studies of CVD in CKD are difficult to interpret because renal impairment is almost always accompanied by confounding factors. These include the underlying disease process itself (for example, diabetes mellitus and systemic vasculitis) and the complications of CKD, such as hypertension, anaemia and inflammation. Kidney donors provide an ideal opportunity to study healthy subjects without manifest vascular disease who experience an acute change from having normal to modestly impaired renal function at the time of uninephrectomy. Prospectively examining the cardiovascular consequences of uninephrectomy using donors as a model of CKD may provide useful insight into the pathophysiology of CVD in CKD and, therefore, into how the CVD risk associated with renal impairment might eventually be reduced.

Comparative hospital economics and patient presentation: vertebroplasty and kyphoplasty for the treatment of vertebral compression fracture.

BACKGROUND AND PURPOSE: Previous studies evaluating vertebral augmentation procedure costs have not made detailed comparisons between vertebroplasty and kyphoplasty. Our study contrasts hospital costs for vertebroplasty versus kyphoplasty for the treatment of vertebral compression fractures in routine clinical practice in the United States. MATERIALS AND METHODS: This retrospective cohort study analyzed 2007-2008 hospital discharge and billing records from the Premier Perspective data base. The primary outcome variable, differences in total hospital cost between vertebroplasty and kyphoplasty, was assessed by using analysis of covariance. RESULTS: Three thousand six hundred seventeen patients received vertebroplasty (64% inpatient, 36% outpatient), and 8118 received kyphoplasty (54% inpatient, 46% outpatient). Approximately 75% were women, and most were white. Mean total unadjusted inpatient costs were $9837 for vertebroplasty versus $13 187 for kyphoplasty (P < .0001). Outpatient vertebroplasty costs were $3319 versus $8100 for kyphoplasty (P < .0001). Lower vertebroplasty costs were largely due to differences in hospital supply and OR. Mean vertebroplasty OR costs were $73.60 (anesthesia), $112.06 (recovery room), and $990.12 (surgery) versus $172.16 (anesthesia), $257.47 (recovery room), and $1,471.49 (surgery) with kyphoplasty. Adjustments for age, sex, admission status, and disease severity accentuated the differences. Mean adjusted inpatient costs were $11 386 for vertebroplasty versus $16 182 for kyphoplasty (P < .0001), and outpatient costs were $2997 for vertebroplasty versus $7010 for kyphoplasty (P < .0001). After adjustments for the same covariates, length-of-stay differences were no longer evident (P = .4945). CONCLUSIONS: Performing vertebroplasty versus kyphoplasty reduces hospital costs by nearly $5000 for inpatient procedures and by more than $4000 for outpatient procedures.