The Economic Burden of Heart Conditions in Brazil.

BACKGROUND: Heart conditions impose physical, social, financial and health-related quality of life limitations on individuals in Brazil. OBJECTIVES: This study assessed the economic burden of four main heart conditions in Brazil: hypertension, heart failure, myocardial infarction, and atrial fibrillation. In addition, the cost-effectiveness of telemedicine and structured telephone support for the management of heart failure was assessed. METHODS: A standard cost of illness framework was used to assess the costs associated with the four conditions in 2015. The analysis assessed the prevalence of the four conditions and, in the case of myocardial infarction, also its incidence. It further assessed the conditions' associated expenditures on healthcare treatment, productivity losses from reduced employment, costs of providing formal and informal care, and lost wellbeing. The analysis was informed by a targeted literature review, data scan and modelling. All inputs and methods were validated by consulting 15 clinicians and other stakeholders in Brazil. The cost-effectiveness analysis was based on a meta-analysis and economic evaluation of post-discharge programs in patients with heart failure, assessed from the perspective of the Brazilian Unified Healthcare System (Sistema Unico de Saude). RESULTS: Myocardial infarction imposes the greatest financial cost (22.4 billion reais/6.9 billion USD), followed by heart failure (22.1 billion reais/6.8 billion USD), hypertension (8 billion reais/2.5 billion USD) and, finally, atrial fibrillation (3.9 billion reais/1.2 billion USD). Telemedicine and structured telephone support are cost-effective interventions for achieving improvements in the management of heart failure. CONCLUSIONS: Heart conditions impose substantial loss of wellbeing and financial costs in Brazil and should be a public health priority.

The Economic Burden of Heart Conditions in Brazil / Os Custos das Doenças Cardíacas no Brasil

Abstract Background: Heart conditions impose physical, social, financial and health-related quality of life limitations on individuals in Brazil. Objectives: This study assessed the economic burden of four main heart conditions in Brazil: hypertension, heart failure, myocardial infarction, and atrial fibrillation. In addition, the cost-effectiveness of telemedicine and structured telephone support for the management of heart failure was assessed. Methods: A standard cost of illness framework was used to assess the costs associated with the four conditions in 2015. The analysis assessed the prevalence of the four conditions and, in the case of myocardial infarction, also its incidence. It further assessed the conditions' associated expenditures on healthcare treatment, productivity losses from reduced employment, costs of providing formal and informal care, and lost wellbeing. The analysis was informed by a targeted literature review, data scan and modelling. All inputs and methods were validated by consulting 15 clinicians and other stakeholders in Brazil. The cost-effectiveness analysis was based on a meta-analysis and economic evaluation of post-discharge programs in patients with heart failure, assessed from the perspective of the Brazilian Unified Healthcare System (Sistema Unico de Saude). Results: Myocardial infarction imposes the greatest financial cost (22.4 billion reais/6.9 billion USD), followed by heart failure (22.1 billion reais/6.8 billion USD), hypertension (8 billion reais/2.5 billion USD) and, finally, atrial fibrillation (3.9 billion reais/1.2 billion USD). Telemedicine and structured telephone support are cost-effective interventions for achieving improvements in the management of heart failure. Conclusions: Heart conditions impose substantial loss of wellbeing and financial costs in Brazil and should be a public health priority.

Resumo Fundamento: As doenças cardíacas impõem limitações à qualidade de vida nos aspectos físicos, sociais, financeiros e de saúde no Brasil. Objetivos: Este estudo avaliou o custo de quatro importantes doenças cardíacas no Brasil: hipertensão, insuficiência cardíaca, infarto do miocárdio e fibrilação atrial. Além disso, avaliou a relação de custo-efetividade de telemedicina e suporte telefônico estruturado para o manejo de insuficiência cardíaca. Métodos: Um custo padrão da estrutura de enfermidade foi usado para avaliar os custos associados às quatro condições em 2015. Analisou-se a prevalência das quatro doenças e, em caso de infarto do miocárdio, também sua incidência. Avaliaram-se ainda as despesas associadas ao tratamento, a perda de produtividade a partir da redução do emprego, os custos do fornecimento de assistência formal e informal e o bem-estar perdido referentes às condições. A análise teve por base uma revisão de literatura-alvo, varredura de dados e modelagem. Todos os inputs e métodos foram validados por 15 clínicos consultores e outras partes interessadas no Brasil. A análise de custo-efetividade baseou-se em uma meta-análise e uma avaliação econômica de programas após a alta de pacientes com insuficiência cardíaca, considerados a partir da perspectiva do Sistema Único de Saúde do Brasil. Resultados: Infarto do miocárdio acarretou o mais alto custo financeiro (R$ 22,4 bilhões/6,9 bilhões de dólares), seguido de insuficiência cardíaca (R$ 22,1 bilhões/6,8 bilhões de dólares), hipertensão (R$ 8 bilhões/2,5 bilhões de dólares) e, finalmente, fibrilação atrial (R$ 3,9 bilhões/1,2 bilhão de dólares). Telemedicina e suporte telefônico estruturado são intervenções custo-efetivas para o aprimoramento do manejo da insuficiência cardíaca. Conclusões: As doenças cardíacas determinam substanciais custos financeiros e perda de bem-estar no Brasil e deveriam ser uma prioridade de saúde pública.

Obtaining a follow-up appointment before discharge protects against readmission for patients with acute coronary syndrome and heart failure: A quality improvement project.

BACKGROUND: Cardiac patients have a high risk of readmission following hospital discharge. The aim of our project was to examine the factors associated with increased readmission rate, with a view to eventually decrease the rate of readmission for patients admitted to the hospital due to acute coronary syndrome (ACS) or heart failure. METHODS: Patients admitted to the cardiac step-down unit at a single private hospital from 2015 to 2016 were included in our study. Interventions that were employed included: (1) improved pre-discharge follow-up appointment scheduling, (2) medication education by a pharmacist, and (3) timely discharge planning. Our primary outcome of interest was all-cause rate of hospital readmission within 30days. We conducted a multivariate analysis to determine the factors that were predictive of readmission rate. RESULTS: 578 patients were included in the study and 402 were diagnosed with ACS (69.9%). The rate of readmission was 14.2% for patients with heart failure, compared to 7.5% for patients with ACS. Following the bundle of interventions, patients were significantly more likely to receive an appointment (45.6% vs. 75.4%, p<0.001), medication education from a pharmacist (38.5% vs. 56.7%, p=0.006), and a timely discharge (47.1% vs. 76.0%, p<0.001). Readmission rate was comparable following the intervention (8.6% vs. 9.7%), but patients that received an appointment had 0.374 times lower odds of being readmitted (p=0.004). CONCLUSIONS: While our package of interventions did not lead to a significant decline in our readmission rate, patients who received a follow-up appointment prior to discharge were strongly protected against readmission.

Healthcare Expenditure and Productivity Cost Savings from Reductions in Cardiovascular Disease and Type 2 Diabetes Associated with Increased Intake of Cereal Fibre among Australian Adults: A Cost of Illness Analysis.

An ageing population and growing prevalence of chronic diseases including cardiovascular disease (CVD) and type 2 diabetes (T2D) are putting increased pressure on healthcare expenditure in Australia. A cost of illness analysis was conducted to assess the potential savings in healthcare expenditure and productivity costs associated with lower prevalence of CVD and T2D resulting from increased intake of cereal fibre. Modelling was undertaken for three levels of increased dietary fibre intake using cereal fibre: a 10% increase in total dietary fibre; an increase to the Adequate Intake; and an increase to the Suggested Dietary Target. Total healthcare expenditure and productivity cost savings associated with reduced CVD and T2D were calculated by gender, socioeconomic status, baseline dietary fibre intake, and population uptake. Total combined annual healthcare expenditure and productivity cost savings of AUD$17.8 million-$1.6 billion for CVD and AUD$18.2 million-$1.7 billion for T2D were calculated. Total savings were generally larger among adults of lower socioeconomic status and those with lower dietary fibre intakes. Given the substantial healthcare expenditure and productivity cost savings that could be realised through increases in cereal fibre, there is cause for the development of interventions and policies that encourage an increase in cereal fibre intake in Australia.

La carga económica de las condiciones cardíacas en venezuela / The economic burden of heart conditions in venezuela

En Venezuela, las condiciones cardíacas imponen limitaciones físicas, sociales, financieras y de salud relacionadas con la calidad de vida de los individuos. Objetivos: Este estudio valoró la carga económica de cuatro condiciones cardíacas en Venezuela: hipertensión, insuficiencia cardíaca, infarto de miocardio y fibrilación auricular. Adicionalmente se evaluó el costo-efectividad de la telemedicina y el soporte telefónico estructurado para el manejo de la insuficiencia cardíaca.Métodos: Se utilizó un marco de costo de enfermedad estándar para valorar los costos asociados con las cuatro condiciones en 2015. El análisis evaluó la prevalencia e (en caso de infarto de miocardio) incidencia de las condiciones, los gastos asociados con el tratamiento médico, las pérdidas de productividad por reducción en el empleo, los costos de proveer cuidado formal e informal y la pérdida de bienestar. El análisis estuvo basado en información recolectada mediante una revisión de literatura y estadísticas, y modulación de datos. Todas las entradas de datos y métodos fueron validados mediante la consulta de quince clínicos y expertos en Venezuela. El análisis de costo-efectividad fue basado en un meta-análisis y en una evaluación económica de programas para pacientes con insuficiencia cardíaca dados de alta, valorado desde la perspectiva del Programa Nacional de Salud. Resultados: El infarto de miocardioimpone el mayor costo financiero (3,5 millones de bolívares/553 millones de USD), seguido por hipertensión arterial (3,4 millones de bolívares/539 millones de USD), la insuficiencia cardíaca (3,3 millones debolívares/522 millones de USD) y, finalmente, fibrilación auricular (0,4 miles de millones de bolívares/66 millones de USD). La telemedicina y el soporte telefónico estructurado son intervenciones costo-efectivas para alcanzar mejoras en el manejo de la insuficiencia cardíaca. Conclusiones: Las condiciones cardíacas imponen una pérdida sustancial de bienestar y de costos financieros en Venezuela y deberían ser una prioridad de salud pública

Heart conditions impose physical, social, financial and health related quality of life limitations on individuals in Venezuela. Objectives: This study assessed the economic burden of four main heart conditions in Venezuela: hypertension, heart failure, myocardial infarction, and atrial fibrillation. In addition, the cost-effectiveness of telemedicine and structured telephone support for the management of heart failure was assessed. Methods: A standard cost of illness framework was used to assess the costs associated with the four conditions in 2015. The analysis was informed by a targeted literature review, data scan and modeling. All inputs and methods were validated by consulting fifteen clinicians and other stakeholders in Venezuela. The cost-effectiveness analysis was based on a meta-analysis and economic evaluation of post-discharge programs in patients with heart failure, assessed from the perspective of the National Health Fund. Results: Myocardial infarction imposes the greatest financial cost (3.5 million bolivares/553 million USD), followed by hypertension (3.4 million bolivares/539 million USD), heart failure (3.3 million bolivares/522 million USD) and, finally, atrial fibrillation (0.4 billion bolivares/66 million USD).Telemedicine and structured telephone support are cost effective interventions for achieving improvements in the management of heart failure. The analysis assessed the prevalence and (in the case of myocardial infarction) incidence of the conditions, the associated expenditures on health care treatment, productivity losses from reduced employment, costs of providing formal and informal care, and lost wellbeing. Conclusions: Heart conditions impose substantial loss of wellbeing and financial costs in Venezuela and should be a public health priority(AU)

Microarray testing in clinical diagnosis: an analysis of 5,300 New Zealand patients.

BACKGROUND: The use of Microarray (array CGH) analysis has become a widely accepted front-line test replacing G banded chromosome studies for patients with an unexplained phenotype. We detail our findings of over 5300 cases. RESULTS: Of 5369 pre and postnatal samples, copy number variants (CNVs) were detected in 28.3 %, of which ~40 % were deletions and ~60 % were duplications. 96.8 % of cases with a CNV <5 Mb would not have been detected by G banding. At least 4.9 % were determined to meet the minimum criteria for a known syndrome. Chromosome 17 provided the greatest proportion of pathogenic CNVs with 65 % classified as (likely) pathogenic. X chromosome CNVs were the most commonly detected accounting for 4.2 % of cases, 0.7 % of these being classified as cryptic (likely) pathogenic CNVs. CONCLUSIONS: Microarray analysis as a primary testing strategy has led to a significant increase in the detection of CNVs (~29 % overall), with ~9 % carrying pathogenic CNVs and one syndromic case identified per 20 referred patients. We suggest these frequencies are consistent with other heterogeneous studies. Conversely, (likely) pathogenic X chromosome CNVs appear to be greater compared with previous studies.

The Diagnosis of Choriocarcinoma in Molar Pregnancies: A Revised Approach in Clinical Testing.

BACKGROUND: Hydatidiform moles occur in approximately 1 in 1,500 pregnancies; however, early miscarriages or spontaneous abortions may not be correctly identified as molar pregnancies due to poor differentiation of chorionic villi. METHODS: The current clinical testing algorithm used for the detection of hydatidiform moles uses a combination of morphological analysis and p57 immunostaining followed by ploidy testing to establish a diagnosis of either a complete or partial molar pregnancy. We review here 198 referrals for fluorescence in situ hybridization (FISH) ploidy testing, where the initial diagnosis based on morphology is compared to the final diagnosis based on a combination of morphology, FISH and p57 immunohistochemical (IHC) staining. RESULTS: Approximately 40% of cases were determined to be genetically abnormal, but only 28.8% of cases were diagnosed as molar pregnancies. The underestimation of complete molar pregnancies and those with androgenetic inheritance was also found to be likely using conventional diagnostic methods, as atypical p57 staining was observed in approximately 10% of cases. CONCLUSIONS: Our findings suggest that a revised approach to testing products of conception is necessary, with cases screened according to their clinical history in order to distinguish molar pregnancy referrals from hydropic pregnancies.

12q14 Microdeletions: Additional Case Series with Confirmation of a Macrocephaly Region.

To date, there have been only a few reports of patients carrying a microdeletion in chromosome 12q14. These patients usually present with pre- and postnatal growth retardation, and developmental delay. Here we report on two additional patients with both genotype and phenotype differences. Similar to previously published cases, one patient has haploinsufficiency of the HMGA2 gene and shows severe short stature and developmental delay. The second patient is only one of a handful without the loss of the HMGA2 gene and shows a much better growth profile, but with absolute macrocephaly. This patient's deletion is unique and hence defines a likely macrocephaly locus that contributes to the general phenotype characterising the 12q14 syndrome.

SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia.

Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

Microduplication of 3p26.3 implicated in cognitive development.

We report here a 34-month-old boy with global developmental delay referred for molecular karyotyping and fragile X studies. Molecular karyotype analysis revealed a microduplication in the 3p26.3 region involving part of the CHL1 and CNTN6 genes. Several deletions, one translocation, and one duplication have previously been described in this region of chromosome 3. The CHL1 gene has been proposed as a dosage-sensitive gene with a central role in cognitive development, and so the microduplication reported here appears to be implicated in our patient's phenotype.

A turner syndrome patient carrying a mosaic distal x chromosome marker.

A skin sample from a 17-year-old female was received for routine karyotyping with a set of clinical features including clonic seizures, cardiomyopathy, hepatic adenomas, and skeletal dysplasia. Conventional karyotyping revealed a mosaic Turner syndrome karyotype with a cell line containing a small marker of X chromosome origin. This was later confirmed on peripheral blood cultures by conventional G-banding, fluorescence in situ hybridisation and microarray analysis. Similar Turner mosaic marker chromosome cases have been previously reported in the literature, with a variable phenotype ranging from the mild "classic" Turner syndrome to anencephaly, agenesis of the corpus callosum, complex heart malformation, and syndactyly of the fingers and toes. This case report has a phenotype that is largely discordant with previously published cases as it lies at the severe end of the Turner variant phenotype scale. The observed cytogenetic abnormalities in this study may represent a coincidental finding, but we cannot exclude the possibility that the marker has a nonfunctioning X chromosome inactivation locus, leading to functional disomy of those genes carried by the marker.

A case of 17q21.31 microduplication and 7q31.33 microdeletion, associated with developmental delay, microcephaly, and mild dysmorphic features.

Concurrent cryptic microdeletion and microduplication syndromes have recently started to reveal themselves with the advent of microarray technology. Analysis has shown that low-copy repeats (LCRs) have allowed chromosome regions throughout the genome to become hotspots for nonallelic homologous recombination to take place. Here, we report a case of a 7.5-year-old girl who manifests microcephaly, developmental delay, and mild dysmorphic features. Microarray analysis identified a microduplication in chromosome 17q21.31, which encompasses the CRHR1, MAPT, and KANSL1 genes, as well as a microdeletion in chromosome 7q31.33 that is localised within the GRM8 gene. To our knowledge this is one of only a few cases of 17q21.31 microduplication. The clinical phenotype of patients with this microduplication is milder than of those carrying the reciprocal microdeletions, and suggests that the lower incidence of the former compared to the latter may be due to underascertainment.

Array comparative genomic hybridization identifies a heterozygous deletion of the entire KCNJ2 gene as a cause of sudden cardiac death.

BACKGROUND: Large gene rearrangements, not detectable by standard molecular genetic sequencing techniques, are present in a minority of patients with long QT syndrome. We aimed to screen for large rearrangements in genes responsible for long QT syndrome as part of the molecular autopsy of a 36-year-old woman who died suddenly and had a negative autopsy. A retrospective analysis of an ECG identified a long QT interval, but sequencing of known LQT genes was uninformative. METHODS AND RESULTS: Array comparative genomic hybridization was used to screen for deletions and duplications in 101 genes implicated in cardiac disorders and sudden death using a postmortem blood sample. A 542 kb deletion encompassing the entire KCNJ2 gene was identified in the decedent. The mother had electrocardiographic U-wave changes consistent with Andersen-Tawil syndrome and exaggerated by exercise but none of the characteristic noncardiac features. Fluorescence in situ hybridization confirmed the deletion in the decedent and established its presence in the mother. CONCLUSIONS: A novel application of array comparative genomic hybridization and fluorescence in situ hybridization has identified that long QT syndrome and sudden cardiac death may occur as a result of a deletion of an entire gene. The case also supports recent research suggesting that noncardiac features of Andersen-Tawil syndrome occur only with missense or minor gene rearrangements in the KCNJ2 gene, resulting in a dominant negative effect on Kir2.x channels.

Warfarin Management Pathway: A clear and safe algorithm, from admission to discharge.

Warfarin is the most commonly prescribed anticoagulant in the UK and the one most frequently associated with both fatal medication errors and litigation claims [1]. Its life-threatening interactions and side effects are a concern for all doctors. Identifying and implementing solutions to achieve safer prescribing and monitoring is imperative to improve patient safety. The National Patient Safety Agency (NPSA) has outlined the major risks associated with anticoagulant therapy and sought to establish safer practice [1]. The monitoring of safety indicators has been highlighted as a solution. This quality improvement project (QIP) introduces a management algorithm for oral anticoagulant therapy in hospital patients, validated through a completed audit cycle. It was completed at one district general hospital (DGH) in England and involved all inpatient wards. Doctors and pharmacists were interviewed to assess their knowledge of the correct pathways for management of patients on warfarin. The number of errors on hospital warfarin charts was audited over three weeks. These results, coupled with senior haematological advice led to the production of an algorithm illustrating the gold-standard pathway for warfarin management from admission to discharge. It was emailed to all doctors in the Trust and a laminated copy attached to hospital Pneumatic Tube System (PTS) machines. The warfarin charts were re-audited over the following three weeks. The results showed a marked decrease in errors and incomplete anticoagulation referrals as well as a reduction in doctors' anxiety around prescribing warfarin.

A case of primary amenorrhoea.

OBJECTIVE: To report a case of primary amenorrhoea and to describe an approach to evaluation. METHODS: Primary amenorrhoea can be due to diverse causes and needs detailed and astute evaluation. We report the case of a 17 years old individual born and brought up as a female, who was brought to us with primary amenorrhoea. Approach to such a patient with a review of available published literature is described. RESULTS: After detailed history, biochemical testing, imaging and karyotyping, we found that this patient had a XY karyotype with normal uterus, fallopian tubes and vagina, but streak gonads. CONCLUSION: Swyer syndrome (46,XY gonadal dysgenesis), a sex reversal disorder characterized by a phenotypic female with non-functional streak gonads, poorly developed secondary sexual characters, primary amenorrhoea and 46,XY karyotype was diagnosed. This patient was treated with gonadectomy and sex hormone replacement.

Implications of a Chr7q21.11 Microdeletion and the Role of the PCLO Gene in Developmental Delay.

We report here a 4-year-old boy with global developmental delay who was referred for karyotyping and fragile X studies. A small interstitial deletion on chromosome 7 at band 7q21 was detected in all cells examined. Subsequent molecular karyotype analysis gave the more detailed result of a 6.3 Mb heterozygous deletion involving the interstitial chromosome region 7q21.11. In this relatively gene-poor region, the presynaptic cytomatrix protein, Piccolo (PCLO) gene appears to be the most likely candidate for copy number loss leading to a clinical phenotype. G-banded chromosome analysis of the parents showed this deletion was inherited from the father. Molecular karyotype analysis of the father's genome confirmed that it was the same deletion as that seen in the son; however, the father did not share the severity of his son's phenotype. This cytogenetically-visible deletion may represent another example of a chromosomal rearrangement conferring a variable phenotype on different family members.

Clinical Outcomes and Counselling Issues regarding Partial Trisomy of Terminal Xp in a Child with Developmental Delay.

Female carriers of balanced translocations involving an X chromosome and an autosome offer genetic counselling challenges. This is in view of the number of possible meiotic outcomes, but also due to the impact of X chromosome-localised genes that are no longer subject to gene silencing through the X chromosome inactivation centre. We present a case where delineation of the extent of X chromosome-localised genes on the derivative autosome using molecular karyotyping offers critical information in the context of genetic counselling.

Delineation of 2q32q35 deletion phenotypes: two apparent "proximal" and "distal" syndromes.

We report on three patients with interstitial deletions of the long arm of chromosome 2 involving bands 2q32.1-q35. They presented with wide-ranging phenotypic variation including facial dysmorphisms, cleft palate, learning difficulties, behavioural issues and severe heart defects. Microarray analysis confirmed an 8.6 Mb deletion in patients 1 and 2 and a 24.7 Mb deletion in patient 3. We discuss the genes involved in the deleted regions including MYO1B, GLS, FRZB, SATB2, and CPS1 and compare the phenotype with those reported in the literature. Taken together, these data suggest that there is a spectrum of disease severity such that patients with deletions encompassing the region of 2q32.1q32.2, which includes the FRZB gene, show an apparently milder phenotype compared to those that lie further distal in 2q32.3q35 that encompasses the SATB2 gene.