Acute myocardial infarction incidence and hospital mortality: routinely collected national data versus linkage of national registers

Background and Objective To compare levels of and trends in incidence and hospital mortality of first acute myocardial infarction (AMI) based on routinely collected hospital morbidity data and on linked registers. Cases taken from routine hospital data are a mix of patients with recurrent and first events, and double counting occurs when cases are admitted for an event several times during 1 year. By linkage of registers, recurrent events and double counts can be excluded. Study Design and Setting In 1995 and 2000, 28,733 and 25,864 admissions for AMI were registered in the Dutch national hospital discharge register. Linkage with the population register yielded 21,565 patients with a first AMI in 1995 and 20,414 in 2000. Results In 1995 and 2000, the incidence based on the hospital register was higher than based on the linked registers in men (22% and 23% higher) and women (18% and 20% higher). In both years, hospital mortality based on the hospital register and on linked registers was similar. The decline in incidence between 1995 and 2000 was comparable whether based on standard hospital register data or linked data (18% and 20% in men, 15% and 17% in women). Similarly, the decline in hospital mortality was comparable using either approach (11% and 9% in both men and women). Conclusion Although the incidence based on routine hospital data overestimates the actual incidence of first AMI based on linked registers, hospital mortality and trends in incidence and hospital mortality are not changed by excluding recurrent events and double counts. Since trends in incidence and hospital mortality of AMI are often based on national routinely collected data, it is reassuring that our results indicate that findings from such studies are indeed valid and not biased because of recurrent events and double counts

Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element

Due to its similarity to humans, the pig is increasingly being considered as a good animal model for studying a range of human diseases. Despite their physiological similarities, differential expression of the myosin heavy chain (MyHC) IIB gene (MYH4) exists in the skeletal muscles of these species, which is associated with a different muscle phenotype. The expression of different MyHC isoforms is a critical determinant of the contractile and metabolic characteristics of the muscle fibre. We aimed to elucidate whether a genomic mechanism was responsible for the drastically different expression of MYH4 between pigs and humans, thus improving our understanding of the pig as a model for human skeletal muscle research. We utilized approximately 1 kb of the MYH4 promoter from a domestic pig and a human (which do and do not express MYH4, respectively) to elucidate the role of the promoter sequence in regulating the high expression of MYH4 in porcine skeletal muscle. We identified a 3 bp genomic difference within the proximal CArG and Ebox region of the MYH4 promoter of pigs and humans that dictates the differential activity of these promoters during myogenesis. Subtle species-specific genomic differences within the CArG-box region caused differential protein-DNA interactions at this site and is likely accountable for the differential MYH4 promoter activity between pigs and humans. We propose that the genomic differences identified herein explain the differential activity of the MYH4 promoter of pigs and humans, which may contribute to the differential expression patterns displayed in these otherwise physiologically similar mammals. Further, we report that both the pig and human MYH4 promoters can be induced by MyoD over- expression, but the capacity to activate the MYH4 promoter is largely influenced by the 3 bp difference located within the CArG-box region of the proximal MYH4 promoter

Study of recent and future trends in place of death in Belgium using death certificate data: a shift from hospitals to care homes

<p>Abstract</p> <p>Background</p> <p>Since most patients prefer out-of-hospital death, place of death can be considered an indicator of end-of-life care quality. The study of trends in place of death is necessary to examine causes of shifts, to evaluate efforts to alter place of death and develop future policies. This study aims to examine past trends and future projections of place of death.</p> <p>Methods</p> <p>Analysis of death certificates (decedents aged ≥ 1 year) in Belgium (Flanders and Brussels Capital region) 1998-2007. Trends in place of death were adjusted for cause of death, sociodemographic characteristics, environmental factors, numbers of hospital beds, and residential and skilled nursing beds in care homes. Future trends were based on age- and sex-specific mortality prognoses.</p> <p>Results</p> <p>Hospital deaths decreased from 55.1% to 51.7% and care home deaths rose from 18.3% to 22.6%. The percentage of home deaths remained stable. The odds of dying in a care home versus hospital increased steadily and was 1.65 (95%CI:1.53-1.78) in 2007 compared to 1998. This increase could be attributed to the replacement of residential beds by skilled nursing beds. Continuation of these trends would result in the more than doubling of deaths in care homes and a decrease in deaths at home and in hospital by 2040.</p> <p>Conclusions</p> <p>Additional end-of-life care resources in care homes largely explain the decrease in hospital deaths. Care homes will become the main locus of end-of-life care in the future. Governments should provide sufficient skilled nursing resources in care homes to fulfil the end-of-life care preferences and needs of patients.</p

Hospitalisations at the end of life: using a sentinel surveillance network to study hospital use and associated patient, disease and healthcare factors

<p>Abstract</p> <p>Background</p> <p>Hospital deaths following several hospital admissions or long hospital stays may be indicative of a low quality of dying. Although place of death has been extensively investigated at population level, hospital use in the last months of life and its determinants have been studied less often, especially in Europe and with a general end-of-life patient population. In this study we aim to describe hospital use in the last three months of life in Belgium and identify associated patient, disease and healthcare factors.</p> <p>Methods</p> <p>We conducted a retrospective registration study (13 weeks in 2004) with the Belgian Sentinel Network of General Practitioners, an epidemiological surveillance system representative of all GPs in Belgium, covering 1.75% of the total Belgian patient population. All registered non-sudden or expected deaths of patients (aged one year or older) at the GPs' practices were included. Bivariate and regression analyses were performed.</p> <p>Results</p> <p>The response rate was 87%. The GPs registered 319 deaths that met inclusion criteria. Sixty percent had been hospitalised at least once in the last three months of life, for a median of 19 days. The percentage of patients hospitalised increased exponentially in the last weeks before death; one fifth was admitted in the final week of life. Seventy-two percent of patients hospitalised at least once in the final three months died in hospital. A palliative treatment goal, death from cardiovascular diseases, the expression of a wish to die in an elderly home and palliative care delivery by the GP were associated with lower hospitalisation odds.</p> <p>Conclusion</p> <p>Hospital care plays a large role in the end of patients' lives in Belgium, especially in the final weeks of life. The result is a high rate of hospital deaths, showing the institutionalised nature of dying. Patients' clinical conditions, the expression of preferences and also healthcare characteristics such as being treated as a palliative care patient, seem to be associated with hospital transfers. It is recommended that hospitalisation decisions are only made after careful consideration. Short admissions in the final days of life should be prevented in order to make dying at home more feasible.</p

Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth

We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20ppm in feed) or Reporcin (recombinant growth hormone; GH; 10mg/48hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p=0.002) and muscle weights (Vastus Lateralis: p<0.001; Semitendinosus: p=0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p<0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p<0.05) and 7 (p<0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p<0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth

Utilization of acute and long-term care in the last year of life: comparison with survivors in a population-based study

Background. It is well-known that the use of care services is most intensive in the last phase of life. However, so far only a few determinants of end-of-life care utilization are known. The aims of this study were to describe the utilization of acute and long-term care among older adults in their last year of life as compared to those not in their last year of life, and to examine which of a broad range of determinants can account for observed differences in care utilization. Methods. Data were used from the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified population-based cohort of 3107 persons aged 55 ? 85 years at baseline and representative of the Netherlands, follow-up cycles took place at 3, 6 and 9 years. Those who died within one year directly after a cycle were defined as the "end-of-life group" (n = 262), and those who survived at least three years after a cycle were defined as the "survivors". Utilization of acute and long-term care services, including professional and informal care, were recorded at each cycle, as well as a broad range of health-related and psychosocial variables. Results. The end-of-life group used more care than the survivors. In the younger-old this difference was most pronounced for acute care, and in the older-old, for long-term care. Use of both acute and long-term home care in the last year of life was fully accounted for by health problems. Use of institutional care at the end of life was partly accounted for by health problems, but was not fully explained by the determinants included. Conclusion. This study shows that severity of health problems are decisive in the explanation of the increase in use of care services towards the end-of-life. This information is essential for an appropriate allocation of professional health care to the benefit of older persons themselves and their informal caregivers. © 2009 Pot et al; licensee BioMed Central Ltd

The Beta-adrenergic agonist, Ractopamine, increases skeletal muscle expression of Asparagine Synthetase as part of an integrated stress response gene program

Abstract Synthetic beta-adrenergic agonists (BA) have broad biomedical and agricultural application for increasing lean body mass, yet a poor understanding of the biology underpinning these agents is limiting further drug discovery potential. Growing female pigs (77 ± 7 kg) were administered the BA, Ractopamine (20 ppm in feed), or the recombinant growth hormone (GH), Reporcin (10 mg/48 hrs injected) for 1, 3, 7, 13 (n = 10 per treatment, per time point) or 27 days (n = 15 per treatment). Using RNA-sequencing and inferred pathway analysis, we examined temporal changes to the Longissimus Dorsi skeletal muscle transcriptome (n = 3 per treatment, per time point) relative to a feed-only control cohort. Gene expression changes were affirmed by quantitative-PCR on all samples (n = 164). RNA-sequencing analysis revealed that BA treatment had greater effects than GH, and that asparagine synthetase (Asns) was the 5th most significantly increased gene by BA at day 3. ASNS protein expression was dramatically increased by BA treatment at day 7 (p < 0.05). The most significantly increased gene at day 3 was activating transcription factor 5 (Atf5), a transcription factor known to regulate ASNS gene expression. Gene and protein expression of Atf4, another known regulator of Asns expression, was not changed by BA treatment. Expression of more than 20 known Atf4 target genes were increased by BA treatment, suggesting that BA treatment induces an integrated stress response (ISR) in skeletal muscle of pigs. In support of this, mRNA expression of sestrin-2 (Sesn2) and cyclin-dependant kinase 1 alpha (Cdkn1a), two key stress-responsive genes and negative regulators of cellular growth, were also strongly increased from day 3 of BA treatment. Finally, tRNA charging was the most significantly enriched pathway induced by BA treatment, suggesting alterations to the translational capacity/efficiency of the muscle. BA-mediated changes to the skeletal muscle transcriptome are highly indicative of an integrated stress response (ISR), particularly genes relating to amino acid biosynthesis and protein translational capacity