RESUMO
Aims: Homozygous familial hypercholesterolaemia (FH) is a rare inherited disorder characterized by extreme hypercholesterolaemia from birth, accelerated atherosclerosis, and premature death. Many forms of lipid-lowering therapies have been used in the past, but definitive evidence of benefit has been lacking. We therefore undertook a retrospective survey of lipid levels and clinical outcomes of FH homozygotes treated with a combination of lipid-lowering measures between 1990 and 2014 in South Africa and the UK. Methods and results: We divided 133 previously statin-naive homozygotes into quartiles according to their on-treatment levels of serum cholesterol and compared the occurrence of any death, cardiovascular death, and major adverse cardiovascular events (MACE) between the quartiles during 25 years of follow-up, using Cox and competing risks regression analysis. Patients in Quartile 4, with an on-treatment serum cholesterol >15.1 mmol/L, had a hazard ratio of 11.5 for any death compared with those in Quartile 1, with an on-treatment cholesterol of < 8.1 mmol/L. Those in Quartiles 2 and 3 combined, with on-treatment cholesterol of 8.1-15.1 mmol/L had a hazard ratio of 3.6 compared with Quartile 1. These differences were statistically significant (P < 0.001) and remained so after adjustments for confounding factors (P = 0.04). Significant differences between quartiles were also evident for cardiovascular deaths and MACE. Conclusion: These findings provide unequivocal evidence that the extent of reduction of serum cholesterol achieved by a combination of therapeutic measures, including statins, ezetimibe, lipoprotein apheresis, and evolocumab, is a major determinant of survival in homozygous FH.
Assuntos
Colesterol/sangue , Hiperlipoproteinemia Tipo II/mortalidade , Adolescente , Adulto , Anticolesterolemiantes/uso terapêutico , Feminino , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Familial hypercholesterolaemia (FH) is an autosomal dominant disease of lipid metabolism, which leads to early coronary heart disease. Mutations in LDLR, APOB and PCSK9 can be detected in 80% of definite FH (DFH) patients. This study aimed to identify novel FH-causing genetic variants in patients with no detectable mutation. METHODS AND RESULTS: Exomes of 125 unrelated DFH patients were sequenced, as part of the UK10K project. First, analysis of known FH genes identified 23 LDLR and two APOB mutations, and patients with explained causes of FH were excluded from further analysis. Second, common and rare variants in genes associated with low-density lipoprotein cholesterol (LDL-C) levels in genome-wide association study (GWAS) meta-analysis were examined. There was no clear rare variant association in LDL-C GWAS hits; however, there were 29 patients with a high LDL-C SNP score suggestive of polygenic hypercholesterolaemia. Finally, a gene-based burden test for an excess of rare (frequency <0.005) or novel variants in cases versus 1926 controls was performed, with variants with an unlikely functional effect (intronic, synonymous) filtered out. CONCLUSIONS: No major novel locus for FH was detected, with no gene having a functional variant in more than three patients; however, an excess of novel variants was found in 18 genes, of which the strongest candidates included CH25H and INSIG2 (p<4.3×10(-4) and p<3.7×10(-3), respectively). This suggests that the genetic cause of FH in these unexplained cases is likely to be very heterogeneous, which complicates the diagnostic and novel gene discovery process.
Assuntos
LDL-Colesterol/genética , Hiperlipoproteinemia Tipo II/genética , Apolipoproteínas B/genética , Estudo de Associação Genômica Ampla , Humanos , Mutação/genética , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/genética , Receptores de LDL/genética , Serina Endopeptidases/genéticaRESUMO
The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBPα expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3'UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis.
Assuntos
Tecido Adiposo/metabolismo , Inibidor de Quinase Dependente de Ciclina p15/genética , Regulação da Expressão Gênica , Hiperlipidemia Familiar Combinada/genética , Células 3T3-L1 , Adipogenia/genética , Tecido Adiposo/patologia , Animais , Ciclo Celular/genética , Células HEK293 , Haplótipos , Humanos , Hiperlipidemia Familiar Combinada/patologia , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
A national agenda has been established for mental health systems to move toward a recovery model of care. Recovery principles are embedded in the foundations of nursing science and practice. Orem's Self-Care Deficit Nursing Theory (SCDNT) is in alignment with the ideals of recovery and can provide a structure for changing cultures on inpatient psychiatric units. SCDNT can guide research activities that link a patient's self-care abilities to improved recovery model outcomes. This paradigm shift is an opportunity for psychiatric nursing to return to its roots and deliver care that is patient-centered and conducive to recovering from mental illness.
Assuntos
Transtornos Mentais/enfermagem , Transtornos Mentais/reabilitação , Modelos de Enfermagem , Teoria de Enfermagem , Assistência Centrada no Paciente , Autocuidado/psicologia , Atividades Cotidianas/psicologia , Humanos , Relações Enfermeiro-Paciente , Avaliação de Resultados em Cuidados de Saúde , Alta do Paciente , Satisfação do Paciente , Qualidade de Vida/psicologia , Autocuidado/métodos , Estados UnidosRESUMO
This study explored the difference between male and female psychiatric nurses' job performance and job satisfaction levels on an acute care inpatient unit. The amount of time male (n = 28) and female (n = 45) nurses spent on 10 specific functions and roles during a shift were observed and recorded. The nurses also self-rated the amount of time they spent on these specific functions and roles. The observed and self-rated functions were then correlated with job satisfaction. Female nurses were observed and self-rated as spending significantly more time on patient care activities, and these activities were significantly correlated with higher job satisfaction levels. Male nurses who self-rated spending more time on patient care activities had significantly lower job satisfaction scores. Findings confirm the concepts from social role theory that gender identity and expectations influence job performance in psychiatric nursing. The results offer insight for increasing job satisfaction and recruitment/retention efforts.
Assuntos
Identidade de Gênero , Papel do Profissional de Enfermagem/psicologia , Enfermeiros/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Enfermagem Psiquiátrica/organização & administração , Mulheres Trabalhadoras/psicologia , Adulto , Idoso , Análise de Variância , Atitude do Pessoal de Saúde , California , Feminino , Humanos , Relações Interprofissionais , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Enfermeiros/organização & administração , Pesquisa Metodológica em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Teoria Psicológica , Autoimagem , Fatores Sexuais , Estatísticas não Paramétricas , Estudos de Tempo e Movimento , Mulheres Trabalhadoras/estatística & dados numéricosRESUMO
This study recorded the amount of time 73 nurses working on inpatient psychiatric units spent on specific functions during a shift. The nurses also rated the amount of time they actually spent on the functions versus the amount of time they ideally would like to spend. Nurses spent only 2.18 minutes per shift teaching symptom management, and close to 2 hours on paperwork. Correlations between time spent in specific functions and job satisfaction indicate that nurses who spent more time with direct patient care were more satisfied. The results offer insight for increasing job satisfaction and retention/recruitment efforts.
Assuntos
Hospitalização , Satisfação no Emprego , Transtornos Mentais/enfermagem , Papel do Profissional de Enfermagem/psicologia , Enfermagem Psiquiátrica , Adulto , Idoso , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , North Carolina , Relações Enfermeiro-Paciente , Registros de Enfermagem , Garantia da Qualidade dos Cuidados de Saúde , Inquéritos e Questionários , Estudos de Tempo e Movimento , Adulto JovemRESUMO
AIMS: To examine the changes in coronary, all-cause, and cancer mortality in patients with heterozygous familial hypercholesterolaemia (FH) before and after lipid-lowering therapy with statins. METHODS AND RESULTS: A total of 3382 patients (1650 men) aged <80 years were recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2006 for 46 580 person-years. There were 370 deaths, including 190 from coronary heart disease (CHD) and 90 from cancer. The standardized mortality ratio (compared with the population in England and Wales) was calculated before and from 1 January 1992. In patients aged 20-79 years, CHD mortality fell significantly by 37% (95% CI = 7-56) from 3.4- to 2.1-fold excess. Primary prevention resulted in a 48% reduction in CHD mortality from 2.0-fold excess to none, with a smaller reduction of nearly 25% in patients with established disease. Coronary mortality was reduced more in women than in men. In patients without known CHD at registration, all-cause mortality from 1992 was 33% (21-43), lower than in the general population, mainly due to a 37% (21-50) lower risk of fatal cancer. CONCLUSION: The results emphasize the importance of early identification of FH and treatment with statins.
Assuntos
Doença das Coronárias/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/mortalidade , Neoplasias/mortalidade , Adulto , Idoso , Doença das Coronárias/complicações , Inglaterra/epidemiologia , Métodos Epidemiológicos , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/prevenção & controle , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Sistema de Registros/estatística & dados numéricos , País de Gales/epidemiologia , Adulto JovemRESUMO
This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Benzimidazóis/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Homozigoto , Hiperlipoproteinemia Tipo II/terapia , Mutação , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Benzimidazóis/efeitos adversos , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/efeitos adversos , Doenças Cardiovasculares/genética , Terapia Combinada , Consenso , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Inibidores de PCSK9 , Fenótipo , Pró-Proteína Convertase 9/metabolismo , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Reino UnidoRESUMO
UNLABELLED: Background- Combined hyperlipidemia is a common disorder characterized by a highly atherogenic lipoprotein profile and increased risk of coronary heart disease. The etiology of the lipid abnormalities (increased serum cholesterol and triglyceride or either lipid alone) is unknown. METHODS AND RESULTS: We assembled 2 large cohorts of families with familial combined hyperlipidemia (FCHL) and performed disease and quantitative trait linkage analyses to evaluate the inheritance of the lipid abnormalities. Chromosomal regions 6q16.1-q16.3, 8p23.3-p22, and 11p14.1-q12.1 produced evidence for linkage to FCHL. Chromosomes 6 and 8 are newly identified candidate loci that may respectively contribute to the triglyceride (logarithm of odds [LOD], 1.43; P=0.005) and cholesterol (LOD, 2.2; P=0.0007) components of this condition. The data for chromosome 11 readily fulfil the guidelines required for a confirmed linkage. The causative alleles may contribute to the inheritance of the cholesterol (LOD, 2.04 at 35.2 cM; P=0.0011) component of FCHL as well as the triglyceride trait (LOD, 2.7 at 48.7 cM; P=0.0002). CONCLUSIONS: Genetic analyses identify 2 potentially new loci for FCHL and provide important positional information for cloning the genes within the chromosome 11p14.1-q12.1 interval that contributes to the lipid abnormalities of this highly atherogenic disorder.
Assuntos
Colesterol/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 6 , Cromossomos Humanos Par 8 , Hiperlipidemia Familiar Combinada/genética , Hiperlipidemia Familiar Combinada/metabolismo , Triglicerídeos/genética , Adulto , Idoso , Colesterol/metabolismo , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: Combined hyperlipidemia is a common disorder, characterized by a highly atherogenic lipoprotein profile and a substantially increased risk of coronary heart disease. The purpose of this study was to establish whether variations of apolipoprotein A5 (APOA5), a newly discovered gene of lipid metabolism located 30 kbp downstream of the APOA1/C3/A4 gene cluster, contributes to the transmission of familial combined hyperlipidemia (FCHL). METHODS AND RESULTS: We performed linkage and association tests on 128 families. Two independent alleles, APOA5c.56G and APOC3c.386G, of the APOA1/C3/A4/A5 gene cluster were overtransmitted in FCHL (P=0.004 and 0.007, respectively). This was paired with reduced transmission of the common APOA1/C3/A4/A5 haplotype (frequency 0.4461) to affected subjects (P=0.012). The APOA5c.56G genotype accounted for 7.3% to 13.8% of the variance in plasma triglyceride levels in probands (P<0.004). The APOC3c.386G genotypes accounted for 4.4% to 5.1% of the variance in triglyceride levels in FCHL spouses (P<0.007), suggesting that this allele marks a FCHL quantitative trait as well as representing a susceptibility locus for the condition. CONCLUSIONS: A combined linkage and association analysis establishes that variation at the APOA1/C3/A4/A5 gene cluster contributes to FCHL transmission in a substantial proportion of northern European families.
Assuntos
Apolipoproteína A-I/genética , Apolipoproteínas A/genética , Apolipoproteínas C/genética , Apolipoproteínas/genética , Hiperlipidemia Familiar Combinada/genética , Alelos , Apolipoproteína A-V , Apolipoproteína C-III , Europa (Continente)/epidemiologia , Feminino , Ligação Genética , Predisposição Genética para Doença , Variação Genética , Haplótipos/genética , Humanos , Hiperlipidemia Familiar Combinada/sangue , Hiperlipidemia Familiar Combinada/epidemiologia , Masculino , Família MultigênicaRESUMO
BACKGROUND AND AIMS: There is a paucity of data concerning the influence of lipid-lowering therapy on cardiovascular (CV) outcomes in patients with homozygous familial hypercholesterolaemia (FH). To redress this a retrospective analysis was undertaken of the demographic features, lipid levels, low density lipoprotein receptor and Autosomal Recessive Hypercholesterolaemia gene mutations, CV outcomes and vital status of 44 FH homozygotes referred to a single centre in the UK between 1964 and 2014. METHODS: Data were obtained from past publications, case records and death certificates. Differences in categorical and continuous variables between living and dead patients were analysed using Fisher's exact test and an independent t-test respectively. RESULTS: During the 50 years covered by this survey 13 patients have died, 30 are still alive and 1 was lost to follow up. The mean age of Alive patients was 32.6 ± 11.5 versus 28.3 ± 14.9 years in Dead ones (P = 0.31) and they were born 18 years later (P = 0.0001). Pre-treatment serum total cholesterol (TC) was similar in Alive and Dead (20.2 ± 5.1 v 21.3 ± 4.4 mmol/l, P = 0.52) but on-treatment TC was lower in Alive than Dead (8.1 ± 2.8 v 14.5 ± 6.0 mmol/l, P = 0.0001) and CV adverse events were far less frequent (eg aortic stenosis, 33% v 77%, P = 0.02). CONCLUSIONS: The lower on-treatment TC and fewer CV adverse events in FH homozygotes still living reflect advances in apheresis and drug therapy since the 1990s. Further improvements in prognosis can be expected with the impending introduction of novel lipid-lowering agents.
Assuntos
Doenças Cardiovasculares/terapia , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/genética , Adolescente , Adulto , Anticolesterolemiantes/uso terapêutico , Estenose da Valva Aórtica/tratamento farmacológico , Remoção de Componentes Sanguíneos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , LDL-Colesterol/sangue , Estudos de Coortes , Feminino , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/terapia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Mutação , Receptores de LDL/sangue , Receptores de LDL/genética , Estudos Retrospectivos , Reino Unido , Adulto JovemRESUMO
Evidence based treatment of cardiovascular risk factors on outcome in women is still inconclusive given the very large numbers needed to achieve a significant difference in cardiovascular event. Although numerous studies of the effect of hormone replacement therapy (HRT) on risk factors have suggested benefit, the only data from a randomised control trial of HRT in secondary prevention was neutral. Coronary disease-primary prevention: (a) Statins: Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEX CAPS). The only randomised controlled trial (RCT) to include women. There were fewer coronary heart disease (CHD) events in women but no difference in mortality. (b) HRT: no completed RCT-the results from Womens Health Initiative (WHI) and Women Intervention Study of Long Duration of Oestrogen in the Menopause (WISDOM) are awaited, the former likely to complete in 2004. There are numerous reports of positive observational epidemiological studies for HRT. There is little evidence for statin use in women who will probably not qualify for treatment on global CHD risk assessment, familial hypercholesterolemia and type 2 diabetes excepted. HRT is, therefore, not only appropriate for its multiple effects on lipoproteins, vascular function and insulin sensitivity but also for prevention of osteoporosis. Coronary disease- SECONDARY PREVENTION: (a) Statins: the major measurable effect of these drugs is to reduce total and LDL cholesterol. In RCT trials, the Scandanavian Simvastatin Survival Study (4S), the Cholesterol and Recurrent Event (CARE) and Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID), approximately 20% of subjects were female, in whom CHD events, but not CHD or total mortality were reduced. (b) HRT: there is data available from a single RCT of continuous combined premarin and medroxyprogesterone acetate (MPA) against placebo, The Heart Estrogen Replacement Study (HERS). A study of 2763 women and mean duration of 4.1 years. This study was neutral, with no reduction in CHD events or mortality. There were more events in the first year, and fewer in years 3-5. Other studies of HRT have been observational and positive for HRT. The effects of treatment on lipoproteins with statins, HRT and combination of statin and HRT have been investigated. In secondary prevention for hyperlipidemic women to achieve cholesterol <5, low density lipoprotein (LDL)<3 mmol/l statins will be first choice, possibly with HRT additionally for its other benefits on cardiovascular risk factors.
Assuntos
Doença das Coronárias/prevenção & controle , Terapia de Reposição de Estrogênios , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/prevenção & controle , Lovastatina/uso terapêutico , Doença das Coronárias/mortalidade , Feminino , Humanos , Metabolismo dos Lipídeos , Pós-Menopausa , Prevenção Primária , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
BACKGROUND: A high-density lipoprotein cholesterol level (HDL-C) <1 mmol/L is associated with increased cardiovascular morbidity and mortality. In clinical trials, fibrates have been shown to increase levels of HDL-C, with subsequent reduction in cardiovascular risk. OBJECTIVE: This study evaluated the use of fenofibrate 267 mg/d in a routine lipid clinic setting to determine how much HDL-C could be increased in everyday clinical practice. METHODS: Blood samples from patients who had taken fenofibrate 267 mg/d between 1998 and 2001 at the Lipid Clinic, Charing Cross Hospital, London, United Kingdom, were analyzed for changes in total cholesterol (TC), HDL-C, and triglycerides during follow-up. RESULTS: Sixty-five consecutive patients (49 men, 16 women; mean age, 54 +/- 1.2 years) were included in the study. The follow-up period ranged from 1 to 36 months (mean, 9.6 months +/- 26.7 days). Patients achieved a 6% overall increase in HDL-C, from 0.91 +/- 0.03 mmol/L to 0.97 +/- 0.03 mmol/L (P = 0.016). The TC/HDL-C ratio decreased by 21% from 7.0 +/- 0.3 mmol/L to 5.5 +/- 0.2 mmol/L (P < 0.001). Patients with lower levels of HDL-C at baseline (<0.9 mmol/L) showed the most improvement, with an 8% increase (P < 0.05). Twenty-eight patients (43%) reached a target HDL-C posttherapy value >1.0 mmol/L. Thirty-nine patients (responders) had increases in their HDL-C levels; 26 patients (nonresponders) had decreases or no change in their HDL-C levels. For the 26 (40%) patients in whom HDL-C did not increase, the TC/HDL-C ratio decreased by 12% from 6.5 +/- 0.3 mmol/L to 5.7 +/- 0.3 mmol/L (P = 0.003). CONCLUSIONS: Fenofibrate 267 mg/d is well tolerated and can achieve significant increases in HDL-C levels in clinical practice. However, these results should be confirmed in a larger routine clinical setting because of the discrepancies between the results of some clinical trials.
Assuntos
HDL-Colesterol/sangue , Fenofibrato/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Feminino , Fenofibrato/administração & dosagem , Hospitais Universitários , Humanos , Hiperlipidemias/metabolismo , Hipolipemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar/estatística & dados numéricos , Receptores Citoplasmáticos e Nucleares/agonistas , Estudos Retrospectivos , Fatores de Transcrição/agonistas , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
Including preventive models of health care in undergraduate education is essential as the nursing profession moves increasingly to community-based care. Traditionally, mental health curricula have focused primarily on psychopathology. This article presents current research in the attachment and temperament literature, which provides sound evidence for the need to synthesize prevention of mental illness concepts into undergraduate education. A curriculum model that integrates concepts from psychiatry and public health to prepare nursing students to promote mental health is described.
Assuntos
Enfermagem em Saúde Comunitária/educação , Bacharelado em Enfermagem , Transtornos Mentais/enfermagem , Transtornos Mentais/prevenção & controle , Psicologia/educação , Currículo , Humanos , Transtornos Mentais/psicologia , Apego ao Objeto , São Francisco , TemperamentoRESUMO
Patients with autosomal dominant hypercholesterolemia (ADH) have a high risk of developing cardiovascular disease that can be effectively treated using statin drugs. Molecular diagnosis and family cascade screening is recommended for early identification of individuals at risk, but up to 40% of families have no mutation detected in known genes. This study combined linkage analysis and exome sequencing to identify a novel variant in exon 3 of APOB (Arg50Trp). Mass spectrometry established that low-density lipoprotein (LDL) containing Arg50Trp APOB accumulates in the circulation of affected individuals, suggesting defective hepatic uptake. Previously reported mutations in APOB causing ADH have been located in exon 26. This is the first report of a mutation outside this region causing this phenotype, therefore, more extensive screening of this large and highly polymorphic gene may be necessary in ADH families. This is now feasible due to the high capacity of recently available sequencing platforms.
RESUMO
OBJECTIVE: To assess the relationship of levels of inflammatory risk markers to presence of clinical coronary artery disease (CAD) in patients with treated heterozygous familial hypercholesterolaemia. DESIGN: A cross-sectional study of patients on the Simon Broome Familial Hyperlipidaemia Register. SETTING: Six hospital outpatient clinics in the UK. PARTICIPANTS: A total of 211 men and 199 women with heterozygous familial hypercholesterolaemia. MAIN OUTCOME MEASURES: Analysis of conventional risk factors and concentrations of high-sensitivity C-reactive protein (hsCRP), lipoprotein(a), serum intercellular adhesion molecule (sICAM), interleukin-6 (IL-6) and lipoprotein-associated phospholipase A2 (LpPLA2) mass. RESULTS: CAD was present in 104 men and in 55 women; the mean ages of onset were 43.1 and 46.5 years, respectively. On univariate analysis there was a positive relationship of CAD with age, male sex, smoking, IL-6 and sICAM, and an inverse relationship with low-density lipoprotein (LDL) and LpPLA2. On multivariate analysis, age, smoking, low LDL and low LpPLA2 were associated with CAD. When LpPLA2 values were adjusted for apoB and aspirin usage, there was no significant difference between those with and without CAD. Only age and smoking were independently associated with CAD in men, and IL-6 and lipoprotein(a) in women. CONCLUSIONS: Although on univariate analysis inflammatory marker levels were associated with CAD in these patients, the majority of the associations, including that for hsCRP, disappeared when corrected for smoking and apoB. This may be because atherosclerotic plaques in these statin-treated patients were quiescent or an effect of aspirin usage. In this observational study newer risk markers were not usefully associated with the presence or absence of symptomatic CAD.
RESUMO
PROBLEM: In order to understand the risks and protective factors associated with poor health outcomes in adolescent mothers and their children, nurses need to design rigorous longitudinal research. Attrition of subjects can contribute to sampling error. Recruitment and retention efforts need to be optimized. METHODS: In a 4-year longitudinal study with adolescent mothers and their babies, the design for tracking included frequent phone calls, progressive monetary incentives, gifts, and one phone number of an alternative contact. FINDINGS: Of the 97 mother-infant dyads recruited, retention was 54% at 6 months and 38% at final data collection. Successful strategies included persistence in making contacts and utilizing alternative contact numbers. CONCLUSIONS: Retention rates for this study were low. With today's technology, many additional strategies need to be employed to improve retention rates with adolescent mothers.
Assuntos
Estudos Longitudinais , Mães/psicologia , Pesquisa Metodológica em Enfermagem/organização & administração , Seleção de Pacientes , Gravidez na Adolescência/psicologia , Sujeitos da Pesquisa/psicologia , Adolescente , Telefone Celular , Barreiras de Comunicação , Emoções Manifestas , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Relações Mãe-Filho , Pobreza , Gravidez , Enfermagem Psiquiátrica , Psicologia do Adolescente , Pesquisadores/educação , Pesquisadores/provisão & distribuição , Viés de SeleçãoRESUMO
Familial hypercholesterolaemia is one of the most common dominantly inherited disorders to be identified in primary care, leading to raised serum cholesterol evident from the first year of life. Around 1 in 500 people are affected by this condition, but less than 15% of these are currently attending lipid clinics, suggesting that the vast majority are unrecognised in general practice. The recently released National Institute for Health and Clinical Excellence evidence-based guideline on the identification and management of familial hypercholesterolaemia provides an opportunity to bridge this gap. Primary care has a role in systematic and opportunistic case finding, such as recognising the relevance of a family history of premature coronary heart disease and/or grossly elevated cholesterol. Although affected individuals need specialist care, GPs can reinforce the information provided by specialists and support cascade screening to other affected members of the extended family.