Dementia early diagnosis: triggers, supports and constraints affecting the decision to engage with the health care system

Objectives: There is very often a lengthy delay between first noticing symptoms of dementia and making first contact with Health Care Professionals (HCPs). This article identifies influences on the decision to contact HCPs for the first time.

Method: Qualitative thematic analysis of 20 case studies of carer experience. Participants were carers of people who attended Memory Clinic services.

Results: Key themes emerging were: triggers, supports and constraints. The analysis draws out the social nature of the decision to engage with the health care system, considering the negotiations that occur and the areas that are contested.

Conclusions: Constraints generate delays at several points during the journey from first noticing something may be amiss to making first contact with an HCP. Supports and Triggers legitimise carer's actions to contact HCPs for the first time.     

The role of the medical registrar

The medical registrar in the acute on-call and out-of-hours setting is usually considered to be one of the busiest and most challenging jobs in the entire hospital. This is perhaps a reflection of the changes in the structure and organisation of acute medicine precipitated by the European Working Time Directive and Modernising Medical Careers. As well as the general feeling that medicine is being increasingly viewed as a default referral option by other specialties who are themselves becoming ever more sub-specialised. This article explores what the pragmatic role of the medical registrar broadly should be. The Medical Workforce Unit at the Royal College of Physicians is launching an initiative, part funded by the Department of Health, to answer this difficult question.     

Risk factors for metabolic syndrome independently predict arterial stiffness and endothelial dysfunction in patients with chronic kidney disease and minimal comorbidity

OBJECTIVE

Metabolic syndrome (MS) is common in patients with chronic kidney disease (CKD), but its contribution to arterial stiffness and endothelial dysfunction in CKD is not well defined. We hypothesized that risk factors for MS would independently predict arterial stiffness and endothelial dysfunction in CKD patients.

RESEARCH DESIGN AND METHODS

Risk factors for MS, carotid-femoral pulse wave velocity (CF-PWV) and flow-mediated dilation (FMD) as measures of arterial stiffness and endothelial dysfunction, respectively, were assessed in 113 minimally comorbid CKD patients and in 23 matched control subjects.

RESULTS

CF-PWV correlated with systolic blood pressure (SBP), waist circumference, and plasma glucose (r² = 0.25, 0.09, and 0.09; P < 0.01 for all). FMD correlated with SBP (r² = 0.09; P < 0.01) and waist circumference (r² = 0.03; P < 0.05). CF-PWV increased progressively (r² = 0.07; P < 0.01) with increasing number of risk factors for MS. In multiple linear regression, SBP and waist circumference were independent determinants of CF-PWV, whereas only SBP predicted FMD.

CONCLUSIONS

The number of MS risk factors is an important determinant of arterial stiffness in CKD patients irrespective of the degree of renal impairment. Although BP remains the major determinant of arterial stiffness and endothelial dysfunction, waist circumference independently predicts arterial stiffness. MS risk factors, particularly abdominal girth, are potential targets for future interventional studies in patients with CKD.Chronic kidney disease (CKD) is common and associated with an increased risk of cardiovascular disease (CVD) (1). Conventional (Framingham) CVD risk factors, including high blood pressure (BP), hypercholesterolemia, and diabetes, all of which are common in CKD patients, only partly explain the high cardiovascular risk (2). CKD is now regarded as an independent risk factor for CVD (1,3), and we have recently shown that renal dysfunction also contributes to arterial stiffness and endothelial dysfunction in a group of minimally comorbid CKD patients (4).Increased arterial stiffness, as measured by pulse wave velocity (PWV), is a commonly recognized feature of CKD (4), a marker of cardiovascular risk (5,6), and an independent predictor of mortality and survival in dialysis patients (6). The vascular endothelium is an important regulator of arterial stiffness (7), and endothelial dysfunction is also a common feature of CKD (8) and a predictor of CVD (9).Metabolic syndrome (MS) is a clustering of metabolic abnormalities and risk factors for CVD and includes abdominal obesity, hyperglycemia, hypertension, hypertriglyceridemia, and reduced HDL cholesterol (10). As MS is associated with increased risks of diabetes and CVD (11,12), its treatment and prevention have become one of the major public health challenges worldwide. The risk factors for MS, either together or individually, are also associated with arterial stiffness and endothelial dysfunction both in health (13,14) and disease (15,16).MS is widely prevalent in CKD (17) and is itself a risk factor for CKD (18). Although a recent study has suggested that MS and its risk factors contribute to arterial stiffness and endothelial dysfunction in dialysis patients (19), there are no data relating to predialysis CKD. This is clearly important because targeting MS risk factors in early CKD may retard CKD progression, delaying the onset of dialysis and its associated morbidity, as well as reducing the overall risk of CVD.In this current study, we investigated the relationships of MS and its individual components to arterial stiffness and endothelial dysfunction in CKD patients across a wide range of renal function from early CKD to predialysis. Importantly, we planned to recruit patients without diabetes or cardiovascular comorbidity. We hypothesized that the presence of MS, or its components, would be associated with increased arterial stiffness and endothelial dysfunction and that these relationships would be independent of renal function and other well-established risk factors for CVD.     

Genome-wide association studies establish that human intelligence is highly heritable and polygenic

General intelligence is an important human quantitative trait that accounts for much of the variation in diverse cognitive abilities. Individual differences in intelligence are strongly associated with many important life outcomes, including educational and occupational attainments, income, health and lifespan. Data from twin and family studies are consistent with a high heritability of intelligence, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated adults with data on 549,692 single nucleotide polymorphisms (SNPs) and detailed phenotypes on cognitive traits. We estimate that 40% of the variation in crystallized-type intelligence and 51% of the variation in fluid-type intelligence between individuals is accounted for by linkage disequilibrium between genotyped common SNP markers and unknown causal variants. These estimates provide lower bounds for the narrow-sense heritability of the traits. We partitioned genetic variation on individual chromosomes and found that, on average, longer chromosomes explain more variation. Finally, using just SNP data we predicted ～1% of the variance of crystallized and fluid cognitive phenotypes in an independent sample (P=0.009 and 0.028, respectively). Our results unequivocally confirm that a substantial proportion of individual differences in human intelligence is due to genetic variation, and are consistent with many genes of small effects underlying the additive genetic influences on intelligence.     

MMPI-2 restructured form over-reporting scales in first-episode psychosis

MMPI-2-RF over-reporting scales for physical, cognitive, or psychological symptoms were examined in 130 consecutive referrals to a first-episode psychosis (FEP) clinic. Although acutely ill upon presentation, consistent and responsive profiles were obtained in 79% of the sample. There was no indication of under-reporting on defensive scales, and anticipated elevations were observed on clinical scales sensitive to thought disorder, ideas of persecution, and aberrant experiences. The Infrequent Somatic (Fs), Symptom Validity Scale (FBS-r), and Response Bias (RBS) scales did not indicate somatic or cognitive over-reporting, but the Infrequent Psychopathology Scale (Fp-r) showed a moderate elevation that may suggest a propensity for over-reporting or an effect of clinical symptoms on the over-reporting scale. Clinician ratings of positive symptoms of psychosis were related to the Fp-r. Although the over-reporting classifications with the RBS were relatively low, RBS scores were directly related to positive and general symptoms of psychosis. The MMPI-2-RF appears to have clinical value in an acutely ill FEP sample. The sample was not prone to over-reporting pathology, but associations between both the Fp-r and the RBS with clinical symptoms will warrant further investigation.     

Endovascular treatment of intracranial aneurysms: review of current practice

Subarachnoid haemorrhage remains a major cause of morbidity and mortality throughout the world. Of those suffering the condition, 15% are known to die before they reach hospital and half of all patients die within 1 month of presentation. Of those patients who survive the initial 30 days, just under half are believed to remain dependent for their normal activities of daily living. In the vast majority of cases, SAH results from the rupture of an intracranial aneurysm. After patient stabilisation, primary treatment is focused on the prevention of re-bleeding. Until recently, this exclusively involved the surgical clipping of the ruptured aneurysm via a craniotomy. The early 1990s, with the introduction of aneurysmal coiling via endovascular intervention, heralded the dawn of a new treatment option. Presently, endovascular therapy largely supersedes surgical intervention in the management of intracranial aneurysms in the developed world. Moreover, with the emergence of new technologies and approaches for the treatment of aneurysms, the field of neurovascular intervention is only likely to expand further. However, due to its relative infancy, unanswered questions regarding long term endovascular outcome remain. This is particularly pertinent to newer techniques of embolisation for which data on complete aneurysmal occlusion rates are limited. Thus, to understand fully the capability and limitations of this treatment, further well constructed randomised controlled trials are a necessity.     

Sequelae and survivorship in patients treated with 131I-MIBG therapy

Background:

¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae.

Methods:

Fifty-eight patients with metastatic NETs and CCTs who had received ¹³¹I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated.

Results:

In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of ¹³¹I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of ¹³¹I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function.

Conclusion:

Long follow up of ¹³¹I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.