Showing papers in "QJM: An International Journal of Medicine in 2007"

Scleroderma renal crisis: patient characteristics and long-term outcomes.

Abstract: Background: Scleroderma renal crisis (SRC) is an important complication of systemic sclerosis, causing acute renal failure, and usually hypertension. Aims: To review the clinical and pathological features of SRC, and correlate them with renal outcomes and mortality. Design: Retrospective case series. Methods: We identified 110 cases of SRC managed at a single centre between 1990 and 2005. Results: SRC occurred in 5% of scleroderma cases under follow-up. Cases were predominantly female (81%), with diffuse cutaneous disease (78%). RNA polymerase antibodies were found in 59% of cases tested. Almost all (108/110) received treatment with ACE inhibitors (ACEIs). Dialysis was not required in 36%, was required temporarily (for up to 3 years) in 23%, was required permanently in 41%. Patients not on dialysis showed improvement in estimated glomerular filtration rate after SRC (mean change +23 ml/min over 3 years). Poor renal outcome was associated with lower blood pressure at presentation, and with higher age in those requiring dialysis. Steroid use, microangiopathic haemolytic anaemia, and antibody profile were not related to renal outcome. In the 58 renal biopsies available for clinical correlation, acute changes of mucoid intimal thickening in arteries and fibrinoid necrosis in arterioles were associated with a poorer renal outcome. Mortality was high (59% survival at 5 years), and was higher in men. Discussion: Despite the efficacy of ACEIs in managing SRC, the poor long-term outcome warrants evaluation for additional treatments for this devastating complication of systemic sclerosis.

Cognitive assessment in the elderly: a review of clinical methods

Abstract: Doctors are poor at predicting patients’ cognitive function based on a routine, non-cognitive evaluation alone.1,,2 Cognitive assessment is a valuable clinical skill. It facilitates the diagnosis of disorders that impair thinking, and allows for more accurate estimates of functional ability to be made. Cognition also predicts mortality during hospital admissions.3 These benefits are clearly of practical value, and cognitive assessment may also be a skill that could be used in the Directly Observed Procedural Skills (DOPS) framework for on-going evaluation of training geriatricians and neurologists. As people age, changes occur within the brain that lead to differences in thinking and behaviour.4 Distinguishing these from the early stages of an abnormal (disease) process is fairly arbitrary; definitions usually depend upon an impact on social, functional or occupational activities. To further cloud the picture, there is a diagnosis of ‘cognitive impairment not dementia’ (CIND) also available to the clinician, which sits somewhere between normal ageing and dementia. Dementia rises in prevalence from 65 years, and to ∼33% of those aged >85 years.5–8 CIND is even more common, with an estimated prevalence of around 17% in people aged >65 years.9 Of course, changes in cognition are not specific to either CIND or dementia: other common causes in the elderly include delirium and depression. Two or more of these are frequently found within a single patient. Other, psychiatric (or ‘non-organic’), cognitive disorders (e.g. schizophrenia) are beyond the scope of this text. Cognitive assessment is commonly used for the following reasons: (i) screening for cognitive impairment; (ii) differential diagnosis of cause; (iii) rating of severity of disorder, or monitoring disease progression. These three factors form the basis of the structure of this review. A wide … Address correspondence to Dr H. Woodford, Department of Medicine for the Elderly, Cumberland Infirmary, Carlisle CA2 7HY. email: henry.woodford{at}ncumbria-acute.nhs.uk

Pulmonary aspergillosis: a clinical update

Abstract: Aspergillus spp may cause a variety of pulmonary diseases, depending on immune status and the presence of underlying lung disease. These manifestations range from invasive pulmonary aspergillosis in severely immunocompromised patients, to chronic necrotizing aspergillosis in patients with chronic lung disease and/or mildly compromised immune systems. Aspergilloma is mainly seen in patients with cavitary lung disease, while allergic bronchopulmonary aspergillosis is described in patients with hypersensitivity to Aspergillus antigens. Recent major advances in the diagnosis and management of pulmonary aspergillosis include the introduction of non-invasive tests, and the development of new antifungal agents, such as azoles and echincandins, that significantly affect the management and outcome of patients with pulmonary aspergillosis. This review provides a clinical update on the epidemiology, risk factors, clinical presentation, diagnosis and management of the major syndromes associated with pulmonary aspergillosis.

Spinal epidural abscess in clinical practice.

Abstract: Spinal epidural abscess (SEA) is a rare but severe infection requiring prompt recognition. The major prognostic factor for a favourable outcome is early diagnosis, leading to appropriate treatment. In clinical practice, a diagnosis of SEA is often not considered, particularly in the early stages of the disease when neurological symptoms are not apparent. Knowledge of persons at risk, clinical features and the required diagnostic procedures may decrease the number of initially misdiagnosed cases. Clinical signs, duration of symptoms and the rate of neurological deterioration show a high inter-individual variability, and the classic triad (spinal pain, fever and neurological deficit) is often not found, especially not at first presentation to a physician. However, most patients complain of severe localized back pain. Inflammatory parameters in the blood are generally elevated, but not specific. Gadolinium-enhanced magnetic resonance imaging is the most sensitive, specific and accurate imaging method. Although neurosurgical decompression is still the treatment of choice in the majority of cases, less invasive procedures (e.g. computed tomography-guided needle aspiration) or antimicrobial treatment alone can be applied in selected cases. The choice of the most appropriate therapy should be discussed immediately after a confirmed diagnosis in consultation with infectious disease, radiology and spinal surgery specialists. The outcome of SEA is largely influenced by the severity and duration of neurological deficits prior to surgery, stressing the importance of early recognition.

Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review

Abstract: Atrial fibrillation (AF) is associated with an increased stroke risk that may be reduced by therapeutic anticoagulation. However, anticoagulation is associated with an increased risk of bleeding that in some patients may outweigh the benefits in reducing the risk of stroke. We systematically reviewed the literature for risk factors of anticoagulation-related bleeding complications in patients with AF, as part of the formulation of recently published national guidelines for the management of AF. We identified nine studies that reported anticoagulation-related bleeding complications in AF patients. The following patient characteristics were identified as having supporting evidence for being risk factors for anticoagulation-related bleeding complications: advanced age, uncontrolled hypertension, history of myocardial infarction or ischaemic heart disease, cerebrovascular disease, anaemia or a history of bleeding, and the concomitant use of other drugs such as antiplatelet agents. The presence of diabetes mellitus, controlled hypertension and gender were not identified as significant risk factors. Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients. There is a need for further research in this area to help physicians to balance the risks and benefits of anticoagulation in AF patients.

Adherence to insulin and its association with glycaemic control in patients with type 2 diabetes

Abstract: Background: Good glycaemic control improves outcomes in patients with type 2 diabetes, but the extent to which this depends on adherence to insulin treatment is uncertain. Aim: To investigate the association between adherence to insulin and glycaemic control in insulin-treated patients with type 2 diabetes. Design: Observational records-based study. Methods: We studied all patients with type 2 diabetes who were resident in Tayside, Scotland from 1 January 1995 to 30 September 2001, and who were treated with insulin. Adherence to insulin treatment was measured as the annual number of days of insulin coverage on the recommended dose, calculated from the amount of drug dispensed at community pharmacies and the recommended dose level for each patient. The association between glycaemic control (HbA1c), and adherence was determined, as was the influence of covariates, including age, sex, duration of diabetes and number of injections per day. Results: A total of 1099 people were studied: 574 (52%) males and 525 (48%) females, mean ± SD age 62 ± 12 years, diabetes duration 10 ± 7 years. Median time in the study (time for which insulin was dispensed) was 1107 (range 366–2446) days. Insulin prescribed was 58.0 ± 33.3 IU/day and insulin collected from pharmacies was 53.6 ± 27.1 IU/day. Mean adherence to insulin was thus 70.6%±17.7%. Adherence to insulin ( p = 0.0021), BMI ( p = 0.0001) and diabetes duration ( p = 0.0314) were all significant predictors of HbA1c. Discussion: Adherence to insulin appears poor in these type 2 diabetes patients, and there was a significant relationship between adherence and long-term metabolic control.

Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort Study

Abstract: INTRODUCTION: Sarcopenia, the loss of muscle mass and strength with age, is significantly associated with type 2 diabetes in older people. AIM: To determine whether there is a relationship between grip strength and features of the metabolic syndrome. DESIGN: Cross-sectional study. METHODS: Data were collected on grip strength, fasting glucose, triglycerides and HDL cholesterol, blood pressure, waist circumference and 2 h glucose after an oral glucose tolerance test, in a population-based sample of 2677 men and women aged 59-73 years. RESULTS: In men and women combined, a standard deviation (SD) decrease in grip strength was significantly associated with higher: fasting triglycerides (0.05 SD unit increase, 95%CI 0.02-0.09, p = 0.006); blood pressure (OR 1.13, 95%CI 1.04-1.24, p = 0.004); waist circumference (0.08 SD unit increase, 95%CI 0.06-0.10, p DISCUSSION: Our findings suggest that impaired grip strength is associated with the individual features, as well as with the overall summary definitions, of the metabolic syndrome. The potential for grip strength to be used in the clinical setting needs to be explored.

Symptoms of autonomic dysfunction in chronic fatigue syndrome

Abstract: Background: Chronic fatigue syndrome (CFS) is common and its cause is unknown. Aim: To study the prevalence of autonomic dysfunction in CFS, and to develop diagnostic criteria. Design: Cross-sectional study with independent derivation and validation phases. Methods: Symptoms of autonomic dysfunction were assessed using the Composite Autonomic Symptom Scale (COMPASS). Fatigue was assessed using the Fatigue Impact Scale (FIS). Subjects were studied in two groups: phase 1 (derivation phase), 40 CFS patients and 40 age- and sex-matched controls; phase 2 (validation phase), 30 CFS patients, 37 normal controls and 60 patients with primary biliary cirrhosis. Results: Symptoms of autonomic dysfunction were strongly and reproducibly associated with the presence of CFS or primary biliary cirrhosis (PBC), and correlated with severity of fatigue. Total COMPASS score >32.5 was identified in phase 1 as a diagnostic criterion for autonomic dysfunction in CFS patients, and was shown in phase 2 to have a positive predictive value of 0.96 (95%CI 0.86–0.99) and a negative predictive value of 0.84 (0.70–0.93) for the diagnosis of CFS. Discussion: Autonomic dysfunction is strongly associated with fatigue in some, but not all, CFS and PBC patients. We postulate the existence of a ‘cross-cutting’ aetiological process of dysautonomia-associated fatigue (DAF). COMPASS >32.5 is a valid diagnostic criterion for autonomic dysfunction in CFS and PBC, and can be used to identify patients for targeted intervention studies.

Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review

Abstract: Several drugs, or categories of drugs, listed by the WHO and other writers and used in the treatment of chronic disease, are consistently associated with weight gain as a side effect and considered 'obesogenic'. The extent to which they may contribute to the multifactorial process behind obesity is not well documented. We systematically reviewed papers from Medline 1966-2004, Embase 1980-2004, PsycINFO 1967-2004, and Cochrane Register of Controlled Trials, to determine the effect on body weight of some drugs that are believed to favour weight gain. We included randomized controlled studies of adult participants (>18 years) prescribed a drug considered obesogenic, that compared the 'obesogenic' drug with placebo, an alternative drug or other treatment, and that had a duration of at least 3 months: 43 studies totalling 25,663 subjects met these criteria. The main objective of the majority of studies was to compare the efficacy and safety of drug therapy, with weight change recorded under safety outcomes; weight change was a primary outcome measure in only six studies. There was evidence of weight gain for all drugs included, up to 10 kg at 52 weeks. Differences in dosage, patient population, duration of treatment and dietary advice make generalization of the results difficult. Data on body weight are often not recorded in published clinical trials or is reported in insufficient detail. This side-effect has potentially serious consequences, and should be mentioned to patients. Weight management measures should be routinely considered when prescribing drugs known to promote weight gain. Future clinical trials should always document weight changes.

Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram

Abstract: Background: Although QT prolongation is associated with increased risk of torsade de pointes (TdP), the precise relationship is not well defined. Aim: To evaluate the performance of a QT nomogram in assessing the risk of TdP from QTRR combinations. Design: Systematic review. Methods: We systematically searched MEDLINE/EMBASE for cases of drug-induced TdP. Controls were patients taking non-cardiotoxic drugs in overdose. Inclusion criteria were definite TdP, normal ECG before or after the event, association with a drug/toxin and QTRR measurements available. The upper bound of a QTRR cloud diagram developed from human preclinical studies was converted into a QT nomogram [QT vs. heart rate (HR)]. QTHR combinations for TdP cases and controls were plotted with the QT nomogram, and curves corresponding to a QTc 440 ms and QTc 500 ms for comparison (Bazetts correction). Results: We identified 129 cases of TdP. TdP cases occurred at lower HR values with longer QT intervals, with most cases occurring at HR 3090 bpm. Controls were more evenly distributed, with HR 40160 bpm. The sensitivity and specificity of the QT nomogram were 96.9 (95CI 93.999.9) and 98.7 (95CI 96.8100), respectively. For Bazett QTc 440 ms, sensitivity and specificity were 98.5 (95CI 96.3100) and 66.7 (95CI 58.674.7), respectively, whereas for Bazett QTc 500 ms they were 93.8 (95CI 89.698.0) and 97.2 (95CI 94.3100), respectively. Discussion: The QT nomogram is a clinically relevant risk assessment tool that accurately predicts arrhythmogenic risk for drug-induced QT prolongation. Further prospective evaluation of the nomogram is needed.

Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis.

Abstract: Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Better understanding of its pathophysiology has led to the development of targeted therapies that have dramatically improved outcomes. The key to therapeutic success lies in identifying individuals who will have severe destructive disease as early as possible, so that effective treatment can be initiated before irreversible damage occurs. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. We discuss anti-CCP antibody testing in rheumatoid arthritis, with an emphasis on diagnostic performance, prognostic capability, and relevance to pathogenesis and new treatment paradigms in rheumatoid arthritis.

A medical definition of fatigue in multiple sclerosis

Abstract: Summary Background: The symptom of fatigue has been described in a variety of ways but absence of a single taxonomy may be hindering research into this prevalent symptom. Objective: To define the symptom of fatigue, as experienced by patients with multiple sclerosis (MS), in terms of a common framework, typical of a medical history. Design: Qualitative phase followed by crosssectional questionnaire survey. Method: Forty patients, with clinically definite MS, underwent semi-structured interviews which were analysed within a common framework of: experience (with derived themes of motor, cognitive, somatic/ energy, sleep, other features) cadence (i.e. short-term variability), chronicity, precipitating and aggravating factors, relieving factors, severity and associated features. The prevalence of each feature of fatigue, emergent from the interviews, was subsequently determined by questionnaire survey of a further 635 MS patients. Results: Despite variance across patients, fatigue could be described within the derived themes and framework. Nearly all themes were endorsed by the majority of questionnaire respondents. In summary, fatigue could be defined as reversible motor and cognitive impairment, with reduced motivation and desire to rest. It could appear spontaneously or may be brought on by mental or physical activity, humidity, acute infection and food ingestion. It was relieved by daytime sleep or rest without sleep. It could occur at any time but was usually worse in the afternoon. Conclusion: A framework, not only derived from patient experience but also meaningful in a medical context, was shown to be capable of describing fatigue in a large cross-section of MS patients. The definition may facilitate inter-disease comparison of fatigue as well as physiological enquiry.

The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis.

Abstract: We evaluated the effect of supplementation with vitamin D(3) (excluding the potential effect of calcium supplementation) on the risk of fall and fracture, primarily in postmenopausal women, using a systematic literature review of MEDLINE, EMBASE, BIOSIS and the Cochrane Database of Systematic Reviews for the period January 1985 to June 2005. Studies examining the effect of vitamin D versus placebo on the risk of fall or fracture in postmenopausal females were of particular interest. Studies of vitamin D in combination with calcium were also included where the control group was treated with calcium alone. Studies of men and women where results for men and women were not presented separately were included. Nine studies met the inclusion criteria. Our primary meta-analyses examined the effect of vitamin D(3) on the risk of fall or fracture; additional analyses examined baseline and difference between baseline and final levels of several serum and urinary biochemical markers. The pooled relative risk (RR) for vitamin D(3) preventing falls was 0.88 (95%CI 0.78-1.00). For fractures, the pooled RR for vitamin D(3) preventing non-vertebral fractures was 0.96 (95%CI 0.84-1.09) and the pooled RR for vitamin D(3) preventing vertebral fractures was 1.22 (95%CI 0.64-2.31). In a subgroup analysis of post-menopausal women, the pooled RR for vitamin D(3) preventing falls was 0.92 (95%CI 0.75-1.12) and in preventing non-vertebral fractures the pooled RR was 0.81 (95%CI 0.48-1.34). There is a trend towards a reduction in the risk of fall among patients treated with vitamin D(3) alone compared with placebo, suggesting that vitamin D(3) should be an integral part of effective osteoporosis management.

Multiple myeloma: causes and consequences of delay in diagnosis.

Abstract: Background: Myeloma is a serious and usually fatal haematological malignancy with reported mortality of 10–20% within the first 2 months of presentation. Symptoms are non-specific, and patients thus present to a range of medical practitioners. Aim: To analyse the causes and consequences of a delay in diagnosis of myeloma. Design: Retrospective case review. Methods: The number and type of disease–related complications present at diagnosis of 92 patients with myeloma were categorized according to the medical practitioner to whom the patient initially presented, the time before diagnosis and the status of the patient at study end in 2006. Overall and disease-free survival were analysed. Results: Duration of symptoms 46 months prior to diagnosis was seen in 40% of the patients, of whom 450% had initially consulted a general practitioner. The most common presenting symptom (67%) was bone pain. The most common complications present at diagnosis were anaemia (54%), bone disease (45%) and renal failure (36%), with the highest frequency of complications in the group experiencing symptoms for 46 months. All patients in this group had two or more complications, while 40% in the group with symptoms for <3 months had no complications. A prolonged time to diagnosis had a significant effect on disease-free survival from both onset of first symptoms (p ¼ 0.043) and from diagnosis (p ¼ 0.003), but not on overall survival. Discussion: A prolonged delay before diagnosis is associated with a significant impact on the clinical course of multiple myeloma. There is a need to raise awareness of the presentation of this condition, especially among general practitioners.

Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study

Abstract: BACKGROUND: Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data relate bone density, lipid profile and anthropometric measures. AIM: To investigate these relationships in a large, well-characterized cohort of men and women (The Hertfordshire Cohort Study). METHODS: Men (n = 465) and women (n = 448) from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur. RESULTS: BMD at the lumbar spine (males r = 0.15, p = 0.001; females r = 0.14, p = 0.003) and total femoral region (males r = 0.18, p = 0.0001; females r = 0.16, p = 0.0008) was related to serum triglyceride level, even after adjustment for waist-hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r = -0.15, p = 0.001) and total femoral BMD in both sexes (males r = -0.15, p = 0.002; females r = -0.23, p DISCUSSION: In this cohort, relationships between lipid profile and BMD were robust to adjustment for one measure of central obesity (waist-hip ratio), but not total body fat. This broadly supports the idea that adiposity may confound the relationship between lipids and bone mass.

Vascular access in haemodialysis patients: a modifiable risk factor for bacteraemia and death.

Abstract: Summary Background: Bacteraemia and the development of sepsis syndrome is second only to cardiovascular disease as the leading cause of death in patients on renal replacement therapy. Aim: To determine the contributions of laboratory and clinical variables to the risk of bacteraemia and death in haemodialysis patients. Design: Retrospective analysis. Methods: We analysed all patients receiving haemodialysis in our renal unit at the beginning of January 2004 (n ¼ 263), recording clinical and laboratory variables for each patient at study entry. Bacteraemia and mortality were recorded for the subsequent 18-month period. Multivariate analysis using a Cox proportional hazards model was used to test for independent associations between variables and outcomes. Results: During the study period, 45 patients (17.1%) developed bacteraemia and 65 (24.7%) died. Under multivariate analysis, use of dialysis catheters at study entry was a major factor in the development of bacteraemia and death with hazard ratios (HR) of 5.4 (p <0 .001) and 2.8 (p ¼ 0.012), respectively, for tunnelled central venous catheters vs. arteriovenous fistulas (AVFs) and 3.1 (p ¼ 0.01) and 3.4 (p ¼ 0.001), respectively, for non-tunnelled central venous catheters vs. AVFs. Elevated CRP at study entry was independently associated with bacteraemia (HR 1.5 per unit log-CRP, p ¼ 0.006). Low serum albumin (HR 0.92, p ¼ 0.005) was independently associated with death. Discussion: Use of synthetic vascular access catheters and heightened inflammatory state both have strong independent associations with subsequent bacteraemia and death. Bacteraemia surveillance strategies should be developed, with consideration of vascular access type and baseline inflammatory state as key components.

Extrinsic allergic alveolitis: incidence and mortality in the general population.

Abstract: Background: Extrinsic allergic alveolitis (EAA) is an important clinical entity, but its incidence and significance in the general population are uncertain. Aim: To estimate the incidence of EAA, and resulting mortality, in the UK. Design: General-population-based cohort study in a UK primary care database (THIN). Methods: THIN patients with an incident diagnosis of EAA were compared with a general population cohort whose members were 4:1 matched with EAA patients by age, sex and GP practice. Follow-up started at the first diagnosis of EAA (and at the same date in the matched controls) and ended at death or end of follow-up, whichever came first. Poisson, logistic, and Cox proportional hazard regression models were used; mortality rate, odd ratios, and hazard ratios were calculated. Results: We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at ∼0.9 cases per 100 000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39–0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05–4.33). Discussion: The incidence of EAA in the UK population appears to be stable overtime, and suggests about 600 new cases of EAA each year. People with EAA are less likely to smoke than the general population, but have a markedly increased mortality rate.

The MTHFR 677C->T polymorphism and the risk of congenital heart defects: a literature review and meta-analysis.

Abstract: Summary Background: Periconceptional folic acid supplementation may protect against congenital heart defects (CHDs). Identification of candidate genes in folate metabolism has suggested that the 677C!T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene may be particularly associated with the risk of CHDs. Aim: To assess the relationship between MTHFR 677C!T and CHDs by literature review and metaanalysis. Methods: Studies were identified by searches of electronic literature for papers focussing on MTHFR 677C!T and the risk of any type of CHD. Both case-control comparisons and transmission-disequilibrium tests (TDTs) in family-based designs were included. Results: We found 13 eligible studies. Of 10 casecontrol studies, four focused on the fetal polymorphism, two studied the maternal polymorphism, and a further four investigated both. Three further publications used a family-based association study to assess the effect of the T allele on cardiac development. Overall analysis yielded odds ratios of 1.3 (95%CI 0.97–1.73) and 1.2 (95%CI 0.83–1.74) for fetal and maternal MTHFR TT genotypes, respectively. TDTs revealed no association between fetal 677T allele and CHDs. Discussion: This relatively small meta-analysis found no substantial evidence of increased CHD risk in individuals with MTHFR 677CT and TT genotypes. Heterogeneity regarding population background, study design and type of heart defects complicates the pooling and comparison of the studies. The effect of modification by periconceptional folic acid intake should be taken into account. Further larger studies and well-defined phenotypic subcategory analyses are needed to decide whether the MTHFR 677C!T polymorphism of the affected child and/or their mother is truly a risk factor for the development of CHDs.

Cerebral hyperperfusion syndrome following carotid endarterectomy

Abstract: Extracranial internal carotid artery stenosis accounts for 15–20% of ischaemic strokes and carotid endarterectomy (CEA) is the most frequently performed surgical intervention in stroke prevention.1 The risk of stroke and death associated with the operation has been estimated at about 5.6% (95%CI 4.4–6.9).2 Neurological complications following CEA are usually ischaemic in nature, due to embolization or occlusion of the carotid artery. However, in a small subset of patients, cerebral hyperperfusion or reperfusion causes post-operative neurological dysfunction,3 characterized by ipsilateral headache, focal seizure activity, focal neurological deficit and ipsilateral intracerebral haemorrhage or oedema. Although rare, it can lead to significant morbidity and mortality if not correctly recognized and treated.4 The haemodynamic changes following CEA are complex and vary between patients.5–7 The main reason to perform CEA is removal of the source of emboli originating from carotid plaques. However, following successful endarterectomy there is increased blood flow in the ipsilateral carotid artery in almost all patients, related to the degree of pre-operative stenosis and hypoperfusion. In patients without pre-operative hypoperfusion, flow velocities generally peak on the first post-operative day and return to pre-operative values after 4–5 days. However, in patients with pre-operative hypoperfusion, flow velocities may remain high for many weeks.8,,9 Although cerebral blood flow (CBF) and perfusion increase in almost all patients following CEA, hyperperfusion is usually defined as a >100% increase in CBF compared to the pre-operative baseline.3 Hyperperfusion following CEA occurs in some 9–14% of patients, but only a minority develop symptoms as a result.10–12 Cerebral hyperperfusion syndrome (CHS) is a clinical triad of ipsilateral headache, seizure and focal neurological symptoms occurring in the absence of cerebral ischaemia.3,,11 It is accompanied by post-operative hypertension in almost all patients. The earliest description of CHS is a case …

Human heart-type fatty-acid-binding protein as a point-of-care test in the early diagnosis of acute myocardial infarction.

Abstract: Background: At very early stages of acute myocardial infarction (AMI), highly sensitive biomarkers are still lacking. Aim: To evaluate the utility of human heart-type fatty acid-binding protein (h-FABP) for early diagnosis of AMI. Design: Prospective diagnostic study. Methods: Consecutive patients presenting to the emergency department with chest pain or dyspnoea within 24 h of symptom onset were included. At presentation, the h-FABP test result was compared to the standard diagnostic work-up, including repeated ECG and troponin T measurements. Sensitivity analysis was performed for inconclusive tests. Results: We enrolled 280 patients presenting to hospital with a median symptom onset of 3 h (IQR 2–6 h): 109 (39%) had AMI. At presentation, h-FABP had a sensitivity of 69% (95%CI 59–77) and specificity of 74% (95%CI 66–80); 45 tests were false-positive and 34 were false-negative. Omitting inconclusive tests increased sensitivity and specificity only slightly. AMI was identified significantly earlier by h-FABP than by troponin T (24 vs. 8 patients, p = 0.005). Discussion: Although h-FABP can help to detect myocardial damage at an early stage in patients with chest pain or dyspnoea, it appears unsuitable as a stand-alone test for ruling out AMI.

Economic analysis of treatments reducing coronary heart disease mortality in England and Wales, 2000-2010.

Abstract: Background: Coronary heart disease (CHD) in the UK affects similar to 3 million people, with > 100 000 deaths annually. Mortality rates have halved since the 1980s, but annual NHS treatment costs for CHD exceed 2 pound billion. Aim: To examine the cost-effectiveness of specific CHD treatments in England and Wales. Methods: The IMPACT CHD model was used to calculate the number of life-years gained (LYG) from specific cardiological interventions from 2000 to 2010. Cost-effectiveness ratios (costs per LYG) were generated for each specific intervention, stratified by age and sex. The robustness of the results was tested using sensitivity analyses. Results: In 2000, medical and surgical treatments together prevented or postponed approximately 25 888 deaths in CHD patients aged 25-84 years, thus generating similar to 194 929 extra life-years between 2000 and 2010 (range 143 131-260 167). Aspirin and beta-blockers for secondary prevention following myocardial infarction or revascularisation, for angina and heart failure were highly cost-effective (<1000 pound per LYG). Other secondary prevention therapies, including cardiac rehabilitation, ACE inhibitors and statins, were reasonably cost-effective (1957 pound, 3398 pound and 4246 pound per LYG, respectively), as were CABG surgery (3239- pound 4601 pound per LYG) and angioplasty (3845- pound 5889 pound per LYG). Primary angioplasty for myocardial infarction was intermediate (6054- pound 12 pound 057 per LYG, according to age), and statins in primary prevention were much less cost-effective (27 pound 828 per LYG, reaching 69 pound 373 per LYG in men aged 35-44). Results were relatively consistent across a wide range of sensitivity analyses. Discussion: The cost-effectiveness ratios for standard CHD treatments varied by over 100-fold. Large amounts of NHS funding are being spent on relatively less cost-effective interventions, such as statins for primary prevention, angioplasty and CABG surgery. This merits debate.

Laboratory risk factors for hospital mortality in acutely admitted patients

Abstract: Summary Background: Many factors affecting hospital mortality in acutely admitted patients are poorly understood. Although scoring systems exist for critically ill patients, usually in intensive care units (ICUs), there are no specific mortality prediction systems for general acute admissions. Aim: To assess the relationship between simple admission laboratory variables on the risk of in-patient mortality. Design: Retrospective analysis of hospital admissions and laboratory databases. Methods: Where possible, all deceased patients in the 12-month period of study were matched with two surviving controls. The laboratory database was then analysed for admission investigations, including serum sodium, plasma glucose, and white blood cell (WCC) count. Abnormalities of these variables were then compared between cases (those who subsequently died), and controls (those who survived). Results: There were 16 219 admissions, with an overall mortality of 7.6%. We investigated 602 cases and 1073 controls. Hyperglycaemia (glucose 411.0 mmol/l) (OR 2.0, p < 0.0001); severe hyponatraemia (sodium <125 mmol/l) (OR 4.0, p < 0.0001); and leukocytosis (WCC 410 � 10 9 /l) (OR 2.0, p < 0.001) were significantly associated with mortality. The respective associations on logistic regression analysis were: glucose, OR 1.7, p ¼ 0.02; sodium, OR 4.4, p < 0.0001; WCC, OR 1.5, p ¼ 0.006. Low glucose levels, high sodium levels, and low WCC levels were also associated with increased mortality, leading to ‘U-shaped’ mortality associations. The effect of more than one laboratory abnormality being present was cumulative, in a linear fashion. Discussion: Plasma glucose, serum sodium and WCC are measured in most acutely admitted patients, and abnormalities of these variables have associations with in-hospital mortality. This may provide the basis for the development of a mortality risk scoring system.

Relative tachycardia in patients with sepsis: an independent risk factor for mortality

Abstract: Background: Excess activation of the sympathetic nervous system may be a risk factor for mortality in patients with the systemic inflammatory response syndrome (SIRS) or sepsis. Aim: To examine whether excessive tachycardia, relative to the degree of fever is an independent risk factor for death in patients with SIRS. Design: Prospective observational study. Setting: Departments of medicine in three university hospitals in Israel, Germany and Italy. Methods: We collected data for 3382 patients with SIRS, whether community- or hospital-acquired, 91% with sepsis, as part of an ongoing trial. Results: Overall 30-day mortality was 12% (408/3382). The pulse/temperature ratio was significantly higher in patients who died than in survivors: mean ± SD 2.55 ± 0.57 vs. 2.40 ± 0.48 bpm/°C ( p < 0.0001). Excessive tachycardia was significantly associated with a mortality in a logistic model accounting for other strong predictors of mortality (OR 1.54, 95%CI 1.10–2.17). Patients with septic shock were the only group for whom this association did not hold. Discussion: Our data are compatible with the hypothesis that some patients with sepsis experience an excess activation of the sympathetic nervous system, leading to a fatal outcome.

Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia

Abstract: Background: Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. Aim: To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. Design: Retrospective record review. Methods: From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. Results: Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels ( p = 0.027), lower plasma renin activity ( p = 0.037), and higher plasma aldosterone concentrations ( p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients ( p = 0.023), but not different between unilateral APA and BAH ( p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. Discussion: Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.

The value of clinical features in the diagnosis of acute pulmonary embolism: systematic review and meta-analysis.

Abstract: Background: Clinical assessment of patients with suspected pulmonary embolus (PE) is used to estimate the probability of PE and determine what (if any) diagnostic testing is required. Aim: We aimed to estimate the diagnostic value of individual clinical features used to determine the pre-test probability of acute PE. Design: Systematic review and meta-analysis. Methods: We searched electronic databases (1966 to May 2007) and the bibliographies of retrieved articles for any article that reported the diagnostic performance of clinical features compared to a reference standard diagnostic test in patients with suspected acute pulmonary embolism. Likelihood ratios were calculated for each feature and pooled using a random effects model, as implemented by MetaDiSc statistical software. Results: We identified 18 studies for inclusion with a total of 5997 patients. The most useful features (pooled likelihood ratio) for ruling in PE were syncope (2.38), shock (4.07), thrombophlebitis (2.20), current DVT (2.05), leg swelling (2.11), sudden dyspnoea (1.83), active cancer (1.74), recent surgery (1.63), haemoptysis (1.62) and leg pain (1.60); while the most useful features for ruling out PE were the absence of sudden dyspnoea (0.430), any dyspnoea (0.521) and tachypnea (0.561). All other clinical features had likelihood ratios near to one. Many of the analyses involved pooling results that had significant heterogeneity, so these estimates should be used with caution. Conclusions: Individual clinical features only slightly raise or lower the probability of PE. In isolation, they have limited diagnostic value and none can be used to rule in or rule out PE without further testing.

Hip fractures after stroke and their prevention

Abstract: Increased fracture risk is a recognized complication following stroke. Bone loss following a hemiplegic stroke has been proposed as a major risk factor for post-stroke hip fracture, with a recent focus on the development of novel therapeutic measures to prevent bone loss and fractures after stroke. We briefly review the literature on the epidemiology and pathophysiology of bone loss and hip fracture after stroke, and then critically review recent studies on preventive strategies.

Medical and legal confusion surrounding gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)

Abstract: Background: Gamma-hydroxybutyrate (GHB) is used as a recreational drug, with significant associated morbidity and mortality; it is therefore a class C drug under the Misuse of Drugs Act (1971). However, its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD) remain legally available despite having similar clinical effects. Aim: The aim of this study was to determine whether the relative proportions of self-reported ingestions of GHB or its precursors GBL and 1,4BD were similar to those seen in analysis of seized drugs. Design and methods: Retrospective review of our clinical toxicology database to identify all cases of self-reported recreational GHB, GBL and 1,4BD use associated with ED presentation in 2006. Additionally all seized substances on people attending local club venues were analysed by a Home Office approved laboratory to identify any illicit substances present. Results: In 2006, there were a total of 158 ED presentations, of which 150 (94.9%) and 8 (5.1%) were GHB and GBL self-reported ingestions respectively; 96.8% (153) were recreational use. Of the 418 samples seized, 225 (53.8%) were in liquid form; 85 (37.8%) contained GHB and 140 (62.2%) contained GBL. None of the seized samples contained 1,4BD and there were no self-reported 1,4BD ingestions. Conclusions: Self-reported GHB ingestion was much more common than GBL ingestion, whereas GBL was more commonly found in the seized samples. These differences suggest that GBL use may be more common than previously thought and we suggest that there should be further debate about the legal status of the precursors of GHB.

Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy.

Abstract: BACKGROUND Although in reversible takotsubo cardiomyopathy (TC), wall motion generally recovers dramatically within a few weeks, there are few data on changes in autonomic function in this condition. AIM To investigate cardiac autonomic function in the acute and chronic phases of TC. METHODS Ten patients with TC (mean age 70.1 +/- 13.7 years) underwent cardiac catheterization on the first hospital day, when left ventricular (LV) ejection fraction (EF) was calculated. A Holter electrocardiographic study was performed within 3 days after the onset of symptoms (0 months) and 3 months after discharge (3 months). The standard deviation of the mean cycle length of normal-normal R-R (NN) intervals over 24 h (SDNN), and the 24-h standard deviation of the mean value of the difference between the NN intervals for each 5-min segment (SDANN), were calculated according to time-area analysis of heart rate variability over 24 h. Frequency domain analysis was also done. RESULTS Coronary angiography in the acute and chronic phases revealed no significant stenosis in any TC patient. LV wall motion returned to normal in 17.6 +/- 6.4 days. LVEF was 45.7 +/- 8.8% in the acute phase and 69.8 +/- 6.8% after the improvement of wall motion (p < 0.001). Between 0 months and 3 months, SDNN and SDANN improved significantly, from 88.8 +/- 35.5 to 109.5 +/- 33.4 ms (p = 0.01) and from 79.9 +/- 34.7 to 99.3 +/- 40.3 ms (p = 0.03), respectively. No significant changes were observed in frequency domain parameters. DISCUSSION These results support our previous hypothesis that TC might be caused by neurogenic stunning of the myocardium, due to acute autonomic dysfunction.

Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures

Abstract: Background: Which diagnostic procedures should be used to differentiate between idiopathic and malignant pleural effusions, is not well established. Aim: To identify which parameters allow differentiation between idiopathic and malignant pleural effusions. Design: Case-note review. Methods: Over a 12-year period, we treated 1014 consecutive pleural effusion patients, of whom 346 were diagnosed as having an idiopathic or malignant aetiology. We analysed medical history, chest X-ray, pleural fluid analysis (biochemical, microbiological and cytological), chest CT scan and additional examinations that were used according to clinical findings, and compared them with the eventual diagnosis and outcome. Results: Eighty-three patients with idiopathic effusions and 263 with malignant effusions were included. Idiopathic pleural effusion resolved in 47 patients, improved in 20 and persisted in 16. Biochemical pleural fluid analysis did not predict these outcomes. A history of neoplasm, chest X-ray and CT features, as well as additional examinations according to clinical findings, established a diagnosis or suspicion of malignancy in 256 (97.7%) of the 263 patients who received a diagnosis of malignant effusion. Diagnostic thoracoscopy was helpful in seven patients in whom malignant disease was strongly suspected, despite the absence of other pathological findings. Discussion: Non-invasive complementary examinations generally allowed accurate differentiation between malignant and idiopathic effusions. Patients with idiopathic pleural effusions generally had favourable outcomes.

Similarities, overlap and differences between burnout and prolonged fatigue in the working population

Abstract: Background: Burnout and prolonged fatigue are related but distinct concepts that have seldom been empirically compared. Aim: To examine similarities, overlap and differences between burnout and prolonged fatigue. Design: Observational study. Methods: We analysed baseline data from the Maastricht Cohort Study on Fatigue at Work ( n = 12 140). The discriminative abilities of the Checklist Individual Strength (CIS) and the Maslach Burnout Inventory–General Survey (MBI-GS) were evaluated using principal component analysis. Overlap, similarities and differences regarding health, work and demographic factors between subgroups were assessed. Results: The discriminative abilities of the CIS and MBI-GS appeared to be moderate. Prolonged fatigue and burnout cases overlapped considerably. The subgroup consisting of cases with concurrent fatigue and burnout tended to have poorer outcomes in terms of health and work factors than the subgroups with either prolonged fatigue or burnout. Similar patterns were found for subjective fatigue and exhaustion. Discussion: There appear to be some relevant differences between burnout and prolonged fatigue, with respect to work and health factors. Burnout and prolonged fatigue can occur both separately and simultaneously. Having both conditions simultaneously seems to be associated with worse outcomes than having either alone.