Showing papers in "QJM: An International Journal of Medicine in 2004"
TL;DR: The history, physiology, current indications for and effects of hyperbaric oxygen therapy are outlined, and the history and literature surrounding its use are outlined.
Abstract: Hyperbaric oxygen therapy (HBO) is increasingly used in a number of areas of medical practice. It is a unique intervention whose method of action is not well understood. Clinicians may request its use for their patients, but often will not fully understand its mechanisms. It is hoped that this review and discussion of HBO and the literature surrounding its use may be useful to clinicians who are unsure whether their patients will benefit from this exciting intervention.
Hyperbaric oxygen therapy is defined by the Undersea and Hyperbaric Medical Society (UHMS) as a treatment in which a patient intermittently breathes 100% oxygen while the treatment chamber is pressurized to a pressure greater than sea level (1 atmosphere absolute, ATA).1 The pressure increase must be systemic, and may be applied in monoplace (single person) or multiplace chambers. Multiplace chambers are pressurized with air, with oxygen given via face-mask, hood tent or endotracheal tube; while monoplace chambers are pressurized with oxygen.
We began by obtaining the most recent UHMS committee report,1 and performed Medline searches (1966 to present), with the search terms ‘hyperbaric’ and ‘oxygen’, combining this basic search with searches for each of the thirteen indications recommended by the UHMS. Using information from these papers, and the resulting references, this paper outlines the history, physiology, current indications for and effects of hyperbaric oxygen therapy.
Hyperbaric therapy was first documented in 1662, when Henshaw built the first hyperbaric chamber, or ‘domicilium’.2 Since this time, reports of beneficial effects from increased pressure have increased, and by 1877, chambers were used widely for many conditions, though there was little scientific rationale or evidence. In 1879, the surgical application of hyperbaric therapy in prolonging safe anaesthesia was realized and explored.3
In 1927, Cunningham4 reported improvement in circulatory disorders at sea level …
Address correspondence to Dr C.N.A. Bell, Division of Oral & Maxillo-Facial Surgery, Bristol Dental Hospital, Lower Maudlin Street, Bristol BS1 2LY. e-mail: chris.bell{at}bristol.ac.uk
434 citations
TL;DR: Fatigue can profoundly disrupt the occupational and social functioning of MS patients, but is not directly captured in either the EDSS or the EQ-5D; further investigation of the patient-perceived benefits of disease-modifying therapy, particularly in relation to symptoms of fatigue, may be valuable.
Abstract: Background: Extensive use of the EDSS measure of disease severity by clinicians, and the EQ-5D measure of quality of life by healthcare decision-makers, may not adequately reflect patient perceptions of the range and impact of their symptoms.
Aim: To investigate the perceptions of MS patients in relation to specific symptoms and their general health-related quality of life.
Design: Questionnaire-based surveys.
Methods: Two consecutive postal surveys were sent to people whose contact details were on the database of the MS Trust. The first was sent to all 8614. Of 3403 respondents, 1992 agreed to participate in a second survey.
Results: In the first survey (response rate 40%), 1993 respondents (88%) reported moderate or severe fatigue; of 266 receiving disease-modifying therapy, 109 (41%) felt it improved their fatigue. In the second (response rate 78%), mean EQ-5D Index and z scores on the related quality of life deficit were significantly lower for respondents with relapsing or progressive disease than for those with benign disease. In the former groups (total n = 1178), over 90% reported problems with mobility and usual activities, and over 80% reported problems with pain. The lowest mean SF-36 scores were for role-physical, physical functioning and vitality, vitality being higher in respondents receiving beta interferon vs. those who were not ( p < 0.0001). Vitality was highly correlated with social functioning (0.58), general health (0.51) and mental health (0.50).
Discussion: Fatigue can profoundly disrupt the occupational and social functioning of MS patients, but is not directly captured in either the EDSS or the EQ-5D. Further investigation of the patient-perceived benefits of disease-modifying therapy, particularly in relation to symptoms of fatigue, may be valuable.
236 citations
TL;DR: The prevalence of chronic leg ulceration is approximately one-third of that predicted by previous studies using similar methodologies in the 1980s, which may be a consequence of both increasing ulcer chronicity and age.
Abstract: Background: Current prevalence estimates of chronic leg ulceration are frequently based on studies from the 1980s. During the last decade, major changes have occurred in the application of evidence-based practice to this condition.
Aim: To determine the prevalence and cause of leg ulceration in a defined geographical population after 8 years of providing standardized evidence based protocols of care.
Design: Prospective survey.
Methods: Patients with leg ulceration of >4 weeks duration) within an integrated acute and community leg ulcer service were ascertained, interviewed and clinically assessed, using a standardized questionnaire on medical history, ulcer details and non-invasive vascular investigation to describe causes. Ulcers were classified by aetiology.
Results: We identified 113 patients in a population of 252 000, giving a crude prevalence of 0.45/1000 (95%CI 0.37–0.54/1000): 0.34/1000 in men, 0.54/1000 in women. Rates were highly dependent on age, increasing to 8.29 (men) and 8.06/1000 (women) in those aged >85 years. Of the responders, 62/113 (55%) had their ulcer for >1 year. Uncomplicated venous ulceration was observed in only 59/138 (43%) ulcerated limbs; a further 21 had ulceration primarily due to arterial disease. Complex causes were present in 48 (35%) limbs, mostly venous disease in combination with diabetes (35%), lymphoedema (42%) and rheumatoid arthritis (26%).
Discussion: Our prevalence of chronic leg ulceration is approximately one-third of that predicted by previous studies using similar methodologies in the 1980s. Patients with ulceration have more complex aetiologies than previously recognized, which may be a consequence of both increasing ulcer chronicity and age.
222 citations
TL;DR: Impaired walking can be a marker of both disability and disease progression, and is therefore an important outcome measure in the treatment and rehabilitation of diseases such as MS and Parkinson's disease (PD).
Abstract: Difficulty in walking is a major feature of neurological disease, and loss of mobility is the activity of daily living on which patients place the most value.1 Consequently, how to measure and assess this is of importance to any member of the inter-disciplinary team. In clinical practice, the World Health Organization international classification of functioning (ICF)2 is often adopted as the underlying framework for the assessment of mobility, which is an individual's ability to move about effectively in their environment.2 The ICF also introduces the constructs of performance (what an individual does in his environment) and capacity (ability to execute a task or action). This has a clear impact on the current methodology for the assessment of mobility.
Different pathologies and impairments culminate in abnormal or reduced walking. For instance, in multiple sclerosis (MS), impairments such as weakness and spasticity from pyramidal tract lesions, loss of proprioception and co-ordination from dorsal column and cerebellar lesions, vestibular and visual dysfunction, cognitive and mood disturbance and pain may all contribute (Figure 1). In primary muscle disease, mobility is determined by weakness but secondary factors such as weight gain, contractures, fatigue and breathlessness may have important impacts. The degree of impairment has a non-linear relationship with activity and participation. For example leg strength and walking speed are poorly correlated,3 while many personal and environmental factors may influence the impact of similar degrees of loss of walking on mobility. Figure 1.
Framework of international classification of function (ICF) as illustrated by mobility in MS.
Impaired walking can be a marker of both disability and disease progression, and is therefore an important outcome measure in the treatment and rehabilitation of diseases such as MS and Parkinson's disease (PD). In some cases, measurement of mobility may have a direct influence on access to treatment. …
Address correspondence to Dr O.R. Pearson, Section of Neurology, University of Wales College of Medicine, Cardiff CF14 4XN. e-mail: pearsonor{at}cardiff.ac.uk
172 citations
TL;DR: PBC patients and their families have a wide susceptibility to autoimmunity, which supports an autoimmune aetiology and suggests that the genetic basis of PBC is likely to be expressed, at least in part, through factors controlling immune tolerance in general.
Abstract: Background: Primary biliary cirrhosis (PBC) is a chronic liver disease with autoimmune features but uncertain aetiology. Increased risk of PBC among relatives of patients may reflect common environmental factors, or inherited immunogenetic susceptibility. Associations between PBC and other autoimmune diseases have been reported, but their true extent and pattern is unknown.
Aim: To examine the prevalence and association patterns of autoimmune disease in a representative group of PBC patients.
Design: Clinical cohort study.
Methods: We clinically assessed members of a geographically-based PBC patient cohort ( n = 160) for the presence of additional autoimmune disease, using established specific diagnostic criteria.
Results: Some 53% of patients had at least one additional autoimmune condition, and 63% had serum autoantibodies other than AMA or ANA. AMA+ patients had a significantly lower prevalence of additional autoimmunity than AMA− patients (49% vs. 79%; p < 0.01). The greatest relative increase in disease prevalence was for scleroderma (8% of patients). Autoimmune disease was present in 14% of first-degree relatives.
Discussion: PBC patients and their families have a wide susceptibility to autoimmunity. This observation supports an autoimmune aetiology and suggests that the genetic basis of PBC is likely to be expressed, at least in part, through factors controlling immune tolerance in general.
168 citations
TL;DR: The strengths and weaknesses of H-FABP as a clinically applicable marker of myocyte necrosis in the context of acute coronary syndromes are reviewed.
Abstract: Heart fatty-acid-binding protein (FABP) is a small cytosolic protein that is abundant in the heart and has low concentrations in the blood and in tissues outside the heart. It appears in the blood as early as 1.5 h after onset of symptoms of infarction, peaks around 6 h and returns to baseline values in 24 h. These features of H-FABP make it an excellent potential candidate for the detection of acute myocardial infarction (AMI). We review the strengths and weaknesses of H-FABP as a clinically applicable marker of myocyte necrosis in the context of acute coronary syndromes.
147 citations
TL;DR: To determine the degree to which variance in Gaucher disease is determined by non-heritable factors, case reports of monozygotic and dizygotic twin pairs are presented.
Abstract: Background: Non-neuronopathic (type 1) Gaucher's disease, a recessive disorder caused by glucocerebrosidase deficiency, shows marked variability in the severity and extent of clinical expression: many individuals who harbour two mutant alleles remain mildly affected or asymptomatic. Despite much effort, it is not possible accurately to predict disease severity from the genotype, or to identify those patients destined to develop severe disease and meriting early treatment.
Aim: To determine the degree to which variance in Gaucher disease is determined by non-heritable factors.
Design: Case reports of monozygotic and dizygotic twin pairs.
Results: For the monozygotic twin pair, homozygous for the frequent N370S glucocerebrosidase allele, there was no evidence that significant lipid storage was ever initiated in the unaffected twin. In contrast, pathological storage of glucocerebroside has been present in the macrophages of both members of the dizygotic twin pair (compound heterozygotes for the N370S and L444P alleles) from an early age but, by the age of 57 years, only one has developed symptoms.
Discussion: Non-heritable factors influence Gaucher disease expression in genetically predisposed individuals. Understanding the interactions between heritable and non-heritable factors will be critical for an analysis of pathogenesis, and the treatment of individuals predisposed to Gaucher disease.
147 citations
TL;DR: Plant production of pharmaceuticals holds great potential, and may become an important production system for a variety of new biopharmaceutical products.
Abstract: Modern biotechnology has resulted in a resurgence of interest in the production of new therapeutic agents using botanical sources. With nearly 500 biotechnology products approved or in development globally, and with production capacity limited, the need for efficient means of therapeutic protein production is apparent. Through genetic engineering, plants can now be used to produce pharmacologically active proteins, including mammalian antibodies, blood product substitutes, vaccines, hormones, cytokines, and a variety of other therapeutic agents. Efficient biopharmaceutical production in plants involves the proper selection of host plant and gene expression system, including a decision as to whether a food crop or a non-food crop is more appropriate. Product safety issues relevant to patients, pharmaceutical workers, and the general public must be addressed, and proper regulation and regulatory oversight must be in place prior to commercial plant-based biopharmaceutical production. Plant production of pharmaceuticals holds great potential, and may become an important production system for a variety of new biopharmaceutical products.
136 citations
TL;DR: All risk indices performed similarly, although the Ost had somewhat better sensitivity and somewhat lower specificity than the other indices at the cut-offs evaluated, and the OST and other risk indices are effective and efficient tools to help target high-risk women for DXA testing.
Abstract: Background: Risk indices have been developed to identify women at risk of low bone mineral density (BMD) who should undergo BMD testing.
Aim: To compare the performance of four risk indices in White ambulatory women in Belgium.
Design: Epidemiological cross-sectional study.
Methods: Records were analysed for 4035 postmenopausal White women without Paget's disease or advanced osteoarthritis, seen at an out-patient osteoporosis centre between January 1996 and September 1999. Osteoporosis risk index scores were compared to bone density T-scores. The ability of each risk index to identify women with low BMD (T-score < −2.0) or osteoporosis (T < −2.5) was evaluated.
Results: Using an Osteoporosis Self-Assessment Tool (OST) score <2 to recommend DXA referral, sensitivity ranged from 85% at the lumbar spine to 97% at the total hip to detect BMD T-scores of ≤ −2.5, and specificity ranged from 34% at the total hip to 37% at the femoral neck and lumbar spine. The negative predictive value was high at all skeletal sites (89–99%), demonstrating the usefulness of the OST to identify patients who have normal BMD and should not receive DXA testing. All risk indices performed similarly, although the OST had somewhat better sensitivity and somewhat lower specificity than the other indices at the cut-offs evaluated. Among the 11–12% of women who were classified as highest risk using OST or the Osteoporosis Index of Risk (OSIRIS), 81–85% had low bone mass and 68–74% had osteoporosis.
Discussion: The performance of these risk indices among women in Belgium was similar to that reported earlier for other samples in Asian countries, the US, and the Netherlands. The OST and other risk indices are effective and efficient tools to help target high-risk women for DXA testing.
134 citations
TL;DR: Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation and act synergistically with anti-atherogenic agents, such as fibrates and statins to improve endotheliopathy in diabetes.
Abstract: Increased oxidative stress in diabetes mellitus may underlie the development of endothelial cell dysfunction by decreasing the availability of nitric oxide (NO) as well as by activating pro-inflammatory pathways. In the arterial wall, redox imbalance and oxidation of tetrahydrobiopterin (BH4) uncouples endothelial nitric oxide synthase (eNOS). This results in decreased production and increased consumption of NO, and generation of free radicals, such as superoxide and peroxynitrite. In the mitochondria, increased redox potential uncouples oxidative phosphorylation, resulting in inhibition of electron transport and increased transfer of electrons to molecular oxygen to form superoxide and other oxidant radicals. Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation. CoQ supplementation may also act synergistically with anti-atherogenic agents, such as fibrates and statins, to improve endotheliopathy in diabetes.
133 citations
TL;DR: Infants presenting with symptoms and signs of severe malaria but a negative malaria film require immediate antibiotic treatment, and the role of bacteraemia is determined.
Abstract: Background: Early recognition of children at highest risk of dying and the targeting of appropriate drug therapy are vital to the improvement of paediatric care in developing countries. This will rely upon the development of simple clinically-based algorithms and treatment guidelines.
Aim: To determine the role of bacteraemia in children presenting with clinical signs and symptoms of severe malaria.
Design: Retrospective analysis of blood culture results following prospective data collection.
Methods: We studied 251 children presenting with symptoms and signs of severe malaria to a tertiary referral centre in Ghana. Blood was taken for malaria blood films, bacterial culture and haemograms.
Results: On the basis of clinical signs alone, malaria-film-positive ( n = 182) and -negative ( n = 69) patients were indistinguishable. Some 40% of film-negative patients were bacteraemic, vs. 12% of film-positive patients. Severe malaria and bacteraemia were not positively associated. Film-negative bacteraemic patients had a mortality of 39%, primarily affecting the age group <30 months.
Discussion: Infants presenting with symptoms and signs of severe malaria but a negative malaria film require immediate antibiotic treatment.
TL;DR: There are no well-designed, large, placebo-controlled, double-blind studies comparing treatments, and accordingly, the evidence surrounding the management of impacted cerumen is inconsistent, allowing few conclusions.
Abstract: Summary In the UK, some 2.3 million people suffer cerumen (‘ear wax’) problems serious enough to warrant management, with approximately 4 million ears syringed annually. Impacted cerumen is a major cause of primary care consultation, and a common comorbidity in ENT patients, the elderly, infirm and people with mental retardation. Despite this, the physiology, clinical significance and management implications of excessive and impacted cerumen remain poorly characterized. There are no well-designed, large, placebo-controlled, double-blind studies comparing treatments, and accordingly, the evidence surrounding the management of impacted cerumen is inconsistent, allowing few conclusions. The causes and management of impacted cerumen require further investigation. Physicians are supposed to follow the edicts and principles of evidence-based medicine and clinical governance. Currently, in patients with impacted cerumen, the lack of evidence makes this impossible.
TL;DR: A familiar anecdote that relates, with variations, that experiments with improved factory lighting increased the productivity of workers, showed beyond doubt that productivity related to what the subjects believed, and not to objective changes in their circumstances.
Abstract: ‘The consumer of knowledge can never know what a dicky thing knowledge is until he has tried to produce it’. F.J. Roethlisberger, investigator at Hawthorne
There is a familiar anecdote that relates, with variations, that experiments with improved factory lighting increased the productivity of workers. The outcome seemed clear until someone turned the lighting down to below baseline, whereupon output increased still further. The moral of this tale, referred to as the Hawthorne effect, is that people change their behaviour when they think you are watching it. The story relates to the first of many experiments performed at the Hawthorne works of the Western Electric Company in Chicago from November 1924 onwards. The original aim was to test claims that brighter lighting increased productivity, but uncontrolled studies proved uninterpretable. The workers were therefore divided into matched control and test groups and, to the surprise of the investigators, productivity rose equally in both. In the next experiment, lighting was reduced progressively for the test group until, at 1.4 foot-candles, they protested that they could not see what they were doing. Until then the productivity of both groups had once again risen in parallel. Two volunteers went on to demonstrate that a high output was possible at 0.06 foot-candles, equivalent to moonlight.
The investigators next changed the light bulbs daily in the sight of the workers, telling them that the new bulbs were brighter. The women commented favourably on the change and increased their work-rate, even though the new bulbs were identical to those that had been removed. This and other manoeuvres showed beyond doubt that productivity related to what the subjects believed, and not to objective changes in their circumstances. These at least seem to be the main facts behind the popular legend, although these particular experiments were never written up, …
TL;DR: Dehydration after AIS is strongly independently associated with VTE, reinforcing the importance of maintaining adequate hydration in these patients, and the relationship between biochemical indices of dehydration and VTE after acute ischaemic stroke is evaluated.
Abstract: Background: Although it is widely assumed that dehydration predisposes to venous thromboembolism (VTE), there are no clinical studies to support this.
Aim: To evaluate the relationship between biochemical indices of dehydration and VTE after acute ischaemic stroke (AIS).
Design: Prospective observational study.
Methods: Unselected AIS patients ( n = 102) receiving standard thromboprophylaxis with aspirin and graded compression stockings, underwent serial measurements of serum urea, creatinine and osmolality, and were screened for VTE using magnetic resonance direct thrombus imaging.
Results: Serum osmolality of >297 mOsm/kg, urea >7.5 mmol/l and urea:creatinine ratio (mmol:mmol) >80 a few days post-AIS were associated with odds ratios for VTE of, respectively, 4.7, 2.8 and 3.4 ( p = 0.02, 0.05, 0.02) on multivariable analysis.
Discussion: Dehydration after AIS is strongly independently associated with VTE, reinforcing the importance of maintaining adequate hydration in these patients.
TL;DR: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy over 3 months.
Abstract: Background: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study.
Aim: To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months.
Design: Randomized double-blind placebo-controlled study.
Methods: Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA1c > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically.
Results: Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months ( p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued.
Discussion: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.
TL;DR: This work reviews the management of DKA, and the emerging role of near-patient testing in diagnosing ketosis and monitoring its resolution, and quantifying ketosis allows accurate distinction between simple hyperglycaemia and metabolic decompensation.
Abstract: Diabetic ketoacidosis (DKA) is still a major contributor to morbidity and mortality in diabetes. The triad of hyperglycaemia, ketosis and acidosis can be diagnosed within a few minutes of the patient presenting, by measuring blood glucose and ketones using a meter, and venous blood pH on a blood gas analyser. Quantifying ketosis allows accurate distinction between simple hyperglycaemia and metabolic decompensation. We review the management of DKA, and the emerging role of near-patient testing in diagnosing ketosis and monitoring its resolution.
TL;DR: The condition is eminently treatable, and continued diagnostic surveillance is needed, if cases of potentially fatal hyperinfection are to be avoided.
Abstract: Summary Background: Chronic infections with the nematode worm Strongyloides stercoralis can occur in former WWII Far East prisoners of war (FEPOWs). The condition may be asymptomatic, but frequently causes a characteristic urticarial ‘larva currens’ rash. Under conditions of immunosuppression (particularly systemic corticosteroid treatment) potentially fatal dissemination of larvae (‘hyperinfection‘) may occur. Aim: To review our total experience of strongyloidiasis in former FEPOWs, and investigate its prevalence, characteristics and risk factors. Design: Retrospective case series. Methods: We reviewed 2072 records of all FEPOWs seen at the Liverpool School of Tropical Medicine, 1968–2002. Cases with strongyloidiasis were compared with non-infected controls. Results: There were 248 (12%) with strongyloidiasis. Diagnostic features included larva currens rash (70%), eosinophilia (66%), positive faecal culture (30%), positive faecal microscopy (26%), and positive serology (64%). Mean (� SD) age of cases was 65 � 7 years, and as expected, their blood eosinophil counts were significantly higher than controls (775 vs. 238 � 10 6 /l, p < 0.001). Captivity on the Thai-Burma Railway (vs. elsewhere) was significantly associated with strongyloidiasis (78% cases vs. 40% controls, OR 4.19, CI 2.70–6.81, p < 0.001). In terms of prevalence, strongyloidiasis occurred in 166/1032 men imprisoned on the Burma Railway (16.1%). Malaria (88% vs. 69%, p < 0.001) and tropical ulcer (53% vs. 42%, p < 0.02) were more common amongst cases than controls, probably because these diseases were very common on the Burma Railway. Discussion: S. stercoralis infection is common amongst ex-FEPOWs, particularly those from the Thai-Burma Railway project. It is usually characterized by a ’larva currens’ rash and marked eosinophilia. The condition is eminently treatable, and continued diagnostic surveillance is needed, if cases of potentially fatal hyperinfection are to be avoided.
TL;DR: Preference concerning cardiopulmonary-resuscitation and end-of-life care in elderly patients hospitalized for heart failure remains poor and doctor-patient communication regarding these items remains poor.
Abstract: Background: Heart failure is increasing in prevalence and incidence, with considerable mortality among the elderly.
Aim: To determine preferences concerning cardiopulmonary-resuscitation (CPR) and end-of-life care in elderly patients hospitalized for heart failure.
Design: Prospective interview-based survey.
Methods: Patients >64 years old admitted for acute heart failure were interviewed to address their preferences regarding end-of-life care and cardio-pulmonary resuscitation (CPR) when facing the last stages of their disease.
Results: We interviewed 80 patients (mean age 79 years; 58% women). Thirty-two (40%) expressed a wish not to have CPR. Only two had previously discussed their CPR preferences with their physicians. When recovery from the illness was considered unlikely, 40 (50%) participants preferred to receive treatment at home, 32 (40%) preferred in-hospital management, and 8 (10%) were unsure. Thirty-three patients (41%) expressed a desire for spiritual support, 38 (48%) said not and the remaining 9 (11%) were indifferent.
Discussion: Advance planning of end-of-life procedures and doctor–patient communication regarding these items remains poor and must be improved.
TL;DR: Increasing travel to Latin America from the UK was associated with an increasing number of diagnoses of L. Viannia CL, and ML is likely to emerge as a more frequently imported infection among such travellers.
Abstract: Summary Background: Mucosal leishmaniasis (ML) is an important complication of new world cutaneous leishmaniasis (CL) caused by species of the Leishmania Viannia subgenus. Previous reports of ML among travellers to Latin America are few. Aims: To determine the annual number of cases of CL due to L. Viannia species diagnosed at this institution and to correlate this with changing patterns of travel. Secondly, to document the clinical presentation, diagnosis, treatment and outcome of ML at this institution. Design: Retrospective observational study. Methods: Data were collected from a clinical database, laboratory records, patient case notes and an international passenger survey. Results: Between 1995 and 2003, the annual number of cases of CL (total 79) steadily increased from 4 per year to 18 per year; the estimated number of travellers from the UK to Latin America increased
TL;DR: It is shown that in the absence of a clear contraindication, a corticosteroid should be used in addition to antituberculosis chemotherapy in the management of patients with tuberculous pericarditis.
Abstract: Background: Tuberculous pericarditis is common in Transkei (Eastern Cape). Two randomized trials showed benefits at two years for prednisolone in patients with constrictive pericarditis, and open drainage plus prednisolone in patients with pericardial effusion.
Aim: To see whether the advantages of prednisolone and open drainage were maintained up to 10 years.
Design: Follow-up of randomized, double-blind, placebo-controlled trials.
Methods: All 383 patients (143 constriction, 240 effusion) received the same anti-tuberculosis chemotherapy. They were randomized to prednisolone or placebo for the first 11 weeks, and were followed-up over 10 years. Among the 240 with effusion, 122 were also randomized to immediate open surgical drainage of pericardial fluid versus pericardiocentesis as required. Adverse outcomes were: death from pericarditis, pericardiectomy, repeat pericardiocentesis, and subsequent open drainage.
Results: The 10-year follow-up rate was 96%. In constriction patients, adverse outcomes occurred in 19/70 (27%) prednisolone vs. 28/73 (38%) placebo (p = 0.15), deaths from pericarditis being 2 (3%) vs. 8 (11%), respectively (p = 0.098, Fisher's exact test). In effusion patients, adverse outcomes occurred in 14/27 (52%) with neither drainage nor prednisolone, vs. 4/29 (14%) drainage and prednisolone, 4/35 (11%) drainage and placebo, and 6/31 (19%) prednisolone and no drainage (p = 0.08 for interaction). Drainage eliminated the need for repeat pericardiocentesis. In the 176 with effusion and no drainage, adverse outcomes occurred in 17/88 (19%) prednisolone vs. 35/88 (40%) placebo patients (p = 0.003), with repeat pericardiocentesis 20 (23%) placebo vs. 9 (10%) prednisolone (p = 0.025). In a multivariate survival analysis (stratified by type of pericarditis), prednisolone reduced the overall death rate after adjusting for age and sex (p = 0.044), and substantially reduced the risk of death from pericarditis (p = 0.004). At 10 years, the great majority of surviving patients in all treatment groups were either fully active or out and about, even if activity was restricted.
Discussion: In the absence of a clear contraindication, a corticosteroid should be used in addition to antituberculosis chemotherapy in the management of patients with tuberculous pericarditis.
Abstract: Some 20-25% of UK adults are obese according to the WHO criterion (BMI >/=30 kg/m(2)). Type 2 diabetes, increasingly recognized as a major complication of overweight and obesity, is beginning to appear in UK adolescents, following the trends in the US. Epidemiological data indicate that the prevalence of overweight and obesity has doubled or tripled in the past few decades in the US, in Europe, and even in many developing countries. Thus obesity is increasingly seen as a public health problem requiring concerted action by both governmental and non-governmental organizations. A sound understanding of the root causes is crucial, if strategies for the prevention and treatment of this epidemic are to be developed. Many epidemiological studies suggest that physical activity at work, school or at leisure has declined to minimal levels, and that sedentary behaviours such as television viewing and computer games have become major pastimes. Thus energy requirements are substantially less than those for recent generations. Further, the food industry produces high-calorie foods which children and adults consume as snack meals, giving a substantial surfeit to their daily energy requirement. In children, a few school-based, preventive intervention trials have shown some promising results. Many negative trials have also been reported, and practical difficulties remain in the widespread implementation of appropriate protocols. Initiatives have been introduced by the government to increase the physical education syllabus in school to a minimum of 2 h/week, and the promotion of fruit and vegetables. Further research is required on the physiological and psychological causes of overweight and obesity in children and adults, and randomized, controlled, school and community-based trials are required to pilot preventative initiatives. Monitoring of the progress in prevention at both organizational and outcome level is required, and also of adverse outcomes such as a rise in the prevalence of eating disorders.
TL;DR: Important areas that could be targets for interventions to improve the efficiency of delivering thrombolysis for acute stroke are identified.
Abstract: Background: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is licensed for use within 3 h of acute ischaemic stroke. The less the delay to treatment, the more likely it is to be effective.
Aims: To assess the effectiveness of interventions designed to overcome barriers to rapid administration of thrombolytic therapy.
Design: Systematic review of previous clinical studies.
Methods: We searched for studies that evaluated the effect of an intervention to reduce delays to administration of rt-PA. We searched MEDLINE, EMBASE, the trials register of the Cochrane Stroke Group, and the Cochrane Controlled Trials Register. We sought randomized and non-randomized controlled trials, before-and-after studies, interrupted time series, and observational studies.
Results: We identified 10 non-randomized studies that evaluated interventions that could speed up admission to hospital and administration of rt-PA. The types of interventions included: (a) education programmes for the public to improve their knowledge about symptoms of acute stroke; (b) training programmes for paramedical staff to improve their accuracy of stroke diagnosis and hasten transport of the patient to hospital; (c) helicopter transfer of patients to hospital; (d) training programmes in acute stroke therapy for emergency department staff; and (e) re-organization of in-hospital systems to streamline acute stroke care. Several programmes were multifaceted interventions.
Discussion: We identified important areas that could be targets for interventions to improve the efficiency of delivering thrombolysis for acute stroke. Multifaceted programmes might be more likely to be successful in reducing delays to therapy.
TL;DR: Initial deltaBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy, and a high BNP concentration is not associated with a poor prognosis in this condition.
Abstract: Background: Takotsubo cardiomyopathy is a reversible left ventricular dysfunction with symptoms resembling acute myocardial infarction, but without coronary lesions. Patients have wall motion abnormalities (apical akinesis and basal hyperkinesis), and characteristic left ventricular morphology.
Aim: To investigate plasma brain natriuretic peptide (BNP) concentrations in takotsubo cardiomyopathy.
Methods: Ten consecutive patients with takotsubo cardiomyopathy underwent cardiac catheterization on their first hospital day, and blood was collected to measure BNP. To evaluate acute basal hyperkinesis, the difference in diameter between systole and diastole was measured at 10 mm below the aortic valve (the δBase value).
Results: Coronary angiography revealed no significant stenosis in any patient. Initial ejection fraction was 42.2 ± 7.3%, cardiac index was 1.90 ± 0.39 l/min/m2, and plasma BNP was 522.5 ± 632.9 pg/ml. Ventricular contraction and the ejection fraction were normalized on echocardiography after 17.9 ± 6.3 days. BNP was significantly correlated with δBase, but not with other cardiac parameters.
Discussion: Initial δBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy. In contrast to other diagnoses, a high BNP concentration is not associated with a poor prognosis in this condition.
TL;DR: It is suggested that severe irritability may occur in some statin users, and this adverse effect may be rare, potentially life-threatening adverse effects of drugs must be taken seriously.
Abstract: Background: As use of a drug becomes widespread, the full spectrum of its effects becomes clearer. Although a link has been suggested between low or lowered cholesterol and irritability/aggression, less is known about possible links between irritability and statins.
Aim: To assess the possible connection of statin usage to severe irritability.
Design: Case series.
Methods: Six patients referred or self-referred with irritability and short temper on statin cholesterol-lowering drugs completed a survey providing information on character of behavioural effect, time-course of onset and recovery, and factors relevant to drug adverse effect causality.
Results: In each case the personality disruption, once evident, was sustained until statin use was discontinued; and resolved promptly with drug cessation. In four patients, re-challenge with statins occurred, and led to recrudescence of the problem. All patients experienced other recognized statin adverse effects while on the drug. Manifestations of severe irritability included homicidal impulses, threats to others, road rage, generation of fear in family members, and damage to property.
Discussion: Case series invariably raise more questions than they can answer. These case reports suggest that severe irritability may occur in some statin users. Although this adverse effect may be rare, potentially life-threatening adverse effects of drugs must be taken seriously.
TL;DR: The antibiotic policy was successfully introduced into an elderly care service and reduced both intravenous cephalosporin use and C. difficile diarrhoea cases, leading to a significant reduction in C. Difficile diarrhea cases.
Abstract: Background: Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients.
Aim: To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients.
Design: Retrospective analysis.
Methods: A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data.
Results: Intravenous cephalosporin use fell from 210 to 28 defined daily doses ( p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam ( p < 0.001) and moxifloxacin ( p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07–9.84, p = 0.03).
Discussion: The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.
TL;DR: Two men bitten while handling captive Saharan horned vipers in Europe developed extensive local swelling and life-threatening systemic envenoming, characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro-angiopathic haemolytic anaemia and acute renal failure.
Abstract: Background: The desert horned vipers ( Cerastes cerastes and C. gasperettii ) are the most familiar snakes of the great deserts of North Africa and the Middle East, including the plains of Iraq. They are responsible for many human snake bites. In Western countries, they are popular among exotic-snake keepers.
Aim: To investigate mechanisms of life-threatening envenoming and treatment.
Design: Clinical investigation.
Methods: Clinical and laboratory studies with measurement of serum venom antigen concentrations by enzyme immunoassay.
Results: Two men bitten while handling captive Saharan horned vipers ( Cerastes cerastes ) in Europe developed extensive local swelling and life-threatening systemic envenoming, characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro-angiopathic haemolytic anaemia and acute renal failure. The clinical picture is explicable by the presence in C. cerastes venom of several thrombin-like, Factor-X-activating, platelet-aggregating, haemorrhagic and nephrotoxic components. In one case, prophylactic use of subcutaneous epinephrine may have contributed to intracranial haemorrhage. The roles in treatment of heparin (rejected) and specific antivenom (recommended) are discussed.
Discussion: Cerastes cerastes is capable of life-threatening envenoming in humans. Optimal treatment of envenoming is by early administration of specific antivenom, and avoidance of ineffective and potentially-dangerous ancillary methods.
TL;DR: Type 1 AIH patients usually present with a chronic pattern, but some 25% have an acute presentation resembling that of viral hepatitis, and 'Acute' AIH and viral hepatitis can be reliably differentiated by simple parameters such as gender, gamma-globulin serum levels and AST/ALT ratio.
Abstract: Background: Autoimmune hepatitis (AIH) has three different presentations: chronic, acute and asymptomatic.
Aim: To evaluate AIH presentation in Italian patients and investigate criteria that differentiate between acute-type AIH and acute viral hepatitis.
Design: Prospective observational study.
Methods: Eighty-six consecutive patients with type 1 AIH and 41 with acute viral hepatitis (controls) were studied. ‘Acute’ AIH was defined as recent-onset (<30 days) symptoms (jaundice and/or fatigue and/or fever) with marked alterations in serum liver tests; the ‘asymptomatic’ pattern as the occasional detection of liver abnormalities, and the ‘chronic’ pattern as the presence of signs and/or symptoms of long-lasting liver disease.
Results: Of 86 AIH patients, 59 (68%) presented with the chronic pattern, 22 (26%) with the acute pattern, and 5 (6%) were asymptomatic. ‘Acute’ patients had higher AST, ALT and bilirubin serum levels ( p < 0.0001). No differences were detected with respect to age and serum levels of alkaline phosphatase, γ-GT, albumin or γ-globulin. All three groups had similar prevalences of moderate/severe (vs. mild) histological findings and liver cirrhosis. When compared with controls with acute viral hepatitis, ‘acute’ AIH patients were more often female (82% vs. 24%, p < 0.0001) and had higher serum γ-globulin levels (26.9 vs. 13.4 g/l, p < 0.0001) and AST/ALT ratio (1.20 vs. 0.61, p < 0.0001).
Discussion: Although in Italy type 1 AIH patients usually present with a chronic pattern, some 25% have an acute presentation resembling that of viral hepatitis. ‘Acute’ AIH and viral hepatitis can be reliably differentiated by simple parameters such as gender, gamma-globulin serum levels and AST/ALT ratio.
TL;DR: Older women with the clinical risk factors identified in this study should be investigated for osteoporosis or offered preventive treatment.
Abstract: BACKGROUND:
Common clinical risk factors for fracture in older women have been identified. To date, most of these risk factors have not been confirmed in a UK population.
AIM:
To confirm the important risk factors for fracture in older women.
DESIGN:
Comprehensive cohort study (CCS) with a nested randomized controlled trial.
METHODS:
The CCS included 4292 women aged >70 years. We assessed potential risk factors for fracture, and followed-up participants for 24 months for incidence of non-vertebral fractures.
RESULTS:
Odds ratios (ORs) for predicting any non-vertebral fracture were: previous fracture, 2.67 (95%CI 2.10–3.40); a fall in the last 12 months, 2.06 (95%CI 1.63–2.59); and age (per year increase), 1.03 (95%CI 1.01–1.05). ORs for predicting hip fracture were: previous fracture, 2.31 (95%CI 1.31–4.08); low body weight (<58 kg), 2.20 (95%CI 1.28–3.77); maternal history of hip fracture, 1.68 (95%CI 0.85–3.31); a fall in the last 12 months, 2.92 (95%CI 1.70–5.01); and age (per year increase), 1.09 (95%CI 1.04–1.13). ORs for predicting wrist fracture were: previous fracture, 2.29 (95%CI 1.56–3.34); and a fall in the last 12 months, 1.60 (95%CI 1.10–2.31). Being a current smoker was not associated with an increase in risk, and was consistent across all fracture types.
DISCUSSION:
Older women with the clinical risk factors identified in this study should be investigated for osteoporosis or offered preventive treatment.
TL;DR: The prevalence of thyroid disorders is increased in patients with HCV-related mixed cryoglobulinaemia, and careful monitoring of thyroid function in these patients is suggested.
Abstract: Background: Mixed cryoglobulinaemia (MC), a systemic vasculitis associated with hepatitis C virus (HCV) infection in >90% of cases, is frequently complicated by multiple organ involvement. The prevalence of thyroid disorders in MC has not yet been studied.
Aim: To investigate the prevalence and clinical features of thyroid involvement in patients with HCV-associated MC (HCV + MC).
Design: Case-control study.
Methods: HCV + MC patients ( n = 93, 17 men and 76 women, mean ± SD age 63 ± 10 years, mean disease duration 14 ± 7 years) consecutively referred to the Rheumatology Unit were matched by sex and age (± 2 years) to (i) 93 patients with chronic C hepatitis (CH) without MC and (ii) 93 healthy (HCV-negative) controls from the local population. Measurements included prevalence of hypo- or hyperthyroidism, thyroid autoantibodies, thyroid nodules and thyroid cancer.
Results: By McNemar's χ2 test, the following thyroid abnormalities were significantly more frequent in HCV + MC patients than in HCV-negative controls: serum anti-thyroperoxidase autoantibody (AbTPO) (28% vs. 9%, p = 0.001); serum AbTPO and/or anti-thyroglobulin autoantibody (31% vs. 12%, p = 0.004); subclinical hypothyroidism (11% vs. 2%, p = 0.038); thyroid autoimmunity (35% vs. 16%, p = 0.006). Serum AbTPO were also significantly more frequent in HCV + MC patients than in CH controls (28% vs. 14%, p = 0.035).
Discussion: The prevalence of thyroid disorders is increased in patients with HCV-related mixed cryoglobulinaemia. We suggest careful monitoring of thyroid function in these patients.
TL;DR: Empiric treatment based on limited investigations should be directed according to the nature of infections that are endemic to the populations being studied, and a modified algorithm is proposed.
Abstract: Background HIV-associated focal brain lesions (HFBL) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries, toxoplasma encephalitis (TE) is the most frequent cause, followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes however are poorly suited to developing countries, where treatable infections predominate as causes of HFBL. Aim To determine a practical approach to the management of HFBL in developing countries. Design Case series. Methods Patients (n = 32) were managed based on presumed aetiologies of the focal brain lesions, determined by collating information from CT scans, CSF and blood studies, concurrent non-neurological illness and response to treatment. Results The principal presumed cause of HFBL was tuberculosis (69%). The therapeutic response was good in 69% of patients. Discussion In developing countries, infections are the predominant cause of HFBL, the principal causes being infections that are endemic to the populations being studied. Empiric treatment based on limited investigations should be directed according to the nature of such infections. A modified algorithm is proposed.