Showing papers in "Internal Medicine Journal in 2007"

D‐dimer concentration increases with age reducing the clinical value of the D‐dimer assay in the elderly

Abstract: Background: The D-dimer assay is used as an exclusion test in the assessment of suspected venous thromboembolic disease; patients with a negative result have a low probability of thrombosis. We reviewed the D-dimer results from a hospital and community laboratory using the vidas D-dimer test to assess the influence of age on the D-dimer assay. Methods: D-dimer results from 6631 unselected patients aged more than 16 years were analysed in four age groups and it was shown that the median D-dimer concentration increased with age (16–40 years, 294 ng/mL; 40–60 years, 387 ng/mL; 60–80 years; 854 ng/mL; >80 years, 1397 ng/mL). To test the effect of age on the assay specificity, a cohort of 1897 patients with suspected venous thromboembolic disease was analysed separately. Patients with a negative D-dimer were discharged without further investigation. Patients with a positive result and a clinical suspicion of thrombosis underwent further investigation. One hundred and sixty-five deep vein thrombosis or pulmonary embolus cases were identified. Results: The assay specificity decreased with age from 70% in patients less than 40 years to below 5% in patients more than 80 years. Receiver operator curves were prepared for each age group and the effect of altering the threshold value was analysed. In patients 60–80 years old a threshold value of 1000 ng/mL increased assay specificity to 55% without loss of assay sensitivity. Conclusion: The vidas D-dimer assay with a threshold value of 500 ng/mL has little clinical value as an exclusion test in patients more than 80 years old. The assay specificity is poor (26%) in patients aged 60–80 years but could be improved by increasing the threshold value to 1000 ng/mL. We believe that this should be tested in a prospective trial.

Young people with chronic illness: the approach to transition.

Abstract: As increasing numbers of young people with chronic illness reach adulthood, their ongoing medical care must evolve to be delivered in an adult rather than paediatric setting, a process known as transition. Towards this goal, increasing numbers of paediatric and adult hospitals are engaging in processes to promote the continuity of care for young people with chronic illness. Increasing evidence shows that adverse health consequences occur when inadequate transition arrangements are in place. This article draws from the experience of a transition programme emanating from the Royal Children's Hospital, Melbourne and describes the preparation that can ensure effective transition of young people with chronic illness to adult institutions. In paediatric settings, this includes opportunities for young people to be seen medically on their own to encourage independence with health-care goals and ensuring that adequate health information is transferred to the adult service. In adult institutions, understanding the concept of adolescent development will encourage young people's engagement with the new health-care providers to improve health outcomes. Joint clinics between paediatric and adult health-care teams can improve the transfer of individual patient knowledge, promote a collaborative approach to patient care, facilitate continuity of care and build confidence from both medical and patient perspectives. Including patients in decision-making processes around transition services will encourage youth-focused service developments that will help achieve optimal outcomes in young people with chronic illness.

Geriatric syndromes as predictors of adverse outcomes of hospitalization

Abstract: Aims: The aim of this study was to determine the association between the common geriatric syndromes and predefined adverse outcomes of hospitalization and to identify the most important independent predictors of adverse outcomes using information gained within 24 h of admission in older general medical patients. Methods: A prospective longitudinal cohort study of patients aged ≥75 years admitted to the rapid assessment medical unit in a teaching hospital was carried out. The role of geriatric syndromes in predicting outcomes was examined in univariate and multivariate models. The outcome measures were (i) length of hospital stay (LOS) of 28 days or more, (ii) institutionalization or change in residential care status to a more dependent category at discharge or during 3 months post-discharge, (iii) unplanned readmissions during 3 months and (iv) mortality in hospital or 3 months post-discharge. Results: The presence of geriatric syndromes was significantly associated with increased LOS and institutionalization or change in residential care status to a more dependent category. The factors most predictive of these outcomes were impaired pre-admission functional status in activities of daily living, recurrent falls, urinary incontinence and supported living arrangements. The geriatric syndromes appeared less important in predicting unplanned readmission and death. Conclusion: The presence of geriatric syndromes in older general medical patients is an important determinant of adverse outcomes of hospitalization, particularly of LOS and admission to residential care. The predictors most useful for screening patients for these outcomes, within 24 h of admission, appear to be the presence of certain pre-existing geriatric syndromes before admission.

Pulmonary arterial hypertension in systemic sclerosis: the need for early detection and treatment.

Abstract: Pulmonary arterial hypertension (PAH) is an important cause of mortality in systemic sclerosis (SSc). The symptoms are non-specific and can be ascribed to other features of the disease, so it is often underrecognized until the late stages. Earlier treatment with new agents is associated with better treatment outcomes. The aim of this article is to develop evidence-based guidelines for screening for PAH and interstitial lung disease (ILD) in SSc. PAH occurs in up to 27% of patients with SSc. Abnormal pulmonary function, particularly a disproportionate fall in carbon monoxide diffusing capacity (DLCO), can identify patients in the early stages of PAH, prompting further investigation in high-risk patients (limited SSc of >10 years' duration, symptoms and/or signs of PAH, DLCO 45 mmHg on echocardiography). Right heart catheter remains the diagnostic gold standard. An algorithm for screening with regular pulmonary function tests for the early detection of PAH and ILD in SSc is proposed.

Recruitment of volunteers to improve vitality in the elderly: the REVIVE study.

Abstract: Background Delirium is a common problem for frail, older patients in hospital and a marker of poor outcome and mortality. The aim of this study was to test a volunteer-mediated delirium prevention programme for efficacy, cost-effectiveness and sustainability on an Australian geriatric ward. Methods Two controlled before-and-after studies were conducted. In study 1, 37 patients (>70 years, admitted to the geriatric wards) were enrolled during 5 months in 2003 for intensive individual study. Twenty-one patients received usual care and 16 patients received the volunteer-mediated intervention of daily orientation, therapeutic activities, feeding and hydration assistance, vision and hearing protocols. In study 2, we examined the effects of a general implementation for the whole department by measuring use of assistants in nursing, who were employed for individual nursing of delirious patients. Results In study 1, we found a lower incidence (intervention vs control, 6.3% vs 38%; P = 0.032) and lower severity of delirium (1.2 vs 5.1; P = 0.045). There was a trend towards decreased duration of delirium (5.0 vs 12.5; P = 0.64). In study 2, use of assistants in nursing was reduced by 314 h per month suggesting a total annual saving of 129,186 Australian dollars for the hospital. Conclusion The programme prevents delirium and improves outcomes for elderly inpatients. Cost-effectiveness supports the continuation of the programme and extension to other geriatric units.

Clostridium difficile-associated diarrhoea.

Abstract: Clostridium difficile is an important nosocomial pathogen and the most frequently diagnosed cause of infectious hospital-acquired diarrhoea. Toxigenic strains usually produce toxin A and toxin B, which are the primary virulence factors of C. difficile. Some recently described strains produce an additional toxin, an adenosine-diphosphate ribosyltransferase known as binary toxin, the role of which in pathogenicity is unknown. There has been concern about the emergence of a hypervirulent fluoroquinolone-resistant strain of C. difficile in North America and Europe. The use of fluoroquinolone antimicrobials appears to be acting as a selective pressure in the emergence of this strain. In this review, we describe the current state of knowledge about C. difficile as a cause of diarrhoeal illness.

Analysis of multidisciplinary lung cancer practice

Abstract: Background: The aim of this study was to describe the activity of a lung cancer multidisciplinary clinic (MDC) and examine whether this model of clinical practice results in adherence to best-practice guidelines. Methods: Prospective analysis of demographic and clinical data in 431 patients referred to a lung cancer MDC for the management of known or suspected thoracic malignancy. Adherence was documented to clinically relevant guideline recommendations concerning timely and evidence-based lung cancer management. Results: Of 431 patients, 257 were diagnosed with primary lung cancer, mean age 68 years, 70% men and 90% current smokers or ex-smokers. Only 21% were referred with known malignancy and 28% were asymptomatic. Overall, 51% had stages I and II non-small-cell lung cancer, with this bias towards early-stage disease greatest in patients from rural areas. Histological confirmation of lung cancer was obtained in 92%. There was a high rate of adherence to international guideline recommendations concerning timely lung cancer diagnosis, staging and treatment implementation. Similarly, there was adherence to selected key evidence based recommendations for lung cancer management contained in national guidelines. Conclusion: Within a MDC, patients receive timely diagnosis, staging and treatment according to evidence-based guideline recommendations. The high proportion of patients receiving active treatment has implications for resource allocation. There is a referral bias towards patients with early non-small-cell lung cancer, particularly in rural patients, suggesting that further education about advances in metastatic lung cancer management is required. This study would support the establishment of regional lung cancer services with links to fully resourced MDC.

Hepatitis B virus reactivation following immunosuppressive therapy: guidelines for prevention and management.

Abstract: It is well known that immunosuppressive drugs or cancer chemotherapy can stimulate replication of hepatitis B virus (HBV) and precipitate severe flares of HBV infection. The risk of this syndrome of 'reactivation hepatitis B' is highest in haematopoietic stem cell or solid organ transplant recipients and in those undergoing chemotherapy for haematological malignancies; however, it has been described following almost any form of immunosuppressive treatment. Fortunately, it can be largely prevented by prophylactic therapy with oral anti-HBV nucleoside/nucleotide analogues. Importantly, chronic HBV infection is usually asymptomatic, and most patients at risk are likely to be unaware that they carry the infection. Thus, the key to avoiding this potentially fatal complication of immunosuppressive treatment is to ensure that all patients at risk of chronic HBV infection are screened for the disease before commencing immunosuppressive treatment or chemotherapy.

Sudden cardiac death in the young: a clinical genetic approach.

Abstract: The sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death in the young. Many of the causes of sudden death in the young are due to genetic heart disorders, which can lead to both structural (e.g. hypertrophic cardiomyopathy) and arrhythmogenic (e.g. familial long QT syndrome) abnormalities. Most commonly, sudden cardiac death in the young can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a medical challenge to the clinician involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counsellor and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological and social complexities observed in families in which there has been a young sudden cardiac death.

Sleep health New South Wales: chronic sleep restriction and daytime sleepiness

Abstract: Aims: The aim of this study was to provide the first population-based descriptions of typical sleep duration and the prevalence of chronic sleep restriction and chronic sleepiness in community-dwelling Australian adults. Methods: Ten thousand subjects randomly selected from the New South Wales electoral roll, half aged 18–24 years and the other half aged 25–64 years were posted a questionnaire asking about sleep behaviour, sleepiness and sleep disorders. Results: Responses were received from 3300 subjects (35.6% response rate). The mean ± standard deviation of sleep duration was 7.25 ± 1.48 h/night during the week and 7.53 ± 2.01 h/night in the weekends. Of the working age group, 18.4% reported sleeping less than 6.5 h/night. Chronic daytime sleepiness was present in 11.7%. Logistic modelling indicated that the independent risk factors for excessive daytime sleepiness were being older, sleeping less than 6.5 h per night during the week, getting qualitatively insufficient sleep, having at least one symptom of insomnia and lacking enthusiasm (marker of depression). Conclusion: In New South Wales almost one-fifth of the people are chronically sleep restricted and 11.7% are chronically sleepy. Chronic sleepiness was most commonly associated with voluntarily short sleep durations and symptoms of insomnia and depression. If the experimentally observed health effects of sleep restriction also operate at a population level, this prevalence of chronic sleep restriction is likely to have a significant influence on public health in Australia.

Wegener's granulomatosis in New Zealand: evidence for a latitude-dependent incidence gradient.

Abstract: Background: The aim of the study was to determine whether there was evidence for a geographic gradient in the incidence of Wegener’s granulomatosis (WG) and WG-like disease in New Zealand (NZ). Methods: The National Minimum Dataset of the Ministry of Health, NZ was searched for individual patient discharges coded by the International Classification of Diseases 10th Revision, Australian Modification as either M301 (polyarteritis with lung involvement, including Churg Strauss and allergic granulomatous angiitis) or M313 (WG, necrotizing respiratory granulomatosis) for the period 1 January 1999 to 31 December 2003. Data were standardized using the 2001 NZ census. Results: One hundred and ninety-five patients (95 men) were given a first-time discharge code of either M301 (40 patients) or M313 (155 patients). No gender bias was seen. The rate among Europeans was twice that of NZ Maoris or Asians. The rate of disease peaked in the age band 70–79 years and during winter months. A significant positive north–south geographic gradient was present for M313. No difference in the rate of readmission or time to relapse between geographic regions was found for M313. Conclusion: A north–south gradient in the rate of patient discharges given a diagnostic code of M313 (WG, necrotizing respiratory granulomatosis) was present in NZ. This finding supports the hypothesis that there is a latitude-dependent risk factor(s) for WG possibly common to both global hemispheres.

Current management of acute coronary syndromes in Australia: observations from the acute coronary syndromes prospective audit

Abstract: Background: Acute coronary syndromes (ACS) management is now well informed by guidelines extrapolated from clinical trials. However, most of these data have been acquired outside the local context. We sought to describe the current patterns of ACS care in Australia. Methods: The Acute Coronary Syndrome Prospective Audit study is a prospective multi-centre registry of ST-segment elevation myocardial infarction (STEMI), high-risk non-ST-segment elevation ACS (NSTEACS-HR) and intermediate-risk non-ST-segment elevation ACS (NSTEACS-IR) patients, involving 39 metropolitan, regional and rural sites. Data included hospital characteristics, geographic and demographic factors, risk stratification, in-hospital management including invasive services, and clinical outcomes. Results: A cohort of 3402 patients was enrolled; the median age was 65.5 years. Female and non-metropolitan patients comprised 35.5% and 23.9% of the population, respectively. At enrolment, 756 (22.2%) were STEMI patients, 1948 (57.3%) were high-risk NSTEACS patients and 698 (20.5%) were intermediate-risk NSTEACS patients. Evidence-based therapies and invasive management use were highest among suspected STEMI patients compared with other strata (angiography: STEMI 89%, NSTEACS-HR 54%, NSTEACS-IR 34%, P < 0.001) (percutaneous coronary intervention: STEMI 68.1%, NSTEACS-HR 22.2%, NSTEACS-IR 8.1%, P < 0.001). In hospital mortality was low (STEMI 4.0%, NSTEACS-HR 1.8%, NSTEACS-IR 0.1%, P < 0.001), as was recurrent MI (STEMI 2.4%, NSTEACS-HR: 2.8%, NSTEACS-IR 1.2%, P = 0.052). Conclusion: There appears to be an ‘evidence-practice gap’ in the management of ACS, but this is not matched by an increased risk of in-hospital clinical events. Objective evaluation of local clinical care is a key initial step in developing quality improvement initiatives and this study provides a basis for the improvement in ACS management in Australia.

Effect of long‐term nebulized colistin on lung function and quality of life in patients with chronic bronchial sepsis

Abstract: Recurrent Gram-negative bacterial infection is a significant cause of death in patients with bronchiectasis and severe chronic obstructive pulmonary disease (COPD). Nebulized colistin in cystic fibrosis has shown maintenance of pulmonary function and improved symptom scores. We prospectively followed 18 patients with chronic bronchial sepsis treated with nebulized colistin 30 mg daily. Mean decline in forced expiratory volume in 1 s was significantly slower following commencement of inhaled colistin (44 mL/year vs 104 mL/year, P = 0.035). Mean decline in forced vital capacity was also significantly slower following commencement of colistin (48 mL/year vs 110 mL/year, P = 0.033). Patient-reported quality of life improved following commencement of colistin (3.6 vs 6.2, P = 0.001). No patient had isolates resistant to colistin. No side-effects were reported by patients in the cohort. Use of inhaled colistin in the treatment of bronchiectasis and severe (COPD) in patients with recurrent Gram-negative infections is safe. Inhaled colistin may improve quality of life and slow decline in forced expiratory volume in 1 s and forced vital capacity.

Weather: driving force behind the transmission of severe acute respiratory syndrome in China?

Abstract: Background: The association between weather and severe acute respiratory syndrome (SARS) transmission in Beijing and Hong Kong in the 2003 epidemic was studied to examine the effect of weather on SARS transmission. Methods: Pearson’s correlation analyses and negative binomial regression analyses were used to quantify the correlations between the daily newly reported number of SARS cases and weather variables, using daily disease notification data and meteorological data from the two locations. Results: The results indicate that there were inverse association between the number of daily cases and maximum and/or minimum temperatures whereas air pressure was found to be positively associated with SARS transmission. Conclusion: The study suggests that weather might be a contributory factor in the 2003 SARS epidemic, in particular in the transmission among the community members.

Effects of vitamin E treatment on peroxisome proliferator-activated receptor-alpha expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study.

Abstract: Background Insulin resistance (IR) is commonly associated with non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) may also play a role in the pathogenesis of NASH. A pivotal role in NASH pathogenesis depends on the hypothesis of increased oxidative stress. The aim of our study was to evaluate the effects of supplemental oral vitamin E, a potent antioxidant, on liver functions, PPAR-alpha expression and IR in patients with NASH. Methods Nine patients with biopsy-proven NASH were given oral vitamin E 800 mg daily for 24 weeks. Liver functions, lipid parameters, IR index with homeostatic metabolic assessment and liver histology and PPAR-alpha staining index in biopsy specimens were detected before and after the treatment. Results Seven patients (78%) had IR initially. After 6 months of therapy in nine patients, fasting insulin improved (P = 0.01), but serum cholesterol, triglyceride, fasting blood glucose levels and body mass index remained unchanged. Aspartate aminotransferase and alanine aminotransferase levels decreased (P = 0.01 and P = 0.01, respectively). IR index with homeostatic metabolic assessment resistance improved (P = 0.01), but PPAR-alpha staining index did not change (P = 0.37). Although the histological grade of steatosis decreased (P = 0.01), necroinflammation and fibrosis remained unchanged. In seven patients with IR, however, necroinflammation and PPAR-alpha staining index were improved (P = 0.04 and P = 0.02). Conclusion Vitamin E treatment, in addition to its previously shown beneficial effect by suppressing oxidative stress, may also achieve improvement by reducing IR and PPAR-alpha expression in NASH.

Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming

Abstract: Background: Australian brown snake (genus Pseudonaja) envenoming causes a venom-induced consumptive coagulopathy (VICC). A proportion of cases go on to develop thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and acute renal failure (ARF). Aim: The aim of the study was to define better the natural history and empirical treatments for thrombotic microangiopathy in brown snake envenoming. Methods: A review of brown snake bites recruited to the Australian Snakebite Project (ASP), a national multicentre study of snake envenoming was undertaken. Serial data are recorded on clinical effects and laboratory results, including measurement of venom concentrations. We describe cases of thrombotic microangiopathy and compare these to cases without thrombotic microangiopathy. Results: From 32 cases of brown snake envenoming with severe VICC, four (13%) developed thrombotic microangiopathy, we also included two cases of thrombotic microangiopathy from prior to ASP. All six developed severe thrombocytopenia (<20 × 10−9/L), worst 3 days after the bite and resolving over a week, MAHA with fragmented red blood cells on the blood film and five developed anuric ARF requiring dialysis and lasting 2–8 weeks. All six received antivenom, which was delayed compared with other brown snake-envenoming cases. Four were treated with plasmapheresis. The severity and recovery of the thrombocytopenia, anaemia and renal function were similar with and without plasmapheresis. The median length of stay for MAHA cases was 14 days (interquartile range (IQR) 12–14) compared to 1.8 days (IQR 1.3–2) for all other cases. Conclusion: Thrombotic microangiopathy resulting from brown snake bite appears to have a good prognosis and management should focus on early antivenom therapy and supportive care including dialysis. The role of plasmapheresis is yet to be defined.

Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease.

Abstract: Hydroxyurea (HU) is not infrequently used in patients with sickle cell disease and myeloproliferative disorders. Despite murine data showing adverse effects on sperm counts, motility and morphology, there is little information on the effect of HU on human spermatogenesis. A retrospective review of four adult men who had semen analysis during HU therapy and in three cases after its cessation suggests that HU generally reduces sperm counts and motility and results in abnormal morphology. Cessation of HU in one case with azoospermia resulted in recovery of spermatogenesis; in two of the three cases, however, sperm morphology and mobility remained impaired. Recommendations for fertility management in adult men receiving long-term HU therapy are proposed.

Potentially inappropriate prescribing among Australian veterans and war widows/widowers.

Abstract: This study examined the extent of potentially inappropriate medicine, as defined by explicit criteria, dispensed to Australian veterans using the Repatriation Pharmaceutical Benefits Scheme Pharmacy Claims database. Twenty-one per cent of the 192 363 veterans aged 70 years, with an eligible gold card, were dispensed at least one potentially inappropriate medicine in the first 6 months of 2005. Long-acting benzodiazepines, amitriptyline, amiodarone, oxybutynin and doxepin were the medicines most commonly implicated. Strategies to support quality prescribing of medicines to the elderly must include a focus on these medicines.

Psychological morbidity and burnout in palliative care doctors in Western Australia.

Abstract: Background: Medicine and particularly palliative care are considered to be stressful professions, with risks of psychological morbidity and burnout. There is little published work quantitatively documenting their prevalence among medical practitioners practising in palliative care. Methods: Three questionnaires, including the General Health Questionnaire (GHQ-12) and the Maslach Burnout Inventory, were sent to palliative care practitioners in Western Australia. Results: Forty-one of 43 (95%) practitioners completed the questionnaires. The mean score on the GHQ-12 was 1.9 (range 0–8), with 11 (27%) scoring 4 or more. On the Maslach Burnout Inventory, mean scores on the emotional exhaustion (EE, mean 17.5, range 1–47) and depersonalization subscales (DP, 4.5, 0–24) fell within the low range, with scores for personal accomplishment (39, 32–46) falling within the average range. Ten respondents (24%) scored high on either the EE subscale or the DP subscale, meeting criteria for burnout. GHQ-12 scores were associated with hours of work per week in palliative care (P = 0.004). The EE (P = 0.024) and DP (P = 0.006) components of burnout were associated with years of work in palliative care. Specialist practitioners were more likely to score in the high category for GHQ-12 (odds ratio = 4.8, P = 0.036) and EE (odds ratio = 8.33, P = 0.031). GHQ (P = 0.038) and DP (P = 0.006) scores were higher in those working in tertiary institutions, with tertiary practitioners more likely to be in the high EE category (odds ratio = 7.5, P = 0.034). Conclusion: Levels of psychiatric morbidity and burnout in palliative medicine are not higher than in other specialties.

Effect of chronic diseases and associated psychological distress on health‐related quality of life

Abstract: Background: The purpose of this study was to clarify the correlations between the presence of comorbidities and psychological distress and health-related quality of life (HRQL). This was a population-based cross-sectional study. Methods: Parents and grandparents of students from seven randomly selected primary schools in the city centre were asked to answer questionnaires sent by their children. All subjects were questioned for somatic diseases, psychological distress and HRQL by Health Questionnaire, Hospital Anxiety and Depression scale and short-form-12 health survey, respectively. Results: Out of 5024 parents and grandparents (mean age 52.3 ± 14.3 years, range 20–104 years) of primary school students 4605 returned the questionnaires, a figure that corresponds to the overall response rate of 91.6%. Chronic diseases substantially reduced HRQL and this effect did not differ markedly with the type of chronic disease. Association of comorbidities with psychological distress further impaired HRQL. As the number of chronic diseases was increased, HRQL and physical and mental functioning declined. The worst HRQL was observed in subjects who had five or more comorbidities associated with psychological distress. Conclusion: The present study indicates significant adverse effects of chronic diseases and psychological distress on HRQL in adults, the effect of psychological distress being the most important. Our results lead us to suggest that in the management of comorbidities, the detection of the presence and severity of associated psychological distress and its treatment, besides the specific treatment of comorbidities, may provide dramatic improvement in HRQL of the patients.

Emerging therapies in the long-term management of hyperuricaemia and gout.

Abstract: Gout is a common chronic arthritis that can lead to significant disability. Gout is one of the few rheumatological conditions that can be diagnosed with certainty, has a known cause and can be cured with appropriate therapy. Hypouricaemic agents reduce uric acid concentrations through inhibiting uric acid production (allopurinol) or enhancing uric acid excretion (probenecid, benzbromarone). Allopurinol is the most commonly used hypouricaemic agent but at recommended doses often fails to reduce adequately uric acid concentrations and prevent acute attacks of gout. The use of probenecid is limited by lack of efficacy in renal impairment. In the last few years, new agents in the management of hyperuricaemia and gout have become available. Febuxostat, a new xanthine oxidase inhibitor, is an effective hypouricaemic agent although further data are required for patients with renal impairment and other significant medical conditions. Rasburicase, a recombinant uricase (which catalyses the conversion of uric acid to the more readily excreted allantoin) is available for prevention of tumour lysis syndrome. However, its repeated use, as would be required in chronic gout, is limited by antigenicity. A less antigenic PEGylated uricase can rapidly reduce serum uric acid concentrations and promote resorption of tophi. However, further information with regard to the long-term risks and benefits of these agents is required. These agents may ultimately be used in the short term to rapidly deplete urate stores (induction therapy) followed by long-term therapy with an alternative hypouricaemic agent to prevent subsequent accumulation of uric acid (maintenance therapy).

Fracture prevention strategies in patients presenting to Australian hospitals with minimal-trauma fractures: a major treatment gap.

Abstract: Background: The aim of this study was to examine current fracture prevention strategies through the recognition, investigation and treatment of osteoporosis in patients presenting to acute hospitals with minimal-trauma fracture. Methods: A retrospective audit using a standardized database was conducted in 16 Australian hospitals. This involved 1829 cases of minimal-trauma fracture initially presenting to hospital emergency departments during 2003–2005. Cases of minimal-trauma fracture were retrospectively identified using diagnosis-related group fracture codes and case record review at each site. Relevant data were entered into a standardized database and analysed centrally and independently. Risk factors for osteoporosis, investigations, interventions and discharge follow up were recorded. Results: The percentage of minimal-trauma fracture patients who underwent investigation or initiated therapy designed to prevent subsequent minimal-trauma fracture was obtained. Less than 13% of patients presenting to hospital with minimal-trauma fractures had risk factors for fracture identified. Ten per cent were appropriately investigated, 12% were commenced on calcium and 12% on vitamin D. Eight per cent started bisphosphonates and 1% selective oestrogens receptor modulators in the acute setting. Conclusion: Most patients presenting to Australian hospitals with minimal-trauma fracture are neither investigated nor treated for osteoporosis. As this group is at high risk of subsequent fracture, this is a missed opportunity to reduce fracture burden.

Prevalence of thyroid disease in an older Australian population.

Abstract: Aim: To determine the prevalence of thyroid disease in an older Australian population in a population-based cross-sectional study. Background: Community-living subjects, aged 49 years or older, in two Blue Mountains postcodes were invited to participate in an eye, nutrition and health study between 1997 and 2000. Methods: Three thousand five hundred and nine of the 4489 identified persons participated. Fifty-seven per cent of 3504 who completed questionnaires were women; their mean age was 66.8 years. Thyroid-stimulating hormone (TSH) was measured in 2665 subjects (76% of those completing the questionnaire). The main outcome measures were serum TSH and free thyroxine levels, serum lipids, urate and sugar levels and questionnaire responses. Results: The prevalence of recognized thyroid disease (either self-reported history of thyroid disease or current thyroxine treatment) was 10% (95% confidence interval (CI) 8.9–11.1%). An additional 3.6% (95%CI 2.9–4.3%) of participants had unrecognized thyroid disease (abnormal TSH). The TSH was abnormal in 7.1% (95%CI 5.8–8.4%) of women and 3.7% (95%CI 2.6–4.8%) of men. Sixty-five per cent of those with an abnormal TSH did not report a history of thyroid disease, whereas 25% of those taking thyroxine replacement therapy had an abnormal TSH level. The prevalence of hypothyroidism increased with increasing age in women. The mean fasting cholesterol was 0.36 mmol/L (95%CI 0.15–0.57) higher in hypothyroid subjects than in euthyroid subjects. Conclusion: Thyroid disease in older Australian women is relatively common and may be undiagnosed. Ongoing monitoring of patients on thyroxine replacement therapy is important, given that 25% of treated patients had an abnormal TSH.

First Fracture Project: addressing the osteoporosis care gap.

Abstract: Patients sustaining a low-trauma fracture are at greater risk of subsequent fracture, but as a group are poorly managed. We report the development of our ‘First Fracture Project’, in which we attempt to assess all patients over 50 years of age with a low-trauma fracture attending orthopaedic fracture clinics and treat osteopenia and osteoporosis. We found that the First Fracture Project has greatly increased our success in improving delivery of osteoporosis care to appropriate at-risk patients.

Neurology of Fabry disease.

Abstract: Background: Fabry disease has diverse neurological manifestations, many of which influence morbidity and quality of life. Aims: The aim of the study was to document the clinical and subclinical neurological manifestations in a cohort of Australian patients with Fabry disease, using multiple clinical tools and a multidisciplinary approach. Methods: Participants completed focused questionnaires and underwent clinical neurological examination, Neurocognitive testing using Mini Mental State Examination and Neuropsychiatry Unit Cognitive Screen, Quantitative Sensory Testing (QST), autonomic assessment using RR interval variation, intracranial magnetic resonance imaging (MRI) and audiology. In subsets of patients who had previously undergone QST and/or prospective serial quality-of-life assessments over the previous 5 years, results before and after enzyme replacement therapy were compared. Results: Twenty hemizygotes and two heterozygotes were recruited. The age (mean ± standard deviation (SD)) of male participants was 40.4 ± 11.9 years (range 20–62 years); the women were aged between 20 and 56 years. Increasing age was strongly associated with increasing neurological disability. Clinical peripheral neuropathy predominantly affected thermal sensation in all patients, with variable involvement of pinprick and light touch. QST confirmed these findings. Clinical cerebellar tests were commonly abnormal: this has not been previously reported in the absence of symptomatic cerebrovascular disease. There was hearing loss was in 90% of patients and no patient older than 44 years had normal hearing. MRI lesion prevalence increased with age. Despite neurological complications being common, formal cognitive testing was basically normal. QST thresholds for pain showed a significant change after enzyme replacement therapy. Conclusions: Neurological complications in Fabry disease are common, complex and may be devastating. All patients studied had neurological involvement, with protean and diverse manifestations.

Residential exposure to electric power transmission lines and risk of lymphoproliferative and myeloproliferative disorders: a case–control study

Abstract: Background: Studies have shown an association between electromagnetic fieldsandchildhoodleukaemia.Theaimofthisstudywastodeterminewhether there is an increased risk of lymphoproliferative disorders (LPD) or myeloproliferative disorders (MPD) associated with residence 300 m from high-voltage power lines. Methods: Case‐control study of 854 patients diagnosed with LPD or MPD (including leukaemia, lymphoma and related conditions) aged 0‐94 years comprising all cases diagnosed in Tasmania between 1972 and 1980. Controls were individually matched for sex and approximate age at the time of diagnosis. Results:Comparedwiththosewhohadalwayslived>300 mfromapowerline, those who had ever lived within 50 m had an odds ratio (OR) of 2.06 (95% confidence interval 0.87‐4.91) for developing LPD or MPD (based on 768 adult case‐control pairs); those who had lived between 50 and 300 m had an OR of 1.30 (0.88‐1.91). Adults who had lived within 300 m of a power line during the first 15 years of life had a threefold increase in risk (OR 3.23; 1.26‐8.29); those whohadlivedwithinthesamedistanceaged0‐5 yearshadafivefoldincreasein risk (OR 4.74; 0.98‐22.9). These associations were strengthened when analyses were repeated for 201 pairs with entirely Tasmanian residential histories. Conclusion: Although recognizing that this study has limitations, the results raise the possibility that prolonged residence close to high-voltage power lines, especially early in life, may increase the risk of the development of MPD and LPD later.

Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with metformin.

Abstract: Background: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied. The aim of the present study was to assess the differential effect on glycaemic metabolism and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic syndrome. Methods: All patients began metformin and were randomized to receive pioglitazone or rosiglitazone for 12 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B. Results: Significant decreases in glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, and postprandial plasma insulin were seen after 9 and 12 months in both groups. Homeostasis model assessment index improved at 12 months in both groups. Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group. These variations were significant between groups. Conclusion: The combination of metformin plus thiazolidinediones was able to improve glycaemic control compared with previous therapy. Pioglitazone was associated with a significant improvement in lipid and lipoprotein variables.

Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience.

Abstract: Background: Genetic factors are clearly attributed to the susceptibility of ankylosing spondylitis (AS) The human leucocyte antigen (HLA)-B27 proved to be the very useful marker for diagnosing AS The aim of this study was to determine the prevalence of HLA-B27 subtypes in Taiwan and to investigate whether these subtypes may be of help in predicting the diagnosis of AS Methods: A total of 314 patients with AS and a control group of 71 subjects positive for HLA-B27 detected by flow cytometry analysis were recruited for the study HLA-B27 subtypes were confirmed by the polymerase chain reaction-sequence-specific primers and sequence-specific oligonucleotide probing Results: Four B27 alleles were identified: B*2704, B*2705, B*2706 and B*2707 HLA-B*2704 was the predominant allele There were significant differences in the distribution of HLA-B27 subtypes between patients with AS and controls Five of them who were homozygous for the B*2704 allele were solely found in AS group but not in controls Statistical analysis showed that B*2704 was positively associated with AS, which suggested an increased possibility of having AS Other HLA-B27 subtypes showed no strong correlation with AS Conclusion: In the Taiwanese population, susceptibility to AS was determined by the presence of HLA-B*2704 Although B*2706 was reported to have a negative association with AS in Taiwanese, Thai and Chinese Singaporean populations, we report, in our study, two AS patients with B*2706 (06%) Disease heterogeneity suggests that other than genetic background, many pathogenic factors could be associated with AS This may need to be investigated with a larger group of patients with AS and controls

Delirium in elderly general medical inpatients: a prospective study

Abstract: BACKGROUND: More than 49% of all US hospital days are spent caring for patients with delirium. There are few Australian data on this important condition. The aim of the study was to determine the prevalence and incidence of delirium in older medical inpatients in a metropolitan teaching hospital, the incidence of known risk factors and current practice in identifying and managing patients at risk of this condition. METHODS: Patients aged 65 years or more, and admitted to a general medical unit, were eligible for study inclusion. Participants were screened with an Abbreviated Mental Test Score (AMTS) and chart review. Confusion Assessment Method was used to diagnose delirium if confusion was documented or AMTS < 8. Barthel Index (BI), demographics, delirium risk factors and management were recorded. RESULTS: Prevalent delirium was diagnosed in 19 of 104 (18%) and incident delirium in 2 of 85 (2%) participants. Pre-existing cognitive impairment and admission AMTS < 8 were strongly associated with prevalent delirium (P-values 80 years, Barthel Index < or = 50, use of high-risk medications and electrolyte disturbance were also associated with prevalent delirium. Prevalent delirium was not recognized by the treating unit in 4 of 19 cases (21%). Five of 104 (4.8%) of participants had a formal cognitive assessment on admission. One of 19 patients (5.3%) with prevalent delirium had an orientation device in their room. CONCLUSION: Pre-existing cognitive impairment and admission AMTS are strong predictors of delirium. Despite this, formal cognitive assessment is not routinely carried out in elderly medical patients. Recognition of delirium may be improved by routine cognitive assessment in elderly medical patients.

Vitamin D deficiency in general medical inpatients in summer and winter

Abstract: Background: Vitamin D deficiency is common in various populations worldwide. Adverse effects of vitamin D deficiency are the development of bone disorders; however, other diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and certain cancers have also been linked to vitamin D deficiency. The general medical inpatient population is a group at increased risk of vitamin D deficiency. These patients often have coexistent risk factors for its consequences. This study aims to document a point prevalence of vitamin D deficiency in this population. Methods: Two cross-sectional audits of patients admitted to general medicine units were carried out ‐ the first in mid-November at the end of winter and the second in mid-April and May at the end of summer. Information regarding patients’ comorbidities, medication usage, previous falls and fractures was obtained and serum 25-hydroxyvitamin D, parathyroid hormone and calcium levels were measured. Results: A total of 129 patients was studied (65 in winter and 64 in summer). Ninety-four patients (74%) had 25-hydroxyvitamin D levels 50 nmol/L. Seven patients had severe deficiency (levels 12.5 nmol/L). Average vitamin D levels were lower at the end of winter (35 vs 43 nmol/L, P = 0.007). Of the 37 patients receiving vitamin D supplements, 20 (54%) had 25-hydroxyvitamin D levels 50 nmol/L. Conclusion: Low vitamin D levels were common in this general medical inpatient population. The average vitamin D level was lower in the patient group tested in November following winter. Supplementation of vitamin D did not uniformly prevent deficiency.