Medicine (RMH) - Research Publications
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ItemAntiepileptic Medications Increase Osteoporosis Risk in Male Fabry Patients: Bone Mineral Density in an Australian Cohort(SPRINGER-VERLAG BERLIN, 2014)BACKGROUND: Fabry disease (FD) is an inherited X-linked lysosomal storage disease with widespread clinical manifestations. Small prospective studies have shown increased osteopenia and osteoporosis in male FD patients. Limited information however exists about bone metabolism and osteoporosis risk factors within this group. We reviewed osteoporosis risk factors within our cohort. METHODS: A retrospective analysis of bone mineral density (BMD) results and fracture incidence in 44 patients (22 males and 22 females) was undertaken. Dual X-ray absorptiometry scans were performed at the lumbar spine, hip and femoral neck. The impact of risk factors including renal function, antiepileptic drug (AED), analgesia and vitamin D levels were assessed. RESULTS: Male FD patients had low T scores at all sites (spine -1.2 ± 1.06, hip -1.6 ± 0.9, femoral neck -2.23 ± 1.01). Female T scores showed more typical distribution (spine -0.07 ± 1.47, hip 0.02 ± 1.14, femoral neck -0.49 ± 1.31). A higher incidence of osteopenia and/or osteoporosis occurred in males versus females (spine 46.9% versus 31.8%, hip 75.5% versus 18.2% and femoral neck 86.4% versus 45.5%). Multiple regression analysis showed a 50.8% (p < 0.001) reduction in femoral neck BMD with AED usage, after adjustment for age, gender and renal function. Non-traumatic fractures occurred in 27.3% males over 205 patient-years versus 4.6% in females over 149 patient-years, p = 0.095. CONCLUSIONS: Low bone density was highly prevalent in male patients with increased incidence of non-traumatic fractures. AED usage significantly reduces BMD. Treatment to prevent BMD deterioration will depend on determining the bone turnover status.
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ItemEffect of Reduced Agalsidase Beta Dosage in Fabry Patients: The Australian Experience(SPRINGER-VERLAG BERLIN, 2012)BACKGROUND: In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009. AIM: To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort. METHODS: A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction. RESULTS: Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa. CONCLUSION: This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.
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ItemSevere Infusion Reactions to Fabry Enzyme Replacement Therapy: Rechallenge After Tracheostomy(SPRINGER-VERLAG BERLIN, 2012)A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.
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ItemCarpal Tunnel Syndrome in Fabry Disease(SPRINGER-VERLAG BERLIN, 2012)Carpal tunnel syndrome (CTS) is a common peripheral mononeuropathy affecting up to 4% of the general population, typically women in late middle age. The incidence in patients with Fabry disease (FD) is unclear, but may affect 25% of patients with this X-linked lysosomal storage disease. We report three cases of CTS in young Caucasian male patients with classical FD, who developed CTS symptoms with supportive nerve conduction study (NCS) findings. Two patients had bilateral CTS and two had evidence of concurrent ulnar nerve neuropathy on NCS, suggesting a systemic process contributed to nerve compression. All were receiving enzyme replacement therapy (ERT) and had a moderate burden of FD complications. It is possible that an increase in connective tissue in the intracarpal canal in FD patients may be incited by injury to fibroblasts, via either accumulation of globotriaosylceramide (GL3) or local ischaemia through endothelial injury. The former hypothesis may be a more plausible explanation for the development of CTS, as histology of the flexor retinaculae from our patients has demonstrated fibroblasts with characteristic vacuolation and excessive myxomatous stroma, despite endothelial clearance of GL3 in these patients receiving ERT. CTS should not be overlooked in FD patients and young patients presenting with CTS should be evaluated for an underlying systemic or genetic disorder. Surgical carpal tunnel decompression was effective in our patients, already troubled by long-standing acroparesthesia, in providing sustained relief of symptoms.
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ItemImprovement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry Registry(SPRINGER-VERLAG BERLIN, 2018)Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase, GLA. In patients with Fabry disease, glycosphingolipids accumulate in various cell types, triggering a range of cellular and tissue responses that result in a wide spectrum of organ involvement. Although variable, gastrointestinal symptoms are among the most common and significant early clinical manifestations; they tend to persist into adulthood if left untreated. To further understand the effects of sustained enzyme replacement therapy (ERT) with agalsidase beta on gastrointestinal symptoms in heterozygotes, a data analysis of female patients enrolled in the Fabry Registry was conducted. To be included, females of any age must have received agalsidase beta (average dose 1.0 mg/kg every 2 weeks) for at least 2.5 years. Measured outcomes were self-reported gastrointestinal symptoms (abdominal pain, diarrhea). Outcomes at baseline and last follow-up, and their change from baseline to last follow-up, were assessed. Relevant data were available for 168 female patients. Mean age at the start of ERT was 43 years and mean treatment duration 5.7 years. Baseline pre-treatment abdominal pain was reported by 45% of females and diarrhea by 39%. At last follow-up, 31% reported abdominal pain (p < 0.01) and 27% diarrhea (p < 0.01). The results of this Fabry Registry analysis suggest that while on sustained treatment with agalsidase beta (1.0 mg/kg every 2 weeks), both abdominal pain and diarrhea improved in many female patients with Fabry disease.
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ItemSleep Disturbance, Obstructive Sleep Apnoea and Abnormal Periodic Leg Movements: Very Common Problems in Fabry Disease(SPRINGER-VERLAG BERLIN, 2017)OBJECTIVES: To assess the prevalence of sleep disorder(s) in males with Fabry disease and explore possible association with disease phenotype. BACKGROUND: Fabry disease, an X-linked lysosomal storage disease caused by deficiency in α-galactosidase, results in intracellular accumulation of globotriaosylceramide. It causes organ dysfunction, most significantly affecting renal, cerebrovascular and cardiovascular systems. Respiratory involvement may include obstructive lung disease, reduced diffusing capacity and thickened soft and hard palates. Patients commonly develop small-fibre sensory peripheral neuropathy manifested by acroparaesthesia and pain crises. Combined with self-reported sleep disturbance and snoring, these features suggest an increased risk of sleep disorders. METHODS: In-laboratory polysomnography (PSG) studies and sleep inventory assessments, including Epworth Sleepiness Scale (ESS), were performed in a cohort of male Fabry patients. PSGs were reviewed by a sleep physician. Sleep-disordered breathing and periodic leg movements were targeted for analysis. Associations with renal, cardiovascular and cerebrovascular function were sought. RESULTS: Twenty males underwent overnight PSG. Patient baseline characteristics included age 43.9 ± 10.7 years, BMI 24.3 ± 3.8 kg/m2, neck circumference 39.7 ± 3.3 cm and ESS 9.8 ± 5.1 (7/20, abnormal ESS >10). Abnormal periodic leg movement index (PLMI) was present in 95% (mean frequency 42.4 ± 28.5/min) and sleep-disordered breathing in 50% patients. Periodic leg movements were associated with pain and depression but not with increased cortical arousal. CONCLUSIONS: Sleep-disordered breathing and abnormal PLMI are highly prevalent in patients with FD. The presence of abnormal PLMI alone appears to have minimal impact on sleep disturbance, but is associated with depression and analgesic requirement.
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ItemMinimum technical standards and recommendations for traumatic brain injury specialist rehabilitation teams in sudden-onset disasters (for Disaster Rehabilitation Committee special session) (Abstract)(Elsevier BV, 2018-07)Introduction/Background: Sudden-onset disasters (SODs) result in increased number of survivors with complex and long-term disabling injuries, including traumatic brain injury (TBI) that warrants comprehensive specialist rehabilitation. This presentation highlights the minimum technical standards required for specialised TBI rehabilitation teams and their integration into WHO Emergency Medical Teams (EMTs) to facilitate comprehensive management of TBI survivors in disaster settings. Material and method: A team of medical rehabilitation physicians from the Royal Melbourne Hospital conducted a comprehensive review of literature for TBI management, based on the WHO core-guidelines for ‘Minimum technical standards and recommendations for rehabilitation for EMTs’. These were endorsed by a specialist TBI expert panel in the Asia-Pacific region. Results: Comprehensive rehabilitation programs improve functional outcomes and quality of life of TBI survivors. It is recommended that specialised TBI care teams need to be embedded into EMTs for disaster response and management for early diagnosis, management and social reintegration. This guidance documents the minimum standards for deployment of TBI specialist rehabilitation teams in the context of SODs, including: skill requirements, team configuration and profile, professional competencies for management of TBI and complications, list of required equipment and consumables, information management/dissemination. Conclusion: TBI rehabilitation should commence from the early response phase in SODs by accredited rehabilitation professionals to minimise complications and disability. Integration of specialised TBI rehabilitation professionals into EMTs for disaster response will improve functional outcomes of survivors.
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ItemNo Preview AvailableRefugee health update(Medicine Today, 2012-03-01)
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ItemNo Preview AvailablePrevalence and risk factors for symptoms of common mental disorders in early and late pregnancy in Vietnamese women: A prospective population-based study(Elsevier, 2013-04-05)BACKGROUND: Little is known about the prevalence of and risk factors for common mental disorders (CMD) in pregnant women in low-income countries. The aim of this study was to establish the prevalence of and psychosocial risk factors for clinically significant symptoms of CMD in early and late pregnancy in women in rural Viet Nam. METHODS: A population-based sample of women was surveyed in early and late pregnancy. CMD were assessed by the Edinburgh Postnatal Depression Scale-Viet Nam Validation and psychosocial risks by study-specific structured interviews. RESULTS: In total 497/523 (97%) eligible women were recruited and 419 (84%) provided complete data. Prevalence of CMD only in early pregnancy was 22.4% (95% CI 18.4-26.4); only in late pregnancy was 10.7% (95% CI 7.8-13.7) and at both assessment waves was 17.4% (95% CI 13.8-21.1). Non-economic and economic coincidental life adversity, intimate partner violence, past pregnancy loss, and childhood abuse were positively associated with persistent antenatal CMD. Older age, having a preference for the baby's sex, and nulli- or primiparity were risk factors for CMD in early pregnancy. CONCLUSIONS: Persistent antenatal CMD are prevalent in rural areas of Viet Nam. Psychosocial risk factors play a major role in this significant public health problem.