Intern Med J [journal]
- Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry. [JOURNAL ARTICLE]
- Intern Med J 2016 Jun 28.
Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway, however effectiveness data in a population with significant comorbidities are limited.To describe severe allergic asthma, omalizumab treatment outcomes, and predictors of response among the Australian Xolair Registry participants.A web-based post marketing surveillance registry, was established to characterise the use, effectiveness, and adverse effects of omalizumab (Xolair) for severe allergic asthma.Participants (n = 192) (mean age 51 yrs, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56), significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57) and 52% were using daily oral corticosteroid. Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. Oral corticosteroid use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (p = 0.002) and older age (p = 0.05) predicted magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2), chest pains (n = 1).Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high, despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.
- Spinning : an arising cause of rhabdomyolysis in young female. [JOURNAL ARTICLE]
- Intern Med J 2016 Jun 27.
"Spinning" is an indoor cycling regimen. The number of case reports of spinning-induced rhabdomyolysis (SIR) has increased since 2004 in South Korea.Our aim of this study is evaluating the clinical characteristics of SIR and compared it with other causes of rhabdomyolysis METHODS: From September 1, 2011, to April 30, 2015, patients who were diagnosed with rhabdomyolysis were included. We analysed the incidence of rhabdomyolysis, biochemical parameters and forced hospitalization which was defined as the days from admission to creatinine phosphokinase (CPK) < 2,000 IU/L. Results Among 70 included patients, 13 (18.6%) patients were diagnosed with SIR. The mean age of the patients with SIR was 25.69 ± 5.0 years and most were females under 35 years old (12, 92.3%). Interestingly, the mean duration of spinning exercise before admission was only 59.23 minutes. Moreover, the patients with SIR showed more severe progress than the all-patients-except-SIR (AESIR) group. The serum CPK, AST, and ALT levels of the patients with SIR were stastically significant higher than the patients with AESIR. Additionally, the duration of forced hospitalization was longer than that of the AESIR (p < 0.01).Spinning could be an important cause of rhabdomyolysis in young, unfit females, which is typically severe. A graded exercise program is advised at the first session.
- Cautionary tales in the interpretation of observational studies of effects of clinical interventions. [REVIEW, JOURNAL ARTICLE]
- Intern Med J 2016 Jun 27.
Observational studies of the effectiveness of clinical interventions are proliferating as a result of increasing amounts of 'real-world' clinical data (so called 'big data') contained within clinical registries, administrative datasets and electronic health records. While well-conducted RCTs remain the scientific standard in assessing efficacy of clinical interventions, well-designed observational studies may add to the evidence base of effectiveness in situations where RCTs are of limited value or very difficult to perform. Rather than dismissing observational studies, we need to determine what circumstances may justify doing an observational study and when it is sufficiently rigorous to be considered trustworthy. This article proposes criteria by which users of the literature might make such determinations.
- Endovascular thrombectomy for acute ischaemic stroke - a real world experience. [JOURNAL ARTICLE]
- Intern Med J 2016 Jun 27.
Endovascular thrombectomy for acute ischaemic stroke due to proximal vessel occlusions in the anterior cerebral circulation within 6 hours of stroke onset is now recognized as highly beneficial. Five randomized controlled trials in 2015 showed significant improvement in functional outcome at 90 days compared with intravenous thrombolysis alone. Liverpool hospital is a tertiary referral centre with an acute stroke service including 24/7 intravenous thrombolysis and endovascular thrombectomy.To determine whether good functional outcomes with endovascular thrombectomy are achievable in patients with acute ischaemic stroke under "real world conditions" at an Australian tertiary referral centre.A retrospective analysis of functional outcomes and mortality of 33 consecutive patients undergoing endovascular thrombectomy for acute ischaemic stroke in the anterior circulation at Liverpool hospital over 24 months (2014-2015) including 13 "drip and ship" patients transferred from other centres.Functional outcomes defined as 90 day modified Rankin score (mRs) were similar to published trials with a good outcome noted in 39.4% (mRs 0-2) of patients. Lower admission National Institutes of Health Stroke Scale score and shorter time to recanalization from stroke onset correlated with good outcome (p < 0.05). Outcomes were not statistically different between the local and transferred cases. Mortality was not higher than historical rates for anterior circulation strokes due to proximal vessel lesions.This cohort of patients with anterior cerebral circulation occlusions were treated outside the well-resourced situation of clinical trials and good functional outcomes are similar. The study translates endovascular thrombectomy to a "real world" situation.
- The Benefit of Exercise Training in Pulmonary Hypertension: a Clinical Review. [REVIEW, JOURNAL ARTICLE]
- Intern Med J 2016 Jun 24.
Pulmonary hypertension (PH) is a clinical condition characterized by raised pulmonary artery pressure which results in increased right ventricular afterload and dyspnea. This is accompanied by reduced exercise capacity, quality of life and eventually, death. An increasing range of targeted medications has transformed the treatment of pulmonary arterial hypertension, a specific type of PH. Supervised exercise training is recommended as part of a multi-faceted management plan for PH. However, many questions remain regarding how exercise training improves exercise capacity and quality of life. The optimal exercise regime (frequency, timing, duration and intensity) also remains unclear. This review provides an update on the pathophysiology of exercise impairment in PH, suggests mechanisms by which exercise may improve symptoms and function, and offers evidence-based recommendations regarding the frequency and intensity of an exercise programme for patients with PH.
- Changing prognosis in Paroxysmal Nocturnal Haemoglobinuria disease subcategories; an analysis of International PNH Registry. [JOURNAL ARTICLE]
- Intern Med J 2016 Jun 15.
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disease. Although much progress has been made in the understanding of the pathophysiology of the disease, far less is known with respect to the clinical outcomes of the patients with PNH. Few retrospective studies provide survival estimates and even fewer have explored the clinical heterogeneity of the disease. Haemolytic and aplastic anaemia forms have been recognised as main disease categories with the haemolytic form being associated with worst prognosis by the largest studied cohort some years ago.To describe mortality and causes of death in PNH overall and by PNH Classification and to evaluate risk factors associated with mortality.We analysed data on 2356 patients enrolled in the International PNH Registry with multivariate analyses using time dependent covariates. Patients were classified into haemolytic, aplastic anaemia/PNH syndrome or intermediate PNH.Overall, 122 (5.2%) patients died after enrolment, the incidence according to subcategories being 5.1%, 11.7%, 2.0%, and 4.8% for patients with haemolytic PNH, AA-PNH, intermediate, and insufficient data, respectively. Older age and decreased performance status also affected survival in multivariate analysis. Improved outcome of patients with haemolytic PNH suggests that eculizumab treatment in PNH may be associated with improved survival.A detailed analysis of clinical presentations and causes of death in patients with PNH, overall and by disease subcategories provide evidence that, in the current era, patients with haemolytic PNH are no longer those who harbour the worst prognosis. This finding differs sharply from what has been previously reported.
- The effect of pulmonary function testing on bleomycin dosing in germ cell tumours. [JOURNAL ARTICLE]
- Intern Med J 2016 Jun 15.
The utility of pulmonary function testing (PFT) to detect bleomycin-induced pneumonitis is controversial. We describe its impact on bleomycin dosing in a phase 2 trial of accelerated BEP (bleomycin, etoposide, cisplatin) for advanced germ cell tumours.There were 12 planned weekly bleomycin doses for intermediate-risk and poor-risk disease, and 9 for good-risk disease. Clinical assessments, chest x-ray, DLCO and FVC were done 2-weekly. Bleomycin was ceased for: predefined clinical/radiologic evidence of pulmonary toxicity; >25% reduction in DLCO or FVC. We determined doses planned, received, omitted; and patients receiving all, ≥2/3, <2/3 of planned bleomycin doses.Of 43 eligible patients, 30% had lung metastases. 375 of 471 (80%) of planned bleomycin doses were received; and 30% received <(2) /3 of their planned doses, all for reductions in DLCO. No patient developed other evidence of pulmonary toxicity. Patients with lung metastases were 1.5 times as likely to have a >25% reduction in DLCO (35% vs 24%, p = 0.4), and 1.5 times as likely to receive <(2) /3 of their planned doses (35% vs 24%, p = 0.4). Patients who received less than full doses of bleomycin had worse outcomes if they were of good or poor prognosis.Asymptomatic reductions in DLCO caused 20% of bleomycin doses to be omitted and 30% of patients to receive <(2) /3 of their planned doses. A 25% reduction in DLCO appears too cautious a threshold. Given the potential negative impact of this practice on anti-cancer effect, routine use of PFT to monitor for bleomycin toxicity should be questioned.
- Author reply. [Letter]
- Intern Med J 2016 Jun; 46(6):753.
- Methamphetamine-triggered Takotsubo syndrome and methamphetamine-associated cardiomyopathy: a continuum? [Letter]
- Intern Med J 2016 Jun; 46(6):752-3.
- Author reply. [Letter]
- Intern Med J 2016 Jun; 46(6):751-2.