A 10-years retrospective study on Severe Cutaneous Adverse Reactions (SCARs) in a tertiary hospital in Penang, Malaysia.

INTRODUCTION: Severe cutaneous adverse drug reactions (SCARs) are not uncommon and potentially lifethreatening. Our objective is to study the patient characteristics, the pattern of implicated drugs and treatment outcome among patients with SCARs. METHODS: A 10-year retrospective analysis of SCARs cases in Penang General Hospital was carried out from January 2006 to December 2015. Data collection is based on the Malaysian Adverse Drug Reactions Advisory Committee registry and dermatology clinic records. RESULTS: A total of 189 cases of SCARs were encountered (F:M ratio; 1.2:1.0; mean age of 45 year). The commonest manifestation was Stevens-Johnson Syndrome [SJS] (55.0%), followed by toxic epidermal necrolysis [TEN] (23.8%), drug rash with eosinophilia and systemic symptoms [DRESS] (12.7%), acute generalised exanthematous pustulosis [AGEP] (4.8%), SJS/TEN overlap syndrome (2.6%) and generalised bullous fixed drug eruptions [GBFDE] (1.1%). Mean time to onset for TEN/SJS/Overlap syndrome was 10.5±13 days; AGEP, three days; GBFDE, 2.5±0.7 days, and DRESS, 29.4±5.7 days. The most common drugs implicated were antibiotics (33.3%), followed by allopurinol (18.9%) and anticonvulsant (18.4%). Out of 154 cases of SJS/TEN/overlap syndrome, allopurinol was the commonest causative agents (20.1%). In DRESS, allopurinol accounts for 45.8% of the cases. The mortality rate in SJS, TEN and DRESS were 1.9%, 13.3% and 12.5% respectively. No mortality was observed in AGEP and GBFDE. CONCLUSION: The commonest manifestations of SCARs in our setting were SJS, TEN and DRESS. Allopurinol was the most common culprit. Thus, judicious allopurinol use is advocated and pre-emptive genetic screening for HLAB *5801 should be considered.

Patients' estimates of their sleep times: reliability and impact on diagnosis of obstructive sleep apnoea.

BACKGROUND: Home polysomnography (PSG) is an alternative method for diagnosis of obstructive sleep apnoea (OSA). Some types 3 and 4 PSG do not monitor sleep and so rely on patients' estimation of total sleep time (TST). AIM: To compare patients' subjective sleep duration estimation with objective measures in patients who underwent type 2 PSG for probable OSA. METHODS: A prospective clinical audit of 536 consecutive patients of one of the authors between 2006 and 2013. A standard questionnaire was completed by the patients the morning after the home PSG to record the time of lights being turned off and estimated time of sleep onset and offset. PSG was scored based on the guidelines of the American Academy of Sleep Medicine. RESULTS: Median estimated sleep latency (SL) was 20 min compared with 10 min for measured SL (P < 0.0001). There was also a significant difference between the estimated and measured sleep offset time (median difference = -1 min, P = 0.01). Estimated TST was significantly shorter than the measured TST (median difference = -18.5 min, P = 0.002). No factors have been identified to affect patients' accuracy of sleep perception. Only 2% of patients had a change in their diagnosis of OSA based on calculated apnoea-hypopnoea index. CONCLUSIONS: Overall estimated TST in the patients with probable OSA was significantly shorter than measured with significant individual variability. Collectively, inaccurate sleep time estimation had not resulted in significant difference in the diagnosis of OSA.

Suboptimal management of unfractionated heparin compared with low-molecular-weight heparin in the management of pulmonary embolism.

BACKGROUND: Both low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have been shown to be equivalent in efficacy and safety profiles for the management of pulmonary embolism (PE). AIMS: To assess the real world management of anticoagulation in PE in a tertiary hospital setting. METHODS: An audit of patients with a new diagnosis of PE from March 2011 to March 2012. Data collected included patient demographics, anticoagulant, complication, mortality, time to first administration, frequency of monitoring and dose adjustment for UFH, time to therapeutic range for UFH (based on activated partial thromboplastin time) and length of hospital stay. RESULTS: Of the 211 patients who were included, 139 were admitted through the Emergency Department, and 45 were managed with UFH. There was no significant difference in time to initial dose between those treated with LMWH and UFH (192 vs 98 min, P = 0.16). For UFH, average time to therapeutic range was 594 min (range 87­2257 min). During the course of UFH therapy, only 22% of activated partial thromboplastin time was within therapeutic range, while 44% was above and 33% was below therapeutic range. Average number of UFH dose adjustment was 5. Increasing weight and higher baseline fibrinogen levels significantly delayed time to therapeutic range for patients on UFH (P = 0.02 and 0.04 respectively). Up to 18 months following PE, overall mortality rate was 28%, with no significant difference between LMWH and UFH (28% vs 29%). CONCLUSION: PE was predominantly managed with LMWH. UFH was suboptimally managed when used, although there was no impact on mortality rate.

Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis.

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70-0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.

Management of Atopic Eczema in primary care.

Introduction : Atopic eczema (AE) is a common inflammatory skin dermatosis that is increasing in prevalence. However, it can present in various clinical presentations, which leads to challenges in the diagnosis and treatment of the condition, especially in a primary care setting. The Clinical Practice Guidelines on the Management of Atopic Eczema was developed by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2018. It covers the aspects of diagnosis, severity assessment, treatment, and referral.

Increased vascular permeability precedes cellular inflammation as asthma control deteriorates.

BACKGROUND: Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model. OBJECTIVES: To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration. METHODS: Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods. RESULTS: Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes. CONCLUSIONS: Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.

Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction.

BACKGROUND: Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4-8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration. METHODS: Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphocytes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of high-dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n=42) and non-asthmatic controls (n=28). RESULTS: After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4(+)/CD8(+) T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines. CONCLUSIONS: These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back-titration of ICS therapy is monitored.