Safety and efficacy of warfarin in patients with moderate thrombocytopenia.

INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring anticoagulation are currently sub-optimally treated because of bleeding concerns. Guidance on anticoagulating such patients is currently lacking because of limited data on safety and efficacy of anticoagulation in such patients. METHODS: This retrospective study compared the incidence of bleeding and thrombosis in a cohort of warfarinized patients with sustained platelet counts below 100×109/L against a cohort with normal platelet counts (>140×109/L). Primary outcomes of safety and efficacy were determined by incidence rate ratios (IRR) of bleeding and thrombotic events. International normalized ratio (INR) and platelet counts during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS: 137 thrombocytopenic patients (104,985 patient-exposure days) were compared against 939 normal patients (715,193 patient-exposure days). IRR of minor, major bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57-5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively. Median INR and platelet count readings during minor and major bleeds were 3.60 (IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99×109/L (IQR: 77.0-147.0×109/L) and 115×109/L (IQR: 107.5-169.5×109/L) respectively. CONCLUSION: Warfarinized thrombocytopenic patients are at higher risk of minor bleeding complications with a higher tendency for major bleeding but derive similar benefits against thrombotic events compared to normal patients. Bleeding events are associated with higher INRs. A narrow INR target with an upper limit below 2.5 together with closer anticoagulation monitoring may improve safety of patients.

A filter bank-based source extraction algorithm for heart sound removal in respiratory sounds.

In this paper, we consider the problem of heart sounds (HS) removal from respiratory sounds (RS), and a novel semi-blind single-channel source extraction algorithm is proposed. The proposed method is able to extract the underlying pure RS from the HS corrupted noisy input signals by incorporating the filter banks and template-based matching using FIR filters. For performance evaluation of the presented method, the average power spectral densities (PSD) of the input RS segments without HS have been compared with the PSD of the reconstructed signals over six selected frequency bands from 20 to 800Hz. The proposed method is tested for various types of RS recordings and found effective by yielding an overall maximum spectral difference of 2.8707+/-0.9875dB for a frequency range below 800Hz.

An acoustical respiratory phase segmentation algorithm using genetic approach.

This paper proposes a robust and fully automated respiratory phase segmentation method using single channel tracheal breath sounds (TBS) recordings of different types. The estimated number of respiratory segments in a TBS signal is firstly obtained based on noise estimation and nonlinear mapping. Respiratory phase boundaries are then located through the generations of multi-population genetic algorithm by introducing a new evaluation function based on sample entropy (SampEn) and a heterogeneity measure. The performance of the proposed method is analyzed for single channel TBS recordings of various types. An overall respiratory phase segmentation accuracy is found to be 12 +/- 5 ms for normal TBS and 21 +/- 9 ms for adventitious sounds. The results show the robustness and effectiveness of the proposed segmentation method. The proposed method has been a successful attempt to solve the clinical application challenge faced by the existing phase segmentation methods in terms of respiratory dysfunctions.

Acoustic rhinometry in nasal allergen challenge study: which dimensional measures are meaningful?

BACKGROUND: Acoustic rhinometry (AR) is commonly used as a quantitative assessment of nasal response to nasal allergen challenge (NAC). However, sources of error and physical limitations of various AR area-distance measurements have not been adequately evaluated. OBJECTIVE: To investigate the clinical value of AR measurements, and the relationship between subjective sensation and objective AR measurements in the NAC study. METHODS: Nasal challenge using increasing concentrations of crude Blomia tropicalis (Bt) extracts (0.6, 6, and 60 microg/mL) was performed in 15 adult patients (eight males and seven females) with ongoing persistent allergic rhinitis. Subjective symptom scores of nasal obstruction were recorded together with the objective AR measurements of the minimum cross-sectional area (MCA), distance to MCA and cross-sectional area (CSA) at 3.3, 4.0 and 6.4 cm from the nostril, during the 7 h after the last challenge. RESULTS: The dose-response increase in nasal obstruction score was significantly (P<0.001 for all) associated with decreases in mean MCA (r=0.75), mean CSA3.3 (r=0.54), mean CSA4.0 (r=0.53) and mean CSA6.4 (r=0.20). The mean MCA (+/-SD) for each subjective symptom score 0, 1, 2 and 3 was found to be 0.73 (+/-0.22) cm2, 0.63 (+/-0.29) cm2, 0.33 (+/-0.17) cm2 and 0.21 (+/-0.14) cm2, respectively. When the MCA (left and right separately) reached an area <0.2 cm2, measurements of CSA3.3 and CSA4.0 were significantly reduced by 60-70%. CONCLUSION: This study demonstrates that AR is a useful and objective investigational tool, which correlates well with the sensation of nasal obstruction. MCA, CSA3.3 and CSA4.0 are more reliable measurements than CSA6.4 due to physical limitations. It is important to note that when the MCA is smaller than 0.2 cm2, a common condition in the early-phase reaction, area-distance measurements beyond this point can be misinterpreted and should be considered with caution.

The prevalence of asthma and allergies in Singapore; data from two ISAAC surveys seven years apart.

BACKGROUND AND AIMS: Over the past few decades, the prevalence of asthma has been increasing in the industrialised world. Despite the suggestion of a similar increase in Singapore, the 12 month prevalence of wheeze among schoolchildren in 1994 was 2.5-fold less than that reported in western populations. It was hypothesised that with increasing affluence in Singapore, the asthma prevalence would further increase and approach Western figures. A second ISAAC survey was carried out seven years later to evaluate this hypothesis. METHODS: The cross-sectional data from two ISAAC questionnaire based surveys conducted in 1994 (n = 6238) and in 2001 (n = 9363) on two groups of schoolchildren aged 6-7 and 12-15 years were compared. The instruments used were identical and the procedures standardised in both surveys. RESULTS: Comparing data from both studies, the change in the prevalence of current wheeze occurred in opposing directions in both age groups--decreasing in the 6-7 year age group (16.6% to 10.2%) but increasing to a small extent in the 12-15 year age group (9.9% to 11.9%). The 12 month prevalence of rhinitis did not change; there was an increase in the current eczema symptoms in both age groups. CONCLUSION: The prevalence of current wheeze, a surrogate measure of asthma prevalence, has decreased significantly in the 6-7 year age group. Eczema was the only allergic disease that showed a modest increase in prevalence in both age groups.

The upper and lower airway responses to nasal challenge with house-dust mite Blomia tropicalis.

BACKGROUND: The house dust mite Blomia tropicalis (B. tropicalis) was found to be the most prevalent domestic mite in Singapore. However, its pathogenicity in allergic airway diseases remains to be investigated. METHODS: Twenty adults with persistent allergic rhinitis (PAR) were studied. Five had a history of asthma, and all were asymptomatic except one who was under treatment with low-dose inhaled corticosteroid. Nasal challenge was carried out by nasal spray with phosphate-buffered saline (PBS) and with increasing concentrations of crude B. tropicalis extracts (0.6, 6.0 and 60 micro g/ml) at 15 min intervals. Subjective symptom scores and absolute number of sneezes were recorded together with objective measurements of spirometry (forced expiratory volume in 1 s, FEV1) and acoustic rhinomanometry (volume of the nasal cavity). These were performed at baseline, 5 min after each incremental challenge, and 30 min, 1 h, 3 h, 5 h and 7 h after the last challenge. Meanwhile, concentrations of mediators in nasal secretions (tryptase, leukotriene C4 (LTC4) and eosinophil cationic protein (ECP)) were measured in nasal aspirate samples at similar time intervals. An identical (control) challenge procedure with PBS alone was repeated in seven patients after a washout period of at least 2 weeks. RESULTS: Significant increases in the subjective and objective nasal symptoms, together with a significant increase of tryptase and LTC4 concentrations in nasal secretion, were found 5 min after each challenge with B. tropicalis, but not with PBS. There was no definitive pattern of the late-phase nasal response in either subjective symptoms or objective measurements. Three patients (3/5) with a history of asthma showed a fall in FEV1 readings (33%, 22% and 11% from baseline, respectively) at 7 h post challenge with concomitant mild wheezing in the night. CONCLUSIONS: Our study demonstrates direct evidence of allergic nasal response to B. tropicalis in sensitized adults. It shows that nasal provocation may also provoke concomitant asthmatic symptoms during the late-phase reaction, especially in people with a history of asthma.