Dinesh Saralaya

Tuberculosis in UK cities: workload and effectiveness of tuberculosis control programmes

BackgroundTuberculosis (TB) has increased within the UK and, in response, targets for TB control have been set and interventions recommended. The question was whether these had been implemented and, if so, had they been effective in reducing TB cases.MethodsEpidemiological data were obtained from enhanced surveillance and clinics. Primary care trusts or TB clinics with an average of > 100 TB cases per year were identified and provided reflections on the reasons for any change in their local incidence, which was compared to an audit against the national TB plan.ResultsAccess to data for planning varied (0-22 months). Sputum smear status was usually well recorded within the clinics. All cities had TB networks, a key worker for each case, free treatment and arrangements to treat HIV co-infection. Achievement of targets in the national plan correlated well with change in workload figures for the commissioning organizations (Spearmans rank correlation R = 0.8, P < 0.01) but not with clinic numbers. Four cities had not achieved the target of one nurse per 40 notifications (Birmingham, Bradford, Manchester and Sheffield). Compared to other cities, their loss to follow-up during treatment was usually > 6% (χ2 = 4.2, P < 0.05), there was less TB detected by screening and less outreach. Manchester was most poorly resourced and showed the highest rate of increase of TB. Direct referral from radiology, sputum from primary care and outreach workers were cited as important in TB control.ConclusionTB control programmes depend on adequate numbers of specialist TB nurses for early detection and case-holding.Please see related article: http://www.biomedcentral.com/1741-7015/9/127

Impact of omalizumab on treatment of severe allergic asthma in UK clinical practice: a UK multicentre observational study (the APEX II study).

Objective To describe the impact of omalizumab on asthma management in patients treated as part of normal clinical practice in the UK National Health Service (NHS). Design A non-interventional, mixed methodology study, combining retrospective and prospective data collection for 12 months pre-omalizumab and post-omalizumab initiation, respectively. Setting Data were collected in 22 UK NHS centres, including specialist centres and district general hospitals in the UK. Participants 258 adult patients (aged ≥16 years; 65% women) with severe persistent allergic asthma treated with omalizumab were recruited, of whom 218 (84.5%) completed the study. Primary and secondary outcome measures The primary outcome measure was change in mean daily dose of oral corticosteroids (OCS) between the 12-month pre-omalizumab and post-omalizumab initiation periods. A priori secondary outcome measures included response to treatment, changes in OCS dosing, asthma exacerbations, lung function, employment/education, patient-reported outcomes and hospital resource utilisation. Results The response rate to omalizumab at 16 weeks was 82.4%. Comparing pre-omalizumab and post-omalizumab periods, the mean (95% CIs) daily dose of OCS decreased by 1.61 (−2.41 to −0.80) mg/patient/day (p<0.001) and hospital exacerbations decreased by 0.97 (−1.19 to −0.75) exacerbations/patient (p<0.001). Compared with baseline, lung function, assessed by percentage of forced expiratory volume in 1 s, improved by 4.5 (2.7 to 6.3)% at 16 weeks (p<0.001; maintained at 12 months) and patient quality of life (Asthma Quality of Life Questionnaire) improved by 1.38 (1.18 to 1.58) points at 16 weeks (p<0.001, maintained at 12 months). 21/162 patients with complete employment data gained employment and 6 patients lost employment in the 12-month post-omalizumab period. The mean number of A&E visits, inpatient hospitalisations, outpatient visits (excluding for omalizumab) and number of bed days/patient decreased significantly (p<0.001) in the 12-month post-omalizumab period. Conclusions These data support the beneficial effects of omalizumab on asthma-related outcomes, quality of life and resource utilisation in unselected patients treated in ‘real-world’ clinical practice.

Improved Metered Dose Inhaler Technique When a Coordination Cap Is Used

BACKGROUND Patients often experience problems using metered dose inhalers (MDIs), particularly poor coordination between inhalation start and dose actuation (TsIn: time difference between the start of an inhalation and the actuation of a dose), and fast peak inspiratory flow (PIF). We investigated if a coordination cap (CAP), with instruction to prolong inhalation, solved these problems. METHODS Inhalation profiles [PIF, TsIn, inhalation volume (Vi), inhalation time (Ti)] of patients with stable asthma prescribed an MDI were measured using their real-life technique (MDI). Inhalation profiles were then measured with the cap fitted (MDI+CAP). These patients were then instructed to inhale through the MDI+CAP for 5 sec, and inhalation profiles measured (MDI+CAP+TRAIN). TsIn was only measured for the MDI. RESULTS Resistances of MDI and MDI+CAP were 0.0135 and 0.0243 (cm H2O)(½)/(L/min), respectively. Seventy-one patients were evaluated, with mean [standard deviation (SD)] forced expiratory volume over 1 sec % predicted normal of 78.3% (21.0). Following MDI, MDI+CAP, and MDI+CAP+TRAIN: mean (SD) PIF was 155.6 (61.5), 112.3 (48.4), and 73.8 (34.9) L/min, respectively (p<0.001); mean (SD) Ti was 1.60 (0.60), 1.92 (0.80), and 2.99 (1.03) sec, respectively (p<0.001); and Vi was similar between stages. Twelve patients used a slow flow with the MDI alone, but only two of these patients demonstrated good coordination. With the cap in place (which ensures good coordination), the number of patients using a slow flow increased to 25 for MDI+CAP and to 50 following MDI+CAP+TRAIN. CONCLUSIONS The cap with its effect of increasing resistance to airflow combined with the instruction to prolong inhalation time significantly decreased the inhalation flow.

Early bronchodilator action of glycopyrronium versus tiotropium in moderate-to-severe COPD patients: a cross-over blinded randomized study (Symptoms and Pulmonary function in the moRnING).

Background Morning symptoms associated with COPD have a negative impact on patients’ quality of life. Long-acting bronchodilators with rapid onset may relieve patients’ symptoms. In the Symptoms and Pulmonary function in the moRnING study, we prospectively compared the rapid onset bronchodilator profile of glycopyrronium (GLY) and tiotropium (TIO) during the first few hours after dosing in patients with moderate-to-severe COPD. Methods Patients were randomized (1:1) to receive either once-daily GLY (50 μg) or TIO (18 μg) and corresponding placebos in a cross-over design for 28 days. The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4 hours (AUC0-4h) forced expiratory volume in 1 second (FEV1) after the first dose. The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Questionnaire 3 hours post-inhalation. Results One-hundred and twenty-six patients were randomized (male 70.2%; mean age 65.7 years) and 108 patients completed the study. On Day 1, GLY resulted in significantly higher FEV1 AUC0-4h after the first dose versus TIO (treatment difference [Δ], 0.030 L, 95% confidence interval 0.004–0.056, P=0.025). Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO. Post hoc analysis of the FEV1 AUC0-4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes (Δ=0.029 L, P=0.015), 15 minutes (Δ=0.033 L, P=0.026), and 1 hour (Δ=0.044 L, P=0.014). Safety results were comparable between both treatments. Conclusion The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration, thus extending the clinical data that support a faster onset of action of GLY versus TIO.

P19 Impact of month of initiation of omalizumab on treatment of severe allergic asthma, a sub-analysis of the apex ii study

Introduction and Objectives In asthma, seasonal variation in outcomes is known with seasonal peaks in exacerbation. Allergic inflammation is associated with greater susceptibility to viral infections. The UK real world studies, APEX I and II, demonstrated omalizumab reduced exacerbation frequency, healthcare utilisation, OCS burden and improved lung function in severe allergic asthma patients, but initial analyses excluded an assessment of seasonal impact. Patients initiated during their usual symptom season, may have inadequate time to suppress basophils and mast cells prior to exacerbating and consequently fail their 16 week treatment assessment assessing response. The objective was to determine if season/month of initiation had any impact on response (16 week clincial assessment according to usual clinical practice at each centre), hospital (A and E attendance and/or admission) and ’dose exacerbation’, (OCS dose increase ≥10 mg for ≥3 days) rates. Methods The APEX II data was reanalysed, directly comparing response rate and frequency of exacerbations with time of initiation. We also looked at the pattern of seasonal exacerbations pre- and post- omalizumab initiation. Results In the 258 cases included, response rate at 16 weeks where response was known was 82.4%. Highest response rates were in those initiated on treatment in December (90%) and July (89%) and lowest were January (62%) and August (69%). The total number of ‘hospital exacerbations’, over the 12 month period pre- and post-initiation was reduced from 362 to 151. Pre-initiation, there was a seasonal peak of hospital exacerbations (figure 1) from August to October. This was suppressed by omalizumab, with greatest reduction observed in September (76%) and lowest in March (29%). The total number of ‘dose exacerbations’, over the 12 month period pre- and post-initiation was reduced from 948 to 522. The seasonal pattern was different than for hospital admissions, with a relatively consistent reduction of dose exacerbations across the year. The season/month of initiation was not statistically different for response, hospital and dose exacerbation rates. Conclusions Regardless of the timing of initiation, the response rate to omalizumab is consistent through the year, the biggest observable seasonal effect, was the diminishing of the seasonal peak of hospital exacerbations around early autumn. Please refer to page A257 for declarations of interest in relation to abstract P19. Abstract P19 Figure 1 Impact of omalizumab on hospital exacerbations. 2 point moving average is the average of the previous data point and the current data point.