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Pulmonary nodules are a common finding on computed tomography (CT) scans of the chest. In the United Kingdom (UK) management should follow British Thoracic Society (BTS) Guidelines, which were published in 2015. This review covers key aspects of nodule management also looks at new and emerging evidence since then.

Background Global annual cancer incidence is forecast to rise to 27.5M by 2040, a 62% rise from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities. Methods A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type. Results 117,701 abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis and 85 (4%) a combination. Colorectal, breast and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe or Asia. Conclusions This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.

Lung cancer is the leading cause of cancer-related deaths worldwide, primarily because most people present when the stage is too advanced to offer any reasonable chance of cure. Over the last two decades, evidence has accumulated to show that early detection of lung cancer, using low-radiation dose computed tomography, in people at higher risk of the condition reduces their mortality. Many countries are now making progress with implementing programmes, although some have concerns about cost-effectiveness. Lung cancer screening is complex, and many factors influence clinical and cost-effectiveness. It is important to develop strategies to optimise each element of the intervention from selection and participation through optimal scanning, management of findings and treatment. The overall aim is to maximise benefits and minimise harms. Additional integrated interventions must include at least smoking cessation. In this review, we summarize the evidence that has accumulated to guide optimisation of lung cancer screening, discuss the remaining open questions about the best approach and identify potential barriers to successful implementation.

A global compilation of in situ data is useful to evaluate the quality of ocean-colour satellite data records. Here we describe the data compiled for the validation of the ocean-colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI). The data were acquired from several sources (including, inter alia, MOBY, BOUSSOLE, AERONET-OC, SeaBASS, NOMAD, MERMAID, AMT, ICES, HOT and GeP&CO) and span the period from 1997 to 2018. Observations of the following variables were compiled: spectral remote-sensing reflectances, concentrations of chlorophyll a, spectral inherent optical properties, spectral diffuse attenuation coefficients and total suspended matter. The data were from multi-project archives acquired via open internet services or from individual projects, acquired directly from data providers. Methodologies were implemented for homogenization, quality control and merging of all data. No changes were made to the original data, other than averaging of observations that were close in time and space, elimination of some points after quality control and conversion to a standard format. The final result is a merged table designed for validation of satellite-derived ocean-colour products and available in text format. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) was propagated throughout the work and made available in the final table. By making the metadata available, provenance is better documented, and it is also possible to analyse each set of data separately. This paper also describes the changes that were made to the compilation in relation to the previous version (Valente et al., 2016). The compiled data are available at https://doi.org/10.1594/PANGAEA.898188 (Valente et al., 2019)., Sí

To determine the effects of budesonide and formoterol administered via one pressurized metered-dose inhaler (budesonide/formoterol pMDI) on patient-reported outcomes (PROs) and to determine the contributions of budesonide and formoterol to those effects in adults with asthma.A 12-week, randomized, double-blind, double-dummy, placebo-controlled, multicenter study was conducted in 480 patients agedor = 12 years with mild-to-moderate persistent asthma. After a 2-week run-in period during which current asthma therapy was discontinued, patients were randomized to receive two inhalations twice daily of budesonide/formoterol pMDI 80/4.5 microg (160/9 microg), budesonide pMDI 80 microg (160 microg), formoterol via dry powder inhaler (DPI) 4.5 microg (9 microg), or placebo.Analyses included a subpopulation of 405 patients agedor = 18 years. PROs included the standardized Asthma Quality of Life Questionnaire (AQLQ(S)), the Medical Outcomes Study (MOS) Sleep Scale, the Patient Satisfaction with Asthma Medication (PSAM) questionnaire, and asthma control variables (recorded via electronic diaries), such as asthma symptoms, rescue medication use, and nighttime awakenings due to asthma. Patient and physician global assessments were collected at the end of the study.Patients agedor = 18 years receiving budesonide/formoterol pMDI reported significantly greater improvements from baseline in AQLQ overall and domain scores, MOS Sleep Scale domain scores, and asthma control variables than patients receiving placebo (por = 0.033). Improvements from baseline in AQLQ(S) overall and domain scores, daily asthma symptoms scores, percentage of symptom-free days, percentage of rescue medication-free days, and percentage of asthma control days were significantly greater in patients receiving budesonide/formoterol pMDI versus formoterol DPI (por = 0.042). Patients receiving budesonide/formoterol pMDI reported significantly greater PSAM scores than did patients in all other treatment arms (por = 0.004). Study limitations may include the fact that the formoterol-alone arm used a different device and formulation than the other active arms as well as the absence of a treatment arm with budesonide and formoterol administered concomitantly in separate inhalers. In addition, these results may not be generalized to all patients with asthma, as this analysis included only patients agedor = 18 years.Patients receiving treatment with budesonide/formoterol pMDI experienced significantly greater improvements from baseline in asthma-related quality of life, quality of sleep, and asthma control and greater satisfaction with treatment than patients receiving placebo. The combination of budesonide and formoterol in one pMDI is beneficial in improving how a patient feels and functions as a result of treatment.

Topical corticosteroids are the recommended first-line treatment for all severities of persistent asthma and moderate to severe allergic rhinitis. Potential adrenal suppression resulting from corticosteroid administration necessitates monitoring of children participating in clinical studies. Measurement of pretreatment cortisol concentrations is necessary to assess effects on adrenal function.Plasma cortisol concentrations are assay dependent; normal reference range values must be obtained for each assay. Our objective is to provide these values for children as determined by HPLC.Two multicenter, randomized, double-blind, placebo-controlled studies evaluating basal and cosyntropin-stimulated morning plasma cortisol concentrations for patients aged 5 to younger than 12 months with asthma and patients aged 2 to younger than 6 yr with allergic rhinitis using HPLC were conducted.Main planned outcomes of these studies are reported elsewhere. This manuscript reports plasma cortisol concentration reference range values.In general, mean basal plasma cortisol concentrations (n = 177) (mean +/- sd, nmol/liter) were similar among the 5 to younger than 9 months, 9 to younger than 12 months, 2 to younger than 3 yr, 3 to younger than 4 yr, 4 to younger than 5 yr, and 5 to younger than 6 yr age groups (218 +/- 149, 281 +/- 144, 257 +/- 105, 231 +/- 83, 298 +/- 118, and 237 +/- 65, respectively) and increased to comparable levels 60 min after cosyntropin stimulation (n = 178; 622 +/- 176, 638 +/- 176, 697 +/- 99, 655 +/- 103, 662 +/- 113, and 610 +/- 68, respectively). However, patients younger than 12 months had wider ranges of basal and stimulated values.Basal and cosyntropin-stimulated morning plasma cortisol concentrations of children aged 5 to younger than 12 months and 2 to younger than 6 yr were consistently measurable, with the large majority similar among the age groups examined, and comparable with those reported elsewhere for adults.

Background Recent guidelines recommend intranasal corticosteroids as first-line treatment for managing persistent symptoms of moderate to severe allergic rhinitis (AR). However, in children, long-term continual treatment with corticosteroids has raised concerns about potential growth suppression. Objective To evaluate the effects of the recommended once-daily dose of budesonide aqueous nasal spray on growth velocity, as measured with stadiometry, in children with perennial AR. Methods In this double-blind, placebo-controlled, multicenter study, 229 prepubertal children (mean age, 5.9 years; age range, 4-8 years) with perennial AR were randomized (2:1) to receive budesonide aqueous nasal spray, 64 μg (32 μg per nostril) once daily, or placebo for 1 year. The change from baseline in growth velocity, height after treatment, and the percentage of patients whose percentile for height decreased from baseline to the end of treatment were evaluated. Results Growth velocity was not significantly different between the 2 groups. The least-squares mean ± SE growth velocity during treatment was 5.91 ± 0.11 cm per year for children receiving budesonide and 6.19 ± 0.16 cm per year for those receiving placebo. The mean difference in growth velocity between the 2 groups was 0.27 ± 0.18 cm per year (95% confidence interval, −0.07 to 0.62 cm per year). After treatment, the mean ± SD height was 128.8 ± 8.7 cm for children receiving budesonide and 128.2 ± 8.8 for those receiving placebo. The percentage of children whose percentile for height decreased during treatment was not significantly different between the 2 groups (budesonide, 59%, placebo, 54%; P = .64). The incidence and types of adverse events and the mean 24-hour urinary cortisol-creatinine ratio were similar for the 2 groups. Conclusions Treatment with budesonide aqueous nasal spray, 64 μg once daily, for 1 year did not suppress growth velocity compared with placebo and was well tolerated in prepubertal children with perennial AR.

Background: Inhaled corticosteroids (ICSs) are the preferred maintenance therapy for adults and children with mild, moderate and severe persistent asthma, with the addition of a long-acting β2-adrenoceptor agonist to ICS therapy recommended for patients with moderate or severe persistent asthma. The efficacy and safety of the combination of budesonide and formoterol delivered via dry powder inhaler (DPI) is well documented. Objective: To compare the efficacy and safety of budesonide/formoterol pressurised metered-dose inhaler (budesonide/formoterol pMDI; Symbicort™ pMDI, AstraZeneca LP, Wilmington, DE, USA) with budesonide pMDI (Pulmicort® pMDI, AstraZeneca, Lund, Sweden), formoterol DPI (Oxis® Turbuhaler®, AstraZeneca, Lund, Sweden), budesonide plus formoterol in separate inhalers (budesonide pMDI + formoterol DPI) and placebo. Study design: This was a 12-week randomised, double-blind, double-dummy, placebo-controlled study. Setting: This multicentre study was conducted in the respiratory specialty clinical practice setting. Patients: The study included 596 patients ≥12 years of age with moderate to severe persistent asthma previously receiving ICSs. Interventions: After 2 weeks on budesonide pMDI 80µg × two inhalations (160μg) twice daily, patients received budesonide/formoterol pMDI 160μg/4.5μg × two inhalations (320μg/9μg); budesonide pMDI 160μg × two inhalations (320μg) + formoterol DPI 4.5μg × two inhalations (9μg); budesonide pMDI 160μg × two inhalations (320μg); formoterol DPI 4.5μg × two inhalations (9μg); or placebo twice daily. Main outcome measures: There were two prespecified primary efficacy variables: mean change from baseline in morning predose forced expiratory volume in 1 second (FEV1), obtained approximately 12 hours after the most recent administration of study medication at home and immediately before the next administration of study medication at the clinic; and mean change from baseline in 12-hour FEV1, assessed as the average change in FEV1 from serial spirometry over the 12-hour period after administration of the morning dose of study medication at the clinic. Results: Mean changes from baseline in morning predose FEV1 at end of treatment were greater (p ≤ 0.049) with budesonide/formoterol pMDI (0.19L) versus budesonide pMDI (0.10L), formoterol DPI (−0.12L) and placebo (−0.17L). Mean changes from baseline in 12-hour FEV1 were greater (p ≤ 0.001) with budesonide/formoterol pMDI after 1 day (0.37L), 2 weeks (0.34L) and at end of treatment (0.37L) versus budesonide pMDI (0.11, 0.15 and 0.15L) and placebo (0.09, −0.03 and −0.03L), and after 2 weeks and at end of treatment versus formoterol DPI (0.19 and 0.17L). Fewer (p ≤ 0.025) patients receiving budesonide/formoterol pMDI versus monoproducts or placebo met worsening asthma criteria. Results were similar in the budesonide/formoterol pMDI group and the budesonide pMDI + formoterol DPI group on all measures. All treatments were well tolerated with similar safety profiles. Conclusions: In this population, twice-daily budesonide/formoterol pMDI provides asthma control significantly greater than the monocomponents or placebo and comparable with budesonide pMDI + formoterol DPI. Safety profiles were similar for all treatments.

Background Sensory attributes of intranasal corticosteroid (INS) products vary. Objective To evaluate patient preferences for INS sensory attributes and the degree to which attributes influence patients' willingness to adhere to therapy. Methods We conducted a cross-sectional study with 120 individuals across 4 US allergy/immunology clinics. Respondents chose between pairs of hypothetical INSs differing in sensory attribute composition. We measured the strength of preferences for 6 sensory attributes (smell, taste, aftertaste, throat rundown, nose runout, and feel of spray in nose or throat). Preferences were measured for 3 intensity levels of each sensory attribute (eg, no taste, weak taste, and strong taste). Other outcomes included an importance score for each sensory attribute and patients' willingness to adhere to therapy with an INS with the lowest intensity levels of each sensory attribute vs one with moderate intensity levels. Results Preferences decreased with increasing intensity levels of each sensory attribute. Aftertaste was the most important attribute in 28% of patients, taste in 19%, throat rundown in 18%, nose runout in 12%, smell in 11%, and feel of spray in 7%. If instructed to take an INS daily for 3 months, 77% of patients stated that they would definitely be able to follow their physician's advice (willingness to adhere) if given one containing the lowest level of each sensory attribute vs 4% if given one having moderate levels ( P Conclusions Patient preferences are inversely related to increasing intensity levels of sensory attributes and affect patients' willingness to adhere to therapy. Application of patient preferences when selecting INSs could improve adherence.

Background Intranasal corticosteroids are safe and effective for treating allergic rhinitis in adults. Since children may receive more systemic corticosteroid on a dose-per-weight basis than adults, the safety of corticosteroid therapy in pediatric patients is an important issue. Objective To determine the effects of treatment with budesonide aqueous nasal spray using the recommended oncedaily dose for adults and children 6 years and older on hypothalamic-pituitary-adrenal (HPA) axis function in pediatric patients with allergic rhinitis. Methods In a 6-week, multicenter, doubleblind, placebocontrolled study, 78 patients aged 2 to 5 years with allergic rhinitis were treated with budesonide aqueous nasal spray (64 μg/d) or placebo. Mean change in morning plasma cortisol levels from baseline to study end 0, 30, and 60 minutes after low-dose (10-μg) cosyntropin stimulation and mean change in the difference from 0 to 30 minutes and from 0 to 60 minutes after cosyntropin stimulation were used to evaluate HPA axis function. Results Mean change from baseline to study end in plasma cortisol levels 0, 30, and 60 minutes after cosyntropin stimulation and the difference from 0 to 30 minutes and from 0 to 60 minutes were not significantly different between the treatment and placebo groups ( P > .05 for all). At the end of the study, 3 budesonide aqueous nasal spray and 6 placebo patients were classified as having subnormal HPA axis function. The safety and tolerability profile of budesonide aqueous nasal spray was comparable to that of placebo. Conclusions Administration of budesonide aqueous nasal spray for 6 weeks was well tolerated and safe and had no measurable suppressive effects on HPA axis function in patients aged 2 to 5 years with allergic rhinitis.

This study evaluated the psychometric properties of content validity, construct validity, and test-retest reliability of a 23-item Sensory Perceptions Questionnaire (SPQ) used to survey sensory perceptions of intranasal corticosteroid sprays. Two patient cohorts (men and women agedor =18 years who had at least a 1-year history of allergic rhinitis and had been using a corticosteroid nasal spray) were enrolled. The content validity and construct validity of the SPQ questions were evaluated using a cognitive debriefing method after cohort 1 (n=15) completed the SPQ. Test-retest reliability (assessed with intraclass correlation coefficients [ICCs] of the SPQ questions) was evaluated in cohort 2 (n=50), after they answered a Web-based version of the SPQ on two occasions, each separated by 7 days. In cohort 1, 7 of 15 patients believed all relevant sensory perceptions were addressed in the questionnaire. Although 8 patients mentioned at least 1 sensory perception that was not addressed, only 4 sensory perceptions were mentioned by more than 1 patient, and none was mentioned reliably by more than 2 patients. Those 4 sensory perceptions not addressed in the SPQ were all intentionally excluded, because they were potential symptoms of rhinitis or adverse events associated with intranasal corticosteroid spray use. Patients regarded the questions as straightforward, nonburdensome, and nonthreatening, signs suggesting the questions were not likely to challenge the construct validity of the SPQ. The responses to 2 questions (one in which patients were asked to indicate whether they were pleased or displeased overall with a particular spray; the other to indicate their overall product preference) were somewhat influenced by the effectiveness of the sprays. Results of test-retest reliability (cohort 2) showed both high (0.8) and low (0.7) ICCs. A high degree of correspondence between the 2 administrations produced a low between-patient variance, which likely resulted in lower ICCs. The SPQ adequately represents the sensory attributes reported by patients regarding intranasal corticosteroid spray use and, overall, is a valid measure of patient preference based on sensory perception.

The UK has been highlighted, by the International Cancer Benchmarking Project and the EUROCARE groups, as a country with one of the lowest lung cancer survival rates. It has been postulated that this is due to an excess of early deaths, delays in diagnosis are thought to contribute to this problem. A recent study showed that 30% of patients with lung cancer die within the first 90 days and they have seen their GP on average five times in the four months before diagnosis, suggesting there may be opportunities to diagnose these patients earlier in the disease process. The challenge GPs face is to identify and refer those at risk as early as possible and to maintain a high index of suspicion if symptoms persist. The SIGN guideline reiterates the importance of performing a chest X-ray in those in whom the suspicion of lung cancer has been raised and not to be falsely reassured by a normal chest X-ray in a high-risk patient. The initial investigation of choice in secondary care remains a CT scan of the chest and abdomen, followed by PET-CT scanning in those deemed suitable for potentially curative treatment. Smoking cessation reduces the risk of post-operative and systemic treatment-related complications and also reduces the chance of cancer recurrence. Surgery remains the initial treatment of choice for those with early stage disease in NSCLC who are deemed fit enough. Those who have early stage NSCLC (stage I or stage II) who are either medically inoperable or decline surgery should be offered radical radiotherapy. Hospital follow-up should be continued while patients are receiving treatment, complemented by clinical nurse specialist input alongside community support. All patients should have access to specialist palliative care teams. Those with palliative care input have improved quality of life and symptom control and fewer hospitalisations.

Few studies have evaluated inhaled corticosteroid (ICS)/long-acting beta(2)-adrenergic agonist combination therapy in asthmatic children. This study was designed to evaluate the safety (primary) and clinical benefits (secondary) of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide dry powder inhaler (DPI) in children with persistent asthma. This was a 26-week, multicenter, randomized, open-label U.S. study of 187 children 6-11 years of age previously receiving ICS. After 1 week of usual ICS therapy, subjects received twice-daily budesonide/formoterol pMDI 160/4.5 micrograms x 2 inhalations (320/9 micrograms; n = 124) or budesonide DPI 200 micrograms x 2 inhalations (400 micrograms [320 micrograms delivered ex-mouthpiece]; n = 63). Budesonide/formoterol and budesonide were well tolerated with a similar incidence of adverse events (AEs) (84.6% and 85.7%, respectively), most of mild or moderate intensity. Treatment-related AE incidence was low (5.4%) and similar across groups (budesonide/formoterol, 4.9%; budesonide, 6.3%). No clinically important treatment differences were observed for 12-lead electrocardiograms, hematology, serum glucose and potassium, and 24-hour urinary cortisol. Compared with budesonide, budesonide/formoterol decreased health care use (urgent care visits and interference with daily activities [child] or work [caregiver]; p < or = 0.012) and improved health-related quality of life (Pediatric Asthma Quality of Life Questionnaire [standardized] and Pediatric Asthma Caregiver Quality of Life Questionnaire overall scores; p < or = 0.006) and pulmonary function (predose forced expiratory volume in 1 second and forced expiratory flow during the middle half of exhalation; p < or = 0.007). In this 26-week study of asthmatic children (6-11 years), safety profiles were similar and clinical benefits were greater with budesonide/formoterol than with budesonide.

Asthma guidelines recommend titrating maintenance medications to the lowest effective dose. This study assessed the efficacy and tolerability of reducing the frequency of dosing in patients previously controlled with twice-daily budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) to once-daily regimens of BUD/FM pMDI or BUD pMDI. This was a 12-week, randomized, double-blind, double-dummy, placebo (PBO)/active-controlled, multicenter study (N = 752) of patients aged > or =16 years with mild to moderate asthma. After 4-5 weeks on single-blind BUD/FM pMDI 160/9 micrograms twice daily (320/18 micrograms daily), patients with stable asthma received BUD/FM pMDI 160/9 micrograms twice daily (320/18 micrograms daily; morning and evening), BUD/FM pMDI 320/9 micrograms once daily (evening), BUD/FM pMDI 160/9 micrograms once daily (evening), BUD pMDI 320 micrograms once daily (evening), or PBO. BUD/FM (once or twice daily) was more effective (p < or = 0.003) than BUD and PBO on evening peak expiratory flow (primary variable), morning pulmonary function assessments, daily symptoms, and nighttime rescue medication use. Twice-daily BUD/FM was more effective (p < or = 0.05) than both once-daily doses for evening pulmonary function assessments and daytime rescue medication use. All treatments were well tolerated. Once- or twice-daily BUD/FM showed better efficacy than BUD once daily or PBO; results generally were more favorable with twice-daily dosing compared with both once-daily dosing regimens, which had one-half the daily FM dose.

Patient-reported outcomes (PROs) are important for evaluating asthma therapy.To evaluate PROs in adults with moderate to severe persistent asthma receiving budesonide and formoterol administered via 1 pressurized metered-dose inhaler (pMDI).This 12-week, double-blind, double-dummy, placebo-controlled, multicenter study randomized 596 patients 12 years or older to budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg); budesonide pMDI 160 microg x 2 inhalations (320 microg) + formoterol dry powder inhaler (DPI) 4.5 microg x 2 inhalations (9 microg); budesonide pMDI 160 microg x 2 inhalations (320 microg); formoterol DPI 4.5 microg x 2 inhalations (9 microg); or placebo, each twice daily, after 2 weeks of budesonide pMDI 80 microg x 2 inhalations (160 microg) twice daily. PROs were assessed in 553 patients 18 years or older using the standardized Asthma Quality of Life Questionnaire (AQLQ[S]), Medical Outcomes Survey (MOS) Sleep Scale, Patient Satisfaction With Asthma Medication (PSAM) questionnaire, diary data, and global assessments.Patients receiving budesonide/formoterol reported significantly greater improvements from baseline on the AQLQ(S) and asthma control variables (based on symptoms and rescue medication use; all P.001) vs placebo. Clinically important improvements (increase ofor = 0.5 points) from baseline to end of treatment in AQLQ(S) overall scores were achieved by 43.6% of patients receiving budesonide/formoterol vs 22.6% of patients receiving placebo (P = .001). The MOS Sleep Scale scores generally showed no differences among treatment groups. Patients receiving budesonide/formoterol had significantly greater PSAM questionnaire scores and better outcomes on physician-patient global assessments at end of treatment vs placebo (all Por = .001).Significantly greater improvements in health-related quality of life and asthma control and greater treatment satisfaction were observed with budesonide/formoterol pMDI vs placebo.

Onset of bronchodilation of budesonide/formoterol in one pressurized metered-dose inhaler (pMDI) has not been evaluated in asthma.To evaluate time to onset of clinically significant bronchodilation (or = 15% improvement in forced expiratory volume in 1 second) and patient-perceived onset of effect (OE) in patients previously receiving inhaled corticosteroids.In two 12-week studies, patients 12 years and older with moderate to severe (study 1; n = 596) and mild to moderate (study 2; n = 480) persistent asthma received budesonide/formoterol pMDI, budesonide pMDI plus formoterol dry powder inhaler (study 1 only), budesonide pMDI, formoterol dry powder inhaler, or placebo. Postdose time to 15% or greater improvement in forced expiratory volume in 1 second and patient-perceived OE (assessed in a subset of patients 18 years and older [study 1, n=553; study 2, n=405]) were evaluated [corrected]More budesonide/formoterol-treated patients achieved onset of clinically significant bronchodilation within 15 minutes (median, 13 minutes) of administration at randomization vs those taking budesonide or placebo (P.001). More patients receiving budesonide/formoterol vs budesonide and placebo reported feeling their study medication begin to work right away (Por = .004; end of week 1). Similar results (P.001) were observed for patient satisfaction with how quickly they felt their medication begin to work (except budesonide/formoterol vs budesonide, study 1 [P = .073]). Time to onset of clinically significant bronchodilation and patient-perceived OE of budesonide/formoterol and formoterol were similar.Budesonide/formoterol demonstrated a more rapid onset of clinically significant bronchodilation and a greater percentage of patients who perceived their medication working right away vs budesonide or placebo.

reported the results of 2 randomized controlled trials in which a greater proportion of patients reported satisfaction with the sensory profile of budesonide aqueous nasal spray than fluticasone propionate nasal spray. The sensory attributes included in these studies were smell, taste, aftertaste, feel of spray in nose/throat, ABSTRACT OBJECTIVE: Sensory attributes of intranasal corticosteroids (INSs) differ by product based on chemical composition. We previously reported that patients are able to demonstrate preferences for certain INS sensory attributes, which may affect their willingness to adhere to therapy. As part of the same study, we also sought to determine if these same patients are willing to pay for products not containing certain sensory attributes. METHODS: We conducted a 2-part cross-sectional study of 120 patients with allergic rhinitis at 4 allergy and immunology clinics in the United States in November and December 2003. In the first part of the study, the patients chose between pairs of hypothetical INS products that differed in the intensity of 6 sensory attributes (smell, taste, aftertaste, throat rundown, nose runout, and feel of spray in nose/throat; results were reported in the Annals of Allergy, Asthma & Immunology (2004;93:345-50)). In the second part of the study, reported here, discrete choice experiment methodology was used in which the patients chose among hypothetical INS products that differed in the intensity of the 6 sensory attributes and monthly copayments of $15, $30, and $50. Each sensory attribute was characterized by 3 intensity levels, e.g., no aftertaste (mild intensity), weak aftertaste (moderate intensity), or strong aftertaste (severe intensity). The strength of preferences, shown as marginal willingness to pay to avoid certain sensory attributes, was measured in U.S. dollars per month. We also evaluated the effect of annual household income on willingness to pay. RESULTS: Demographic results indicated that 86.7% of participants had prior experience with at least 2 INS products. Seven patients (5.8%) were excluded from the willingness-to-pay analysis due to inconsistent responses to the logic checks used to confirm patient engagement in the study instrument. On average, the 113 remaining patients were willing to pay $11 (95% confidence interval (CI), $9-$13) per month in 2003 dollars to get an INS with no smell instead of strong smell, $12 (95% CI, $10-$14) for no taste instead of strong taste, $20 (95% CI, $18-$22) for no aftertaste instead of strong aftertaste, $10 (95% CI, $9-$12) for no throat rundown instead of a lot of throat rundown, $11 (95% CI, $9-$13) for no nose runout instead of a lot of nose runout, and $6 (95% CI, $4-$8) for a spray with a wet feel instead of a dry feel. Comparing moderate intensity levels of each sensory attribute with the mildest, only 3 attributes had statistically significant willingness to pay: aftertaste, throat rundown, and nose runout. Patients with a higher income were willing to pay more to avoid a lot of throat rundown and nose runout than those with a low income (P

Intranasal corticosteroids are effective for the treatment of allergic rhinitis. Sensory attributes associated with these sprays may affect patient preference and adherence to treatment regimens.These 2 studies compared patients' perceptions of and preferences for specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS).In 2 multicenter, randomized, single-blind (patient), single-dose, 2-period, 1-day crossover studies, adults with mild to moderate allergic rhinitis received single doses of BANS (one 32-pg spray per nostril in both studies, 64-microg total dose) and FPNS (two 50-microg sprays per nostril in study 1, 200-pg total dose; one 50-microg spray per nostril in study 2, 100-microg total dose). Study 1 compared the once-daily recommended starting doses of BANS and FPNS, and study 2 compared BANS with half the once-daily recommended dose of FPNS to balance the number of actuations for delivery of study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and indicated their product preference (if any).A total of 110 women and 71 men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. None had previously used BANS or FPNS. In both studies, fewer patients perceived scent or taste (both P0.001 in both studies), forceful spray (P0.001 in both studies), and a wet feel in both the nose and throat (study 1, P0.004; study 2, P0.002) with BANS than with FPNS. In addition, more patients in both studies liked the spray force (study 1, P0.01; study 2, P0.001) and moisture content in the throat (study 1, P0.001; study 2, P0.006) of BANS and indicated a greater overall satisfaction with the sensory features of BANS than those of FPNS (study 1, P0.001; study 2, P0.015). In analyses that included all responding patients, 54.4% of patients in study 1 preferred BANS and 37.8% preferred FPNS (P0.022). In study 2, 47.4% preferred BANS and 41.1% preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4% in study 2 who specified a product preference, 59.0% preferred BANS and 41.0% preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4% preferred FPNS in study 2 (not significant).On the basis of perceptions of specific sensory attributes reported after 1 administration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than half the QD recommended starting dose of FPNS.

Introduction Around 5% of CT pulmonary angiograms (CTPA) are indeterminate, usually due to incomplete contrast enhancement of pulmonary arteries, motion artefact or difficulty interpreting small peripheral filling defects. While BTS guidelines propose good quality negative CTPA as sufficient grounds to not treat for pulmonary embolism (PE), response to indeterminate CTPA is not addressed. No previous study has investigated variation in radiologists′ reporting and clinicians′ response to indeterminate CTPA′s. Methods Records of 51 patients with indeterminate CTPA were retrospectively reviewed for radiologist′s reporting, clinicians′ documentation of such, and clinical outcomes. Results Reports included “no large central PE” (n=25), “no obvious PE within the limitations of the study” (n=14), “unable to exclude segmental/subsegmental PE” (n=5), and “equivocal filling defects of uncertain significance” (n=4). 17/51 (33%) stated: “PE cannot be excluded.” Further imaging was suggested in only 2 cases. Clinicians documented recognition of technical shortcomings, reported by radiologists, in only 16/51 cases (31%), and recorded “no PE” in 29/51 (57%). Clinicians assessed pre-test probability in 8/51 (8%). 36 patients had the diagnosis of PE dismissed without further tests, of whom 26 were treated for other acute cardio-respiratory conditions revealed on CTPA. 0 had one or more additional tests (repeat CTPA, V/Q scan or Doppler u/s), confirming thrombo-embolic disease in 2. Further investigation was significantly more likely following scans stating “PE cannot be excluded” than all other reports; both overall (47% vs 6%, p Conclusion There is a lack of clear guidance, and considerable variation in radiological reporting of, and clinicians′ response to indeterminate CTPA. Un-ambiguous reporting, repeat clinical assessment, appropriate consideration of alternative diagnoses, and further investigation where appropriate may reduce the risks of missed diagnosis or unwarranted anti-coagulation.

Rationale RPNS, a recently developed nasal glucocorticosteroid for AR, was compared to BANS with known efficacy for AR, and placebo, using the EEU, a controlled-pollen exposure setting. Methods This double-blind, randomized, placebo-controlled, parallel-group study of 291 adults ≥16 years of age with seasonal (ragweed) AR evaluated 3 doses of RPNS (20, 100, 200 μg) with BANS (128 μg) and placebo once daily for 8 days (3 pretreatment days followed by 5 days consisting of 3 hour EEU challenge sessions). Primary efficacy variables were changes in morning and evening total nasal symptom score (TNSS) and peak nasal inspiratory flow (PNIF). Results Only the 200-μg dose of RPNS significantly reduced morning TNSS compared with placebo (P=.007); no RPNS treatment group demonstrated significant differences in evening TNSS compared with placebo. However, BANS treatment significantly reduced morning TNSS compared with placebo (P Conclusion Rofleponide palmitate nasal spray was less effective than budesonide aqueous nasal spray 128 μg for the relief of symptoms of seasonal AR when compared with placebo and at doses up to 100 μg upon comparing both active medications. Both active medications were well tolerated.

Rationale ICSs are a preferred therapy for persistent asthma. We assessed the impact of the pregnancy labeling upgrade of budesonide dry-powder inhaler (BUD DPI) to Category B on future treatment choices. Methods Allergists and pulmonologists (A/Ps) and primary care physicians (PCPs) who had been practicing for 2-25 years were selected from a marketing database and surveyed regarding asthma treatment choices. Results The 75 A/Ps treated an average of 113 patients with asthma per month, whereas the 77 PCPs treated 53; 24% of each group were females of childbearing age (15–44 years). A/Ps and PCPs frequently prescribed ICS for nonpregnant women (62% vs 58%) and pregnant patients in need of asthma therapy (68% vs 63%). However, A/Ps were twice as likely than PCPs to be aware of a Category B ICS treatment option (56% vs 27%); 55% of A/Ps versus 31% of PCPs knew that this ICS was BUD DPI. With this new awareness, A/Ps and PCPs reported that they would likely prescribe BUD DPI for 51% and 62%, respectively, of their next 20 patients of childbearing age in need of ICS therapy versus 27% and 34% of their previous 20. A/Ps and PCPs projected prescribing BUD DPI for 61% and 76%, respectively, of their next 20 pregnant asthma patients appropriate for ICS therapy versus 32% and 39% of their previous 20. Conclusion Increased awareness of the availability of a Category B ICS (BUD DPI) will allow appropriate consideration of treatment options by physicians treating pregnant patients with persistent asthma.