Assessment of clinical workload for general and specialty genetic counsellors at an academic medical center: a tool for evaluating genetic counselling practices.

With genomics influencing clinical decisions, genetics professionals are exponentially called upon as part of multidisciplinary care. Increasing demand for genetic counselling, a limited workforce, necessitates practices improve efficiency. We hypothesised that distinct differences in clinical workload exist between various disciplines of genetic counselling, complicating practice standardisation and patient volume expectations. We thus sought to objectively define and assess workload among various specialties of genetic counselling. Twelve genetic counsellors (GCs), representing 9.3 clinical FTE, in general or specialty (cancer, cardiovascular or prenatal) services at an academic health system developed a data collection tool for assessing time and complexity. Over a 6-week period, the data were recorded for 583 patient visits (136 general and 447 specialty) and analysed comparing general versus specialty GCs. Variables were compared with hierarchical linear models for ordinal or continuous data and hierarchical logistic models for binary data. General GCs completed more pre- and post-visit activities (P=0.011) and spent more time (P=0.009) per case. General GCs reported greater case discussion with other providers (P<0.001), literature review (P=0.026), exploring testing options (P=0.041), electronic medical record review (P=0.040), insurance preauthorization (P=0.05) and fielding patient inquiries (P=0.003). Lesser redundancy in referral indication was observed by general GCs. GCs in general practice carry a higher pre- and post-visit workload compared with GCs in specialty practices. General GCs may require lower patient volumes than specialty GCs to allow time for additional pre- and post-visit activities. Non-clinical activities should be transferred to support staff.

Compound heterozygous mutations in the SCN5A-encoded Nav1.5 cardiac sodium channel resulting in atrial standstill and His-Purkinje system disease.

An 11-year-old girl on evaluation for syncope was found to have progressive sinus node dysfunction and His-Purkinje system disease with atrial standstill. Genetic analysis revealed compound heterozygous mutations of the SCN5A gene in a novel combination.

Growth velocity reduced with once-daily fluticasone furoate nasal spray in prepubescent children with perennial allergic rhinitis.

BACKGROUND: The effect of fluticasone furoate nasal spray (FFNS) on growth in prepubescent children has not been evaluated. OBJECTIVE: To characterize the difference in mean prepubescent growth velocities, as determined by stadiometry, between patients treated continuously for 1 year with FFNS 110 mcg once daily and placebo nasal spray. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group 76-week safety study. Nasal symptom assessments were used as a measure of adherence. Eligible patients were ages 5 to <8.5 years at screening and had at least a 1-year clinical history and diagnosis of perennial allergic rhinitis, including a positive skin test or specific IgE to an appropriate perennial allergen within the past year. RESULTS: One hundred eighty-six patients in the FFNS group and 187 patients in the placebo group completed the entire 52-week treatment period. During treatment, the least squares mean growth velocity was 5.19 cm/y for the FFNS group and 5.46 cm/y for the placebo group; mean difference, -0.270 cm/y (95% CI, -0.48 to -0.06 cm/y). Other safety assessments, including 24-hour urinary cortisol excretion, were comparable between the treatment groups. Daily reflective total nasal symptom scores declined similarly in both the FFNS and placebo groups. CONCLUSION: Once-daily treatment with FFNS over 52 weeks in prepubescent children resulted in a small reduction in growth velocity compared with placebo. Clinicians will need to balance the reduction in growth observed with FFNS to its potential for clinical benefit.

Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma.

OBJECTIVE: To investigate the clinical benefits of 'add-on' therapy with GSK2190915 in combination with the inhaled corticosteroid (ICS) fluticasone propionate (FP) and the ICS/long-acting beta 2 agonist (LABA) combination FP/salmeterol in asthmatic subjects. METHODS: Both studies were cross-over, randomized, double-blind, double-dummy and placebo-controlled in subjects with a forced expiratory volume in 1 second (FEV1) best of >50 and ≤80% of predicted. Add-on to ICS: Subjects (n = 162) aged ≥12 years received FP 100 µg twice daily (BID) plus GSK2190915 100 mg once daily (QD); GSK2190915 300 mg QD; montelukast 10 mg QD; salmeterol 50 µg BID or placebo. Add-on to ICS/LABA: Female subjects (n = 145) aged ≥18 years received FP/salmeterol 250/50 µg BID plus GSK2190915 300 mg QD, montelukast 10 mg QD or placebo. In both studies, the primary endpoint was trough FEV1 at the end of the treatment period. Secondary endpoints included a range of objective and patient-reported measures of efficacy. RESULTS: Add-on to ICS: There was no statistically significant difference in the primary endpoint between either dose of GSK2190915 (add-on to FP) and placebo. Nominally statistically significant increases were demonstrated for GSK2190915 300 mg add-on relative to placebo for mean morning peak expiratory flow (p = 0.049), percentage of symptom-free days (p = 0.035) and percentage of symptom-free 24 h periods (p = 0.030). Add-on to ICS/LABA: There were no statistically significant differences on the primary endpoint between treatment regimens. Nominally statistically significant decreases were demonstrated in daytime (p = 0.023), night-time (p = 0.041) and 24 h (p = 0.019) short-acting beta 2 agonist usage with FP/salmeterol + GSK2190915 300 mg vs. FP/salmeterol + placebo. CONCLUSION: There was no clinically significant improvement in the primary endpoint following GSK2190915 add-on treatment; however, improvements in a range of secondary endpoints and biomarker data provided evidence of pharmacological activity. Improvements in response to background treatment may have been a limitation in both studies. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT01156792 and NCT01248975.

No mucosal atrophy and reduced inflammatory cells: active-controlled trial with yearlong fluticasone furoate nasal spray.

BACKGROUND: Fluticasone furoate nasal spray (FFNS) and mometasone furoate nasal spray (MFNS) are well tolerated and more effective than placebo at relieving the symptoms of seasonal and perennial allergic rhinitis. Effects of FFNS on the nasal histology have not been previously reported. This study examines the effects of FFNS and MFNS, administered daily for 1 year, on the nasal mucosa in subjects with perennial allergic rhinitis. METHODS: Subjects with perennial allergic rhinitis were randomized 1:1 to q.d., open-label treatment with FFNS, 110 µg, or MFNS, 200 µg, for 1 year. These groups and a healthy control group that did not receive study medication underwent nasal biopsies at baseline and 12 months. RESULTS: The nasal biopsy population comprised 96 participants (37 using FFNS, 42 using MFNS, and 17 healthy controls). Epithelial thickness did not change appreciably from baseline to week 52 in any of the groups and mean change from baseline did not differ between FFNS and MFNS (least square mean difference, -0.001 mm, 95% confidence interval, -0.007, 0.006). Although not tested for significance, improvements over baseline were observed in epithelial histology in the FFNS group with more epithelium including intact columnar and ciliated epithelial cells. No appreciable change in the percentage of goblet cells was established. FFNS and MFNS were associated with decreases in epithelial and subepithelial nasal mucosal eosinophils and basophils from baseline to week 52. The percentage of subjects with no inflammatory cells at week 52 was 49 and 33% for eosinophils and 46 and 24% for basophils, for FFNS and MFNS, respectively. CONCLUSION: Yearlong therapy with either FFNS or MFNS showed no changes in epithelial thickness or the percentage of goblet cells as well as a reduction in inflammatory cell infiltrate. FFNS was associated with improvements in epithelial histology. These data support the long-term safety of FFNS in subjects with perennial allergic rhinitis.

HPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitis.

The effects of intranasal corticosteroids (INSs) on the hypothalamic-pituitary-adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 microg once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2-11 yr with a 1-yr history of PAR (6 months for patients aged 2-3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88-1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 microg QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR.

Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray.

BACKGROUND: Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated. OBJECTIVE: To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR. METHODS: A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate. RESULTS: A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment. CONCLUSION: Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.