A Novel Mutation Involving the Initiation Codon of FGF3 in a Family Described with Complete Inner Ear Agenesis, Microtia and Major Microdontia (LAMM Syndrome)

LAMM syndrome (OMIM #610706) is a rare autosomal recessive syndrome characterized by the association of Michel aplasia, microdontia and malformation of the external ear. Different mutations in FGF3 gene were reported in several families presenting with this syndrome. Clinical features and genetic results observed in a family with LAMM syndrome are reported. The diagnosis of isolated Michel aplasia was initially made in this family composed of two affected children. Microtia and microdontia was recently evidenced in both patients suggesting the diagnosis of LAMM syndrome. New auditory and orodental iconography was performed permitting to describe the patients’ phenotype in depth and to report rare findings of LAMM syndrome. The sequencing of FGF3 gene identified a novel missense mutation (c.2T>G), substituting the first initiator methionine in arginine, in the fibroblast growth factor 3 (FGF3) at the homozygous state in both patients. LAMM syndrome was confirmed and appropriate genetic counseling performed

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Can adherence to antihypertensive therapy be used to promote adherence to statin therapy?

Richard&amp;nbsp;H Chapman1, Elise M Pelletier1, Paula J Smith1, Craig&amp;nbsp;S Roberts21US Health Economics and Outcomes Research, IMS Health, Falls Church, VA, USA; 2Global Outcomes Research, Pfizer Inc, New York, NY, USAObjective: To compare adherence with statin therapy in patients switching to single-pill amlodipine besylate/atorvastatin calcium with patients adding a separate statin to their amlodipine regimen.Methods: We identified hypertensive patients prescribed amlodipine who switched to amlodipine/atorvastatin (switch) or added a statin to their amlodipine regimen (add-on) from July 2004 to June 2007. Propensity score matching (1 switch:3 add-on) was applied based on &amp;lsquo;nearest neighbor&amp;rsquo; approach. The primary adherence measure was patients with proportion of days covered (PDC) &amp;ge;0.80 at 180 days; secondary measures included mean PDC and persistence. A sensitivity analysis was performed, accounting for total statin/amlodipine exposure.Results: Among 4556 matched patients (n = 1139 switch; n = 3417 add-on), mean age was 53.9 years and 52.1% were male. After 180 days, adherence with statin therapy was higher for the switch vs add-on cohort (50.8% vs 44.3%; P &amp;lt; 0.001). After adjusting for pre-index amlodipine adherence, the switch cohort was more likely to be adherent than the add-on cohort (odds ratio: 1.64 [95% confidence interval: 1.42 to 1.89]). Persistence was higher in the switch than the add-on cohort (127.6 vs 117 days; P &amp;lt; 0.001).Conclusion: Hypertensive patients taking amlodipine who initiated statin therapy via single-pill amlodipine/atorvastatin were more likely to remain adherent to their statin than patients adding a separate statin to their antihypertensive regimen.Keywords: adherence, amlodipine, atorvastatin, cardiovascular disease, persistence, single-pil

Economic Outcomes Associated with Microvascular Complications of Type 2 Diabetes Mellitus: Results from a US Claims Data Analysis

Background Patients with diabetes mellitus have been shown to be at high risk for both macrovascular and microvascular complications (MVC). Recent studies have focused on MVC and their effect on the healthcare system, but limited published data exist on long-term costs associated with MVC in patients with type 2 diabetes mellitus (T2DM). Abstract: Objective The objective of this study was to compare resource utilization and medical costs over a 12-month period among patients diagnosed with T2DM with versus without MVC in a managed-care population. Abstract: Methods Patients aged ≥18 years, diagnosed with T2DM between 1 January 2003 and 31 December 2004 were identified in an administrative claims database of approximately 55 million beneficiaries in private and public health plans. The date of the first T2DM diagnosis during this period was the 'index date' for each patient. All patients had to have a minimum of 12 months of continuous enrolment both prior to and following the index date. MVC was identified during the 12 months prior to the first T2DM diagnosis and these patients were matched (1 : 2) by age, sex and ten co-morbid conditions to those with no evidence of MVC during the entire study period. Abstract: Results Among the 15 326 MVC patients included in the study, 61% had a history of peripheral neuropathy, 28% diabetic retinopathy and 19% nephropathy. Compared with 30 652 patients without MVC, the MVC patients were more likely to use oral antidiabetics and insulin and had a higher co-morbidity score. Over 12 months, patients with MVC had more (mean 0.3 vs 0.2; p < 0.001) and longer (mean length of stay 1.79 days vs 0.85 days; p < 0.001) hospital stays; physician office visits (19.7 vs 13.7; p < 0.001); and prescriptions for oral antidiabetic (6.3 vs 5.6 scripts; p < 0.001) and insulin (0.7 vs 0.2 scripts; p < 0.001) use. Average total costs per patient over 12 months were &dollar;US14 414 with MVC versus &dollar;US8669 without MVC (p < 0.001). Abstract: Conclusion This study indicates that in patients with T2DM, MVC is associated with significant consumption of healthcare resources. Mean total costs with MVC were almost double those of patients without MVC over a 12-month period.