Fibrinogen concentrate and maternal outcomes in severe postpartum hemorrhage: A population-based cohort study with a propensity score-matched analysis

Study objectiveFibrinogen concentrate is used to treat severe postpartum hemorrhage despite limited evidence of its effectiveness in obstetric settings. We aimed to explore the association between its administration and maternal outcomes in women with severe postpartum hemorrhage.Design, setting and patientsThis secondary analysis of the EPIMOMS prospective population-based study, exploring severe maternal morbidity, as defined by national expert consensus (2012–2013, 182,309 deliveries, France), included all women with severe postpartum hemorrhage and transfused with red blood cells during active bleeding.MeasurementsThe primary endpoint was maternal near-miss or death, and the secondary endpoint the total number of red blood cells units transfused.InterventionsWe studied fibrinogen concentrate administration as a binary variable and then by the timing of its administration. We used multivariable analysis and propensity score matching to account for potential indication bias.Main resultsAmong the 730 women with severe postpartum hemorrhage and transfused, 313 (42.9%) received fibrinogen concentrate, and 142 (19.5%) met near-miss criteria or died. The risk of near-miss or death was not significantly lower among the women treated with fibrinogen concentrate than among those not treated, in either the multivariable analysis (adjusted RR = 1.03; 95% CI, 0.72–1.49; P = 0.855) or the propensity score analysis (RR = 0.85; 95% CI, 0.55–1.32; P = 0.477). Among women treated with fibrinogen concentrate, administration more than three hours after red blood cell transfusion started was associated with a higher risk of near-miss or death than administration before or within 30 min after the transfusion began (adjusted RR = 2.07; 95% CI, 1.10–3.89; P = 0.024). Results were similar for the secondary endpoint.ConclusionsThe use of fibrinogen concentrate in severe postpartum hemorrhage needing red blood cell transfusion during active bleeding is not associated with improved maternal outcomes.     

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).

Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.

Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).

Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).

Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.

Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.     

A multicenter evaluation of a sample to answer real-time PCR assay for toxigenic C. difficile in symptomatic subjects

We evaluated the performance of the Luminex ARIES® C. difficile Assay on 984 stool specimens prospectively collected from patients being tested for CDI at 4 clinical laboratories in the United States. Results were compared to direct and enriched toxigenic culture. Positive percent agreement (PPA) of the ARIES® C. difficile Assay was 98.1% versus direct toxigenic culture, and sensitivity versus direct plus enriched toxigenic culture was 90.5%. Negative percent agreement (NPA) of the ARIES® C. difficile Assay against direct culture was 92.6%, and specificity versus direct plus enriched toxigenic culture was 95.8%. The ARIES® C. difficile Assay was also compared to the results of routine (molecular, antigen, and/or toxin) methods for C. difficile testing used at each institution. The PPA of the ARIES® C. difficile Assay ranged from 82.9% to 100%. NPA values against these commercial assays ranged from 94.5% to 100%.     

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium’s Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response.     

Transcatheter Aortic Valve Replacement in Low-Risk Bicuspid and Tricuspid Patients: Meta-Analysis

BackgroundMost pivotal transcatheter aortic valve replacement (TAVR) trials have excluded patients with bicuspid aortic stenosis (AS). This study compared TAVR in low-risk patients with bicuspid AS to those with tricuspid AS, incorporating data from prospective trials.MethodsWe selected prospective US low-risk TAVR trials containing a bicuspid arm for this meta-analysis, examining outcomes at 30 days. Study results were pooled using a hierarchical Bayesian random-effects model.ResultsIncluded were 3 Food and Drug Administration (FDA)-approved investigational device exemption (IDE) trials that enrolled a total of 1810 low-risk patients with symptomatic severe AS for TAVR. We compared 380 bicuspid patients with 1430 tricuspid patients. Event rates at 30 days overall were low, with similar mortality (odds ratio [OR], 0.38; 95% credible interval [CrI]: 0.08, 1.78; I², 0%), non-disabling stroke (OR, 0.45; 95% CrI: 0.15, 1.07; I², 9%), and permanent pacemaker implantation (OR, 0.86; 95% CrI: 0.41, 1.47; I², 59%). There were statistically significant differences in disabling stroke (OR, 0.16; 95% CrI: 0.01, 0.90; I², NA) and coronary obstruction (OR, 0.21; 95% CrI: 0.05, 0.91) that disappeared after sensitivity analysis by adding a single event to the tricuspid arm. Hemodynamics were similar at 30 days.ConclusionsPreliminary data from the FDA-approved IDE trials of low-risk patients with bicuspid AS undergoing TAVR demonstrated 30-day outcomes comparable to low-risk tricuspid patients, except for a trend toward higher stroke in bicuspid patients. Randomized trials are warranted to reassure the safety and long-term outcome of TAVR in patients with severe bicuspid AS.