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.     

Arrogance in the Workplace: Implications for Mental Health Nurses

Cultures of performativity may contribute to organizational and individual arrogance. Workplace organizations have individuals who at various times will display arrogance, which may manifest in behaviours, such as an exaggerated sense of self-importance, dismissiveness of others, condescending behaviors and an impatient manner. Arrogance is not a flattering label and irrespective of the reason or the position of power, in the context of organizational behaviors, may not be useful and may even be detrimental to the work environment. Thus, it is timely to reflect on the implications of arrogance in the workplace. Advocacy and empowerment can be undermined and relationships adversely impacted, including the achievement of positive consumer outcomes. This paper provides an introduction to arrogance, and then discusses arrogance to promote awareness of the potential consequences of arrogance and its constituent behaviors.     

A study for evaluating the effect of the deltoid-flap repair in massive rotator cuff defects

The repair of massive cuff defects by direct suture often is impossible. In these cases, a repair by musculo–tendineous flaps (latissimus-dorsi, pectoralis or deltoideus) is required. It was the goal of this study to evaluate the result of delta-flap repair in case of massive cuff defects with a diameter of 5 cm or more. Between 1998 and 2000 for all patients who were suffering from a massive rotator cuff tear more than 5 cm a deltoid transfer was performed. A total of 20 patients (14 male, 6 female; age: 60.9 ± 8.7 years) were available for a follow-up after 47.2 ± 8.0 (range, 36 to 60) month. The operation included an arthroscopic evaluation, acromioplasty with resection of the lateral clavicular end, and biceps tenodesis. The cuff defect was repaired by transfer a muscular flap from the anterior part of the deltoid (about 2×6 cm) into the defect. The patients subjectively rated their result—10 excellent, 9 good, and 1 poor. Preoperatively, the Constant amounted 26.3 ± 5.1 points. At follow-up, the score significantly increased to 74.5 ± 8.5 points. The acromiohumeral distance increased from 4.9 ± 1.1 to 9.2 ± 1.7 mm. In MRI examination of 11 patients all had an intact flap. Two complications (a wound hematoma and a deep infection) did not influence the result. The repair of massive rotator cuff tears by a deltoid transfer produces acceptable clinical and radiological results.     

The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis

Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.” Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly influenced. Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. Conclusion The vagal nerve is therefore an important modulator of the immune system. W. Kessler and T. Traeger contributed equally to this work Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Prevalence of H pylori associated 'high risk gastritis' for development of gastric cancer in patients with normal endoscopic findings

INTRODUCTION H pylori infection is an established risk factor for development of gastric cancer[1,2]. According to the model of carcinogenesis of the intestinal type adenocarcinoma proposed by Correa, the multi-step development starts from the condition o…