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.     

Treatment of Acquired Bilateral Nevus of Ota-Like Macules (Hori''s Nevus) with a Combination of the 532 nm Q-Switched Nd:YAG Laser Followed by the 1,064 nm Q-Switched Nd:YAG Is More Effective: Prospective Study

BACKGROUND: Acquired bilateral nevus of Ota-like macules (Hori's nevus) is a common dyschromatosis among Asian women. Q-switched lasers have been used successfully as a treatment modality. OBJECTIVE: The purpose of this study was to compare the efficacy of using the Q-switched 532 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser followed by the 1,064 nm laser versus the Q-switched 1,064 nm Nd:YAG laser alone in the treatment of Hori's nevus. METHODS: This is a prospective left-right comparative study. Ten women with bilateral Hori's nevus were recruited and treated with a combination of the Q-switched 532 and 1,064 nm Nd:YAG lasers on the right cheek and the Q-switched 1,064 nm Nd:YAG laser alone on the left cheek. Only one laser treatment session was performed. The degree of pigmentation was objectively recorded with a mexameter. Subjective assessment was made by both patients and two blinded, nontreating dermatologists. RESULTS: At 6 months, there was a statistically significant difference (p = .009) of 35.10 points using objective mexameter measurements between the two sides, favoring the side treated with a combination of 532 and 1,064 nm laser treatment. Subjective grading by the patients and blinded dermatologists also confirmed that combination therapy was more successful after one treatment. Although combination treatment had a higher incidence of mild postinflammatory changes, this disappeared within 2 months. CONCLUSIONS: Concurrent use of the Q-switched 532 nm Nd:YAG laser in combination with the 1,064 nm laser is more effective in pigment clearance than the Q-switched 1,064 nm Nd:YAG laser alone for Hori's nevi.     

Agenesis of the Gallbladder Revisited Laparoscopically

Gallbladder agenesis is an extremely rare disease. Necropsy incidence has been reported to be 0.016%. Failure lo locate the gallbladder at the time of a planned cholecystectomy can be very challenging. We report such a case during a laparoscopic cholecystectomy. The indication for surgery in these patients are complaints of gallbladder symptoms along with a false-positive ultrasound study. During exploration, an abnormal location of the gallbladder has to be excluded. Ectopic gallbladder locations include intrahepatic, lesser omentum, retroperitoneal, retrohepatic, within the falciform ligament, retroduodenal, and retrohepatic areas. Thorough exploration and cholangiography are essential. Embryologically, the gallbladder and cystic duct arise from the caudal portion of the hepatic bud. All of the previously reported cases of gallbladder agenesis have shown an absence of both the gallbladder and cystic duct. We report an embryological oddity wherein a patent cystic duct was found along with an agenetic gallbladder. This is the first case report of this finding, along with this being the first absent gallbladder discovered laparoscopically.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Inborn errors of the urea cycle

Inborn errors of the urea cycle are an important cause of hyperammonaemia throughout childhood, and are associated with high morbidity and mortality rates. If they are diagnosed early and treated appropriately, the outcome for affected children is significantly improved.