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.     

Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

The exact location of hemorrhage complicating anticoagulant therapy is sometimes difficult to establish. We present a case in which imaging with 99mTc-labeled red cells had a significant role in the diagnosis of soft-tissue bleeding in a paraplegic patient receiving long-term anticoagulation.     

The incidence of AIDS among blacks and Hispanics

Compared with whites, the acquired immune deficiency syndrome (AIDS) has affected blacks and Hispanics disproportionately. The cumulative incidence (CI) for black men was 2.6, and for Hispanic men 2.5, times the rate for white men. Intravenous (IV) needle use alone does not account for this difference. Not counting IV needle-using cases, the CIs for black and Hispanic men were 1.7 times the CI for white men. Although there were fewer cases in women than men, the white-to-minority disparity was greater for women. The CIs for black and Hispanic women were 12.2 and 8.5 times, respectively, the CI for white women. Prevention programs are urgently needed and should focus on risky behavior (IV needle sharing and receptive anal intercourse), not just risk groups.     

Inability to assess breath sounds during air medical transport by helicopter

This study assessed the capabilities of a traditional and an amplified stethoscope used by flight nurses to assess breath sound during air medical transport in an MBB BO-105 helicopter. We developed a normal breath sound model using a prerecorded tape of breath sounds interspersed with segments without breath sounds; the recorder had been placed in the chest wall of a resuscitation training manikin. Flight nurses completed control listening sessions in a quiet environment and experimental sessions during flight using a traditional stethoscope for half of the sessions and an amplified stethoscope for the remaining half. In the quiet environment, flight nurses accurately reported the presence or absence of breath sounds in 110 (92%) of 120 trials. During helicopter flight, none of the flight nurses heard breath sounds during any of the recorded segments with either the traditional stethoscope or the amplified stethoscope. We conclude that flight nurses are unable to hear normal breath sounds using a traditional or amplified stethoscope during flight in a medically configured MBB BO-105 helicopter. Improved stethoscopes, innovative methods of listening, and reduction of aircraft noise are potential solutions to the problems of breath sound assessment during air medical transport.     

Role of CT in excluding major arterial injury after blunt thoracic trauma

The role of CT in the diagnosis of major vascular rupture following blunt decelerating chest trauma is controversial. Its value in excluding major arterial injury has not yet been determined. During a 12-month period we obtained dynamic enhanced thoracic CT studies in 20 patients with blunt decelerating thoracic trauma who had abnormal or equivocal mediastinal contours on chest radiographs. In all cases diagnosis was confirmed by either digital subtraction (18 patients) or conventional thoracic angiography (two patients). CT scans showed evidence of direct aortic injury in three patients and evidence of mediastinal hematoma in five others. Four of these eight patients had major arterial injury verified angiographically and at surgery. In two patients the CT scan was considered equivocal; both patients had normal thoracic angiograms. CT excluded direct vascular injury or mediastinal hematoma in 10 patients. All 10 had normal thoracic angiograms. This preliminary study suggests that, in patients sustaining blunt decelerating thoracic trauma, thoracic CT may be more valuable than chest radiography in excluding major vascular injury and, in some cases, may reduce the need for thoracic angiography.     

Reduced cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and mild hemorrhage in cats.

The authors investigated the effects of transient, mild hemorrhagic hypotension after fluid-percussion traumatic brain injury on intracranial pressure, cerebral blood flow (CBF), cerebral oxygen delivery (CBF x arterial O2 content), and electroencephalographic (EEG) activity. Adult mongrel cats were anesthetized with 1.6% isoflurane in N2O:O2 (70:30) and prepared for trauma and for radioactive microsphere CBF measurement. Isoflurane concentration was decreased to 0.8%, and the cats were randomly assigned to one of four control groups or to an experimental group. Animals in the four control groups underwent either mild hemorrhage (18 ml.kg-1) immediately followed by resuscitation with equal volumes of 10% Hetastarch (eight cats), mild hemorrhage followed by replacement of shed blood (six cats), isovolemic hemodilution with 18 ml.kg-1 of Hetastarch (six cats), or moderate (2.2 atm) trauma alone (eight cats). The experimental group received a combination of trauma and mild hemorrhage followed by resuscitation with Hetastarch (eight cats). Mild hemorrhage produced no significant changes in CBF, renal blood flow, or cardiac output. Following resuscitation from mild hemorrhage, mean arterial blood pressure, cardiac output, renal blood flow, and CBF were not significantly different from baseline; cardiac output and renal blood flow did not differ significantly from baseline 2 hours after Hetastarch resuscitation. Neither hemorrhage nor trauma alone produced significant decreases in CBF or in EEG activity, but trauma followed by hemorrhage and resuscitation produced significant (p less than 0.01) decreases in CBF, cerebral oxygen delivery, and EEG score. These data demonstrate that, following traumatic brain injury, even mild hemorrhagic hypotension is associated with significant deficits in cerebral oxygen availability and neurological function.