Vectored Thermal Pulsation as a Treatment for Meibomian Gland Dysfunction: A Review Spanning 15 Years.

The LipiFlow Thermal Pulsation System received its first marketing clearance for the treatment of meibomian gland dysfunction (MGD) 13 years ago. Since then, the evidence evaluating the effectiveness and safety of LipiFlow as a treatment for MGD has grown significantly. The objective of this comprehensive review was to summarize all clinical reports evaluating the effectiveness and safety of LipiFlow over the past 15 years. The literature was systematically reviewed, and 55 unique articles had subjective (patient-reported outcomes) and objective (meibomian gland function, tear production, and ocular staining) outcomes for extraction. Data were collected from 2101 patients and 3521 eyes treated with LipiFlow. Of these, effectiveness was evaluated in 2041 patients and 3401 eyes, and safety was evaluated in 1448 patients and 2443 eyes. Taken together, the studies demonstrate that a single 12-min treatment with LipiFlow safely improves signs and symptoms of MGD and associated evaporative dry eye disease (DED), and the benefits persist up to 3 years in some cases. The findings are corroborated by multiple meta-analyses and consensus guidelines. While some studies showed that daily eyelid hygiene, warm compress, and/or massage had a similar benefit to a single LipiFlow, these treatments were limited by inconvenience, discomfort, and non-compliance. The majority of studies evaluating safety reported no discomfort or pain associated with LipiFlow treatment, which supports the patient acceptability of LipiFlow therapy. All adverse events (AEs) related to LipiFlow were transient, non-vision-threatening, and did not require treatment. No studies reported serious AEs. The data obtained from 55 studies conducted globally overwhelmingly show that LipiFlow is effective and safe for the treatment of MGD and associated evaporative DED. The conclusions are supported by the diversity of the patient populations (geography, race, disease severity, and diagnosis), the large population treated with LipiFlow, the meta-analyses, and that this review analyzed all published clinical studies to date.

Safety of lidocaine 15% and prilocaine 5% topical ointment used as local anesthesia for intense pulsed light treatment.

BACKGROUND: Literature cautions against applying lidocaine 15%/prilocaine 5% over an area larger than 300 cm(2). The area of the face, neck, and chest is 400 cm(2) or greater. OBJECTIVE: To investigate the safety of lidocaine 15%/prilocaine 5% topical anesthetic ointment used as anesthesia for intense pulsed light (IPL) treatment. METHODS AND MATERIALS: Lidocaine 15%/prilocaine 5% ointment was applied to the face only (n=10) for 30 +/- 15 minutes or to the face, neck, and chest (n=10) for a total of 60 +/- 15 minutes before IPL. Blood lidocaine and prilocaine levels were measured. Adverse events were recorded. RESULTS: For the entire cohort, blood was drawn 25.6 +/- 6.6 minutes after IPL was completed. In the face only group, the mean lidocaine level was 0.122 +/- 0.125 microg/mL, and the mean prilocaine level was 0.048 +/- 0.029 microg/mL. In the face, neck, and chest group, the mean lidocaine level was 0.272 +/- 0.208 microg/mL, and the mean prilocaine level was 0.087 +/- 0.060 microg/mL. No adverse events related to systemic toxicity were observed or reported to the nurse. At the 24-hour follow-up, no subject reported symptoms of systemic toxicity after leaving the clinic. CONCLUSION: Under the conditions of this study, topical lidocaine 15%/prilocaine 5% produces low levels of systemic absorption.

Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania: a randomized, 12-week, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of olanzapine, divalproex, and placebo in a randomized, double-blind trial in mild to moderate mania (DSM-IV-TR criteria). METHOD: The study was conducted from October 2004 to December 2006. A total of 521 patients from private practices, hospitals, and university clinics were randomly assigned to olanzapine (5-20 mg/day), divalproex (500-2500 mg/day), or placebo for 3 weeks; those completing continued with a 9-week double-blind extension. Efficacy (mean change in Young Mania Rating Scale [YMRS] total score was the primary outcome) and safety were assessed. RESULTS: After 3 weeks of treatment, olanzapine-treated (N = 215) and placebo-treated (N = 105) patients significantly differed in YMRS baseline-to-endpoint total score change (p = .034; least squares [LS] mean: -9.4 and -7.4, respectively). Such changes were not significantly different between olanzapine vs. divalproex (N = 201) or divalproex vs. placebo. After 12 weeks of treatment, olanzapine- and divalproex-treated patients significantly differed in YMRS baseline-to-endpoint changes (p = .004; LS mean: -13.3 and -10.7, respectively). Of observed cases, 35.4% (35/99; 3 weeks) to 57.1% (28/49; 12 weeks) had valproate plasma concentrations lower than the recommended valproate therapeutic range, but these patients' YMRS scores were lower than those of patients with valproate concentrations above/within range. Compared with divalproex, after 12 weeks, olanzapine-treated patients had significant increases in weight (p < .001) and in glucose (p < .001), triglyceride (p = .003), cholesterol (p = .024), uric acid (p = .027), and prolactin (p < .001) levels. Divalproex-treated patients had significant decreases in leukocytes (p = .044) and platelets (p < .001) compared with olanzapine after 12 weeks of treatment. The incidence of potentially clinically significant weight gain (>/= 7% from baseline) was higher with olanzapine than with divalproex (3-week: p = .064, 6.4% vs. 2.7%; 12-week: p = .002, 18.8% vs. 8.5%; respectively). CONCLUSION: Olanzapine was significantly more efficacious than placebo but not divalproex at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Olanzapine-treated patients had significantly greater increases in weight and in glucose, cholesterol, triglyceride, uric acid, and prolactin levels than divalproex-treated patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00094549.

Olanzapine plus carbamazepine v. carbamazepine alone in treating manic episodes.

BACKGROUND: Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania. AIMS: To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes. METHOD: Randomised, double-blind, 6-week trial of olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day; n=58) v. placebo plus carbamazepine (n=60) followed by open-label, 20-week olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day, n=86), with change in manic symptoms as main outcome measure. Safety and pharmacokinetics were also evaluated. RESULTS: There were no significant differences (baseline to endpoint) in efficacy measures between treatment groups, but at 6 weeks triglyceride levels were significantly higher (P=0.008) and potentially clinically significant weight gain (>or=7%) occurred more frequently (24.6% v. 3.4%, P=0.002) in the combined olanzapine and carbamazepine group. Carbamazepine reduced olanzapine concentrations but olanzapine had no effect on carbamazepine concentrations. CONCLUSIONS: The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern.

Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats.

RATIONALE: Most adult smokers start smoking during their adolescence. This adolescent initiation may be due to multiple factors, but little evidence is available regarding whether their brains are differentially sensitive to the addictive effects of nicotine during adolescence. OBJECTIVE: To test the hypothesis that adolescents are more sensitive than adults to nicotine's rewarding actions. METHODS: An unbiased, counterbalanced, place-conditioning procedure was used to examine drug-induced reward and locomotor activity. Early adolescent (postnatal day 28), late adolescent (P38) and adult (P90) rats received either saline or nicotine (0.125, 0.25 or 0.5 mg/kg, s.c.) and were tested for place conditioning. RESULTS: During early adolescence, a single nicotine injection (0.5 mg/kg) induced significant conditioned place preference (CPP). In contrast, during late adolescence or adulthood, nicotine did not induce CPP after either one or four conditioning trials. Initial locomotor responses to acute nicotine administration during the first conditioning trial also differed with age, with no effect at P28, but substantial inhibitory responses at all doses studied (0.125-0.5 mg/kg) at later ages. Although not differing in their initial locomotor response to nicotine, there was a significantly greater tolerance/sensitization during the second and subsequent drug exposures in late adolescents than in adults. CONCLUSIONS: These findings provide evidence that adolescent brain is differentially sensitive to both the acute and repeated effects of nicotine relative to adult brain. Furthermore, there are significant differences in nicotine sensitivity between early and late phases of adolescence.

Sustained spinal cord compression: part I: time-dependent effect on long-term pathophysiology.

BACKGROUND: The objective of this study is to determine whether there is a relationship between the duration of sustained spinal cord compression and the extent of spinal cord injury and the capacity for functional recovery after decompression. METHODS: Sixteen dogs underwent sustained spinal cord compression for thirty or 180 minutes. The cords were compressed with use of a loading device with a hydraulic piston. A pressure transducer was attached to the surface of the piston, which transmitted real-time spinal cord interface pressures to a data-acquisition system. Somatosensory evoked potentials were monitored during a sixty-minute recovery period as well as at twenty-eight days after the injury. Functional motor recovery was judged throughout a twenty-six-day period after the injury with use of a battery of motor tasks. The volume of the lesion and damage to the tissue were assessed with both magnetic resonance imaging and histological analysis. RESULTS: Sustained spinal cord compression was associated with a gradual decline in interface pressure. Despite this, there was continuous decline in the amplitude of the somatosensory evoked potentials, which did not return until the cord was decompressed. Within one hour after the decompression, the dogs in the thirty-minute-compression group had recovery of somatosensory evoked potentials, but no animal had such recovery in the 180-minute group. Recovery of the somatosensory evoked potentials in the thirty-minute group was sustained over the twenty-eight days after the injury. Motor tests demonstrated rapid recovery of hindlimb motor function in the thirty-minute group, but there was considerable impairment in the 180-minute group. Within two weeks after the injury, balance, cadence, stair-climbing, and the ability to walk up an inclined plane were significantly better in the thirty-minute group than in the 180-minute group. The longer duration of compression produced lesions of significantly greater volume, which corresponded to the long-term functional outcome. CONCLUSIONS: The relatively rapid viscoelastic relaxation of the spinal cord during the early phase of sustained cord compression suggests that there are mechanisms of secondary injury that are linked to tissue displacement. Longer periods of displacement allow propagation of the secondary injury process, resulting in a lack of recovery of somatosensory evoked potentials, limited functional recovery, and more extensive tissue damage.

Cerebral spinal fluid pressure: effects of body position and lumbar subarachnoid drainage in a canine model.

STUDY DESIGN: This study used in vivo an model of subarachnoid cerebrospinal fluid pressure measurement. OBJECTIVES: To examine the relation between subarachnoid cerebrospinal fluid pressure in the cervical and lumbar spine and varying body positions, and to test the hypothesis that increasing body inclination and lumbar subarachnoid drainage decreases cervical cerebrospinal fluid pressures. SUMMARY OF BACKGROUND DATA: Cerebrospinal fluid leaks are a recognized complication of anterior or posterior cervical surgery. Conflicting opinion exists regarding the benefits of postoperative patient positioning and lumbar subarachnoid drainage. METHODS: Subarachnoid cerebrospinal fluid pressure of 7 beagles was monitored via two angiocatheters attached to pressure transducers inserted into the subarachnoid space through laminectomies at C3 and L4. Pressure measurements were taken when body position was inclined to 30 degrees, 60 degrees, and 90 degrees. A lumbar durotomy was performed to simulate the effects of lumbar subarachnoid drainage. The body was repositioned to 90 degrees, and pressure was measured. RESULTS: As inclination increased from 0 degrees to 90 degrees, the mean cervical cerebrospinal fluid pressure significantly decreased. The mean lumbar subarachnoid pressure significantly increased as inclination increased from 0 degrees to 90 degrees. Lumbar durotomy plus repositioning to 90 degrees resulted in a significant reduction in cervical cerebrospinal fluid subarachnoid pressure, with pressures dropping by 46%. Lumbar cerebrospinal fluid subarachnoid pressure dropped to zero after lumbar durotomy plus repositioning to 90 degrees. CONCLUSIONS: Cerebrospinal fluid pressures in the subarachnoid space of both the cervical and lumbar spines are affected by changes in body position. Both patient positioning and lumbar drainage may be important in reducing cervical cerebrospinal fluid pressure, and may reduce the occurrence of cerebrospinal fluid leaks after primary dural repair in the neck.