Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK)

The present study, which was designed as a prospective, double-masked, randomized, controlled, single-site study, was conducted to compare the effects of 3 approved ophthalmic nonsteroidal anti-inflammatory drugs-nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories, Inc., Fort Worth, Tex), ketorolac tromethamine ophthalmic solution 0.4% (Acular LS; Allergan, Irvine, Calif), and bromfenac 0.09% (Xibromtrade mark; ISTA Pharmaceuticals, Irvine, Calif)-on corneal reepithelialization and postoperative pain control in patients undergoing photorefractive keratectomy. In addition to nonsteroidal anti-inflammatory drugs, each patient received an antibiotic-moxifloxacin hydrochloride ophthalmic solution 0.5% (nepafenac group) or gatifloxacin ophthalmic solution 0.3% (ketorolac and bromfenac groups). All treatments were administered 3 times daily beginning 1 d preoperatively and continuing for 1 wk postoperatively; prednisolone acetate 1.0% was administered concurrently 4 times daily. Bandage contact lenses were replaced at each postoperative visit for corneal staining and epithelial defect grading. Self-evaluation of pain relief was recorded on postoperative days 1 and 3 with the use of a visual analog scale. A total of 29 patients (58 eyes) were enrolled and underwent bilateral custom photorefractive keratectomy. Mean time to reepithelialization was 5.50+/-1.59 d for the nepafenac 0.1% group, 5.62+/-1.23 d for the ketorolac 0.4% group, and 7.25+/-2.53 d for the bromfenac 0.09% group. A significant difference was detected between nepafenac 0.1% and bromfenac 0.09% and between ketorolac 0.4% and bromfenac 0.09% (P<.05). Significant reductions in pain scores were observed with nepafenac 0.1% on day 1 (-1.13) and day 3 (-1.32), ketorolac 0.4% on day 3 (-0.88), and bromfenac 0.09% on day 3 (-0.83). No adverse events were reported. Eyes treated with nepafenac 0.1% or ketorolac 0.4% achieved complete reepithelialization significantly faster than those treated with bromfenac 0.09%. Daily contact lens removal and application of fluorescein may have delayed reepithelialization in the overall population; however, the effect would have been the same in all 3 groups. Pain relief with nepafenac 0.1% was achieved sooner than with ketorolac 0.4% or bromfenac 0.09%.     

Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: a phase II, randomized, double-masked trial

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of nepafenac ophthalmic suspension 0.03% and 0.1% for the treatment of postoperative pain and photophobia in patients undergoing excimer photoreactive keratectomy (PRK). METHODS: In this 7-day, randomized, double-masked, parallel-group trial at 2 sites, patients undergoing PRK surgery were randomly assigned to receive nepafenac ophthalmic suspension 0.03% or 0.1%, or diclofenac sodium ophthalmic solution 0.1%. Patients were treated on day 0 (surgery) and day 1 (the day after surgery). The dose regimen for all 3 treatments was the same. On day 0, patients received 2 drops in the operative eye -1 hour before surgery; 2 drops within 1 hour after surgery; 1 drop -4 hours after the first postoperative dose; and 1 drop -8 hours after the first postoperative dose. On day 1, patients instilled 1 drop of study drug QID. Thereafter, the study medication was discontinued. In the perioperative period, study personnel instilled the drops. The patients instilled the drops when they went home. Patients recorded pain and photophobia from day 0 through day 2, rating pain from 0 to 9 on a visual analog scale (0=none, 9=extreme) and photophobia from 0 to 3 on an ordinal, categoric scale (0=none, 3=severe). Patients were permitted to take acetaminophen 500 mg as needed for pain. They returned for postoperative follow-up visits on days 1, 3, and 7. Adverse events were documented when reported by the patients themselves, and when study personnel asked about specific events. RESULTS: Sixty patients (20 per group) were enrolled. On the day of surgery, there were no significant differences between groups, except at 3 hours after surgery, when the nepafenac 0.03% group had a significantly higher mean pain score than the nepafenac 0.1% group (4.0 vs 3.0; P<0.038). On day 2, the nepafenac 0.1% group had less pain at bedtime than the diclofenac group (mean score, 1.9 vs 3.1; P<0.024) and less photophobia in the morning (mean score, 1.2 vs 1.8; P<0.023). For the nepafenac 0.03% group, the mean pain and mean photophobia scores were 2.5 and 1.6, respectively. There were no significant differences between the 3 treatment groups in the proportion of patients who took acetaminophen for pain at any time point (P=NS). There was no statistically significant difference in corneal re-epithelialization rates among the 3 groups. Adverse events were infrequent, and no serious adverse events occurred. Two ocular adverse events related to therapy occurred: a corneal infiltrate in 1 patient in the nepafenac 0.03% group; and ocular discomfort in 1 patient in the nepafenac 0.1% group. Both patients continued the study. CONCLUSIONS: Both nepafenac 0.03% and 0.1% were effective for treatment of pain and photophobia in these patients undergoing PRK surgery. There was no difference in the proportion of patients who took rescue acetaminophen for pain. All treatments were well tolerated in these patients.     

Prostaglandin E<Subscript>2</Subscript> Inhibition of Ketorolac 0.45%, Bromfenac 0.09%, and Nepafenac 0.1% in Patients Undergoing Phacoemulsification

Introduction  

We compared the prostaglandin E₂ (PGE₂) inhibition of three topical nonsteroidal antiinflammatory drugs (NSAIDs): ketorolac 0.45%, bromfenac 0.09%, and nepafenac 0.1% at peak dosing levels in patients previously scheduled to undergo phacoemulsification.     

Postoperative Subcutaneous Instillation of Low-Dose Ketorolac But Not Hydromorphone Reduces Wound Exudate Concentrations of Interleukin-6 and Interleukin-10 and Improves Analgesia Following Cesarean Delivery

The objectives of this study were to test the effects of low-dose ketorolac and hydromorphone added to continuous local anesthetic wound instillation on surgical-site inflammatory mediators, postoperative pain, and opioid consumption. Sixty healthy women undergoing cesarean delivery were enrolled in this randomized, double-blinded study. Patients were randomized to receive a subcutaneous wound instillation of bupivacaine .5% at 10 mg/hour (active control), bupivacaine .5% with ketorolac .6 mg/hour, or bupivacaine .5% with hydromorphone .04 mg/hour for 48 hours postcesarean. Wound exudate was sampled at 4, 24, and 48 hours postcesarean and assayed for interleukins IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-12, tumor necrosis factor (TNF-α), interferon (INF-γ), and granulocyte-macrophage colony stimulating factor (GM-CSF). The addition of ketorolac to bupivacaine significantly decreased IL-6 (P = .012) and IL-10 (P = .005) compared to plain bupivacaine. Ketorolac, but not hydromorphone, was associated with a decrease in pain (P = .018) and analgesic use (P = .020) following cesarean delivery. Our results are compatible with the view that significant analgesics effects are mediated through local modulation of inflammatory events. Low-dose ketorolac administered into surgical wounds exert significant anti-inflammatory and analgesic effects and may be a valuable analgesic alternative to systemic nonsteroidal anti-inflammatories (NSAIDs) but with potentially fewer side effects.PerspectiveThis article demonstrates that low-dose ketorolac administered into wounds modulates local inflammatory events, decreases postoperative pain, and reduces opioid consumption. These results suggest that administration of NSAIDs into surgical wounds may be an analgesic alternative to higher systemic dosing of NSAIDs.     

Use of a splint following open carpal tunnel release: A comparative study

This study was undertaken to compare the clinical effectiveness and costs of postoperative splintage and late rehabilitation with a bulky bandage dressing versus early rehabilitation after carpal tunnel release. In this comparative study, 46 patients were randomly divided into 2 groups. In each group, 3 patients were excluded because of improper follow-up, leaving a total of 40 patients. Group 1 used a splint (exercises given 3 wk postoperatively) and group 2 was given a bulky bandage (exercises provided immediately) after open release. Patients were assessed preoperatively and at the first and third postoperative months with the Questionnaire of Levine for Clinical Assessment of Carpal Tunnel Syndrome. The 2 groups were similar in terms of preoperative functional status scores and in controls at the first and third months (P=.549,P=.326,P=.190). When both groups were compared, no statistical significance was found regarding symptom severity scale scores preoperatively and at the first postoperative month (P=.632 vsP=.353). At the third month, scores were lower in favor of group 2 (P=.023). Additionally, 16 of 20 patients (80%) in group 1 reported a heavy feeling and discomfort caused by the splint. This problem was not reported by the patients in group 2. The cheapest splint on the market was 9 times more expensive than a bulky dressing. The investigators concluded that postoperative immobilization with a splint has no detectable benefits. Use of bulky dressings and abandonment of the use of postoperative splints may prevent unnecessary expenditures without sacrificing patient comfort or compromising the course of healing in carpal tunnel surgery.     

A comparison of ciprofloxacin/dexamethasone with neomycin/polymyxin/ hydrocortisone for otitis externa pain

Ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) and neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (NPH) were compared for relief of pain in patients with acute otitis externa. Patients received 7 d of treatment with CIP/DEX twice daily or NPH 3 times daily. Ear pain was assessed by patients/caregivers twice daily and by the study investigator on days 3, 8, and 18 (4-point scale). Higher percentages of CIP/DEX-treated patients had relief of severe pain over time (P=.0013) and relief of significant pain (moderate or severe pain) over time (P=.0456), compared with NPH-treated patients. The percentage of CIP/DEX-treated patients with severe pain decreased rapidly within the first 12 h; this contrasted with an increase in pain among NPH-treated patients. CIP/DEX-treated patients had significantly less inflammation (P=.0043) and edema (P=.0148) than NPH-treated patients. Overall, these results support greater pain relief attained over the first 3 d in patients with acute otitis externa treated with CIP/DEX compared with NPH and a rapid reduction in severe pain after initiation of treatment.     

A Double-Blind Randomized Controlled Trial of Continuous Intravenous Ketorolac vs Placebo for Adjuvant Pain Control After Renal Surgery

ObjectiveTo evaluate the efficacy and safety of a novel, continuous intravenous infusion of ketorolac, a powerful nonopioid analgesic, for postoperative pain control.Patients and MethodsA prospective, double-blind, randomized, placebo-controlled trial of a continuous infusion of ketorolac tromethamine in 1 L of normal saline vs placebo was performed in 135 patients aged 18 to 75 years after laparoscopic donor nephrectomy or percutaneous nephrolithotomy completed from October 7, 2008, through July 21, 2010. Primary study end points were the 24-hour differences in visual analog pain scores and total narcotic consumption, whereas secondary end points were differences in urine output, serum creatinine level, and hemoglobin level.ResultsThe study was stopped after randomization of 135 patients (68 in the ketorolac group and 67 in the placebo group) when interim analysis indicated that the difference in mean pain scores between the 2 groups (difference, 0.6) was smaller than the 1-point threshold set forth in the power calculations. No statistically significant change was noted in hemoglobin levels from preoperative to postoperative values (P=.13) or in postoperative serum creatinine levels (P=.13).ConclusionAlthough continuous infusion of ketorolac produced only a modest decrease in the use of narcotics, it appears to offer a safe therapeutic option for nonnarcotic pain control.Trial Registrationclinicaltrials.gov Identifiers: NCT00765128 and NCT00765232     

Aqueous prostaglandin E<Subscript>2</Subscript> of cataract patients at trough ketorolac and bromfenac levels after 2 days dosing

Introduction  Ketorolac 0.4% administered four times daily (q.i.d.) has long been used safely and effectively for the alleviation of ocular inflamation and pain and the prevention of intraoperative miosis in patients undergoing cataract surgery. Bromfenac ophthalmic solution 0.09% was recently developed as an ocular anti-inflammatory drug with a twice-daily (b.i.d.) dosing regimen. This study was designed to evaluate if b.i.d. dosing with bromfenac 0.09%, in comparison with q.i.d. dosing with ketorolac 0.4%, provides adequate trough nonsteroidal anti-inflammatory drug levels that were effective enough to reduce aqueous prostaglandin (PG) E₂ levels of patients after cataract surgery toward the end of its dosing cycle. Methods  In this single-center, investigator-masked trial, patients undergoing cataract surgery were randomized to receive either ketorolac 0.4% q.i.d. or bromfenac 0.09% b.i.d. for 2 days preoperatively. Aqueous humor was collected at the start of surgery 6 hours after the last dose of ketorolac 0.4% and 12 hours after the last dose of bromfenac 0.09%. Aqueous PGE₂ levels and drug concentrations were evaluated by a competitive enzyme immunoassay and reverse-phase HPLC-mass spectroscopy, respectively. Results  A total of 61 patients received ketorolac 0.4% (n=30) or bromfenac 0.09% (n=31). The mean (±SD) aqueous PGE₂ level was 285.6±141.9 pg/mL in patients treated with ketorolac 0.4% and 386.2±131.0 pg/mL in patients treated with bromfenac 0.09% (P=0.006). The mean (±SD) aqueous concentrations of ketorolac and bromfenac were 83.6±73.8 ng/mL and 9.2±6.6 ng/mL, respectively (P<0.001). Conclusions  Ketorolac 0.4% maintained significantly higher aqueous concentrations and lowered aqueous PGE₂ levels significantly more than bromfenac 0.09% at trough levels. Ketorolac 0.4% administered q.i.d. may provide a more sustained control of intraocular inflammation and pain than bromfenac 0.09% administered b.i.d.     

Single dose of ketotifen fumarate .025% vs 2 weeks of cromolyn sodium 4% for allergic conjunctivitis

This single-masked, contralateral-eye, active-controlled allergen-challenge study compared ketotifen fumarate .025% and cromolyn sodium 4% ophthalmic solutions in the prevention of ocular itching, tearing, and redness induced by allergen challenge. After a confirmatory conjunctival provocation test (CPT), 56 patients randomly received masked study medication (placebo in one eye, cromolyn in the other eye) four times daily for 2 weeks. At visit 3, patients received one drop of ketotifen in the eye previously treated with placebo and cromolyn in the other eye. Ocular comfort was assessed 30 seconds postinstillation, and a CPT was conducted 15 minutes and 4 hours postinstillation to evaluate ocular itching, tearing, and redness. Forty-seven patients were analyzed for efficacy. At the 15-minute and 4-hour challenges, ketotifen was superior to cromolyn in preventing itching (P<.001) at all assessments and redness (ciliary, conjunctival, and episcleral) (P≤.001 ) at most assessments. Tearing scores were higher in cromolyn-treated eyes than in ketotifen-treated eyes. Patients reported greater comfort in the ketotifentreated than in the cromolyn-treated eye (P= .066). The most common adverse event was burning/stinging with cromolyn. A single dose of ketotifen was superior to a 2-week four-times-daily regimen of cromolyn in alleviating symptoms of allergic conjunctivitis in the conjunctival allergen-challenge model.     

Short-term tolerability of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in glaucoma and/or ocular hypertension: A prospective,randomized, double-masked,active-controlled,three-period crossover pilot study

Objective: The aim of this study was to compare symptoms and anterior segment tolerability with short-term (3-day) administration of once-daily timolol hemihydrate 0.5%, timolol maleate in sorbate 0.5%, and generic timolol maleate gel-forming solution 0.5% in the treatment of glaucoma and/or ocular hypertension.Methods: In this prospective, randomized, double-masked, active-controlled, 3-period crossover pilot study, eligible patients had primary open-angle, pigmentdispersion, or exfoliation glaucoma, and/or ocular hypertension in ≥1 eye; had a best corrected visual acuity of 1.0 or better in each eye, as measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing chart; were receiving 1 glaucoma medication; and had an untreated intraocular pressure (IOP) of ≤28 mm Hg in both eyes after washout (if required) at visit 2 (day 0). Patients were assigned to receive, in randomized order, timolol hemihydrate 0.5%, timolol in sorbate 0.5%, or generic timolol gelforming solution 0.5%, 1 drop each morning (~8 am) in the qualified eye(s) (washout IOP ≤28 mm Hg) for 3 days. Each treatment period was separated by a 7-day washout period. At all baseline and end-of-treatment study visits, patients completed a solicited symptom survey (used for the assessment of stinging or burning [grade 0 = none to 4 = severe] and blurred or dimmed vision [grade 0 = none to 4 = severe], among other parameters) and underwent ETDRS, Goldmann applanation tonometry, slit-lamp biomicroscopy, anterior segment staining (corneal, conjunctival nasal, and conjunctival temporal staining), conjuncti-val hyperemia assessment, measurement of tear breakup time, and Schirmer's testing with anesthesia. At end-of-treatment assessments, patients were questioned about adverse events.Results: Thirty patients were enrolled (15 men, 15 women; mean [SD] age, 66.3 [8.9] years; white, 19 patients, black, 11; primary open-angle glaucoma, 17; ocular hypertension, 13). Mean (SD) stinging or burning grade was significantly greater with timolol in sorbate compared with timolol hemihydrate and timolol gel-forming solution (0.9 [0.9] vs 0.4 [0.6] and 0.2 [0.6], respectively; P < 0.001). The between-treatment differences on anterior segment staining, conjunctival hyperemia, tear breakup time, and Schirmer's testing with anesthesia were not significant, with the exception of the change from baseline in conjunctival nasal staining by count, which was significantly higher with timolol gel-forming solution compared with timolol hemihydrate and timolol in sorbate (3.1 [13.4] vs ?2.9 [10.1] and ?3.0 [8.0], respectively; P = 0.04). On the solicited symptom survey, timolol gel-forming solution was associated with a poorer mean score on blurred or dimmed vision compared with timolol hemihydrate and timolol in sorbate (0.3 [0.7] vs 0.1 [0.3] and 0.0 [0.2], respectively; P = 0.02). Mean best corrected ETDRS visual acuity immediately after instillation was significantly lower with timolol gel-forming solution compared with timolol hemihydrate and timolol in sorbate (49.6 [8.4] vs 53.0 [6.1] and 53.1 [6.7], respectively; P = 0.007). The mean 24-hour trough IOP did not differ significantly between the 3 treatments.Conclusions: In this pilot study that compared the symptoms and tolerability of once-daily timolol hemihydrate 0.5%, timolol in sorbate 0.5%, and timolol gel-forming solution 0.5% in these patients with glaucoma and/or ocular hypertension, short-term (3-day) administration of timolol in sorbate was associated with more stinging or burning compared with timolol hemihydrate and timolol gel-forming solution. Timolol gel-forming solution was associated with more postinstillation blurred or dimmed vision compared with timolol hemihydrate and timolol in sorbate.     

Preoperative Gabapentin for Acute Post‐thoracotomy Analgesia: A Randomized,Double‐Blinded,Active Placebo‐Controlled Study

Background: The role of preoperative gabapentin in postoperative pain management is not clear, particularly in patients receiving regional blockade. Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain. We examined the effect of preoperative gabapentin in thoracotomy patients. Methods: Adults undergoing elective thoracotomy were enrolled in this prospective, randomized, double‐blinded, placebo‐controlled study, and randomly assigned to receive 600 mg gabapentin or active placebo (12.5 mg diphenhydramine) orally within 2 hours preoperatively. Standardized management included thoracic epidural infusion, intravenous patient‐controlled opioid analgesia, acetaminophen and ketorolac. Pain scores, opioid use and side effects were recorded for 48 hours. Pain was also assessed at 3 months. Results: One hundred twenty patients (63 placebo and 57 gabapentin) were studied. Pain scores did not significantly differ at any time point (P = 0.53). Parenteral and oral opioid consumption was not significantly different between groups on postoperative day 1 or 2 (P > 0.05 in both cases). The frequency of side effects such as nausea and vomiting or respiratory depression was not significantly different between groups, but gabapentin was associated with decreased frequency of pruritus requiring nalbuphine (14% gabapentin vs. 43% control group, P < 0.001). The frequency of patients experiencing pain at 3 months post‐thoracotomy was also comparable between groups (70% gabapentin vs. 66% placebo group, P = 0.72). Conclusions: A single preoperative oral dose of gabapentin (600 mg) did not reduce pain scores or opioid consumption following elective thoracotomy, and did not confer any analgesic benefit in the setting of effective multimodal analgesia that included thoracic epidural infusion.     

Effect of 2-speed geared manual wheelchair propulsion on shoulder pain and function

Finley MA, Rodgers MM. Effect of 2-speed geared manual wheelchair propulsion on shoulder pain and function.

Objective

To investigate the impact of a manual 2-gear drive wheelchair wheel (MAGICWheels) on shoulder pain and function in manual wheelchair users.

Design

A single-group, repeated-measures pre- and postdesign with baseline and retention.

Setting

General community.

Participants

Full-time manual wheelchair users (N=17) currently experiencing shoulder pain (mean age, 46±14y; wheelchair use, 15±10y).

Intervention

Five-month trial using a 2-gear wheelchair wheel.

Main Outcomes Measures

The Wheelchair Users Shoulder Pain Index (WUSPI), Wheelchair Users Functional Assessment (WUFA), and timed hill climb test with rating of perceived exertion (RPE).

Results

There was significant reduction in shoulder pain after the intervention at week 2 (P=.004) through week 16 (P=.015). The difference was not found at week 20; however, 1 participant reported an increase in pain from unrelated factors during week 20. Change from baseline was calculated without this subject’s data; there was a significant reduction in shoulder pain (P=.003). There was no difference in WUFA after using the 2-gear wheel (P=.06). Hill climb time was longer when using the 2-gear wheel (P=.01), but no difference in the RPE (P=.13) resulted. Shoulder pain during the 4-week retention phase showed a trend toward increasing, as indicated by increased WUSPI scores. There was not a significant percentage increase, however, in comparison with the final week of using the MAGICWheels (P<.05).

Conclusions

There were pain reductions 2 weeks after using the MAGICWheels, indicating a rapid response to the intervention. These findings indicate the potential for shoulder pain reduction with the use of a manual drive wheel during mobility, even in highly functional manual wheelchair users.     

A combined analysis of two studies assessing the ocular comfort of antiallergy ophthalmic agents

BACKGROUND: Many topical agents with similar efficacies are available for the treatment of ocular allergies. In addition to efficacy, comfort is an important criterion because it affects overall patient satisfaction, compliance, and in turn efficacy. OBJECTIVE: The goal of this study was to compare the comfort profiles of permirolast, ketorolac, cromolyn, and nedocromil ophthalmic solutions using combined results from 2 separate clinical trials. METHODS: Two clinical trials were conducted. Adults with asymptomatic eyes were included in the first study. In this single-center, 7-day, prospective, double-blind, single-dose, crossover, parallel-group study, subjects were randomized to be bilaterally dosed with pemirolast, cromolyn, or ketorolac at each of 3 visits. Study 2 was a single-center, 1-day, prospective, randomized, double-blind, single-dose, contralateral, active-control study in which subjects received pemirolast in 1 eye and nedocromil in the contralateral eye. In both studies, subjects completed a pre- and postinstillation ocular comfort questionnaire: the primary variable was overall ocular discomfort, measured on a 4-point scale original to these studies (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Half-increments were permitted. Secondary variables included burning/stinging, foreign-body sensation, tearing, and photophobia. RESULTS: Forty-five subjects (29 women, 16 men; mean [SD] age, 35.9 [12.6] years) were enrolled in study 1; 48 subjects (30 women, 18 men; mean [SD] age, 33.6 [10.2] years) were enrolled in study 2. In study 1, overall discomfort was significantly lower with pemirolast than with cromolyn (P = 0.001) or ketorolac (P < 0.001). In terms of overall discomfort, the number of subjects with a clinically significant increase (>/=1 unit) in score was significantly lower with pemirolast compared with ketorolac (P = 0.021). Burning/stinging and tearing were also significantly lower with pemirolast than with cromolyn (P < 0.001 and P = 0.014, respectively). Mean changes in score compared with preinstillation were consistently lower with pemirolast than with cromolyn for both burning/stinging (P < 0.001) and tearing (P = 0.014). In study 2, overall discomfort was significantly lower with pemirolast than with nedocromil (P < 0.001). The number of subjects with a clinically significant increase in overall discomfort score was significantly lower with pemirolast than with nedocromil (P = 0.007). No changes in ocular tolerability parameters were reported in either study. CONCLUSION: In these single-dose studies, pemirolast was found to be significantly more comfortable than cromolyn, ketorolac, or nedocromil.     

Expression of soluble CD27 and interleukins-8 and -10 in B-cell chronic lymphocytic leukemia: Correlation with disease stage and prognosis

Investigators in this study explored levels of soluble CD27 (sCD27), interleukin (IL)-8, and IL-10 in B-cell chronic lymphocytic leukemia (B-CLL), and the correlation of these levels with disease stage and prognosis. Plasma IL-8, IL-10, and sCD27 levels were assessed with enzyme-linked immunosorbent assay tests in 22 healthy donors and 70 patients with B-CLL (49 men and 21 women). Mean patient age was 61.57 y (range, 44–75 y). Mean healthy donor age was 62.09 y (range, 40–72 y). In the study group, mean values were as follows: plasma IL-8, 284.758 pg/mL (0–1000 pg/mL); plasma IL-10, 26.152 pg/mL (0–100 pg/mL); sCD27, 731.357 U/mL (139.9–1000 U/mL); white blood cell count, 59.9 × 10⁹/L (0.8–250.0 × 10⁹/L); hemoglobin count, 11.2 g/dL (5.0–16.2 g/dL); platelet count, 162.5 × 109/L (29.8–317 × 10⁹/L); B₂ microglobulin (B₂M) 3350.2 mg/L (274.7–7499.9 mg/L); CD38, 19.5%; and lactate dehydrogenase (count, 497.5 U/L (263.0–1507 U/L). Patients represented all Rai stages, with 22.9% at stage 0, 11.4% at stage I, 11.4% at stage II, 41.4% at stage III, and 12.9% at stage IV. Plasma levels of IL-8, IL-10, and sCD27 were correlated between study and control groups; significantly higher IL-8 (P=.001) and sCD27 (P=.000) levels were found, but the IL-10 level was not significant (P=.139). Plasma IL-10 (P=.01) and sCD27 (P=.008) were positively correlated with Rai stage, but IL-8 was not (P=.146). Levels of sCD27 were significantly correlated with values for B₂M (P=.000), hemoglobin (P=.028), lactate dehydrogenase (P=.001), CD19 (P=.03), and IL-10 (P=.000). IL-8 was significantly correlated with white blood cell (P=.000) count, and CD38 (P=.001) and CD5 (P=.006) levels. IL-10 was significantly correlated with B₂M (P=.017), CD19 (P=.000), platelet (P=.002), and CD27 (P=.000). In survival distributions for CD27, IL-8 and IL-10 were found to have more significant relationships for all parameters (P=.0000). In conclusion, the authors suggest that sCD27, IL-8, and IL-10 are more significant prognostic factors for B-CLL when compared with others, and these values should correlate with new prognostic factors (eg, zeta-associated protein-70, mutated/unmutated immunoglobulin variable heavy chain).     

Safety and efficacy of ketorolac in children after cardiac surgery

Objective  To evaluate the nephrotoxic and opioid-sparing effects of ketorolac in children after cardiac surgery. Design  A retrospective cohort study. Setting  A Cardiac Critical Care Unit in a university-affiliated children’s hospital. Subjects  Children less than 18 years of age who underwent low-risk cardiac surgery from July 2002 to December 2005. Results  Among 248 children studied, 108 received ketorolac and 140 did not. The ketorolac group was older, included a larger proportion of atrial septum defect repairs and a smaller proportion of ventricular septum defect repairs compared to the control group. The median change in serum creatinine did not differ between the ketorolac group and the control group (% change [IQR]); 12% [1–25] increase versus 12% [−3 to 31] increase, P = 0.86. On postoperative day 0 or 1, the ketorolac group received less opioids than control group. There was no difference in duration of mechanical ventilation or in length of stay between groups. Conclusion  Ketorolac started in the first 12 h after a low-risk cardiac surgery in children is not associated with a measurable difference in renal function. The data suggest that ketorolac may be effective in reducing the exposure to opioids. Further studies are required to define subsets of children after cardiac surgery who could safely benefit from ketorolac therapy to reduce pain.     

Butylscopolammonium bromide does not provide additional analgesia when combined with morphine and ketorolac for acute renal colic

Objective: To evaluate the effect of adding butylscopolammonium bromide (BB) to morphine and ketorolac in the treatment of acute renal colic in the ED. Methods: A prospective, double‐blind, randomized controlled trial of i.v. triple therapy (morphine, ketorolac and BB) versus double therapy (morphine and ketorolac) in adult ED patients with a clinical diagnosis of acute renal colic and a pain rating greater than five on a 10 cm visual analogue scale (VAS). VAS was recorded at time 0, 20 and 40 min. Patients received rescue morphine at 20 or 40 min according to the protocol if needed. We compared pain reduction and the need for rescue analgesia at 4 min between two groups. Results: Eighty‐nine patients were randomized over a 13 month period. A total of 46 (51.7%) patients received BB in addition to morphine and ketorolac. The mean difference in change in pain score in the triple therapy group and double therapy group was 7.1 cm (95% CI 6.4–7.8) and 5.9 cm (95% CI 5.1–6.7), respectively (P= 0.024). Rescue morphine was required by 7/46 (15.2% [95% CI 4.4–20.6]) patients in the triple therapy group and 14/43 (32.6% [95% CI 18.0–47.1]) in the double therapy group (OR 0.37 [95% CI 0.133–1.038]). Conclusions: Although the addition of BB to morphine and ketorolac appeared to show a statistically significant reduction in pain compared with morphine and ketorolac alone, a reduction of 1.2 cm on VAS is unlikely to be clinically significant.     

A randomized, double-masked, clinical study of the efficacy of four nonsteroidal anti-inflammatory drugs in pain control after excimer laser photorefractive keratectomy

OBJECTIVE: This study assessed the efficacy of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) after excimer laser photorefractive keratectomy (PRK). BACKGROUND: Inadequate control of pain after PRK surgery can be a severe source of distress to patients and can interfere with their willingness to undergo a second PRK procedure. METHODS: This randomized, double-masked, placebo-controlled clinical study was conducted in 125 patients. Four NSAIDs (diclofenac, flurbiprofen, ketorolac, and indomethacin) were tested against a placebo group (artificial tears). Pain levels after PRK were quantified using Present Pain Intensity (PPI) and Pain Rating Indices based on rank values (PRI[R]) scores, both of which were calculated using patient responses to a modified McGill Pain Questionnaire. The PRI(R) consisted of 4 subscales-sensory (S), affective (A), evaluative (E), and miscellaneous (M)-as well as a total score (T). RESULTS: Three hours after PRK, no differences in PPI scores were found between the ketorolac, diclofenac, and indomethacin groups, whereas placebo was significantly less effective than the NSAIDs. Patients who received flurbiprofen reported PPI scores that were significantly lower (P < 0.001) than those of patients who received diclofenac and indomethacin, but PPI scores in the flurbiprofen and the ketorolac groups did not differ significantly. Twenty-four hours after surgery, patients treated with flurbiprofen, ketorolac, and diclofenac reported the lowest PPI scores compared with those treated with indomethacin and placebo (P < 0.001). Moreover, flurbiprofen-treated patients also had the lowest PRI(R)T scores (P < 0.001). When the pain rating index was examined by subclass, a significantly lower PRI(R)S score was detected in the flurbiprofen group at 24 hours (P < 0.001). The PRI(R)A score was significantly higher in the placebo and indomethacin groups compared with the other groups (P < 0.001). At the 48- and 72-hour time points, flurbiprofen-treated patients again reported significantly lower PPI and PRI(R)T scores (P < 0.001 for both) in pair-wise comparisons with the other treatment groups. The number of patients who self-administered additional oral analgesics did not differ significantly between the groups. However, the mean number of analgesic tablets used was significantly higher in the placebo group than in any NSAID group (P < 0.001). The ketorolac group had the largest number of patients complaining of itching (P < 0.043). No other subjective symptoms were significantly different across groups. Finally, all NSAIDs, except flurbiprofen, prolonged the mean reepithelialization period slightly (P < 0.001). CONCLUSIONS: Flurbiprofen appeared to be the most effective NSAID for the treatment of pain, even at 24 hours after surgery when pain was at a maximum.     

Prognostic factors and COX-2 expression in advanced stage esophageal squamous cell carcinoma

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including squamous cell carcinomas of the esophagus, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to analyze expression of COX-2 in ESCC and to correlate this expression with clinicopathologic parameters and survival. From 1999 to 2003, endoscopic tissue samples from 110 patients with ESCC were collected for analysis. COX-2 expression was examined through immunohistochemical staining. Clinicopathologic data were analyzed to verify significance. COX-2 expression was detected in 50 of 110 ESCC specimens (45%). COX-2 expression was negative to weak in 73% (COX-2 low) and moderate to strong in 27% (COX-2 high) of tumors. Statistical differences between COX-2 high and COX-2 low were found according to status of the stage (stage IVM_1a/IVM_1b) (P=.001): cancer antigen (CA) 19-9 (normal/high) (P=.011), CA 12-5 (normal/high) (P=.011), and CA 15-3 (normal/high) (P=.035). Survival was significantly reduced among patients with high COX-2 expression (median overall survival, 3 mo) when compared with the COX-2 low group (median overall survival, 6 mo) (P=.0001). In the univariate analysis, age, body mass index, stage, COX-2, lactate dehydrogenase, CA 12-5, and CA 15-3 were significant factors for survival. With the use of COX regression analysis, only stage (P=.000), COX-2 (P=.000), lactate dehydrogenase (P=.023), and CA 15-3 (P=.002) were independent prognostic factors. Results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with visceral metastases (IVM_1b). COX-2 overexpression is an unfavorable prognostic factor in ESCC.     

纳布啡联合酮咯酸氨丁三醇预处理对电视胸腔镜外科手术后急性痛觉过敏的影响

目的 观察纳布啡联合酮咯酸氨丁三醇预处理对电视胸腔镜外科手术（VATS）后急性痛觉过敏的影响。方法 选取2020年9月-2021年9月该院择期全身麻醉下行VATS肺叶切除术的Ⅰ期和Ⅱ期非小细胞肺癌患者72例,随机分为对照组（C组）、纳布啡组（N组）和纳布啡联合酮咯酸氨丁三醇组（L组）,每组24例。麻醉诱导前,L组静脉注射纳布啡+酮咯酸氨丁三醇,N组静脉注射纳布啡,C组注射等量生理盐水。于术前、术后6 h、术后24 h和术后48 h时使用电子测痛仪（Von Frey）测定前臂内侧及切口周围机械痛阈值,于术后30 min、术后6 h、术后24 h和术后48 h采用数字分级评分法（NRS）评估疼痛情况,比较3组患者术后48 h内舒芬太尼累积消耗量及不良反应发生情况。结果 3组患者术后6、24和48 h前臂内侧及切口周围机械痛阈值比较,差异有统计学意义（P <0.05）。3组患者术后30 min、6 h和24 h的NRS及术后48 h内舒芬太尼累积消耗量比较,差异有统计学意义（P <0.05）。N组和L组术后6、24和48 h的前臂内侧机械痛阈值及切口周围机械痛阈值均高于C组,术后...     

Treatment of Temporomandibular Dysfunction With Hypertonic Dextrose Injection (Prolotherapy): A Randomized Controlled Trial With Long-term Partial Crossover

ObjectiveTo assess the efficacy and longer-term effectiveness of dextrose prolotherapy injections in participants with temporomandibular dysfunction.Patients and MethodsA randomized controlled trial with masked allocation was conducted from January 14, 2013, through December 19, 2015. Forty-two participants (with 54 joints) meeting temporomandibular dysfunction criteria were randomized (1:1) to 3 monthly intra-articular injections (20% dextrose/0.2% lidocaine or 0.2% lidocaine) followed by as-needed dextrose/0.2% lidocaine injections through 1 year. Primary and secondary outcome measures included a 0 to 10 Numerical Rating Scale score for facial pain and jaw dysfunction; maximal interincisal opening (MIO) measured in millimeters, percentage of joints with 50% or more change (improvement) in pain and function, and satisfaction.ResultsRandomization produced a control group with more female participants (P=.03), longer pain duration (P=.01), and less MIO (P=.01). Upon 3-month analysis, including pertinent covariates, dextrose group participants reported decreased jaw pain (4.3±2.9 points vs 1.8±2.7 points; P=.02), jaw dysfunction (3.5±2.8 points vs 1.0±2.1 points; P=.008), and improved MIO (1.5±4.1 mm vs ?1.8±5.1 mm; P=.006). Control group participants received dextrose injections beginning at 3 months. No between-group differences were noted at 12 months; pooled data suggested that jaw pain, jaw function, and MIO improved by 5.2±2.7 points (68%), 4.1±2.8 points (64%), and 2.1±5.5 mm, respectively. Pain and dysfunction improved by at least 50% in 38 of 54 (70%) and 39 of 54 (72%) jaws, respectively.ConclusionIntra-articular dextrose injection (prolotherapy) resulted in substantial improvement in jaw pain, function, and MIO compared with masked control injection at 3 months; clinical improvements endured to 12 months. Satisfaction was high.Trial Registrationclinicaltrials.gov Identifier: NCT01706172