Topical Nonsteroidal Anti-inflammatory Drugs Research Articles

E6. Breast units: The need for a structured network

To estimate the potential lifetime health gains, healthcare costs, and cost-effectiveness of recommended adjunctive treatments for knee osteoarthritis delivered in addition to established core treatments, relative to core treatment only, from the perspective of the New Zealand (NZ) healthcare sector.Recommended adjunctive knee osteoarthritis treatments were identified in clinical practice guidelines. Evidence of effectiveness was sourced from existing systematic reviews and meta-analyses. Treatment costs were calculated by applying local reference prices to estimated resource use. We used a validated computer simulation model of the impacts of knee osteoarthritis to estimate the cost-effectiveness of each adjunctive treatment at willingness-to-pay thresholds of one (primary), two, and three times per-capita GDP ($NZ52 300).Data were collected on nine recommended adjunctive treatments: aquatic-based exercise, heat therapy, massage therapy, walking cane, cognitive behavioural therapy (CBT), topical non-steroidal anti-inflammatory drugs (NSAIDs), oral NSAIDs, intra-articular corticosteroids, and duloxetine. Relative to core treatments only, walking cane and heat therapy were cost-saving and provided greater QALYs; aquatic exercise and intra-articular corticosteroids were also cost-effective at all WTP thresholds. Topical NSAIDs and CBT were cost-effective only at higher WTP thresholds, while duloxetine, massage therapy, and oral NSAIDs were not cost-effective at any relevant threshold. Results were generally robust to varying modelling assumptions, although topical and oral NSAIDs and CBT became cost-effective in some scenarios.Delivering high-value, low-cost adjunctive interventions for knee osteoarthritis, alongside recommended core treatment, could deliver substantial health gains at low cost to the health system.

Two Cases of Corneal Perforation after Oral Administration of Nonsteroidal Anti-Inflammatory Drugs: Oral Nsaid-Induced Corneal Damage

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

Athletes, NSAID, Coxibs, and the Gastrointestinal Tract

The role of nonsteroidal antiinflammatory drugs (NSAID) in pain and inflammation has been evaluated in many forms over the last decade. Emerging evidence shows that this class of medications has different effects depending on injury type: bone, ligament, tendon, and muscle. There are no clear guidelines about specific NSAID choice, duration of use, or route of administration. Benefit of therapy must be weighed against the side effects of NSAID, specifically with respect to the gastrointestinal and renal systems. It is clear that the side effect profile changes within the subclasses of NSAID, nonspecific cyclo-oxygenase-1 and 2 (COX-1 and COX-2) inhibitors, and more selective COX-2 inhibitors. Safe and effective alternatives may include topical NSAID and acetaminophen.

OARSI recommendations for the management of hip and knee osteoarthritis: Part III: changes in evidence following systematic cumulative update of research published through January 2009

To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009. A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence. Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo. Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.

NSAIDS IN COMBINATION THERAPY FOR THE TREATMENT OF CHRONIC PSEUDOPHAKIC CYSTOID MACULAR EDEMA

The purpose of this study was to evaluate the addition of topical nonsteroidal antiinflammatory drugs (NSAIDs) to intravitreal corticosteroid and antivascular endothelial growth factor injections for the treatment of chronic cystoid macular edema. Thirty-nine patients with chronic pseudophakic cystoid macular edema completed a single-center, randomized, investigator-masked study. All patients were treated with an intravitreal triamcinolone and bevacizumab injection at study entry; the bevacizumab injection was repeated at 1 month. To evaluate the effect of adding an NSAID, patients were randomized to treatment with 1 of 4 topical NSAIDs (diclofenac 0.1%, ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09%) or placebo for 16 weeks. At Weeks 12 and 16, both the nepafenac and bromfenac groups showed a significant reduction in retinal thickness compared with that in placebo (nepafenac, P = 0.0048, bromfenac, P = 0.0113). A difference, however, between these 2 NSAID groups was observed in that only the nepafenac group was able to maintain the demonstrated retinal thickness decrease at Weeks 12 and 16. The nepafenac group also experienced a significant improvement in visual acuity at Weeks 12 (P = 0.0084) and 16 (P = 0.0233). The addition of NSAIDs did not produce an increase in mean intraocular pressure over the course of therapy. Although NSAID therapy seems to potentiate the improvements produced by corticosteroids and antivascular endothelial growth factor therapy for chronic pseudophakic cystoid macular edema, only nepafenac- and bromfenac-treated eyes showed reduced retinal thickness at 12 weeks and 16 weeks. Furthermore, nepafenac produced a sustained improvement in visual acuity.

Redefining the Treatment Paradigm for Post-operative Inflammation Control – The Role of Topical Non-steroidal Anti-inflammatory Drugs

Topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of post-operative ocular inflammation and pain following cataract surgery and for some other clinical applications of ophthalmology, including cystoid macular oedema. Products vary by their pharmacological properties, clinical efficacy and tolerability, which affect their place in therapy for new agents in Europe. The pharmacological properties of topical ophthalmic NSAIDs and their place in current treatment of post-operative ocular inflammation are discussed in this article, focussing on bromfenac, which has been submitted for approval by the European Medicines Agency (EMEA).

A clinical study to assess the efficacy of Triyushnadi Anjana in Kaphaja Abhishyanda with special reference to vernal keratoconjunctivitis

Vernal keratoconjunctivitis / spring catarrh is a variety of exogenous allergic conjunctivitis, which is a very troublesome ocular disease of childhood and in the adolescent age group. The child suffers from intense itching, grittiness, discharge, redness, lacrimation, photophobia, and so on, thereby, decreasing his learning hours. The troublesome features are aggravated in the spring season / hot climate that lasts for years together and rarely persists after adolescence. Mast cell stabilizers, topical Nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids are the available treatment options that too with symptomatic relief and potential side effects, which limits the long-term use of these medicines. The clinical picture of vernal keratoconjunctivitis / spring catarrh is very similar to Kaphaja Abhishyanda, and Triyushnadi Anjana Bhaishajya Ratnavali (B.R.), and its treatment was clinically tried on the patients attending the Netra Roga OPD of the R.G. Government P.G. Ayurveda College Hospital at Paprola (H.P.). A proper protocol and performa was adopted with strict inclusion and exclusion criteria. In the first phase, a pilot study was conducted on 38 clinically diagnosed patients with vernal keratoconjunctivitis, and it gave 100% relief in photophobia, foreign body (FB) sensation, and lacrimation, with marked relief in other features. Encouraged by this pilot work, Triyushnadi Anjana (TA) and 2% sodium cromoglycate (mast cell stabilizer) eye drops in the second-phase clinical trial on 32 patients were tried clinically to evaluate the comparative efficacy. In the second clinical trial, the patients were randomly divided into two groups and Group I was given sodium cromoglycate 2% eye drops and Group II was given TA. The outcome of this study verified the results of the first phase pilot study, and on comparison of the results of the two groups in the second clinical study it was observed that the TA-treated group showed better results. Transient irritation in the eyes was reported by all patients after application of TA, which was relieved by keeping the eyes closed for a few minutes. None of the patients reported any adverse action of the trial drug. Thus, it can be concluded that TA is a safe, cost-effective, and potent Ayurvedic alternative in the treatment of vernal keratoconjunctivitis / spring catarrh.

Comparison of the Effects of Prophylactic Nonsteroidal Anti-inflammatory Drugs on Macular Edema After Cataract Surgery

Purpose: To evaluate and compare the efficacy of prophylactic administration of topical nonsteroidal anti-inflammatory (NSAID) drugs on macular edema (ME) following cataract surgery. Methods: The present open-label non-masked randomized (random number assignment) study was comprised of 90 eyes. Thirty eyes were administered Diclofenac sodium 0.1%, and 30 eyes were administered Pranoprofen 0.1% starting three days before surgery and continued for one month after surgery. The remaining 30 eyes made up the control group. The results consisted of the measurements of foveal thickness (FT), macular thickness (MT), and total macular volume (TMV), which were quantified by optical coherence tomography (OCT, Carl Zeiss Meditec) before and one month after phacoemulsification surgery. Results: At one month, there were statistically significant differences in FT in the Diclofenac group (0.4810.9 ) and the Pranoprofen group (1.8714.7 ) (p18.6 ). In addition, there was a statistically significant difference in MT between the control group (71.0690.8 ) and the Diclofenac group (15.1936.1 ) (p70.93 ). Between the control group and the NSAID groups, only the Diclofenac group showed statistical differences in TMV throughout the observational period. Conclusions: Used prophylactically after cataract surgery, the NSAIDS eye drops were effective in reducing postoperative ME.

Randomized Controlled Trial of Diclofenac Sodium Gel in Knee Osteoarthritis

Nonsteroidal anti-inflammatory drugs have dose-related adverse effects. Topical nonsteroidal anti-inflammatory drugs may offer local efficacy with low systemic drug levels. This study assessed the efficacy and safety of topical diclofenac sodium 1% gel (DSG) in mild to moderate symptomatic knee osteoarthritis. In a randomized, double-blind, vehicle-controlled trial, 492 adults aged >or=35 years with symptomatic knee osteoarthritis of >or=6 months' duration were randomized to DSG 4 g (n = 254) or vehicle (n = 238) 4 times daily for 12 weeks. Primary efficacy outcomes at week 12 were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, WOMAC physical function subscale, and global rating of disease. Secondary outcomes included these outcomes assessed after 1, 4, and 8 weeks, and pain on movement assessed using a 100-mm visual analog scale. All adverse events were recorded. At week 12, the DSG group had significant decreases versus the vehicle group in mean WOMAC pain (P = 0.01), mean WOMAC physical function (P = 0.001), and mean global rating of disease (P < 0.001). Efficacy outcomes significantly favored DSG versus vehicle beginning at week 1. Application site reactions occurred in 5.1% and 2.5% of patients in the DSG and vehicle groups, respectively. The incidence of gastrointestinal disorders was 5.9% with DSG and 5.0% with vehicle. Over a 3-month treatment period, topical treatment with DSG achieved statistically and clinically significant improvements of pain and measures of physical function in patients with knee osteoarthritis.

Fondaparinux 2.5mg for the Treatment of Symptomatic, Isolated Superficial Vein Thrombosis (SVT): Preliminary Data From the Randomized Placebo-Controlled CALISTO Trial (on Behalf of the CALISTO Investigators).

Abstract 171▪▪This icon denotes an abstract that is clinically relevant. Introduction:SVT is a common disease, associated with risks of clinically relevant venous thromboembolic complications. Currently, treatment of isolated SVT (i.e. without concomitant deep-vein thrombosis, DVT, or pulmonary embolism, PE) is based on analgesic agents, topical or oral nonsteroidal anti-inflammatory drugs, elastic stockings and occasionally surgery. Previous clinical trials have suggested the benefit of an extended antithrombotic therapy. Yet the optimal antithrombotic treatment remains unknown. Fondaparinux (Arixtra®) is a synthetic selective inhibitor of factor Xa with a favorable benefit-risk profile in the prevention and treatment of venous and arterial thrombosis in various medical and surgical settings. The large-scale, double-blind, randomized, placebo-controlled, CALISTO trial was designed to evaluate the benefit-risk ratio of fondaparinux 2.5 mg subcutaneously once daily during 45 days in 3000 patients with symptomatic, isolated SVT of the lower limbs documented by compression ultrasound (CUS). Methods:The study concerned male or female patients 18 years of age or greater with acute symptomatic isolated SVT of the lower limbs at least 5 cm long documented by standard CUS. After randomization (Day 1), subjects received fondaparinux 2.5 mg or placebo subcutaneously once daily up to Day 45. Study treatments were administered on an outpatient basis. Follow-up continued up to Day 75. Permitted medications included analgesic agents, topical non-steroidal anti-inflammatory drugs, graduated compression (elastic) stockings, aspirin at low dose (up to 325 mg per day) and other oral antiplatelet agents if the subject was receiving these drugs at the time of screening for a chronic medical condition. The primary efficacy outcome was confirmed symptomatic thromboembolic complications (a composite of PE, DVT, extension of SVT with thrombus head ≤3 cm from the saphenofemoral junction or recurrence of SVT) or all-cause death up to Day 45. Safety outcomes included major bleeding, clinically relevant non-major bleeding and death. All efficacy and safety outcomes were adjudicated by a central adjudication committee, unaware of treatment assignment. Results:The study started in March 2007 and inclusions were completed on May 15th 2009, with the recruitment of 3002 patients. The follow-up of the last patient was completed on July 31st 2009. Overall, on blinded preliminary data available on June 23rd 2009 (n=2994), the median age of patients was 58 [range: 19-92] years; 63.9% were women; 37.0% were obese (BMI ≥30 kg/m2). The main predisposing risk factors for SVT were varicose veins (88.6%) and a history of SVT (11.9%). More than one SVT was observed on baseline CUS in 19.2% of patients. The qualifying SVT predominantly involved the great saphenous vein alone (64.6% of patients). At Day 45, the overall incidence of adjudicated and adjudicated-pending symptomatic thromboembolic complications or death was 4.4% (Table). There was one adjudicated major bleeding. The final results according to treatment groups will be presented during the congress. Conclusions:There is an unmet medical need for an evidence-based anticoagulant treatment for isolated SVT. CALISTO is the first large randomized, controlled trial designed to establish standard anticoagulant therapy in patients with isolated SVT. It also provides a large database on the clinical characteristics of this disease.TableOverall incidence of adjudicated and adjudicated-pending symptomatic thromboembolic complications or deathN=2994Day 45 n (%)Follow-Up Period (Day 46 to Day 75), n (%)Thromboembolic complications or death*132 (4.4%)12 (0.4%)PE8 (0.3%)1 (0.0%)DVT21 (0.7%)1 (0.0%)Extension of SVT85 (2.8%)4 (0.1%)Recurrence of SVT30 (1.0%)6 (0.2%)Death3 (0.1%)0 (0.0%)*Patients with more than one clinical event were counted only once Disclosures:Décousus:GSK: Consultancy, Research Funding. Leizorovicz:GSK: Consultancy.

Allergic contact dermatitis caused by diclofenac cream

A 40-year-old man presented with a severe rash on his left forearm. One week earlier, he had experienced tendonitis in his left elbow and had treated it with diclofenac cream, a topical nonsteroidal anti-inflammatory drug (NSAID), applied four times daily. The area had become slightly erythematous

VITREOUS NONSTEROIDAL ANTIINFLAMMATORY DRUG CONCENTRATIONS AND PROSTAGLANDIN E2 LEVELS IN VITRECTOMY PATIENTS TREATED WITH KETOROLAC 0.4%, BROMFENAC 0.09%, AND NEPAFENAC 0.1%

To assess vitreous concentrations of nonsteroidal antiinflammatory drugs (NSAIDs) and prostaglandin E(2) in patients treated with NSAIDs before vitrectomy. This was an investigator-masked, randomized, multicenter study. Patients received ketorolac 0.4% 4 times a day, bromfenac 0.09% 2 times a day, nepafenac 0.1% 3 times a day, or no NSAID for 3 days before surgery. Nonsteroidal antiinflammatory drugs and prostaglandin E(2) levels were determined in vitreous samples collected at the beginning of surgery. Thirty-one patients were included in the analyses. The mean (SD) vitreous concentrations were as follows: ketorolac 2.8 (3.2) ng/mL, bromfenac 0.96 (0.31) ng/mL, nepafenac 1.1 (0.6) ng/mL, and amfenac 2.0 (0.8) ng/mL aligned with the initial concentrations of the topical NSAIDs. Mean (SD) vitreous prostaglandin E(2) levels of the control patients and those treated with ketorolac 0.4%, bromfenac 0.09%, or nepafenac 0.1% were 270.6 (91.7) pg/mL, 189.6 (50.2) pg/mL, 247.2 (38.3) pg/mL, and 267.7 (99.7) pg/mL, respectively. Patients treated with ketorolac 0.4% had significantly lower prostaglandin E(2) levels than those treated with no NSAID (P = 0.047) or nepafenac 0.1% (P = 0.028). All three NSAIDs penetrated into the vitreous cavity. Topical therapy with ketorolac may lower preoperative vitreous prostaglandin E(2) levels, which may have a clinical impact on the management of prostaglandin-mediated diseases, including cystoid macular edema.

Ophthalmic utility of topical bromfenac, a twice-daily nonsteroidal anti-inflammatory agent

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the formation of prostaglandin by cyclooxygenases. Several agents in this class have been approved for the treatment of postoperative pain and inflammation following cataract surgery. Bromfenac 0.09% (Xibrom™, ISTA Pharmaceuticals, USA) is a relatively new topical NSAID that exhibits ocular penetration and duration of action sufficient to permit twice-daily dosing. Bromfenac dosed twice-daily was clearly superior to placebo for postoperative pain and inflammation in a large, controlled trial and compares favorably with other NSAIDs in smaller studies. Adverse events associated with use have been minimal in large studies, although there are reports of corneal compromise with bromfenac use in cases of preexisting corneal disease. The comfort and reduced frequency of use offered by bromfenac would be expected to improve patient compliance, which would in turn be expected to result in adoption of bromfenac over other NSAIDs by many physicians. However, head-to-head trials comparing bromfenac with other NSAIDs using a twice-daily dosing schedule have not been undertaken. Bromfenac and other NSAIDs are seeing expanded use for the treatment and prevention of cystoid macular edema, and could have clinical utility in other diseases of vascular permeability.

Topical rubefacients for acute and chronic pain in adults.

Rubefacients (containing salicylates or nicotinamides) cause irritation of the skin, and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. A non-Cochrane review in 2004 found limited evidence for efficacy. To review current evidence for efficacy and safety of topically applied rubefacients in acute and chronic painful musculoskeletal conditions in adults. Cochrane CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Randomised, double blind, placebo or active controlled clinical trials of topical rubefacient for musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions. Two review authors independently assessed trials for inclusion and quality, and extracted data. Relative benefit or risk and number needed to treat to benefit or harm (NNT or NNH) were calculated with 95% confidence intervals (CI). Acute and chronic conditions were analysed separately. Six placebo and one active controlled studies (560 and 137 participants) in acute pain, and seven placebo and two active controlled studies (489 and 90 participants) in chronic pain were included. All used topical salicylates. The evidence in acute conditions was not robust; using only better quality, valid studies, there was no difference between topical rubefacient and topical control, though overall, including lower quality studies, the NNT for clinical success compared with placebo was 3.2 (95% CI: 2.4 to 4.9). In chronic conditions the NNT was 6.2 (95% CI: 4.0 to 13) compared with topical placebo. Adverse events and withdrawals occurred more often with rubefacients than placebo, but analyses were sensitive to inclusion of individual studies, so not robust. There were insufficient data to draw conclusions against active controls. The evidence does not support the use of topical rubefacients containing salicylates for acute injuries, and suggests that in chronic conditions their efficacy compares poorly with topical non-steroidal antiinflammatory drugs (NSAIDs). Topical salicylates seem to be relatively well tolerated in the short-term, based on limited data. There is no evidence at all for topical rubefacients with other components.

NSAIDs applied to the skin: a very topical subject

Healers have used plants containing salicylates to alleviate pain, infl ammation and fever for millennia. The clinical and commercial success of acetylsalicylic acid (aspirin) prompted the development of the plethora of non-steroidal anti-infl ammatory drugs (NSAIDs) available today. Although commonplace, there is a danger that therapeutic familiarity can breed toxicological contempt. NSAIDs can cause serious, even life-threatening gastrointestinal, cardiovascular and other side effects. The risk of adverse events prompted the search for better-tolerated alternatives, including topical preparations. Despite some initial scepticism, a growing body of clinical and pharmacological evidence suggests that topical NSAIDs offer an effective and well-tolerated treatment for several conditions that produce chronic or acute pain. This article briefl y describes the history of NSAIDs and how they work, before focusing on the use of topical NSAIDs as a therapeutic option.

MASTALGIA

Mastalgia is a common clinical symptom experienced by up to 70% of women at some stage of their life. A wide varietyof therapeutic agents are available for the treatment of mastalgia. Both evening primrose oil and non steroidal anti-inflammatory drugs havebeen assessed in randomised controlled trials and demonstrated to be effective. The objective of this Quasi experimental study was tocompare the efficacy and safety of topical nonsteroidal anti-inflammatory drugs with evening primrose oil in the treatment of mastalgia. Westudied 90 female patients presenting with breast pain from 25 July 2006 to 25 July 2007 at the surgical outpatient department of CMHKharian. The patients were divided into three groups. Group-1 was given capsule Effamol (evening primrose oil), group-2 topical brufen geland group-3 topical Vaseline for two months. Patients were followed every two weeks for two months. Response was assessed using Cardiffbreast pain score. Side effects of drugs were recorded at each follow up. Out of 30 patients of group-1,14 (46.6%) had clinically significantresponse at the end of 8 weeks treatment as compared to 27 (90%) in group-2.5 (16.6%) patients of group-1 showed mild side effects whilenone in group-2 had any side effect, p- value was &lt; 0.0001 showing highly significant statistical difference between 2 groups. Topicalnonsteroidal anti-inflammatory drugs are safe and effective as compared to evening primrose oil in the treatment of mastalgia.

Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis

While topical non-steroidal anti-inflammatory drugs are considered safe, their long-term efficacy for osteoarthritis has been suspect. We conducted a 12-week, double-blind, double-dummy, randomized controlled trial of topical diclofenac (TDiclo) in a vehicle solution containing dimethyl sulfoxide (DMSO) in 775 subjects with radiologically confirmed, symptomatic primary osteoarthritis of the knee. This 5-arm study compared TDiclo with a placebo solution, the DMSO vehicle, oral diclofenac (ODiclo) and the combination of TDiclo+ODiclo for relieving the signs and symptoms of knee osteoarthritis. Subjects applied study solution, 40 drops four times daily, and took one study tablet daily for 12weeks. Co-primary efficacy variables were WOMAC pain and physical function and a patient overall health assessment. Secondary variables were WOMAC stiffness and patient global assessment (PGA) of the knee osteoarthritis. TDiclo was superior to placebo for pain (−6.0 vs. −4.7, P=0.015), physical function (−15.8 vs. −12.3, P=0.034), overall health (−0.95 vs. −0.37, P<0.0001), and PGA (−1.36 vs. −1.01, P=0.016), and was superior to DMSO vehicle for all efficacy variables. No significant difference was observed between DMSO vehicle and placebo or between TDiclo and ODiclo. The commonest adverse event associated with TDiclo was dry skin (18.2%). Fewer digestive system and laboratory abnormalities were observed with TDiclo than with ODiclo. Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events. TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to, but tolerability better than ODiclo. DMSO vehicle was no more efficacious than placebo.

Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery

This study compared the post-cataract surgery anti-inflammatory effects of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on postoperative anterior chamber inflammation and corneal swelling. Seventy-two patients with no eye disease other than cataract were enrolled in a prospective, randomized study to undergo phacoemulsification combined with intraocular lens implantation. After cataract surgery, patients were randomized to treatment with bromfenac, betamethasone or both agents. Twenty-five eyes were assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment group. Inflammatory reactions in the anterior chamber were measured with laser flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Intraocular pressure (IOP) and corneal thickness were measured at the same time-points. Best corrected visual acuity (BCVA) was measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Specular microscope endothelial photography of the central region of the cornea was performed preoperatively and at 3 months after surgery. There were no significant differences among the bromfenac, betamethasone and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness. Cystoid macular oedema was present in one eye treated with betamethasone. There were no significant differences in anti-inflammatory effects among the three treatments. These findings suggest that bromfenac is as effective as betamethasone in minimizing inflammatory reactions after cataract surgery.

Safety and efficacy of diclofenac sodium 1% gel in unilateral and bilateral osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have demonstrated effectiveness in patients with osteoarthritis (OA) while minimizing systemic NSAID exposure. This randomized double-blind trial examined the efficacy and safety of diclofenac sodium topical gel 1% (DSG) in patients with mild to moderate knee OA. 420 adults aged ≥35 years with symptomatic Kellgren-Lawrence Grade 1–3 OA of ≥6 months' duration in 1 or both knees were randomized to apply DSG 4 g (n = 208) or vehicle (n = 212) 4 times daily to each symptomatic knee for 12 weeks.

Acanthamoeba keratitis with perforation after corneal crosslinking and bandage contact lens use

A 32-year-old man with keratoconus developed corneal melting 5 days after riboflavin/ultraviolet-A corneal collagen crosslinking (CXL). Corneal scraping was positive for Acanthamoeba. The patient was unaware that he was wearing a bandage contact lens and repeatedly rinsed his face and eyelids with tap water. Because of corneal perforation, a large therapeutic keratoplasty à chaud was performed. Although CXL is considered a safe procedure, this case emphasizes the potential risks. We discuss the potential effects of deepithelialization, contact lens placement, instillation of topical nonsteroidal antiinflammatory drugs and anesthetic agents, and the possible role of apoptosis when performing CXL treatment for keratoconus.