Topical Nonsteroidal Anti-inflammatory Drugs Research Articles

Cystoid macular edema after cataract surgery in a patient with previous severe iritis following argon laser peripheral iridoplasty

This report describes a patient who had exaggerated responses to different inflammatory stimuli represented by laser and incisional surgery, respectively. These separate episodes should have a common link represented by a genetic predisposition to abnormal release of proinflammatory mediators within the eye. This 51-year old Hispanic woman showed a narrow iridocorneal angle with plateau iris configuration. Nd-YAG laser peripheral iridotomy was successfully performed to both eyes. No substantial changes in the iridotrabecular angle occurred despite patent iridotomies, thus confirming the diagnosis of plateau iris configuration. Argon laser iridoplasty was then performed to the right eye, while the left eye was scheduled for a later session. A severe inflammatory reaction within the anterior chamber developed after tapering of a one-week course of steroid therapy. Phacoemulsification of the lens was performed some months later when no signs of inflammation were detectable; no intraoperative complications occurred during surgery and an intraocular lens was placed. Cystoid macular edema developed four weeks after surgery despite no apparent risk factors, and resolved completely after anti-inflammatory medical therapy. Based on this case report, the unusual occurrence of severe iritis after laser treatment should be regarded as a risk factor for any other incisional or nonincisional procedures because it might indicate that the patient’s ocular tissues are prone to release of abnormally elevated proinflammatory mediators. Although further studies are needed to confirm this predisposition, prophylactic adjunctive topical nonsteroidal anti-inflammatory drug administration after cataract surgery should be considered in such cases in order to prevent potentially sight-threatening conditions.

Postsurgical Cystoid Macular Edema

Cystoid macular edema (CME) is a primary cause of postoperative reduced vision. It may occur even when the intraoperative course is successful for operations such as cataract and vitreoretinal surgery. Its incidence following modern cataract surgery is 0.1%-2.35%. This risk is increased if there are certain preexisting systemic or ocular conditions and when there are intraoperative complications. The etiology of CME is not completely understood. Prolapsed or incarcerated vitreous and postoperative inflammatory processes have been proposed as causative agents. Pseudophakic CME is characterized by poor postoperative visual acuity. Fluorescein angiography is indispensable in the workup of CME, showing the classical perifoveal petaloid staining pattern and late leakage of the optic disk. Optical coherence tomography is a useful diagnostic tool, which displays cystic spaces in the outer nuclear layer. The most important differential diagnoses include age-related macular degeneration and other causes of CME such as diabetic macular edema. Most cases of pseudophakic CME resolve spontaneously. The value of prophylactic treatment is doubtful. First-line treatment of postsurgical CME should include topical nonsteroidal anti-inflammatory drugs and corticosteroids. Oral carbonic anhydrase inhibitors can be considered complementary. In cases of resistant CME, periocular or intraocular corticosteroids present an option. Antiangiogenic agents, though experimental, should be considered for nonresponsive persistent CME. Surgical options should be reserved for special indications.

Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions.

Topical Nonsteroidal Anti-Inflammatory Drugs for Osteoarthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of the treatment of osteoarthritis (OA) but have dose- and age-related risks of gastrointestinal, cardiovascular, and renal adverse events (AEs). As a result, US and international guidelines recommend caution when prescribing oral NSAIDs, particularly in older patients and those with significant comorbidities. For OA of the hands and knees, topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic distribution. Treatment-related cardiovascular, renal, and other serious AEs with topical NSAIDs have not been reported. At present, only 2 topical NSAIDs are approved in the United States for the treatment of OA: diclofenac sodium 1% gel for hand or knee OA and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution for knee OA. Clinical trial data for these products have demonstrated efficacy superior to placebo or similar to oral diclofenac with AE profiles similar to placebo, except for application site reactions. In large double-blind trials, gastrointestinal AEs were infrequent and did not include ulcers, perforations, or bleeding. The purpose of this brief review is to examine the data from controlled double-blind trials evaluating the use of topical NSAIDs in patients with OA. Articles included were identified via a search of PubMed covering the period from January 1, 2005 through March 31, 2010. Reference lists from OA treatment guidelines and meta-analyses were reviewed for additional citations of importance.

Should Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) be Prescribed to the Older Adult?

The prevalence of chronic pain increases with age, exceeding 50% in individuals aged ≥65 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay of chronic pain management but carry significant dose-related risks of cardiovascular, renal, haematological and other systemic adverse events (AEs). Older patients have an increased risk of these AEs and are more likely to take multiple medications that can potentially interact with NSAIDs. In particular, older patients are more likely to have cardiovascular disease and a natural age-related decline in renal function, increasing the risks of cardiovascular, haematological and renal AEs. Given these risks, recent guidelines for the management of chronic pain in the elderly recommend using NSAIDs rarely and only in carefully selected patients. NSAIDs currently available in the US fall into three categories: nonselective NSAIDs that act via inhibition of cyclo-oxygenase (COX)-1 and COX-2; celecoxib, a selective inhibitor of COX-2; and topical NSAIDs that inhibit both COX-1 and COX-2 but result in much less systemic NSAID exposure than oral formulations. Topical NSAIDs have demonstrated efficacy similar to oral NSAIDs, with an incidence of AEs similar to placebo; however, these agents are an option only in patients with localized pain in superficial joints. Safe pain management in older patients therefore requires cautious choice of selective and nonselective oral NSAIDs, topical NSAIDs or non-NSAID analgesics. This article discusses the risks and benefits of NSAID therapy, reviews its mechanism of action as the source of adverse effects and provides recommendations for maximizing NSAID safety, particularly in older patients. Articles cited in this review were identified via a search of PubMed (January 2005 to November 2009) and a manual search of reference lists from the articles identified in that search. Priority was given to articles discussing NSAID use in older populations, clinical trials of high quality, reports on NSAID safety and AEs, and treatment guidelines.

A Comparative Subjective Assessment Study of PENNSAID® and Voltaren Gel®, Two Topical Formulations of Diclofenac Sodium

Osteoarthritis (OA) is a chronic degenerative joint disease that is debilitating for many individuals. While oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain a common and effective treatment approach to managing OA, concerns over cardiovascular and gastrointestinal adverse events can potentially limit their use. Various formulations of topical NSAIDs have been shown to provide effective localized treatment with minimal adverse events. A patient perception study was conducted to evaluate patient preference between topical diclofenac sodium gel and that of diclofenac sodium topical solution with the penetration enhancer dimethyl sulfoxide (DMSO). Twenty-four healthy volunteers were randomized and asked to administer one dose of the topical products. Surveys were provided and assessed immediately after application, 5 minutes after application, and after the application had dried to gauge subjects' overall experience with the topical preparation. Overall, each drug's application was well tolerated and no adverse events were reported. Results of the patient preference survey demonstrated that topical diclofenac solution with DMSO had a number of characteristics that were rated significantly better than for diclofenac sodium gel. Mean subjective responses to topical diclofenac solution with DMSO were also more favorable for most items in the questionnaire, and more subjects preferred or highly preferred topical diclofenac solution with DMSO over diclofenac sodium gel.

Pharmacological Therapies for Osteoarthritis of the Hand

Osteoarthritis (OA) of the hand is highly prevalent in US senior citizens, developing in >50% of individuals aged >60 years. Hormonal, genetic and inflammatory mechanisms are known to increase the risk of hand OA and influence the course of the disease. However, the underlying processes in the development of hand OA are not well understood, and there is no known disease-modifying drug. Likewise, surgical interventions for affected hand joints have not proven as successful as joint replacement for the knee or hip. Current treatment of hand OA focuses on reducing pain and improving patient function to improve quality of life. Pharmacological approaches have included several oral therapies, such as paracetamol (acetaminophen), oral nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, all of which carry a risk of adverse events that typically increases with age. Topical NSAIDs, recently approved in the US, appear to provide efficacy similar to that of oral NSAIDs for hand OA, with less systemic NSAID exposure. Intra-articular corticosteroids and hyaluronic acid have also shown modest symptomatic efficacy with generally good tolerability. Two proposed disease-modifying therapies, chondroitin sulfate and hydroxychloroquine, have had unclear effects on disease modification in clinical trials. This review of pharmacotherapies for the treatment of hand OA focuses on their efficacy and safety in elderly patients. Articles cited herein were identified via a search of PubMed from January 2005 to November 2009. The bibliographies of articles identified through this search were searched manually for additional references of interest.

Treatment of postoperative macular edema

Abstract Purpose Cystoid macular edema (CME) is a frequent complication of a number of interventions in ophthalmology, such as cataract surgery (Irvine‐Gass syndrome), laser procedures, and trabeculectomy. The purpose of this talk is to present the latest bibliographic data regarding the appropriate treatment of postoperative CME. Methods A review of the existing literature concerning the treatment of postoperative CME is performed. Characteristic personal cases are presented. Results In more than two‐thirds of the cases, postoperative CME resolves spontaneously within weeks or months. Prophylactic topical treatment with indomethacin or flurbiprofen seems to reduce the frequency of clinical and angiographic CME, but its beneficial effect on final visual acuity is not established. Curative therapy includes topical corticosteroids; topical non‐steroidal anti‐inflammatory drugs (e.g. ketorolac); oral acetazolamide; sub‐Tenon or intravitreal injection of triamcinolone acetonide; intravitreal injection of anti‐VEGF drugs; and pars plana vitrectomy. The indications, role, and efficacy of each of the above treatment modalities are discussed, based on the latest bibliographic data. Conclusion Most cases of postoperative CME are mild and resolve spontaneously. In refractory cases, sub‐Tenon or intravitreal injection of triamcinolone acetonide can be effective, but the risk of ocular hypertony is high. Intravitreal injection of anti‐VEGF drugs offers promising results, yet large‐scale randomized studies are necessary to validate their utility. Finally, pars plana vitrectomy is the treatment of choice when vitreomacular traction and/or epiretinal membrane is present.

Modern Management of Mild-to-Moderate Joint Pain due to Osteoarthritis: A Holistic Approach

Osteoarthritis (OA) is the most common form of arthritis and it is often associated with significant disability and impaired quality of life. Once thought to be caused by an age-related 'wearing out' of articular cartilage, it is now recognized to be a dynamic process in which cartilage degradation alternates with repair. Several expert guidelines for the management of OA exist, which concur in their recommendations for a stepwise approach to the employment of pharmacological agents and the introduction of suggestions to extend the use of agents such as topical non-steroidal anti-inflammatory drugs, especially for mild-to-moderate forms of the disease. They also emphasize the importance of non-pharmacological measures, such as nutraceuticals, education, diet, exercise and the use of aids in improving signs and symptoms and slowing progression. In many countries, effective medicinal and nutraceutical agents are available 'over-the-counter'. This review explains the modern approach to the management of mild-to-moderate osteoarthritic pain.

Time to significant pain reduction following DETP application vs placebo for acute soft tissue injuries

Objective:Nonsteroidal anti-inflammatory drugs (NSAIDs) provide fast and effective acute pain relief, but systemic administration has increased risk for some adverse reactions. The diclofenac epolamine 1.3% topical patch (DETP) is a topical NSAID with demonstrated safety and efficacy in treatment of acute pain from minor soft tissue injuries. Significant pain reduction has been observed in clinical trials within several hours following DETP application, suggesting rapid pain relief; however, this has not been extensively studied for topical NSAIDs in general. This retrospective post-hoc analysis examined time to onset of significant pain reduction after DETP application compared to a placebo patch for patients with mild-to-moderate acute ankle sprain, evaluating the primary efficacy endpoint from two nearly identical studies.Research design and methods:Data from two double-blind, randomized, parallel-group, placebo-controlled studies (N = 274) of safety and efficacy of the DETP applied once daily for 7 days for acute ankle sprain were evaluated post-hoc using statistical modeling to estimate time to onset of significant pain reduction following DETP application.Main outcome measures:Pain on active movement on a 100 mm Visual Analog Scale (VAS) recorded in patient diaries; physician- and patient-assessed tolerability; and adverse events.Results:DETP treatment resulted in significant pain reduction within approximately 3 hours compared to placebo. Within-treatment post-hoc analysis based on a statistical model suggested significant pain reduction occurred as early as 1.27 hours for the DETP group. The study may have been limited by the retrospective nature of the analyses. In both studies, the DETP was well tolerated with few adverse events, limited primarily to application site skin reactions.Conclusion:The DETP is an effective treatment for acute minor soft tissue injury, providing pain relief as rapidly as 1.27 hours post-treatment. Statistical modeling may be useful in estimating time to onset of pain relief for comparison of topical and oral NSAIDs.

A Review of Topical Diclofenac Use in Musculoskeletal Disease

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for the treatment of musculoskeletal disorders. Osteoarthritis is the most common form of arthritis in humans and its prevalence rises with age. Oral NSAIDs have potential associated toxicities that must be monitored for and can limit the use of these drugs in certain populations including people of older age. Topical NSAIDs are now being recognized as an option for the treatment strategy of osteoarthritis. We review the efficacy and safety of one of the most common topical NSAIDS, topical diclofenac, for the treatment of osteoarthritis.

Update on the Use of Topical NSAIDs for the Treatment of Soft Tissue and Musculoskeletal Pain: A Review of Recent Data and Current Treatment Options

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have an emerging role in the treatment of certain types of acute pain. In addition to their convenience, efficacy, and safety, they are an attractive option, particularly when considering current concerns about the safety of traditional NSAIDs and cyclooxygenase-2 (COX-2) inhibitors (coxibs). Topical analgesics act largely within the peripheral nervous system. Studies have demonstrated that topical NSAIDs penetrate the skin and distribute to the target tissues underlying the application site. Because the pharmacologically effective dose is delivered at the site of pain, there is minimal systemic absorption and risk of related adverse events. Topical NSAIDs have been used for many years in Europe, with extensive post-marketing data available for some of the agents. Three topical NSAID formulations have recently been approved for use in the United States: the diclofenac epolamine topical patch 1.3% (DETP), diclofenac sodium 1% gel, and diclofenac sodium topical solution 1.5%. Topical NSAIDs provide a therapeutic option for treatment of acute, localized, soft tissue injuries or painful conditions in areas of the body that can be readily treated using the topical route of administration. This article reviews available data on the use of topical NSAID therapy.

Safety and Efficacy of Topical Diclofenac Sodium 1% Gel in Knee Osteoarthritis: A Randomized Controlled Trial

Background: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may provide an alternative to oral NSAIDs to relieve pain from osteoarthritis (OA), reducing systemic exposure. This 12-week, randomized, double-blind, parallel-group, multicenter trial examined the efficacy and safety of topical diclofenac sodium 1% gel (DSG) for symptomatic knee OA. Methods: Eligible patients were aged ≥ 35 years with symptomatic Kellgren-Lawrence grade (KLG) 1 to 3 OA in 1 or both knees for ≥ 6 months. Patients meeting entry criteria applied DSG 4 g or vehicle 4 times daily to the symptomatic knee(s). Primary endpoints were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and global rating of benefit at week 12. Pain on movement at week 4 was an additional primary endpoint for European regulatory purposes. Secondary endpoints included primary outcomes at weeks 1, 4, and 8; WOMAC stiffness subscale; spontaneous pain; global rating of disease; and global evaluation of treatment. Subanalyses were performed according to KLG, the number of knees treated, and age. Results: Four hundred twenty patients were randomly assigned to DSG (n = 208) or vehicle (n = 212). At week 12, DSG provided significantly greater reductions in WOMAC pain (52.6% vs 43.1%; P = 0.008) and physical function (49.7% vs 39.4%; P = 0.004) versus vehicle and provided significant improvements in most secondary endpoints. Treatment-related adverse events (AEs) were infrequent (DSG, 7.7%; vehicle, 4.2%), with application site dermatitis being the most common AE (DSG, 4.8%; vehicle, 0%). No treatment-related gastrointestinal or serious AEs occurred with DSG. Conclusion: Topical DSG treatment provided effective pain relief and functional improvement of OA in 1 or both knees and was well tolerated, irrespective of disease severity or patient age.

Clinically Meaningful Relief of Osteoarthritis in Randomized Controlled Trials of Diclofenac Sodium 1% Gel

PURPOSE: To compare rates of clinically meaningful response in patients with hand and knee osteoarthritis (OA) treated with diclofenac sodium 1% gel (DSG) versus placebo rubefacient gel (PRG). Over-the-counter topical rubefacients are often used in sports medicine but have poor efficacy and are not recommended in evidence-based guidelines for OA (National Institute for Health and Clinical Excellence clinical guideline 59), whereas topical nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended ahead of oral NSAIDs. However, many US physicians lack experience with topical NSAIDs and may be skeptical that they offer meaningful benefit compared with more familiar topical rubefacients. METHODS: In a post hoc analysis, patients from 2 double-blind trials of DSG in knee or hand OA were classified based on Osteoarthritis Research Society International (OARSI) criteria for clinically significant response. Patients were randomized to apply DSG or PRG 4 times daily (hand, 8 g/d/hand for 8 weeks to 2 hands; knee, 16 g/d for 12 weeks to 1 knee). OARSI response was defined as improvement ≥50% and absolute change ≥20 points on 100-point scales measuring pain or physical function, or improvement ≥20% and absolute change ≥10 in ≥2 of the following: pain, global rating of disease, and physical function. RESULTS: Clinically significant improvement was achieved by 56%-71% of patients treating knee OA and hand OA with DSG, which was significantly superior to response rates with PRG at most time points (Table). CONCLUSIONS: DSG provided clinically meaningful improvement in OA pain for the majority of patients with hand or knee OA, and for a significantly greater proportion of patients compared with PRG. Supported by Endo Pharmaceuticals Inc.

Preoperative Nonsteroidal Anti-inflammatory Drug or Steroid and Outcomes after Trabeculectomy: A Randomized Controlled Trial

To investigate the benefit of preoperative treatment with either topical nonsteroidal anti-inflammatory drug (NSAID) or steroid in terms of clinical outcomes following trabeculectomy.Prospective, randomized placebo-controlled trial.Sixty-one patients.Between July 2005 and October 2007, 61 consecutive medically uncontrolled glaucoma patients scheduled for first-time trabeculectomy were randomized to 1 of 3 study topical medication groups: nonsteroidal anti-inflammatory drugs (ketorolac), steroids (fluorometholone), or placebo (artificial tears). Patients instilled 1 drop 4 times daily for 1 month before the procedure and were examined on days 1 and 2, at weeks 1, 2, and 4, and at months 3, 6, 12, 18, and 24 after trabeculectomy.Incidence of postoperative surgical or medical interventions (needling, laser suture lysis, needling revision, and intraocular pressure [IOP]-lowering medication).Fifty-four patients (54 eyes) were entered for analysis. The mean number of preoperative medications was 2.3+/-0.9. The mean baseline IOP was 21.0+/-6.0 mmHg. The mean postoperative target IOP was 16.5+/-1.8 mmHg. The mean follow-up was 23.6+/-4.0 months. The percentage of patients requiring needling within the first year was 41% in the placebo group, 6% in the NSAID, and 5% in the steroid group (P = 0.006). The percentage of patients requiring IOP-lowering medication to reach the target IOP at 1 year was 24% in the placebo group, 18% in the NSAID group, and 0% in the steroid group (P = 0.054 overall; P = 0.038 for steroids vs. others). The log-rank test showed a significant (P = 0.019) difference in medication-free survival curves between the different groups. More specifically, patients in the steroid group needed significantly less medication over the total follow-up (P = 0.007).Topical ketorolac or fluorometholone for 1 month before surgery was associated with improved trabeculectomy outcomes in terms of likelihood of postoperative needling. In the steroid group, there was a significantly reduced need for additional postoperative IOP-lowering medication compared with the other groups.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topical NSAID Therapy for Musculoskeletal Pain

Systematic reviews previously reported in the literature document that topical nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in relieving pain in acute and chronic painful musculoskeletal disorders including osteoarthritis, tendonitis, and muscle strains. Because several topical NSAIDs are available, with important differences among the formulations, there is a need to address and summarize the evidence of their effectiveness and safety. We searched Medline and Cochrane CENTRAL databases for clinical trials and systematic reviews of topical NSAIDs in musculoskeletal pain, using the following keywords: "NSAID,""nonsteroidal,""antiinflammatory,""topical,""cream,""gel,""solution,""lotion,""patch,"plaster,""musculoskeletal,""tendonitis,""strain,""sprain,""trauma," and word roots "pain" and "arthritis." Topical NSAIDs may vary significantly in their absorption kinetics and pharmacodynamic effects, based on NSAID molecule and the formulation chosen. Some topical NSAID formulations have been shown to be more effective than placebo in multiple studies, or to have comparable efficacy and a better safety profile than oral NSAIDs for single joint osteoarthritis and acute muscle injuries. In acute and chronic low back pain, widespread musculoskeletal pain, and in peripheral neuropathic pain syndromes, the current evidence does not support the use of topical NSAIDs.

Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review.

To systematically review the literature on reported adverse effects (AE) associated with use of topical nonsteroidal antiinflammatory drugs (NSAID) in older adults with osteoarthritis (OA). A systematic search of Medline (1950 to November 2009), Scopus, Embase, Web of Science, Cochrane databases, Dissertation and American College of Rheumatology meeting abstracts was performed to identify original randomized controlled trials, case reports, observational studies, editorials, or dissertations reporting AE from topical NSAID in older adults with OA. Information was sought on study and participant characteristics, detailed recording of application site, and systemic AE as well as withdrawals due to AE. The initial search yielded 953 articles of which 19 met eligibility criteria. Subjects receiving topical NSAID reported up to 39.3% application site AE, and up to 17.5% systemic AE. Five cases of warfarin potentiation with topical agents were reported, 1 resulting in gastrointestinal bleeding. In formal trials, the withdrawal rate from AE ranged from 0 to 21% in the topical agents, 0 to 25% in the oral NSAID, and 0 to 16% in the placebo group. Although topical NSAID are safer than oral NSAID (fewer severe gastrointestinal AE), a substantial proportion of older adults report systemic AE with topical agents. The withdrawal rate due to AE with topical agents is comparable to that of oral NSAID. Given the safety profile and withdrawal rates described in this study, further data are needed to determine the incremental benefits of topical NSAID compared to other treatment modalities in older adults with OA.

Safety of diclofenac sodium 1% gel for knee osteoarthritis in patients with comorbidities

Osteoarthritis (OA) is associated with elevated risk of cardiovascular disease (CVD), relative risk increasing with younger age.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a risk of cardiovascular adverse events (AEs), increasing with dose and duration of use. 2 Topical NSAIDs reduce systemic NSAID exposure, offering potential benefits. The safety and efficacy of topical diclofenac sodium 1% gel (DSG) in patients with knee OA pain were established in 3 double-blind randomized trials, wherein 721 patients (aged ≥35 y) with radiographically mild to moderate knee OA applied DSG 4 grams 4 times daily per knee to 1 or both knees for 12 weeks.

Photoallergic contact dermatitis

Photoallergic contact dermatitis (PACD) presents in patients after certain exogenous agents come into contact with the skin in the presence of ultraviolet and/or visible light. The best method currently available for investigating PACD is photopatch testing. However, photopatch testing as an investigation is under-used by clinicians, and therefore PACD may go undetected in many patients. To highlight the importance of PACD and photopatch testing when investigating patients with a photo-exposed site dermatosis. A comprehensive review of the available literature relating to PACD and photopatch testing. Experimental evidence suggests that PACD is a delayed type hypersensitivity reaction. Various agents have been historically shown to cause PACD, but currently the most common photosensitizers are sunscreens and topical non-steroidal anti-inflammatory drugs. Photopatch testing has in the past been subject to differing methodologies; however, a European consensus methodology now exists and should allow a greater comparison of results across centres. As chemical, pharmaceutical, and cosmetic industries produce new agents, photopatch testing of such agents in humans before release in the marketplace may prevent widespread contact with potent photosensitizers. It will also be important for ongoing multi-centre studies of existing agents to be conducted in order to keep the photopatch test batteries used by clinicians investigating PACD up to date.

E3. The future of sentinel lymph node biopsy

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.