DMSO (Topical)

Plantar fasciitis is the most common cause of heel pain in adults with an overall prevalence of 0.85% in the adult population of the US, affecting over 2 million adults annually. Most current treatment modalities are not supported by sufficient evidence to recommend one particular strategy over another. Topical application of analgesics for soft tissue pain is well established, however the plantar fascia presents challenges in this regard due to thick skin, fibrotic tissue, and an often thickened fat pad. Sixty-two patients with plantar fasciitis were randomized to a placebo controlled trial testing the efficacy of a topical solution of plant terpenes containing camphor, menthol, eugenol, eucalyptol, and vanillin. Skin permeation of the mixture was enhanced with 15% dimethylsulfoxide (DMSO), 1% limonene, and rosemary oil. One ml of solution was applied topically twice daily, and pain scores evaluated on Day 0, Day 1, Day 3, and Day 10. Using the validated foot function index 78.1% of patients reported an 85% or greater decrease in their total pain score by day 10 while placebo treatment was without effect (One Way ANOVA, P < 0.01). This study adapts the treatment modality of topical analgesia for soft tissue pain to a problematic area of the body and shows therapeutic promise.ClinicalTrials.gov Identifier: NCT05467631. © 2024. The Author(s).

The aim of this double-blind, placebo-controlled, randomized study was to investigate whether topical melatonin administered during radiation therapy could increase the quality of life in patients with primary breast cancer. Patients were followed from the first radiation fraction until 3 weeks after the last. The patients applied 1 g of cream to the irradiated area of the skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or a placebo cream. Outcomes were the European Organisation for Research and Treatment of Cancer's quality-of-life questionnaires for breast cancer (QLQ-C30 and QLQ-BR23) on the last day of radiation therapy. As a secondary outcome, we evaluated the breast symptom (BS) scores over the entire duration of the trial in a repeated measures linear model. We included 65 patients and had 17 drop-outs, thus totaling 26 and 22 patients in the melatonin and placebo groups, respectively. BS scores on the last day of radiation did not differ between groups (p = .333). However, the linear model analyzing BS for the entire duration showed that melatonin significantly decreased the symptoms (p = .001). There was no difference in the BS score on the last day of radiation, however, we found that the patients in the melatonin group had significantly lower BS scores over the entire duration of the trial. © 2022 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.

Skin cancer is the most common cancer in the United States and among Caucasians worldwide, with more people diagnosed each year than all other cancers combined. Basal cell cancer is the most common form with an estimated 4.3 million cases diagnosed annually, and treatment costs estimated at $4.8 billion. The objective of this study was to compare efficacy of a topical solution consisting of 30% ascorbic acid in 95% dimethylsulfoxide with topical imiquimod in the treatment of basal cell carcinoma. Twenty-five patients with 29 biopsy confirmed basal cell carcinomas were randomly assigned to receive either the topically applied ascorbic acid treatment twice daily for 8 weeks or topical imiquimod, a standard and well characterized topical treatment. After 8 weeks, post-treatment biopsy of lesions showed complete resolution of 13/15 (86.7%) in the ascorbic acid group, while 8/14 (57.1%) lesions in the IMQ group were resolved (p < 0.05 Chi Square). Topical ascorbic acid was superior at 8 weeks, and non-inferior at 12 weeks to topical imiquimod in the treatment of low risk nodular and superficial lesions. In addition, ascorbic acid was associated with fewer adverse effects than imiquimod. 70% of patients in the imiquinod group showed residual hypopigmentation at 30mo follow up versus 0% in the ascorbate group.

Background Although topical amphotericin B cream is effective for the treatment of nondermatophyte mold onychomycosis in vitro, studies of its effectiveness and safety in vivo are limited. Objectives We studied the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide cream (amphotericin B cream) in nondermatophyte mold onychomycosis using the vehicle cream 30% dimethyl sulfoxide cream as control. Methods This randomized controlled study was conducted between January 2019 and November 2020. Patients diagnosed with nondermatophyte mold onychomycosis were randomly divided into two groups of ten patients each: one treated with amphotericin B cream and the other with the vehicle cream. Clinical and mycological cure as well as safety were evaluated. Results Ten patients each treated with amphotericin B cream and the vehicle cream were included in the study, but only nine patients in the vehicle cream group were available for follow up. All the 19 evaluable patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of these. Mycological cure was achieved in 8 (80%) patients treated with amphotericin B cream and in 4 (44.4%) patients using the control (vehicle) cream. Clinical cure was achieved in 7 (70%) patients treated with amphotericin B cream, but only in 2 (22.2%) patients on the control cream. No adverse events were observed. Limitations The small sample size and the fact that PCR fungal identification that provides accurate identification of fungal species was not performed are limitations of our study. Conclusion Topical amphotericin B cream was both very effective and safe in the treatment nondermatophyte mold onychomycosis. The control (vehicle) cream containing 30% dimethyl sulfoxide also demonstrated some antifungal activity.

Dimethyl sulfoxide (DMSO) is a molecule with a long history in pharmaceutics and is now well established as a penetration enhancer in topical pharmaceutical formulations. It is currently used for this purpose in diclofenac sodium topical solution (approved in the United States to treat signs and symptoms of osteoarthritis) and idoxuridine topical solution (approved in Europe for the treatment of herpes zoster). This article reviews the mechanism of action of DMSO as a pharmaceutical penetration enhancer, the characteristics of the molecule that facilitate transdermal drug delivery, and studies of efficacy and safety. The clinical use of pharmaceutical-grade DMSO as a penetration enhancer is supported by the robust data that have accumulated over the past 3 decades demonstrating the favorable safety and tolerability profile. Dimethyl sulfoxide is a safe and effective mechanism for facilitating the transdermal delivery of both hydrophilic and lipophilic medications to provide localized drug delivery.

Pharmacologic chelators do not effectively penetrate cell membranes and blood-brain barrier. This study assesses methylsulfonylmethane (MSM) as a permeability enhancer and an excipient to facilitate EDTA transport across biologic membranes, and to make possible localized, regional chelation. Topical application of MSM with C(14)EDTA onto the rat cornea led to uptake of the C(14)EDTA in all tested ocular tissues. Without MSM, EDTA did not penetrate the eye. The ability of MSM to deliver EDTA into an eye provides an opportunity for regional chelation therapy. Additionally, these studies suggest that MSM could also be an adjuvant for delivering ciprofloxacin and other chemical compounds to specific, local tissue sites.

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 12 weeks. 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.

During their formation, fish eggs receive a load of contaminants including polychlorinated biphenyls (PCBs) from their mother and then, after spawning, are exposed to pesticides present in water. This is the first study investigating the interaction between PCBs and organophosphorous pesticides in fish. The effect of diazinon was evaluated in mummichog (Fundulus heteroclitus) larvae produced from eggs differentially treated with 3,3',4,4',5 pentachlorobiphenyl (PCB126). A few hours after fertilization, eggs were treated topically with a solution of PCB126 (100 pg/microl) in dimethyl sulfoxide (DMSO) (Group P), DMSO (Group D), or not treated (Group N). Newly hatched larvae from Groups P and D were exposed to diazinon (125-12,900 ng/L) in saltwater and Group N larvae to saltwater alone. Diazinon caused a dose-responsive inhibition of cholinesterase (ChE) activity at environmentally realistic concentrations (> or =361 ng/L), with up to 85% inhibition at 12,900 ng/L. Body length was also inversely related to diazinon at concentrations > or =361 ng/L and was significantly reduced (by 4%) at 12,900 ng/L compared to controls. Mummichog larvae were highly sensitive to PCB126 with an eightfold induction of the activity of ethoxyresorufin-O-deethylase at a dose of 710 pg PCB126 or 3.6 pg TCDD-TEQ/g wet weight. Treatment with PCB126 also caused a slight reduction in body length but no effect on ChE activity. This study indicates that the effects of PCB126 and diazinon on body length are cumulative because no significant synergistic or antagonistic interactions were observed. Longer term studies with several doses of PCB126 are needed to fully assess the overall impact of joint exposure to diazinon and PCB126 on growth and survival of fish larvae.

Nimesulide, celecoxib, and DFU (5, 5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone) are nonsteroidal anti-inflammatory drugs (NSAIDs) with selective cyclo-oxygenase (COX)-2 blocking properties and have potent analgesic and anti-inflammatory activities in oral and parenteral administrations. Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is an extremely potent antinociceptive agent. The present study was conducted to evaluate the antinociception induced by nimesulide, celecoxib, and DFU when topically applied on the tail in the absence or presence of intraperitoneal dexmedetomidine. Antinociception was measured in the radiant tail-flick test after immersion of the tail of rat into a solution of dimethyl sulfoxide (DMSO) containing nimesulide, celecoxib, or DFU. Antinociceptive effect of all drugs peaked at 60 min and decreased gradually to baseline levels at 240 min. Nimesulide had a potency lower than those of celecoxib, and DFU. The antinociceptive effect of dexmedetomidine was blocked by systemic pretreatment of selective alpha(2)-adrenoceptor antagonist, atipamezole. This suggests that antinociceptive effects of dexmedetomidine involve alpha(2)-adrenoceptors. Combination of topical COX-2 inhibitors with intraperitoneal dexmedetomidine yielded additive analgesic effect. These results demonstrate an additive interaction between topical COX-2 inhibitors with intraperitoneal dexmedetomidine. These observations are significant for physicians to combine selective COX-2 inhibitors and dexmedetomidine in the management of pain.

In an effort to find an effective concentration that could minimize the side effect for clinical applications, and to understand the potential synergistic effect of hyperosmotic agents on optical clearing of gastric tissues, porcine stomach tissues (pyloric mucosa) applied with a mixed solution of glycerol and dimethyl sulfoxide (DMSO) are investigated with near infrared reflectance spectroscopy. Five chemical solutions, containing 80% glycerol, 50% DMSO, 50% glycerol with 10% DMSO, 20% DMSO and 30% DMSO, respectively, are prepared and studied; all of which show significant improvement in light transmittance, and thus reduction of the light scattering of tissue. It is found that, among the solutions investigated, 50% glycerol with 30% DMSO achieves the best clearing effect on the improvement of light penetration. Light transmittance is increased approximately 29% and diffuse reflectance decreased approximately 31% at 30 min after the topical application of 50% glycerol with 30% DMSO. This solution shows significantly stronger effect than 80% glycerol on optical clearing even though they have the same osmolarity. 80% glycerol leads to 23% increase of light transmittance and 24% decrease of diffuse reflectance. The mixed solution of 50% glycerol and 20% DMSO has less osmolarity than the solution of 80% glycerol, but they achieve a similar degree of optical clearing. In other words, the clearing effect of glycerol is enhanced by adding DMSO into it. It is suggested that membrane penetration and carrier effect of DMSO probably accounts for this synergistic effect.

Understanding the strengths and limitations of alternative models, such as the Tg.AC assay, for evaluation of the potential carcinogenicity of pharmaceuticals requires assessment of assay specificity through studies that specifically target biologically active compounds that are known to not be carcinogens in rodents. To identify drugs that might provoke a false positive response in the Tg.AC assay, we screened pharmaceuticals for in vitro induction of the gadd153 promoter and the zeta-globin promoter. We have previously found a high correlation between induction of the gadd153 promoter in HepG2 cells and activity in the Tg.AC assay. The three drugs selected through screening 99 noncarcinogenic pharmaceuticals were amiloride, dipyridamole, and pyrimethamine. A 26-week skin paint study was conducted in hemizygous Tg.AC mice with the three drugs at two doses selected by a 4-week dose range finding study. Evidence of systemic toxicity was observed in animals dosed chronically with pyrimethamine or amiloride, but no skin papillomas were observed in mice treated with amiloride, dipyridamole, or pyrimethamine for 26 weeks. All male mice and 80% of female mice treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) in acetone developed a maximal tumor burden. However, mice treated with TPA in a vehicle containing 2.4% DMSO had greatly reduced incidences of papillomas. In summary, the correct negative response was shown in the Tg.AC assay for three noncarcinogenic pharmaceuticals, which adds further favorable evidence of appropriate specificity of this model system. However, vehicle composition must be carefully selected because the outcome of this assay can be confounded by certain commonly used solvents.

Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic treatment against organophosphate nerve agent exposure, and were exposed to the insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET). The purpose of this study was to assess the effects of PB to modulate release of inflammatory biomarkers after topical chemical exposure to chemical mixtures containing permethrin and DEET applied in ethanol or water vehicles. Treatments were topically applied to isolated perfused porcine skin flaps (IPPSFs). Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential inflammatory effects after complex mixture application. IPPSFs (n=4/treatment) were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB. Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate low level organophosphate nerve agent exposure. Timed IPPSF venous effluent samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2) release. Effects on TNF-alpha were vehicle dependent. To probe the potential mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these studies suggest that systemic exposure to PB suppressed IL-8 release at multiple time points in two skin model systems. This interaction merits further study.

Topical drugs avoid many of the problematic side effects of systemic agents. Immersion of the tail of a mouse into a solution of dimethyl sulfoxide (DMSO)-containing morphine produces a dose-dependent, naloxone-sensitive, analgesia (ED(50) 6.1 mM; CL 4.3, 8.4) limited to the portion of the tail exposed to the drug. DMSO alone in this paradigm had no analgesic activity. Like morphine, the opioids levorphanol (ED(50) 5.0 mM; CL 3.8, 7.8) and buprenorphine (ED(50) 1. 1 mM; CL 0.7, 1.5) were effective topical analgesics. Lidocaine also was active in the tail-flick assay (ED(50) 2.5 mM; CL 2.0, 3.4), with a potency greater than morphine. As expected, the free base of lidocaine was more potent than its salt. Combinations of a low dose of lidocaine with a low dose of an opioid yielded significantly greater than additive effects for all opioids tested. Isobolographic analysis confirmed the presence of synergy between lidocaine and morphine, levorphanol and buprenorphine. These studies demonstrate a potent interaction peripherally between opioids and a local anesthetic and offer potential advantages in the clinical management of pain.

Malondialdehyde (MDA) is a product of lipid peroxidation (LPO). In combination with CuCl2 MDA induced single strand breaks in PM2 DNA whereas MDA or CuCl2 alone had no effect. Cu(II) oxidized MDA by a radical mechanism under formation of Cu(I). DNA strand break induction was inhibited by catalase (98%), neocuproine (76%) and DMSO (61%). The synergistic damaging effect of MDA and Cu(II) was also demonstrated in human fibroblasts measured by alkaline elution. The combination MDA/CuCl2 caused extensive DNA breakage while neither MDA nor CuCl2 alone induced DNA damage within the cell. Synergistic cytotoxic effects were observed 18 h after a simultaneous treatment of the cells with MDA and CuCl2 for 1 h.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013. OBJECTIVES: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS. METHODS: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment. MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence

OBJECTIVE: To compare the efficacy and safety of topical nonsteroidal anti-inflammatory drugs (NSAIDs) against placebo and active controls for improving pain and physical function of patients with knee osteoarthritis (OA). We hypothesize that topical NSAIDs will be safe and effective for relieving symptoms in patients with knee OA. METHODS: The authors performed a systematic review according to the PRISMA guidelines, searching PubMed, EMBASE, and Cochrane databases. Randomized control trials that investigated topical NSAIDs that are widely available in many countries against both placebo and active controls in primary knee osteoarthritis were included. Studies that investigated other treatment modalities or treated nonspecific OA were excluded. A meta-analysis was performed to quantify the effect sizes and heterogeneity of the NSAIDs used. RESULTS: Upon initial search, 259 records were identified with 18 studies remaining after duplicate removal, abstract, and full-text screening. All NSAIDs demonstrated statistically significant reduction in at least one parameter of OA symptoms. The majority of included studies (66.7%) evaluated diclofenac. In the meta-analysis, standardized mean differences (SMD) of topical NSAIDs versus placebo were calculated and interpreted as having moderate effect size for improvement in pain (0.365, 95% confidence interval (CI) 0.240, 0.490) and physical function (0.354, 95% CI 0.268, 0.493). With regard to safety, studies that used patches or dimethyl sulfoxide (DMSO) in the carrier reported a higher incidence of adverse events (AEs) than other carriers. Skin AEs were higher in the treatment group than the placebo group and gastrointestinal AEs were lower in the treatment group than placebo. CONCLUSION: Topical diclofenac and ketoprofen are the most rigorously studied topical NSAIDs in the treatment of knee OA and have demonstrated the most significant reduction in pain and improvement of function. Ibuprofen was effective for pain relief and physical function improvement, but more high-powered studies are needed to make a confident comparison of efficacy. Additionally, the 'carrier' used to deliver the topical NSAID has an impact on th

Aim: The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults.Methods: We used standard Cochrane methods. Searches were conducted in MEDLINE, EMBASE and The Cochrane Register of Studies; date of the final search was November 2018. Included studies were randomized, double blinded, with ten or more participants per treatment arm. The primary outcome of "clinical success" was defined as participant-reported reduction in pain of at least 50%. Details of adverse events (AEs) were recorded.Results: For acute pain, 23 studies (5170 participants) were included. Compared to placebo, number needed to treat (NNT) for different formulations were as follows: diclofenac plaster, 4.7 (95% CI 3.7-6.5); diclofenac plaster with heparin, 7.4 (95% CI 4.6-19); and diclofenac Emulgel, 1.8 (95% CI 1.5-2.1). 4.1% (78/1919) reported a local AE. For chronic pain, 21 studies (26 publications) with 5995 participants were included. Formulations included gel, solution with or without DMSO, emulsion and plaster. A clinical success rate of ∼60% (NNT 9.5 [95% CI 7-14.7]) was achieved with a variety of formulations. Local AEs (∼14%) were similar for both diclofenac and placebo.Conclusion: This systematic review of 11,000+ participants demonstrates that topical diclofenac is effective for acute pain, such as sprains, with minimal AEs. The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain but with a higher NNT (worse) compared with acute pain. Formulation does play a part in effectiveness but needs further studies.

BACKGROUND: Pressure ulcers, localised injuries to the skin or underlying tissue, or both, occur when people cannot reposition themselves to relieve pressure on bony prominences. These wounds are difficult to heal, painful, expensive to manage and have a negative impact on quality of life. Prevention strategies include nutritional support and pressure redistribution. Dressing and topical agents aimed at prevention are also widely used, however, it remains unclear which, if any, are most effective. This is the first update of this review, which was originally published in 2013. OBJECTIVES: To evaluate the effects of dressings and topical agents on pressure ulcer prevention, in people of any age, without existing pressure ulcers, but considered to be at risk of developing one, in any healthcare setting. SEARCH METHODS: In March 2017 we searched the Cochrane Wounds Group Specialised Register, CENTRAL, MEDLINE, MEDLINE (In-Process & Other Non-Indexed Citations), Embase, and EBSCO CINAHL Plus. We searched clinical trials registries for ongoing trials, and bibliographies of relevant publications to identify further eligible trials. There was no restriction on language, date of trial or setting. In May 2018 we updated this search; as a result several trials are awaiting classification. SELECTION CRITERIA: We included randomised controlled trials that enrolled people at risk of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias and extracted data. MAIN RESULTS: The original search identified nine trials; the updated searches identified a further nine trials meeting our inclusion criteria. Of the 18 trials (3629 participants), nine involved dressings; eight involved topical agents; and one included dressings and topical agents. All trials reported the primary outcome of pressure ulcer incidence.Topical agentsThere were five trials comparing fatty acid interventions to different treatments. Two trials compared fatty acid to olive oil. Pooled evidence shows that there is no clear difference in pressure ulcer incidence between groups, fatty acid versus olive oil (2 trials, n=1060; RR 1.28, 95% CI 0.76 to 2.

Complex regional pain syndrome (CRPS) is a descriptive term for a complex of symptoms and signs typically occurring following trauma of the extremity. Typical symptomatology includes severe pain, swelling, vasomotor instability and functional impairment of the affected limb. At present there is no one, effective method of treatment of the condition. A large number of treatments have been investigated but major multicentre randomized controlled trials are lacking. This study presents the results of a systematic review of the evidence on effectiveness of treatment methods in CRPS. It is a follow-up to earlier reviews of randomized controlled trials on CRPS treatment published between 1966 and 2016. RESULTS: The review of randomized controlled trials showed that only bisphosphonates were found to give uniformly positive effects, statistically significantly better than placebo. Improvement has been reported with topical dimethyl sulfoxide, systemic steroids, spinal cord stimulation and graded motor imagery/mirror therapy programmes. The available evidence does not support the use of other treatments in CRPS, however they are frequently used in clinical practice. CONCLUSION: Available evidence, although numerous, does not necessarily reflect what is truly effective and what is sham in the management of CRPS.

BACKGROUND: Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode. OBJECTIVES: To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (from inception to April 2016), MEDLINE (from inception to April 2016), the Specialised Register of the Cochrane Sexually Transmitted Infections Review Group (from inception to April 2016), EMBASE (from inception to April 2016), PsycINFO (from inception to April 2016), CINAHL (from inception to April 2016), LILACS (from inception to April 2016), AMED (from inception to April 2016), and the Alternative Medicines Specialised Register (from inception to April 2016). We handsearched a number of relevant journals, searched reference lists of all included studies, databases of ongoing trials, and other Internet databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) on participants with first-episode genital herpes. We excluded vaccination trials, and trials in which the primary objective assessed a complication of HSV infection. DATA COLLECTION AND ANALYSIS: All studies written in English were independently assessed by at least two review authors for inclusion, risk of bias for each trial, and to extract data. Studies requiring translation were assessed for inclusion, trial quality, and data extraction by external translators. MAIN RESULTS: We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials