Effects of topical diclofenac plus heparin (DHEP+H plaster) on somatic pain sensitivity in healthy subjects with a latent algogenic condition of the lower limb.

OBJECTIVE: To evaluate whether a diclofenac epolamine + heparin topical (plaster) is more effective than diclofenac plaster alone in reducing deep somatic hyperalgesia in subjects without spontaneous pain and whether the effect is linked to or independent of the anti-edematous action of heparin. DESIGN: Prospective, double-blind, randomized and controlled, four-arm parallel design trial. SUBJECTS: One hundred and four patients (84 women, 20 men, mean age 42.2 ± 13.3 years), with deep somatic hyperalgesia in one thigh, randomly assigned to one of 4 groups of 26 each. INTERVENTION: Each group underwent one of the following plaster treatments on one thigh: diclofenac+heparin; diclofenac; heparin; placebo, for 7 days, renewing the plaster every 24 hours. OUTCOME MEASURES: Before treatment (day 1), at day 4 and day 8, assessment of (a) pressure and electrical pain thresholds of vastus lateralis and overlying subcutis and skin; and (b) structure/thickness of subcutis and muscle with ultrasounds at the same level. RESULTS: During treatment, in placebo and heparin, no significant threshold changes, except subcutis thresholds which increased slightly (P < 0.02); in diclofenac and diclofenac+heparin, significant increase in all thresholds (0.0001 < P < 0.04). Electrical muscle pain thresholds increased significantly more in diclofenac+heparin than in diclofenac, heparin, and placebo (0.0001 < P < 0.04). In all groups: no edema and thickness changes at ultrasounds in muscle and subcutis. CONCLUSIONS: Topical diclofenac+heparin is significantly more effective than diclofenac alone in reducing muscle hyperalgesia in subjects without spontaneous pain, independently of the anti-edematous action of heparin. The results provide a rationale for the use of diclofenac+heparin also in algogenic conditions without evident signs of injury/edema/hematoma.

Effect of the new 75-mg orodispersible film of sildenafil on erection and sexual quality of life: insights from an observational study.

Background: The newly devised orodispersible film (ODF) of sildenafil is the first phosphodiesterase type 5 inhibitor (PDE5i) available in a 75-mg dose. This intermediate dose and the particular properties of the ODF formulation can improve the clinical management of erectile dysfunction (ED) patients. Aim: We investigated the effects of the sildenafil ODF 75-mg dose on both sexual quality of life and erectile function based on the results from an observational study in daily practice in Italy. Methods: This study was a post hoc analysis of results from an observational, real-life study carried out in ED patients at 6 treatment centers in Italy. All subjects were asked to take the prescribed dose of sildenafil ODF at inclusion (visit 1) and to return for a control visit (visit 2) to confirm or adapt the prescribed dose after a minimum of 4 weeks. An end of study control visit (visit 3) was performed after additional 4 weeks. Outcomes: Erectile function, assessed by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain; sexual quality of life, measured using the sexual quality of life instrument for men (SQoL-M). Results: Among the 36 subjects initially recruited for the 75-mg dose, 5 patients dropped out of the study (2 at visit 2 and 3 at visit 3), none of whom due to treatment inefficacy or serious adverse events. At visit 2, the mean (SD) IIEF-EF scores significantly increased (∆ = 7.97 [4.71], P < 0.0001) as SQoL-M scores also did (∆ = 10.76 [10.46], P < 0.0001). At visit 3, IIEF-EF and SQoL-M scores were still significantly improved compared to baseline (∆ = 10.64 [7.01], P < 0.0001, and ∆ = 18.15 [12.32], P < 0.0001, respectively). By ANCOVA, we found no significant effects for age, BMI, previous use of PDE5i, presence of metabolic comorbidities, or smoking habits on study outcomes at both visits 2 and 3. Clinical implication: The new 75-mg ODF sildenafil formulation is a safe and effective treatment for ED, significantly improving both erectile function and sexual quality of life in patients undergoing treatment. Strengths and limitations: This is the first study assessing the efficacy of the sildenafil ODF 75-mg dose in a real-life setting. However, the small sample size, possible underlying cultural factors, and limited availability of clinically relevant data may have affected the reliability of our results. Conclusion: The use of the 75 mg ODF formulation for sildenafil represents an effective and safe novel treatment option for ED patients.

Development and Validation of IBSA Photographic Scale for the Assessment of Neck Laxity.

OBJECTIVE: To describe the development and validation of the 5-grade photographic IBSA Neck Laxity Scale. METHODS: The scale was developed from 2 real images, which led to the creation of 5 morphed images, representing different degrees of severity of laxity of the neck. For validation, a set of 50 images (25 real and 25 morphed) was created and sent for evaluation to 6 trained raters (physicians) in 2 rounds, 1 month apart. Raters had to assess each image according to the 5-image scale. Inter-rater and intra-rater reliability in both rounds was evaluated. RESULTS: As to intra-rater reliability, single rater kappa scores between 0.69 and 0.87, and a global kappa score of 0.78 were observed. Inter-rater agreement was measured by means of the intra-class correlation coefficient and scores higher than 0.85 were reported, indicating excellent reliability. CONCLUSION: IBSA Neck Laxity Scale is a validated and reliable scale.

Development and Validation of IBSA Photographic Scale for the Assessment of Inner Upper Arm Laxity.

OBJECTIVE: To describe the development and validation of the 5-grade photographic IBSA inner upper arm scale. METHODS: From 2 real-life pictures, a scale made up of 5 morphed images showing increasing severity of inner upper arm laxity was created. For validation, a set of 50 images (half of which real and the other morphed) was developed and sent to 5 trained physicians in two rounds 30 days apart. Raters' task was to make a selection of each image according to the given scale. Inter-rater and intra-rater reliability were evaluated in both rounds. RESULTS: As to intra-rater reliability, single-rater kappa scores between 0.74 and 1.00 and a global kappa score of 0.846 were observed, while inter-rater agreement was calculated with intra-class correlation coefficient reporting scores higher than 0.91, which indicate excellent reliability. CONCLUSION: IBSA inner upper arm laxity scale proved to be a validated and reliable tool.

Systolic vs diastolic blood pressure control in the hypertensive patients of the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni.

BACKGROUND: Previous studies have shown that in the treated fraction of the hypertensive population, blood pressure (BP) control is less common for systolic BP (SBP) than for diastolic BP (DBP) as measured in the physician's office. Whether this phenomenon is artifactually attributable to a temporary increase in BP owing to a "white-coat" effect or represents a true rarity of SBP control in daily life is unknown. METHODS: Data were obtained from the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study population, which involved individuals ranging in age from 25 to 74 years who were representative of the residents of Monza (a city near Milan, Italy) and who were stratified according to sex. Office (an average of 3 sphygmomanometric measurements), home (an average of morning and evening self-measurements using a semiautomatic device), and 24-hour ambulatory (average of measurements performed every 20 minutes during the day and at night) BP values were obtained in all study subjects. In the treated hypertensive patients, BP was regarded as controlled if office values were less than 140 (SBP) or 90 (DBP) mm Hg. Home and 24-hour average SBP and DBP were regarded as controlled if the values were lower than 132/83 and 125/79 mm Hg, respectively. RESULTS: In the study participants (n = 2051), the number of patients with hypertension who were receiving antihypertensive treatment was 398, or approximately 42% of all individuals with hypertension. In-office SBP control by treatment was less frequent than DBP control (29.9% vs 41.5%, P<.05). This was also the case when home and 24-hour SBP and DBP control was considered (38.3% vs 54.6% and 50.8 vs 64.9%, respectively, P<.05 for both). CONCLUSIONS: In the PAMELA population, SBP control by treatment was much less frequent than DBP control by treatment. This was the case not only for office BP values but also for home and 24-hour BP values, demonstrating that inadequate SBP control is not limited to artificial BP-measuring methods but occurs in daily life.

Diclofenac epolamine topical patch relieves pain associated with ankle sprain.

BACKGROUND: Sports-related injuries, such as sprains and strains, commonly occur during exercise and athletic events. Current therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs), which have a high incidence of upper gastrointestinal side effects. The present study assessed the efficacy and safety of the diclofenac epolamine topical patch (DETP, 1.3%), a topical NSAID for the treatment of acute minor sprains and strains. METHODS: This multicenter, randomized, placebo-controlled clinical study enrolled adult patients (n = 134) with acute ankle pain (due to a minor sprain) occurring less than 48 hours prior to entering the study. Patients were treated with either the DETP or a placebo topical patch daily for seven days. Pain intensity was evaluated during the first six hours after application of the patch, and on treatment days 1, 2, 3, and 7. RESULTS: Patients treated with the DETP experienced a significantly greater reduction in pain associated with their ankle injury compared with placebo, beginning four hours after the first patch application (P = 0.02). The DETP was well tolerated and was comparable with placebo in terms of safety. CONCLUSION: Overall, the results of this study demonstrate that the DETP is an effective analgesic for local treatment of pain in mild acute ankle sprain.

Pooled analysis of clinical trial data evaluating the safety and effectiveness of diclofenac epolamine topical patch 1.3% for the treatment of acute ankle sprain.

This pooled analysis assessed the efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) for the treatment of acute mild-to-moderate ankle sprain. Data from 2 randomized, double-blind, placebo-controlled studies enrolling 274 male and female patients aged 18 to 65 years with acute ankle sprain were pooled and evaluated. The primary end point was pain reduction on movement assessed using a 100 mm visual analog scale (VAS). Safety and tolerability were also assessed. Beginning approximately 3 hours after initial treatment, DETP-treated patients experienced statistically significant and sustained lower mean VAS scores in pain intensity on movement (mean ± SD, 54.1 ± 20.0 mm versus 60.3 ± 16.8 mm) compared with placebo-treated patients, representing a 20% versus 13% reduction in VA S pain scores from baseline (P = 0.012). This statistically significant difference in mean VAS score was maintained through day 7 (9.4 ± 14.4 mm versus 18.4 ± 18.2 mm, P < 0.0001). The DETP and placebo patches were well tolerated. These results further confirm the efficacy and safety of DETP for the treatment of acute pain from ankle sprains.

OARSI/OMERACT initiative to define states of severity and indication for joint replacement in hip and knee osteoarthritis. An OMERACT 10 Special Interest Group.

OBJECTIVE: To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of "need for joint replacement surgery," for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). METHODS: New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons' indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. RESULTS: In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%-12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0-100) + physical function (0-100) > 80]. CONCLUSION: These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define "nonresponders" to disease-modifying drugs in OA clinical trials.

Prevalence of left ventricular hypertrophy in hypertensive patients without and with blood pressure control: data from the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni.

Previous studies have shown that in the population, only a minority of treated hypertensive patients achieve blood pressure (BP) control. Whether and to what extent this inadequate control has reflection on hypertension-related organ damage has never been systematically examined. In 2051 subjects belonging to the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) Study population, we measured office, home, and 24-hour ambulatory BP values, together with echocardiographic left ventricular mass and wall thickness. Based on the fraction on antihypertensive treatment and on measurements of increased or normal office, home, or 24-hour ambulatory BP values, subjects were classified as normotensives, untreated hypertensives, treated hypertensives with inadequate BP control, and treated hypertensives with effective BP control. Compared with values in the normotensive group, left ventricular mass index, left ventricular wall thickness, and prevalence of left ventricular hypertrophy were markedly increased not only in untreated hypertensive patients but also in treated hypertensives with inadequate BP control. Echocardiographic abnormalities were less in treated hypertensives with BP control than in patients with inadequate BP control, but values were still clearly greater than in normotensive subjects. This was the case regardless whether BP control was assessed by office, home, and/or ambulatory values. Our data provide evidence that in the hypertensive fraction of the population, cardiac structural alterations can be frequently found in both the presence and absence of antihypertensive treatment. They also imply that even effective treatment of hypertension does not allow complete reversal of the cardiac organ damage characterizing high BP states.