Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers

Objectives: To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster.

Methods: This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40.

Results: The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38.

Conclusions: The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.     

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers

Objective: Ibuprofen is a commonly used non-steroidal anti-inflammatory drug administered to treat injuries, joint pain, and recurrent muscular skeletal pain. The aim of this study was to determine the cutaneous irritancy of a medicated ibuprofen plaster compared with a placebo plaster in healthy volunteers.

Methods: Healthy volunteers (N = 31) were treated at the same time with one ibuprofen and one placebo plaster. The ibuprofen and placebo plaster were applied in a randomized fashion to sites on the left or right side of subjects’ lower backs. At each scheduled visit, the plasters and applications sites were assessed for degree of adhesion and skin irritancy, respectively. The plasters were applied on study Days 1, 2, 3, 5, 8, 10, 12, 15, 17, and 19, with final plaster removal on Day 22.

Results: The ibuprofen medicated plaster compared with placebo had a lower percentage of Grade 1 (23.3% vs. 46.7%, respectively), Grade 2 (10% vs. 20%), and ≥Grade 3 (3% vs. 16.1%) irritancy scores after 21 days of application. The mean irritation score across the study was 0.40 for the ibuprofen medicated plaster and 1.18 for the placebo plaster. The irritation score on Day 22 of the study was 0.53 for the ibuprofen medicated plaster and 1.50 for placebo. The placebo plaster was associated with a higher number of stopped applications due to Grade 3 or above skin reactions compared with the ibuprofen medicated plaster (5 vs. 1, respectively).

Conclusion: The ibuprofen medicated plaster was well tolerated and was associated with lower irritancy than the placebo plaster.     

Evaluation of lorcaserin on progression of prediabetes to type 2 diabetes and reversion to euglycemia

Objectives: Lorcaserin is a selective 5-HT_2C (5-hydroxytryptamine 2C) receptor agonist indicated for weight management. Here, we assess the impact of lorcaserin on progression from prediabetes to type 2 diabetes (T2D) and on reversion from prediabetes to euglycemia.

Methods: This is a post hoc analysis of pooled data from two Phase 3 studies, BLOOM and BLOSSOM (N = 6136), evaluating the impact of lorcaserin on weight and glycemic parameters over 52 weeks in the subpopulation of obese/overweight subjects with prediabetes, alternately defined by fasting plasma glucose (FPG) 100–125 mg/dl or glycated hemoglobin (HbA1c) 5.7–6.4% at baseline.

Results: At Week 52, in the subpopulation with prediabetes, nearly twice as many lorcaserin-treated subjects achieved ≥5% weight loss versus placebo (HbA1c: 55.6% vs. 27.5%, p < 0.001; FPG: 52.8% vs. 28.8%, p < 0.001), and a significantly lower percentage of lorcaserin-treated subjects progressed to T2D versus placebo based on HbA1c (lorcaserin 3.2%, placebo 5.0%, p = 0.032) but not FPG (lorcaserin 1.6%, placebo 2.6%, p = 0.227). A significantly greater proportion of lorcaserin-treated subjects versus placebo also reverted to euglycemia based on both HbA1c (lorcaserin 40%, placebo 29.5%, p < 0.001) and FPG (lorcaserin 52.4%, placebo 46.5%, p = 0.047).

Conclusion: In subjects with prediabetes, lorcaserin may contribute to weight loss and improve glycemic parameters, and thus may help with preventing progression to T2D and promoting reversion to euglycemia.

Clinical trial registration: www.clinicaltrials.gov identifiers are NCT00395135 (BLOOM) and NCT00603902 (BLOSSOM)     

Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin

Objective: The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin.

Methods: The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo).

Results: Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher’s exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset).

Conclusion: B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action.

Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676     

Impact of shoulder internal rotation on normal sensory response during ulnar nerve-biased neurodynamic testing of asymptomatic individuals

Objective: To determine if substitution of shoulder internal rotation for external rotation during the upper limb neurodynamic test (ULNT₃) evokes comparable ulnar nerve sensory responses in asymptomatic individuals.

Methods: Range of motion, quality, quantity, and distribution of sensory responses in 50 asymptomatic individuals during the traditional ULNT₃ were compared to identical measures during an experimental maneuver using shoulder internal rotation. Quality and quantity of sensory responses were recorded using a 10-cm visual analog scale.

Results: Means of sensory responses for traditional and experimental maneuvers, respectively, were as follows: stretching, 3.84 ± 8.85 and 5.38 ± 2.85 cm; burning, 1.82 ± 2.82 and 2.50 ± 3.10 cm; tingling, 2.13 ± 3.12 and 2.18 ± 2.97 cm; and numbness, 1.04 ± 2.17 and 1.01 ± 2.03 cm. A moderate to strong correlation (ICC = 0.51–0.86) was shown to exist between maneuvers; this relationship was significant (p = .001).

Discussion: Results of this study provide evidence that there was no appreciable difference in sensory responses with regard to burning and tingling when substituting shoulder internal rotation for external rotation during the ULNT₃. The results also suggest that there were only marginal differences in the sensory responses of stretching and numbness during the same substitution.

Conclusion: Patients who have limited glenohumeral external rotation due to pain, instability, and/or articular limitation may benefit from this substitution when presenting with signs of ulnar nerve pathodynamics. Further research will be needed to validate this maneuver in a symptomatic population.

Level of Evidence: Level 2b.     

Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks

Objectives: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been associated with weight loss in a broad range of patients with type 2 diabetes mellitus (T2DM). This analysis further evaluated changes in body weight and composition with canagliflozin in two 104-week, Phase 3 studies.

Methods: In Study 1, patients aged 18–80 years (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride as add-on to metformin for a 52-week core treatment period, followed by a 52-week extension period. In Study 2, patients aged 55–80 years (N = 714) received canagliflozin 100 or 300 mg or placebo added to stable background antihyperglycemic agents for a 26-week core treatment period, followed by a 78-week extension period. Percent change from baseline in body weight; proportion of patients with any weight loss, ≥5% weight loss, and ≥10% weight loss; change in body mass index (BMI) and waist circumference; change in body weight across weight-loss quartiles; and changes in body composition were evaluated in both studies.

Results: Canagliflozin 100 and 300 mg provided sustained weight loss versus either glimepiride or placebo over 104 weeks. More patients experienced any weight loss and ≥5% weight loss with canagliflozin versus comparator. Across the 3 highest weight-loss quartiles, canagliflozin provided greater weight loss versus glimepiride or placebo. BMI and waist circumference reductions were observed with canagliflozin 100 and 300 mg versus either glimepiride or placebo over 104 weeks; more patients had BMI or waist circumference reductions with canagliflozin versus comparator. Body composition analysis indicated that the majority of weight loss was due to loss of fat mass. Canagliflozin was generally well tolerated, with increased incidence of adverse events related to the SGLT2 inhibition mechanism.

Conclusions: Canagliflozin 100 and 300 mg provided sustained reductions in body weight, BMI, and waist circumference in a greater proportion of patients with T2DM versus glimepiride or placebo over 104 weeks.

Trial registration: ClinicalTrials.gov NCT00968812, NCT01106651     

A randomized,double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design

Objectives: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.

Results: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS–placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.

Conclusions: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.     

Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment

Objectives: Evaluate the efficacy, duration of effect, and safety of 25 mg SHP465 mixed amphetamine salts (MAS) extended-release versus placebo in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Adults (18–55 years) with ADHD and with ADHD Rating Scale-IV (ADHD-RS-IV) scores ≥24 were randomized to treatment in a double-blind, 2-period, 2-treatment crossover study utilizing the Adult Workplace Environment (AWE), as described by Wigal and Wigal (J Atten Disord 2006;10:92–111). On day 7 of each 7-day treatment period, efficacy was assessed during a 16.5-hour postdose period. The primary endpoint, Permanent Product Measure of Performance (PERMP) total score, was analyzed in the intent-to-treat population using a mixed linear model of analysis of variance. Secondary endpoints, for which the study was not powered, included PERMP problems attempted and answered correctly, ADHD clinician ratings based on counselor observations and inputs during the Time Segment Rating System (Co-ADHD-RS TSRS), and the ADHD self-rating scale (ADHD-SRS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.

Results: The least squares mean (95% CI) treatment difference (SHP465 MAS–placebo) for PERMP total score significantly favored SHP465 MAS over placebo when averaged across all postdose assessments (19.29 [10.95, 27.63]; P < 0.0001), with significant treatment differences favoring SHP465 MAS over placebo observed at 4–16 hours postdose (all P < 0.01). TEAEs observed with SHP465 MAS (≥5% of participants) included insomnia, decreased appetite, dry mouth, headache, and anorexia. Mean pulse and blood pressure increases with SHP465 MAS exceeded those of placebo.

Conclusions: SHP465 MAS (25 mg) was superior to placebo on PERMP total score, with treatment differences observed from 4 to 16 hours postdose; nominal treatment differences on the ADHD-SRS, but not the Co-ADHD-RS TSRS, were also observed. The safety and tolerability profile of SHP465 MAS was similar to previous reports for SHP465 MAS and other long-acting stimulants.

Clinical trials registry: clinicaltrials.gov (NCT00202605; https://clinicaltrials.gov/ct2/show/NCT00202605)     

Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes

Objectives: To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks.

Methods: Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction ≥5% at Week 52 were evaluated. Safety was assessed based on adverse event reports.

Results: Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction ≥5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated.

Conclusions: A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks.

Clinical trial registration: www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.     

Efficacy of methylnaltrexone for the treatment of opiod-induced constipation: a meta-analysis and systematic review

Objective: Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor antagonist, is an effective treatment of opioid induced constipation (OIC) without affecting centrally mediated analgesia. Our objective was to conduct a review and meta-analysis to evaluate the efficacy of methylnaltrexone for treatment of OIC, as well as to provide a clinical discussion regarding newly developed alternatives and provide the current treatment algorithm utilized at our institution.

Methods: We performed a systematic review and meta-analysis of randomized control trials using Cochrane Collaboration Databases and MEDLINE from 2007-present. Literature related to methylnaltrexone, opioids, opioid receptors, opioid antagonists, opioid-induced constipation were reviewed. A meta-analysis was completed with the primary outcome of rescue-free bowel movement (RFBM) within four hours of administration. All pooled analyses were based on random-effects models.

Results: 1239 patients were analyzed; 599 received methylnaltrexone and 640 received placebo. With a 95% CI calculated, the true risk difference is between 0.267 and 0.385, demonstrating a statistically significant difference in RFBM between treatment and placebo groups (p < 0.0001). Both the 0.15 mg/kg, 0.30 mg/kg doses every other day, and 12 mg/day dose were found to have increased risk of RFBM compared to placebo.

Conclusion: Results support the use of methylnaltrexone. Furthermore, the use of methylnaltrexone to induce laxation may decrease use of health care resources, increase work productivity, and improve cost utilization. New treatments have been made available; however, controlled clinical studies are needed to demonstrate long–term efficacy, safety and cost–effectiveness. Possible limitations of this study include the relatively small number of randomized, placebo-controlled trials investigating the efficacy of methylnaltrexone versus placebo. There is also the possibility of publication bias, which may lead to overestimating the efficacy of methylnaltrexone in treating OIC.     

Pulmonary function in pectus excavatum patients before repair with the Nuss procedure

Objectives: Whether the origin of symptoms in pectus excavatum patients (Pex) is related to reduced pulmonary function or impaired cardiovascular performance is debatable. However, pulmonary function testing (PFT) is still part of the evaluation prior to surgical repair in Pex. The purpose of this study was to corroborate our hypothesis that the majority of Pex that qualified for surgery present preoperatively with normal or close to normal PFT.

Methods: After institutional review board approval, preoperative PFT data of Pex who underwent surgical repair were analyzed retrospectively: total lung capacity (TLC), vital capacity (VC), functional residual capacity, forced expiratory volume in 1 second (FEV₁) and maximal expiratory flow at 25% of FVC (MEF₂₅).

Results: 82 patients aged from 9 to 27 years (average, 15 years) underwent PFT. A restrictive pattern (VC<80%) was observed in 45%, an obstructive pattern (FEV1 < 75 %) in 35%, and a normal total lung capacity in 62% of the Pex. No significant correlation was noted between the increasing severity of the Haller index and the PFT.

Conclusion: Adolescent Pex without relevant respiratory symptoms have nearly a normal lung function. We suggest to skip PFT from the routine preoperative assessment in asymptomatic Pex.     

Predictors of future exacerbation risk in patients with asthma

Objectives: Although modern treatment of asthma improves asthma control, some patients still experience exacerbations. The aim of the present study was to detect predictors of asthmatic exacerbations

Methods: We included patients with asthma followed up in asthma clinics of 2 tertiary University hospitals. Demographic and functional characteristics, levels of exhaled NO, and inflammatory biomarkers (IL-13, ΕCP και IL-8) and cell counts in induced sputum were recorded at baseline. Measurements were performed with the patients in stability and were considered as their personal best. Patients received optimal treatment with good compliance and were followed up for 1 year for asthma exacerbations occurrence. Evaluation of the effect of recorded parameters on asthma exacerbations was performed with univariate and multivariate Poisson regression analysis.

Results: 171 patients (118 female) with bronchial asthma (mean age 51.6 ± 13.2 years) were included in the study. The mean number of exacerbations in 1 year of follow up was 0.4 ± 0.8 while the majority of patients (71.9%) did not experience any exacerbation. In multivariate Poisson Regression analysis only 3 characteristics were predictors of future exacerbations: FEV₁ [IRR(95% CI)], [0.970(0.954–0.987)], p = 0.001, high BMI [1.078(1.030–1.129)], p = 0.001, and the need for permanent treatment with oral corticosteroids for asthma control maintenance [2.542(1.083–5.964)], p = 0.032

Conclusion: Optimal guideline-based asthma management results in minimal occurrence of exacerbations in the majority of patients. Predictors of exacerbations are low FEV₁ levels in stability, high BMI and the need for permanent treatment with oral corticosteroids.     

Effect size comparison of ketorolac nasal spray and commonly prescribed oral combination opioids for pain relief after third molar extraction surgery

Objective: Opioids are frequently used for treatment of moderate to severe short-term pain, but concerns exist about this treatment approach. Ketorolac tromethamine nasal spray, a nonsteroidal anti-inflammatory, is indicated for the short-term management of moderate to moderately severe pain requiring analgesia at the opioid level. However, there are no direct comparison studies between ketorolac nasal spray and opioids. The objective of this study was to use an effect size analysis to compare the effectiveness of ketorolac nasal spray with oral combination opioid formulations in treating moderate to severe short-term pain.

Methods: An effect size analysis of three randomized, double-blind, placebo-controlled studies of third molar extraction surgery compared pain relief with ketorolac nasal spray and commonly prescribed combination opioids including hydrocodone/acetaminophen (APAP), oxycodone/APAP, oxycodone/ibuprofen and tramadol HCl/APAP. Effect size comparisons were made using total pain relief scores (TOTPAR6 or TOTPAR8; the weighted sum of pain relief scores through 6 or 8 h). Pain relief was measured using a five-point categorical rating scale (0 = none; 4 = complete). The effect size equivalent correlation, r, was determined using an online effect size calculator. The treatment effect size r compared with placebo was classified using established criteria (small = 0.20–0.49, moderate = 0.50–0.79 and large = ≥ 0.80).

Results: TOTPAR6 data indicated a moderate effect size for ketorolac nasal spray 31.5 mg (0.51) and oxycodone/ibuprofen 5/400 mg (0.64) and a small effect size for hydrocodone/APAP 7.5/500 mg (0.24) and oxycodone/APAP 5/325 mg (0.32). TOTPAR8 data indicated small effect sizes for ketorolac nasal spray (0.48), hydrocodone/APAP 10/650 mg (0.43), tramadol HCl/APAP 75/650 mg (0.35) and tramadol HCl/APAP 37.5/325 mg (0.17).

Conclusion: The treatment effect sizes of ketorolac nasal spray were similar to or higher than the opioid comparators after third molar surgery, a well-accepted pain model. These results support ketorolac nasal spray as an effective treatment for moderate to moderately severe short-term pain.     

Increased mechanosensivity of the greater occipital nerve in subjects with side-dominant head and neck pain – a diagnostic case-control study

Objectives: To investigate differences in pressure pain thresholds (PPTs) and longitudinal mechanosensitivity of the greater occipital nerve (GON) between patients with side-dominant head and neck pain (SDHNP) and healthy controls. Evaluation of neural sensitivity is not a standard procedure in the physical examination of headache patients but may influence treatment decisions.

Methods: Two blinded investigators evaluated PPTs on two different locations bilaterally over the GON as well as the occipitalis longsitting-slump (OLSS) in subjects with SDHNP (n = 38)) and healthy controls (n = 38).

Results: Pressure pain sensitivity of the GON was lower at the occiput in patients compared to controls (p = 0.001). Differences in pressure sensitivity of the GON at the nucheal line, or between the dominant headache side and the non-dominant side were not found (p > 0.05). The OLSS showed significant higher pain intensity in SDHNP (p < 0.001). In comparison to the non-dominant side, the dominant side was significantly more sensitive (p = 0.004).

Discussion: Palpation of the GON at the occiput and the OLSS may be potentially relevant tests in SDHNP. One explanation for an increased bilateral sensitivity may be sensitization mechanisms. Future research should investigate the efficacy of neurodynamic techniques directed at the GON.

Level of Evidence: 3b.     

Inter-tester reliability of selected clinical tests for long-lasting temporomandibular disorders

Objective: Clinical tests used to examine patients with temporomandibular disorders vary in methodological quality, and some are not tested for reliability. The purpose of this cross-sectional study was to evaluate inter-tester reliability of clinical tests and a cluster of tests used to examine patients with long-lasting temporomandibular disorders.

Methods: Forty patients with pain in the temporomandibular area treated by health-professionals were included. They were between 18–70 years, had 65 symptomatic (33 right/32 left) and 15 asymptomatic joints. Two manual therapists examined all participants with selected tests. Percentage agreement and the kappa coefficient (k) with 95% confidence interval (CI) were used to evaluate the tests with categorical outcomes. For tests with continuous outcomes, the relative inter-tester reliability was assessed by the intraclass-correlation-coefficient (ICC_3,1, 95% CI) and the absolute reliability was calculated by the smallest detectable change (SDC).

Results: The best reliability among single tests was found for the dental stick test, the joint-sound test (k = 0.80–1.0) and range of mouth-opening (ICC_3,1 (95% CI) = 0.97 (0.95–0.98) and SDC = 4 mm). The reliability of cluster of tests was excellent with both four and five positive tests out of seven.

Conclusion: The reliability was good to excellent for the clinical tests and the cluster of tests when performed by experienced therapists. The tests are feasible for use in the clinical setting. They require no advanced equipment and are easy to perform.     

Shoulder muscle activity during the modified dynamic relocation test and side-lying shoulder external rotation: a cross-sectional study on asymptomatic individuals

Objectives: (1) to compare activity levels between monitored muscles during the dynamic relocation test (DRT); (2) to assess changes in muscle activation variability over 10 trials; (3) to assess within-muscle difference activity levels between the DRT and the unloaded side-lying shoulder external rotation exercise.

Methods: This is a cross-sectional, laboratory-based, repeated measures study. Thirty asymptomatic individuals performed the DRT and unloaded side-lying external rotation. The order of exercises was randomized. Superficial electromyography was used for recording the supraspinatus, infraspinatus, middle deltoid, posterior deltoid, pectoralis major, and latissimus dorsi muscles. The main outcome measures were mean muscle activity, expressed as % of maximal isometric voluntary contraction.

Results: We found significant between-muscles differences in activity (F_t = 14.11, p < 0.001) during the DRT. Post hoc analysis suggested between-trial variability did not change over the 10 trials, (F = 18.2, p < 0.001). Within-muscle comparisons between the DRT and side-lying shoulder external rotation suggested significant differences between these exercises (F = 32.37, p < 0.001).

Conclusions: considering the monitored muscles, supraspinatus, infraspinatus, pectoralis major, and latissimus dorsi are the main muscles contracting during the DRT. Of all monitored muscles, supraspinatus muscle was the only one presenting higher activity levels during the DRT when compared to the unloaded side-lying shoulder external rotation.     

A preliminary analysis of outcomes and end range procedures used to achieve centralization in people with low back pain

Objectives: To investigate the relationship between clinical outcome and the types of end range procedures used to achieve centralization in a sample of patients with low back pain (LBP) and/or peripheral symptoms.

Methods: Small sample retrospective analysis of an observational cohort. Patients with LBP who centralized during initial visit at two physical therapy clinics were recruited to participate. The types of end range procedures used to achieve centralization were documented during each office visit and a chart review was performed after 4 weeks. Outcomes were determined by improvement in the Oswestry Disability Index (ODI) score after 4 weeks. Statistical analysis determined the association between the types of end range procedures and outcomes.

Results: Thirty-one patients gave consent to participate. Nineteen patients met inclusion criteria and were included in data analysis. After 4 weeks, the improvement in mean ODI scores was 15.89 ± 16.28. Differing end range procedures were used to achieve centralization within this cohort. The types of end range procedures used to achieve centralization were not significantly associated with outcomes.

Discussion: The results observed in this study promote exhausting many different types of end range procedures to determine if centralization can be achieved. Limiting the end range procedures used to assess centralization may fail to identify patients who can achieve centralization and subsequently have positive clinical outcomes. Larger cohort studies investigating relationships between outcomes and the types of end range procedures used to achieve centralization would contribute to management of people with LBP.

Level of Evidence: 4.     

Effects of cervical manipulation on pain,grip force control,and upper extremity muscle activity: a randomized controlled trial

Objectives: Individuals with neck pain experience disrupted grip force control when performing manipulative tasks. Manipulative physical therapy might decrease pain and change the activity of surrounding muscles; however, its effect on upper limb motor control remains undetermined. This study aims to analyze the effects of cervical manipulation on pressure pain threshold (PPT), upper extremity muscle activity along with grip force control in individuals with neck pain.

Methods: Thirty subjects with neck pain were instructed to grasp and lift an object before and after cervical (n = 15) or sham (n = 15) manipulation. The patients’ PPT, electromyographic (EMG) activity of the upper extremity/scapular muscles, and grip force control were analyzed before and after one session of manipulation.

Results: No significant differences were found in the grip force control, PPT and EMG activity variables between groups.

Discussion: These results suggest that a single session of cervical manipulation may not modify upper limb motor control, more specifically grip force control and EMG activity, in patients with cervical pain. Future studies should investigate potential changes in grip force control in patients with different features of neck pain and/or by applying long-term treatment.

Level of Evidence: 1b.     

A double-blind placebo-controlled clinical investigation into pain reduction effect of placing the pain spot outside the intersection area of the two currents of interferential therapy compared to traditional method

Background: Interferential therapy (IFT) is applied to intersect in the painful area but no confirmed effect with this method. Experimentally, the highest voltage of IFT is induced outside the intersection of the two currents. Placing the painful area outside the intersection point (external application) would reveal a better effect.

Objectives: To examine the effect of external application in pain compared to traditional method.

Design: A double-blind placebo-controlled clinical investigation.

Setting: A public hospital.

Participants: 168 LBP subjects.

Interventions: Assignment: (1) external IFT, (2) placebo external IFT, (3) traditional IFT and (4) placebo traditional IFT. Groups 1 and 3 received 20 min of IFT at 100 Hz and groups 2 and 4 received sham IFT.

Main outcome measures: Before and after IFT session, pain severity (VAS), pressure threshold (PPT), pain distribution and ROM were assessed.

Results: IFT changed all outcomes similarly. VAS and ROM improved statistically, P < 0.03. A trend of better VAS reduced with active IFTs.

Conclusions: No therapeutic difference between the two methods.