The Manual Therapy and Strengthening for the Hip (MASH) Trial: Protocol for a Multisite Randomized Trial of a Subgroup of Older Adults With Chronic Back and Hip Pain.

OBJECTIVE: Chronic low back pain (CLBP) is a disabling and costly condition for older adults that is difficult to properly classify and treat. In a cohort study, a subgroup of older adults with CLBP who had elevated hip pain and hip muscle weakness was identified; this subgroup differentiated itself by being at higher risk for future mobility decline. The primary purpose of this clinical trial is to evaluate whether a hip-focused low back pain (LBP) treatment provides better disability and physical performance outcomes for this at-risk group compared with a spine-focused LBP treatment. METHODS: This study is a multisite, single-blinded, randomized controlled, parallel arm, Phase II trial conducted across 3 clinical research sites. A total of 180 people aged between 60 and 85 years with CLBP and hip pain are being recruited. Participants undergo a comprehensive baseline assessment and are randomized into 1 of 2 intervention arms: hip-focused or spine-focused. They are treated twice weekly by a licensed physical therapist for 8 weeks and undergo follow-up assessments at 8 weeks and 6 months after randomization. Primary outcome measures include the Quebec Low Back Disability Scale and the 10-Meter Walk Test, which are measures of self-report and performance-based physical function, respectively. IMPACT: This multicenter, randomized clinical trial will determine whether a hip-focused or spine-focused physical therapist intervention results in improved disability and physical performance for a subgroup of older adults with CLBP and hip pain who are at increased risk of mobility decline. This trial will help further the development of effective interventions for this subgroup of older adults with CLBP.

Effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and physical function in patients with symptomatic knee osteoarthritis: the ETRELKA randomized clinical trial.

OBJECTIVE: To determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis. METHODS: Multi-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes. RESULTS: There was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference -0.06; 95%CI -0.41 to 0.29; P = 0.74), nor throughout the trial duration (P = 0.98). Subgroup analyses did not indicate an interaction between patient/treatment characteristics and treatment effect on WOMAC pain at the end of treatment (P-interaction ≥0.22). The occurrence of adverse events was similar across groups, with 10.4% and 10.6% of patients reporting events in the TENS and placebo TENS groups, respectively (P = 0.95). No relevant differences were observed in secondary outcomes. CONCLUSIONS: TENS does not improve knee osteoarthritis pain when compared to placebo TENS. Therapists should consider other potentially more effective treatment modalities to decrease knee osteoarthritis pain and facilitate strengthening and aerobic exercise. Our findings are conclusive and further trials comparing TENS and placebo TENS in this patient population are not necessary.

A Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy of a Hydrolyzed Chicken Collagen Type II Supplement in Alleviating Joint Discomfort.

Joint pain and disease affects more than one in four adults in the United States. We conducted a double-blind, randomized, placebo-controlled trial to investigate the efficacy of a hydrolyzed chicken collagen type II (HCII) supplement in reducing joint-related discomfort such as pain and stiffness, and in improving mobility. We enrolled adults aged 40-65 (65.5% were women) who had joint discomfort, but had no co-morbidities, and who were not taking pain medications. The participants were randomized to receive either the HCII supplement (n = 47) or a placebo (n = 43) for eight weeks. At the baseline, and at week 4 and week 8, we administered the Western Ontario and McMaster Universities Arthritis Index (WOMAC) survey with three additional wrist-related questions and the Visual Analog Scale for assessments of joint-related symptoms. In the WOMAC stiffness and physical activity domains and in the overall WOMAC score, the HCII group had a significant reduction in joint-related discomforts compared with the placebo group. For example, at week 4, the HCII group had a 36.9% reduction in the overall WOMAC score, compared with a 14.3% reduction in the placebo group (p = 0.027). This HCII product is effective in reducing joint pain and stiffness and in improving joint function among otherwise healthy adults.

Optimizing Chronic Pain Treatment with Enhanced Neuroplastic Responsiveness: A Pilot Randomized Controlled Trial.

Chronic pain affects mental and physical health and alters brain structure and function. Interventions that reduce chronic pain are also associated with changes in the brain. A number of non-invasive strategies can promote improved learning and memory and increase neuroplasticity in older adults. Intermittent fasting and glucose administration represent two such strategies with the potential to optimize the neurobiological environment to increase responsiveness to recognized pain treatments. The purpose of the pilot study was to test the feasibility and acceptability of intermittent fasting and glucose administration paired with a recognized pain treatment activity, relaxation and guided imagery. A total of 32 adults (44% W, 56% M), 50 to 85 years of age, with chronic knee pain for three months or greater participated in the study. Four sessions were completed over an approximate two-week period. Findings indicate the ability to recruit, randomize, and retain participants in the protocol. The procedures and measures were reasonable and completed without incident. Participant adherence was high and exit interview feedback positive. In summary, the pilot study was feasible and acceptable, providing the evidence necessary to move forward with a larger clinical trial.

The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial.

First evidence indicates that the supplementation of specific collagen peptides is associated with a significant reduction in activity-related joint pain in young adults. The purpose of the current investigation was to confirm the efficacy of the same collagen peptides in a comparable study population. In total, 180 active men and women aged between 18 and 30 years with exercise-related knee pain but no diagnosed joint disease completed the trial over a period of 12 weeks. Participants were randomly assigned to the group receiving 5 g of specific collagen peptides (CP-G) or to the placebo group (P-G). For the primary outcome, changes in pain during or after exercise from pre- to post-intervention were assessed by the participants using the Visual Analog Scale (VAS). These changes were additionally evaluated by the examining physician by means of anamnesis and physical examination of the affected knee joint. As secondary outcomes, pain under resting conditions and after 20 squats were compared between the study groups. In addition, the mobility of the knee joint and the use of alternative therapies (e.g., ointments or physiotherapy) were recorded. The supplementation of specific collagen peptides derived from type I collagen with a mean molecular weight of 3 kDa led to a significantly (p = 0.024) higher reduction of exercise-induced knee pain (-21.9 ± 18.3 mm) compared with the placebo group (-15.6 ± 18.5 mm). These findings were consistent with the physician's evaluation (-23.0 ± 19.2 mm vs. -14.6 ± 17.9 mm, p = 0.003). The decrease in pain under resting conditions and after squats did not significantly differ between the groups, as only a small number of participants suffered from pain under these conditions. Due to the clinically unremarkable baseline values, the mobility of the knee joint did not change significantly after the intervention. In conclusion, the current investigation confirmed that the oral intake of bioactive collagen peptides used in the current investigation led to a statistically significant reduction of activity-related joint pain in young active adults suffering from knee joint discomfort.

The immediate effects of passive hip joint mobilization on hip abductor/external rotator muscle strength in patients with anterior knee pain and impaired hip function. A randomized, placebo-controlled crossover trial.

Background: Anterior knee pain (AKP) is often associated with persistent hip muscle weakness and facilitatory interventions may be beneficial for managing patients with AKP (pwAKP). Physiotherapists often employ passive oscillatory hip joint mobilizations to increase hip muscle function. However, there is little information about their effectiveness and the mechanisms of action involved. Objectives: To investigate the immediate effects of passive hip joint mobilization on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function. Design: A double-blinded, randomized, placebo-controlled crossover design. Method: Eighteen patients with AKP participated in two sessions of data collection with one week apart. They received passive hip joint mobilization or placebo mobilization in a randomized order. Eccentric hip muscle strength was measured immediately before and after each intervention using a portable hand-held dynamometer. Results: An ANCOVA with the sequence of treatment condition as the independent variable, the within-subject post-treatment differences as the dependent variable and the within-subject pre-treatment differences as the covariate was conducted. Patients showed a significant mean increase in eccentric hip muscle strength of 7.73% (p = 0.001) for the mobilization condition, compared to a mean decrease of 4.22% for the placebo condition. Seventeen out of eighteen participants reported having no pain during any of the strength testing. Conclusion: These data suggest that passive hip joint mobilization has an immediate positive effect on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function, even in the absence of current pain.

Effect of laying on of hands as a complementary therapy for pain and functioning in older women with knee osteoarthritis: A randomized controlled clinical trial.

AIM: To assess the effects of laying on of hands (LooH) as a complementary therapy to kinesiotherapy, on pain, joint stiffness, and functional capacity of older women with knee osteoarthritis (KOA) compared to a control group. METHODS: In this randomized controlled clinical trial, participants were assigned into 3 groups: LooH with a spiritual component ("Spiritist passe" Group - SPG), LooH without a spiritual component (LooH Group - LHG), and a control group receiving no complementary intervention (Control Group - CG). Patients were assessed at baseline, 8 weeks, and 16 weeks. Primary outcomes were joint stiffness and functional capacity (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and pain (WOMAC and visual analog scale). Secondary outcomes were anxiety, depression, mobility, and quality of life. Differences between groups were evaluated using an intention-to-treat approach. RESULTS: A total of 120 women (mean age = 69.2 ± 5.2 years) with KOA were randomized (40 participants per group). At 8 weeks, SPG differed significantly from the LHG for WOMAC Functional Status (between-group difference in the change = 0.97; 95% CI: 0.35 to 1.59, P = .001); Anxiety levels (between-group difference in the change = 1.38; 95% CI: 0.11 to 2.65, P = .027); and also from the CG for all outcomes with exception of WOMAC Stiffness. After 16 weeks, SPG differed significantly from the LHG only for WOMAC Functional Status (between-group difference in the change = 0.92; 95% CI: 0.32 to 1.52, P = .001]) and also from the CG for all outcomes with exception of WOMAC Stiffness and timed up-and-go. CONCLUSION: Our results suggest that LooH with a "spiritual component" may promote better long-term functional outcomes than both LooH without a "spiritual component" and a control group without LooH.

Effects of Vitamin D Supplementation on Disabling Foot Pain in Patients With Symptomatic Knee Osteoarthritis.

OBJECTIVE: The present study was undertaken to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over 2 years in patients with symptomatic knee osteoarthritis (OA). METHODS: A post hoc study was conducted from a randomized, double-blind, placebo-controlled trial named the Vitamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25-hydroxyvitamin D levels between 12.5 nmoles/liter and 60 nmoles/liter were included and randomly allocated to either monthly vitamin D3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and disabling foot pain was defined as at least 1 of the 10 functional limitation items (items 1-9 and 11) being documented as on "most/every day(s)" in the last month. A repeated-measures, mixed-effects model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders. RESULTS: A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8 ± 7.3, with 23.7% of participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in the vitamin D group than in the placebo group (-0.03 versus 1.30; P = 0.013) and more improvement in those maintaining sufficient vitamin D levels (n = 226) than those who did not (n = 114) (-0.09 versus 2.19; P = 0.001). CONCLUSION: Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.

Should ice application be replaced with neurocryostimulation for the treatment of acute lateral ankle sprains? A randomized clinical trial.

STUDY DESIGN: Single-blind parallel group randomized clinical trial. OBJECTIVES: To compare the effects of neurocryostimulation (NCS) with those of traditional ice application on functional recovery, pain, edema and ankle dorsiflexion range of motion (ROM) in individuals receiving physiotherapy treatments for acute lateral ankle sprains (LAS). BACKGROUND: Ankle sprain is a very common injury and its management is often costly, with important short- and long-term impacts on individuals and society. As new methods of therapy using cold (cryotherapy) are emerging for the treatment of musculoskeletal conditions, little evidence exists to support their use. NCS, which provokes a rapid cooling of the skin with the liberation of pressured CO2, is a method believed to accelerate the resorption of edema and recovery in the case of traumatic injuries. METHODS: Forty-one participants with acute LAS were randomly assigned either to a group that received in-clinic physiotherapy treatments and NCS (experimental NCS group, n = 20), or to a group that received the same in-clinic physiotherapy treatments and traditional ice application (comparison ice group, n = 21). Primary (Lower Extremity Functional Scale - LEFS) and secondary (visual analog scale for pain intensity at rest and during usual activities in the last 48 h, Figure of Eight measurement of edema, and weight bearing lunge for ankle dorsiflexion range of motion) outcomes were evaluated at baseline (T0), after one week (T1), two weeks (T2), four weeks (T4) and finally, after six weeks (T6). The effects of interventions were assessed using two-way ANOVA-type Nonparametric Analysis for Longitudinal Data (nparLD). RESULTS: No significant group-time interaction or group effect was observed for all outcomes (0.995 ≥ p ≥ 0.057) following the intervention. Large time effects were however observed for all outcomes (p <  0.0001). CONCLUSION: Results suggest that neurocryostimulation is no more effective than traditional ice application in improving functional recovery, pain, edema, and ankle dorsiflexion ROM during the first six weeks of physiotherapy treatments in individuals with acute LAS. LEVEL OF EVIDENCE: Therapy, level 1b. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02945618 . Registered 23 October 2016 - Retrospectively registered (25 participants recruited prior to registration, 17 participants after).

Hip-Joint Posture and Movement Alterations Are Associated With High Interference of Pain in the Life of Patients With Greater Trochanteric Pain Syndrome.

OBJECTIVE: Greater trochanteric pain syndrome (GTPS) is a common condition that can cause lateral hip pain. The single-leg-squat test (SLST) may be used by physicians in primary care environments to evaluate patients' dynamic stability. The aim of this study was to evaluate the dynamic stability and strength of lateral abduction hip movements in primary care patients with GTPS in relation to their perceived pain interference in life. METHODS: A descriptive observational study was carried out in a primary health care center. Fifty-four participants with GTPS were included in this study and divided into lower- and higher-interference groups (n = 30 and 19, respectively) according to the Graded Chronic Pain Scale. Participants were evaluated for their lateral abduction hip strength and the SLST. RESULTS: The SLST showed a statistically significant difference between groups with respect to hip-joint posture and movement level (P = .043) but not for other SLST domains or lateral abduction hip strength (P > .05). CONCLUSION: Patients with GTPS with more pain interference in their lives had poorer dynamic stability with respect to hip-joint posture and movements based on the SLST but did not present impaired lateral hip abduction strength in comparison with those who perceived lower pain interference in life.

Estimating contextual effect in nonpharmacological therapies for pain in knee osteoarthritis: a systematic analytic review.

OBJECTIVE: Conduct a systematic review and use meta-analytic techniques to estimate the proportion of total treatment effect that can be attributable to contextual effects (PCE) in adults receiving nonpharmacological, nonsurgical (NPNS) treatments for knee osteoarthritis (OA). DESIGN: We reviewed the published literature to identify five frequently studied NPNS treatments for knee OA: exercise, acupuncture, ultrasound, laser, and transcutaneous electrical nerve stimulation (TENS). We searched for randomized controlled trials (RCTs) of these treatments and abstracted pre- and post-intervention pain scores for groups receiving placebo and active treatments. For each study we calculated the PCE by dividing the change in pain in the placebo group by the change in pain in the active treatment group. We log transformed the PCE measure and pooled across studies using a random effects model. RESULTS: We identified 25 studies for analysis and clustered the RCTs into two groups: acupuncture and topical energy modalities (TEM). 13 acupuncture studies included 1,653 subjects and 12 TEM studies included 572 subjects. The combined PCE was 0.61 (95% CI 0.46-0.80) for acupuncture and 0.69 (95% CI 0.54-0.88) for TEM. CONCLUSION: Our findings suggest that about 61% and 69% of the total treatment effect experienced by subjects receiving acupuncture and TEM treatments, respectively, for knee OA pain may be explained by contextual effects. Contextual effects may include the placebo effect, changes attributable to natural history, and effects of co-therapies. These data highlight the important role of contextual effects in the response to NPNS OA treatments.

Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis.

INTRODUCTION: Observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function. METHODS AND ANALYSIS: A systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥6 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest. ETHICS AND DISSEMINATION: Research ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018107740.

Oral treatments with a flavonoid-enriched fraction from Cecropia hololeuca and with rutin reduce articular pain and inflammation in murine zymosan-induced arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia Loefl. species (Urticaceae) are widely spread across the rainforest in tropical and subtropical regions of Central and South America. Inhabitants of different regions of Brazil employ leaves, fruits and sprouts of Cecropia hololeuca Miq. mainly as anti-inflammatory, anti-asthmatic, expectorant, fever suppressant, and against cough. AIM OF THE STUDY: To evaluate the antinociceptive and anti-inflammatory activities of an aqueous leaf extract of C. hololeuca in a murine model of zymosan-induced arthritis (ZIA) and characterize compounds contributing to these effects. MATERIALS AND METHODS: The crude aqueous extract of C. hololeuca (CAE) was obtained by infusion, screened for antinociceptive and anti-inflammatory activities, and fractionated (solvent partition; RP-2 and Sephadex G-25 column chromatography), yielding fractions that were chemically and pharmacologically investigated. TLC, HPLC-DAD, HPLC-DAD-ESI-MS/MS and NMR analyses were peformed. The antinociceptive activity was assessed by means of acetic acid-induced writhing, hot-plate and rota-rod tests. ZIA was used to evaluate the anti-arthritic activity of oral treatment with CAE, butanolic (BF) and aqueous fraction (AF), as well as the fractions obtained from BF (F2, F2-A and F2-B). Rutin, a flavonoid found in C. hololeuca, was also tested. Mechanical hypernociception, joint edema, local neutrophil recruitment and articular TNF-α quantification were performed to measure the severity of arthritis and identify the anti-inflammatory potential of C. hololeuca. RESULTS: CAE (0.03-1 g/kg, p.o.) showed a dose-related inhibitory effect on acetic acid-induced writhing test, but did not change the pain latency in the hotplate test, nor the first fall time on the rota-rod test. In addition, CAE (1 g/kg, p.o.) inhibited by 65% the mechanical hypernociception, 46% the joint edema, 54% the neutrophil recruitment and 53% the articular TNF-α concentration levels in ZIA. BF (0.4 g/kg, p.o.), AF (0.6 g/kg), F2 (0.1 g/kg) and F2-A (0.045 g/kg), but not F2-B (0.055 g/kg), inhibited the mechanical hypernociception, joint edema and neutrophil recruitment in ZIA. Rutin (0.001-0.03 g/kg, p.o.) produced dose-related inhibitory effects in the mechanical hypernociception, joint edema and neutrophil recruitment, and at 0.03 g/kg also inhibited articular TNF-α synthesis after intra-articular zymosan injection. Isoorientin, isovitexin, rutin and isoquercitrin were identified in the most active fraction (F2-A), along with luteolin and apigenin derivatives, tentatively identified as isoorientin-2″-O-glucoside and isovitexin-2″-O-glucoside. CONCLUSION: This study corroborates the popular use by oral route of aqueous preparations of C. hololeuca against joint inflammatory disorders, such as rheumatoid arthritis. Our results demonstrated for the first time that oral administration of rutin shows antinociceptive and anti-inflammatory effects in ZIA, indicating that this flavonoid is one of the immunomodulatory compounds involved in the anti-arthritic activity of C. hololeuca.

Effectiveness of collagen supplementation on pain scores in healthy individuals with self-reported knee pain: a randomized controlled trial.

The purpose of this study was to examine the effects of 12 weeks collagen peptide (CP) supplementation on knee pain and function in individuals with self-reported knee pain. Healthy physically active individuals (n = 167; aged 63 [interquartile range = 56-68] years) with self-reported knee pain received 10 g/day of CP or placebo for 12 weeks. Knee pain and function were measured with the Visual Analog Scale (VAS), the Lysholm questionnaire, and the Knee injury and Osteoarthritis Outcome Score (KOOS). Furthermore, we assessed changes in inflammatory, cartilage, and bone (bio)markers. Measurements were conducted at baseline and after 12 weeks of supplementation. Baseline VAS did not differ between CP and placebo (4.7 [2.5-6.1] vs. 4.7 [2.8-6.2], p = 0.50), whereas a similar decrease in VAS was observed after supplementation (-1.6 ± 2.4 vs. -1.9 ± 2.6, p = 0.42). The KOOS and Lysholm scores increased after supplementation in both groups (p values < 0.001), whereas the increase in the KOOS and Lysholm scores did not differ between groups (p = 0.28 and p = 0.76, respectively). Furthermore, CP did not impact inflammatory, cartilage, and bone (bio)markers (p values > 0.05). A reduced knee pain and improved knee function were observed following supplementation, but changes were similar between groups. This suggests that CP supplementation over a 12-week period does not reduce knee pain in healthy, active, middle-aged to elderly individuals. Novelty CP supplementation over a 12-week period does not reduce knee pain in healthy, active, middle-aged to elderly individuals. CP supplementation over a 12-week period does not impact on inflammatory, cartilage, and bone (bio)markers in healthy, active, middle-aged to elderly individuals.

The Effect of Neuromuscular Electrical Stimulation During Walking on Muscle Strength and Knee Pain in Obese Women With Knee Pain: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to assess the effectiveness of a hybrid training system with walking that simultaneously applies electrical stimulation to the knee extensors/flexors during walking in obese women with knee pain. DESIGN: This is a randomized, single-blind (assessor), controlled trial. Twenty-eight obese women with knee pain were randomized to 12 weeks of biweekly walking with either hybrid training system with walking or with transcutaneous electrical nerve stimulation (control). Primary outcomes (maximum isokinetic knee extensor torque and maximum isokinetic knee flexor torque) and secondary outcomes (20-m walk time, chair-stand time, stair-climb time, knee pain, and knee-related quality life) were evaluated. Change-point regression analyses were used to model the interaction for the primary outcomes. Two-sample t tests were used on pre-post change scores in secondary outcomes. RESULTS: Knee extensor torque increased significantly more in the hybrid training system with walking group than the control group when baseline knee extensor torque was greater than 57.2 Nm (P = 0.0033). When baseline knee flexor torque was at 30 or 50 Nm, there was a trend toward greater increase in the hybrid training system with walking group than the control group (P = 0.0566, P = 0.0737, respectively). There were no significant differences between groups in secondary outcomes. CONCLUSIONS: These results suggest that hybrid training system with walking is effective for improving knee extensor torque in obese women with knee pain. However, the superiority of hybrid training system with walking may vary depending on baseline knee muscle strength.

Efficacy of low-level laser therapy on pain and disability in knee osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials.

OBJECTIVES: Low-level laser therapy (LLLT) is not recommended in major knee osteoarthritis (KOA) treatment guidelines. We investigated whether a LLLT dose-response relationship exists in KOA. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eligible articles were identified through PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and Cochrane Central Register of Controlled Trials on 18 February 2019, reference lists, a book, citations and experts in the field. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We solely included randomised placebo-controlled trials involving participants with KOA according to the American College of Rheumatology and/or Kellgren/Lawrence criteria, in which LLLT was applied to participants' knee(s). There were no language restrictions. DATA EXTRACTION AND SYNTHESIS: The included trials were synthesised with random effects meta-analyses and subgrouped by dose using the World Association for Laser Therapy treatment recommendations. Cochrane's risk-of-bias tool was used. RESULTS: 22 trials (n=1063) were meta-analysed. Risk of bias was insignificant. Overall, pain was significantly reduced by LLLT compared with placebo at the end of therapy (14.23 mm Visual Analogue Scale (VAS; 95% CI 7.31 to 21.14)) and during follow-ups 1-12 weeks later (15.92 mm VAS (95% CI 6.47 to 25.37)). The subgroup analysis revealed that pain was significantly reduced by the recommended LLLT doses compared with placebo at the end of therapy (18.71 mm (95% CI 9.42 to 27.99)) and during follow-ups 2-12 weeks after the end of therapy (23.23 mm VAS (95% CI 10.60 to 35.86)). The pain reduction from the recommended LLLT doses peaked during follow-ups 2-4 weeks after the end of therapy (31.87 mm VAS significantly beyond placebo (95% CI 18.18 to 45.56)). Disability was also statistically significantly reduced by LLLT. No adverse events were reported. CONCLUSION: LLLT reduces pain and disability in KOA at 4-8 J with 785-860 nm wavelength and at 1-3 J with 904 nm wavelength per treatment spot. PROSPERO REGISTRATION NUMBER: CRD42016035587.

Effectiveness of Mulligan's Mobilization With Movement Techniques on Range of Motion in Peripheral Joint Pathologies: A Systematic Review With Meta-analysis Between 2008 and 2018.

OBJECTIVES: The purpose of this study was to provide an updated systematic review and meta-analysis regarding the effectiveness of mobilization with movement (MWM) techniques on range of motion (ROM). METHODS: An electronic search strategy of the Physiotherapy Evidence Database, PubMed, Cochrane Library, Embase, Google Scholar, and CINAHL was performed between August 2008 and January 2018. Two independent reviewers selected the studies. Only randomized controlled trials were included. The methodology was independently assessed by 2 reviewers using the Physiotherapy Evidence Database scale. The Z indicator was considered for the assessment of statistical significance of ROM change, whereas for each meta-analysis referring to a specific joint pathology, the total mean difference (95% confidence interval) was compared against minimum detectable change values from relevant studies conducted in similar populations to assess clinical significance. RESULTS: Included were 18 studies with 753 participants in 10 separate meta-analyses for ROM. All studies were classified as high quality or medium quality. Peripheral joint MWM seems to produce better therapeutic results in comparison to sham, passive, other active, or no therapeutic approach, regarding improvement of joint ROM in specific peripheral joint pathologies, consistently in all movement directions for shoulder adhesive capsulitis (mean improvement 12.30o-26.09o, P < .02) and hip pain (mean improvement 4.50o-14.80o, P < .0001). CONCLUSION: Mobilization with movement produced a statistically and clinically significant ROM increase consistently in all movement directions for shoulder adhesive capsulitis and hip pain. However, for shoulder impingement, shoulder pain/dysfunction, hamstring tightness, knee osteoarthritis, and chronic ankle instability pathologies, a therapeutic benefit regarding ROM could not be clearly established. Owing to the small number of individual studies included within the separate groups of pathologies examined in our systematic review, methodologically rigorous studies with longer follow-up periods are warranted to better inform the evidence base on the effects of MWM on ROM.

Efficacy and Safety of Honey Bee Venom (Apis mellifera) Dermal Injections to Treat Osteoarthritis Knee Pain and Physical Disability: A Randomized Controlled Trial.

Objectives: To evaluate purified honey bee (Apis mellifera) venom (HBV) biotherapy for the treatment of osteoarthritis (OA) knee pain and physical function. Design and Patients: Five hundred and thirty-eight patients with Kellgren/Lawrence grade 1-3 radiographic knee OA and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥2 were randomized 1:2 to either control ("histamine") or HBV in this double-blind study. Interventions: After a dose escalation period, patients received 12 weekly dermal injections of control ("histamine") or HBV. At each of the 12 weekly visits, a set of 15 dermal injections (each containing 2.75 µg histamine or 100 µg HBV) were administered at prespecified acupuncture points (5 on each knee: knee top, eye-1 medial, eye-2 lateral, ST 34, BL 40 and 5 near the spinous processes: BL 19, 21, 23, 25, and 27). Outcome Measures: Assessments included WOMAC pain and physical function subscales, visual analog scale (VAS), patient global assessment (PGA), and physician global assessment (PhGA). Rescue medication use (acetaminophen) and routine safety parameters were monitored. Results: HBV biotherapy demonstrated a highly significant improvement over control in WOMAC pain score after 12 weeks (1.1 U mean difference; confidence interval [95% CI]: 0.3-2.0; analysis of covariance [ANCOVA] p = 0.0010 with baseline as covariate) that was also sustained 4 weeks post-treatment. Furthermore, WOMAC physical function was significantly improved over control with HBV (3.1 U mean difference; 95% CI: 0.3-5.9; ANCOVA p = 0.0046), and sustained 4 weeks post-treatment. VAS scores were significantly improved with HBV versus control, as well as PGA and PhGA evaluations, which showed that patients responded more favorably ("very good/good") to their overall OA condition (82.0% vs. 62.4% [p = 0.0001] and 82.1% vs. 54.9% [p = 0.0015], respectively). Use of rescue acetaminophen was similar between the groups (77%-78% of patients). HBV was associated with higher incidence of injection site reactions (<5%); however, the overall safety profiles were comparable between the treatment groups. Conclusions: This phase 3 trial demonstrated that HBV biotherapy resulted in significant improvements in knee OA pain and physical function.

Efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for knee osteoarthritis: statistical analysis plan for a randomized controlled trial.

BACKGROUND: Acupuncture is widely used for knee osteoarthritis (KOA), despite contradictory evidence. This study is designed to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. METHODS/DESIGN: This is a multi-center three-arm randomized controlled trial. It will enroll 480 participants with KOA in China. Participants will be randomly assigned 1:1:1 to receive 24 sessions of electro-acupuncture, manual acupuncture, or sham acupuncture over 8 weeks. The primary outcome is the response rate, which is the proportion of patients who achieve the minimal clinically important improvement in pain and function at 8 weeks. The primary outcome will be analyzed using the Z-test with the intention-to-treat set. Secondary outcomes include pain, function, global patient assessment, and quality of life. Full details of the statistical analysis plan for the primary and secondary outcomes will be described in this article. The statistical analysis plan was written and submitted without knowledge of the study data. DISCUSSION: The data will be analyzed according to this pre-specified statistical analysis plan to avoid data-driven analysis and to enhance the transparency of the trial. The aim of the trial is to provide high-quality evidence on the efficacy of acupuncture for KOA. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03366363 . Registered on 20 November 2017.