Randomized, single-blinded, multi-center, parallel-group trial.
To compare the effects of adding electrical dry needling into a program of manual therapy, exercise and ultrasound on pain, function ...and related-disability in individuals with plantar fasciitis (PF).
The isolated application of electrical dry needling, manual therapy, exercise, and ultrasound has been found to be effective for PF. However, no previous study has investigated the combined effect of these interventions in this population.
One hundred and eleven participants (n = 111) with plantar fasciitis were randomized to receive electrical dry needling, manual therapy, exercise and ultrasound (n = 58) or manual therapy, exercise and ultrasound (n = 53). The primary outcome was first-step pain in the morning as measured by the Numeric Pain Rating Scale (NPRS). Secondary outcomes included resting foot pain (NPRS), pain during activity (NPRS), the Lower Extremity Functional Scale (LEFS), the Foot Functional Index (FFI), medication intake, and the Global Rating of Change (GROC). The treatment period was 4 weeks with follow-up assessments at 1 week, 4 weeks, and 3 months after the first treatment session. Both groups received 6 sessions of impairment-based manual therapy directed to the lower limb, self-stretching of the plantar fascia and the Achilles tendon, strengthening exercises for the intrinsic muscles of the foot, and therapeutic ultrasound. In addition, the dry needling group also received 6 sessions of electrical dry needling using a standardized 8-point protocol for 20 minutes. The primary aim was examined with a 2-way mixed-model analysis of covariance (ANCOVA) with treatment group as the between-subjects variable and time as the within-subjects variable after adjusting for baseline outcomes.
The 2X4 ANCOVA revealed that individuals with PF who received electrical dry needling, manual therapy, exercise and ultrasound experienced significantly greater improvements in first-step morning pain (F = 22.021; P<0.001), resting foot pain (F = 23.931; P<0.001), pain during activity (F = 7.629; P = 0.007), LEFS (F = 13.081; P<0.001), FFI Pain Subscale (F = 13.547; P<0.001), FFI Disability Subscale (F = 8.746; P = 0.004), and FFI Total Score (F = 10.65; P<0.001) than those who received manual therapy, exercise and ultrasound at 3 months. No differences in FFI Activity Limitation Subscale (F = 2.687; P = 0.104) were observed. Significantly (X2 = 9.512; P = 0.023) more patients in the electrical dry needling group completely stopped taking medication for their pain compared to the manual therapy, exercise and ultrasound group at 3 months. Based on the cutoff score of ≥+5 on the GROC, significantly (X2 = 45.582; P<0.001) more patients within the electrical dry needling group (n = 45, 78%) achieved a successful outcome compared to the manual therapy, exercise and ultrasound group (n = 11, 21%). Effect sizes ranged from medium to large (0.53<SMD<0.85) at 3 months in favor of the electrical dry needling group.
The inclusion of electrical dry needling into a program of manual therapy, exercise and ultrasound was more effective for improving pain, function and related-disability than the application of manual therapy, exercise and ultrasound alone in individuals with PF at mid-term (3 months).
Therapy, Level 1b.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance ...mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Objective
To evaluate the effects of ultrasound-guided percutaneous electrolysis alone or as an adjunct to other interventions on pain and pain-related disability for musculoskeletal pain ...conditions.
Databases and Data Treatment
Search of MEDLINE database, Allied and Complementary Medicine Database, EMBASE database, Cumulative Index to Nursing & Allied Health Literature database, EBSCO database, PubMed database, Physiotherapy Evidence Database, Cochrane Library database, Scopus database, and Web of Science database. Randomized controlled trials in which at least one group received ultrasound-guided percutaneous electrolysis for treatment of musculoskeletal pain. To be eligible, studies had to include humans and collect outcomes on pain intensity and pain-related disability for musculoskeletal pain syndromes. Data were extracted by two reviewers. The risk of bias was assessed by the Cochrane Guidelines and the quality of evidence was reported using the Grading of Recommendations Assessment, Development and Evaluation approach. Standardized mean differences (SMDs) and random effects were calculated.
Results
Ten studies were included. The meta-analysis found that ultrasound-guided percutaneous electrolysis reduced the mean pain intensity by –2.06 (95% confidence interval CI, –2.69 to –1.42) and the pain intensity as assessed with a visual analog scale or a numeric pain rating scale with a large size effect (SMD = –1.15; 95% CI, –1.48 to –0.81) and also improved pain-related disability with a large size effect (SMD = 0.95; 95% CI, 0.73–1.18) as compared with comparison groups. No differences in effect sizes were found among the short-term, midterm, and long-term follow-ups. The risk of bias was generally low, but the heterogeneity of the overall result downgraded the evidence level. Trials included heterogeneous musculoskeletal pain conditions and short-term, midterm, and long-term follow-ups.
Conclusion
Moderate evidence suggests positive effects of ultrasound-guided percutaneous electrolysis for pain and pain-related disability in musculoskeletal pain conditions relative to a comparison group in the short term, midterm, and long term.
Abstract
Objective
The purpose of this study was to evaluate the effects of trigger point (TrP) dry needling alone or as an adjunct to other interventions on pain intensity and related disability in ...nontraumatic shoulder pain.
Methods
Ten databases were searched from inception to January 2020 for randomized clinical trials in which at least 1 group received TrP dry needling for shoulder pain of musculoskeletal origin with outcomes collected on pain intensity and related disability. Data extraction including participant and therapist details, interventions, blinding strategy, blinding assessment outcomes, and results were extracted by 2 reviewers. The risk of bias (Cochrane Risk of Bias, Cochrane Guidelines), methodological quality (Physiotherapy Evidence Database score), and evidence level (Grading of Recommendations Assessment, Development, and Evaluation approach) were assessed. The search identified 551 publications with 6 trials eligible for inclusion.
Results
There was moderate-quality evidence that TrP dry needling reduces shoulder pain intensity with a small effect (mean difference = −0.49 points, 95% CI = −0.84 to −0.13; standardized mean difference = −0.25, 95% CI = −0.42 to −0.09) and low-quality evidence that TrP dry needling improves related disability with a large effect (mean difference = −9.99 points, 95% CI −15.97 to −4.01; standardized mean difference = −1.14, 95% CI −1.81 to −0.47) compared with a comparison group. The effects on pain were only found at short term. The Cochrane Risk of Bias was generally low, but the heterogenicity of the results downgraded the evidence level.
Conclusion
Moderate- to low-quality evidence suggests positive effects of TrP dry needling for pain intensity (small effect) and pain-related disability (large effect) in nontraumatic shoulder pain of musculoskeletal origin, mostly at short term. Future clinical trials investigating long-term effects are needed.
Impact
Dry needling is commonly used for the management of musculoskeletal pain. This is the first meta-analysis to examine the effects of dry needling on nontraumatic shoulder pain.
During DNA replication replicative polymerases move in discrete mechanical steps along the DNA template. To address how the chemical cycle is coupled to mechanical motion of the enzyme, here we use ...optical tweezers to study the translocation mechanism of individual bacteriophage Phi29 DNA polymerases during processive DNA replication. We determine the main kinetic parameters of the nucleotide incorporation cycle and their dependence on external load and nucleotide (dNTP) concentration. The data is inconsistent with power stroke models for translocation, instead supports a loose-coupling mechanism between chemical catalysis and mechanical translocation during DNA replication. According to this mechanism the DNA polymerase works by alternating between a dNTP/PPi-free state, which diffuses thermally between pre- and post-translocated states, and a dNTP/PPi-bound state where dNTP binding stabilizes the post-translocated state. We show how this thermal ratchet mechanism is used by the polymerase to generate work against large opposing loads (∼50 pN).
The role of polysaccharides and proteoglycans in the formation of calcium carbonate-based biominerals is examined. Biomineralization involves a 4-stage process.
The EQ-5D instrument is the most widely used preference-based health-related quality of life questionnaire in cost-effectiveness analysis of health care technologies. Recently, a version called ...EQ-5D-5L with 5 levels on each dimension was developed. This manuscript explores the performance of a hybrid approach for the modeling of EQ-5D-5L valuation data.
Two elicitation techniques, the composite time trade-off, and discrete choice experiments, were applied to a sample of the Spanish population (n=1000) using a computer-based questionnaire. The sampling process consisted of 2 stages: stratified sampling of geographic area, followed by systematic sampling in each area. A hybrid regression model combining composite time trade-off and discrete choice data was used to estimate the potential value sets using main effects as starting point. The comparison between the models was performed using the criteria of logical consistency, goodness of fit, and parsimony.
Twenty-seven participants from the 1000 were removed following the exclusion criteria. The best-fitted model included 2 significant interaction terms but resulted in marginal improvements in model fit compared to the main effects model. We therefore selected the model results with main effects as a potential value set for this methodological study, based on the parsimony criteria. The results showed that the main effects hybrid model was consistent, with a range of utility values between 1 and -0.224.
This paper shows the feasibility of using a hybrid approach to estimate a value set for EQ-5D-5L valuation data.
Doxorubicin, one of the most effective anticancer drugs currently known, is commonly used against breast cancer. However, its clinical use is restricted by dose-dependent toxicity (myelosuppression ...and cardiotoxicity), the emergence of multidrug resistance and its low specificity against cancer cells. Nanotechnology is a promising alternative to overcome these limitations in cancer therapy as it has been shown to reduce the systemic side-effects and increase the therapeutic effectiveness of drugs. Indeed, the numerous nanoparticle-based therapeutic systems developed in recent years have shown low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. Furthermore, the wide range of nanoparticle systems available may provide a solution to the different problems encountered during doxorubicin-based breast cancer treatment. Thus, a suitable nanoparticle system may transport active drugs to cancer cells using the pathophysiology of tumours, especially their enhanced permeability and retention effects, and the tumour microenvironment. In addition, active targeting strategies may allow doxorubicin to reach cancer cells using ligands or antibodies against selected tumour targets. Similarly, doxorubicin resistance may be overcome, or at least reduced, using nanoparticles that are not recognized by P-glycoprotein, one of the main mediators of multidrug resistance, thereby resulting in an increased intracellular concentration of drugs. This paper provides an overview of doxorubicin nanoplatform-based delivery systems and the principal advances obtained in breast cancer chemotherapy.
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