Acupuncture or Low Frequency Infrared Treatment for Low Back Pain in Chinese Patients: A Discrete Choice Experiment

Acupuncture is a popular but controversial treatment option for low back pain. In China, it is practised as traditional Chinese medicine; other treatment strategies for low back pain are commonly practised as Western medicine. Research on patient preference for low back-pain treatment options has been mainly conducted in Western countries and is limited to a willingness-to-pay approach. A stated-preference, discrete choice experiment was conducted to determine Chinese patient preferences and trade-offs for acupuncture and low frequency infrared treatment in low back pain from September 2011 to August 2012 after approval from the Department of Scientific Research in the study settings. Eight-six adult outpatients who visited the ‘traditional medicine department’ at a traditional Chinese medicine hospital and the ‘rehabilitation department’ at a Western medicine hospital in Guangdong Province of China for chronic low back pain during study period participated in an interview survey. A questionnaire containing 10 scenarios (5 attributes in each scenario) was used to ask participants'' preference for acupuncture, low frequency infrared treatment or neither option. Validated responses were analysed using a nested-logit model. The decision on whether to receive a therapy was not associated with the expected utility of receiving therapy, female gender and higher out-of-pocket payment significantly decreased chance to receive treatments. Of the utility of receiving either acupuncture or low frequency infrared treatment, the treatment sensation was the most important attribute as an indicator of treatment efficacy, followed by the maximum efficacy, maintenance duration and onset of efficacy, and the out-of-pocket payment. The willingness-to-pay for acupuncture and low frequency infrared treatment were about $618.6 and $592.4 USD per course respectively, demonstrated patients'' demand of pain management. The treatment sensation was regarded as an indicator of treatment efficacy and the most important attribute for choosing acupuncture or low frequency infrared treatment. The high willingness-to-pay demonstrated patients'' demand of pain management. However, there may be other factors influencing patients'' preference to receive treatments.     

Decreased Peripheral and Central Responses to Acupuncture Stimulation following Modification of Body Ownership

Acupuncture stimulation increases local blood flow around the site of stimulation and induces signal changes in brain regions related to the body matrix. The rubber hand illusion (RHI) is an experimental paradigm that manipulates important aspects of bodily self-awareness. The present study aimed to investigate how modifications of body ownership using the RHI affect local blood flow and cerebral responses during acupuncture needle stimulation. During the RHI, acupuncture needle stimulation was applied to the real left hand while measuring blood microcirculation with a LASER Doppler imager (Experiment 1, N = 28) and concurrent brain signal changes using functional magnetic resonance imaging (fMRI; Experiment 2, N = 17). When the body ownership of participants was altered by the RHI, acupuncture stimulation resulted in a significantly lower increase in local blood flow (Experiment 1), and significantly less brain activation was detected in the right insula (Experiment 2). This study found changes in both local blood flow and brain responses during acupuncture needle stimulation following modification of body ownership. These findings suggest that physiological responses during acupuncture stimulation can be influenced by the modification of body ownership.     

Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review

While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and blinding credibility.     

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants'' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one''s own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one''s own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.     

Function and “functioning” in ecology: what does it mean?

Many investigations in current ecological research focus on ecological functions, the functions of biodiversity, or the functioning of ecological systems. However, within ecology "function" is used in several different meanings. The most important ones are those of function as denoting either processes, roles, services or the "functioning" of whole systems. Some of these meanings pose considerable problems in terms of their ability to apply them in empirical research. These problems together with the ambiguity of the term "function" constitute considerable impediments for generalizations of research results. In order to improve this situation, the current paper describes the different meanings of "function" and discusses the requirements necessary to unambiguously apply the concept(s) in practice. This is illustrated by the example of current discussions on the "functions of biodiversity".     

Effects of Acupuncture on Sensory Perception: A Systematic Review and Meta-Analysis

Background

The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system.

Methods

Pubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed.

Results

Out of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception.

Conclusions

Our findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture.     

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

Current decision‐guiding algorithms in cancer drug treatment are based on decades of research and numerous clinical trials. For the majority of patients, this data is successfully applied for a systemic disease management. For a number of patients however, treatment stratification according to clinically based risk criteria will not be sufficient. The most effective treatment options are ideally identified prior to the start of clinical drug therapy. This review will discuss the implementation of three‐dimensional (3D) cell culture models as a preclinical testing paradigm for the efficacy of clinical cancer treatment. Patient tumor‐derived cells in 3D cultures duplicate the individual tumor microenvironment with a minimum of confounding factors. Clinical implementation of such personalized tumor models requires a high quality of methodological and clinical validation comparable to other biomarkers. A non‐systematic literature search demonstrated the small number of prospective studies that have been conducted in this area of research. This may explain the current reluctance of many physicians and insurance providers in implementing this type of assay into the clinical diagnostic routine despite potential benefit for patients. Achieving valid and reproducible results with a high level of evidence is central in improving the acceptance of preclinical 3D tumor models.     

Effect of acupuncture on the activity of experimental epileptogenic foci in the hippocampus of rabbits

Experiments were performed on rabbits with electrochemotrodes implanted into the left and right dorsal hippocamp. The evidence was obtained for the first time as to the marked inhibitory effect of acupuncture on epileptogenic foci created by penicillin microinjections into the hippocamp. The most effective was stimulation of the Min-Men point. The antiepileptic effect was potentiated on combined stimulation of the Min-Men and Yao-Yan-Guan points. The efficacy of the procedure was significantly decreased on stimulation of the points of another acupunctural canal. The epileptiform activity was potentiated by affecting the knowingly inactive points. The antiepileptic effect of acupuncture was significantly reduced with an increase in the number of acupunctures. This might be connected with the development of tolerance to enkephalins by which the effect of acupuncture is most likely mediated.     

Do distribution volumes and clearances relate to tissue volumes and blood flows? A computer simulation

Background

Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial.

Methods

Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days.

Results

Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration.

Conclusion

The rate of data completion met our predefined criterion for determining a randomized trial to be feasible (at least 75% of patients tolerated the intervention and provided evaluable data). This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial.     

New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine

Vitamin E (alpha-tocopherol or alphaT) has long been recognized as a classic free radical scavenging antioxidant whose deficiency impairs mammalian fertility. In actuality, alpha-tocopherol is one member of a class of phytochemicals that are distinguished by varying methylation of a chroman head group. Early studies conducted between 1922 and 1950 indicated that alpha-tocopherol was specific among the tocopherols in allowing fertility of laboratory animals. The unique vitamin action of alphaT, combined with its prevalence in the human body and the similar efficiency of tocopherols as chain-breaking antioxidants, led biologists to almost completely discount the "minor" tocopherols as topics for basic and clinical research. Recent discoveries have forced a serious reconsideration of this conventional wisdom. New and unexpected biological activities have been reported for the desmethyl tocopherols, such as gamma-tocopherol, and for specific tocopherol metabolites, most notably the carboxyethyl-hydroxychroman (CEHC) products. The activities of these other tocopherols do not map directly to their chemical antioxidant behavior but rather reflect anti-inflammatory, antineoplastic, and natriuretic functions possibly mediated through specific binding interactions. Moreover, a nascent body of epidemiological data suggests that gamma-tocopherol is a better negative risk factor for certain types of cancer and myocardial infarction than is a alpha-tocopherol. The potential public health implications are immense, given the extreme popularity of alphaT supplementation which can unintentionally deplete the body of gamma-tocopherol. These findings may or may not signal a major paradigm shift in free radical biology and medicine. The data argue for thorough experimental and epidemiological reappraisal of desmethyl tocopherols, especially within the contexts of cardiovascular disease and cancer biology.     

Cluster-randomised controlled trial of community mobilisation in Mumbai slums to improve care during pregnancy, delivery, postpartum and for the newborn

Background

Chronic back pain is a major public health problem and the primary reason patients seek acupuncture treatment. Therefore, an objective assessment of acupuncture efficacy is critical for making informed decisions about its appropriate role for patients with this common condition. This study addresses methodological shortcomings that have plagued previous studies evaluating acupuncture for chronic low back pain.

Methods and Design

A total of 640 participants (160 in each of four arms) between the ages of 18 and 70 years of age who have low back pain lasting at least 3 months will be recruited from integrated health care delivery systems in Seattle and Oakland. They will be randomized to one of two forms of Traditional Chinese Medical (TCM) acupuncture needling (individualized or standardized), a "control" group (simulated acupuncture), or to continued usual medical care. Ten treatments will be provided over 7 weeks. Study participants and the "Diagnostician" acupuncturists who evaluate participants and propose individualized treatments will be masked to the acupuncture treatment actually assigned each participant. The "Therapist" acupuncturists providing the treatments will not be masked but will have limited verbal interaction with participants. The primary outcomes, standard measures of dysfunction and bothersomeness of low back pain, will be assessed at baseline, and after 8, 26, and 52 weeks by telephone interviewers masked to treatment assignment. General health status, satisfaction with back care, days of back-related disability, and use and costs of healthcare services for back pain will also be measured. The primary analysis comparing outcomes by randomized treatment assignment will be analysis of covariance adjusted for baseline value. For both primary outcome measures, this trial will have 99% power to detect the presence of a minimal clinically significant difference among all four treatment groups and over 80% power for most pairwise comparisons. Secondary analyses will compare the proportions of participants in each group that improve by a clinically meaningful amount.

Conclusion

Results of this trial will help clarify the value of acupuncture needling as a treatment for chronic low back pain.

Trial registration

Clinical Trials.gov NCT00065585.     

Acupuncture for migraine prophylaxis: a randomized controlled trial

Background:

Acupuncture is commonly used to treat migraine. We assessed the efficacy of acupuncture at migraine-specific acupuncture points compared with other acupuncture points and sham acupuncture.

Methods:

We performed a multicentre, single-blind randomized controlled trial. In total, 480 patients with migraine were randomly assigned to one of four groups (Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture or sham acupuncture [control]). All groups received 20 treatments, which included electrical stimulation, over a period of four weeks. The primary outcome was the number of days with a migraine experienced during weeks 5–8 after randomization. Our secondary outcomes included the frequency of migraine attack, migraine intensity and migraine-specific quality of life.

Results:

Compared with patients in the control group, patients in the acupuncture groups reported fewer days with a migraine during weeks 5–8, however the differences between treatments were not significant (p > 0.05). There was a significant reduction in the number of days with a migraine during weeks 13–16 in all acupuncture groups compared with control (Shaoyang-specific acupuncture v. control: difference –1.06 [95% confidence interval (CI) –1.77 to –0.5], p = 0.003; Shaoyang-nonspecific acupuncture v. control: difference –1.22 [95% CI –1.92 to –0.52], p < 0.001; Yangming-specific acupuncture v. control: difference –0.91 [95% CI –1.61 to –0.21], p = 0.011). We found that there was a significant, but not clinically relevant, benefit for almost all secondary outcomes in the three acupuncture groups compared with the control group. We found no relevant differences between the three acupuncture groups.

Interpretation:

Acupuncture tested appeared to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture.

Trial Registration:

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00599586","term_id":"NCT00599586"}}NCT00599586About 6%–8% of men and 16%–18% of women in the United States and England experience migraines, with or without an aura.^1,2 A prevalence of 1% has been reported in mainland China,³ compared with 4.7% in Hong Kong and 9.1% in Taiwan.^4,5 A recent Cochrane meta-analysis suggests that acupuncture as migraine prophylaxis is safe and effective and should be considered as a treatment option for willing patients.⁶Although the specific effects acupuncture are controversial, acupuncture, as it is currently practised, clearly differentiates between real acupuncture points and nonacupuncture points. The Chinese Government launched the National Basic Research Program to obtain more data about the specificity of acupuncture points.⁷Trials from Italy and Brazil^8,9 showed that acupuncture was more effective than sham acupuncture in preventing migraines, but other trials have reported no differences.^10–13 There is no evidence that one acupuncture strategy is more effective than another for treating migraines. According to acupuncture theory, a headache on the lateral side is usually defined as a Shaoyang headache. In Jinkuiyi,¹⁴ migraines are said to affect the yang meridians (including the Taiyang, Yangming and Shaoyang meridians). In Lingshu,¹⁵ the Shaoyang meridians are said to go through the lateral side of the body, therefore the Shaoyang meridians are thought to be superior for treating migraines. Some points on the Shaoyang meridians are regarded as being more specific for migraines than other points.¹⁶Our aim was to investigate whether acupuncture at specific acupuncture points was more efficacious in preventing migraine than sham acupuncture at nonacupuncture points. We also investigated whether the efficacy varied when acupuncture points along different meridians or points along the same meridian were used.     

Novel therapeutic approaches in GEP-NETs based on genetic and epigenetic alterations

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies with distinct prognosis based on primary tumor localization, grade, stage and functionality. Surgery remains the only curative option in localized tumors, but systemic therapy is the mainstay of treatment for patients with advanced disease. For decades, the therapeutic landscape of GEP-NETs was limited to chemotherapy regimens with low response rates. The arrival of novel agents such as somatostatin analogues, peptide receptor radionuclide therapy, tyrosine kinase inhibitors or mTOR-targeted drugs, has changed the therapeutic paradigm of GEP-NETs. However, the efficacy of these agents is limited in time and there is scarce knowledge of optimal treatment sequencing. In recent years, massive parallel sequencing techniques have started to unravel the genomic intricacies of these tumors, allowing us to better understand the mechanisms of resistance to current treatments and to develop new targeted agents that will hopefully start an era for personalized treatment in NETs. In this review we aim to summarize the most relevant genomic aberrations and signaling pathways underlying GEP-NET tumorigenesis and potential therapeutic strategies derived from them.     

Transpososome dynamics and regulation in Tn10 transposition

Tn10 is a bacterial transposon that transposes through a non-replicative mechanism. This mode of DNA transposition is widely used in bacteria and is also used by "DNA-based" transposons in eukaryotes. Tn10 has served as a paradigm for this mode of transposition and continues to provide novel insights into how steps in transposition reactions occur and how these steps are regulated. A common feature of transposition reactions is that they require the formation of a higher order protein-DNA complex called a transpososome. A major objective in the last few years has been to better understand the dynamics of transpososome assembly and progression through the course of transposition reactions. This problem is particularly interesting in the Tn10 system because two important host proteins, IHF and H-NS, have been implicated in regulating transpososome assembly and/or function. Interestingly, H-NS is an integral part of stress response pathways in bacteria, and its function is known to be sensitive to changes in environmental conditions. Consequently, H-NS may provide a means of allowing Tn10 to responed to changing environmental conditions. The current review focuses on the roles of both IHF and H-NS on Tn10 transposition.     

Efficacy and safety of Indigo naturalis extract in oil (Lindioil) in treating nail psoriasis: A randomized,observer-blind,vehicle-controlled trial

Treating nail psoriasis is notoriously difficult and lacks standardized therapeutic regimens. Indigo naturalis has been demonstrated to be safe and effective in treating skin psoriasis. This trial was conducted to evaluate the efficacy and safety of refined indigo naturalis extract in oil (Lindioil) in treating nail psoriasis. Thirty-one outpatients with symmetrically comparable psoriatic nails were enrolled. Lindioil (experimental group) or olive oil (control group) was applied topically to the same subjects’ two bilaterally symmetrical psoriatic nails twice daily for the first 12 weeks and then subjects applied Lindioil to both hands for 12 additional weeks. Outcomes were measured using Nail Psoriasis Severity Index (NAPSI) for five nails on one hand and for the single most severely affected nail from either hand. The results show a reduction of NAPSI scores for the 12-week treatment for the Lindioil group (49.8% for one hand and 59.3% for single nail) was superior to the reduction in the scores for the control group (22.9%, 16.3%, respectively). There were no adverse events during the 24 weeks of treatment. This trial demonstrates that Lindioil is a novel, safe and effective therapy for treating nail psoriasis.     

Cost-Effectiveness Analysis of Acupuncture,Counselling and Usual Care in Treating Patients with Depression: The Results of the ACUDep Trial

Background

New evidence on the clinical effectiveness of acupuncture plus usual care (acupuncture) and counselling plus usual care (counselling) for patients with depression suggests the need to investigate the health-related quality of life and costs of these treatments to understand whether they should be considered a good use of limited health resources.

Methods and Findings

The cost-effectiveness analyses are based on the Acupuncture, Counselling or Usual care for Depression (ACUDep) trial results. Statistical analyses demonstrate a difference in mean quality adjusted life years (QALYs) and suggest differences in mean costs which are mainly due to the price of the interventions. Probabilistic sensitivity analysis is used to express decision uncertainty. Acupuncture and counselling are found to have higher mean QALYs and costs than usual care. In the base case analysis acupuncture has an incremental cost-effectiveness ratio (ICER) of £4,560 per additional QALY and is cost-effective with a probability of 0.62 at a cost-effectiveness threshold of £20,000 per QALY. Counselling compared with acupuncture is more effective and more costly with an ICER of £71,757 and a probability of being cost-effective of 0.36. A scenario analysis of counselling versus usual care, excluding acupuncture as a comparator, results in an ICER of £7,935 and a probability of 0.91.

Conclusions

Acupuncture is cost-effective compared with counselling or usual care alone, although the ranking of counselling and acupuncture depends on the relative cost of delivering these interventions. For patients in whom acupuncture is unavailable or perhaps inappropriate, counselling has an ICER less than most cost-effectiveness thresholds. However, further research is needed to determine the most cost-effective treatment pathways for depressed patients when the full range of available interventions is considered.     

Effects of rehabilitative interventions on pain, function and physical impairments in people with hand osteoarthritis: a systematic review

Introduction

Hand osteoarthritis (OA) is associated with pain, reduced grip strength, loss of range of motion and joint stiffness leading to impaired hand function and difficulty with daily activities. The effectiveness of different rehabilitation interventions on specific treatment goals has not yet been fully explored. The objective of this systematic review is to provide evidence based knowledge on the treatment effects of different rehabilitation interventions for specific treatment goals for hand OA.

Methods

A computerized literature search of Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), ISI Web of Science, the Physiotherapy Evidence Database (PEDro) and SCOPUS was performed. Studies that had an evidence level of 2b or higher and that compared a rehabilitation intervention with a control group and assessed at least one of the following outcome measures - pain, physical hand function or other measures of hand impairment - were included. The eligibility and methodological quality of trials were systematically assessed by two independent reviewers using the PEDro scale. Treatment effects were calculated using standardized mean difference and 95% confidence intervals.

Results

Ten studies, of which six were of higher quality (PEDro score >6), were included. The rehabilitation techniques reviewed included three studies on exercise, two studies each on laser and heat, and one study each on splints, massage and acupuncture. One higher quality trial showed a large positive effect of 12-month use of a night splint on hand pain, function, strength and range of motion. Exercise had no effect on hand pain or function although it may be able to improve hand strength. Low level laser therapy may be useful for improving range of motion. No rehabilitation interventions were found to improve stiffness.

Conclusions

There is emerging high quality evidence to support that rehabilitation interventions can offer significant benefits to individuals with hand OA. A summary of the higher quality evidence is provided to assist with clinical decision making based on current evidence. Further high-quality research is needed concerning the effects of rehabilitation interventions on specific treatment goals for hand OA.     

Stochastic ensembles, conformationally adaptive teamwork, and enzymatic detoxification

It has been appreciated for a long time that enzymes exist as conformational ensembles throughout multiple stages of the reactions they catalyze, but there is renewed interest in the functional implications. The energy landscape that results from conformationlly diverse poteins is a complex surface with an energetic topography in multiple dimensions, even at the transition state(s) leading to product formation, and this represents a new paradigm. At the same time there has been renewed interest in conformational ensembles, a new paradigm concerning enzyme function has emerged, wherein catalytic promiscuity has clear biological advantages in some cases. "Useful", or biologically functional, promiscuity or the related behavior of "multifunctionality" can be found in the immune system, enzymatic detoxification, signal transduction, and the evolution of new function from an existing pool of folded protein scaffolds. Experimental evidence supports the widely held assumption that conformational heterogeneity promotes functional promiscuity. The common link between these coevolving paradigms is the inherent structural plasticity and conformational dynamics of proteins that, on one hand, lead to complex but evolutionarily selected energy landscapes and, on the other hand, promote functional promiscuity. Here we consider a logical extension of the overlap between these two nascent paradigms: functionally promiscuous and multifunctional enzymes such as detoxification enzymes are expected to have an ensemble landscape with more states accessible on multiple time scales than substrate specific enzymes. Two attributes of detoxification enzymes become important in the context of conformational ensembles: these enzymes metabolize multiple substrates, often in substrate mixtures, and they can form multiple products from a single substrate. These properties, combined with complex conformational landscapes, lead to the possibility of interesting time-dependent, or emergent, properties. Here we demonstrate these properties with kinetic simulations of nonequilibrium steady state (NESS) behavior resulting from energy landscapes expected for detoxification enzymes. Analogous scenarios with other promiscuous enzymes may be worthy of consideration.