Pain education for patients with non-specific low back pain in Nepal: Protocol of a feasibility randomised clinical trial (PEN-LBP Trial)

Introduction Low back pain (LBP) is the leading cause of years lived with disability in Nepal and elsewhere. Management of LBP that is evidence-based, easily accessible, cost-effective and culturally appropriate is desirable. The primary aim of this feasibility study is to determine if it is feasible to conduct a full randomised clinical trial evaluating the effectiveness of pain education as an intervention for individuals with LBP in Nepal, relative to guideline-based physiotherapy treatment. The findings of the study will inform the planning of a full clinical trial and if any modifications are required to the protocol before undertaking a full trial. Methods/analysis This protocol describes an assessor-blinded feasibility clinical trial investigating feasibility of the pain education intervention in patients with non-specific LBP in a physiotherapy hospital in Kathmandu, Nepal. Forty patients with LBP will be randomly allocated to either pain education or guideline-based physiotherapy treatment (control). Outcomes will be assessed at baseline and at a 1 week post-treatment. The primary outcomes are related to feasibility, including: (1) participant willingness to participate in a randomised clinical trial, (2) feasibility of assessor blinding, (3) eligibility and recruitment rates, (4) acceptability of screening procedures and random allocation, (5) possible contamination between the groups, (6) intervention credibility, (7) intervention adherence, (8) treatment satisfaction and (9) difficulty in understanding the interventions being provided. Ethics/dissemination The protocol was approved by Nepal Health Research Council (NHRC; registration number: 422/2017) and University of Otago Human Ethics Committee for Health (registration number: H17/157). The results of the study will be presented at national and international conferences and published in a peer-reviewed journal. Trial registration number NCT03387228; Pre-results

Results of a feasibility randomised clinical trial on pain education for low back pain in Nepal: The Pain Education in Nepal-Low Back Pain (PEN-LBP) feasibility trial

Objectives The aims of this study were to: (1) develop pain education materials in Nepali and (2) determine the feasibility of conducting a randomised clinical trial (RCT) of a pain education intervention using these materials in Nepal. Design A two-arm, parallel, assessor-blinded, feasibility RCT. Setting A rehabilitation hospital in Kathmandu, Nepal. Participants Forty Nepalese with non-specific low back pain (mean [SD] age 41 [14] years; 12 [30%] women). Interventions Eligible participants were randomised, by concealed, 1:1 allocation, to one of two groups: (1) a pain education intervention and (2) a guideline-based physiotherapy active control group intervention. Each intervention was delivered by a physiotherapist in a single, 1-hour, individualised treatment session. Primary outcome measures The primary outcomes were related to feasibility: recruitment, retention and treatment adherence of participants, feasibility and blinding of outcome assessments, fidelity of treatment delivery, credibility of, and satisfaction with, treatment. Assessments were performed at baseline and at 1 week post-treatment. Secondary outcome measures Pain intensity, pain interference, pain catastrophising, sleep disturbance, resilience, global rating of change, depression and quality of life. Statistical analyses were conducted blind to group allocation. Results Forty participants were recruited. Thirty-eight participants (95%) completed the 1-week post-treatment assessment. Most primary outcomes surpassed the a priori thresholds for feasibility. Several findings have important implications for designing a full trial. Secondary analyses suggest clinical benefit of pain education over the control intervention, with larger decrease in pain intensity (mean difference=3.56 [95% CI 0.21 to 6.91]) and pain catastrophising (mean difference=6.16 [95% CI 0.59 to 11.72]) in the pain education group. Pain intensity would seem an appropriate outcome for a full clinical trial. One minor adverse event was reported. Conclusion We conclude that a full RCT of pain education for back pain in Nepal is feasible and warranted. Trial registration number NCT03387228; Results

Group Differences Between Countries and Between Languages in Pain-Related Beliefs, Coping, and Catastrophizing in Chronic Pain: A Systematic Review

Objective: To evaluate the extent to which pain-related beliefs, appraisals, coping, and catastrophizing differ between countries, language groups, and country economy. / Design: Systematic review. / Methods: Two independent reviewers searched 15 databases without restriction for date or language of publication. Studies comparing pain beliefs/appraisals, coping, or catastrophizing across two or more countries or language groups in adults with chronic pain (pain for longer than three months) were included. Two independent reviewers extracted data and performed the quality appraisal. Study quality was rated as low, moderate, or high using a 10-item modified STROBE checklist. Effect sizes were reported as small (0.20–0.49), medium (0.50–0.79), or large (≥0.80). / Results: We retrieved 1,365 articles, read 42 potential full texts, and included 10 (four moderate-quality, six low-quality) studies. A total of 6,797 adults with chronic pain (33% with chronic low back pain) were included from 16 countries. Meta-analysis was not performed because of heterogeneity in the studies. A total of 103 effect sizes were computed for individual studies, some of which indicated between-country differences in pain beliefs, coping, and catastrophizing. Of these, the majority of effect sizes for pain beliefs/appraisal (60%; eight large, eight medium, and eight small), for coping (60%; seven large, 11 medium, and 16 small), and for catastrophizing (50%; two medium, one small) evidenced statistically significant between-country differences, although study quality was low to moderate. / Conclusions: In 50% or more of the studies, mean scores in the measures of pain beliefs and appraisals, coping responses, and catastrophizing were significantly different between people from different countries

Group differences between countries and between languages in pain-related beliefs, coping, and catastrophizing in chronic pain: A systematic review

Objective. To evaluate the extent to which pain-related beliefs, appraisals, coping, and catastrophizing differ between countries, language groups, and country economy. Design. Systematic review. Methods. Two independent reviewers searched 15 databases without restriction for date or language of publication. Studies comparing pain beliefs/appraisals, coping, or catastrophizing across two or more countries or language groups in adults with chronic pain (pain for longer than three months) were included. Two independent reviewers extracted data and performed the quality appraisal. Study quality was rated as low, moderate, or high using a 10-item modified STROBE checklist. Effect sizes were reported as small (0.20-0.49), medium (0.50-0.79), or large (≥0.80). Results. We retrieved 1,365 articles, read 42 potential full texts, and included 10 (four moderate-quality, six low-quality) studies. A total of 6,797 adults with chronic pain (33% with chronic low back pain) were included from 16 countries. Meta-analysis was not performed because of heterogeneity in the studies. A total of 103 effect sizes were computed for individual studies, some of which indicated between-country differences in pain beliefs, coping, and catastrophizing. Of these, the majority of effect sizes for pain beliefs/appraisal (60%; eight large, eight medium, and eight small), for coping (60%; seven large, 11 medium, and 16 small), and for catastrophizing (50%; two medium, one small) evidenced statistically significant between-country differences, although study quality was low to moderate. Conclusions. In 50% or more of the studies, mean scores in the measures of pain beliefs and appraisals, coping responses, and catastrophizing were significantly different between people from different countries

Clinimetric properties of the Nepali version of the Pain Catastrophizing Scale in individuals with chronic pain

Background: Pain catastrophizing is an exaggerated negative cognitive response related to pain. It is commonly assessed using the Pain Catastrophizing Scale (PCS). Translation and validation of the scale in a new language would facilitate cross-cultural comparisons of the role that pain catastrophizing plays in patient function. Purpose: The aim of this study was to translate and culturally adapt the PCS into Nepali (Nepali version of PCS [PCS-NP]) and evaluate its clinimetric properties. Methods: We translated, cross-culturally adapted, and performed an exploratory factor analysis (EFA) of the PCS-NP in a sample of adults with chronic pain (N=143). We then confirmed the resulting factor model in a separate sample (N=272) and compared this model with 1-, 2-, and 3-factor models previously identified using confirmatory factor analyses (CFAs). We also computed internal consistencies, test–retest reliabilities, standard error of measurement (SEM), minimal detectable change (MDC), and limits of agreement with 95% confidence interval (LOA95%) of the PCS-NP scales. Concurrent validity with measures of depression, anxiety, and pain intensity was assessed by computing Pearson’s correlation coefficients. Results: The PCS-NP was comprehensible and culturally acceptable. We extracted a two-factor solution using EFA and confirmed this model using CFAs in the second sample. Adequate fit was also found for a one-factor model and different two- and three-factor models based on prior studies. The PCS-NP scores evidenced excellent reliability and temporal stability, and demonstrated validity via moderate-to-strong associations with measures of depression, anxiety, and pain intensity. The SEM and MDC for the PCS-NP total score were 2.52 and 7.86, respectively (range of PCS scores 0–52). LOA95%was between -15.17 and +16.02 for the total PCS-NP scores. Conclusion: The PCS-NP is a valid and reliable instrument to assess pain catastrophizing in Nepalese individuals with chronic pain

Influence of epithermal muonic molecule formation on kinetics of the μ\muCF processes in deuterium

The non-resonant formation of $dd\mu$ molecules in the loosely bound state in collisions of non-thermalized $d\mu$ atoms with deuterium molecules D$_2$ has been considered. The process of such a type is possible only for collision energies exceeded the ionization potential of D$_2$. The calculated rates of $dd\mu$ formation in the above-threshold energy region are about one order of magnitude higher than obtained earlier. The role of epithermal non-resonant $\mu$-molecule formation for the kinetics of $\mu$CF processes in D$_2$ gas was studied. It was shown that the non-resonant $dd\mu$ formation by $d\mu$ atoms accelerated during the cascade can be directly observed in the neutron time spectra at very short initial times.Comment: 6 pages, 5 figures, Proceedings of the International Conference on Exotic Atoms and Related Topics EXA-2011, Vienna, Sep 5-9, 201

On the spectral problem of N=4 SYM with orthogonal or symplectic gauge group

We study the spectral problem of N=4 SYM with gauge group SO(N) and Sp(N). At the planar level, the difference to the case of gauge group SU(N) is only due to certain states being projected out, however at the non-planar level novel effects appear: While 1/N-corrections in the SU(N) case are always associated with splitting and joining of spin chains, this is not so for SO(N) and Sp(N). Here the leading 1/N-corrections, which are due to non-orientable Feynman diagrams in the field theory, originate from a term in the dilatation operator which acts inside a single spin chain. This makes it possible to test for integrability of the leading 1/N-corrections by standard (Bethe ansatz) means and we carry out various such tests. For orthogonal and symplectic gauge group the dual string theory lives on the orientifold AdS5xRP5. We discuss various issues related to semi-classical strings on this background.Comment: 25 pages, 3 figures. v2: Minor clarifications, section 5 expande

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites <i>Trypanosoma brucei</i> (<i>T.b.</i>) <i>gambiense</i> or <i>T.b.rhodesiense</i> and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage <i>T.b.rhodesiense</i> infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-͎-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties <i>in vitro</i> and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

Cooling a nanomechanical resonator with quantum back-action

Quantum mechanics demands that the act of measurement must affect the measured object. When a linear amplifier is used to continuously monitor the position of an object, the Heisenberg uncertainty relationship requires that the object be driven by force impulses, called back-action. Here we measure the back-action of a superconducting single-electron transistor (SSET) on a radiofrequency nanomechanical resonator. The conductance of the SSET, which is capacitively coupled to the resonator, provides a sensitive probe of the latter's position;back-action effects manifest themselves as an effective thermal bath, the properties of which depend sensitively on SSET bias conditions. Surprisingly, when the SSET is biased near a transport resonance, we observe cooling of the nanomechanical mode from 550mK to 300mK-- an effect that is analogous to laser cooling in atomic physics. Our measurements have implications for nanomechanical readout of quantum information devices and the limits of ultrasensitive force microscopy (such as single-nuclear-spin magnetic resonance force microscopy). Furthermore, we anticipate the use of these backaction effects to prepare ultracold and quantum states of mechanical structures, which would not be accessible with existing technology.Comment: 28 pages, 7 figures; accepted for publication in Natur