Low back related leg pain: An investigation of construct validity of a new classification system

BACKGROUND: Leg pain is associated with back pain in 25–65% of all cases and classified as somatic referred pain or radicular pain. However, distinction between the two may be difficult as different pathomechanisms may cause similar patterns of pain. Therefore a pathomechanism based classification system was proposed, with four distinct hierarchical and mutually exclusive categories: Neuropathic Sensitization (NS) comprising major features of neuropathic pain with sensory sensitization; Denervation (D) arising from significant axonal compromise; Peripheral Nerve Sensitization (PNS) with marked nerve trunk mechanosensitivity; and Musculoskeletal (M) with pain referred from musculoskeletal structures. OBJECTIVE: To investigate construct validity of the classification system. METHODS: Construct validity was investigated by determining the relationship of nerve functioning with subgroups of patients and asymptomatic controls. Thus somatosensory profiles of subgroups of patients with low back related leg pain (LBRLP) and healthy controls were determined by a comprehensive quantitative sensory test (QST) protocol. It was hypothesized that subgroups of patients and healthy controls would show differences in QST profiles relating to underlying pathomechanisms. RESULTS: 77 subjects with LBRLP were recruited and classified in one of the four groups. Additionally, 18 age and gender matched asymptomatic controls were measured. QST revealed signs of pain hypersensitivity in group NS and sensory deficits in group D whereas Groups PNS and M showed no significant differences when compared to the asymptomatic group. CONCLUSIONS: These findings support construct validity for two of the categories of the new classification system, however further research is warranted to achieve construct validation of the classification system as a whole

Including Systematic Uncertainties in Confidence Interval Construction for Poisson Statistics

One way to incorporate systematic uncertainties into the calculation of confidence intervals is by integrating over probability density functions parametrizing the uncertainties. In this note we present a development of this method which takes into account uncertainties in the prediction of background processes, uncertainties in the signal detection efficiency and background efficiency and allows for a correlation between the signal and background detection efficiencies. We implement this method with the Feldman & Cousins unified approach with and without conditioning. We present studies of coverage for the Feldman & Cousins and Neyman ordering schemes. In particular, we present two different types of coverage tests for the case where systematic uncertainties are included. To illustrate the method we show the relative effect of including systematic uncertainties the case of dark matter search as performed by modern neutrino tel escopes.Comment: 23 pages, 10 figures, replaced to match published versio

The benefit of a mechanical needle stimulation pad in patients with chronic neck and lower back pain: Two randomized controlled pilot studies

Objectives. The objective was to investigate whether a treatment with a needle stimulation pad (NSP) changes perceived pain and/or sensory thresholds in patients with chronic neck (NP) and lower back pain (BP). Methods. 40 patients with chronic NP and 42 patients with chronic BP were equally randomized to either treatment or waiting list control group. The treatment group self-administered a NSP over a period of 14 days. Pain ratings were recorded on numerical rating scales (NRSs). Mechanical detection thresholds (MDTs) and pressure pain thresholds (PPTs) were determined at the site of maximal pain and in the adjacent region, vibration detection thresholds (VDT) were measured at close spinal processes. The Northwick Park Neck Pain Questionnaire (NPQ) and the Oswestry Disability Index (ODI) were utilized for the NP and BP study, respectively. Results. NRS ratings were significantly reduced for the treatment groups compared to the control groups (NP: P =. 021 and BP: P . 001), accompanied by a significant increase of PPT at pain maximum (NP: P =. 032 and BP: P =. 013). There was no effect on VDT and MDT. The NPQ showed also a significant improvement, but not the ODI. Conclusions. The mechanical NSP seems to be an effective treatment method for chronic NP and BP. © 2012 Claudia Hohmann et al

Search for Rare and Forbidden 3-body Di-muon Decays of the Charmed Mesons D+ and Ds+

Using a high statistics sample of photo-produced charm particles from the FOCUS experiment at Fermilab, we report results of a search for eight rare and Standard-Model-forbidden decays: D+, Ds+ > h+/- muon-/+ muon+ (with h=pion or Kaon). Improvement over previous results by a factor of 1.7--14 is realized. Our branching ratio upper limit D+ > pion+ muon- muon+ of 8.8E-6 at the 90% C.L. is below the current MSSM R-Parity violating constraint.Comment: 17 pages, 7 figure file

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy:A Pilot Study

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity with significant sequelae. There is a lack of standardized objective and reliable assessment tools in CIPN. In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles. This article reports on the feasibility and value of RCM in CIPN.Background There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. Patients and Methods Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 x 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. Results In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 +/- 7.1 vs 30.9 +/- 4.2 MC/3 x 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (rho = -0.51), warm detection (rho = -0.47), cold pain (rho = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P <= .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). Conclusions The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression

The use of quantitative sensory testing in cancer pain assessment: A systematic review

Objective: To summarize the literature on the use of quantitative sensory testing (QST) in the assessment of pain in people with cancer and to describe which QST parameters consistently demonstrate abnormal sensory processing in patients with cancer pain. Databases and Data Treatment: Medline, EMBASE, AMED, CINAHL, SCOPUS and CENTRAL were searched for observational or experimental studies using QST in patients with a cancer diagnosis and reporting pain. Search strategies were based on the terms “quantitative sensory testing”, “cancer”, “pain”, “cancer pain” and “assessment”. Databases were searched from inception to January 2019. Data were extracted and synthesized narratively, structured around the different QST modalities and sub‐grouped by cancer pain aetiology (tumour‐ or treatment‐related pain). Results: Searches identified 286 records of which 18 met the eligibility criteria for inclusion. Three studies included patients with tumour‐related pain, and 15 studies included patients with pain from chemotherapy‐induced peripheral neuropathy (CIPN). Across all studies, 50% (9/18) reported sensory abnormities using thermal detection thresholds (cool and warm), 44% (8/18) reported abnormal mechanical detection thresholds using von‐Frey filaments and 39% (7/18) found abnormal pinprick thresholds. Abnormal vibration and thermal pain (heat/cold) thresholds were each reported in a third of included studies. Conclusion: This systematic review highlights the lack of published data characterizing the sensory phenotype of tumour‐related cancer pain. This has implications for our understanding of the underlying pathophysiological mechanisms of cancer pain. Understanding the multiple mechanisms driving cancer pain will help to move towards rational individualized analgesic treatment choices. Significance: This systematic review found that pain in cancer patients is associated with abnormal sensory responses to thermal, mechanical and pinprick stimuli. However, these findings are based primarily on studies of chemotherapy‐induced peripheral neuropathy and data on tumour‐related pain are lacking, warranting further research

Gabapentin for complex regional pain syndrome in Machado-Joseph disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chronic pain is a common problem for patients with Machado-Joseph disease. Most of the chronic pain in Machado-Joseph disease has been reported to be of musculoskeletal origin, but now there seems to be different chronic pain in patients with Machado-Joseph disease.</p> <p>Case presentation</p> <p>A 29-year-old man (Han Chinese, Hoklo) with Machado-Joseph disease experienced severe chronic pain in both feet, cutaneous thermal change, thermal hypersensitivity, focal edema, and sweating and had a history of bone fracture. These symptoms were compatible with a diagnosis of complex regional pain syndrome. After common analgesics failed to relieve his pain, gabapentin was added and titrated to 2000 mg/day (500 mg every six hours) in less than two weeks. This relieved 40% of his pain and led to significant clinical improvement.</p> <p>Conclusions</p> <p>The pathophysiology of complex regional pain syndrome includes peripheral and central sensitizations, the latter of which might be associated with the neurodegeneration in Machado-Joseph disease. In this report, we suggest that gabapentin could inhibit central sensitization as an adjunct for complex regional pain syndrome in patients with Machado-Joseph disease.</p

Bilateral Sensory Abnormalities in Patients with Unilateral Neuropathic Pain; A Quantitative Sensory Testing (QST) Study

In patients who experience unilateral chronic pain, abnormal sensory perception at the non-painful side has been reported. Contralateral sensory changes in these patients have been given little attention, possibly because they are regarded as clinically irrelevant. Still, bilateral sensory changes in these patients could become clinically relevant if they challenge the correct identification of their sensory dysfunction in terms of hyperalgesia and allodynia. Therefore, we have used the standardized quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain (DFNS) to investigate somatosensory function at the painful side and the corresponding non-painful side in unilateral neuropathic pain patients using gender- and age-matched healthy volunteers as a reference cohort. Sensory abnormalities were observed across all QST parameters at the painful side, but also, to a lesser extent, at the contralateral, non-painful side. Similar relative distributions regarding sensory loss/gain for non-nociceptive and nociceptive stimuli were found for both sides. Once a sensory abnormality for a QST parameter at the affected side was observed, the prevalence of an abnormality for the same parameter at the non-affected side was as high as 57% (for Pressure Pain Threshold). Our results show that bilateral sensory dysfunction in patients with unilateral neuropathic pain is more rule than exception. Therefore, this phenomenon should be taken into account for appropriate diagnostic evaluation in clinical practice. This is particularly true for mechanical stimuli where the 95% Confidence Interval for the prevalence of sensory abnormalities at the non-painful side ranges between 33% and 50%

Accelerated expansion from ghost-free bigravity: a statistical analysis with improved generality

We study the background cosmology of the ghost-free, bimetric theory of gravity. We perform an extensive statistical analysis of the model using both frequentist and Bayesian frameworks and employ the constraints on the expansion history of the Universe from the observations of supernovae, the cosmic microwave background and the large scale structure to estimate the model's parameters and test the goodness of the fits. We explore the parameter space of the model with nested sampling to find the best-fit chi-square, obtain the Bayesian evidence, and compute the marginalized posteriors and mean likelihoods. We mainly focus on a class of sub-models with no explicit cosmological constant (or vacuum energy) term to assess the ability of the theory to dynamically cause a late-time accelerated expansion. The model behaves as standard gravity without a cosmological constant at early times, with an emergent extra contribution to the energy density that converges to a cosmological constant in the far future. The model can in most cases yield very good fits and is in perfect agreement with the data. This is because many points in the parameter space of the model exist that give rise to time-evolution equations that are effectively very similar to those of the $\Lambda$CDM. This similarity makes the model compatible with observations as in the $\Lambda$CDM case, at least at the background level. Even though our results indicate a slightly better fit for the $\Lambda$CDM concordance model in terms of the $p$-value and evidence, none of the models is statistically preferred to the other. However, the parameters of the bigravity model are in general degenerate. A similar but perturbative analysis of the model as well as more data will be required to break the degeneracies and constrain the parameters, in case the model will still be viable compared to the $\Lambda$CDM.Comment: 42 pages, 9 figures; typos corrected in equations (2.12), (2.13), (3.7), (3.8) and (3.9); more discussions added (footnotes 5, 8, 10 and 13) and abstract, sections 4.2, 4.3 and 5 (conclusions) modified in response to referee's comments; references added; acknowledgements modified; all results completely unchanged; matches version accepted for publication in JHE