Pain Outcomes in Patients after Artificial Disc Replacement versus Fusion in the Cervical Spine: A Systematic Review of Systematic Reviews

Background: Pain is a major complaint for patients with cervical disc disease and is one of the reasons for surgery. Cervical artificial disc replacement (C-ADR) has been introduced in 2002 to offer an alternative to anterior cervical discectomy and fusion (ACDF) to treat disc disease in the cervical spine and to reduce dysphagia, dislodgement or fracture in the affected segment or an increase motion at the adjacent levels of the cervical spine. Several studies and reviews attempted in the last decade to compare the two procedures head to head and to evaluate whether the new procedure lead to less complications, better clinical outcomes and more patients’ satisfaction. However, less attention was paid to pain outcomes in these studies. Aim: To evaluate the pain outcomes resulted from C-ADR in comparison to ACDF by reviewing the evidence presented in the systematic reviews of randomized clinical trails and other studies containing clinical data. Methods: A combination of the following keywords was used in the search for systematic reviews in [Medline via Ovid, Embase, Cochrane Database of Systematic Reviews, Google scholar]: (total disc replacement, prosthesis, implantation, diskectomy, arthroplasty) and (cervical vertebrae, cervical spine, spine) and (pain, disability, quality of life) and (systematic reviews, reviews, meta-analysis). The initial search was conducted on the 18 August 2013 and then updated on 02/12/2015. Two authors screened the results of the search independently. For the article to be selected for further consideration it has to be a systematic review and/or meta-analysis of trials that attempted to compare between the two interventions at the cervical region in which the pain relief was a primary or a secondary outcome. Results: The electronic search produced 881 hits of which 145 were duplicates. Twenty more articles were identified through manual search. Initial screening of the abstracts resulted in selection of 68 articles for further evaluation. The final judgement of the two reviewers was to include 10 systematic reviews and/or metaanalyses in this overview. The number of randomised trials reviewed by the selected reviews varies from 2 to 27. Other discrepancie

Effect of age, sex and gender on pain sensitivity: A narrative review

© 2017 Eltumi And Tashani. Introduction: An increasing body of literature on sex and gender differences in pain sensitivity has been accumulated in recent years. There is also evidence from epidemiological research that painful conditions are more prevalent in older people. The aim of this narrative review is to critically appraise the relevant literature investigating the presence of age and sex differences in clinical and experimental pain conditions. Methods: A scoping search of the literature identifying relevant peer reviewed articles was conducted on May 2016. Information and evidence from the key articles were narratively described and data was quantitatively synthesised to identify gaps of knowledge in the research literature concerning age and sex differences in pain responses. Results: This critical appraisal of the literature suggests that the results of the experimental and clinical studies regarding age and sex differences in pain contain some contradictions as far as age differences in pain are concerned. While data from the clinical studies are more consistent and seem to point towards the fact that chronic pain prevalence increases in the elderly findings from the experimental studies on the other hand were inconsistent, with pain threshold increasing with age in some studies and decreasing with age in others. Conclusion: There is a need for further research using the latest advanced quantitative sensory testing protocols to measure the function of small nerve fibres that are involved in nociception and pain sensitivity across the human life span. Implications: Findings from these studies should feed into and inform evidence emerging from other types of studies (e.g. brain imaging technique and psychometrics) suggesting that pain in the older humans may have unique characteristics that affect how old patients respond to intervention

An experimental investigation of the effect of age and sex/gender on pain sensitivity in healthy human participants

© 2018 El-Tumi et al. Background: Ageing is associated with alterations of the structure and function of somatosensory tissue that can impact on pain perception. The aim of this study was to investigate the relationship between age and pain sensitivity responses to noxious thermal and mechanical stimuli in healthy adults. Methods: 56 unpaid volunteers (28 women) aged between 20 and 55 years were categorised according to age into one of seven possible groups. The following measurements were taken: thermal detection thresholds, heat pain threshold and tolerance using a TSA-II NeuroSensory Analyzer; pressure pain threshold using a handheld electronic pressure algometer; and cold pressor pain threshold, tolerance, intensity and unpleasantness. Results: There was a positive correlation between heat pain tolerance and age (r = 0.228, P = 0.046), but no statistically significant differences between age groups for cold or warm detection thresholds, or heat pain threshold or tolerance. Forward regression found increasing age to be a predictor of increased pressure pain threshold (B = 0.378, P = 0.002), and sex/gender to be a predictor of cold pressor pain tolerance, with women having lower tolerance than men (B =-0.332, P = 0.006). Conclusion: The findings of this experimental study provide further evidence that pressure pain threshold increases with age and that women have lower thresholds and tolerances to innocuous and noxious thermal stimuli. Significance: The findings demonstrate that variations in pain sensitivity response to experimental stimuli in adults vary according to stimulus modality, age and sex and gender

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

Connective tissue metabolites following bone marrow transplantation in children

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN006571 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Investigating antisense oligonucleotides for reducing ACTH production in an in vitro model of Cushing’s disease

Background: Cushing’s disease (CD) is caused by high levels of blood cortisol resulting from excess secretion of adrenocorticotropic hormone (ACTH) from a corticotroph adenoma in the anterior pituitary gland. Clinical features include hypertension, diabetes, osteoporosis, and depression. If untreated CD has an increased mortality of five-fold owing to cardiovascular comorbidities, stroke and raised vulnerability to infection. Transsphenoidal surgery is considered the first-line treatment, but remission is achieved in only 65% of cases and the relapse rate is high. Furthermore, medical treatments are often accompanied by unpleasant side-effects. Antisense therapy is a technique for suppressing gene expression at the level of translation using antisense oligonucleotides (ASOs) against the mRNA of interest. Aims: Using an in vitro AtT-20 cell model, the overall aim of the project was to investigate antisense therapy as a treatment for CD by targeting ASOs against ACTH�encoding Pomc mRNA thereby reducing production of the hormone. Methods: Computer-aided design of POMC ASOs, transfection of ACTH�hypersecreting AtT-20 cells with POMC ASOs, measurement of ACTH by immunoassay and the innate immune response by ELISA, qualitative and quantitative assessment of ASO nuclease degradation, and statistical analysis using ANOVA and Student’s t tests. Results: Following ASO design guidelines and using ASO design programs, four POMC ASOs targeted at different exon sites were selected for experimentation. The ASOs were used unmodified, with a phosphorothioate-modified backbone, or with 2’- O-methyl- or locked nucleic acid (LNA)-modified end-nucleotides. All POMC ASOs significantly reduced ACTH secretion from AtT-20 cells when compared with untreated cells or control ASOs (14-59% of normal ACTH levels; ANOVA, P > 0.05). LNA�modified POMC ASOs were the most effective when used at lower concentrations (1 nM) and over time (five days). Modified ASOs were more stable to nuclease degradation. None of the ASOs appeared to stimulate the expression of cytokines associated with the innate immune response

Topical tacrolimus may be effective in the treatment of oral and perineal Crohn's disease

BACKGROUND—Crohn's disease of the mouth or perineum is more common in young people, and notably resistant to treatment. However, there is increasing evidence that topical therapy with tacrolimus (FK506) may be effective in skin diseases resistant to cyclosporin because of its high uptake in inflamed skin and subsequent reduction in keratinocyte chemokine production.
PATIENTS AND METHODS—Tacrolimus ointment was made up inhouse from the intravenous or oral formulation and suspended in appropriate vehicles for perioral or perianal administration at an initial concentration of 0.5 mg/g. This was administered open label to eight children (aged 5-18 years) with treatment resistant oral (three patients) and/or ulcerating perineal (six patients) Crohn's disease.
RESULTS—Marked improvement was seen in 7/8 patients within six weeks and healing within 1-6 months. One child with gross perineal and colonic disease showed little response. Two of the responders showed rebound worsening when tacrolimus was stopped or the dosage reduced rapidly, and one of these eventually required proctectomy. Slower weaning of drug concentration has been successful in 6/8 patients, with four receiving intermittent treatment and two on regular reduced dosage (0.1-0.3 mg/g) with follow up times of six months to 3.5 years. Serum concentrations of tacrolimus were undetectable in all patients.
CONCLUSIONS—Topical tacrolimus at low concentrations (0.5 mg/g) shows promise in the management of childhood perineal and oral Crohn's disease, with no evidence of significant systemic absorption. However, rapid weaning or abrupt cessation of therapy may cause rebound worsening of disease. Further controlled studies are required to assess the efficacy and safety of this treatment.


Keywords: Crohn's disease; tacrolimus; childre