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Objectives: The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis., Methods: Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed., Results: In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon- γ , interleukin- (IL-) 8, and 10 was shown. No side effects were described., Conclusion: This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments., Competing Interests: None of the authors have conflicts of interest to declare., (Copyright © 2021 C. Brock et al.)

Objective: This study aimed to explore individual and structural factors in patients with cancer and their potential association with customary non-attendance in general practice., Materials and Methods: We conducted a population-based cross-sectional study of all patients aged 50-89 years who were diagnosed with an incident cancer in 2009-2013 in Denmark. We investigated associations between being a customary non-attender (defined as having no consultations in general practice in the 19-36 months before diagnosis) and selected patient-related factors (demography, socioeconomic status), health-related factors (multimorbidity) and structural factors (urbanisation degree, list size of general practice and use of out-of-hours services) using logistic regression., Results: A total of 123,943 cancer patients were included; 11,567 (9.3%) of these were non-attenders. Non-attendance was associated with being more than 70 years of age, being single, having short or long education and being financially affluent. Non-attendance was rarely seen in cancer patients with (multi)morbidity, in individuals living in an area with 2,000-99,999 inhabitants and in individuals having contact with the out-of-hours services., Conclusion: Specific groups of cancer patients were more often customary non-attenders in general practice. General practice may need to reach out more directly to these patients to ensure more timely cancer diagnosis., (© 2019 John Wiley & Sons Ltd.)

Objective: Specialised follow-up care after cancer treatment is changing towards increased involvement of general practice. To ensure timely detection of new cancer events, knowledge is warranted on the timing of cancer recurrence (CR) and second primary cancer (SPC), including risk factors for CR., Methods: This population-based register study included 67,092 patients diagnosed with malignant melanoma, bladder, lung, ovarian, endometrial, colorectal and breast cancer in Denmark in 2008-2016. The time from primary cancer to CR or SPC and risk factors for prolonged time to CR were analysed and stratified on sex and primary cancer type., Results: Cancer recurrence proportions ranged from 6% to 35%. The risk of CR increased profoundly within the first 3 years and then levelled off, except for breast cancer. A total of 3%-6% of patients had SPC, with monotonously increasing cumulative incidence proportions. Besides primary tumour characteristics, lower educational level, living alone and comorbidity were associated with earlier CR. For example, in female malignant melanoma, HRs and 95% confidence intervals were 0.47 (0.37-0.61) for high educational level, 1.40 (1.16-1.68) for living alone and 2.38 (1.53-3.70) for high comorbidity., Conclusion: The results may inform stratified risk assessment in decision of frequency, location and duration of post-cancer follow-up care., (© 2019 John Wiley & Sons Ltd.)

Background: Activation of TRPM8 and TRPA1 receptors generates cold and cold pain sensations, respectively, and is presumably important in clinical pain manifestations, such as cold hyperalgesia. This study investigated the interaction between TRPM8 and TRPA1 receptors through stimulation of glabrous human skin (volar forearm) by topical administration of 40% L-menthol and 10% trans-cinnamaldehyde (CA), individually and in combination., Methods: Sensory manifestations were assessed in 10 healthy volunteers via a platform of 11 quantitative sensory (thermal and mechanical stimuli) and vasomotor tests (skin temperature, perfusion and axon-reflex-flare) in a double-blinded randomized crossover design., Results: Cold pain threshold was increased (p < 0.01, cold allodynia) by L-menthol alone and L-menthol + CA in combination but unaffected by CA. Mechanical pain threshold was significantly decreased (mechanical hyperalgesia) by all three substances (p < 0.01), with a significant intergroup difference found between CA alone and the less decreased L-menthol + CA (p < 0.05). Application of CA alone and L-menthol + CA in combination showed an increase in skin temperature and perfusion significantly larger than that induced by L-menthol alone (p < 0.05). An axon-reflex-flare was present after CA administration, but was significantly reduced upon addition of L-menthol (p < 0.01)., Conclusion: This study elucidates the potential of L-menthol as a counter-irritant to secondary neurogenic inflammation and provides evidence of an intricate interplay between cold receptors TRPA1 and TRPM8, warranting further investigation of the neural coding of cold pain perception., (© 2014 European Pain Federation - EFIC®)

Background: Cold allodynia and cold hyperalgesia are both elusive features of neuropathic pain, particularly in patients with various polyneuropathies. Numerous studies have suggested that topical application of L-menthol causes temporary cold hypersensitivity and thus acts as a proxy for associated symptoms. This review summarizes studies on L-menthol-induced nociception, cold allodynia and cold hyperalgesia in vitro, in animals and in humans., Methods: A comprehensive literature search was performed using the PubMed and Google Scholar databases until February 2013. Obtained manuscripts were reviewed for relevancy and reference lists of the retrieved articles were cross-checked for additional important studies. Solely the literature regarding topical application of L-menthol in humans was attained systematically. Of the total identified studies (96), 10 met the inclusion criteria being controlled studies applying L-menthol at a concentration of ≥ 30%., Results: The extracted data are meticulously compared and presented with emphasis on clarity and transparency. In seven animal studies, cold allodynia or hyperalgesia was successfully established utilizing various methods. Eight studies in healthy volunteers unanimously reported a significant increase in cold pain threshold, representing cold allodynia and increased supra-threshold cold pain sensitivity, thus demonstrating cold hyperalgesia., Conclusions: Topical high-concentration L-menthol consistently induces cold hypersensitivity in animals and humans, thus constituting a predictable surrogate model of cold allodynia and hyperalgesia. Understanding translational features of this model and its underlying mechanisms could be valuable in preclinical and human phases of drug development and in improving current treatment of patients with polyneuropathy., (© 2013 European Pain Federation - EFIC®)

Background: The prognosis of men with clinically localized prostate cancer is highly variable, and it is difficult to counsel a man who may be considering avoiding, or delaying, aggressive therapy. After collecting data on a large cohort of men who received no initial active prostate cancer therapy, the aim was to develop, and to internally validate, a nomogram for prediction of disease-specific survival., Methods: Working with 6 cancer registries within England and numerous hospitals in the region, a population-based cohort of men diagnosed with prostate cancer between 1990 and 1996 was constructed. All men had baseline serum prostate-specific antigen (PSA) measurements, centralized pathologic grading, and centralized review of clinical stage assignment. Based on the clinical and pathologic data from 1911 men, a statistical model was developed and validated that served as the basis for the nomogram. The discrimination and calibration of the nomogram were assessed with use of one-third of the men, who were omitted from modeling and used as a test sample., Results: The median age of the included men was 70.4 years. The 25th and 75th percentiles of PSA were 7.3 and 32.6 ng/mL respectively, and the median was 15.4 ng/mL. Forty-two percent of the men had high-grade disease. The nomogram predicted well, with a concordance index of 0.73, and had good calibration., Conclusions: An accurate tool was developed for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counseling and clinical trial design., (2007 American Cancer Society)

Objective: To determine whether the conduct of the second stage of labor and delivery technique influences the incidence of rupture of the anal sphincter., Material and Method: A total of 1072 primipara delivered vaginally at term at Rigshospitalet in 1998. A questionnaire on prenatal risk factors, conduct of the second stage of labor, and delivery technique was completed by the attending midwife immediately after delivery in 90 cases with rupture of the sphincter and in two subsequent controls (n = 164), matched by use of vacuum extractor and episiotomy., Results: Partial or total sphincter rupture was found in 8.4% of primipara who delivered vaginally, in 20.9% of those delivered by vacuum extraction, and in 6.4% of those with episiotomy only. The prenatal risk factors--maternal age, birth weight, shoulder dystocia, and edema of the perineum were found to have a statistically significant effect on the incidence of rupture of the sphincter ani. In non-instrumental vaginal deliveries easing of the perineum over the caput as it advanced helped prevent a rupture of the anal sphincter. Vacuum extraction performed with the woman in a semi-recumbant position was associated with an increased risk of rupture of the anal sphincter, whereas attention to the perineum during extraction decreased the risk., Conclusions: The significant effect of prenatal risk factors did not explain a correlation between delivery technique and rupture of the sphincter ani. The present study indicates that a reduction in the incidence of sphincter rupture may be accomplished by improved obstetric care: fewer vacuum extractions and improved delivery technique.

Objective: To compare the clinical indications for delivery by cesarean section (CS) in singleton pregnancies in two Danish counties with different CS rates, and to describe the relation between CS in the two counties and parity, mother's age, type of delivery department, gestational age at birth, and birthweight., Design: A population-based, follow-up study based on antecedent data., Setting: Two Danish counties, where women deliver in obstetric as well as surgical departments, with a CS rate of 8.3% and 15.2%, respectively., Subjects: All pregnant women in the two counties who delivered in 1989., Main Outcome Measures: Comparison of the rates of CS in the two counties carried out for five well-defined clinical indications: Previous cesarean section, breech presentation, dystocia, fetal distress, and other. SECONDARY MEASURES: Neonatal and maternal outcomes., Results: In the county with the higher frequency of CS, all indications for CS were used significantly more often, except from 'fetal distress' in primiparous women. In this county 'breech presentation' was the commonest indication among primiparous women, whereas 'fetal distress' was the most common in the county with the lower CS rate. For multiparous women the highest CS rates in both counties were found among women who had had a previous CS. The major difference between the two counties was the threefold greater risk of CS indicated by 'dystocia' among multiparous women in the county with the higher CS rate., Conclusion: The regional differences in CS could not be explained by differences between the two populations or by an increased rate of a single indication, but could be due to differences in obstetric practice or expectations or demands from the pregnant women.