Chronic fatigue syndrome; an approach combining self-management with graded exercise to avoid exacerbations.

Controversy regarding the aetiology and treatment of patients with chronic fatigue syndrome (CFS) continues to affect the medical professions. The Cochrane collaboration advises practitioners to implement graded exercise therapy for CFS sufferers using cognitive behavioural principles. In contrast there is evidence that exercise can induce symptom exacerbations in CFS where too vigorous exercise/activity promotes immune dysfunction, which in turn increases symptoms in patients with CFS. When designing and implementing an exercise programme it is important to be aware of both these seemingly opposing view points in order to deliver a programme without any detrimental effects on CFS pathophysiology. Using evidence from both the biological and clinical sciences, the present manuscript explains that graded exercise therapy for people with CFS can be safely undertaken without detrimental effects to the immune system. Exercise programs should be designed to cater for individual physical capabilities and should also account for the fluctuating nature of symptoms commonly reported by people with CFS. In line with cognitive behaviourally and graded exercise-based strategies, self-management for people with CFS involves encouraging the patients to pace their activities and respect their physical and mental limitations with the ultimate aim of improving their everyday function

Effect of Nitrosamine (NNAT) on Embryogenesis: Evidence from a Study Using Avian Embryos Exposed to NNAT

Background Birth defects are a known cause of infant death in the United States with higher rates in the Midwest perhaps due to higher use of agrichemicals for farm activities. Nitrate and atrazine are two of the most prevalent agrichemicals contaminating drinking water supplies. When ingested together, in the acidic environment of the human stomach, they can react to form a nitrosamine, NNAT. Many nitrosamines are known to be mutagenic, carcinogenic and teratogenic. Significance Preliminary studies have suggested that NNAT is a teratogen and mutagen. Several other agrichemical compounds have been detected in Nebraska groundwater wells that have the potential to nitrosate and studies are underway to evaluate the risk of adverse birth outcomes associated with exposure to these compounds. In this study, we evaluated growth in chick embryos after exposure to NNAT. Hypothesis We hypothesize that the embryo exposed to NNAT would have delayed development compared to unexposed embryos. Experimental design Three groups of eggs were observed in the study: the treatment group was treated with different doses of NNAT dissolved in Dimethyl sulfoxide (DMSO), the vehicle control group were treated with only DMSO and the untreated group (control). The air sac of the treatment groups was injected with varying concentrations of NNAT at one time to stimulate an acute response and at different times for a chronic response. Result/Data: All analysis was done on SAS 9.4. The effect of treatments on the weight and survival of the embryos were determined using analysis of covariance (ANCOVA) and multiple logistic regression respectively. The effect of treatment was found to be significant on the embryo treated with NNAT after adjusting for the effect of the positions of the eggs during incubation (p\u3c0.0001). Embryos that were untreated (controls) had the highest weight (weight=0.34g), and as the dose of NNAT was increased during treatment the weight of the embryo decreased significantly after incubation for 5 days : 0.245 µmol/l of NNAT (weight=0.15g, p=0.0009), 1.11 µmol/l of NNAT (weight=0.13g, p=0.004), 2.22 µmol/l of NNAT (weight=0.11g, p=0.01) and 3.33 µmol/l of NNAT (weight=0.12g, p=0.01). Also, it was found that the odds of survival among the embryo decreased linearly with increased dose when treated with NNAT as compared to the untreated embryos: 1.11 µmol/l of NNAT vs untreated (OR=0.250 95% C.I. 0.078-0.799), 2.22 µmol/l of NNAT vs. untreated (OR=0.120 95% C.I. 0.042-0.347) and 3.33 µmol/l of NNAT vs untreated (OR=0.106 95% C.I. 0.036-0.311) Conclusion: This study has revealed that weight and odds of survival of embryo exposed to NNAT decreased after 5 days of incubation. Dose-effect of the treatment was also observed during the development of embryos exposed to NNAT. Additional studies, however, is needed to evaluate the toxic effects of DMSO on the chick’s embryo before a conclusion can be reached.https://digitalcommons.unmc.edu/coph_pres/1008/thumbnail.jp

An Analysis of Correlation Between Agrichemical Contaminated Wells and Birth Defects in Nebraska

Background: Evidences that agrichemicals might be associated with the incidence of birth defects are inconsistent. Objectives: Examine whether Triazine, Acetanilide, Carbamothioate, Nitrate, Trifluralin and Uracil present in well-water are associated with birth defect rates in Nebraska Counties Identify the well types contaminated with these pesticides. Methods: Birth defects data obtained from Nebraska Department of Human and Health Services were merged with data on wells tested for agrichemicals obtained from Quality-Assessed Agrichemical Contaminant Database for Nebraska Ground Water. The 33 contaminants sampled from the wells were sub classified into 6 predictors and expressed as percentages for analysis in a multiple regression model with birth defect rates as the response variable. The pesticides sampled from the wells were also categorized into parent and degradate to examine the nature of pesticide associated with birth defects. Due to multicollinearity, triazine, acetanilide and trifluralin were summed together. Results The percentage for triazine and nitrate in domestic wells were 10.6% and 21.5% respectively. Birth defect rates were discovered to correlate with triazine (r= 0.21 p=0.041). triazine- acetanilide-trifluralin together was found to be linearly associated with birth defect rates in the multiple linear regression model (p=0.012). A stronger correlation was found between the parent contaminants and birth defect rates(r=0.22 p=0.034) than the degradate. (r=0.15 p=0.163). Conclusion: This study suggests an association between birth defect and percent of wells positive for agrichemical compounds. However, this association does not imply causation but provides direction for future investigation.https://digitalcommons.unmc.edu/coph_pres/1003/thumbnail.jp

Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies

Background Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. Method Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. Results A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. Conclusion Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. Trial registration FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013

The prognosis for individuals on disability retirement An 18-year mortality follow-up study of 6887 men and women sampled from the general population

BACKGROUND: Several studies have shown a markedly higher mortality rate among disability pensioners than among non-retired. Since most disability pensions are granted because of non-fatal diseases the reason for the increased mortality therefore remains largely unknown. The aim of this study was to evaluate potential explanatory factors. METHODS: Data from five longitudinal cohort studies in Sweden, including 6,887 men and women less than 65 years old at baseline were linked to disability pension data, hospital admission data, and mortality data from 1971 until 2001. Mortality odds ratios were analyzed with Poisson regression and Cox's proportional hazards regression models. RESULTS: 1,683 (24.4%) subjects had a disability pension at baseline or received one during follow up. 525 (7.6%) subjects died during follow up. The subjects on disability pension had a higher mortality rate than the non-retired, the hazards ratio (HR) being 2.78 (95%CI 2.08–3.71) among women and 3.43 (95%CI 2.61–4.51) among men. HR was highest among individuals granted a disability pension at young ages (HR >7), and declined parallel to age at which the disability pension was granted. The higher mortality rate among the retired subjects was not explained by disability pension cause or underlying disease or differences in age, marital status, educational level, smoking habits or drug abuse. There was no significant association between reason for disability pension and cause of death. CONCLUSION: Subjects with a disability pension had increased mortality rates as compared with non-retired subjects, only modestly affected by adjustments for psycho-socio-economic factors, underlying disease, etcetera. It is unlikely that these factors were the causes of the unfavorable outcome. Other factors must be at work

Complete experimental toolbox for alignment-free quantum communication

Quantum communication employs the counter-intuitive features of quantum physics to perform tasks that are im- possible in the classical world. It is crucial for testing the foundations of quantum theory and promises to rev- olutionize our information and communication technolo- gies. However, for two or more parties to execute even the simplest quantum transmission, they must establish, and maintain, a shared reference frame. This introduces a considerable overhead in communication resources, par- ticularly if the parties are in motion or rotating relative to each other. We experimentally demonstrate how to circumvent this problem with the efficient transmission of quantum information encoded in rotationally invariant states of single photons. By developing a complete toolbox for the efficient encoding and decoding of quantum infor- mation in such photonic qubits, we demonstrate the fea- sibility of alignment-free quantum key-distribution, and perform a proof-of-principle alignment-free entanglement distribution and violation of a Bell inequality. Our scheme should find applications in fundamental tests of quantum mechanics and satellite-based quantum communication.Comment: Main manuscript: 7 pages, 3 figures; Supplementary Information: 7 pages, 3 figure

Sick-leave track record and other potential predictors of a disability pension. A population based study of 8,218 men and women followed for 16 years

<p>Abstract</p> <p>Background</p> <p>A number of previous studies have investigated various predictors for being granted a disability pension. The aim of this study was to test the efficacy of sick-leave track record as a predictor of being granted a disability pension in a large dataset based on subjects sampled from the general population and followed for a long time.</p> <p>Methods</p> <p>Data from five ongoing population-based Swedish studies was used, supplemented with data on all compensated sick leave periods, disability pensions granted, and vital status, obtained from official registers. The data set included 8,218 men and women followed for 16 years, generated 109,369 person years of observation and 97,160 sickness spells. Various measures of days of sick leave during follow up were used as independent variables and disability pension grant was used as outcome.</p> <p>Results</p> <p>There was a strong relationship between individual sickness spell duration and annual cumulative days of sick leave on the one hand and being granted a disability pension on the other, among both men and women, after adjustment for the effects of marital status, education, household size, smoking habits, geographical area and calendar time period, a proxy for position in the business cycle. The interval between sickness spells showed a corresponding inverse relationship. Of all the variables studied, the number of days of sick leave per year was the most powerful predictor of a disability pension. For both men and women 245 annual sick leave days were needed to reach a 50% probability of transition to disability. The independent variables, taken together, explained 96% of the variation in disability pension grantings.</p> <p>Conclusion</p> <p>The sick-leave track record was the most important predictor of the probability of being granted a disability pension in this study, even when the influences of other variables affecting the outcome were taken into account.</p

Fatigue Intervention by Nurses Evaluation - The FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]

Background: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP). Methods and design: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients' homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions' mechanisms of change, and also GPs' drivers and barriers towards referral

Anatomy and Pathology Eyes in Various Species Can Shorten to Compensate for Myopic Defocus

PURPOSE. We demonstrated that eyes of young animals of various species (chick, tree shrew, marmoset, and rhesus macaque) can shorten in the axial dimension in response to myopic defocus. METHODS. Chicks wore positive or negative lenses over one eye for 3 days. Tree shrews were measured during recovery from induced myopia after 5 days of monocular deprivation for 1 to 9 days. Marmosets were measured during recovery from induced myopia after monocular deprivation, or wearing negative lenses over one or both eyes, or from wearing positive lenses over one or both eyes. Rhesus macaques were measured after recovery from induced myopia after monocular deprivation, or wearing negative lenses over one or both eyes. Axial length was measured with ultrasound biometry in all species. RESULTS. Tree shrew eyes showed a strong trend to shorten axially to compensate for myopic defocus. Of 34 eyes that recovered from deprivation-induced myopia for various durations, 30 eyes (88%) shortened, whereas only 7 fellow eyes shortened. In chicks, eyes wearing positive lenses reduced their rate of ocular elongation by two-thirds, including 38.5% of eyes in which the axial length became shorter than before. Evidence of axial shortening in rhesus macaque (40%) and marmoset (6%) eyes also occurred when exposed to myopic defocus, although much less frequently than that in eyes of tree shrews. The axial shortening was caused mostly by the reduction in vitreous chamber depth. CONCLUSIONS. Eyes of chick, tree shrew, marmoset, and rhesus macaque can shorten axially when presented with myopic defocus, whether the myopic defocus is created by wearing positive lenses, or is the result of axial elongation of the eye produced by prior negative lens wear or deprivation. This eye shortening facilitates compensation for the imposed myopia. Implications for human myopia control are significant