Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: design of a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Patients with Chronic Tension Type Headache (CTTH) report functional and emotional impairments (loss of workdays, sleep disturbances, emotional well-being) and are at risk for overuse of medication. Manual therapy may improve symptoms through mobilisation of the spine, correction of posture, and training of cervical muscles.</p> <p>We present the design of a randomised clinical trial (RCT) evaluating the effectiveness of manual therapy (MT) compared to usual care by the general practitioner (GP) in patients with CTTH.</p> <p>Methods and design</p> <p>Patients are eligible for participation if they present in general practice with CTTH according to the classification of the International Headache Society (IHS).</p> <p>Participants are randomised to either usual GP care according to the national Dutch general practice guidelines for headache, or manual therapy, consisting of mobilisations (high- and low velocity techniques), exercise therapy for the cervical and thoracic spine and postural correction. The primary outcome measures are the number of headache days and use of medication. Secondary outcome measures are severity of headache, functional status, sickness absence, use of other healthcare resources, active cervical range of motion, algometry, endurance of the neckflexor muscles and head posture. Follow-up assessments are conducted after 8 and 26 weeks.</p> <p>Discussion</p> <p>This is a pragmatic trial in which interventions are offered as they are carried out in everyday practice. This increases generalisability of results, but blinding of patients, GPs and therapists is not possible.</p> <p>The results of this trial will contribute to clinical decision making of the GP regarding referral to manual therapy in patients with chronic tension headache.</p

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432

A microscale protein NMR sample screening pipeline

As part of efforts to develop improved methods for NMR protein sample preparation and structure determination, the Northeast Structural Genomics Consortium (NESG) has implemented an NMR screening pipeline for protein target selection, construct optimization, and buffer optimization, incorporating efficient microscale NMR screening of proteins using a micro-cryoprobe. The process is feasible because the newest generation probe requires only small amounts of protein, typically 30–200 μg in 8–35 μl volume. Extensive automation has been made possible by the combination of database tools, mechanization of key process steps, and the use of a micro-cryoprobe that gives excellent data while requiring little optimization and manual setup. In this perspective, we describe the overall process used by the NESG for screening NMR samples as part of a sample optimization process, assessing optimal construct design and solution conditions, as well as for determining protein rotational correlation times in order to assess protein oligomerization states. Database infrastructure has been developed to allow for flexible implementation of new screening protocols and harvesting of the resulting output. The NESG micro NMR screening pipeline has also been used for detergent screening of membrane proteins. Descriptions of the individual steps in the NESG NMR sample design, production, and screening pipeline are presented in the format of a standard operating procedure

Rules Governing Selective Protein Carbonylation

BACKGROUND:Carbonyl derivatives are mainly formed by direct metal-catalysed oxidation (MCO) attacks on the amino-acid side chains of proline, arginine, lysine and threonine residues. For reasons unknown, only some proteins are prone to carbonylation. METHODOLOGY/PRINCIPAL FINDINGS:we used mass spectrometry analysis to identify carbonylated sites in: BSA that had undergone in vitro MCO, and 23 carbonylated proteins in Escherichia coli. The presence of a carbonylated site rendered the neighbouring carbonylatable site more prone to carbonylation. Most carbonylated sites were present within hot spots of carbonylation. These observations led us to suggest rules for identifying sites more prone to carbonylation. We used these rules to design an in silico model (available at http://www.lcb.cnrs-mrs.fr/CSPD/), allowing an effective and accurate prediction of sites and of proteins more prone to carbonylation in the E. coli proteome. CONCLUSIONS/SIGNIFICANCE:We observed that proteins evolve to either selectively maintain or lose predicted hot spots of carbonylation depending on their biological function. As our predictive model also allows efficient detection of carbonylated proteins in Bacillus subtilis, we believe that our model may be extended to direct MCO attacks in all organisms

Study protocol for a pragmatic randomised controlled trial in general practice investigating the effectiveness of acupuncture against migraine

<p>Abstract</p> <p>Background</p> <p>Migraine is a chronic neurologic disease that can severely affect the patient's quality of life. Although in recent years many randomised studies have been carried out to investigate the effectiveness of acupuncture as a treatment for migraine, it remains a controversial issue. Our aim is to determine whether acupuncture, applied under real conditions of clinical practice in the area of primary healthcare, is more effective than conventional treatment.</p> <p>Methods/Design</p> <p>The design consists of a pragmatic multi-centre, three-armed randomised controlled trial, complemented with an economic evaluation of the results achieved, comparing the effectiveness of verum acupuncture with sham acupuncture, and with a control group receiving normal care only.</p> <p>Patients eligible for inclusion will be those presenting in general practice with migraine and for whom their General Practitioner (GP) is considering referral for acupuncture. Sampling will be by consecutive selection, and by randomised allocation to the three branches of the study, in a centralised way following a 1:1:1 distribution (verum acupuncture; sham acupuncture; conventional treatment). Secondly, one patient in three will be randomly selected from each of the acupuncture (verum or sham) groups for a brain perfusion study (by single photon emission tomography). The treatment with verum acupuncture will consist of 8 treatment sessions, once a week, at points selected individually by the acupuncturist. The sham acupuncture group will receive 8 sessions, one per week, with treatment being applied at non-acupuncture points in the dorsal and lumbar regions, using the minimal puncture technique. The control group will be given conventional treatment, as will the other two groups.</p> <p>Discussion</p> <p>This trial will contribute to available evidence on acupuncture for the treatment of migraine. The primary endpoint is the difference in the number of days with migraine among the three groups, between the baseline period (the 4 weeks prior to the start of treatment) and the period from weeks 9 to 12. As a secondary aspect, we shall record the index of laterality and the percentage of change in the mean count per pixel in each region of interest measured by the brain perfusion tomography, performed on a subsample of the patients within the real and sham acupuncture groups.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN98703707.</p

Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for Chronic Daily Headache: Protocol for a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity.</p> <p>Methods</p> <p>Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks.</p> <p>Results</p> <p>Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/(NCT01157208)">(NCT01157208)</a></p

How might acupuncture work? A systematic review of physiologic rationales from clinical trials

BACKGROUND: Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. METHODS: The author conducted a PubMed search to obtain a fair sample of acupuncture clinical trials published in English in 2005. Each article was reviewed for a physiologic rationale, as well as study objectives and outcomes, experimental and control interventions, country of origin, funding sources and journal type. RESULTS: Seventy-nine acupuncture clinical trials were identified. Twenty-six studies (33%) offered no physiologic rationale. Fifty-three studies (67%) posited a physiologic basis for acupuncture: 33 (62% of 53) proposed neurochemical mechanisms, 2 (4%) segmental nervous system effects, 6 (11%) autonomic nervous system regulation, 3 (6%) local effects, 5 (9%) effects on brain function and 5 (9%) other effects. No rationale was proposed for stroke; otherwise having a rationale was not associated with objective, positive or negative findings, means of intervention, country of origin, funding source or journal type. The dominant explanation for how acupuncture might work involves neurochemical responses and is not reported to be dependent on treatment objective, specific points, means or method of stimulation. CONCLUSION: Many acupuncture trials fail to offer a meaningful rationale, but proposing a rationale can help investigators to develop and test a causal hypothesis, choose an appropriate control and rule out placebo effects. Acupuncture may stimulate self-regulatory processes independent of the treatment objective, points, means or methods used; this would account for acupuncture's reported benefits in so many disparate pathologic conditions