Diagnosis and treatment of musculoskeletal chest pain: design of a multi-purpose trial

<p>Abstract</p> <p>Background</p> <p>Acute chest pain is a major health problem all over the western world. Active approaches are directed towards diagnosis and treatment of potentially life threatening conditions, especially acute coronary syndrome/ischemic heart disease. However, according to the literature, chest pain may also be due to a variety of extra-cardiac disorders including dysfunction of muscles and joints of the chest wall or the cervical and thoracic part of the spine. The diagnostic approaches and treatment options for this group of patients are scarce and formal clinical studies addressing the effect of various treatments are lacking.</p> <p>Methods/Design</p> <p>We present an ongoing trial on the potential usefulness of chiropractic diagnosis and treatment in patients dismissed from an acute chest pain clinic without a diagnosis of acute coronary syndrome. The aims are to determine the proportion of patients in whom chest pain may be of musculoskeletal rather than cardiac origin and to investigate the decision process of a chiropractor in diagnosing these patients; further, to examine whether chiropractic treatment can reduce pain and improve physical function when compared to advice directed towards promoting self-management, and, finally, to estimate the cost-effectiveness of these procedures. This study will include 300 patients discharged from a university hospital acute chest pain clinic without a diagnosis of acute coronary syndrome or any other obvious cardiac or non-cardiac disease. After completion of the clinic's standard cardiovascular diagnostic procedures, trial patients will be examined according to a standardized protocol including a) a self-report questionnaire; b) a semi-structured interview; c) a general health examination; and d) a specific manual examination of the muscles and joints of the neck, thoracic spine, and thorax in order to determine whether the pain is likely to be of musculoskeletal origin. To describe the patients status with regards to ischemic heart disease, and to compare and indirectly validate the musculoskeletal diagnosis, myocardial perfusion scintigraphy is performed in all patients 2–4 weeks following discharge. Descriptive statistics including parametric and non-parametric methods will be applied in order to compare patients with and without musculoskeletal chest pain in relation to their scintigraphic findings. The decision making process of the chiropractor will be elucidated and reconstructed using the CART method. Out of the 300 patients 120 intended patients with suspected musculoskeletal chest pain will be randomized into one of two groups: a) a course of chiropractic treatment (therapy group) of up to ten treatment sessions focusing on high velocity, low amplitude manipulation of the cervical and thoracic spine, mobilisation, and soft tissue techniques. b) Advice promoting self-management and individual instructions focusing on posture and muscle stretch (advice group). Outcome measures are pain, physical function, overall health, self-perceived treatment effect, and cost-effectiveness.</p> <p>Discussion</p> <p>This study may potentially demonstrate that a chiropractor is able to identify a subset of patients suffering from chest pain predominantly of musculoskeletal origin among patients discharged from an acute chest pain clinic with no apparent cardiac condition. Furthermore knowledge about the benefits of manual treatment of patients with musculoskeletal chest pain will inform clinical decision and policy development in relation to clinical practice.</p> <p>Trial registration</p> <p>NCT00462241 and NCT00373828</p

Differential Scanning Fluorometry Signatures as Indicators of Enzyme Inhibitor Mode of Action: Case Study of Glutathione S-Transferase

Differential scanning fluorometry (DSF), also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST) as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH). Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization

Improving patient adherence to lifestyle advice (IMPALA): a cluster-randomised controlled trial on the implementation of a nurse-led intervention for cardiovascular risk management in primary care (protocol)

Background Many patients at high risk of cardiovascular diseases are managed and monitored in general practice. Recommendations for cardiovascular risk management, including lifestyle change, are clearly described in the Dutch national guideline. Although lifestyle interventions, such as advice on diet, physical exercise, smoking and alcohol, have moderate, but potentially relevant effects in these patients, adherence to lifestyle advice in general practice is not optimal. The IMPALA study intends to improve adherence to lifestyle advice by involving patients in decision making on cardiovascular prevention by nurse-led clinics. The aim of this paper is to describe the design and methods of a study to evaluate an intervention aimed at involving patients in cardiovascular risk management. Methods A cluster-randomised controlled trial in 20 general practices, 10 practices in the intervention arm and 10 in the control arm, starting on October 2005. A total of 720 patients without existing cardiovascular diseases but eligible for cardiovascular risk assessment will be recruited. In both arms, the general practitioners and nurses will be trained to apply the national guideline for cardiovascular risk management. Nurses in the intervention arm will receive an extended training in risk assessment, risk communication, the use of a decision aid and adapted motivational interviewing. This communication technique will be used to support the shared decision-making process about risk reduction. The intervention comprises 2 consultations and 1 follow-up telephone call. The nurses in the control arm will give usual care after the risk estimation, according to the national guideline. Primary outcome measures are self-reported adherence to lifestyle advice and drug treatment. Secondary outcome measures are the patients' perception of risk and their motivation to change their behaviour. The measurements will take place at baseline and after 12 and 52 weeks. Clinical endpoints will not be measured, but the absolute 10-year risk of cardiovascular events will be estimated for each patient from medical records at baseline and after 1 year. Discussion The combined use of risk communication, a decision aid and motivational interviewing to enhance patient involvement in decision making is an innovative aspect of the intervention. Trial registration Current Controlled Trials ISRCTN5155672

Local Abundance Patterns of Noctuid Moths in Olive Orchards: Life-History Traits, Distribution Type and Habitat Interactions

Local species abundance is related to range size, habitat characteristics, distribution type, body size, and life-history variables. In general, habitat generalists and polyphagous species are more abundant in broad geographical areas. Underlying this, local abundance may be explained from the interactions between life-history traits, chorological pattern, and the local habitat characteristics. The relationship within taxa between life-history traits, distribution area, habitat characteristics, and local abundance of the noctuid moth (Lepidoptera: Noctuidae) assemblage in an olive orchard, one of the most important agro-ecosystems in the Mediterranean basin, was analyzed. A total of 66 species were detected over three years of year-round weekly samplings using the light-trap method. The life-history traits examined and the distribution type were found to be related to the habitat-species association, but none of the biological strategies defined from the association to the different habitats were linked with abundance. In contrast to general patterns, dispersal ability and number of generations per year explained differences in abundance. The relationships were positive, with opportunistic taxa that have high mobility and several generations being locally more abundant. In addition, when the effect of migrant species was removed, the distribution type explained abundance differences, with Mediterranean taxa (whose baricenter is closer to the studied area) being more abundant

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

J/psi production as a function of charged-particle pseudorapidity density in p-Pb collisions at root s(NN)=5.02 TeV

We report measurements of the inclusive J/ψ yield and average transverse momentum as a function of charged-particle pseudorapidity density dNch/dη in p–Pb collisions at sNN=5.02TeV with ALICE at the LHC. The observables are normalised to their corresponding averages in non-single diffractive events. An increase of the normalised J/ψ yield with normalised dNch/dη, measured at mid-rapidity, is observed at mid-rapidity and backward rapidity. At forward rapidity, a saturation of the relative yield is observed for high charged-particle multiplicities. The normalised average transverse momentum at forward and backward rapidities increases with multiplicity at low multiplicities and saturates beyond moderate multiplicities. In addition, the forward-to-backward nuclear modification factor ratio is also reported, showing an increasing suppression of J/ψ production at forward rapidity with respect to backward rapidity for increasing charged-particle multiplicity