Establishing consensus for the assessment of chronic pain in children and young people with cerebral palsy: a Delphi study.

PURPOSE: Inconsistent and inadequate pain assessment practices in cerebral palsy (CP) have resulted from a lack of standardisation of pain assessment, limited use of appropriate tools and failure to integrate disability and biopsychosocial models. To assist with improving consistency, this study aimed to establish consensus from key stakeholders regarding domains considered essential for measuring chronic pain in children and young people with CP. METHOD: A modified electronic Delphi study was conducted on 83 stakeholders, including clinicians, researchers, people with CP and parents of children with CP. Participants rated 18 domains sourced from existing literature as either "core", "recommended", "exploratory" or "not required". RESULTS: After two rounds of surveys, 12 domains were considered core: pain location, pain frequency, pain intensity, changeable factors, impact on emotional wellbeing, impact on participation, pain communication, influence on quality of life, physical impacts, sleep, pain duration and pain expression. CONCLUSION: These domains reflect the complexity of pain in a heterogeneous population where medical comorbidities are common and communication and intellectual limitations impact significantly on the ability of many to self-report. The domains will be utilised to build a framework of pain assessment specific to children and young people with CP guided by the biopsychosocial model.Implications for rehabilitationChronic pain is under-identified and poorly assessed in the cerebral palsy (CP) population.The perspectives of clinicians, researchers and consumers are vital for developing a framework for chronic pain assessment in CP.Consensus of key stakeholders found 12 domains considered essential to incorporate into a chronic pain assessment model in CP.

Multiplexed Functional Assessment of Genetic Variants in CARD11.

Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used a "cloning-free" saturation genome editing approach in a diploid cell line to simultaneously score 2,542 variants for decreased or increased function in the region of CARD11 associated with immunodeficiency. We also described an exon-skipping mechanism for CARD11 dominant-negative activity. The classification of reported clinical variants was sensitive (94.6%) and specific (88.9%), which rendered the data immediately useful for interpretation of seven coding and splicing variants implicated in immunodeficiency found in our clinic. This approach is generalizable for variant interpretation in many other clinically actionable genes, in any relevant cell type.

'Just lie there and die': barriers to access and use of general practitioner out-of-hours services for older people in rural Ireland.

INTRODUCTION: Demographic changes and shifting populations mean growing numbers of older people are living alone in rural areas. General practitioner (GP) out-of-hours (GPOOH) services have an essential role in supporting older people to remain living in their own homes and communities for as long as possible, but little is known about use of GPOOH services by this cohort. This research examines how rurality impacts accessibility and utilisation of GPOOH services by people aged 65 years or more in rural Ireland. METHODS: Conducted in the mainly rural counties of Cavan and Monaghan in the north-east of Ireland, this research used a mixed methods approach. Questionnaires and focus groups were conducted with 48 older people in six locations across both counties. A thematic analysis was conducted on the data using NVivo software. RESULTS: The challenge for older rural populations includes difficulties accessing transport and the limited availability of support networks during times of a health crisis, especially at night. The present findings show such challenges are further compounded by a lack of information about available services. Rurality complicates each of these challenges, because it adds to the vulnerability of older adults. This is most acutely felt by those who live alone and those living the furthest from GPOOH treatment centres. The most important concern for older people, when unwell outside doctor surgery hours, is the need for access to medical care as quickly as possible. Inability to use GPOOH services leads many older people to seek help from accident and emergency departments, where faster access to clinical care is sometimes assumed. CONCLUSIONS: For rural-dwelling older people, becoming ill outside GP surgery hours is complex and the barriers faced are often insurmountable at times of greatest need. Worries about accessibility and lack of information give rise to a hesitancy to use GPOOH services in a population that is already known to be reluctant to ask for help, even when such help is justified. In turn, the lack of familiarity with what is a fundamental community health service further impacts the willingness of older adults to call on GPOOH services for help when needed. Addressing the impact of rurality on access and use of out-of-hours medical services is essential to enable more older adults to live longer in their rural homes and communities, supported by services that are responsive to their needs regardless of where they live. Given GPOOH is the only current alternative out-of-hours medical service to accident and emergency departments, more research is urgently needed on both accessibility of GPOOH services by older adults and the impact of inaccessibility on use of emergency services by older people in rural areas.

Treatment Selection Choices Should Not Be Based on Benefits or Costs Alone: A Head-to-Head Randomized Controlled Trial of Antiviral Drugs for Hepatitis C.

BACKGROUND: Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS: We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience. Tolerability was assessed at each visit and reasons for discontinuation of treatment and severity of adverse events due to PI treatment were adjudicated using a blinded adjudication committee. The primary outcome was difference in tolerability between boceprevir vs. telaprevir. Secondary outcomes included viral response rates and cost-per cure achieved. RESULTS: Higher rates of treatment discontinuations and/or severe DAA associated adverse events were seen in 10/25 (40%) patients randomized to telaprevir compared to 2/25 (8%) patients randomized to boceprevir (RR: 5; 95% CI: 1.2, 20; p<0.01). Cure rates did not appear to be significantly different between groups (telaprevir vs. boceprevir: RR 1.23; 95% CI: 0.76, 1.99; p = 0.39). On an intention-to-treat basis, total cost per cure was $44,329 for boceprevir vs. $57,115 for telaprevir. The significant side effect profile of telaprevir combined with the availability of highly efficacious second generation DAAs led to the early discontinuation of the trial. CONCLUSION: Telaprevir is associated with a significantly higher rate of severe adverse events leading to treatment discontinuations, hospitalizations or severe anemia and a substantially higher cost per SVR when compared to boceprevir. Real-time, point of care, pragmatic randomized controlled trials are necessary for guidance beyond just acquisition costs and to make evidence-based formulary selections when multiple effective treatments are available. (Clinicaltrials.gov registration: NCT02113631).

Body composition for health and performance: a survey of body composition assessment practice carried out by the Ad Hoc Research Working Group on Body Composition, Health and Performance under the auspices of the IOC Medical Commission.

BACKGROUND: Successful performers in weight-sensitive sports are characterised by low body mass (BM) and fat content. This often requires chronic energy restriction and acute weight loss practices. AIM: To evaluate current use of body composition (BC) assessment methods and identify problems and solutions with current BC approaches. METHODS: A 40-item survey was developed, including demographic and content questions related to BC assessment. The survey was electronically distributed among international sporting organisations. Frequencies and χ(2) analyses were computed. RESULTS: 216 responses were received, from 33 countries, representing various institutions, sports and competitive levels. Of the sample, 86% of respondents currently assess BC, most frequently using skinfolds (International Society for the Advancement of Kinanthropometry (ISAK): 50%; non-ISAK, conventional: 40%; both: 28%), dual energy X-ray absorptiometry (38%), bioelectrical impedance (29%), air displacement plethysmography (17%) and hydrostatic weighing (10%). Of those using skinfolds, more at the international level used ISAK, whereas conventional approaches were more reported at regional/national level (p=0.006). The sport dietitian/nutritionist (57%) and physiologist/sports scientist (54%) were most frequently the professionals assessing BC, followed by MDs and athletic trainers, with some reporting coaches (5%). 36% of 116 respondents assessed hydration status and more (64%) did so at international than regional/national level (36%, p=0.028). Of 125 participants answering the question of whether they thought that BC assessment raised problems, 69% said 'yes', with most providing ideas for solutions. CONCLUSIONS: Results show high use of BC assessment but also a lack of standardisation and widespread perception of problems related to BM and BC in sport. Future work should emphasise standardisation with appropriate training opportunities and more research on BC and performance.

Prediction of driving ability in people with relapsing-remitting multiple sclerosis using the stroke driver screening assessment.

The ability to drive is often affected in individuals with multiple sclerosis (MS) because of the motor, visual, or cognitive deficits commonly associated with the condition. In this study, we investigated the accuracy with which the Stroke Driver Screening Assessment (SDSA), an established battery for the prediction of driving performance of stroke survivors, would predict driving performance of individuals with MS. Driving performance of 44 individuals with relapsing-remitting MS (mean ± SD age, 46 ± 11 years; 37 females and 7 males) who were currently driving at least once a month was predicted using their performance on the SDSA. Outcomes of a road test and the Useful Field of View (UFOV) test were used as measures of driving ability. Participants' performance on both the road and UFOV tests was predicted with more than 80% accuracy. The SDSA was more accurate in predicting who would pass the two tests than who would fail the tests. The SDSA battery appears to be a good predictor of driving performance of individuals with relapsing-remitting MS, especially those who have sufficient cognitive skills to continue driving. Larger studies are needed to definitively establish its predictive accuracy and confirm the validity of the predictions.

Seat vibration in military propeller aircraft: characterization, exposure assessment, and mitigation.

INTRODUCTION: There have been increasing reports of annoyance, fatigue, and even neck and back pain during prolonged operation of military propeller aircraft, where persistent multi-axis vibration occurs at higher frequencies beyond human whole-body resonance. This paper characterizes and assesses the higher frequency vibration transmitted to the occupants onboard these aircraft. METHODS: Multi-axis accelerations were measured at the occupied seating surfaces onboard the WC/C-130J, C-130H3, and E-2C Hawkeye. The effects of the vibration were assessed in accordance with current international guidelines (ISO 2631-1:1997). The relative psychophysical effects of the frequency components and the effects of selected mitigation strategies were also investigated. RESULTS: The accelerations associated with the blade passage frequency measured on the passenger seat pans located on the side of the fuselage near the propeller plane of the C-130J (102 Hz) and C-130H3 (68 Hz) were noteworthy (5.19 +/- 1.72 ms(-2) rms and 7.65 +/- 0.71 ms(-2) rms, respectively, in the lateral direction of the aircraft). The psychophysical results indicated that the higher frequency component would dominate the side passengers' perception of the vibration. Balancing the props significantly reduced the lower frequency propeller rotation vibration (17 Hz), but had little effect on the blade passage frequency vibration. CONCLUSIONS: The relationships among the frequency, vibration direction, and seat measurement sites were complex, challenging the development of seating systems and mitigation strategies. Psychophysical metrics could provide a tool for optimizing mitigation strategies, but the current international vibration standard may not provide optimum assessment methods for evaluating higher frequency operational exposures.

Challenges and opportunities for positron-emission tomography in personalized medicine.

Of the non-invasive functional imaging tools available, positron-emission tomography (PET) is generally expected to have the greatest potential for delivering the vision of personalized medicine. This can be achieved by the production of designer PET probes with exquisite sensitivity that can profile key biological processes that are specific to a disease. However, the challenge for the PET field will be its capability to produce and supply cost-effective PET probes to the wider community. This will most likely be achieved through the provision of long-lived PET radioisotopes with imaging qualities that match the performance of the evolving PET camera technology and chemistry that is amenable to kit formulations. Additionally, of the emerging PET radiotracers, (64)Cu has the optimum chemistry and emission characteristics for the wider application of PET in personalized medicine.

A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain.

OBJECTIVE: To investigate whether the combination of standard medical care (SMC) and short-term cognitive-behavioral family treatment (CBT) in the treatment of recurrent abdominal pain (RAP) was more effective than SMC alone. METHODS: Children recently diagnosed with RAP via physician examination were randomized into SMC (n = 29) and SMC plus CBT (n = 40) groups. Outcome measures included multiple dimensions of child and parent reported child pain, somatization, and functional disability, and school absences and physician contacts. RESULTS: Children and parents participating in the combined SMC + CBT intervention reported significantly less child and parent reported child abdominal pain than children in the SMC intervention immediately following the intervention and up to 1 year following study entry, as well as significantly fewer school absences. Significant differences in functional disability and somatization were not revealed. CONCLUSIONS: These results, in combination with previous studies, add support to the effectiveness of CBT intervention in reducing the sensory aspects of RAP. Results are discussed with respect to the cost-benefit of integrated medical and short-term psychological services.

The effects of a National Breast and Cervical Cancer Early Detection Program on social disparities in breast cancer diagnosis and treatment in Massachusetts.

OBJECTIVE: To assess social disparities in breast cancer diagnosis and treatment by comparing the stage at diagnosis and treatment of women diagnosed with breast cancer through a National Breast and Cervical Cancer Early Detection Program (NBCCEDP) for low income and uninsured women in Massachusetts, the Women's Health Network (WHN), to other breast cancer patients in the state. METHODS: We linked data from the WHN and the Massachusetts Cancer Registry (MCR). We compared 331 WHN women and 13,372 other breast cancer patients in Massachusetts diagnosed from 1995 to 1999. We used logistic regression, controlling for age, race/ethnicity, marital status, region of residence, and stage, where appropriate. RESULTS: Compared to other breast cancer patients reported to the MCR, WHN women were just as likely to be diagnosed at an advanced stage (III or IV), treated with surgery, chemotherapy, and hormone therapy, and treated with complete mastectomy versus partial mastectomy. WHN women were less likely to receive radiation therapy (odds ratio = 0.7; 95% confidence interval = 0.6-0.9), particularly after partial mastectomy, and had a slightly longer time from diagnosis to treatment than other breast cancer patients (p < 0.01). CONCLUSIONS: Women diagnosed with breast cancer through a NBCCEDP in Massachusetts had similar stage and treatment patterns as other breast cancer patients in the state, except for the use of radiation therapy.

State trends in uninsurance among individuals aged 18 to 64 years: United States, 1992-2001.

OBJECTIVES: We analyzed state-specific uninsurance trends among US adults aged 18 to 64 years. METHODS: We used logistic regression models to examine Behavioral Risk Factor Surveillance System data for uninsurance from 1992 to 2001 in 47 states. RESULTS: Overall, uninsurance rates increased in 35 states and remained unchanged in 12 states. Increases were observed among people aged 30 to 49 years (in 34 states) and 50 to 64 years (in 24 states), and increases were also observed among individuals at middle and low income levels (in 39 states and 19 states, respectively), individuals employed for wages (in 33 states), and the self-employed (in 18 states). CONCLUSIONS: Among adults aged 18-64, rates of uninsurance increased in most states from 1992 through 2001. Decreased availability of employer-sponsored health insurance, rising health care costs, and state fiscal crises are likely to worsen the growing uninsurance problem.

Population aging and implications for epidemic cardiovascular disease in Sub-Saharan Africa.

Within the clinical and public health communities, it is often unnoticed that the developing world is experiencing an aging population with its attendant increase in the burden of chronic, noncommunicable diseases. From July 1999 to July 2000, 77% of the world's net gain in elderly persons occurred in developing countries. In Sub-Saharan Africa alone, the number of persons aged 65 years and older is expected to increase by 50% in 2015, from 19.3 million to 28.9 million. This demographic change has profound implications for developing countries that already shoulder a huge burden of communicable diseases, especially the HIV/AIDS epidemic, and continue to be challenged by basic infrastructure needs and economic development. In the 30-year period from 2000 to 2030, the population of elderly persons is projected to double in many Sub-Saharan African countries including the Democratic Republic of Congo, Mozambique, Cameroon, and Ghana. The scale and magnitude of these demographic changes are unprecedented. Since advancing age is the most powerful independent predictor of cardiovascular morbidity and mortality, the impact of these demographic changes on heart disease and stroke will be substantial. Aggressive efforts in promoting healthy aging and the prevention of cardiovascular risk factors will be crucial in preventing an impending cardiovascular epidemic in these countries.

The assessment of pain behavior: implications for applied psychophysiology and future research directions.

Persons who have pain engage in behaviors such as resting in bed, taking medication, moving in a guarded fashion, or grimacing that communicate the fact that pain is being experienced. Pain-related behaviors increasingly are viewed as an important target in pain assessment. Traditionally, pain behavior has been assessed through interview or self-recording methods (e.g. diary records). Pain behaviors, however, are overt and can be recorded through direct observation. Over the past 20 years, observation methods have been developed to assess pain behavior in patients having persistent pain conditions. Although these methods are not widely used in applied psychophysiological settings, they potentially could be quite useful. The purpose of this paper is to review the literature on such observation methods. The paper is divided into five parts. The first part provides a description of the basic elements of pain behavior observation protocols. The second part presents information on the psychometric properties of the most commonly used protocols. The third part highlights applications of pain behavior observation protocols. The fourth part briefly describes the strengths and limitations of pain behavior observation. The paper concludes with a discussion of the implications of pain behavior observation for applied psychophysiology and future directions for research and practice in this area.

Recent advances and future directions in the biopsychosocial assessment and treatment of arthritis.

This article provides an overview of the emerging literature on biopsychosocial assessment and treatment for two of the most common forms of arthritis: osteoarthritis and rheumatoid arthritis. The article is divided into 3 parts. In the 1st part, the basic elements of the biopsychosocial approach to assessing and treating persons having arthritis is described. In the 2nd part, the authors evaluate studies of biopsychosocial approaches to the assessment of arthritis pain and disability. Six research areas are reviewed: learned helplessness, depression, stress, pain coping, self-efficacy, and the social context of arthritis. The 3rd part of the article reviews studies that testing the efficacy of biopsychosocial treatment approaches for persons having osteoarthritis and rheumatoid arthritis.

Recommendations for improving the quality of care through stroke centers and systems: an examination of stroke center identification options: multidisciplinary consensus recommendations from the Advisory Working Group on Stroke Center Identification Options of the American Stroke Association.

BACKGROUND AND PURPOSE: The American Stroke Association (ASA) assembled a multidisciplinary group of experts to develop recommendations regarding the potential effectiveness of establishing an identification program for stroke centers and systems. "Identification" refers to the full spectrum of models for assessing and recognizing standards of quality care (self-assessment, verification, certification, and accreditation). A primary consideration is whether stroke center identification might improve patient outcomes. METHODS: In February 2001, ASA, with the support of the Stroke Council's Executive Committee, decided to embark on an evaluation of the potential impact of stroke center identification. HealthPolicy R&D was selected to prepare a comprehensive report. The investigators reported on models outside the area of stroke, ongoing initiatives within the stroke community (such as Operation Stroke), and state and federal activities designed to improve care for stroke patients. The investigators also conducted interviews with thought leaders in the stroke community, representing a diverse sampling of specialties and affiliations. In October 2001, the Advisory Working Group on Stroke Center Identification developed its consensus recommendations. This group included recognized experts in neurology, emergency medicine, emergency medical services, neurological surgery, neurointensive care, vascular disease, and stroke program planning. RESULTS: There are a variety of existing identification programs, generally falling within 1 of 4 categories (self-assessment, verification, certification, and accreditation) along a continuum with respect to intensity and scope of review and consumption of resources. Ten programs were evaluated, including Peer Review Organizations, trauma centers, and new efforts by the National Committee on Quality Assurance and the Joint Commission on the Accreditation of Healthcare Organizations to identify providers and disease management programs. The largest body of literature on clinical outcomes associated with identification programs involves trauma centers. Most studies support that trauma centers and systems lead to improved mortality rates and patient outcomes. The Advisory Working Group felt that comparison to the trauma model was most relevant given the need for urgent evaluation and treatment of stroke. The literature in other areas generally supports the positive impact of identification programs, although patient outcomes data have less often been published. In the leadership interviews, participants generally expressed strong support for pursuing some form of voluntary identification program, although concerns were raised that this effort could meet with some resistance. CONCLUSIONS: Identification of stroke centers and stroke systems competencies is in the best interest of stroke patients in the United States, and ASA should support the development and implementation of such processes. The purpose of a stroke center/systems identification program is to increase the capacity for all hospitals to treat stroke patients according to standards of care, recognizing that levels of involvement will vary according to the resources of hospitals and systems.

Can an increased copper requirement in copper-tolerant Mimulus guttatus explain the cost of tolerance? II. Reproductive phase.

Circumstantial evidence suggests that plants that have evolved metal tolerance are at a disadvantage on normal soil, i.e. there is a cost of tolerance. One hypothesis for the cause of this cost is that individuals have a greater requirement for copper, and so suffer micronutrient deficiency on normal soils, as a result of a reduced uptake, distribution and/or utilization of copper. We provided highly and less copper-tolerant plants of Mimulus guttatus Fischer ex DC. (the common monkey flower) with sub-optimal copper, and demonstrated the importance of copper as an essential micronutrient during the reproductive phase, both in the production of viable pollen and in seed set. We also looked at the effect of sub-optimal copper supply on the growth of the microgametophyte, and the efficiency with which seed was set. No evidence was found that highly tolerant plants have an increased copper requirement during the reproductive phase. This is in agreement with earlier work on Mimulus guttatus, which investigated the copper requirement of highly tolerant plants during vegetative growth and found that any differences in copper requirement were small. The 'metal requirement hypothesis' is, therefore, not the sole explanation for the cost of copper tolerance in M. guttatus.

Can an increased copper requirement in copper-tolerant Mimulus guttatus explain the cost of tolerance?: I. Vegetative growth.

If metal tolerant plants, by virtue of their tolerance mechanism, are less efficient at the uptake, distribution or utilization of metals then essential micronutrient deficiency may occur at the low levels of metal supply found on non-mine soils. This argument forms the basis of the metal requirement hypothesis put forward to explain the lower fitness of tolerant individuals on uncontaminated soil, the so called'cost of tolerance'. In this paper, copper balance was investigated in Mimulus guttatus Fischer ex. DC (the yellow monkey flower) for plants with or without the major tolerance gene which confers primary tolerance, and plants with few or many modifier genes which control degree of tolerance. No conclusive evidence to support an increased copper requirement in plants with the major tolerance gene, and/or many modifier genes was shown. Any differences in copper requirement found during vegetative growth were small, and were deemed insufficient to explain the apparent cost of tolerance.