Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials.

ObjectiveTumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.MethodsThe REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.ResultsThe REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials.ConclusionsThe REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research

Abdominal functional electrical stimulation to improve respiratory function after spinal cord injury: a systematic review and meta-analysis

Objectives: Abdominal functional electrical stimulation (abdominal FES) is the application of a train of electrical pulses to the abdominal muscles, causing them to contract. Abdominal FES has been used as a neuroprosthesis to acutely augment respiratory function and as a rehabilitation tool to achieve a chronic increase in respiratory function after abdominal FES training, primarily focusing on patients with spinal cord injury (SCI). This study aimed to review the evidence surrounding the use of abdominal FES to improve respiratory function in both an acute and chronic manner after SCI. Settings: A systematic search was performed on PubMed, with studies included if they applied abdominal FES to improve respiratory function in patients with SCI. Methods: Fourteen studies met the inclusion criteria (10 acute and 4 chronic). Low participant numbers and heterogeneity across studies reduced the power of the meta-analysis. Despite this, abdominal FES was found to cause a significant acute improvement in cough peak flow, whereas forced exhaled volume in 1 s approached significance. A significant chronic increase in unassisted vital capacity, forced vital capacity and peak expiratory flow was found after abdominal FES training compared with baseline. Conclusions: This systematic review suggests that abdominal FES is an effective technique for improving respiratory function in both an acute and chronic manner after SCI. However, further randomised controlled trials, with larger participant numbers and standardised protocols, are needed to fully establish the clinical efficacy of this technique

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Selecting effective incentive structures in health care: A decision framework to support health care purchasers in finding the right incentives to drive performance

<p>Abstract</p> <p>Background</p> <p>The Ontario health care system is devolving planning and funding authority to community based organizations and moving from steering through rules and regulations to steering on performance. As part of this transformation, the Ontario Ministry of Health and Long-Term Care (MOHLTC) are interested in using incentives as a strategy to ensure alignment – that is, health service providers' goals are in accord with the goals of the health system. The objective of the study was to develop a decision framework to assist policymakers in choosing and designing effective incentive systems.</p> <p>Methods</p> <p>The first part of the study was an extensive review of the literature to identify incentives models that are used in the various health care systems and their effectiveness. The second part was the development of policy principles to ensure that the used incentive models are congruent with the values of the Ontario health care system. The principles were developed by reviewing the Ontario policy documents and through discussions with policymakers. The validation of the principles and the suggested incentive models for use in Ontario took place at two meetings. The first meeting was with experts from the research and policy community, the second with senior policymakers from the MOHLTC. Based on the outcome of those two meetings, the researchers built a decision framework for incentives. The framework was send to the participants of both meetings and four additional experts for validation.</p> <p>Results</p> <p>We identified several models that have proven, with a varying degree of evidence, to be effective in changing or enabling a health provider's performance. Overall, the literature suggests that there is no single best approach to create incentives yet and the ability of financial and non-financial incentives to achieve results depends on a number of contextual elements. After assessing the initial set of incentive models on their congruence with the four policy principles we defined nine incentive models to be appropriate for use in Ontario and potentially other health care systems that want to introduce incentives to improve performance. Subsequently, the models were incorporated in the resulting decision framework.</p> <p>Conclusion</p> <p>The design of an incentive must reflect the values and goals of the health care system, be well matched to the performance objectives and reflect a range of contextual factors that can influence the effectiveness of even well-designed incentives. As a consequence, a single policy recommendation around incentives is inappropriate. The decision framework provides health care policymakers and purchasers with a tool to support the selection of an incentive model that is the most appropriate to improve the targeted performance.</p

Measuring and explaining mortality in Dutch hospitals; The Hospital Standardized Mortality Rate between 2003 and 2005

Background. Indicators of hospital quality, such as hospital standardized mortality ratios (HSMR), have been used increasingly to assess and improve hospital quality. Our aim has been to describe and explain variation in new HSMRs for the Netherlands. Methods. HSMRs were estimated using data from the complete population of discharged patients during 2003 to 2005. We used binary logistic regression to indirectly standardize for differences in case-mix. Out of a total of 101 hospitals 89 hospitals remained in our explanatory analysis. In this analysis we explored the association between HSMRs and determinants that can and cannot be influenced by hospitals. For this analysis we used a two-level hierarchical linear regression model to explain variation in yearly HSMRs. Results. The average HSMR decreased yearly with more than eight

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy

Perspectives on supporting fathers affected by postnatal depression and a history of violence

Intimate partner violence in the perinatal period is a significant problem that remains underscreened, underdiagnosed and undertreated. The establishment of evidence-based guidelines to enable health visitors to identify couples experiencing violence and offer appropriate support has been hampered by the complex interplay between maternal and paternal mental health problems and violence. This study explored the experiences of UK fathers who voluntarily engaged with services designed to eliminate their ideation to violence. The findings indicate that the tendency to violence is increased by stresses associated with the transition to parenthood. Men felt pressured by concerns for their partner's mental health, changes in the relationship, sleep disturbances and the burden of infant care they assumed when the mother was unable to cope. Health visitors are ideally placed to assess for factors linked to the emergence of violence and put in place interventions to minimise occurrence

A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R0 from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R0. \ud \ud Data and Methods. On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions. \ud \ud Findings. We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R0 of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R0 in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population. \ud \ud Interpretation: Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed

Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

<p>Abstract</p> <p>Background</p> <p>Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180.</p> <p>Methods</p> <p>Here we studied the interaction of mouse lymph node lymphocytes, co-cultured <it>in vitro </it>with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells.</p> <p>Results</p> <p>Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25⁺) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes.</p> <p>Conclusion</p> <p>Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells.</p