Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Background Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes. Methods Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use. Results With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes. Conclusions These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes

The highly accurate anteriolateral portal for injecting the knee

<p>Abstract</p> <p>Background</p> <p>The extended knee lateral midpatellar portal for intraarticular injection of the knee is accurate but is not practical for all patients. We hypothesized that a modified anteriolateral portal where the synovial membrane of the medial femoral condyle is the target would be highly accurate and effective for intraarticular injection of the knee.</p> <p>Methods</p> <p>83 subjects with non-effusive osteoarthritis of the knee were randomized to intraarticular injection using the modified anteriolateral bent knee versus the standard lateral midpatellar portal. After hydrodissection of the synovial membrane with lidocaine using a mechanical syringe (reciprocating procedure device), 80 mg of triamcinolone acetonide were injected into the knee with a 2.0-in (5.1-cm) 21-gauge needle. Baseline pain, procedural pain, and pain at outcome (2 weeks and 6 months) were determined with the 10 cm Visual Analogue Pain Score (VAS). The accuracy of needle placement was determined by sonographic imaging.</p> <p>Results</p> <p>The lateral midpatellar and anteriolateral portals resulted in equivalent clinical outcomes including procedural pain (VAS midpatellar: 4.6 ± 3.1 cm; anteriolateral: 4.8 ± 3.2 cm; p = 0.77), pain at outcome (VAS midpatellar: 2.6 ± 2.8 cm; anteriolateral: 1.7 ± 2.3 cm; p = 0.11), responders (midpatellar: 45%; anteriolateral: 56%; p = 0.33), duration of therapeutic effect (midpatellar: 3.9 ± 2.4 months; anteriolateral: 4.1 ± 2.2 months; p = 0.69), and time to next procedure (midpatellar: 7.3 ± 3.3 months; anteriolateral: 7.7 ± 3.7 months; p = 0.71). The anteriolateral portal was 97% accurate by real-time ultrasound imaging.</p> <p>Conclusion</p> <p>The modified anteriolateral bent knee portal is an effective, accurate, and equivalent alternative to the standard lateral midpatellar portal for intraarticular injection of the knee.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00651625">NCT00651625</a></p

The use of evidence in public governmental reports on health policy: an analysis of 17 Norwegian official reports (NOU)

<p>Abstract</p> <p>Background</p> <p>Governments increasingly require policy documents to be evidence-based. This paper analyses the use of scientific evidence in such documents by reviewing reports from government-appointed committees in Norway to assess the committees' handling of questions of effect.</p> <p>Methods</p> <p>This study uses the 'Index of Scientific Quality' (ISQ) to analyse all Norwegian official reports (NOUs) that were: (1) published by the Norwegian Ministry of Health and Care Services during 1994-1998 (N = 20); and (2) concerned with questions of effect either because these were included in the mandate or as a result of the committee's interpretation of the mandate. The ISQ is based on scientific criteria common in all research concerning questions of effect. The primary outcome measure is an ISQ score on a five-point scale.</p> <p>Results</p> <p>Three reports were excluded because their mandates, or the committees' interpretations of them, did not address questions of effect. For the remaining 17 NOUs in our study, overall ISQ scores were low for systematic literature search and for explicit validation of research. Two reports had an average score of three or higher, while scores for five other reports were not far behind. How committees assessed the relevant factors was often unclear.</p> <p>Conclusion</p> <p>The reports' evaluations of health evidence in relation to questions of effect lacked transparency and, overall, showed little use of systematic processes. A systematic, explicit and transparent approach, following the standards laid down in the ISQ, may help generate the evidence-based decision-making that Norway, the UK, the EU and the WHO desire and seek. However, policy-makers may find the ISQ criteria for assessing the scientific quality of a report too narrow to adequately inform policy-making.</p

Exploiting Clinical Trial Data Drastically Narrows the Window of Possible Solutions to the Problem of Clinical Adaptation of a Multiscale Cancer Model

The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics

Policy

Policy is the intentional process in which an unforeseeable number of actors, bearers of specific interests and ideas, continuously interact with each other in order not only to maintain or increase their power but also to deal with and to solve problems perceived to have collective relevance or impact. This definition includes all the relevant dimensions that policy scholars have emphasized and focused on when treating the concept of policy. It is not a parsimonious definition, but it can be considered most useful to capture the object without losing relevant characteristics. Furthermore, this definition allows to consider policy as politics in action, which means to connect in a structured way the activities through which collective problems are treated and eventually solved with the political process, in which political actors compete for power