Use of Physiotherapy Prior to Total Knee Arthroplasty-Results of the Prospective FInGK Study

Background: Data regarding physiotherapy (PT) utilization prior to total knee arthroplasty (TKA) are insufficient. Therefore, this study aims to examine which percentage of patients receive PT within 12 months prior to TKA and which factors are associated with its use. Methods: Consecutive patients (≥18 years) undergoing primary or revision TKA in a German university hospital were recruited. A questionnaire including information on PT utilization, demography, and socioeconomics was collected one day prior to surgery and linked to medical hospital records. Multivariable logistic regression was conducted to determine variables associated with the use of PT. Results: A total of 241 out of 283 (85%) patients participated (60% female; mean age: 68.4 years). Overall, 41% received PT at least once during 12 months prior to TKA, women more frequently than men (48% vs. 29%). Although high disease burden was associated with increased utilization, about one in two in this condition did not receive PT. Multivariable logistic regression showed that age 75+ years, low education level, and moderate-to-severe depressive symptoms were associated with decreased PT utilization. Conclusions: We found low use of recommended PT management in patients prior to TKA. This potential underuse was even higher in some vulnerable subgroups, indicating inequalities. Prescribers as well as patients should integrate PT more consistently into osteoarthritis management

Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT). Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC),distant control (DC) and overall survival (OS),measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used. Results: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-,2-,3-year OS rates were 63, 42, 28 %,the LRC rates were 81, 60, 40 %,and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology. Conclusions: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM

Modelling food security: Bridging the gap between the micro and the macro scale

Achieving food and nutrition security for all in a changing and globalized world remains a critical challenge of utmost importance. The development of solutions benefits from insights derived from modelling and simulating the complex interactions of the agri-food system, which range from global to household scales and transcend disciplinary boundaries. A wide range of models based on various methodologies (from food trade equilibrium to agent-based) seek to integrate direct and indirect drivers of change in land use, environment and socio-economic conditions at different scales. However, modelling such interaction poses fundamental challenges, especially for representing non-linear dynamics and adaptive behaviours. We identify key pieces of the fragmented landscape of food security modelling, and organize achievements and gaps into different contextual domains of food security (production, trade, and consumption) at different spatial scales. Building on in-depth reflection on three core issues of food security – volatility, technology, and transformation – we identify methodological challenges and promising strategies for advancement. We emphasize particular requirements related to the multifaceted and multiscale nature of food security. They include the explicit representation of transient dynamics to allow for path dependency and irreversible consequences, and of household heterogeneity to incorporate inequality issues. To illustrate ways forward we provide good practice examples using meta-modelling techniques, non-equilibrium approaches and behavioural-based modelling endeavours. We argue that further integration of different model types is required to better account for both multi-level agency and cross-scale feedbacks within the food system.</p

Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia

<p>Abstract</p> <p>Background</p> <p>Although most guidelines recommend the use of cholinesterase inhibitors (ChEIs) for mild to moderate Alzheimer's Disease, only a small proportion of affected patients receive these drugs. We aimed to study if geriatric comorbidity and polypharmacy influence the prescription of ChEIs in patients with dementia in Germany.</p> <p>Methods</p> <p>We used claims data of 1,848 incident patients with dementia aged 65 years and older. Inclusion criteria were first outpatient diagnoses for dementia in at least three of four consecutive quarters (incidence year). Our dependent variable was the prescription of at least one ChEI in the incidence year. Main independent variables were polypharmacy (defined as the number of prescribed medications categorized into quartiles) and measures of geriatric comorbidity (levels of care dependency and 14 symptom complexes characterizing geriatric patients). Data were analyzed by multivariate logistic regression.</p> <p>Results</p> <p>On average, patients were 78.7 years old (47.6% female) and received 9.7 different medications (interquartile range: 6-13). 44.4% were assigned to one of three care levels and virtually all patients (92.0%) had at least one symptom complex characterizing geriatric patients. 13.0% received at least one ChEI within the incidence year. Patients not assigned to the highest care level were more likely to receive a prescription (e.g., no level of care dependency vs. level 3: adjusted Odds Ratio [OR]: 5.35; 95% CI: 1.61-17.81). The chance decreased with increasing numbers of symptoms characterizing geriatric patients (e.g., 0 vs. 5+ geriatric complexes: OR: 4.23; 95% CI: 2.06-8.69). The overall number of prescribed medications had no influence on ChEI prescription and a significant effect of age could only be found in the univariate analysis. Living in a rural compared to an urban environment and contacts to neurologists or psychiatrists were associated with a significant increase in the likelihood of receiving ChEIs in the multivariate analysis.</p> <p>Conclusions</p> <p>It seems that not age as such but the overall clinical condition of a patient including care dependency and geriatric comorbidities influences the process of decision making on prescription of ChEIs.</p

Targeted delivery of a phosphoinositide 3-kinase γ inhibitor to restore organ function in sepsis

Jaundice, the clinical hallmark of infection-associated liver dysfunction, reflects altered membrane organization of the canalicular pole of hepatocytes and portends poor outcomes. Mice lacking phosphoinositide 3-kinase-γ (PI3Kγ) are protected against membrane disintegration and hepatic excretory dysfunction. However, they exhibit a severe immune defect that hinders neutrophil recruitment to sites of infection. To exploit the therapeutic potential of PI3Kγ inhibition in sepsis, a targeted approach to deliver drugs to hepatic parenchymal cells without compromising other cells, in particular immune cells, seems warranted. Here, we demonstrate that nanocarriers functionalized through DY-635, a fluorescent polymethine dye, and a ligand of organic anion transporters can selectively deliver therapeutics to hepatic parenchymal cells. Applying this strategy to a murine model of sepsis, we observed the PI3Kγ-dependent restoration of biliary canalicular architecture, maintained excretory liver function, and improved survival without impairing host defense mechanisms. This strategy carries the potential to expand targeted nanomedicines to disease entities with systemic inflammation and concomitantly impaired barrier functionality