An integrated framework of personalized medicine: from individual genomes to participatory health care

Abstract Promising research developments in both basic and applied sciences, such as genomics and participatory health care approaches, have generated widespread interest in personalized medicine among almost all scientific areas and clinicians. The term personalized medicine is, however, frequently used without defining a clear theoretical and methodological background. In addition, to date most personalized medicine approaches still lack convincing empirical evidence regarding their contribution and advantages in comparison to traditional models. Here, we propose that personalized medicine can only fulfill the promise of optimizing our health care system by an interdisciplinary and translational view that extends beyond traditional diagnostic and classification systems

Cost-Effectiveness and Cost-Utility of Early Levodopa in Parkinson's Disease

Background: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40 weeks followed by levodopa/carbidopa 100/25 mg three times per day for 40 weeks (delayed-start).Objective: This paper reports the results of the economic evaluation performed alongside the LEAP-study.Methods: Early-start treatment was evaluated versus delayed-start treatment, in which the cost-effectiveness analysis (CEA) and the cost-utility analysis (CUA) were performed from the societal perspective, including health care costs among providers, non-reimbursable out-of-pocket expenses of patients, employer costs of sick leave, and lowered productivity while at work. The outcome measure for the CEA was the extra cost per unit decrease on the Unified Parkinson's Disease Rating Scale 80 weeks after baseline. The outcome measure for the CUA was the extra costs per additional quality adjusted life year (QALY) during follow-up.Results: 212 patients in the early-start and 219 patients in the delayed-start group reported use of health care resources. With savings of D 59 per patient (BCa 95% CI: -829, 788) in the early-start compared to the delayed-start group, societal costs were balanced. The early-start group showed a mean of 1.30 QALYs (BCa 95% CI: 1.26, 1.33) versus 1.30 QALYs (BCa 95% CI: 1.27, 1.33) for the delayed-start group. Because of this negligible difference, incremental cost-effectiveness and cost-utility ratios were not calculated.Conclusion: From an economic point of view, this study suggests that early treatment with levodopa is not more expensive than delayed treatment with levodopa.Neurological Motor Disorder

An integrated framework of personalized medicine: from individual genomes to participatory health care

Abstract Promising research developments in both basic and applied sciences, such as genomics and participatory health care approaches, have generated widespread interest in personalized medicine among almost all scientific areas and clinicians. The term personalized medicine is, however, frequently used without defining a clear theoretical and methodological background. In addition, to date most personalized medicine approaches still lack convincing empirical evidence regarding their contribution and advantages in comparison to traditional models. Here, we propose that personalized medicine can only fulfill the promise of optimizing our health care system by an interdisciplinary and translational view that extends beyond traditional diagnostic and classification systems

Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase

Peripheral decarboxylase inhibitors (PDIs) prevent the conversion of levodopa to dopamine in the blood by the enzyme aromatic L-amino acid decarboxylase (AADC). Alterations in enzyme activity may contribute to the required higher dosages of levodopa observed in many patients with Parkinson’s disease. We evaluated the effect of levodopa/PDI use on serum AADC enzyme activity. Serum AADC enzyme activity was evaluated in three independent cohorts of patients with Parkinson’s disease or parkinsonism (n = 301) and compared between patients on levodopa/PDI vs. patients not on this medication. AADC enzyme activity was elevated in 62% of patients on levodopa/PDI treatment, compared to 19% of patients not on levodopa/PDI (median 90 mU/L vs. 50 mU/L, p < 0.001). Patients with elevated AADC activity had longer disease duration and higher doses of levodopa/PDI. These findings may implicate that peripheral AADC induction could underlie a waning effect of levodopa, necessitating dose increases to maintain a sustained therapeutic effect

Durvalumab after chemoradiotherapy in patients with stage III non-small-cell lung cancer: real-world outcomes versus clinical trial results

Aim: We investigated the effectiveness of durvalumab post-concurrent CRT (cCRT) and post-sequential CRT (sCRT) versus cCRT and sCRT alone and compared these outcomes with the PACIFIC trial. Methods: Four cohorts of stage III NSCLC patients who received CRT were included: cCRT with and without durvalumab, sCRT with and without durvalumab. PFS and OS were analyzed using Cox regression. Results: Durvalumab improved PFS (cCRT: aHR = 0.69, sCRT: aHR = 0.71) and OS (cCRT: aHR = 0.71, sCRT: aHR = 0.32), although not all results were significant. PFS was longer in the real-world than in the trial, while OS did not differ. Conclusion: Durvalumab after CRT improved the survival outcomes. The difference between PFS in our study and the trial may be due to differences in follow-up methods. Plain language summary We assessed a medicine called durvalumab on patients with non-small cell lung cancer who received chemoradiotherapy in a real-world setting. We compared their outcomes with those from a clinical trial. Patients who received two types of chemoradiotherapy with or without durvalumab were included, and their progression-free survival (PFS) and overall survival (OS) outcomes were analyzed. We found that patients treated with durvalumab had better PFS and OS than those treated without durvalumab. PFS was longer in the real-world than in the clinical trial, but OS was similar. The difference in PFS may be due to differences in measuring PFS

Fosfor en plantstrategie sturen biodiversiteit in duingraslanden

De vegetatie in kalkrijke en kalkarme duingraslanden verschilt niet alleen in soortenrijkdom, maar ook in strategie om fosfor op te nemen uit de bodem. In kalkrijke duinen komen veel mycorrhizaplanten voor met een schimmelnetwerk rond de wortels, maar in kalkarme duinen vooral niet-mycorrhizaplanten. In dit artikel gaan we in op hoe dit komt, wat dit betekent voor de biodiversiteit en de gevoeligheid voor hoge stikstofdepositie, en waarom het zo belangrijk is de pH in de bodem hoog te houden

ParkinsonNet:A low-cost health care innovation with a systems approach from the Netherlands

Item does not contain fulltextParkinsonNet, a low-cost innovation to optimize care for patients with Parkinson disease, was developed in 2004 as a network of physical therapists in several regions in the Netherlands. Since that time, the network has achieved full national reach, with 70 regional networks and around 3,000 specifically trained professionals from 12 disciplines. Key elements include the empowerment of professionals who are highly trained and specialized in Parkinson disease, the empowerment of patients by education and consultation, and the empowerment of integrated multidisciplinary teams to better address and manage the disease. Studies have found that the ParkinsonNet approach leads to outcomes that are at least as good as, if not better than, outcomes from usual care. One study found a 50 percent reduction in hip fractures and fewer inpatient admissions. Other studies suggest that ParkinsonNet leads to modest but important cost savings (at least US$439 per patient annually). These cost savings outweigh the costs of building and maintaining the network. Because of ParkinsonNet's success, the program has now spread to several other countries and serves as a model of a successful and scalable frugal innovation

Dance classes improve self-esteem and quality of life in persons with Parkinson’s disease

Introduction: Dance can reduce motor symptoms in persons with Parkinson’s disease (PD). However, the effect on psychosocial wellbeing, including self-esteem and quality of life is less clear. Methods: Forty-nine persons with PD (Hoehn and Yahr stage 1–4) participated in weekly dance classes for a consecutive period of 22 weeks, 36 participants completed the classes. Two baseline measurements (T1a and T1b) were performed during a 2-week control period prior to the dance classes. Post-measurements (T2) were performed immediately after 22 weeks of dance classes. Primary outcome was self-esteem as measured with the Rosenberg Self-Esteem Score. Results: Self-esteem scores were stable across the two baseline measurements and improved significantly after the dance classes (1.5 points improvement between T1b and T2, 95% CI 0.3, 2.7; p = 0.012). Additionally, quality of life as measured with the Parkinson’s Disease Questionnaire 39 improved significantly (3.4 points reduction between T1b and T2, 95%CI − 5.7, − 1.2; p = 0.003) as did motor symptoms as measured with the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale—part III (6.2 points reduction between T1b and T2, 95%CI − 10.1, − 2.4; p = 0.002). Balance confidence as measured with the Activities-Specific Balance Confidence Scale did not change. Discussion and conclusions: Dance classes seem to improve self-esteem, quality of life and motor symptoms in persons with PD. These effects should be investigated further in a randomized clinical trial. Clinical message: Dance classes may be a valuable complementary treatment option in people with PD to improve not only motor symptoms, but also self-esteem and quality of life

Waterkwaliteit grondwater : Bodembiologische bescherming

In dit rapport wordt dieper ingegaan op de zogenoemde bodembiologische barrière, de bescherming van het grondwater die wordt geboden door organismen in de bodem die stoffen afbreken. Het rapport laat zien in welke bodems een hoger dan wel een lager zelfreinigend vermogen wordt verwacht. Deze studie maakt onderdeel uit van het project Grondwater van de Kennisimpuls Waterkwaliteit