Using Design Thinking for Co-Creating an Integrated Care Pathway Including Hospital at Home for Older Adults with an Acute Moderate-Severe Respiratory Infection in the Netherlands

Introduction: Acute respiratory infections are common in frail, community-dwelling older people and are accompanied by considerable diagnostic and prognostic uncertainties. Inadequately coordinated care is associated with unnecessary hospital referral and admission with potential iatrogenic harm. Therefore, we aimed to co-create a regional integrated care pathway (ICP), including a hospital at home journey. Developing the ICP: Tasked with using design thinking methodology, stakeholders from regional healthcare facilities, together with patient representatives, were assigned to different focus groups based on their expertise. The focus of each session was to co-create ideal patient journeys suitable for embedding in the ICP. Results: Based on these sessions, a regional cross-domain ICP was developed that comprises three patient journeys. The first journey included a hospital at home track, the second a tailored visit, with priority assessment, to regional emergency departments, and the third concerned referral to readily available nursing home ‘recovery-beds’ under the supervision of an elderly care medicine specialist. Conclusion: Using design thinking and involving end-users during the whole process, we created an ICP for community-dwelling frail older people with moderate-severe acute respiratory infections. This resulted in three realistic patient journeys, including a hospital at home track, which will be implemented and evaluated in the near future

Effects of methimazole on the elimination of irinotecan

Purpose: To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole. Methods: A patient treated for colorectal cancer with single agent irinotecan received methimazole co-medication for Graves' disease. Irinotecan pharmacokinetics and side effects were followed during a total of four courses (two courses with and two courses without methimazole). Results: Plasma concentrations of the active irinotecan metabolite SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean increase of 14 and 67%, respectively) with methimazole co-medication, compared to irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate increased with 47% during concurrent treatment. Other possible confounding factors did not change over time. Specific adverse events due to methimazole co-treatment were not seen. Conclusions: Additional in vitro experiments suggest that these results can be explained by induction of UGT1A1 by methimazole, leading to higher SN-38G concentrations. The prescribed combination of these drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise physicians to be very careful in combining methimazole with regular irinotecan doses, especially in patients who are prone to irinotecan toxicity

Silver nanowires with optimized silica coating as versatile plasmonic resonators

Metal nanoparticles are the most frequently used nanostructures in plasmonics. However, besides nanoparticles, metal nanowires feature several advantages for applications. Their elongation offers a larger interaction volume, their resonances can reach higher quality factors, and their mode structure provides better coupling into integrated hybrid dielectric plasmonic circuits. It is crucial though, to control the distance of the wire to a supporting substrate, to another metal layer or to active materials with sub nanometer precision. A dielectric coating can be utilized for distance control, but it must not degrade the plasmonic properties. In this paper, we introduce a controlled synthesis and coating approach for silver nanowires to fulfill these demands. We synthesize and characterize silver nanowires of around 70 amp; 8201;nm in diameter. These nanowires are coated with nm sized silica shells using a modified Stöber method to achieve a homogeneous and smooth surface quality. We use transmission electron microscopy, dark field microscopy and electron energy loss spectroscopy to study morphology and plasmonic resonances of individual nanowires and quantify the influence of the silica coating. Thorough numerical simulations support the experimental findings showing that the coating does not deteriorate the plasmonic properties and thus introduce silver nanowires as usable building blocks for integrated hybrid plasmonic system

A Mitochondrial calcium dynamics - checks and balances of energy physiology

Mitochondria conserve the energy released from metabolic redox reactions and supply the cell with ATP. When the rate of respiratory metabolism does not match ATP demand active regulation of mitochondrial function is essential. For plants particularly sophisticated regulation strategies can be expected, to ensure maintenance of homeostasis in the presence of frequent environmental changes. Yet, the mechanisms by which such control is achieved in vivo are poorly understood. Calcium acts as a key regulator of mitochondrial energy metabolism in mammals by modulating the activity TCA cycle dehydrogenases. Calcium flux into the matrix is controlled by the recently identified mitochondrial uniporter complex. Plants contain homologues of components of the uniporter, but their function has been unclear. To understand how mitochondrial calcium dynamics are regulated and what their impact is on energy metabolism, we have combined reverse genetics with in vivo sensing of calcium. Fluorescent protein sensors and quantitative confocal imaging allow monitoring of mitochondrial energy physiology in living Arabidopsis tissues. We have found that several homologues of components of the mitochondrial calcium uniporter complex localize to mitochondria in Arabidopsis. Mutant lines have shown severely altered mitochondrial calcium levels and abnormal organellar calcium transients, providing a novel genetic handle on the dissection of the role of calcium regulation in plant mitochondria. We will discuss the specific impact of de-regulated mitochondrial calcium on the physiological network and the function of plant mitochondria

Report on short-term side effects of treatments with 177Lu- octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours

Purpose: Treatment with the radiolabelled somatostatin analogue177Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to177Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination. Methods: Seven patients were treated with 7.4 GBq177Lu-octreotate and capecitabine (1650 mg/m2per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles. Results: None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia. Conclusions: Treatment with the combination of177Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with177Lu-octreotate as single agent with regard to anti-tumour effects and side effects

A self-interaction corrected pseudopotential scheme for magnetic and strongly-correlated systems

Local-spin-density functional calculations may be affected by severe errors when applied to the study of magnetic and strongly-correlated materials. Some of these faults can be traced back to the presence of the spurious self-interaction in the density functional. Since the application of a fully self-consistent self-interaction correction is highly demanding even for moderately large systems, we pursue a strategy of approximating the self-interaction corrected potential with a non-local, pseudopotential-like projector, first generated within the isolated atom and then updated during the self-consistent cycle in the crystal. This scheme, whose implementation is totally uncomplicated and particularly suited for the pseudopotental formalism, dramatically improves the LSDA results for a variety of compounds with a minimal increase of computing cost.Comment: 18 pages, 14 figure

Strong-correlation effects in Born effective charges

Large values of Born effective charges are generally considered as reliable indicators of the genuine tendency of an insulator towards ferroelectric instability. However, these quantities can be very much influenced by strong electron correlation and metallic behavior, which are not exclusive properties of ferroelectric materials. In this paper we compare the Born effective charges of some prototypical ferroelectrics with those of magnetic, non-ferroelectric compounds using a novel, self-interaction free methodology that improves on the local-density approximation description of the electronic properties. We show that the inclusion of strong-correlation effects systermatically reduces the size of the Born effective charges and the electron localization lengths. Furthermore we give an interpretation of the Born effective charges in terms of band energy structure and orbital occupations which can be used as a guideline to rationalize their values in the general case.Comment: 10 pages, 4 postscript figure

The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5.

Objective: Currently, there is no effective medical treatment for patients with pituitary-dependent Cushing’s disease. A novel somatostatin (SS) analogue, named SOM230, with high binding affinity to SS receptor subtypes sst1, sst2, sst3 and sst5 was recently introduced. We compared the in vitro effects of the sst2-preferring SS analogue octreotide (OCT) and the multi-ligand SOM230 on ACTH release by human and mouse corticotroph tumour cells. Methods: By quantitative RT-PCR the sst subtype expression level was determined in human corticotroph adenomas. In vitro, the inhibitory effect of OCT and SOM230 on ACTH release by dispersed human corticotroph adenoma cells and mouse AtT20 corticotroph adenoma cells was determined. In addition, the influence of dexamethasone on the responsiveness to OCT and SOM230 was studied. Results: Corticotroph adenomas expressed predominantly sst5 mRNA (six out of six adenomas), whereas sst2 mRNA expression was detected at significantly lower levels. In a 72 h incubation with 10 nmol/l SOM230, ACTH release was inhibited in three out of five cultures (range –30 to –40%). Ten nmol/l OCT slightly inhibited ACTH release in only one of five cultures (– 28%). In AtT20 cells, expressing sst2, sst3 and sst5, SOM230 inhibited ACTH secretion with high potency (IC50 0.2 nmol/l). Dexamethasone (10 nmol/l) pre-treatment did not influence the sensitivity of the cells to the inhibitory effect of SOM230, suggesting that sst5 is relatively resistant to negative control by glucocorticoids. Conclusions: The selective expression of sst5 receptors in corticotroph adenomas and the preferential inhibition of ACTH release by human corticotroph adenoma cells by SOM230 in vitro, suggest that SOM230 may have potential in the treatment of patients with pituitary-dependent Cushing’s disease