Interprofessional collaboration in the home care setting: perspectives of people receiving home care, relatives, nurses, general practitioners, and therapists-results of a qualitative analysis.

BACKGROUND: About one million people in need of home care in Germany are assisted by 15,400 home care services. Home healthcare is mostly a complex endeavour because interprofessional collaboration is often challenging. This might negatively impact patient safety. The project interprof HOME aims to develop an interprofessional person-centred care concept for people receiving home care in a multistep approach. In one of the work packages we explored how people receiving home care, relatives, nurses, general practitioners, and therapists (physiotherapists, occupational therapists, and speech therapists) perceive collaboration in this setting. METHODS: Semi-structured interviews were conducted with 20 people receiving home care and with 21 relatives. Additionally, we worked with nine monoprofessional focus groups involving nurses of home care services (n = 17), general practitioners (n = 14), and therapists (n = 21). The data were analysed by content analysis. RESULTS: Three main categories evolved: "perception of interprofessional collaboration", "means of communication", and "barriers and facilitators". People receiving home care and relatives often perceive little to no interprofessional collaboration and take over a significant part of the organisational coordination and information exchange. Interprofessional collaboration in steady care situations does exist at times and mostly occurs in coordination tasks. Contact and information exchange are rare, however, interprofessional personal encounters are sporadic, and fixed agreements and permanent contact persons are not standard. These trends increase with the complexity of the healthcare situation. Joint collaborations are often perceived as highly beneficial. Means of communications such as telephone, fax, or e-mail are used differently and are often considered tedious and time-consuming. No interprofessional formal written or electronic documentation system exists. Personal acquaintance and mutual trust are perceived as being beneficial, while a lack of mutual availability, limited time, and inadequate compensation hinder interprofessional collaboration. CONCLUSIONS: Interprofessional collaboration in home care occurs irregularly, and coordination often remains with people receiving home care or relatives. While this individual care set-up may work sufficiently well in low complex care situations, it becomes vulnerable to disruptions with increasing complexity. Close interactions, joint collaboration, and fixed means of communication might improve healthcare at home. The findings were integrated into the development of the person-centred interprofessional care concept interprof HOME. TRIAL REGISTRATION: This study is registered on the International Clinical Trails registry platform ClinicalTrials.gov as NCT05149937 on 03/11/2021.

Prehabilitation in older patients prior to elective cardiac procedures (PRECOVERY): study protocol of a multicenter randomized controlled trial.

BACKGROUND: Previous studies have demonstrated the efficacy of rehabilitation after a cardiovascular procedure. Especially older and multimorbid patients benefit from rehabilitation after a cardiac procedure. Prehabilitation prior to cardiac procedures may also have positive effects on patients' pre- and postoperative outcomes. Results of a current meta-analysis show that prehabilitation prior to cardiac procedures can improve perioperative outcomes and alleviate adverse effects. Germany currently lacks a structured cardiac prehabilitation program for older patients, which is coordinated across healthcare sectors. METHODS: In a randomized, controlled, two-arm parallel group, assessor-blinded multicenter intervention trial (PRECOVERY), we will randomize 422 patients aged 75 years or older scheduled for an elective cardiac procedure (e.g., coronary artery bypass graft surgery or transcatheter aortic valve replacement). In PRECOVERY, patients randomized to the intervention group participate in a 2-week multimodal prehabilitation intervention conducted in selected cardiac-specific rehabilitation facilities. The multimodal prehabilitation includes seven modules: exercise therapy, occupational therapy, cognitive training, psychosocial intervention, disease-specific education, education with relatives, and nutritional intervention. Participants in the control group receive standard medical care. The co-primary outcomes are quality of life (QoL) and mortality after 12 months. QoL will be measured by the EuroQol 5-dimensional questionnaire (EQ-5D-5L). A health economic evaluation using health insurance data will measure cost-effectiveness. A mixed-methods process evaluation will accompany the randomized, controlled trial to evaluate dose, reach, fidelity and adaptions of the intervention. DISCUSSION: In this study, we investigate whether a tailored prehabilitation program can improve long-term survival, QoL and functional capacity. Additionally, we will analyze whether the intervention is cost-effective. This is the largest cardiac prehabilitation trial targeting the wide implementation of a new form of care for geriatric cardiac patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00030526). Registered on 30 January 2023.

Cost-Effectiveness of Inter-Professional Collaboration to Reduce Hospitalisations in Nursing Home Residents: Results from the German Interprof ACT Trial.

Background: The German multi-centre cluster-randomised controlled trial interprof ACT investigated interventions to increase inter-professional collaboration between nursing home (NH) staff and local general practitioners to reduce hospitalisations and improve nursing homes residents' (NHRs) quality of life. The trial was funded by the German Health Care Innovation Fund. Methods: Cost-effectiveness of interprof ACT interventions was evaluated and compared to current standard of care (SOC) over 12 months, including 622 NHRs in 34 NHs in Germany. Multiplying resource use of healthcare services with German-specific unit costs generated costs. Health outcome was measured in quality-adjusted life-years QALYs), utility by multiplying EQ-5D-5L values with German-specific utility weights. Incremental cost-effectiveness analysis used an intention-to-treat approach and scenario analyses (SAs). Net-benefit-regression and cost-effectiveness acceptability curves addressed uncertainty. A German healthcare insurance perspective was assumed. Results: Base case results showed non-significant cost savings of 851.88€ and non-significant QALY loss of -0,056. Discussion: Dependency levels at baseline were non-significantly higher in IG compared to control group (CG). Lack of baseline costing data eliminated possibility to evaluate changes in costs due to the interprof ACT measures for both groups. Conclusion: Interprof ACT interventions are not cost-effective compared to current SOC.

Cluster randomised trial of a complex interprofessional intervention (interprof ACT) to reduce hospital admission of nursing home residents.

BACKGROUND: Some hospital admissions of nursing home residents (NHRs) might be attributed to inadequate interprofessional collaboration. To improve general practitioner-nurse collaboration in nursing homes (NHs), we developed an intervention package (interprof ACT) in a previous study. OBJECTIVE: To assess the impact of interprof ACT on the proportion of hospitalisation and other clinical parameters within 12 months from randomisation among NHRs. METHODS: Multicentre, cluster randomised controlled trial in 34 German NHs. NHRs of the control group received usual care, whereas NHRs in the intervention group received interprof ACT. Eligible NHs had at least 40 long-term care residents. NHs were randomised 1:1 pairwise. Blinded assessors collected primary outcome data. RESULTS: Seventeen NHs (320 NHRs) were assigned to interprof ACT and 17 NHs (323 NHRs) to usual care. In the intervention group, 136 (42.5%) NHRs were hospitalised at least once within 12 months from randomisation and 151 (46.7%) in the control group (odds ratio (OR): 0.82, 95% confidence interval (CI): [0.55; 1.22], P = 0.33). No differences were found for the average number of hospitalisations: 0.8 hospitalisations per NHR (rate ratio (RR) 0.90, 95% CI: [0.66, 1.25], P = 0.54). Average length of stay was 5.7 days for NHRs in the intervention group and 6.5 days in the control group (RR: 0.70, 95% CI: [0.45, 1.11], P = 0.13). Falls were the most common adverse event, but none was related to the study intervention. CONCLUSIONS: The implementation of interprof ACT did not show a statistically significant and clinically relevant effect on hospital admission of NHRs.

Implementation, mechanisms of change and contextual factors of a complex intervention to improve interprofessional collaboration and the quality of medical care for nursing home residents: study protocol of the process evaluation of the interprof ACT intervention package.

BACKGROUND: To improve interprofessional collaboration between registered nurses (RNs) and general practitioners (GPs) for nursing home residents (NHRs), the interprof ACT intervention package was developed. This complex intervention includes six components (e.g., shared goal setting, standardized procedures for GPs' nursing home visits) that can be locally adapted. The cluster-randomized interprof ACT trial evaluates the effects of this intervention on the cumulative incidence of hospital admissions (primary outcome) and secondary outcomes (e.g., length of hospital stays, utilization of emergency care services, and quality of life) within 12 months. It also includes a process evaluation which is subject of this protocol. The objectives of this evaluation are to assess the implementation of the interprof ACT intervention package and downstream effects on nurse-physician collaboration as well as preconditions and prospects for successive implementation into routine care. METHODS: This study uses a mixed methods triangulation design involving all 34 participating nursing homes (clusters). The quantitative part comprises paper-based surveys among RNs, GPs, NHRs, and nursing home directors at baseline and 12 months. In the intervention group (17 clusters), data on the implementation of preplanned implementation strategies (training and supervision of nominated IPAVs, interprofessional kick-off meetings) and local implementation activities will be recorded. Major outcome domains are the dose, reach and fidelity of the implementation of the intervention package, changes in interprofessional collaboration, and contextual factors. The qualitative part will be conducted in a subsample of 8 nursing homes (4 per study group) and includes repeated non-participating observations and semistructured interviews on the interaction between involved health professionals and their work processes. Quantitative and qualitative data will be descriptively analyzed and then triangulated by means of joint displays and mixed methods informed regression models. DISCUSSION: By integrating a variety of qualitative and quantitative data sources, this process evaluation will allow comprehensive assessment of the implementation of the interprof ACT intervention package, the changes induced in interprofessional collaboration, and the influence of contextual factors. These data will reveal expected and unexpected changes in the procedures of interprofessional care delivery and thus facilitate accurate conclusions for the further design of routine care services for NHRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03426475 . Registered on 07/02/2018.

Effects of strategies to improve general practitioner-nurse collaboration and communication in regard to hospital admissions of nursing home residents (interprof ACT): study protocol for a cluster randomised controlled trial.

BACKGROUND: In Germany, up to 50% of nursing home residents are admitted to a hospital at least once a year. It is often unclear whether this is beneficial or even harmful. Successful interprofessional collaboration and communication involving general practitioners (GPs) and nurses may improve medical care of nursing home residents. In the previous interprof study, the six-component intervention package interprof ACT was developed to facilitate collaboration of GPs and nurses in nursing homes. The aim of this study is to evaluate the effectiveness of the interprof ACT intervention. METHODS: This multicentre, cluster randomised controlled trial compares nursing homes receiving the interprof ACT intervention package for a duration of 12 months (e.g. comprising appointment of mutual contact persons, shared goal setting, standardised GPs' home visits) with a control group (care as usual). A total of 34 nursing homes are randomised, and overall 680 residents recruited. The intervention package is presented in a kick-off meeting to GPs, nurses, residents/relatives or their representatives. Nursing home nurses act as change agents to support local adaption and implementation of the intervention measures. Primary outcome is the cumulative incidence of hospitalisation within 12 months. Secondary outcomes include admissions to hospital, days admitted to hospital, use of other medical services, prevalence of potentially inappropriate medication and quality of life. Additionally, health economic and a mixed methods process evaluation will be performed. DISCUSSION: This study investigates a complex intervention tailored to local needs of nursing homes. Outcomes reflect the healthcare and health of nursing home residents, as well as the feasibility of the intervention package and its impact on interprofessional communication and collaboration. Because of its systematic development and its flexible nature, interprof ACT is expected to be viable for large-scale implementation in routine care services regardless of local organisational conditions and resources available for medical care for nursing home residents on a regular basis. Recommendations will be made for an improved organisation of primary care for nursing home residents. In addition, the results may provide important knowledge and data for the development and evaluation of further strategies to improve outpatient care for elderly care-receivers. TRIAL REGISTRATION: ClinicalTrials.gov NCT03426475 . Initially registered on 7 February 2018.

Reduction of potentially inappropriate medication in the elderly: design of a cluster-randomised controlled trial in German primary care practices (RIME).

BACKGROUND: Potentially inappropriate medication (PIM) is considered to have potentially more harmful than beneficial health effects in elderly patients. A German example for a PIM list is the PRISCUS list that has been available since 2010. PIMs are associated with an increased risk of hospitalisation and adverse health outcomes. Furthermore, drug-drug interactions (DDI) may pose additional risks to patients. It is not yet clear how numbers of PIM and DDI can be reduced in community-dwelling seniors in primary care; nor is it clear whether patients would benefit from such deprescribing. METHODS: The cluster-randomised controlled study on the "Reduction of potentially Inappropriate Medication in the Elderly" (RIME study) is designed to examine whether an intervention based on the PRISCUS list can lower the proportion of community-dwelling people of ⩾70 years taking at least one PIM and/or medication inducing at least one dangerous DDI. The intervention consists of professional education and training on the reduction of PIM and DDI, and will be offered to either general practitioners (GPs) alone or GPs and their office staff in the experimental study arm. The control group will be offered professional education and training on more general issues of prescribing in the elderly, not specifically addressing PIM or DDI. The primary endpoint is the difference in the proportion of patients with at least one PIM or DDI between the start of the study and study closure after 12 months as compared between intervention and control group. Secondary endpoints include overall mortality, number of hospitalisations during the course of the study, quality of life and costs. Secondary analyses will be explorative, with the cluster randomisation being factored in. DISCUSSION: The RIME study will contribute to answering the question of whether an intervention based on the PRISCUS list can reduce the proportion of community-dwelling seniors aged ⩾70 years with at least one PIM and/or DDI, and whether this will result in positive health effects, for example, as regards hospitalisations. TRIAL REGISTRATION: The Study has been registered in the German Clinical Trials Register (DRKS) under the number DRKS00003610.

Subjective Comparison of Pre-Lens Tear Film Stability of Daily Disposable Contact Lenses Using Ring Mire Projection.

PURPOSE: To subjectively evaluate the in vivo tear film stability of three daily disposable contact lenses (DDCLs) using placido ring reflection at lens wear times of 5 mins and 8 and 12 hrs. PATIENTS AND METHODS: This prospective, randomized, observer-masked, 3-way crossover study evaluated 28 subjects with good tear film stability. In vivo tear film stability was assessed for three DDCLs (nelfilcon A, etafilcon A, omafilcon A) on three different days over 12 hrs of lens wear. Time to first distortion by non-invasive keratography drying-up time (NIK-DUTf) was assessed by reviewing the captured videos. Lens wettability was also graded subjectively by three investigators using a scale from 0 (no visible distortions) to 3 (distortions in more than one-third of the ring reflection zone). Medians were analyzed statistically. RESULTS: Mean NIKDUTf at 8 hrs was longer for nelfilcon A and shorter for etafilcon A and omafilcon A, but the differences were not significant. NIK-DUTf did not differ significantly among nelfilcon A, etafilcon A and omafilcon A DDCLs at all visits (p=0.36). Subjective wettability grades after 5 mins, 8 hrs, and 12 hrs differed significantly for etafilcon A (P <0.01) and omafilcon A (p < 0.01), but not for nelfilcon A (p = 0.05), DDCLs. CONCLUSION: Grading was sufficiently sensitive to differentiate the wettability performances of the three lens materials. Nelfilcon A maintained wettability over the wearing period, whereas etafilcon A material showed faster dewetting at 8 and 12 hrs than at 5 mins after lens insertion.

General practitioners' concepts on issuing out-of-pocket prescriptions for hypnotics and sedatives in Germany.

BACKGROUND: In Germany, almost 50% of prescriptions for benzodiazepines and drugs as Zolpidem and Zopiclone are as out-of-pocket (OOP) prescriptions-requiring patients to buy the drug at their own expense-although almost 90% of the population has statutory health insurance covering medication costs. OBJECTIVE: To understand why general practitioners (GPs) choose this prescribing method since needed medications are insurance covered, and unnecessary drugs should not be prescribed at all. METHODS: In this qualitative study, 17 semi-structured interviews with GPs were conducted, audio recorded and transcribed verbatim. Transcripts were analysed with grounded theory to extract a model explaining the described behaviour. RESULTS: Knowing the significant medical risks and insecurity about regulations makes GPs wish to avoid hypnotics and sedatives. They achieve this by 'Creating a barrier' (central phenomenon) and employing the strategy 'Using an out-of-pocket prescription', which not only generates costs for the patient but also reduces the physicians´ legal and financial accountability. The perceived patient type, expected problem duration and diagnosis influence the decision about the prescription form: patients with an alcohol or drug addiction or those with 'uncomplicated' insomnia are more likely to receive an OOP prescription. Patients with any psychiatric diagnosis will likely receive a statutory health insurance prescription. DISCUSSION: Current regulations do not provide guidance to GPs regarding hypnotics and sedatives. A clear regulatory framework and guidelines could possibly reduce physicians' defensive attitudes about these drugs and their use of OOP prescriptions. The approach to use OOP prescriptions as a barrier to reduce patients' medication use lacks evidence regarding effectiveness.

Interprofessional collaboration in nursing homes (interprof): development and piloting of measures to improve interprofessional collaboration and communication: a qualitative multicentre study.

BACKGROUND: Given both the increase of nursing home residents forecast and challenges of current interprofessional interactions, we developed and tested measures to improve collaboration and communication between nurses and general practitioners (GPs) in this setting. Our multicentre study has been funded by the German Federal Ministry of Education and Research (FK 01GY1124). METHODS: The measures were developed iteratively in a continuous process, which is the focus of this article. In part 1 "exploration of the situation", interviews were conducted with GPs, nurses, nursing home residents and their relatives focusing on interprofessional interactions and medical care. They were analysed qualitatively. Based on these results, in part 2 "development of measures to improve collaboration", ideas for improvement were developed in nine focus groups with GPs and nurses. These ideas were revisited in a final expert workshop. We analysed the focus groups and expert workshop using mind mapping methods, and finally drew up the compilation of measures. In an exploratory pilot study "study part 3" four nursing homes chose the measures they wanted to adopt. These were tested for three months. Feasibility and acceptance of the measures were evaluated via guideline interviews with the stakeholders which were analysed by content analyses. RESULTS: Six measures were generated: meetings to establish common goals, main contact person, standardised pro re nata medication, introduction of name badges, improved availability of nurse/GP and standardised scheduling/ procedure for nursing home visits. In the pilot study, the measures were implemented in four nursing homes. GPs and nurses reviewed five measures as feasible and acceptable, only the designation of a "main contact person" was not considered as an improvement. CONCLUSIONS: Six measures to improve collaboration and communication could be compiled in a multistep qualitative process respecting the perspectives of involved stakeholders. Five of the six measures were positively assessed in an exploratory pilot study. They could easily be transferred into the daily routine of other nursing homes, as no special models have to exist in advance. Impact of the measures on patient oriented outcomes should be examined in further research. TRIAL REGISTRATION: Not applicable.

Homologous Recombination and Xylella fastidiosa Host-Pathogen Associations in South America.

Homologous recombination affects the evolution of bacteria such as Xylella fastidiosa, a naturally competent plant pathogen that requires insect vectors for dispersal. This bacterial species is taxonomically divided into subspecies, with phylogenetic clusters within subspecies that are host specific. One subspecies, pauca, is primarily limited to South America, with the exception of recently reported strains in Europe and Costa Rica. Despite the economic importance of X. fastidiosa subsp. pauca in South America, little is known about its genetic diversity. Multilocus sequence typing (MLST) has previously identified six sequence types (ST) among plant samples collected in Brazil (both subsp. pauca and multiplex). Here, we report on a survey of X. fastidiosa genetic diversity (MLST based) performed in six regions in Brazil and two in Argentina, by sampling five different plant species. In addition to the six previously reported ST, seven new subsp. pauca and two new subsp. multiplex ST were identified. The presence of subsp. multiplex in South America is considered to be the consequence of a single introduction from its native range in North America more than 80 years ago. Different phylogenetic approaches clustered the South American ST into four groups, with strains infecting citrus (subsp. pauca); coffee and olive (subsp. pauca); coffee, hibiscus, and plum (subsp. pauca); and plum (subsp. multiplex). In areas where these different genetic clusters occurred sympatrically, we found evidence of homologous recombination in the form of bidirectional allelic exchange between subspp. pauca and multiplex. In fact, the only strain of subsp. pauca isolated from a plum host had an allele that originated from subsp. multiplex. These signatures of bidirectional homologous recombination between endemic and introduced ST indicate that gene flow occurs in short evolutionary time frames in X. fastidiosa, despite the ecological isolation (i.e., host plant species) of genotypes.

Older patients' perceived burdens of their health problems: a cross-sectional analysis in 74 German general practices.

BACKGROUND: Older patients often experience the burden of multiple health problems. Physicians need to consider them to arrive at a holistic treatment plan. Yet, it has not been systematically investigated as to which personal burdens ensue from certain health conditions. OBJECTIVE: The objective of this study is to examine older patients' perceived burden of their health problems. PATIENTS AND METHODS: The study presents a cross-sectional analysis in 74 German general practices; 836 patients, 72 years and older (mean 79±4.4), rated the burden of each health problem disclosed by a comprehensive geriatric assessment. Patients rated each burden using three components: importance, emotional impact, and impact on daily activities. Cluster analyses were performed to define patterns in the rating of these components of burden. In a multilevel logistic regression analysis, independent factors that predict high and low burden were explored. RESULTS: Patients had a median of eleven health problems and rated the burden of altogether 8,900 health problems. Four clusters provided a good clustering structure. Two clusters describe a high burden, and a further two, a low burden. Patients attributed a high burden to social and psychological health problems (especially being a caregiver: odds ratio [OR] 10.4, 95% confidence interval [CI] 4.4-24.4), to specific symptoms (eg, claudication: OR 2.3, 95% CI 1.3-4.0; pain: OR 2.3, 95% CI 1.6-3.1), and physical disabilities. Patients rated a comparatively low burden for most of their medical findings, for cognitive impairment, and lifestyle issues (eg, hypertension: OR 0.2, 95% CI 0.2-0.3). CONCLUSION: The patients experienced a relatively greater burden for physical disabilities, mood, or social issues than for diseases themselves. Physicians should interpret these burdens in the individual context and consider them in their treatment planning.

Lombards on the move--an integrative study of the migration period cemetery at Szólád, Hungary.

In 2005 to 2007 45 skeletons of adults and subadults were excavated at the Lombard period cemetery at Szólád (6th century A.D.), Hungary. Embedded into the well-recorded historical context, the article presents the results obtained by an integrative investigation including anthropological, molecular genetic and isotopic (δ(15)N, δ(13)C, (87)Sr/(86)Sr) analyses. Skeletal stress markers as well as traces of interpersonal violence were found to occur frequently. The mitochondrial DNA profiles revealed a heterogeneous spectrum of lineages that belong to the haplogroups H, U, J, HV, T2, I, and K, which are common in present-day Europe and in the Near East, while N1a and N1b are today quite rare. Evidence of possible direct maternal kinship was identified in only three pairs of individuals. According to enamel strontium isotope ratios, at least 31% of the individuals died at a location other than their birthplace and/or had moved during childhood. Based on the peculiar 87 Sr/86 Sr ratio distribution between females, males, and subadults in comparison to local vegetation and soil samples, we propose a three-phase model of group movement. An initial patrilocal group with narrower male but wider female Sr isotope distribution settled at Szólád, whilst the majority of subadults represented in the cemetery yielded a distinct Sr isotope signature. Owing to the virtual absence of Szólád-born adults in the cemetery, we may conclude that the settlement was abandoned after approx. one generation. Population heterogeneity is furthermore supported by the carbon and nitrogen isotope data. They indicate that a group of high-ranking men had access to larger shares of animal-derived food whilst a few individuals consumed remarkable amounts of millet. The inferred dynamics of the burial community are in agreement with hypotheses of a highly mobile lifestyle during the Migration Period and a short-term occupation of Pannonia by Lombard settlers as conveyed by written sources.

In vivo evaluation of an oral self-microemulsifying drug delivery system (SMEDDS) for leuprorelin.

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for the model peptide drug leuprorelin to prove a protective effect against luminal enzymatic metabolism. In order to incorporate leuprorelin into microemulsion droplets (o/w), the commercially available hydrophilic leuprolide acetate was modified by hydrophobic ion paring with sodium oleate. The obtained hydrophobic leuprolide oleate was dissolved in the SMEDDS formulation (30% (m/m) Cremophor EL, 30% (m/m) Capmul MCM, 10% (m/m) propylene glycol and 30% (m/m) Captex 355) in a concentration of 4 mg/g showing a mean droplet size of 50.1 nm when dispersed in a concentration of 1% (m/v) in phosphate buffer pH 6.8. The microemulsion was able to shield leuprolide oleate from enzymatic degradation by trypsin and α-chymotrypsin, so that after 120 min 52.9% and 58.4%, respectively, of leuprolide oleate were still intact. Leuprolide acetate dissolved in an aqueous control solution was completely metabolized by trypsin within 60 min and by α-chymotrypsin within 5 min. Moreover, an in vivo study in rats showed a 17.2-fold improved oral bioavailability of leuprolide oleate SMEDDS compared to a leuprolide acetate control solution. This is the first time, to our knowledge, that hydrophobic ion pairing is utilized in order to incorporate a peptide drug in SMEDDS and evidence of a protective effect of oil-in-water (o/w) microemulsion droplets against enzymatic degradation of a peptide drug was provided. According to these results, the system could be likely a novel platform technology to improve the oral bioavailability of peptide drugs.

The association between IGF-I/IGFBP-3 and subclinical end points: epidemiology faces the limits.

BACKGROUND: The variation in laboratory measurements represents a challenge in clinical practice and epidemiological research. The use of different analytical platforms might have led to different results, which were often discussed in the interpretation of conflicting results. We aim to study the impact of two different IGF-I and IGF binding protein 3 assays on published epidemiological studies. METHODS: We compared epidemiological results based on the previous gold standard Nichols Advantage, which is no longer available, with these based on the IDS-iSYS assay. The latter follows the recently proposed Keswick criteria. We reinvestigated published association studies between IGF-I or IGF binding protein 3 and anthropometry, subclinical cardiovascular diseases including intima-media thickness or left ventricular mass index, and hard end points like mortality and single-nucleotide polymorphisms of our genome-wide association study in the Study of Health in Pomerania. RESULTS: We demonstrated that there are significant differences in the associations of IGF-I measured by the Nichols or IDS-iSYS assay and subclinical outcomes including intima-media thickness and left ventricular mass index. However, concerning hard outcomes like mortality or single-nucleotide polymorphisms, our analyses revealed similar results with comparable regression estimates. CONCLUSION: With our study we queried not only the accuracy of measurement but also the effect of different methods on study results. The establishment of laboratory standards like the Keswick criteria should be enforced to allow reliable comparisons of different methods and thus clinical and epidemiological studies. Single-center studies have to be interpreted carefully. Moreover, to assure the reliability of studies, their results should be replicated in a meta-analysis, and a generated hypothesis by epidemiology should be proven by intervention studies.

Development and in vitro evaluation of a buccal drug delivery system based on preactivated thiolated pectin.

The aim of this study was to evaluate the potential of preactivated thiolated pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation containing this novel polymer and the model drug lidocaine was prepared and investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and drug release in comparison to formulations based on pectin (Pec) and thiolated pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition of any other excipient due to self-crosslinking thiol groups. Under same conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by 4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous environment during several hours and were able to take up water. Mucoadhesion of pectin on buccal tissue could be improved significantly, value of total work of adhesion increased in the following rank order: Pec-Cys-MNA > Pec-Cys > Pec. The retention time of a model drug incorporated in gel formulations on buccal mucosa under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5 h 3-fold higher amount of a model drug was to be found on tissue after application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution revealed an immediate release. According to these results, the self-crosslinking pectin-derivative is a promising tool for buccal application.

Development and in vivo evaluation of papain-functionalized nanoparticles.

The aim of the present study was to develop a novel nanoparticulate delivery system being capable of penetrating the intestinal mucus layer by cleaving mucoglycoprotein substructures. Nanoparticles based on papain grafted polyacrylic acid (papain-g-PAA) were prepared via ionic gelation and labeled with fluorescein diacetate. In vitro, the proteolytic potential of papain modified nanoparticles was investigated by rheological measurements and diffusion studies across fresh porcine intestinal mucus. The presence of papain on the surface and inside the particles strongly decreases viscosity of the mucus leading to facilitated particle transition across the mucus layer. Results of the permeation studies revealed that enzyme grafted particles diffuse through mucus layer to a 3.0-fold higher extent than the same particles without enzyme. Furthermore, the penetration behavior of the nanocarriers along the gastrointestinal tract of Sprague Dawley rats was investigated after oral administration of nanoparticles formulated as enteric coated capsules. The majority of the papain functionalized particles was able to traverse across the mucus layer and remained in the duodenum and jejunum of the small intestine where drug absorption primarily occurs. Polymeric nanoparticles combined with mucolytic enzymes that are capable of overcoming intestinal mucus barriers offer an encouraging new attempt for mucosal drug delivery.

Continuous cultivation of human hamstring tenocytes on microcarriers in a spinner flask bioreactor system.

Tendon healing is a time consuming process leading to the formation of a functionally altered reparative tissue. Tissue engineering-based tendon reconstruction is attracting more and more interest. The aim of this study was to establish tenocyte expansion on microcarriers in continuous bioreactor cultures and to study tenocyte behavior during this new approach. Human hamstring tendon-derived tenocytes were expanded in monolayer culture before being seeded at two different seeding densities (2.00 and 4.00 3 106 cells/1000 cm2 surface) on CytodexTM type 3 microcarriers. Tenocytes' vitality, growth kinetics and glucose/ lactic acid metabolism were determined dependent on the seeding densities and stirring velocities (20 or 40 rpm) in a spinner flask bioreactor over a period of 2 weeks. Gene expression profiles of tendon extracellular matrix (ECM) markers (type I/III collagen, decorin, cartilage oligomeric protein [COMP], aggrecan) and the tendon marker scleraxis were analyzed using real time detection polymerase chain reaction (RTD-PCR). Type I collagen and decorin deposition was demonstrated applying immunolabeling. Tenocytes adhered on the carriers, remained vital, proliferated and revealed an increasing glucose consumption and lactic acid formation under all culture conditions. "Bead-to-bead" transfer of cells from one microcarrier to another, a prerequisite for continuous tenocyte expansion, was demonstrated by scanning electron microscopy. Type I and type III collagen gene expression was mainly unaffected, whereas aggrecan and partly also decorin and COMP expression was significantly downregulated compared to monolayer cultures. Scleraxis gene expression revealed no significant regulation on the carriers. In conclusion, tenocytes could be successfully expanded on microcarriers. Therefore, bioreactors are promising tools for continuous tenocyte expansion.

Synthesis of transparent aminosilane-derived silica based networks for entrapment of sensitive materials.

A novel sol-gel synthesis route is reported which results in the formation of optically transparent silica based hydro- and xerogels from an aminosilane precursor in aqueous solutions. These materials can be used for entrapment of microalgae and light-harvesting complex (LHC) samples.

Preactivated thiomers: evaluation of gastroretentive minitablets.

The object of this study was to evaluate the potential of a recently developed preactivated thiolated pectin derivative as mucoadhesive excipient in drug delivery to the gastric cavity. Pectin (Pec) was chemically modified with L-cysteine (Cys). The free thiol groups of resulting thiomer were activated with 2-mercaptonicotinic acid (MNA) in order to improve stability and reactivity of attached thiol groups over a broad pH range. Multiunit dosage form properties of the resulting conjugate (Pec-Cys-MNA) were compared to unmodified pectin and the intermediate thiolated using rosuvastatin calcium as a model drug in loaded minitablets. Obtained results were compared with unmodified pectin and the intermediate thiolated pectin. Approximately half of attached thiol groups (507 µmol/g polymer) have been preactivated. Minitablets were evaluated regarding mucoadhesive properties, hardness, disintegration behavior, swelling characteristics and release of rosuvastatin calcium. Mediated by covalent bonds between the polymer and cysteine-rich subdomains in mucus, total work of adhesion increased more than 5-fold. The modification had no impact on hardness of compressed tablets but implementation of the aromatic ligand went along with reduction in hydrophilic properties. Disintegration time was prolonged more than 2-fold while water uptake capacity increased. Weight gain for Pec-Cys-MNA was at least 16-fold. Further, a sustained release of rosuvastatin calcium over 36 h was determined. Neither biodegradability nor CaCo-2 cell viability was affected. The study shows that Pec-Cys-MNA is a promising excipient for the development of mucoadhesive gastric dosage form.