Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8±3.5% in encapsulated and 42.9±5.2% in nonencapsulated islets (P<0.2). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P<0.001). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0±6.1% versus 24.8±5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation

Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 µg ethinyl estradiol and 3 mg drospirenone

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 µg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweigh

Alginate Composition Effects on a Neural Stem Cell-Seeded Scaffold

The purpose of this study was to evaluate the effects of alginate composition on the neurotrophic factor release, viability, and proliferation of encapsulated neural stem cells (NSCs), as well as on the mechanical stability of the scaffold itself. Four compositions were tested: a high guluronic acid (68%) and a high mannuronic acid (54%) content alginate, with or without a poly-L-lysine (PLL) coating layer. Enzyme-linked immunosorbent assay was used to quantify the release of brain-derived neurotrophic factor, glial-derived neurotrophic factor, and nerve growth factor from the encapsulated cells. All three factors were detected from encapsulated cells only when a high L-guluronic acid alginate without PLL was used. Additionally, capsules with this composition remained intact more frequently when exposed to solutions of low osmolarity, potentially indicating superior mechanical stability. Alginate beads with a PLL-coated, high D-mannuronic acid composition were the most prone to breakage in the osmotic pressure test, and were too fragile for histology and proliferation assays after 1 week in vitro. NSCs survived and proliferated in the three remaining alginate compositions similarly over the 21-day study course irrespective of scaffold condition. NSC-seeded alginate beads with a high L-guluronic acid, non-PLL-coated composition may be useful in the repair of injured nervous tissue, where the mechanism is the secretion of neuroprotective factors. We verify the neuroprotective effects of medium conditioned by NSC-seeded alginate beads on the serum withdrawal-mediated death of PC-12 cells here.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78133/1/ten.tec.2008.0302.pd

Norwegian translation, cultural adaption and testing of the Person-centred Practice Inventory - Staff (PCPI-S)

Background: Person-centred health care has widespread recognition, but there are few instruments aimed at measuring the provision of person-centred practice among health care professionals across a range of settings. The Person-centred Practice Inventory – Staff (PCPI-S) is a new instrument for this purpose, theoretically aligned with McCormack & McCance’s person-centred framework, which has been translated and culturally adapted into Norwegian. Methods: The study used a two-stage research design involving: translation and cultural adaption of the PCPI-S from English to Norwegian language (phase 1), and a quantitative cross sectional survey following psychometric evaluation (phase 2). Confirmatory factor analysis was used to examine the theoretical measurement model. Results: The translation and cultural adaption was carried out according to ten recommend steps. Discrepancies were addressed and revised by all translators until consensus was reached on a reconciled version of the translation. A sample of 258 health care staff participated in the survey. The model fit statistics were overall positive; the model requires minor modifications and these are mostly confined to correlated errors. Conclusions: The translation and cultural adaption process of the PCPI-S from English to Norwegian language was a demanding process in order to retain the conceptual meanings of the original instrument. Overall, the psychometric properties of the tool were acceptable, but testing on a larger sample size is recommended.publishedVersio

Stimulation programs for pediatric drug research – do children really benefit?

Most drugs that are currently prescribed in pediatrics have not been tested in children. Pediatric drug studies are stimulated in the USA by the pediatric exclusivity provision under the Food and Drug Administration Modernization Act (FDAMA) that grants patent extensions when pediatric labeling is provided. We investigated the effectiveness of these programs in stimulating drug research in children, thereby increasing the evidence for safe and effective drug use in the pediatric population. All drugs granted pediatric exclusivity under the FDAMA were analyzed by studying the relevant summaries of medical and clinical pharmacology reviews of the pediatric studies or, if these were unavailable, the labeling information as provided by the manufacturer. A systematic search of the literature was performed to identify drug utilization patterns in children. From July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity. Most frequent drug groups were anti-depressants and mood stabilizers, ACE inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti-inflammatory and anti-rheumatic drugs. The distribution of the different drugs closely matched the distribution of these drugs over the adult market, and not the drug utilization by children

Sleep disturbances in an arctic population: The Tromsø Study

<p>Abstract</p> <p>Background</p> <p>Prevalence estimates for insomnia range from 10 to 50% in the adult general population. Sleep disturbances cause great impairment in quality of life, which might even rival or exceed the impairment in other chronic medical disorders. The economic implications and use of health-care services related to chronic insomnia represent a clinical concern as well as a pronounced public health problem. Hypnotics are frequently prescribed for insomnia, but alcohol and over-the-counter sleep aids seem to be more widely used by insomniacs than prescription medications. Despite the complex relationship between insomnia and physical and mental health factors, the condition appears to be underrecognized and undertreated by health care providers, probably due to the generally limited knowledge of the causes and natural development of insomnia.</p> <p>Methods/Design</p> <p>The Tromsø Study is an ongoing population-based cohort study with five previous health studies undertaken between 1974 and 2001. This protocol outlines a planned study within the sixth Tromsø Study (Tromsø VI), aiming at; 1) describing sleep patterns in a community-based sample representative of the general population of northern Norway, and 2) examining outcome variables of sleep disturbances against possible explanatory and confounding variables, both within a cross-sectional approach, as well as retrospectively in a longitudinal study – exploring sleep patterns in subjects who have attended two or more of the previous Tromsø studies between 1974 and 2009. First, we plan to perform a simple screening in order to identify those participants with probable sleep disturbances, and secondly to investigate these sleep disturbances further, using an extensive sleep-questionnaire. We will also collect biological explanatory variables, i.e. blood samples, weight, height and blood pressure. We plan to merge data on an individual level from the Tromsø VI Study with data from the Norwegian Prescription Database (NorPD), which is a national registry including data for all prescription drugs issued at Norwegian pharmacies. Participants with sleep disturbances will be compared with pair-matched controls without sleep disturbances.</p> <p>Discussion</p> <p>Despite ongoing research, many challenges remain in the characterization of sleep disturbances and its correlates. Future mapping of the biological dimensions, natural history, as well as the behavioral and drug-related aspects of sleep disturbances in a representative population samples is clearly needed.</p

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Can antibiotic prescriptions in respiratory tract infections be improved? A cluster-randomized educational intervention in general practice – The Prescription Peer Academic Detailing (Rx-PAD) Study [NCT00272155]

BACKGROUND: More than half of all antibiotic prescriptions in general practice are issued for respiratory tract infections (RTIs), despite convincing evidence that many of these infections are caused by viruses. Frequent misuse of antimicrobial agents is of great global health concern, as we face an emerging worldwide threat of bacterial antibiotic resistance. There is an increasing need to identify determinants and patterns of antibiotic prescribing, in order to identify where clinical practice can be improved. METHODS/DESIGN: Approximately 80 peer continuing medical education (CME) groups in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. A multifaceted intervention has been tailored, where key components are educational outreach visits to the CME-groups, work-shops, audit and feedback. Prescription Peer Academic Detailers (Rx-PADs), who are trained GPs, will conduct the educational outreach visits. During these visits, evidence-based recommendations of antibiotic prescriptions for RTIs will be presented and software will be handed out for installation in participants PCs, enabling collection of prescription data. These data will subsequently be linked to corresponding data from the Norwegian Prescription Database (NorPD). Individual feedback reports will be sent all participating GPs during and one year after the intervention. Main outcomes are baseline proportion of inappropriate antibiotic prescriptions for RTIs and change in prescription patterns compared to baseline one year after the initiation of the tailored pedagogic intervention. DISCUSSION: Improvement of prescription patterns in medical practice is a challenging task. A thorough evaluation of guidelines for antibiotic treatment in RTIs may impose important benefits, whereas inappropriate prescribing entails substantial costs, as well as undesirable consequences like development of antibiotic resistance. Our hypothesis is that an educational intervention program will be effective in improving prescription patterns by reducing the total number of antibiotic prescriptions, as well as reducing the amount of broad-spectrum antibiotics, with special emphasis on macrolides

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015