A governance model for integrated primary/ secondary care for the health-reforming first world: results of a systematic review

Internationally, key health care reform elements rely on improved integration of care between the primary and secondary sectors. The objective of this systematic review is to synthesise the existing published literature on elements of current integrated primary/secondary health care. These elements and how they have supported integrated healthcare governance are presented.A systematic review of peer-reviewed literature from PubMed, MEDLINE, CINAHL, the Cochrane Library, Informit Health Collection, the Primary Health Care Research and Information Service, the Canadian Health Services Research Foundation, European Foundation for Primary Care, European Forum for Primary Care, and Europa Sinapse was undertaken for the years 2006-2012. Relevant websites were also searched for grey literature. Papers were assessed by two assessors according to agreed inclusion criteria which were published in English, between 2006-2012, studies describing an integrated primary/secondary care model, and had reported outcomes in care quality, efficiency and/or satisfaction.Twenty-one studies met the inclusion criteria. All studies evaluated the process of integrated governance and service delivery structures, rather than the effectiveness of services. They included case reports and qualitative data analyses addressing policy change, business issues and issues of clinical integration. A thematic synthesis approach organising data according to themes identified ten elements needed for integrated primary/secondary health care governance across a regional setting including: joint planning; integrated information communication technology; change management; shared clinical priorities; incentives; population focus; measurement - using data as a quality improvement tool; continuing professional development supporting joint working; patient/community engagement; and, innovation.All examples of successful primary/secondary care integration reported in the literature have focused on a combination of some, if not all, of the ten elements described in this paper, and there appears to be agreement that multiple elements are required to ensure successful and sustained integration efforts. Whilst no one model fits all systems these elements provide a focus for setting up integration initiatives which need to be flexible for adapting to local conditions and settings

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (≥ 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified

Trainability of cold induced vasodilatation in fingers and toes

Subjects that repeatedly have to expose the extremities to cold may benefit from a high peripheral temperature to maintain dexterity and tissue integrity. Therefore, we investigated if repeated immersions of a hand and a foot in cold water resulted in increased skin temperatures. Nine male and seven female subjects (mean 20.4; SD 2.2 years) immersed their right (trained) hand and foot simultaneously in 8°C water, 30 min daily for 15 days. During the pre and post-test (days 1 and 15, respectively) the left (untrained) hand and foot were immersed as well. Pain, tactile sensitivity and skin temperatures were measured every day. Mean (SD) toe temperature of the trained foot increased from 9.49°C (0.89) to 10.03°C (1.38) (p < 0.05). The trained hand, however, showed a drop in mean finger temperature from 9.28°C (0.54) to 8.91°C (0.44) (p < 0.001) and the number of cold induced vasodilation (CIVD) reactions decreased from 52% during the first test to 24% during the last test. No significant differences occurred in the untrained extremities. Pain diminished over time and tactile sensitivity decreased with skin temperature. The combination of less CIVD responses in the fingers after training, reduced finger skin temperatures in subjects that did show CIVD and the reduced pain and tactile sensitivity over time may lead to an increased risk for finger cold injuries. It is concluded that repeated cold exposure of the fingers does not lead to favorable adaptations, but may instead increase the injury risk

Heritable symbionts in a world of varying temperature

Heritable microbes represent an important component of the biology, ecology and evolution of many plants, animals and fungi, acting as both parasites and partners. In this review, we examine how heritable symbiont–host interactions may alter host thermal tolerance, and how the dynamics of these interactions may more generally be altered by thermal environment. Obligate symbionts, those required by their host, are considered to represent a thermally sensitive weak point for their host, associated with accumulation of deleterious mutations. As such, these symbionts may represent an important determinant of host thermal envelope and spatial distribution. We then examine the varied relationship between thermal environment and the frequency of facultative symbionts that provide ecologically contingent benefits or act as parasites. We note that some facultative symbionts directly alter host thermotolerance. We outline how thermal environment will alter the benefits/costs of infection more widely, and additionally modulate vertical transmission efficiency. Multiple patterns are observed, with symbionts being cold sensitive in some species and heat sensitive in others, with varying and non-coincident thresholds at which phenotype and transmission are ablated. Nevertheless, it is clear that studies aiming to predict ecological and evolutionary dynamics of symbiont–host interactions need to examine the interaction across a range of thermal environments. Finally, we discuss the importance of thermal sensitivity in predicting the success/failure of symbionts to spread into novel species following natural/engineered introduction

What do hospital decision-makers in Ontario, Canada, have to say about the fairness of priority setting in their institutions?

BACKGROUND: Priority setting, also known as rationing or resource allocation, occurs at all levels of every health care system. Daniels and Sabin have proposed a framework for priority setting in health care institutions called 'accountability for reasonableness', which links priority setting to theories of democratic deliberation. Fairness is a key goal of priority setting. According to 'accountability for reasonableness', health care institutions engaged in priority setting have a claim to fairness if they satisfy four conditions of relevance, publicity, appeals/revision, and enforcement. This is the first study which has surveyed the views of hospital decision makers throughout an entire health system about the fairness of priority setting in their institutions. The purpose of this study is to elicit hospital decision-makers' self-report of the fairness of priority setting in their hospitals using an explicit conceptual framework, 'accountability for reasonableness'. METHODS: 160 Ontario hospital Chief Executive Officers, or their designates, were asked to complete a survey questionnaire concerning priority setting in their publicly funded institutions. Eight-six Ontario hospitals completed this survey, for a response rate of 54%. Six close-ended rating scale questions (e.g. Overall, how fair is priority setting at your hospital?), and 3 open-ended questions (e.g. What do you see as the goal(s) of priority setting in your hospital?) were used. RESULTS: Overall, 60.7% of respondents indicated their hospitals' priority setting was fair. With respect to the 'accountability for reasonableness' conditions, respondents indicated their hospitals performed best for the relevance (75.0%) condition, followed by appeals/revision (56.6%), publicity (56.0%), and enforcement (39.5%). CONCLUSIONS: For the first time hospital Chief Executive Officers within an entire health system were surveyed about the fairness of priority setting practices in their institutions using the conceptual framework 'accountability for reasonableness'. Although many hospital CEOs felt that their priority setting was fair, ample room for improvement was noted, especially for the enforcement condition

Identification of a possible role of thymine DNA glycosylase (TDG) in epigenome maintenance

Thymine DNA glycosylase (TDG) was discovered as an enzyme capable of removing uracil (U) and thymine (T) from G/U and G/T mispairs, respectively. Owing to this ability, TDG was proposed to initiate restoration of C/G pairs at sites of cytosine or 5-methycytosine (5-meC) deamination. In addition to products of base deamination, the substrate spectrum of TDG covers a wide range of DNA base damages resulting from base oxidation and alkylation. TDG was also found to engage in physical and functional interactions with transcription factors, and more recent evidence supports additional interactions with the de novo DNA methyltransferases Dnmt3a and 3b in the context of gene transcription. Together with its biochemical properties, these observations suggest that TDG might be targeted to gene regulatory sequences as part of a macromolecular assembly to control their functional integrity. TDG may counteract the mutagenic effects of C and 5-meC deamination in CG-rich regions and/or be involved in the maintenance of CpG promoter methylation patterns. A tight regulation of CpG methylation at gene regulatory regions is critical for accurate gene expression, proper cellular differentiation and embryonic development. A somewhat surprising but in this context consistent finding was that, in contrast to other DNA glycosylases, TDG is essential for proper fetal development since a targeted knockout of the gene leads to embryonic lethality. To gain insights into the biological functions of TDG, we aimed to establish and apply biochemical fractionation procedures for high affinity purification and structural and functional characterization of TDG containing proteins complexes. The first part of the thesis was concerned with biochemical characterization of the protein interaction network of TDG in living mammalian cells. To this end, I applied different approaches allowing high affinity isolation of protein complexes from mammalian cells, such as the tandem affinity purification (TAP) method as well as immunoprecipitation of endogenous protein and of the TDGa isoform from TdgA overexpressing embryonic stem (ES) cells. These efforts, however, did not reveal any TDG interacting partners in subsequent mass spectrometry (MS) analyses. These results were surprising, as TDG was previously reported to interact with transcription factors and DNA methyltransferases. Remarkably, however, all previously identified protein interactors of TDG were discovered in screen with the respective partner proteins, and under conditions of simultaneous overexpression of both interacting proteins. The only proteins ever identified in screen with TDG were Sumo1 and Sumo3, which turned out to covalently modify the glycosylase. For this reason, we decided to pursue our search with classical cell fractionation experiments. We first did gel filtration experiments from total cell lysates and showed that TDG is indeed able to form distinct multiprotein complexes in undifferentiated mouse embryonic stem cells that may also contain the RNA helicase p68. Further subcellular fractionation experiments then revealed that TDG is present in all cell compartments, with a significant fraction of nuclear TDG being associated with chromatin, together with p68 and de novo DNA methyltransferases. Together with published findings, these results suggested that protein complexes containing TDG might act in a chromatin-associated context, at gene regulatory regions. The developmental phenotype of Tdg-/- knockout mice and the interactions of TDG with factors involved in developmental gene regulation (e.g. retinoic acid receptors RAR/RXR) implicate a function of TDG during early development and cell differentiation, at times governed by dynamic changes in gene expression, DNA methylation and histone modifications. Such changes have been studied using a well-established during in vitro differentiation of ES cells to lineage committed neuronal progenitors (NPs). We thus aimed to address the function of TDG as part of chromatin associated protein complexes during the process of retinoic acid induced differentiation of ES cells to NPs. In the second part of the thesis we made use of a this well-established in vitro differentiation system to examine the genome-wide localization of TDG to chromatin by TDG chromatin immunoprecipitation (ChIP) and to correlate TDG association to chromatin with gene expression and DNA methylation changes linked to cellular differentiation. TDG ChIP combined with high throughput sequencing showed that TDG associates with high preference to CpG islands in promoters of actively transcribed genes or genes poised for transcriptional activation. Such CpG rich sequences are normally unmethylated in mammalian genomes. Interestingly, we found TDG to localize to promoters of many genes controlling pluripotency (e.g. Oct4, Nanog) and developmental processes (e.g. Sfrp2, Tgfb2, Gata6), thus, supporting a function of TDG in cell differentiation and/or embryonic development. As different lines of circumstantial evidence have associated TDG with changes in CpG methylation following activation of hormone responsive gene promoters, we went on to further test genome-wide promoter methylation in Tdg+/- and Tdg-/- NPs making use of a combination of methylated DNA immunoprecipitation (MeDIP) and microarray technology. This showed that the loss of TDG does not affect global promoter DNA methylation. Nevertheless, there were a number of significant differences, suggesting that TDG might affect the CpG methylation pattern at some promoters. Also, owing to the limited resolution of the MeDIP method, however, we could not exclude an involvement of TDG in the control of DNA methylation of specific promoter CpGs. Additional bisulfite sequencing of promoters of TDG bound developmental genes (e.g. Sfrp2, Tgfb2) in NPs and differentiated mouse embryonic fibroblasts (MEFs) have indeed proved that loss of TDG affects local changes in DNA methylation at particular CpGs. Subsequent analysis of genome-wide gene expression profiles of ES cells and differentiated Tdg+/- and Tdg-/- NPs revealed that a limited number of genes (229) are differentially regulated in ES, whereas substantial differences in gene expression in were observed in NPs (1022 genes). This implicated a specific function of TDG in the regulation of cell differentiation triggered gene expression changes. Detailed analysis of the expression of the Pax6 gene, accurate regulation of which is essential for proper neuron development, showed that its promoter is bound by TDG and that its transcription is inappropriately regulated upon further differentiation of Tdg-/- NPs into the neuronal lineage. Whereas Tdg+/- NPs efficiently downregulated Pax6 (50x) and further differentiated into neuron-like cells, Tdg-/- NPs only partially downregulated Pax6 gene expression (6x) and underwent apoptosis at day 2 after plating in neuronal medium. This phenotype was complemented by expression of TDGa, clearly implicating TDG in the regulation of Pax6 expression during differentiation of ES cells to terminal neurons. We further observed misregulation of pluripotency genes (e.g. Oct4) regulated by TDG bound promoters during early differentiation of ES cells. In the absence of TDG, ES cells showed the tendency to enter spontaneous and/or RA induced differentiation, suggesting a role for TDG in the regulation of pluripotency. During RA induced differentiation we further observed the activation of the neuron specific gene Lrrtm2 exclusively in TDG proficient cells. In addition, ChIP experiments showed that transcription factors involved in the activation of the Lrrtm2 gene (e.g. COUP-TFI, RAR) are not recruited to the respective promoter in Tdg-/- cells, suggesting that TDG might act passively as a scaffold factor important for the recruitment of transcription factors to promoter regions. I set out to clarify the biological function of TDG by investigating its molecular interactions in mammalian cells. I found that TDG, as a DNA repair enzyme, associates tightly with chromatin, where it localizes with high preference to CpG island promoters of active genes and genes poised to be expressed. I also found that the loss of TDG causes misregulation of genes during cell differentiation and that this appears to be related to a function of TDG in establishing and/or maintaining CpG methylation pattern in gene regulatory sequences. These discoveries implicate a novel function of DNA repair, in the maintenance not only of the genome, but also the epigenome

A cross sectional evaluation of an alcohol intervention targeting young university students

BACKGROUND: Hazardous drinking has been found to be higher among young university students compared to their non-university peers. Although young university students are exposed to new and exciting experiences, including greater availability and emphasis on social functions involving alcohol there are few multi strategy comprehensive interventions aimed at reducing alcohol-related harms. METHODS: Random cross sectional online surveys were administered to 18-24 year old students studying at the main campus of a large metropolitan university in Perth, Western Australia. Prior to the completion of the second survey an alcohol intervention was implemented on campus. Completed surveys were received from 2465 (Baseline; T1) and 2422 (Post Year 1: T2) students. Students who consumed alcohol in the past 12 months were categorised as low risk or hazardous drinkers using the Alcohol Use Disorders Identification Test (AUDIT). Due to the cross sectional nature of the two samples two-tailed two-proportion z-test and two sample t-tests were employed to determine statistical significance between the two time periods for categorical and continuous variables respectively. RESULTS: At T1 and T2 89.1 % and 87.2 % of the total sample reported drinking alcohol in the past month respectively. Hazardous levels of alcohol consumption reduced slightly between T1 (39.7 %) and T2 (38 %). In both time periods hazardous drinkers reported significantly higher mean scores for experienced harm, second-hand harm and witnessed harm scores compared to low risk drinkers (p &lt;0.001). Hazardous drinkers were significantly more likely to experience academic problems due to their alcohol consumption and to report more positive alcohol expectations than low risk drinkers at both time periods (p &lt;0.001). CONCLUSIONS: Harms and problems for students who report hazardous drinking are of concern and efforts should be made to ensure integrated and targeted strategies reach higher risk students and focus on specific issues such as driving while intoxicated and alcohol related unplanned sexual activity. However there is also a need for universal strategies targeting all students and low risk drinkers as they too are exposed to alcohol harms within the drinking and social environment. Changing the culture of the university environment is a long term aim and to effect change a sustained combination of organisational actions, partnerships and educational actions is required