Regional variation in primary care improvement strategies and policy: case studies that consider qualitative contextual data for performance measurement in three Canadian provinces

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordOBJECTIVE: To explore regional primary care improvement strategies that are potentially determinants of primary care performance. DESIGN: Multiple comparative embedded case study. SETTING: Three regions in Canada: Fraser East, British Columbia; Eastern Ontario Health Unit, Ontario; Central Zone, Nova Scotia. DATA SOURCES: (1) In-depth interviews with purposively selected key informants (eg, primary care decision-makers, physician leads, regulatory agencies) and focus groups with patients and clinicians (n=68 participants) and (2) published and grey literature (n=205 documents). OUTCOME MEASURES: Variations in spread and uptake of primary care improvement strategies across the three study regions. NVivo (V.11) was used to manage data and perform content analysis to identify categories within and across cases. The coding structure was developed by researchers through iterative collaboration, using inductive and deductive processes. RESULTS: Six overarching primary care improvement strategies, differing in focus and spread, were implemented across the three study regions: interprofessional team-based approaches, provider skill mix expansion, physician groups and networks, information systems, remuneration and performance measurement and reporting infrastructure. CONCLUSION: The addition of information on regional improvement strategies to primary care performance reports could add important contextual insights into primary care performance results. This could help identify possible drivers of reported performance outcomes and levers for change in practice, regional and system-level settings.Canadian Institutes of Health ResearchMichael Smith Foundation for Health Researc

Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients

Background: Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms. Methods: The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13). Results: In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter. Conclusions: This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD. © 2012 Pace et al

Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice

<p>Abstract</p> <p>Background</p> <p>We reported that roflumilast, a phosphodiesterase 4 inhibitor, given orally at 5 mg/kg to mice prevented the development of emphysema in a chronic model of cigarette smoke exposure, while at 1 mg/kg was ineffective. Here we investigated the effects of roflumilast on the volume density (V_V) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure.</p> <p>Methods</p> <p>Slides were obtained from blocks of the previous study and V_Vwas assessed immunohistochemically and by point counting using a grid with 48 points, a 20× objective and a computer screen for a final magnification of 580×. Neutrophils were marked with myeloperoxidase antibody, macrophages with Mac-3, dendritic cells with fascin, B-lymphocytes with B220, CD4+ T-cells with CD4+ antibody, and CD8+T-cells with CD8-α. The significance of the differences was calculated using one-way analysis of variance.</p> <p>Results</p> <p>Chronic smoke exposure increased neutrophil V_Vby 97%, macrophage by 107%, dendritic cell by 217%, B-lymphocyte by 436%, CD4+ by 524%, and CD8+ by 417%. The higher dose of roflumilast prevented the increase in neutrophil V_Vby 78%, macrophage by 82%, dendritic cell by 48%, B-lymphocyte by 100%, CD4+ by 98% and CD8+ V_Vby 88%. The lower dose of roflumilast did not prevent the increase in neutrophil, macrophage and B-cell V_Vbut prevented dendritic cells by 42%, CD4+ by 55%, and CD8+ by 91%.</p> <p>Conclusion</p> <p>These results indicate (<it>i</it>) chronic exposure to cigarette smoke in mice results in a significant recruitment into the lung of inflammatory cells of both the innate and adaptive immune system; (<it>ii</it>) roflumilast at the higher dose exerts a protective effect against the recruitment of all these cells and at the lower dose against the recruitment of dendritic cells and T-lymphocytes; (<it>iii</it>) these findings underline the role of innate immunity in the development of pulmonary emphysema and (<it>iiii</it>) support previous results indicating that the inflammatory cells of the adaptive immune system do not play a central role in the development of cigarette smoke induced emphysema in mice.</p

A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616]

BACKGROUND: IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity. OBJECTIVE OF THE STUDY: The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACE(i )and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF. DESIGN: After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor(®), 100 (2 × 50) patients with IgAN and a urinary P/C ratio ≥ 0.6 (males) and ≥ 0.8 (females) and an estGFR ≥ 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor(® )for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two

Clues from nearby galaxies to a better theory of cosmic evolution

The great advances in the network of cosmological tests show that the relativistic Big Bang theory is a good description of our expanding universe. But the properties of nearby galaxies that can be observed in greatest detail suggest a still better theory would more rapidly gather matter into galaxies and groups of galaxies. This happens in theoretical ideas now under discussion.Comment: published in Natur

Good adherence to HAART and improved survival in a community HIV/AIDS treatment and care programme: the experience of The AIDS Support Organization (TASO), Kampala, Uganda

BACKGROUND: Poor adherence to highly active antiretroviral therapy (HAART) may result in treatment failure and death. Most reports of the effect of adherence to HAART on mortality come from studies where special efforts are made to provide HAART under ideal conditions. However, there are few reports of the impact of non-adherence to HAART on mortality from community HIV/AIDS treatment and care programmes in developing countries. We therefore conducted a study to assess the effect of adherence to HAART on survival in The AIDS Support Organization (TASO) community HAART programme in Kampala, Uganda. METHODS: The study was a retrospective cohort of 897 patients who initiated HAART at TASO clinic, Kampala, between May 2004 and December 2006. A total of 7,856 adherence assessments were performed on the data. Adherence was assessed using a combination of self-report and pill count methods. Patients who took 95%. The crude death rate was 12.2 deaths per 100 patient-years, with a rate of 42.5 deaths per 100 patient-years for non-adherent patients and 6.1 deaths per 100 patient-years for adherent patients. Non-adherence to ART was significantly associated with mortality. Patients with a CD4 count of less than 50 cells/mm3 had a higher mortality (HR = 4.3; 95% CI: 2.22-5.56) compared to patients with a CD4 count equal to or greater than 50 cells/mm3 (HR = 2.4; 95% CI: 1.79-2.38). CONCLUSION: Our study showed that good adherence and improved survival are feasible in community HIV/AIDS programmes such as that of TASO, Uganda. However, there is need to support community HAART programmes to overcome the challenges of funding to provide sustainable supplies particularly of antiretroviral drugs; provision of high quality clinical and laboratory support; and achieving a balance between expansion and quality of services. Measures for the early identification and treatment of HIV infected people including home-based VCT and HAART should be strengthened

The Eastern Origins of the Rise of the West and the “Return” of Asia

With the current interest in China (and India) proliferating within the Western Academy, this article claims that what we are witnessing today is not the rise but the “return” of China (and India). Many academics assume that the West has been the dominant civilization in the world economy in the last 500 years and that the current “rise” of China threatens to knock the West off its perch. However, this article provides an alternative take to this cherished axiom of Eurocentric world history by inverting the standard belief that the West pioneered modernity and then expanded outwards to remake the world. Thus, I argue not only that globalization preceded the rise of the West but that it was Eastern-led on the one hand and that it enabled the Western breakthrough into modernity on the other. This, in turn, rests on my claim that Chinese development stems back not to 1978 but to 960 ce as the Sung Dynasty emerged and subsequently undertook a quasi-industrial miracle. Moreover, between 1450/1492 and ca. 1830 China lay at the centre of the nascent global economy, fanning the integration process alongside other key non-Western regions such as India and West Asia/North Africa. And, while the West was the dominant player after ca. 1830 down to the turn of the third millennium, nevertheless, what we witness today is the return of China to the centre of the global economy whence it came

The significance of measuring monocyte tissue factor activity in patients with breast and colorectal cancer

Monocytes express tissue factor (mTF) in several conditions including cancer where levels may be valuable in assessing tumour presence and progression. Using a two-stage kinetic chromogenic assay (KCA), mTF levels were measured in controls [normal subjects (n = 60) and patients undergoing hernia repair or cholecystectomy (n = 60)], in patients with benign and malignant disease of the breast (n = 83) and of the large bowel (n = 62). This was performed under fresh (resting) conditions and after incubation for 6 h without (unstimulated) and with (stimulated) Escherichia coli endotoxin. The malignant groups showed higher mTF levels than each of the three controls for resting (P &lt; 0.05 breast, P &lt; 0.05 colorectal) unstimulated (P &lt; 0.05 breast, P &lt; 0.05 colorectal) and stimulated cells (P &lt; 0.001 breast, P &lt; 0.01 colorectal). Similarly, the benign inflammatory groups had higher mTF levels than controls for resting (P &lt; 0.05 colorectal), unstimulated (P &lt; 0.05 colorectal) and stimulated cells (P &lt; 0.01 breast, P &lt; 0.01 colorectal). There was no significant difference between malignant and benign inflammatory groups in each organ. mTF levels showed an increase corresponding to that of histological tumour progression and were higher in non-surviving patients. In conclusion, mTF levels are raised in malignant and inflammatory disease compared to controls and patients with non-inflammatory conditions. Stimulated cells give better discrimination between the groups and may be of value in identifying high risk individuals. mTF levels showed an association with tumour grade or stage and the patients' survival time

The breadth of primary care: a systematic literature review of its core dimensions

Background: Even though there is general agreement that primary care is the linchpin of effective health care delivery, to date no efforts have been made to systematically review the scientific evidence supporting this supposition. The aim of this study was to examine the breadth of primary care by identifying its core dimensions and to assess the evidence for their interrelations and their relevance to outcomes at (primary) health system level. Methods: A systematic review of the primary care literature was carried out, restricted to English language journals reporting original research or systematic reviews. Studies published between 2003 and July 2008 were searched in MEDLINE, Embase, Cochrane Library, CINAHL, King's Fund Database, IDEAS Database, and EconLit. Results: Eighty-five studies were identified. This review was able to provide insight in the complexity of primary care as a multidimensional system, by identifying ten core dimensions that constitute a primary care system. The structure of a primary care system consists of three dimensions: 1. governance; 2. economic conditions; and 3. workforce development. The primary care process is determined by four dimensions: 4. access; 5. continuity of care; 6. coordination of care; and 7. comprehensiveness of care. The outcome of a primary care system includes three dimensions: 8. quality of care; 9. efficiency care; and 10. equity in health. There is a considerable evidence base showing that primary care contributes through its dimensions to overall health system performance and health. Conclusions: A primary care system can be defined and approached as a multidimensional system contributing to overall health system performance and health

Different regulation of cigarette smoke induced inflammation in upper versus lower airways

Background: Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure. Methods: C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3 alpha, RORc, IL-17, FoxP3, and TGF-beta 1 in nasal turbinates and lungs by RT-PCR. Results: In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3a and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs. Conclusions: Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model