Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Improving the physician-patient cardiovascular risk dialogue to improve statin adherence

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the effectiveness of a patient education program developed to facilitate statin adherence.</p> <p>Methods</p> <p>A controlled trial was designed to test the effectiveness of a multifaceted patient education program to facilitate statin adherence. The program included a brief, in-office physician counseling kit followed by patient mailings. The primary end point was adherence to filling statin prescriptions during a 120-day period. Patients new to statins enrolled and completed a survey. Data from a national pharmacy claims database were used to track adherence.</p> <p>Results</p> <p>Patients new to statin therapy exposed to a patient counseling and education program achieved a 12.4 higher average number of statin prescription fill days and were 10% more likely to fill prescriptions for at least 120 days (<it>p </it>= .01).</p> <p>Conclusion</p> <p>Brief in-office counseling on cardiovascular risk followed by patient education mailings can be effective in increasing adherence. Physicians found a one-minute counseling tool and pocket guidelines useful in counseling patients.</p

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

Social disparities in the use of colonoscopy by primary care physicians in Ontario

<p>Abstract</p> <p>Background</p> <p>It is unclear if all persons in Ontario have equal access to colonoscopy. This research was designed to describe long-term trends in the use of colonoscopy by primary care physicians (PCPs) in Ontario, and to determine whether PCP characteristics influence the use of colonoscopy.</p> <p>Methods</p> <p>We conducted a population-based retrospective study of PCPs in Ontario between the years 1996-2005. Using administrative data we identified a screen-eligible group of patients aged 50-74 years in Ontario. These patients were linked to the PCP who provided the most continuous care to them during each year. We determined the use of any colonoscopy among these patients. We calculated the rate of colonoscopy for each PCP as the number of patients undergoing colonoscopies per 100 screen eligible patients. Negative binomial regression was used to identify factors associated with the rate of colonoscopy, using generalized estimating equations to account for clustering of patients within PCPs.</p> <p>Results</p> <p>Between 7,955 and 8,419 PCPs in Ontario per year (median age 43 years) had at least 10 eligible patients in their practices. The use of colonoscopy by PCPs increased sharply in Ontario during the study period, from a median rate of 1.51 [inter quartile range (IQR) 0.57-2.62] per 100 screen eligible patients in 1996 to 4.71 (IQR 2.70-7.53) in 2005. There was substantial variation between PCPs in their use of colonoscopy. PCPs who were Canadian medical graduates and with more years of experience were more likely to use colonoscopy after adjusting for their patient characteristics. PCPs were more likely to use colonoscopy if their patient populations were predominantly women, older, had more illnesses, and if their patients resided in less marginalized neighborhoods (lower unemployment, fewer immigrants, higher income, higher education, and higher English/French fluency).</p> <p>Conclusions</p> <p>There is substantial variation in the use of colonoscopy by PCPs, and this variation has increased as the overall use of colonoscopy increased over time. PCPs whose patients were more marginalized were less likely to use colonoscopy, suggesting that there are inequities in access.</p

Vignette studies of medical choice and judgement to study caregivers' medical decision behaviour: systematic review

BACKGROUND: Vignette studies of medical choice and judgement have gained popularity in the medical literature. Originally developed in mathematical psychology they can be used to evaluate physicians' behaviour in the setting of diagnostic testing or treatment decisions. We provide an overview of the use, objectives and methodology of these studies in the medical field. METHODS: Systematic review. We searched in electronic databases; reference lists of included studies. We included studies that examined medical decisions of physicians, nurses or medical students using cue weightings from answers to structured vignettes. Two reviewers scrutinized abstracts and examined full text copies of potentially eligible studies. The aim of the included studies, the type of clinical decision, the number of participants, some technical aspects, and the type of statistical analysis were extracted in duplicate and discrepancies were resolved by consensus. RESULTS: 30 reports published between 1983 and 2005 fulfilled the inclusion criteria. 22 studies (73%) reported on treatment decisions and 27 (90%) explored the variation of decisions among experts. Nine studies (30%) described differences in decisions between groups of caregivers and ten studies (33%) described the decision behaviour of only one group. Only six studies (20%) compared decision behaviour against an empirical reference of a correct decision. The median number of considered attributes was 6.5 (IQR 4-9), the median number of vignettes was 27 (IQR 16-40). In 17 studies, decision makers had to rate the relative importance of a given vignette; in six studies they had to assign a probability to each vignette. Only ten studies (33%) applied a statistical procedure to account for correlated data. CONCLUSION: Various studies of medical choice and judgement have been performed to depict weightings of the value of clinical information from answers to structured vignettes of care givers. We found that the design and analysis methods used in current applications vary considerably and could be improved in a large number of cases

Evaluation of a large scale implementation of disease management programmes in various Dutch regions: a study protocol

Background. Disease management programmes (DMPs) have been developed to improve effectiveness and economic efficiency withi

Validation of the Work Observation Method By Activity Timing (WOMBAT) method of conducting time-motion observations in critical care settings: an observational study

<p>Abstract</p> <p>Background</p> <p>Electronic documentation handling may facilitate information flows in health care settings to support better coordination of care among Health Care Providers (HCPs), but evidence is limited. Methods that accurately depict changes to the workflows of HCPs are needed to assess whether the introduction of a Critical Care clinical Information System (CCIS) to two Intensive Care Units (ICUs) represents a positive step for patient care. To evaluate a previously described method of quantifying amounts of time spent and interruptions encountered by HCPs working in two ICUs.</p> <p>Methods</p> <p>Observers used PDAs running the Work Observation Method By Activity Timing (WOMBAT) software to record the tasks performed by HCPs in advance of the introduction of a Critical Care clinical Information System (CCIS) to quantify amounts of time spent on tasks and interruptions encountered by HCPs in ICUs.</p> <p>Results</p> <p>We report the percentages of time spent on each task category, and the rates of interruptions observed for physicians, nurses, respiratory therapists, and unit clerks. Compared with previously published data from Australian hospital wards, interdisciplinary information sharing and communication in ICUs explain higher proportions of time spent on professional communication and documentation by nurses and physicians, as well as more frequent interruptions which are often followed by professional communication tasks.</p> <p>Conclusions</p> <p>Critical care workloads include requirements for timely information sharing and communication and explain the differences we observed between the two datasets. The data presented here further validate the WOMBAT method, and support plans to compare workflows before and after the introduction of electronic documentation methods in ICUs.</p

Efficacy of interventions to increase the uptake of chlamydia screening in primary care: a systematic review

<p>Abstract</p> <p>Background</p> <p>As most genital chlamydia infections are asymptomatic, screening is the main way to detect and cases for treatment. We undertook a systematic review of studies assessing the efficacy of interventions for increasing the uptake of chlamydia screening in primary care.</p> <p>Methods</p> <p>We reviewed studies which compared chlamydia screening in the presence and the absence of an intervention. The primary endpoints were screening rate or total tests.</p> <p>Results</p> <p>We identified 16 intervention strategies; 11 were randomised controlled trials and five observational studies, 10 targeted females only, five both males and females, and one males only. Of the 15 interventions among females, six were associated with significant increases in screening rates at the 0.05 level including a multifaceted quality improvement program that involved provision of a urine jar to patients at registration (44% in intervention clinics vs. 16% in the control clinic); linking screening to routine Pap smears (6.9% vs. 4.5%), computer alerts for doctors (12.2% vs. 10.6%); education workshops for clinic staff; internet-based continuing medical education (15.5% vs. 12.4%); and free sexual health consultations (16.8% vs. 13.2%). Of the six interventions targeting males, two found significant increases including the multifaceted quality improvement program in which urine jars were provided to patients at registration (45% vs. 15%); and the offering by doctors of a test to all presenting young male clients, prior to consultation (29 vs. 4%).</p> <p>Conclusions</p> <p>Interventions that promoted the universal offer of a chlamydia test in young people had the greatest impact on increasing screening in primary care.</p

Prevention of anxiety and depression in the age group of 75 years and over: a randomised controlled trial testing the feasibility and effectiveness of a generic stepped care programme among elderly community residents at high risk of developing anxiety and depression versus usual care [ISRCTN26474556]

BACKGROUND: In frail elderly, the effects of depression and anxiety are deep encroaching. Indicated prevention studies, aimed at subjects with subthreshold disorder, have shown that well designed interventions are capable of reducing the incidence of depression and anxiety. In this randomised prevention trial for elderly, living in the community and suffering from subthreshold depression and anxiety, a stepped care programme was put together to be tested versus usual (GP) care. METHODS/DESIGN: Design: randomised controlled trial. (See figure 1: organisation chart) together with two other projects, this project is part of a national consortium that investigates the prevention of anxiety and depressive disorders in later life using a stepped care programme. The three projects have their own particular focus. This project is aimed at elderly living in the community. Inclusion: subjects with a high risk for depression and anxiety without clinical evidence of these syndromes. The participants are 75 years of age and over and have subthreshold symptoms of depression and or anxiety: they score above the cut-off point on the self-report Centre for Epidemiologic Studies Depression (CES-D) scale, but the criteria for a major depressive disorder or anxiety disorder (panic disorder, agoraphobia, social phobia, generalized anxiety disorder) according to a validated interview, the Mini International Neuropsychiatric Interview (MINI) are not fulfilled. Outcomes: primary outcome: incidence of a depressive or anxiety disorder over a period of two years (MINI); secondary outcome: a positive influence of the intervention, a stepped care programme, on symptoms of depression and anxiety and on quality of life as assessed with the CES D, the HADS A and the SF36 respectively (i.e. stabilisation or improvement of symptoms) [see table 1]. Measurements: Take place at baseline and at 3, 6, 9, 12, 18 and 24 months. Trained independent evaluators assess depression and anxiety status, the primary end point (6, 12, 18, 24 months) [see table 2]. DISCUSSION: Late-life depression and anxiety are characterised by high prevalence, unfavourable prognosis, reduced quality of life, excess mortality and substantial societal costs. No health service, however well equipped, will be able to effectively treat all elderly with depression and anxiety. Therefore, development of (cost) effective means to prevent these disorders is very important