Systematically reviewing qualitative and quantitative evidence to inform management and policy-making in the health field

Policy-makers and managers have always used a wide range of sources of evidence in making decisions about policy and the organization of services. However, they are under increasing pressure to adopt a more systematic approach to the utilization of the complex evidence base. Decision-makers must address complicated questions about the nature and significance of the problem to be addressed; the nature of proposed interventions; their differential impact; cost-effectiveness; acceptability and so on. This means that Cochrane-style reviews alone are not sufficient. Rather, they require access to syntheses of high-quality evidence that include research and non-research sources, and both qualitative and quantitative research findings. There is no single, agreed framework for synthesizing such diverse forms of evidence and many of the approaches potentially applicable to such an endeavour were devised for either qualitative or quantitative synthesis and/or for analysing primary data. This paper describes the key stages in reviewing and synthesizing qualitative and quantitative evidence for decision-making and looks at various strategies that could offer a way forward. We identify four basic approaches: narrative (including traditional 'literature reviews' and more methodologically explicit approaches such as 'thematic analysis', 'narrative synthesis', 'realist synthesis' and 'meta-narrative mapping'), qualitative (which convert all available evidence into qualitative form using techniques such as 'meta-ethnography' and 'qualitative cross-case analysis'), quantitative (which convert all evidence into quantitative form using techniques such as 'quantitative case survey' or 'content analysis') and Bayesian meta-analysis and decision analysis (which can convert qualitative evidence such as preferences about different outcomes into quantitative form or 'weights' to use in quantitative synthesis). The choice of approach will be contingent on the aim of the review and nature of the available evidence, and often more than one approach will be required.     

Parental attitudes about sexually transmitted infection vaccination for their adolescent children

OBJECTIVES: To evaluate parental attitudes about adolescent vaccination as a function of vaccine characteristics, including whether the vaccine prevented a sexually transmitted infection (STI), and to explore possible sociodemographic predictors of acceptability of STI vaccines. DESIGN: Participants were 278 parents who accompanied their children (69.1% female, aged 12-17 years) to appointments at medical clinics. By using computer-based questionnaires, parents rated 9 hypothetical vaccine scenarios, each of which was defined along 4 dimensions: mode of transmission (STI or non-STI), severity of infection (curable, chronic, or fatal), vaccine efficacy (50%, 70%, or 90%), and availability of behavioral methods for prevention (available or not available). Willingness by parents to vaccinate their adolescents under each vaccine scenario was assessed on a scale that ranged from 0 to 100. Conjoint analysis was used to determine the relative contribution of each dimension to the ratings. RESULTS: The mean vaccine scenario rating was 81.3. Sexually transmitted infection vaccines (mean, 81.3) were not rated differently than non-STI vaccines (mean, 80.0). Conjoint analysis indicated that severity of infection and vaccine efficacy had the strongest influence on ratings, followed by availability of behavioral prevention. Mode of transmission had a negligible effect on ratings. Child age (P = .08) and sex (P = .77), parent age (P = .32) and education (P = .34), insurance status (P = .08), and data collection site (P = .48) were not significantly associated with STI vaccine acceptability. CONCLUSIONS: Parents were accepting of the idea of vaccinating their adolescent children against STIs. The most salient issues were severity of infection and vaccine efficacy, not sexual transmissibility. Parents also favored vaccines for infections that had no method of behavioral prevention available.     

CASK and Dlg form a PDZ protein complex at the mammalian neuromuscular junction

Membrane-associated guanylate kinases (MAGUKs) are modular adapter proteins that serve as scaffolding molecules and anchor channels and receptors via their PDZ (PSD-95, Dlg, Zo-1) domains. Calcium, calmodulin-associated serine/threonine kinase (CASK) is a MAGUK that is critical at synapses in the central nervous system and at cell-cell junctions because of its interactions with channels, receptors, and structural proteins. We show via confocal microscopy that CASK and another MAGUK, Discs Large (Dlg), are present at the mammalian neuromuscular junction in skeletal muscle. Immunoprecipitation data from mouse muscle show that CASK associates with Dlg, providing evidence of a MAGUK protein complex at this synapse. These data indicate that CASK and Dlg may act as a scaffold for organizing receptors and channels at the postsynaptic membrane of the neuromuscular junction.     

Cardiovascular physiology during supine cycle ergometry and dobutamine stress

PURPOSE: This study compared cardiac hemodynamics during supine cycle ergometry and dobutamine stress. METHODS: Thirty-two healthy volunteers (19 female, 13 male, 23.5 +/- 3.5 yr old) completed respective tests on separate days and in random order. Heart rate, blood pressure, and cardiac output were recorded at baseline and peak stress. Echocardiographic measures included left ventricular end-diastolic dimension, fractional shortening, heart rate corrected velocity of circumferential fiber shortening, end-systolic wall stress, and the difference between measured and predicted fiber shortening for measured wall stress. RESULTS: Compared with peak exercise, dobutamine infusion resulted in lower cardiac output (12 +/- 2 vs 16 +/- 4 l x min(-1), P < 0.0001), heart rates (163 +/- 7 vs 175 +/- 12 beats x min(-1), P < 0.0001), and systolic blood pressure (160 +/- 22 vs 185 +/- 20 mm Hg, P < or = 0.0001). Echocardiography demonstrated smaller left ventricular end-diastolic dimension (4.2 +/- 0.7 vs 4.5 +/- 0.7 cm, P = 0.013), higher fractional shortening (0.55 +/- 0.07 vs 0.50 +/- 0.06%, P < 0.001), higher VCFc (2.07 +/- 0.36 vs 1.54 +/- 0.20 circs x s(-1), P < 0.001) higher VCFdiff (0.94 +/- 0.35 vs 0.48 +/- 0.20 circs x s(-1), P < 0.001), and lower end-systolic wall stress (25 +/- 11 vs 42 +/- 16 g x cm(-2), P < 0.001). The stress-velocity relationship during dobutamine demonstrated higher y-intercept and steeper slope, indicating greater load-independent contractility. CONCLUSION: The cardiovascular adaptation to exercise and dobutamine stress differ significantly. Cardiac output during peak exercise is greater than during peak dobutamine secondary to increased heart rate and stroke volume. Despite a greater increase in contractility and decrease in afterload, a smaller increase in cardiac output during dobutamine stress may be secondary to limited ventricular preload.     

Adrenomedullin is increased in the portal circulation during chronic sepsis in rats

BACKGROUND: A clinical hallmark of sepsis is an early, hyperdynamic cardiac phase (increased cardiac output) that degrades to a hypodynamic phase, which results in poor gut perfusion and subsequent gastrointestinal (GI) hypoxemia, tissue ischemia, necrosis and loss of gut barrier function. Studies in rat cecal-ligation and puncture suggest that the potent vasodilator adrenomedullin (AM) might initiate or maintain the hypodynamic phase. We hypothesize that AM expression is increased in acute Escherichia coli bacteremia and chronic E coli-Bacteroides fragilis sepsis. METHODS: Acute bacteremia: male Sprague-Dawley rats were anesthetized (urethane/alpha-chloralose), tracheotomized, and cannulated for monitoring blood pressure (MABP) and heart rate (HR) and for infusion of E coli (10(9) colony-forming units [CFU] E coli per 1 mL normal saline) and blood sampling. Arterial blood was withdrawn for arterial blood gas (ABG) measurements every 60 minutes. After 6 hours, we harvested lung, liver, kidney, spleen, and small intestine tissue samples and drew arterial and portal blood for AM enzyme-linked immunosorbent assay (ELISA). Chronic sepsis: a sterile gauze pad was implanted and animals recovered for 5 days. Twenty-four hours (10(9) CFU E coli and 10(9) CFU B fragilis per 1 mL normal saline; 1 injection) or 72 hours (2 injections) after the inoculation of the back sponge, rats were anesthetized, intubated, and cannulated as above. MABP, HR, and ABG were measured for 1 hour before tissue and serum harvest for AM ELISA. RESULTS: Sepsis increased HR and MABP in all groups. Acute sepsis caused a respiratory alkalosis and pH was also elevated in chronic sepsis. Serum AM levels were increased in all groups compared with baseline and remained elevated at every time point, but were not different between saline controls and septic animals at any time point, except for the portal serum from the 72-hour chronic sepsis, which was elevated. CONCLUSIONS: These data suggest that surgical manipulation alone is sufficient to stimulate AM secretion, most probably from endothelial cells. While the AM levels were decreasing at 72 hours compared with 6 hours or 24 hours in the arterial blood and the saline control portal blood, it remained elevated in the septic portal samples, suggesting that the sepsis-induced increase of AM was derived from the gut by a different mechanism than that which elevated arterial serum levels.     

Mitochondrial dysfunction in autistic patients with 15q inverted duplication

Two autistic children with a chromosome 15q11-q13 inverted duplication are presented. Both had uneventful perinatal courses, normal electroencephalogram and magnetic resonance imaging scans, moderate motor delay, lethargy, severe hypotonia, and modest lactic acidosis. Both had muscle mitochondrial enzyme assays that showed a pronounced mitochondrial hyperproliferation and a partial respiratory chain block most parsimoniously placed at the level of complex III, suggesting candidate gene loci for autism within the critical region may affect pathways influencing mitochondrial function.