Wendy Babidge

A Systematic Review of Strategies to Improve Prophylaxis for Venous Thromboembolism in Hospitals

Objective:To assess the effectiveness of different strategies for increasing the uptake of prophylaxis for venous thromboembolism (VTE) in hospitalized patients through a systematic review of the literature. Methods:Literature databases and the Internet were searched from 1996 to May 2003. Studies of strategies to improve VTE prophylaxis practice were included. Studies where no policy or guideline was implemented or where the focus of the study was not VTE prevention were excluded. Results:Thirty studies were included. The quality of the available evidence was average with the majority of studies being uncontrolled before and after design and thus limited by the historical nature of much of the available data. Adherence to guidelines and the provision of adequate prophylaxis were poor in studies which relied on passive dissemination of guidelines. In general, the use of multiple strategies was more effective than a single strategy used in isolation. The most effective strategies incorporated a system for reminding clinicians to assess patients for VTE risk, either electronic decision-support systems or paper-based reminders, and used audit and feedback to facilitate the iterative refinement of the intervention. There were no studies adequately powered to demonstrate a reduction in rates of VTE. Insufficient evidence was available to make useful comparisons of strategies in terms of costs and resource utilization. Conclusions:Passive dissemination of guidelines is unlikely to improve VTE prophylaxis practice. A number of active strategies used together, which incorporate some method for reminding clinicians to assess patients for DVT risk and assisting the selection of appropriate prophylaxis, are likely to result in the achievement of optimal outcomes.

Rapid reviews versus full systematic reviews: An inventory of current methods and practice in health technology assessment

OBJECTIVES This review assessed current practice in the preparation of rapid reviews by health technology assessment (HTA) organizations, both internationally and in the Australian context, and evaluated the available peer-reviewed literature pertaining to the methodology used in the preparation of these reviews. METHODS A survey tool was developed and distributed to a total of fifty International Network of Agencies for Health Technology Assessment (INAHTA) members and other selected HTA organizations. Data on a broad range of themes related to the conduct of rapid reviews were collated, discussed narratively, and subjected to simple statistical analysis where appropriate. Systematic searches of the Cochrane Library, EMBASE, MEDLINE, and the Australian Medical Index were undertaken in March 2007 to identify literature pertaining to rapid review methodology. Comparative studies, guidelines, program evaluations, methods studies, commentaries, and surveys were considered for inclusion. RESULTS Twenty-three surveys were returned (46 percent), with eighteen agencies reporting on thirty-six rapid review products. Axiomatic trends were identified, but there was little cohesion between organizations regarding the contents, methods, and definition of a rapid review. The twelve studies identified by the systematic literature search did not specifically address the methodology underpinning rapid review; rather, many highlighted the complexity of the area. Authors suggested restricted research questions and truncated search strategies as methods to limit the time taken to complete a review. CONCLUSIONS Rather than developing a formalized methodology by which to conduct rapid reviews, agencies should work toward increasing the transparency of the methods used for each review. It is perhaps the appropriate use, not the appropriate methodology, of a rapid review that requires future consideration.

Rapid versus full systematic reviews: Validity in clinical practice?

Introduction:  Rapid reviews are being produced with greater frequency by health technology assessment (HTA) agencies in response to increased pressure from end‐user clinicians and policy‐makers for rapid, evidence‐based advice on health‐care technologies. This comparative study examines the differences in methodologies and essential conclusions between rapid and full reviews on the same topic, with the aim of determining the validity of rapid reviews in the clinical context and making recommendations for their future application.

SULFIDES IMPAIR SHORT CHAIN FATTY ACID BETA -OXIDATION AT ACYL-COA DEHYDROGENASE LEVEL IN COLONOCYTES : IMPLICATIONS FOR ULCERATIVE COLITIS

The disease process of ulcerative colitis (UC) is associated with a block in β-oxidation of short chain fatty acid in colonic epithelial cells which can be reproduced by exposure of cells to sulfides. The aim of the current work was to assess the level in the β-oxidation pathway at which sulfides might be inhibitory in human colonocytes. Isolated human colonocytes from cases without colitis (n = 12) were exposed to sulfide (1.5 mM) in the presence or absence of exogenous CoA and ATP. Short chain acyl-CoA esters were measured by a high performance liquid chromatographic assay. 14CO2 generation was measured from [1-14C]butyrate and [6-14C]glucose. 14CO2 from butyrate was significantly reduced (p < 0.001) by sulfide. When colonocytes were incubated with hydrogen sulfide in the presence of CoA and ATP, butyryl-CoA concentration was increased (p < 0.01), while crotonyl-CoA (p < 0.01) and acetyl-CoA (p < 0.01) concentrations were decreased. These results show that sulfides inhibit short chain acyl-CoA dehydrogenase. As oxidation of n-butyrate governs the epithelial barrier function of colonocytes the functional activity of short chain acyl-CoA dehydrogenase may be critical in maintaining colonic mucosal integrity. Maintaining the functional activity of dehydrogenases could be an important determinant in the expression of ulcerative colitis.

Human colonocyte detoxification

Detoxification or biotransformation of drugs and xenobiotics are usually linked with liver metabolism, yet colonocytes of the gastrointestinal tract have an equal capacity to mediate these processes.1 2 This brief overview specifically discusses the ability of human colonocytes, but not other tissues, to detoxify chemical agents and relates pertinent findings to ulcerative colitis and some aspects of colon cancer. Failure to detoxify, leading to epithelial cell damage, or an exaggerated capacity to biotransform, leading to carcinogen formation in colonocytes, have been the main implications in disease processes. In general, two categories of detoxification processes are recognised (table 1)3 4: phase I reactions concern oxidation, reduction and hydrolysis within the cytosol, and phase 2 reactions require ATP and concern conjugation with a donor substrate synthesised in the cell. Both reactions need enzymes such as oxidoreductases, hydrolases, transferases, and lyases. Amongst these may be subclasses, genetic polymorphism and variability of enzyme activity in organs and along the gastrointestinal tract. Particularly, differences in enzyme activity in the proximal and distal colon may occur.5 6 View this table: Table 1 Detoxification and biotransformation reactions found in human colonocytes Biochemists, pharmacologists, toxicologists, molecular biologists, geneticists, oncologists, and gastroenterologists are involved in this field of study, from each of which information is now drawn together. Many new toxicological advances made with liver and lung tissues still have to be applied to colonocytes and would be a fruitful area of future research. The subject of clinical gastrointestinal toxicology7 makes it possible to bridge a gap between colonic disease, genetics and the ability to detect initiating or promoting factors in ulcerative colitis and colon cancer. Cytochrome P-450 are a superfamily of haem containing mono-oxygenases8 acting in the metabolism of foreign compounds, as well as synthesis of steroids and bile components. The P-450 superfamily of enzymes is …

Lung volume reduction surgery in emphysema: a systematic review

The aim of this study was to systematically review the literature regarding the safety and efficacy of lung volume reduction surgery (LVRS) in patients with emphysema. Studies on LVRS to August 2000 were identified using MEDLINE, Embase, Current Contents, and the Cochrane Library. Human studies of patients with upper, lower or diffuse distributions of emphysema were included. All types of bullous emphysema were excluded. A surgeon and researcher independently assessed the retrieved articles for their inclusion in the review. When LVRS was compared with medical management, at 2 years LVRS was associated with a higher FEV1 and at least equivalent survival. The use of staple excision of selected areas of lung appeared to be more efficacious than laser ablation. There is insufficient evidence to show preference for median sternotomy or videoscopically assisted thoracotomy, as the more safe and efficacious procedure. In highly selected patients with emphysema LVRS is deemed an acceptable treatment. To fully evaluate the safety and efficacy of LVRS, outcomes beyond 2 years must be included. The results of prospective randomized trials between medical management and LVRS, now in progress, are essential before a final assessment can be made.

Ultrasound-assisted lipoplasty.

Background: Ultrasound‐assisted lipoplasty (UAL) has been associated with particular types of complications and uncertain long‐term effects arising from interactions between ultrasonic energy and living tissue. The present review seeks to address these issues.

Nitric oxide effect on coloncyte metabolism: Co-action of sulfides and peroxide

Luminal levels of nitric oxide/nitrite are high in colitis. Whether nitric oxide is injurious or protective to human colonocytes is unknown and the role of nitric oxide in the genesis of colitis unclear. The aims were to establish whether nitric oxide was injurious to oxidation of substrates (n-butyrate and D-glucose) in isolated human and rat colonocytes both alone and in the presence of hydrogen sulfide and hydrogen peroxide, agents implicated in cell damage of colitis. Nitric oxide generation from S-nitrosoglutathione was measured by nitrite appearance. Colonocytes were isolated and incubated with [1-14C] butyrate or [6-14C] glucose and 2.6 μM nitric oxide, 1.5 mM sodium hydrogen sulfide or 2.5 mM hydrogen peroxide. Acyl-CoA esters were measured by high performance liquid chromatography, 14CO2 radiochemically and lactate/ketones by enzymic methods. Results indicate that nitric oxide very significantly (p < .001) reduced acyl-CoA formation but did not impair 14CO2 generation. Peroxide and sulfide with nitric oxide resulted in significant reduction (p < 0.01) of substrate oxidation to CO2. Sulfide significantly stimulated release of nitric oxide from S-nitrosoglutathione. The principal conclusion is that nitric oxide diminishes CoA metabolism in colonocytes. CoA depletion has been observed in chronic human colitis for which a biochemical explanation has been lacking. For acute injurious action in human colonocytes nitric oxide requires co-action of peroxide and sulfide to impair oxidation of substrates in cells. From current observations treatment of colitis should aim to reduce simultaneously nitric oxide, peroxide and sulfide generation in the colon.

Effect of sulphide on short chain acyl-CoA metabolism in rat colonocytes.

BACKGROUND: It has been proposed that the diminished n-butyrate oxidation observed in ulcerative colitis may be the result of sulphide induced inhibition of short chain acyl-coenzyme A (acyl-CoA) dehydrogenase activity. AIM: To examine the acyl-CoA ester profiles in isolated rat colonic epithelial cells treated in vitro with sodium hydrogen sulphide (NaHS). METHODS: Isolated rat colonic epithelial cell suspensions were incubated for 10 minutes in the presence of [1-14C] n-butyrate (5 mM), with and without NaHS (1.5 mM). Incubations were carried out both in the presence and the absence of exogenous CoA and ATP. Metabolic performance was assessed by 14CO2 production and by acyl-CoA ester production measured by HPLC with ultraviolet detection. RESULTS: Results are given as mean (SEM). For colonocytes incubated in the presence of exogenous CoA and ATP, treatment with NaHS significantly diminished 14CO2 production (control 0.97 (0.06) mumol/g dry weight cells/min, treated 0.26 (0.09) mumol/g dry weight cells/min, p = 0.0019), was associated with an increase in butyryl-CoA concentrations in the final reaction mixture at 10 minutes (control 2.55 (0.28) mumol/g dry weight cells, treated 3.32 (0.32) mumol/g dry weight cells, p = 0.002), and a reduction in crotonyl-CoA concentrations (control 0.274 (0.02) mumol/g dry weight cells, treated 0.120 (0.04) mumol/g dry weight cells, p = 0.008). The mean concentration of acetyl-CoA in the reaction mixture at 10 minutes was not significantly different between control and sulphide treated incubations. There were no significant differences in acyl-CoA ester profiles observed when cells were incubated in the absence of exogenous CoA and ATP. CONCLUSIONS: These results support the view that sulphides inhibit n-butyrate oxidation in colonic epithelial cells by inhibiting short chain acyl dehydrogenation of activated fatty acids.

Patterns of Surgical Treatment for Women with Breast Cancer in Relation to Age

Abstract:  Although treatment recommendations have been advocated for all women with early breast cancer regardless of age, it is generally accepted that different treatments are preferred based on the age of the patient. The aim of this study was to assess the pattern of breast cancer surgery after adjusting for other major prognostic factors in relation to patient age. Data on cancer characteristics and surgical procedures in 31,298 patients with early breast cancer reported to the National Breast Cancer Audit between 1999 and 2006 were used for the study. There was a close association between age and surgical treatment pattern after adjusting for other prognostic factors, including tumor size, histologic grade, number of tumors, lymph node positivity, lymphovascular invasion (LVI), and extensive intraduct component. Breast Conserving Surgery (BCS) was highest among women aged ≤40 years (OR = 1.140; 95% CI: 1.004–1.293) compared to women aged 51–70 years (reference group). BCS was lowest in women aged >70 years (OR = 0.498, 95% CI: 0.455–0.545). Significantly more women aged ≤50 years underwent more than one operation for breast conservation (20.4–24.8%) compared with women aged >50 years (11.4–17.0%). Women aged >70 years were more likely to receive no surgical treatment, 3.5% versus 1.0–1.3% in all other age groups (≤40, 41–50 51–70 years). There is an association between patient age and the type of breast cancer surgery for women in Australia and New Zealand. Women age ≤40 years are more likely to undergo BCS despite having adverse histologic features and have more than one procedure to achieve breast conservation. Older women (>70 years) more commonly undergo mastectomy and are more likely to receive no surgical treatment.