Compression Bandaging in Treatment of Venous Leg Ulcer - Essay Example

? Compression Bandaging in Treatment of Venous Leg Ulcer Introduction Persistent and long duration ulcers thatdo not heal within six weeks are known as chronic ulcers. Most common causes of leg ulcers include venous disease or arterial disease or both. 81% of leg ulcers are due to venous diseases, as surveyed by Health department of Ireland. (Dealey,1999) Venous ulcerations occur due to the venous hypertension. Normally when the leg is moved, calf muscles compress these veins which encourage the flow of blood along the vein. The valves ensure that the blood moves from capillaries towards heart. Thrombosis and varicosity injure the valves present in the veins of legs. These valves are supposed to stop the back flow or reflux of blood. If damaged, then blood can flow in any direction and can cause hypertension in veins. As a result capillaries loose there shape and become distorted. (Dealey,1999) Afterwards, an inflammatory cascade occurs which vary, in both time and its severity, among different individuals. (Bergan,2007).Swelling, a fluid discharging wound and damage to the skin with a uniformly distributed background of hyper pigmentation, dispersed purpuric macules, erythema, scaling, excoriations may also be present as an indicator of the severity of the condition. (Frankel, 2006) The common sites of ulceration are legs and other areas surrounding ankle.(Frankel,2006). To heal long duration chronic leg ulcers various approaches have been embarked on after extensive research studies. Most of the patients have multiple co morbidities, which complicate there potential to heal. As well as patients have to visit doctors on regular basis for frequent change of dressings and for follow up on wound’s condition which increase financial burden. Recurrences are common in the case of venous leg ulcers and can become chronic very easily.(Tavernelli, Reifs&Larsent, 2010) Review: “SYSTEMIC REVIEW OF COMPRESSION TREATMENT FOR VENOUS LEG ULCERS” by Flectcher A., Cullum N., Sheldon T A.(1997). Introduction: The study is conducted to improve the outcomes of venous leg ulcer patients. The research article is fairly original as it is published in a peer reviewed journal (British Medical Journal). Academic journals acts as quality control and ensure that the subject is not only accurate and is properly presented and hence ensures its originality.(Bauer&Brazer, 2010). In this paper, systemic investigation is conducted using data sets from original researches (Primary sources). This work is frequently cited by other authors. The study is conducted by Professor Trevor A. Sheldon and his fellow researcher Alison Fletcher associated with NHS centre for Review and Dissemination, University of York, York. In the introduction, authors describe VLU (Venous leg ulcer) as the chronic condition which can easily recur. The main aim clearly states that the effectiveness of compression bandage as a healing agent for VLU will be determined along with its cost effectiveness. The paper describes compression bandaging as the first line treatment for venous leg ulcers when any arterial disease is absent to complicate the condition. However, determination of the most effective treatment for curing VLU is still under observation by the researchers and medical health practitioners. Therefore, NHS health technology assessment programme commissioned a systemic review to determine the extent of effectiveness of compression bandaging. Methodology The study was designed by selecting relevant data from specialized data basis including Medline, CINHAL, and EMBASE as well as manual search. Search was complemented by scrutiny of the citations, contact with various authors and original manufacturers. All the data was included, disregarding the publication date, status or language. However, complete data is not given in the paper and is referenced to Cochrane Library database. Using fixed effect (peto) method which weights each study and the relationship of dependent variable against its outcomes are determined. Thus, 24 relevant randomized control trials are selected out of which six are unpublished and are stated. However, details of these trials are not given. Inclusion criteria of these studies and along with data extracted was discussed and reviewed but not mentioned in the paper. Unfortunately, the paper only gives the results of these trials. Systemic review is an appropriate method to propose a future agenda when existing agendas fail to solve the clinical problem or to decrease the literature overload and, minimize the uncertainty, if the same question is researched in many studies. (Clark,2011) Results: Three trials which were selected for the study, compared the use of compression and non- compression bandage, whereas, others highlighted the difference between different types of compression bandage. Elastic multilayer high compression vs. inelastic compression (six trials) shows significant increase in odds of healing at 3 months with high compression bandage (HCB). Three small studies found no difference between FLB and SSB use. Comparison between Multilayer HCB and single layer (4trials) show higher rate of healing with multilayer HCB. Trial between medium and high compression bandage system gave unclear results. Compression Hosiery and intermittent pneumatic compression found higher healing rates than compression bandaging. Although, results showing appropriate outcomes are shown in figures and tables, there is no evidence of how the data was collected. The study does not determine the causes or the number of participants who were dropped out of study. Quality of the primary source is assessed and is given in the form of a table. The results are unclear and the quality of the outcomes depends on the quality of primary sources, which are only briefly described in the paper. Appropriate statistical method i.e. fixed effect (peto) method is used to pool the results considering the homogeneity among results. Although it can cause bias if there are substantial differences between control group sizes but otherwise, it gives appropriate result.( Athanasiou,Debas&Darzi, 2010) Discussion: Trials show increase in healing as the compression increased, which was the aim of the study. However, the quality of the studies included was poor; this was limitation of the study. Cost effectiveness associated with a particular high compression system is not clear and thus identifies a future research issue. Researchers suggest increase use of any type of high compression bandage for treatment of uncomplicated venous leg ulcers which is not concluded from the review but it is assumed sensible. High quality systemic reviews include both published and unpublished relevant researches after assessing their quality (Stone, 2002). The researches included in this systemic review had no particular exclusion criteria. More researches are required to determine the cost effectiveness of the treatment. Future systemic reviews should include more information about the patients receiving the intervention and the settings in which they received it. In order to minimize the effects of bias, unpublished and published trials outcomes should be compared. (Borenstein,2009) REVIEW OF: A PROSPECTIVE RANDOMIZED TRIAL OF FOUR-LAYER VERSUS SHORT STRETCH COMPRESSION BANDAGES FOR THE TREATMENT OF VENOUS LEG ULCERS (SCRIVEN JM, TAYLOR LE, WOOD AJ, BELL PR, NAYLOR AR, & LONDON NJ. (1998)) Introduction: The work is based on an original research. It includes a study designed for the purpose of expanding knowledge, including the collection of data from sampling, intervention, observation. Researches using human subjects to simply verify any existing hypothesis or theory are included in original research.(Middlebury) . In the introduction financial burden of the treatment of venous leg ulcer on health resources is described by the author, which is around ?200-?4000 per annum (PALFREYMAN SJ, LOCHIEL R, & MICHAELS JA, 1998)and ?150-?600 (Wilson,1989) per annum as suggested by NHS, in United Kingdom. Introduction clearly states that the topic of investigation is the comparison between two high compression bandage systems i.e. four layer system and short stretch bandage system. As a review, previous researches are also mentioned in the study which concentrates the importance of determining the most effective treatment. Blair et al and Moffat et al suggest that three quarter limbs cure after 12 weeks of four layer bandage use. Duby et al suggest the healing rates of 44%(four layer) and 40%(short stretch) which directly leads us to the question i.e. which one of them is the most effective? Randomized trial is used to address this clinically and economically challenging issue. Sampling: Patients with active lower limb ulcers were recruited from venous ulcer assessment clinic, after assessing the ulcerative limb. Method of assessment is described as color duplex scanning to define venous anatomy, function, and venous reflux in each limb. Limbs with venous ulcers were included in the study. The inclusion criteria for the venous limb was >0.5 Sec. duration and Ankle Brachial Pressure index of >0.8. 53 patients (64 ulcerated limbs) were chosen eligible for the study. Out of 53, one died and 2 failed to participate in the study, which were considered as treatment failure and were included in analysis of intention to treat results. Thus exclusion of the participants is defined in the paper. Study Design: The study design is well described. Randomization is achieved by sealed envelopes. Two groups, differing in their ulcer area were separated as well as patients with bilateral disease had each limb separately randomized. Limbs which don’t heal within 12 weeks duration or ulcers deteriorate within that time were excluded from the study. Though Randomized trials are often more costly, complex and have to be highly selective. It is the best method to determine the affectivity of a treatment or comparison between the two treatments.(Lake,2007) Blinded randomized trial provide unbiased endpoints. This study design provides an average of both known and unknown factors between intervention and comparison groups and provides a basis for statistical tests.(Green,1997) The study was conducted on true to life settings as patients were bandaged at initial hospital visit and size of ulcer and leg volumes were measured at the time and then observations were carried out for 12 weeks with the uniform interval of 4 weeks. Methodology: Methods to measure outcomes were Leg volume measurement by multiple disc models after marking accurate area on leg; this was done after regular intervals of time. Same investigator performed the measurements to control the reproducibility of the technique and to control errors. Ulcer area was measured by computerized Planimetry of tracing which was observed after two weeks interval. Bandaging and dressing technique was performed by an experience staff nurse. Brands and procedure of application of bandage remains same throughout the study and is well described. Appropriate outcomes were chosen at the end of the 12 week trial and results were recorded. Analysis was performed on Intention to treat basis. Data Analysis & Result: Data was analyzed using non parametric statistics. Two groups were compared using Mann Whitney U statistics which is appropriate to test whether the samples are drawn from identical distributions (Comrey,1975). Healing rates were measured by Kaplan-Meier log plots. Kaplan Meier log plot is advantageous when we have censored data i.e. when a patients withdraws from a study before the outcome is generated and it gives median survival time.(Lee,1980) Thus, reliable data is collected using this method. The method is approved by ethical committee. There is no statement of testing the outcomes for validity or reliability. After one year of trial healing rates were found to be 55% with one minor complication for FLB and 575 with four major complications for short stretch bandage. Results are clearly presented in the form of tables. Discussion: Discussion of the author describes compression bandage as the most effective treatment which does not match with the aim of the study. As the study was conducted to determine which one of the high compression bandages is most efficacious which is still unclear. Sources of systemic bias are described by the author as FLB arm had higher median ulcer area compare to SSB, due to broad range of ulcer area included in the study. Furthermore, average ulcer area was misleading due to the same reason of broad range of ulcers included. Researcher found no significant difference between two types of bandages and encouraged the outpatient bandaging of the larger ulcers. SSBs were found to have lower cost than FLB but more chances of complications, thus risk benefit ratio should be borne in mind prior to its use. The study design and method is quite clear and appropriate but the results are still not very clear as was the aim of the study. Additional research is still required to determine the most cost effective method of treatment for venous leg ulcer patients. Systemic biases can be minimized by selecting a proper study design and proper exclusion criteria for future researches. Increasing the sample size does not help to reduce the bias. The paper fails to describe the exclusion criteria. Bottom of Form REVIEW: FOUR LAYER BANDAGE COMPARED WITH SHORT STRETCH BANDAGE FOR VENOUS LEG ULCERS: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS WITH DATA FROM INDIVIDUAL PATIENTS Introduction:Bottom of Form The study is conducted by Researchers who are affiliated with reputable institutions. Susen O’ Meara, J Tierney, Nicky Callum( head of research department), 3.Proffessor of health statistics, J Martin Bland, Professor Peter JF, Trevor Mole Stats Manager and, consultant surgeon Mark Scriven. Research study is published in British Medical Journal and is frequently cited. The authors of the review concluded from previous researches that four layer bandage increases the healing rate but no significant difference is found between different types of high compression bandage. Review describes the limitations of the previous work. This is a well conducted and reliable review. Aim of the research is clearly stated, which is comparison of the four layer bandage with the short stretch bandage in compression treatment for venous leg ulcers. Methodology: Eligible studies from MEDLINE, EMBASE, CINHAL (2002-2005), Cochrane Wound group Specialized Register, Cochrane Central Register of Controlled Trials and National Research Register for additional sources with no restrictions to date, language or location. Primary investigators were invited for additional information. Only randomized control trials of four layer bandage compared with Short stretch bandage treatment of venous leg ulcer were eligible for the study. Out of 128 only 5 completed the protocol. Studies were excluded on the basis of information in the title or abstract, ineligible intervention, not randomized control, irretrievable raw data. Two reviewers faced disagreement when independently selected trials for inclusion but situation was resolved with discussion. Primary outcome of interest was time to healing; secondary outcome of interest was recurrence of ulcer or change of site of ulcer, change in ulcer area and, adverse effects. No statement regarding the study environment (realistic or controlled) of the primary researches is present. No discussion regarding the feasibility or appropriateness of the study design is mentioned in the paper but it is considered appropriate because it reviews all the selected studies relevant to the topic and can conclude a reliable result and precision of the result can be increased with limited the sources of errors and bias (Mulrow& Cook, 1998). Quality of the studies included is assessed using Cochrane Collaboration Tool which examined the competence of randomization, blinding, allocation in order to control bias( Higgins&Green,2008). Quality of individual patient data was assessed by trialists who checked completeness, duplication, validity and integrity of the randomization. Baseline data consisted of age, sex, ulcer duration, patient history, ulcer area, ankle mobility, ABPI and ankle circumference, ulcer infection, appearance of wound bed. Outcomes were measured when ulcer status was determined (healed or not healed), recurrence status, date of healing or recurrence. Analysis of Data: Analysis was done by intention to treat basis. For both treatment groups, non-stratified Kaplan-Meier survival curves were generated with time to healing taken as dependant variable, for both treatment groups. Healing was the event and type of bandage was the factor. Cox proportional hazards models were run to generate hazard ratio to approximate time of healing. Sensitivity analysis was also performed to estimate robust standard errors. Preliminary analysis was performed without considering the baseline characterstics and then follows up with an analysis where these covariates are entered into the model. Secondary outcomes of recurrence could not be conducted due to lack of data. Tests for interaction of bandage type and baseline characters are conducted. Bandage type incidences were calculated by odds ratio using 95% Confidence of interval. Secondary tests allowed the assessment of heterogeneity between the trials using x2 and I2 Statistics. Appropriate levels of data is selected as data checking procedures had low levels of errors such as inconsistent dates, values, discrepancies between individual patient data and published trial reports. These errors were corrected through discussion with relevant investigators. Adequacy of the statistical model is also assessed. Logistic regression statistical test required 10 events per variable to reduce bias in regression coefficient. (Jiang, 2005) All models generated by met analysis met this recommendation. Information regarding participant drop out during the trial was achieved from primary investigators of the study but the reasons of their drop out is not mentioned in the paper. Results: Data was available for 5 trials (n=797) follow up ranging from 3 to 12 months. Median time of healing was 90 days for FLB and 99 days for SSB. Further analysis using bandage type as covariate revealed no significant difference between healing times. When all significant co variants were included in the analysis Hazard Ratio was found to be 1.3 (95%CI: 1.09, 1.58; p=0.005) in favor of FLB. Similar results were available with other covariates as (primary or recurrent ulceration) were available. No interaction between bandage type and baseline characteristics. No statistically significant difference in adverse events between bandage type between trials (n=546) was reported. Thus, the chance of healing increases 30% with FLB than SSB with consistent benefits. Strengths and weaknesses of the research are also identified. Discussion: Author states that the Generalizibility of the results from this review is possible for the patients treated in community or as outpatients. Further researches should be conducted in the fields of recurrence of the ulcers, change in ulcer area and cost effectiveness. Staff skills and adverse effects can also be further researched. Comments: The review addressed a clear research question and relevant studies were included in the analysis. A detailed inclusion criterion of the studies, descriptive study design, intervention and outcomes are given. Search strategy included several studies to minimize the publication and search biases because all systemic reviews are susceptible to publication bias(Egger&Smith,1998). The process of study selection, methods of collection and assessing is reported in detail and was done with suitable thoroughness. Therefore, it is believed that this review is well constructed and reported with reliable and consistent data. Review: IN SEARCH OF OPTIMAL COMPRESSION THERAPY FOR VENOUS LEG ULCERS: A META-ANALYSIS OF STUDIES COMPARING DIVERSE BANDAGES WITH SPECIFICALLY DESIGNED STOCKINGS Introduction: The research study is published in Journal of vascular surgery and is conducted by Felix Amster, Torsten Willenberg and Werner Blatter and their designations with affiliated institutions are well defined in the paper. The review of the paper concludes that stockings were more effective than bandages for healing venous leg ulcers and had a higher rate of ulcer healing than any other treatment. Compression therapy is considered the most effective(Partsch,Ruckley&Bradbury,1999) combined with the superficial venous surgery(Howard&Kothari,2008). High compression and multilayered is more effective than single layer non compression therapy (O’Meara,Cullum, Nelson,2009)(Partsch,2003)but due to unclear quality of the studies and potential sources of bias, affectivity is still not well defined. Aim of the study is stated in the introduction. Author’s Objective is to compare the medical compression stocking affectivity with bandages in VLU treatment. Methodology: Studies were selected from MEDLINE, EMBASE, current contents and Cochrane library. Reference list of selected articles were hand searched. Studies in English, French and German were considered. Unpublished data was not selected. Randomized control trials with any type of bandage treatment against compression stockings for VLU treatment were selected. Missing data was retrieved through contact with the primary investigator. No specific feature for ulcer was defined. Specific exclusion criteria in the paper are defined as cause of ulcer other than venous, heart disease, cancer, diabetes, ABPI 0.8 and no contraindications to Oxpentifylline. However, criteria on which the diagnosis of venous ulcer was based were not stated and thus, it seems phelebography or duplex imagings were not done to confirm any venous disease(Garjraj,Jopp&Stacey,1990). This factor could have affected the uniform selection of participants among four centers. The study design is realistic as was conducted in 4 health centers in Europe and Ireland. The participants of the study were of good health and appropriate nutritional value as described in the paper and were suitable for the study. Each layer used a two layer method of bandaging which was standard for all four centers. There is also a statement regarding permission from the ethics committee at each centre and patients acknowledgement of the task being conducted. Neither description of how research was explained to participants is present nor regarding the treatment of patients facing adverse effects. Thus, quality of ethical standard is difficult to assess for the readers. Researcher did not mention any ethical issues. Study Design: The study design is appropriate for determining the affectivity of the treatment. Placebo controlled, randomized, double blind, parallel group study is conducted and it help to minimize biases (Lake,2007). Setting for the data collection is not explicitly defined but it is likely to have been the community. Both participants and researchers were blinded from the treatment but no further description is available as to what measures were taken to achieve blinding. Blinding or double blinding is important but not obligatory for evidence based medicine practices (Howick,2011). It is not stated that from which method randomization is achieved. Eighty patients (42 receiving placebo and 38 receiving Oxpentifylline) were selected for the task which suited both Chi square test and logrank method, with odds ratio to calculate rate of healing and is considered appropriate. Both groups received same doses of either placebo or Oxpentifylline for six months. Researcher does not describe her own role at any point during the study. Appropriate outcomes were chosen at the endpoint. Primary end point is the complete healing of the ulcer and secondary end point is the change of site of ulcer. Ulcers were traced initially and by computerized software (AUTOCAD), these tracings were measured and thus considered appropriate but no justification of the chosen method is stated. At the start of study, one larger ulcer was considered reference and healing rate of all the ulcers were compared to this ulcer. Reproducibility was maintained by trained observers during the whole measurement procedure but paper fails to describe their names and designations for authentication.Bottom of Form No statement regarding the validity or reliability of these outcome measures is stated. Appropriate data was analyzed by life table methods which accounts for reference ulcer healed at each visit with relevant drop out rate. Results: Ratio of ulcer healed by the end of the study was 34% to 64% in placebo and Oxpentifylline groups. Participant drop out was higher in placebo group due to its increased side effects (9/42) then (3/38) in Oxpentifylline group. Reasons of these drop outs are clearly stated in the paper. 3 pateints of Oxpentifylline group left due to Diarrhea, dyspnea, Oedema, depression. 7 of placebo left due to purpura, diarrhea, dizziness, cellulite, 2 left due to lower tolerance and pemphigoid ulcer diagnosis. Discussion: The discussion of the researcher clearly identifies Oxpentifylline as the most effective treatment of the VLU as was the aim of the study. Researcher further describes previous researches in this field and their shortcomings, thus, putting forth a new question for future research. Oxpentifylline improves oxygen delivery to ischemic tissues (James, 1984) and reduces linkage of Polymorphonuclear leucocytes (BERTOCCHI F, PROSERPIO P, LAMPUGNANI MG, DETANA E, 1988) and this process justifies its benefits in VLU treatment. Comments: Additional researches are required to determine the treatment more effective and safer than Oxpentifylline as there are many adverse effects associated to it (BMA,1944). Overall, the question addressed in the study is well responded. Study design was appropriate for research but few errors in diagnosis of venous disease, data extraction and analysis might be present as they are not in detail in the paper. No description of minimizing sources of systemic biases or limitations of the design was described. High compression bandage system can be a safer approach for the treatment of non complicated ulcers. So for future research different types of compression bandages can be tested for affectivity with standard Oxpentifylline regimen. REFRENCES: Top of Form GAJRAJ H, JOPP-MCKAY A, & STACEY MC. (1990). Oxpentifylline treatment of venous leg ulcers. BMJ (Clinical Research Ed.). 300. Bottom of Form Top of Form POLIT, D. F., & BECK, C. T. (2004). Nursing research: principles and methods. Philadelphia, Lippincott Williams & Wilkins. Bottom of Form Top of Form COOPER, H. M., HEDGES, L. V., & VALENTINE, J. C. (2009). The handbook of research synthesis and meta-analysis. New York, Russell Sage Foundation. Bottom of Form Top of Form MULROW, C. D., & COOK, D. (1998). Systematic reviews: synthesis of best evidence for health care decisions. Philadelphia, Pa, American College of Physicians. FELIX AMSLER TORSTEN WILLENBERG & WERNER BLATTLER.(2009). In search of optimal compression therapy for venous leg ulcers: a meta-analysis of studies comparing diverse bandages with specifically designed stockings. Journal of Vascular Surgery.668-674 SCRIVEN JM, TAYLOR LE, WOOD AJ, BELL PR, NAYLOR AR, & LONDON NJ. (1998). A prospective randomised trial of four-layer versus short stretch compression bandages for the treatment of venous leg ulcers. Annals of the Royal College of Surgeons of England. 80, 215-20. TAVERNELLI K, REIF S, & LARSEN T. (2010). Managing venous leg ulcers in the home. Ostomy/Wound Management. 56, 10-2. FLETCHER A, CULLUM N, & SHELDON TA. (1997). A systematic review of compression treatment for venous leg ulcers. BMJ (Clinical Research Ed.). 315, 576-80. Top of Form O'MEARA S, TIERNEY J, CULLUM N, BLAND JM, FRANKS PJ, MOLE T, & SCRIVEN M. (2009). Four layer bandage compared with short stretch bandage for venous leg ulcers: systematic review and meta-analysis of randomised controlled trials with data from individual patients. BMJ (Clinical Research Ed.). 338. GOHEL, MANJIT S, BARWELL, JAMIE R, TAYLOR, MAXINE, CHANT, TERRY, FOY, CHRIS, EARNSHAW, JONOTHAN J, HEATHER, BRIAN P, MITCHELL, DAVID C, WHYMAN, MARK R, & POSKITT, KEITH R. (n.d.). Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial. BMJ Publishing Group Ltd. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1914523. Top of Form HIGGINS, J. P. T., & GREEN, S. (2008). Cochrane handbook for systematic reviews of interventions. Chichester, England, Wiley-Blackwell. Top of Form Bottom of Form Top of Form Bottom of Form Bottom of Form Bottom of Form PARTSCH H, RUCKLEY CV, FOWKES FGR, BRADBURY . (1999).Venous Disease Compression therapy: is it worthwhile? London: SpringerVerlag. p. 117-25. HOWARD DGJ, HOWARD A, KOTHARI A, WALES L, GUEST M, DAVIES AH.(2008). The role of super?cial venous surgery in the management of venous ulcers: a systematic review. Eur J Vasc Endovasc Surg ,36:458-65. O’MEARA S, CULLUM NA, NELSON EA(2009). Compression for venous leg ulcers (Cochrane review). In: The Cochrane Library, Issue 1, Oxford: Update software PARTSCH H.(2003). Evidenced compression therapy. VASA ;(Suppl 63):1-39 JAMES DR.(1984), Holland BM, Hughes MR, Jones JG, Wardrop CAJ. Oxpentrifylline: effects on red cell deformabilitv and oxygen availability front the blood in intermittent claudication. Clinical Hemorrheologv .4:525-3 BERTOCCHI F, PROSERPIO P, LAMPUGNANI MG, DETANA E.(1988) The effect of Oxpentifylline on polymorphonuclear cell adhesion to cultured endothelial cells. A preliminary report. In: Mandell GL, Novick WrJ, eds. Penioxifvl/inei and leukoctiie function. Somerville, New Jersey: Hoechst-Roussel Pharmaceuticals:68-74. Top of Form JIANG, Y. (2005). A simulation study of the number of events per variable in logistic regression analysis. Thesis (M.S.)--University of Texas Health Science Center at Houston, School of Public Health, 2005. Top of Form EGGER, M., & SMITH, G. D. (1998). Meta-analysis: Bias in location and selection of studies. BMJ : British Medical Journal. 316, 61. Bottom of Form Bottom of Form Top of Form BRITISH MEDICAL ASSOCIATION. (1944). Journal of neurology, neurosurgery and psychiatry. London, British Medical Association. Top of FormPALFREYMAN SJ, LOCHIEL R, & MICHAELS JA. (1998). A systematic review of compression therapy for venous leg ulcers. Vascular Medicine (London, England). 3, 301-13. WILSON E (1989). Prevention and treatment of venous leg ulcers.Health Trends ; 21: 97Bottom of Form Top of Form GREEN SB. (1997). The advantages of community-randomized trials for evaluating lifestyle modification.Controlled Clinical Trials. 18, 506-13. Bottom of Form Top of Form LAKE, J. (2007). Textbook of integrative mental health care. New York, Thieme. Bottom of Form Top of Form COMREY, A. L. (1975). Elementary statistics: a problem solving approach. Homewood, Ill, Dorsey Press. Bottom of Form Top of Form BLAIR SD, WRIGHT DD, BACKHOUSE CM, RIDDLE E, & MCCOLLUM CN. (1988). Sustained compression and healing of chronic venous ulcers. BMJ (Clinical Research Ed.). 297, 1159-61. Top of Form MOFFATT, C. J., FRANKS, P. J., OLDROYD, M., BOSANQUET, N., BROWN, P., GREENHALGH, R. M., & MCCOLLUM, C. N. (n.d.). Community clinics for leg ulcers and impact on healing. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1883915. Bottom of Form Bottom of Form Top of Form LEE, E. T. (1980). Statistical methods for survival data analysis. Belmont, Calif, Lifetime Learning Publications. Bottom of Form Top of Form STONE, P. (2002). What is a systemic review? Applied Nursing Research. 15, 52-53. Bottom of Form Top of Form ATHANASIOU, T., DEBAS, H. T., & DARZI, A. (2010).Key topics in surgical research and methodology. Heidelberg, Springer. Top of Form BORENSTEIN, M. (2009). Introduction to meta-analysis. Chichester, U.K., John Wiley & Sons. Bottom of Form Bottom of Form BAUER, S. C., & BRAZER, S. D. (2012). Using research to lead school improvement: turning evidence into action. Thousand Oaks, Calif, SAGE MIDDLEBURY.(2002). Original Research.(Retrieved on January 24 2012)http://www.middlebury.edu/academics/resources/irb/procedures/definitions/defineOrigResearch Top of Form CLARKE J. (2011). What is a systematic review? .Evidence-Based Nursing. 14. Top of Form HOWICK, J. (2011). The philosophy of evidence-based medicine. Chichester, West Sussex, UK, Wiley-Blackwell, BMJ Books. Bottom of Form Top of Form COLGAN MP, DORMANDY JA, JONES PW, SCHRAIBMAN IG, SHANIK DG, & YOUNG RA. (1990). Oxpentifylline treatment of venous ulcers of the leg. BMJ (Clinical Research Ed.). 300, 972-5. FRANKEL, D. H. (2006). Field guide to clinical dermatology. Philadelphia, PA, Lippincott Williams & Wilkins. DEALEY, C. (1999). The care of wounds a guide for nurses. Oxford, Blackwell Science. http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=51704. BERGAN, J. J., & SHORTELL, C. K. (2007). Venous ulcers. Amsterdam, Elsevier Academic Press. http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=203330. Bottom of Form Read More