 |
|
What Proportion of Dermatological Patients Receive Evidence-Based Treatment?
Damiano Abeni, MD, MPH;
Carlo René Girardelli, MD;
Cinzia Masini, MD;
Rossella Aprea, ScD;
Carmelo Franco Melchi, MD;
Pietro Puddu, MD;
Paolo Pasquini, MD, MPH
Arch Dermatol. 2001;137:771-776.
ABSTRACT
| |
Objective To determine the proportion of dermatological patients who are offered evidence-based therapy in the routine dermatological practice.
Methods For every patient seen for the first time at one of our tertiary hospital setting clinics between April and May 1999, the primary diagnosis and the primary intervention were recorded. For each primary diagnosis–primary intervention combination, evidence was searched for in electronic databases from January 1966 to December 1999. The proportion of patients who were offered evidence-based interventions was calculated as the main outcome measure.
Results With a study sample of 136 patients, 61 different diagnosis-treatment couples were generated and 94 queries on electronic databases were performed (to account for "primary interventions" including more than 1 drug or treatment modality). Eighty-seven (64%) of 136 patients received evidence-based interventions. Evidence from randomized controlled trials was found for 69 patients (50.7% of the sample). Controlled studies lacking randomization or double blinding or including fewer than 20 patients per treatment group dealt with treatments offered to 14 patients (10.3%). The treatments offered to 4 patients (2.9%) were judged to have self-evident validity (ie, trials unanimously judged unnecessary). Symptomatic and supportive measures accounted for most interventions lacking substantial evidence (36% of the patients), but we had to include in this class other important treatment regimens, mainly for rare conditions.
Conclusions Most of the study patients received evidence-based care. However, published trials should be carefully appraised, and relevance of clinical end points should be evaluated together with methodological issues. More accessible, clinically oriented, evidence-based information sources are needed.
INTRODUCTION
DERMATOLOGY is considered to be a highly empirical field of medicine, and therapeutic interventions in dermatological patients are said to be based simply on "experience" in many instances.1 However, we found only 1 report in the literature on the topic of the extent to which evidence-based medicine influences clinical decisions in the day-to-day practice of a dermatology department.2 The authors of that study, a retrospective review of a sample of case notes from 115 outpatients, conclude that most treatments offered to the patients are based on scientific evidence. However, they do consider a "primary level"2 of evidence, derived from randomized controlled trials (accepted at "face value,"2 without undertaking critical appraisal), and also a "secondary level"2 of evidence, derived "by transference"2 between diseases with pathogenic or clinical similarities or by "careful well-documented follow-up studies."2
We therefore designed the present study to determine the extent to which our own patients are offered evidence-based therapy, by applying more stringent criteria on the evidence available, according to the well-known principles and methods of evidence-based medicine, as already applied in the field of general medicine.3 We also aimed at highlighting areas of intervention where evidence is in fact not available and should be.
PATIENTS, MATERIALS, AND METHODS
PATIENTS AND DATA COLLECTION
We included every adult patient (ie, aged  18 years) seen for the first time and treated at one of the clinics of Istituto Dermopatico dell'Immacolata (a dermatological reference center for central and southern Italy) in April and May 1999. Medical records were reviewed by a member of the clinical team (C.R.G.) and by an external observer (C.M.) who recorded the primary diagnosis and the primary intervention for each patient together with demographic information and clinical history.
Primary diagnosis was defined as the condition for which the patient was seeking dermatological help at that time. Primary intervention was the treatment that represented the most important attempt to cure, alleviate, or care for the patient with respect to the primary diagnosis given, and it could be a combination of more than 1 drug or treatment modality. Other adjunctive treatment (eg, supportive) that the team caring for the patient considered a nonessential part of the primary intervention was indicated as "associated" therapy.
BIBLIOGRAPHIC SEARCH
For each primary diagnosis–primary intervention combination, we searched evidence in electronic databases (MEDLINE, NHS Center for Review and Dissemination, Cochrane Library, and the Controlled Trials Registry) from January 1966 to December 1999.
An original search strategy was developed by modifying the one proposed by default in PubMed4 and presently considered the standard bibliographic search strategy for clinicians looking to find the best evidence in caring for their patients.5 We developed 23 different strategies and tested them on 3 diagnosis-treatment combinations of dermatological relevance. We then chose the most sensitive and specific for identifying relevant trials, systematic reviews, and meta-analyses (Figure 1). When we were unable to identify any trials with this search strategy, "wider" queries (ie, more sensitive) were tried to find out whether the more specific one had missed relevant work. Traditional reviews, overviews, and the American Academy of Dermatology guidelines of care were reference searched for relevant trials but were not considered as sources of evidence per se.
|
|
|
|
The search strategy used in this study.
|
|
|
EVALUATION OF THE EVIDENCE
The articles were independently evaluated by 2 of us (an epidemiologist [D.A.] and a dermatologist [C.M.]) and considered relevant if they dealt with living human beings, were prospective, and compared 2 or more interventions (one of which could be a placebo or a treatment of proven efficacy). Articles in English, Italian, French, German, and Spanish languages were assessed.
Trials dealing with a combination of diseases that were analyzed as a whole were excluded, and trials considering nonclinical outcomes or involving healthy individuals in whom the disease was experimentally induced (eg, contact dermatitis) were considered and critically appraised only if no other source of evidence could be found.
The quality of each trial was ranked by applying a modified version of Sackett's criteria for clinical evidence6: (1) type A trials, large, randomized, double-blind, placebo-controlled studies; (2) type B trials, also randomized, double-blind, placebo-controlled studies, but they include a small number of patients, yielding an imprecise point estimate of treatment effects and increasing the likelihood of high false-positive and/or false-negative errors; (3) type C trials, lack 1 or more of the above-mentioned criteria (or they do not include precise information on study design) or include fewer than 20 patients in each treatment group. When more than 1 type A or B trial was available as supporting evidence, type C trials were not considered. The quality of the trials and their clinical significance were further appraised by applying the checklist proposed by Downs and Black7 that contains questions on reporting, external validity, internal validity, and power of the study to detect a clinically important effect.
Evidence-based reviews and meta-analyses were also included as sources of evidence while case reports and case series were not. Disagreements were resolved by discussion.
OUTCOME MEASURES
On the basis of the evidence found, every primary intervention was classified as follows: a, intervention with evidence from randomized controlled trials (type A or type B study); b, intervention with evidence from type C studies only, as described in the paragraph above; c, intervention based on convincing nonexperimental evidence, defined as interventions whose validity is so evident that randomized trials were unanimously judged unnecessary or, if a placebo would have been involved, unethical; and d, intervention in common use but not meeting the criteria defined for either experimental or convincing nonexperimental evidence.
As already reported in previous work,3 we chose to select patients, and not therapeutic interventions, as the denominator for our proportions to be estimated. The proportion of patients who were offered an intervention and were classified as a, b, or c was calculated as the main outcome measure.
RESULTS
During the study period, 152 new patients were cared for. No primary diagnosis was made for 3, and another 13 patients were not given any specific therapy (just examinations and reassurance), leaving a study sample of 136 participants. After analysis of the medical records, 61 different diagnosis-treatment combinations were generated.
When "primary therapies" included more than 1 drug or treatment modality, queries on electronic databases were generated both for the single components of the treatment and for the association of them. As a result, we performed 94 queries on electronic databases of biomedical publications and identified a total of 1832 articles. Of these, 329 were selected and evaluated. The other 1503 were excluded because they did not fulfill 1 or more of the criteria described in the "Evaluation of Evidence" subsection of the "Patients, Materials, and Methods" section, or because it was impossible for us to properly evaluate them (eg, language unknown to any of the authors and coworkers and no abstract available in English with sufficient information) or to locate them (eg, very old issues of journals untraceable in libraries in Italy).
The results of the study are summarized in Table 1. Eighty-seven patients (64%) were judged by our criteria to have received evidence-based interventions. Approximately half of the patients (69/136) received interventions previously shown to do more good than harm in 1 or more randomized controlled trials. Another 14 patients (10.3%) received interventions for which evidence could be found only from type C trials, therefore not allowing us to reach definite conclusions on the value of the treatment under analysis. However, 24 of the participants who received evidence-based therapy also received additional non–evidence-based treatment (mainly supportive and symptomatic measures and antibiotics) considered to be part of the primary therapy by the clinical team. Forty-nine patients (36% of the sample) received interventions without substantial experimental evidence.
|
|
|
|
Table 1. Evidence on Therapeutic Interventions
|
|
|
Table 2 and Table 3 provide the diagnosis-treatment combinations, a summary of the grade of evidence that could be traced for each of them, and the number of patients treated accordingly. A selection of the references of the more relevant trials, or other evidence-based articles, is given in Table 2.
|
|
|
|
Table 2. Evidence-Based Therapeutic Interventions
|
|
|
|
|
|
|
Table 3. Interventions Without Substantial Experimental Evidence
|
|
|
COMMENT
As already documented by Ellis and coworkers3 for general medicine, and despite more pessimistic expectations based on common beliefs, it was found that in dermatological practice as well most of the patients were offered evidence-based interventions, at least in the setting of a referral facility with special commitment to research. The proportion of evidence-based health care, as reviewed on a useful website38 is quite variable depending on the different specialties and study designs. Most of the studies reported, including the one by Jemec and coworkers,2 consider the therapeutic interventions as the denominator of the proportions. Using the patients rather than the interventions as the denominator for our proportions was particularly useful from a practical point of view as treatments that are rarely used and less investigated did not receive the same weight as common ones, which involve the majority of patients and have had good-quality trials.
Our observed proportions should probably be considered as minimum estimates of the proportion of patients receiving evidence-based treatment in our study. In fact, we used only search tools and information sources available to clinicians in our institute. Had we had person-time to devote to a systematic hand search of the relevant literature and had we obtained funding to subscribe to expensive electronic databases or to pay for translations for languages we do not know (eg, Japanese, Russian, Norwegian), the estimated proportion could have been higher. Systematic reviews are needed to narrow the gap between the amount of information that may be retrieved by clinicians during their practice and all the information that is potentially available. In fact, the diagnosis-therapy combinations for which we were able to find evidence-based reviews or meta-analyses were only 8, involving 21 patients, or 15.4% of the study sample. Evidence-based reviews are an invaluable tool to help the dermatologist who needs to be up-to-date on evidence without spending whole days in a library appraising hundreds of good and, often, bad articles. The effort of the Cochrane Skin Group39 and others in producing such publications is of utmost importance for clinical practice.
Our estimate of the proportion of patients receiving evidence-based therapy may have been affected also by the referral pattern to our institute and the case mix generated by choosing a single clinic (this choice contributed to the exclusion of patients referred to other specific clinics operating in our institute, eg, pigmented lesions), a short period (with differential selection of "seasonal" diseases), and, more importantly, patients seen for the first time. At the end of the study we realized that this last choice led to the preferential selection of diseases with high incidence and short duration. In fact, patients with chronic conditions (eg, psoriasis), and particularly those with low-incidence diseases (eg, systemic sclerosis), although seen in the clinic tended to be excluded because of previous visits. More comprehensive studies are needed to better define the level of evidence-based interventions when considering different groups of diseases and different settings of care although in the same field.
As a cautionary note, it is important to point out that even good trials, conducted for high-prevalence diseases, such as psoriasis and atopic dermatitis, often failed in defining clinically significant outcomes, as is the case for topical steroids where efficacy was almost always assessed in a period of a few weeks with no information on further follow-up and relapses.40
On the other hand, given the high cost of producing experimental evidence, low-profile, low-technology interventions, though considered effective in common experience (eg, eosin in eczema, or sulfur ointment in scabies), are usually not tested by means of controlled trials because conducting trials on them is probably judged to be worthless while many good-quality trials have been conducted for high-cost, high–marketing interest interventions (eg, ketoconazole for seborrheic dermatitis). This is in accordance with the fact that the majority of good trials are funded by pharmaceutical industries or directly conducted by their research teams (eg, 13 of 22, or 59%, in our list of references).
Only four patients (2.9%) were judged to be offered self-evident treatments because in the field of dermatology there are really few conditions for which conducting a placebo-controlled trial should be considered unethical. Besides, there have been repeated demonstrations that treatments previously thought to be "self-evidently" effective were in fact useless or even harmful. On the other hand, many of the symptomatic and supportive measures we included in Table 3 could probably be considered self-evidently effective, at least when considering the goal of simply relieving symptoms (eg, emollients for conditions with dry skin, or topical corticosteroids for acute inflammatory skin reactions).
Symptomatic and supportive measures account for most of the interventions included in Table 3. However, also well-accepted and important treatment regimens for conditions such as discoid lupus erythematosus,41 psoriatic arthritis, or severe drug eruptions42 had to be included among treatments lacking substantial evidence of their effectiveness at the time patients were visited. In many instances, only case reports and case series have been produced, particularly for rare conditions, for which trials need to be multicentric in design if reliable evidence is to be attained.
Even in the cases in which good experimental evidence is produced, a second line of problems arises when trying to find the evidence, critically appraise it, and get it into practice. Electronic databases are not always available, are sometimes too expensive, and are not as easy to search as thought. We compared the results of search strategies developed by one of us (C.M.) (dubbed the "naive dermatologist" strategies) with those obtained by an experienced librarian (R.A.), and observed that the naive dermatologist found many useless articles and missed some important ones.
In addition, when articles are identified, their validity must be carefully assessed, as many so-called trials are produced with flawed designs and unreliable results or unwarranted conclusions. Case reports and case series are particularly at risk for drawing conflicting conclusions and for showing "effectiveness" of treatments that is purely due to well-known phenomena such as placebo effect, selection bias, and regression toward the mean.
As noted, well-designed and well-conducted trials also may fail in defining clinically relevant outcomes (such as trials with a few weeks' follow-up in life-long diseases) and generally have problems with external validity (ie, the results are true for the small and highly selected group of patients on which they were conducted but may not be applicable to most of the patients with that disease).
Finally, bringing research findings into clinical practice requires constant and rigorous updating of the physicians who tend to remain adherent to traditional interventions (eg, rifampin for acne) even if better options have become available, or, on the contrary, may be induced by commercial pressure to apply new treatment regimens still lacking substantial evidence on their validity.
AUTHOR INFORMATION
A cooperative effort of the Clinical Epidemiology Unit of the Istituto Dermopatico dell' Immacolata–Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology
Accepted for publication March 28, 2001.
This work was partially funded by the "Progetto Ricerca Finalizzata 1998" of the Italian Ministry of Health, Rome, Italy.
Presented in part at the 58th Annual Meeting of the American Academy of Dermatology, San Francisco, Calif, March 10-15, 2000.
The authors thank the following dermatologists for their help in the preparation of medical records: G. Cianchini, MD, S. Pallotta, MD, L. Colonna, MD, G. Di Lella, MD, M. Giani, MD, E. Scala, MD, L. Pirrotta, MD, E. C. Guerra, MD, G. Monticone, MD, and C. Barbieri, MD; and V. Salvatori who collected the papers to be reviewed.
Corresponding author: Damiano Abeni, Clinical Epidemiology Unit, Istituto Dermopatico dell'Immacolata, Via Monti di Creta 104, 00167 Rome, Italy (e-mail: d.abeni{at}idi.it).
From the Istituto Dermopatico dell'Immacolata, Rome, Italy.
REFERENCES
| |
1. Bigby M. Snake oil for the 21st century. Arch Dermatol. 1998;134:1512-1514.
FREE FULL TEXT
2. Jemec GB, Thorsteinsdottir H, Wulf HC. Evidence-based dermatologic out-patient treatment. Int J Dermatol. 1998;37:850-854.
FULL TEXT
|
ISI
| PUBMED
3. Ellis J, Mulligan I, Sackett DL, et al. Inpatient general medicine is evidence based. Lancet. 1995;346:407-410.
FULL TEXT
|
ISI
| PUBMED
4. Haynes RB, Wilczynski N, McKibbon KA, et al. Developing optimal search strategies for detecting clinically sound studies in MEDLINE. J Am Med Inform Assoc. 1994;1:447-458.
FREE FULL TEXT
5. Bigby M. Evidence-based medicine in a nutshell. Arch Dermatol. 1998;134:1609-1618.
FREE FULL TEXT
6. Sackett DL. Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest. 1989;95(suppl 2):2S-4S.
7. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52:377-384.
ABSTRACT
8. Goh CL, Gan SL. Efficacies of a barrier cream and an afterwork emollient cream against cutting fluid dermatitis in metalworkers: a prospective study. Contact Dermatitis. 1994;31:176-180.
FULL TEXT
|
ISI
| PUBMED
9. Halkier-Sorensen L, Thestrup-Pedersen K. The efficacy of a moisturizer (Locobase) among cleaners and kitchen assistants during everyday exposure to water and detergents. Contact Dermatitis. 1993;29:266-271.
FULL TEXT
|
ISI
| PUBMED
10. Medansky RS, Handler RM. Analysis of a new corticosteroid aerosol in treatment of contact dermatitis. Cutis. 1978;21:108-110.
ISI
| PUBMED
11. Gupta AK, Shear NH, Lester RS, Baxter ML, Sauder DN. Betamethasone dipropionate polyacrylic film-forming lotion in the treatment of hand dermatitis. Int J Dermatol. 1993;32:828-829.
ISI
| PUBMED
12. Lucky AW, Leach AD, Laskarzewski P, Wenck H. Use of an emollient as a steroid-sparing agent in the treatment of mild to moderate atopic dermatitis in children. Pediatr Dermatol. 1997;14:321-324.
ISI
| PUBMED
13. Klein PA, Clark RAF. An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol. 1999;135:1522-1525.
FREE FULL TEXT
14. Charman C. Atopic eczema. BMJ. 1999;318:1600-1604.
FREE FULL TEXT
15. Ortonne JP, Lacour JP, Vitetta A, Le Fichoux Y. Comparative study of ketoconazole 2% foaming gel and betamethasone dipropionate 0.05% lotion in the treatment of seborrhoeic dermatitis in adults. Dermatology. 1992;184:275-280.
ISI
| PUBMED
16. Koo J, Cuffie CA, Tanner DJ, et al. Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study. Clin Ther. 1998;20:283-291.
FULL TEXT
|
ISI
| PUBMED
17. Katz HI, Prawer SE, Medansky RS, et al. Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Dermatologica. 1991;183:269-274.
ISI
| PUBMED
18. Naldi L. Psoriasis. Clin Evidence. 1999;1:167-177.
19. Kragballe K, Barnes L, Hamberg KJ, et al. Calcipotriol cream with or without concurrent topical corticosteroid in psoriasis: tolerability and efficacy. Br J Dermatol. 1998;139:649-654.
FULL TEXT
|
ISI
| PUBMED
20. Finn AFJ, Kaplan AP, Fretwell R, Qu R, Long J. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. 1999;104:1071-1078.
FULL TEXT
|
ISI
| PUBMED
21. Dubertret L, Murrieta AM, Tonet J. Efficacy and safety of mizolastine 10 mg in a placebo-controlled comparison with loratadine in chronic idiopathic urticaria: results of the MILOR Study. J Eur Acad Dermatol Venereol. 1999;12:16-24.
ISI
| PUBMED
22. Carlborg L. Cyproterone acetate versus levonorgestrel combined with ethinyl estradiol in the treatment of acne: results of a multicenter study. Acta Obstet Gynecol Scand Suppl. 1986;134:29-32.
PUBMED
23. Redmond GP, Olson WH, Lippman JS, Kafrissen ME, Jones TM, Jorizzo JL. Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial. Obstet Gynecol. 1997;89:615-622.
ABSTRACT
24. Plewig G, Petrozzi JW, Berendes U. Double-blind study of doxycycline in acne vulgaris. Arch Dermatol. 1970;101:435-438.
FULL TEXT
|
ISI
| PUBMED
25. Dahl MV, Katz HI, Krueger GG, et al. Topical metronidazole maintains remissions of rosacea. Arch Dermatol. 1998;134:679-683.
FREE FULL TEXT
26. Breneman DL, Stewart D, Hevia O, Hino PD, Drake LA. A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. Cutis. 1998;61:44-47.
ISI
| PUBMED
27. Maurel A, Betrancourt JC, Van Frenkel R, Thuillez C. Action du Buflomedil sur la microcirculation cutanée étudiée par un test de provocation au froid: étude multicentrique, double aveugle versus placebo. J Mal Vasc. 1995;20:127-133.
ISI
| PUBMED
28. Rudofsky G. Intravenous prostaglandin E1 in the treatment of venous ulcers—a double-blind, placebo-controlled trial. Vasa Suppl. 1989;28:39-43.
PUBMED
29. Hebjorn M, Olsen O, Haakansson T, Andersen B. A randomized trial of fistulotomy in perianal abscess. Scand J Gastroenterol. 1987;22:174-176.
PUBMED
30. Caceres-Rios H, Rueda M, Ballona R, Bustamante B. Comparison of terbinafine and griseofulvin in the treatment of tinea capitis. J Am Acad Dermatol. 2000;42:80-84.
FULL TEXT
|
ISI
| PUBMED
31. Bunney MH, Nolan MW, Williams DA. An assessment of methods of treating viral warts by comparative treatment trials based on a standard design. Br J Dermatol. 1976;94:667-679.
FULL TEXT
|
ISI
| PUBMED
32. Volmink J, Lancaster T, Gray S, Silagy C. Treatments for postherpetic neuralgia—a systematic review of randomized controlled trials. Fam Pract. 1996;13:84-91.
FREE FULL TEXT
33. Njoo MD, Spuls PI, Bos JD, Westerhof W, Bossuyt PMM. Nonsurgical repigmentation therapy in vitiligo: meta-analysis of the literature. Arch Dermatol. 1998;134:1532-1540.
FREE FULL TEXT
34. Stelzer KJ, Griffin TW. A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's sarcoma. Int J Radiat Oncol Biol Phys. 1993;27:1057-1061.
ISI
| PUBMED
35. Shepherd FA, Beaulieu R, Gelmon K, et al. Prospective randomized trial of two dose levels of interferon alfa with zidovudine for the treatment of Kaposi's sarcoma associated with human immunodeficiency virus infection: a Canadian HIV Clinical Trials Network study. J Clin Oncol. 1998;16:1736-1742.
ABSTRACT
36. Belisle S, Love EJ. Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study. Fertil Steril. 1986;46:1015-1020.
ISI
| PUBMED
37. Nanni CA, Alster TS. Optimizing treatment parameters for hair removal using a topical carbon-based solution and 1064-nm Q-switched neodymium:YAG laser energy. Arch Dermatol. 1997;133:1546-1549.
ABSTRACT
38. Booth A. What proportion of healthcare is evidence based? Resource Guide. Available at: http://www.shef.ac.uk/~scharr/ir/percent.html. Accessed February 14, 2001.
39. Williams H, Adetugbo K, Po AL, Naldi L, Diepgen T, Murrell D. The Cochrane Skin Group: preparing, maintaining, and disseminating systematic reviews of clinical interventions in dermatology. Arch Dermatol. 1998;134:1620-1626.
FREE FULL TEXT
40. Williams HC. Do topical steroids reduce relapses in adults with atopic dermatitis? Arch Dermatol. 1999;135:1530-1531.
FREE FULL TEXT
41. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for cutaneous lupus erythematosus. J Am Acad Dermatol. 1996;34:830-836.
FULL TEXT
|
ISI
| PUBMED
42. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for cutaneous adverse drug reactions. J Am Acad Dermatol. 1996;35:458-461.
FULL TEXT
|
ISI
| PUBMED
SECTION EDITORS:
Damiano Abeni, MD, MPH, Istituto Dermopatico dell'Immacolata, Rome, Italy
Michael Bigby, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
Paolo Pasquini, MD, MPH, Istituto Dermopatico dell'Immacolata, Rome, Italy
Moyses Szklo, MD, MPH, DrPH, Johns Hopkins University, Baltimore, Md
Hywel Williams, PhD, FRCP, Queens Medical Centre, Nottingham, England
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Evidence-Based Medicine: Do We Use Guidelines or Mindlines?
Tsai
Arch Dermatol 2005;141:773-774.
FULL TEXT
|
