Therapeutic decision making of physicians

In this review the therapeutic decision-making process of physicians is described. This process is divided into two steps: the generation of a limited set of possible options (the evoked set) and the selection from this evoked set of a treatment for a specific patient. Factors that are important in both steps are reviewed. Behavioural and decision-making theories in general and decision-making analysis of physicians in particular are discussed to identify possible shortcomings in their decision-making process. Based on this information a model of the drug choice process is presented. With reference to this model possible ways of influencing drug choices of physicians are discussed.     

Treatment of actinic keratoses with sequential combination of 5-fluorouracil and photodynamic therapy

Actinic keratoses (AKs) are traditionally treated with cryotherapy, curettage, and 5-fluorouracil (5-FU, Efudex, ICN Pharmaceuticals, Inc.), all of which are associated with adverse effects. Although photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) offers a treatment alternative, current protocols require 14 to 18 hours incubation with ALA and patients experience pain during light treatment. Fifteen patients with multiple and diffuse facial AKs applied 5-FU nightly for 5 days and underwent PDT with ALA (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) on the sixth day. ALA was applied to their entire faces and remained in contact with the skin for 30 to 45 minutes under low-intensity visible light. After removing ALA, faces received a single pass of 560- to 1200-nm intense pulsed light (VascuLight or Lumenis One, Lumenis). At 1 month and at 1 year post-treatment, 90% of treated AKs had resolved in all but one patient. Erythema resolved 7 to 10 days after treatment. Patients with multiple diffuse AKs may benefit from the application of 5-FU for 5 days followed by ALA-PDT with intense pulsed light activation.     

Pharmacoeconomic analysis of the treatment of multiple actinic keratoses

Actinic keratosis (AK) is common and lesions may progress to squamous cell carcinoma. The choice of therapy depends mainly on 2 factors: the efficacy of therapeutic options and the number of lesions present. Cryotherapy alone is suitable for treating a few lesions, whereas topical medications, photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or either in combination with cryotherapy are appropriate for treating multiple (>15) lesions. When combinations are necessary, the total cost to treat multiple AKs to 100% clearance becomes important. This report provides a simple pharmacoeconomic analysis of 4 FDA-cleared therapies (imiquimod, diclofenac, 5-fluorouacil [5-FU], and ALA PDT) for AK given in combination with cryotherapy. This analysis assumes standard costs of procedures and office visits (based on April 2007 reimbursement data) and 2 treatment courses (medications: imiquimod, diclofenac, 5-FU) or sessions (ALA PDT) of each modality followed by cryotherapy to 100% clearance. The total cost of each combination is $725.17 for ALA PDT, $845.07 for diclofenac, $942.13 for 5-FU, and $1,473.39 for imiquimod. When phase III trial efficacies of the 4 modalities are considered, the actual cost of using imiquimod or diclofenac increases because additional treatments may be required. Among these 4 FDA-cleared therapies for multiple AK lesions, ALA PDT is the least expensive treatment and imiquimod is the most expensive treatment under the stated assumptions.     

Pulse therapy with 5-FU in eradicating actinic keratoses with less than recommended dosage

Pulse therapy has been used for many years, but rarely in a clinical setting. This article describes a clinical study designed to determine the efficacy of pulse therapy with 5-FU for patients with multiple actinic keratoses. The results indicated that pulse therapy was indeed effective in eradicating most of the actinic keratoses while causing less discomfort or disfigurement than the FDA recommended dose, especially for patients with less severe and milder forms of actinic keratoses.     

Cutaneous human papillomaviruses as recurrence factor in actinic keratoses

Actinic keratoses (AK) are common, premalignant lesions cause mainly by UV DNA damage. Progression into squamous cell carcinoma may be influenced by other several factors such as chronic chemical exposure or viral infection. A carcinogenic role of Human Papillomaviruses (HPV) in early steps of skin tumour development was recently hypothesized; moreover the presence of HPV DNA seems to be higher in cancer precursor lesions. The aim of this work is to identify the presence of HPV DNA in biopsies from Actinic Keratoses (AK) and from normal skin samples collected from dermatological healthy subjects in Italy, in order to evaluate the severity and the clinical evolution of the HPV positive lesions. The DNA test revealed 37% HPV positivity in AK patients versus 0% in the control group; many different genotypes and variants were identified by direct sequencing of PCR product. The HPV positive AK were usually clinically indistinguishable from the HPV negative. All AK lesions were removed by laser treatment, but AK lesions recurred in all HPV positive patients after a period of 45-60 days whereas the same disappeared in the HPV negative ones. These data permit to hypothesize that the presence of HPV DNA could be an aggravating factor for AK lesion severity and recurrence.     

Diclofenac sodium 3% gel in the treatment of actinic keratoses postcryosurgery

BACKGROUND: Actinic keratoses are increasingly common skin lesions that are evaluated and treated by dermatologists on a daily basis. It is estimated that more than 90% of actinic keratoses in the US are treated by destructive therapies, such as cryosurgery. The purpose of this study was to evaluate the efficacy of sequential therapy of cryosurgery followed by diclofenac sodium 3% gel. METHODS: This prospective, double-arm, multicenter, open-label, phase 4 study was performed at 82 community dermatology centers in the US. A total of 714 subjects who had a clinical diagnosis of actinic keratosis with between 5 and 15 lesions contained in a target area such as the forehead, scalp, and hands were enrolled in the study. These subjects were randomized into 2 arms of the study: cryosurgery alone and cryosurgery followed by diclofenac sodium 3% gel for a period of 90 days. Lesion counts were assessed at baseline, and 45, 75, 105, and 135 days after cryosurgery. RESULTS: Of the 521 patients enrolled in the study who successfully completed all of the visits concluding on day 135, 277 were in the cryosurgery alone arm and 244 were in the cryosurgery followed by diclofenac sodium 3% gel arm. At the conclusion of the study, 46% of the subjects in the cryosurgery followed by the use of diclofenac sodium 3% gel arm achieved 100% cumulative (target plus new lesions) lesion clearance compared to 21% in the cryosurgery alone arm (P < .0001). One hundred percent target lesion clearance was achieved in 64% of the subjects in the active arm compared to 32% in the cryosurgery alone arm (P < .0001). CONCLUSIONS: With the increased prevalence of actinic keratoses, it is important to consider and evaluate emerging therapeutic options. The sequential treatment with cryosurgery followed by diclofenac sodium 3% gel for 90 days is well tolerated and can provide a therapeutic modality that may provide patients with actinic keratoses a more successful outcome than monotherapy with cryosurgery by effectively treating clinical and subclinical lesions.     

Short incubation PDT versus 5-FU in treating actinic keratoses

The efficacy of photodynamic therapy (PDT) using broad area treatment with 5-aminolevulinic acid (ALA) has not been compared to topical 5-fluorouracil (5-FU) in the treatment of actinic keratoses (AK). The purpose of this study was to compare the efficacy and tolerability of PDT using short incubation time, broad area treatment with ALA plus activation with either blue light or laser light to topical 5-FU in the treatment of AK of the face and scalp. Thirty-six subjects with AK of either the face or scalp were randomized to receive either application of ALA for 1 hour followed by activation with blue light or pulsed dye laser or topical 5-FU. Efficacy was evaluated by grading AK lesions and photoaging signs. Tolerability was assessed by scoring crusting/erosions, erythema and stinging/burning. Treatment with PDT using ALA plus blue light was as effective as topical 5-FU in clearing AK. PDT using ALA plus laser light was the least effective treatment. All treatments made improvements in the signs of photoaging. Both PDT treatments were better tolerated than 5-FU. In conclusion, broad area PDT treatment with ALA plus activation with blue light appears to be as effective as 5-FU in the treatment of AK. ALA plus laser light is somewhat less effective than the above therapies. Efficacy could likely be improved with further study of laser parameters and incubation times.     

Imiquimod 3.75% cream (Zyclara) for the treatment of actinic keratoses

INTRODUCTION: actinic keratosis is a premalignant disease with a high incidence and is a strong predictor for the development of squamous cell carcinoma. Various treatment options have been established over recent years, including topical treatment with imiquimod, 5-fluorouracil, diclofenac or photodynamic therapy, cryotherapy and surgical procedures. AREAS COVERED: this review covers basic and clinical experiences with imiquimod 3.75% for topical treatment of actinic keratosis of the face and balding scalp and its comparators with special focus on imiquimod 5%. It also covers pharmacology of imiquimod 3.5% and its contribution to the current treatment options of actinic keratoses. EXPERT OPINION: imiquimod 3.75% is an interesting, safe and well-tolerated treatment option for actinic keratoses of the face or balding scalp especially in respect of compliance, as it is indicated for daily use for a shorter time period (2 times, 2-week cycles) and approved for use on larger areas compared with imiquimod 5%. Data from current trials indicate lower efficacy compared with imiquimod 5% cream when applied three times a week for 16 weeks or for two 4-week cycles with a 4-week no-treatment interval, but indicate similar efficacy when compared with a twice-weekly schedule for 16 weeks. An additive effect was observed when combining cryosurgery followed by imiquimod 3.75%.     

Impact of pharmacist consultation versus a decision aid on decision making regarding hormone replacement therapy

Objective To compare the effects of pharmacist consultation versus a decision aid on women's decisional conflict regarding use of hormone replacement therapy (HRT) and subsequent satisfaction with the decision‐making process. Setting A family medicine clinic in Canada. Method The study was a prospective, randomised comparative trial. Peri‐ and post‐menopausal female patients aged 48 to 52 years were invited to participate. Volunteers (n=128) received either a private consultation with a pharmacist or a take‐home decision aid. Data collection was undertaken prior to the intervention and again following an appointment with a physician to discuss HRT. Outcome measures included: perception of being informed about HRT, decisional conflict, satisfaction with the education and the decision made regarding HRT, and adherence to HRT if prescribed. Telephone follow‐up occurred three and 12 months after the physician appointment. Key findings After discussing HRT with their physicians, 35 of 91 women (38.5%) chose HRT, 15 (16.5%) declined it and 41 (45.1%) opted to delay their decision. Both interventions significantly increased women's perception of being informed about this form of therapy and decreased decisional conflict. Satisfaction with the education and with the HRT decision was high. More postmenopausal women in the pharmacist group reached a yes/no decision than in the decision aid group. Of those initiating HRT during the study (n =18), 16.7% had discontinued it at 12 months. Conclusion Consultation with a pharmacist and use of a decision aid are both effective methods for decreasing decisional conflict in peri‐ and post‐menopausal women considering HRT.     

The treatment of actinic keratoses with a combination of 5-fluorouracil and imiquimod creams

BACKGROUND: 5-fluorouracil (5-FU) and imiquimod creams are accepted topical therapies for actinic keratosis (AK). Both are associated with a prolonged course of treatment with an inflammatory response that may preclude the treatment process. OBJECTIVES: To describe the treatment regimen and the extent of side effects in the use of the combined application of 5-FU and imiquimod creams in patients presenting with AKs and to demonstrate the convenience and ease of the methodology of this regimen. METHODS: The patients applied 5-FU and imiquimod creams to their lesions daily for one week each month over the course of 3 months. The patients were seen after the completion of each one-week course to evaluate their progress and side effects. RESULTS: There were 64 patients in the study, 48 of whom completed the study and demonstrated a clearing of their AKs by the end of the third course of treatment. All of the patients developed an inflammatory response at the sites of their AKs as well as at subclinical sites with no apparent AKs. Nearly all of these inflammatory reactions were confined to localized sites without involvement of the surrounding skin. CONCLUSIONS: Therapy with the combined application of 5-FU and imiquimod creams is a relatively rapid and convenient form of therapy as compared to the separate use of each medication.     

Radiolabelled peptides and monoclonal antibodies for therapy decision making in inflammatory diseases

Radiolabelled peptides and monoclonal antibodies are an emerging class of radiopharmaceuticals for imaging inflammation with clinical implications for several chronic inflammatory disorders for diagnosis, therapy decision making and follow up. In the last decades, a number of novel monoclonal antibodies and peptides have been introduced for the treatment of different inflammatory disorders and also labelled with a variety of radionuclides depending upon the specific applications, diagnostic or therapeutic, by using direct or indirect methods. These radiopharmaceuticals bind to their targets with high affinity and specificity and therefore have an excellent diagnostic potential for the imaging of patients with chronic inflammatory diseases. In this review article we describe the characteristics of peptides, cytokines and monoclonal antibodies with a particular emphasis on their role in therapy decision making and follow up in different inflammatory diseases.     

Toxicology in business decision making

More than ever before, toxicology and its sister health sciences and technologies are needed as members of the business team to ensure sound business decision making for both new and existing businesses. Yet the marriage of toxicology and business is an uneasy one since toxicology is both the bringer of bad news and a major resource for the solution of problems. Both business and toxicology have much to learn about each other to make the marriage work and to make full use of toxicology's scientific advice in reaching sound decisions on the safe production, distribution, and handling of a company's products. Toxicology also has a central and difficult role in helping business navigate the turbulent waters of regulation or of potential or actual litigation. From his own experience in organizing a corporate health, safety, and environmental department, the author describes the concepts that must be understood and the marshaling of resources needed to ensure that toxicology can play its full role in business decision making.     

Laser-mediated photodynamic therapy of actinic cheilitis

Actinic cheilitis (AC) is a common precancerous condition for which a safe, effective, rapid, and cosmetically favorable treatment is needed. The objective of this study was to assess the safety and efficacy of the long-pulsed pulsed dye laser (LP PDL) (595 nm) with photodynamic therapy (PDT) for the treatment of AC. This study was designed to be a prospective, proof-of concept pilot study to assess safety and efficacy of LP PDL in conjunction with topical 20% 5-aminolevulinic acid solution PDT for the treatment of AC. Control patients received LP PDL alone. The setting was an outpatient clinical research center. A volunteer sample of 21 patients with biopsy-proven AC was enrolled (age range, 42-86 years; skin types I-III). All patients were refractory to prior therapies. Patients with a history of herpes labialis were pre-treated with famcyclovir. Nineteen patients received one-to-three treatments of topical 20% 5-aminolevulinic acid for 2-3 hours, followed by LP PDL (595 nm) at monthly intervals. Two control patients received one treatment with LP PDL alone. Patients in the ALA-LP PDL group were followed at 1, 2, 3, 6, 9, and 12 months. Clearance of AC was assessed by clinical evaluation. Control patients were followed to the one month interval. We observed none-to-mild pain; slight-to-moderate erythema; no crusting, purpura, or scarring; treatment time of less than one minute; and complete resolution of post-operative erythema by day three. Complete clearance was achieved in 13/19 (68%) of patients following a mean of 1.8 treatments (7/13 (37%) after one, 2/13 (11%) after two, and 1/13 (21%) after three treatments). Patients were followed for a mean of 4.1 (range 1-12) months. Among the remaining cases, partial clearing was achieved in two patients, recurrence during the follow-up interval was observed in one patient, and failure to follow-up occurred in three patients. Post-operative impetiginization occurred in three patients with erosive AC, which resolved with dicloxacillin therapy. Among the control patients, no clearing was observed. Treatment of AC using LP PDL (595 nm) at nonpurpuric parameters following topical application of 5-aminolevulinic acid at short incubation times is safe and effective. It may offer the advantages of rapid incubation, treatment, and recovery times, minimal discomfort, excellent cosmetic outcome, and good efficacy rates. Patients with erosive AC should receive antibacterial prophylaxis. Multiple treatments may be required for complete clearing.