Cost-effectiveness of methotrexate and Goeckerman therapy: a flawed analysis.
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Cost-Benefit Analysis↗
Biomedical subjects
J Koo
Publications and source records attributed to J Koo.
Systemic sequential therapy of psoriasis: a new paradigm for improved therapeutic results.
Sequential therapy is a treatment strategy involving the use of specific therapeutic agents in a deliberate sequence to optimize the therapeutic outcome. The rationale for this strategy in psoriasis is that it is a chronic disease requiring long-term maintenance therapy as well as quick relief of symptoms and that some therapies available for psoriasis are better suited for rapid clearance while others are more appropriate for long-term maintenance. Sequential therapy involves 3 main steps: (1) the clearing, or "quick-fix" phase; (2) the transitional phase; and (3) the maintenance phase. In the example of sequential systemic therapy described in this article, an acute exacerbation of psoriasis is brought under control promptly with the use of cyclosporine at maximum dermatologic dose (5 mg/kg daily). After 1 month, the transitional phase is initiated with the gradual introduction of acitretin as a maintenance agent. Once the maximum tolerated dose of acitretin has been established, cyclosporine is gradually tapered and acitretin is continued for long-term maintenance with phototherapy (UVB or PUVA) added for improved control if needed. The author proposes sequential therapy with cyclosporine and acitretin as a viable option for patients with psoriasis who require systemic therapy and desire an alternative to methotrexate.
Acitretin↗
Duration of remission of psoriasis therapies.
The armamentarium of therapies for psoriasis continues to expand with drugs such as tazarotene, calcipotriene, and acitretin approved in recent years. New forms of old treatments such as cyclosporine and anthralin have also been introduced. Frequently, inadequate attention is devoted to duration of remission. The purpose of this article is to examine the duration of remission reported with many therapies currently used for psoriasis. Studies examining duration of remission are included. Among our conclusions were the following: the definitions of remission/relapse used in various studies differ, duration of remission is influenced by the natural history of each patient's disease, among topical monotherapies anthralin and tazarotene appear to induce longer remissions than calcipotriene and corticosteroids, among systemic agents longer remissions occur with etretinate than cyclosporine or methotrexate but compared with the remission rate of phototherapeutic modalities, especially Goeckerman and PUVA therapy, the remission rates are much less.
Humans↗
Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.
PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.
Age of Onset↗
Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey.
We analyzed data from the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study to test the hypothesis that vitamin D from sunlight exposure, diet, and supplements reduces the risk of breast cancer. We identified 190 women with incident breast cancer from a cohort of 5009 white women who completed the dermatological examination and 24-h dietary recall conducted from 1971-1974 and who were followed up to 1992. Using Cox proportional hazards regression, we estimated relative risks (RRs) for breast cancer and 95% confidence intervals, adjusting for age, education, age at menarche, age at menopause, body mass index, alcohol consumption, and physical activity. Several measures of sunlight exposure and dietary vitamin D intake were associated with reduced risk of breast cancer, with RRs ranging from 0.67-0.85. The associations with vitamin D exposures, however, varied by region of residence. The risk reductions were highest for women who lived in United States regions of high solar radiation, with RRs ranging from 0.35-0.75. No reductions in risk were found for women who lived in regions of low solar radiation. Although limited by the relatively small size of the case population, the protective effects of vitamin D observed in this prospective study are consistent for several independent measures of vitamin D. These data support the hypothesis that sunlight and dietary vitamin D reduce the risk of breast cancer.
Adult↗
Endoscopic perforation of the rectum presenting initially as a change in voice.
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Aged↗
Random population-wide genetic damage induced in replicating cells treated with methotrexate.
Low lethality treatment of the NIH 3T3 mouse cell line with methotrexate (MTX) during exponential multiplication results in heterogeneous, heritable reduction in growth rate of most if not all the replicatively surviving cells. The effective concentrations of MTX are 10 to 100 times higher in molecular, cellular and developmental biology medium 402 (MCDB 402) than in Dulbecco's modification of Eagle's medium (DMEM) medium because of the folate-sparing presence of adenine, thymidine and, particularly, of folinic acid in MCDB 402 medium. The reduced growth rates are detectable during early passages of surviving populations before the faster growing cells dominate them. The heritable effect is most clearly demonstrated by sequestered cloning of many individual cells immediately after drug treatment, and repeatedly measuring the growth rates of the clones in serial passages. After 7-10 passages of the clones, there is an increase in growth rate of some of the slow growing clones presumably due to the generation and selection of faster growing cells. Evidence from mutagenic studies at a single genetic locus in other cell lines suggests that heritable reductions in growth rate arise from chromosome aberrations although point mutations may also contribute to the effect. Clastogenic changes can be induced by a wide variety of mutagens and carcinogens, many of which are used in chemotherapy of cancer and other chronic diseases. The population-wide, heritable damage to cells may be the source of, or may contribute to, late-occurring side effects of treatment in cancer and other chronic diseases.
3T3 Cells↗
Traditional Chinese medicine for the treatment of dermatologic disorders.
Traditional Chinese medicine (TCM) is an alternative method of therapy that can be administered in oral, topical, or injectable forms. It emphasizes the importance of using many herbs that are combined in different formulations for each individual patient. Among some segments of the patient population, it has become increasingly popular as a mode for treating dermatologic diseases. As a result, it is now worthwhile for dermatologists throughout the West to gain some familiarity with this method. Yet, dermatologists are largely unfamiliar with TCM and may possess some misconceptions. We attempt to give a general overview of TCM through the discussion of different clinical studies involving various TCMs. Some proposed mechanisms of action of TCM are also presented. A discussion of adverse effects, including hepatotoxic effects and the need for close monitoring is discussed. A warning regarding the possible contamination of TCMs is also included. Since it is not possible to discuss the application of TCM for every skin disorder, psoriasis and atopic dermatitis are used as the prototype in illustrating the use of TCM. In the future, perhaps a better understanding of TCM will be gained through more systematic analysis and controlled studies with a placebo arm. It is our hope that this article will provide an overview of the efficacy, mechanism of action, as well as adverse effects of TCM.
Drugs, Chinese Herbal↗
Cyclosporine consensus conference: with emphasis on the treatment of psoriasis.
Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine's use in rotational therapy.
Contraindications↗
A randomized, double-blind study comparing the efficacy, safety and optimal dose of two formulations of cyclosporin, Neoral and Sandimmun, in patients with severe psoriasis. OLP302 Study Group.
This study compared the efficacy, safety and optimal dose of two formulations of cyclosporin, Sandimmun and Neoral, in patients with severe, chronic plaque-type psoriasis. Patients were randomized on a 1:1 basis to 24 weeks of treatment with Neoral (n = 152) or Sandimmun (n = 157). The starting dose of each formulation was 2.5 mg/kg per day. Dose increases to maintain efficacy were allowed after 4 weeks. In patients who achieved remission, the dose was down-titrated at 4-week intervals from week 16. The maximum permitted dose for each formulation was 5.0 mg/kg per day. Neoral produced a more rapid response than Sandimmun: remission rates were higher for Neoral during the first 8 weeks of treatment. The number of dose reductions for safety was similar in both treatment groups, but there were more dose increases to maintain efficacy in the Sandimmun group (198) than the Neoral group (146). The number of patients with dose reductions after week 16 was higher for Neoral (n = 83) than for Sandimmun (n = 73). The frequency and nature of adverse events were similar for both treatment groups. The mean dose required to control the disease was approximately 10% lower with Neoral and fewer dose changes were needed. The increased bioavailability and reduced pharmacokinetic variability of cyclosporin provided by the Neoral formulation may facilitate short-course, intermittent therapy.
Adolescent↗
Guideline for the management of breast lumps.
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Family Practice↗
Cyclosporine as maintenance therapy in patients with severe psoriasis.
BACKGROUND: Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. OBJECTIVE: Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. METHODS: After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. RESULTS: During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. CONCLUSION: Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.
Administration, Oral↗
Neoral in psoriasis therapy: toward a new perspective.
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Cyclosporine↗
Advances in psoriasis therapy.
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Absorption↗
Enteric duplication in the adult, derived from the foregut, midgut and hindgut: presentation, patterns and literature review.
Duplication of the alimentary tract may affect patients of all ages. Although they are relatively rare, the importance of these congenital lesions lies in the fact that they readily mimic other surgical disease processes and may result in significant morbidity if left untreated. Prompt recognition and treatment using combined radiologic and surgical management are generally associated with an excellent outcome. Three patients who presented with intestinal duplication arising from each of the major embryologic origins are reported. Their clinical histories reveal the spectrum of presentation associated with these lesions and provide a framework for a discussion of current management strategies.
Adult↗
Calcipotriol/calcipotriene (Dovonex/Daivonex) in combination with phototherapy: a review.
BACKGROUND: Calcipotriol/calcipotriene (Dovonex/Daivonex) ointment plus phototherapy has been used in the treatment of psoriasis. OBJECTIVE: We will attempt to clarify two issues: First, is there any benefit to combining the above treatment modalities? Second, is there any increased risk associated with the use of the combination? METHODS: A complete review of the literature revealed four studies dealing with the combination of calcipotriol with UVB phototherapy and three studies dealing with the combination of calcipotriol with PUVA phototherapy. RESULTS: These studies showed an advantage to the use of the combination compared with the use of either treatment alone. CONCLUSION: Topical calcipotriol enhances the effect of UVB and PUVA phototherapy.
Calcitriol↗
Need for quality-control testing of extemporaneously prepared oral solids.
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Aspirin↗
Comparison of once-daily versus pharmacokinetic dosing of aminoglycosides in elderly patients.
PURPOSE: Once-daily dosing has been suggested as an alternative method of dosing aminoglycosides that would reduce their toxicity while maintaining efficacy. There have been no studies published to date comparing once-daily dosing and pharmacokinetic dosing of aminoglycosides. We conducted a randomized controlled trial comparing the safety and effectiveness of 4 mg/kg IV once-daily dosing of gentamicin or tobramycin with a pharmacokinetic dosing method using an initial dose of 2 mg/kg IV every 12 hours. PATIENTS AND METHODS: Ninety-six patients were randomly assigned to either the once-daily dosing group (4 mg/kg) or the pharmacokinetic dosing group (initial dose of 2 mg/kg every 12 hours). In the once-daily dosing group, the dosing interval was extended by 12 to 24 hours to maintain a serum trough concentration < 1.5 mg/L regardless of the peak concentration. Dosing in the other group was adjusted based on the individual pharmacokinetic data to achieve a serum peak concentration of 6 to 10 mg/L and a trough concentration below 1.5 mg/L. The patients studied were predominantly elderly males (mean age 69 years). All patients were assessed for treatment efficacy and nephrotoxicity. RESULTS: There was no significant difference between the two groups with regard to clinical and bacteriologic efficacy. Incidence of nephrotoxicity was 24% in the once-daily group and 14% in the pharmacokinetic dosing group but the difference was not statistically significant (P = 0.13). Unlike previous studies, we found a correlation between high serum peak concentration and incidence of nephrotoxicity in the once-daily dosing group. Nephrotoxicity developed in six out of 10 patients (60%) with an initial serum peak concentration greater than 12.0 mg/L compared to two out of 24 patients (8.3%) with an initial peak concentration less than 12.0 mg/L (P < 0.001) in the once-daily group. Serum peak concentrations in the pharmacokinetic dosing group were not correlated with nephrotoxicity. CONCLUSIONS: Once-daily dosing and pharmacokinetic dosing of aminoglycosides appear to have equal efficacy and toxicity. However, in the elderly population, high serum peak concentrations that occur with once-daily aminoglycoside dosing may increase the risk of nephrotoxicity.
Aged↗