Patient engagement in clinical guidelines development: input from > 1000 members of the Canadian Osteoporosis Patient Network.

Patient engagement in clinical guidelines development is essential. The results of a self-administered online survey identified themes important to people living with osteoporosis and will inform the development of Osteoporosis Canada clinical guidelines recommendations. INTRODUCTION: Patient engagement is essential in the development of high-quality and relevant guidelines for osteoporosis management. Osteoporosis Canada (OC) is updating its national clinical practice guidelines in collaboration with people living with osteoporosis in the process. METHODS: Using electronic mail, we contacted 6937 members of the Canadian Osteoporosis Patient Network (COPN) to provide input on the selection of relevant content, outcomes, and research questions via a self-administered online survey. Close-ended questions were analyzed using descriptive statistics, and conventional content analysis was conducted for open-ended questions. RESULTS: A total of 1108 individuals completed the survey (97% women, 86% stated they lived with osteoporosis). Most participants considered it critical to have recommendations on physical activity and exercise (74%), fall prevention (69%), nutrition (68%), and initial bone mineral density testing (67%). In addition to preventing fractures, over 75% of respondents stated that consideration of preserving quality of life and ability to perform daily activities, preventing admission to long-term care and fracture-related death, and avoiding serious harms from medications were essential outcomes to consider in evaluating the evidence. In terms of selection of research questions, seven themes emerged from the content analysis including pharmacotherapy, screening and monitoring, diet and supplements, education, exercise, alternative therapies, and pain management. CONCLUSIONS: Patients emphasized that autonomy, mobility, and quality of life are highly valued outcomes and must be integral to practice guideline development. As expected, guidance on pharmacotherapy, screening and monitoring, and fracture prevention were priorities identified to be included in osteoporosis management guidelines.

Recent Advances in Small Molecule and Biological Therapeutic Approaches in the Treatment of Psoriasis.

New treatments continue to be developed for psoriasis. In this review, we aim to summarize the results of the major published studies on biologic and small molecule drugs for the treatment of psoriasis. We emphasize the safety, efficacy, and tolerability of these treatment options. A review of the MEDLINE database was conducted for each class of medication. Randomized controlled trials were identified for each medication; data on efficacy, safety, and tolerability were reviewed. Biologic and small molecule treatment options are more effective than placebo, although there were few head-to-head trials to assess relative efficacy between biologics and small molecule treatments. These drugs offer favorable safety profiles with only rare serious adverse events reported. Biologic and small molecule drugs offer diverse therapeutic regimens, particularly in patients with recalcitrant disease.

Ultraviolet phototherapy for cutaneous diseases: a concise review.

Phototherapy is the use of non-ionizing radiation, primarily in the ultraviolet spectrum, to treat disease. In dermatology, ultraviolet (UV) phototherapy remains an established, lower cost, and often preferred option for many common skin conditions, despite the introduction of newer potent biologics. This article introduces a principal therapeutic modality in the treatment of psoriasis, atopic dermatitis (eczema), vitiligo, and morphea among other diseases where oral manifestations may be present, providing basic information about the use of UVA, UVB, and PUVA. Practical considerations and side effects of phototherapy are described. Phototherapy is an effective treatment for many illnesses and carries a relatively benign side-effect profile.

Safety, Feasibility, and Biomarker Effects of High-Dose Vitamin D Supplementation Among Women at High Risk for Breast Cancer.

Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer prevention. We examined the safety, feasibility, and biomarker effects of high-dose vitamin D among women at high risk for breast cancer. Forty high-risk women, defined as a 5-year breast cancer risk ≥1.67% per the Gail model, lobular or ductal carcinoma in situ, were assigned to a 1-year intervention of vitamin D3 20,000 IU or 30,000 IU weekly. Participants were monitored for toxicity every 3 months, underwent serial blood draws at baseline, 6 and 12 months, and a digital mammogram at baseline and 12 months. Biomarker endpoints included serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), insulin-like growth factor (IGF-1), IGF binding protein (IGFBP-3), and mammographic density (MD) using Cumulus software. From November 2007 to January 2011, we enrolled 40 women; 37 were evaluable at 6 months and 30 at 12 months. One patient was taken off study for hypercalciuria; otherwise, the intervention was well tolerated. From baseline to 12 months, mean serum 25(OH)D and 1,25(OH)2D rose from 20.0 to 46.9 ng/ml and 69.7 to 98.1 pg/ml, respectively (p<0.01). Serum PTH decreased by 12% at 6 months and IGF-1/IGFBP-3 ratio decreased by 4.3% at 12 months (p<0.05). There was no significant change in MD regardless of menopausal status or dose level. We demonstrated that 1 year of high-dose vitamin D3 was associated with a significant increase in circulating vitamin D levels and favorable effects on IGF signaling, but no significant change in MD.

Associations between first-time expectant women's representations of attachment and their physiological reactivity to infant cry.

Associations among 53 primiparous women's Adult Attachment Interview classifications (secure-autonomous vs. insecure-dismissing) and physiological and self-reported responses to infant crying were explored. Heart rate, skin conductance levels, and respiratory sinus arrhythmia (RSA) were recorded continuously. In response to the cry, secure-autonomous women demonstrated RSA declines, consistent with approach-oriented responses. Insecure-dismissing women displayed RSA and electrodermal increases, consistent with behavioral inhibition. Furthermore, insecure-dismissing women rated the cries as more aversive than secure-autonomous women. Nine months postpartum, secure-autonomous women, who prenatally manifested an approach-oriented response to the unfamiliar cry stimulus, were observed as more sensitive when responding to their own distressed infant, whereas women classified prenatally as insecure-dismissing were observed as less sensitive with their own infants.

Vitamine D analogue-based therapies for psoriasis.

Topical vitamin D3 analogues are a mainstay of treatment in mild to moderate plaque psoriasis. Vitamin D3 analogues exert their effect in psoriasis via binding nuclear vitamin D3 receptors on genes involved in cellular proliferation, differentiation and inflammation. Currently available synthetic vitamin D3 analogues include calcipotriol, maxacalcitol, tacalcitol and calcitriol. These agents are only minimally systemically absorbed and therefore have few systemic side effects. Local irritation is the most frequently noted side effect and can be managed by combining vitamin D3 analogues with other topical or systemic therapies, such as topical corticosteroids or narrow-band UVB phototherapy. The use of a vitamin D agent helps improve the efficacy of topical corticosteroids for psoriasis and helps minimize the potential for adverse events associated with topical corticosteroid treatment. Care should be taken when combining with other topical therapies due to potential inactivation of either agent. Topical vitamin D3 analogues can be a cost-effective addition to a psoriasis treatment regimen, especially when compliance is encouraged by the tolerability of these agents and more costly systemic agents are avoided.

What's new in the management of psoriasis?

Psoriasis treatment is evolving through better understanding of patients with psoriasis and the pathogenesis of the disease itself. Current treatment plans for psoriasis consist of topical medications for mild-moderate or localized psoriasis and more systemic agents for more generalized and moderate-severe psoriasis. New methods of treatment involve not only prescriptions, but patient education and support through organizations such as the National Psoriasis Foundation. The effectiveness of topical treatments have been improved by a better understanding of increasing patients' adherence to medications and new treatments--new vehicles and combination treatments--that enhance patients' adherence behaviors. Phototherapy, with or without an oral retinoid, remains a key component of psoriasis treatment. More convenient and specific monitoring of methotrexate and biologic medications provide these standards of care in psoriasis better and safer patient outcomes. New anti-IL-12/23 therapies offer another more specific option in the management of chronic plaque psoriasis. Dermatologists should recognize and educate patients about the recently recognized association between psoriasis and vascular disease. Psoriasis management can include counseling patients to obtain appropriate screening for cardiovascular risk.

TNF-alpha inhibitors in dermatology.

To date, the US FDA has approved three tumor necrosis factor (TNF)-a inhibitors for use in dermatology. Etanercept (Enbrel, Amgen-Wyeth), a fully human fusion protein of TNF receptor II bound to the Fc component of human IgG1, is approved for use in psoriasis (2004) and psoriatic arthritis (2002). Infliximab (Remicade, Centocor) is a chimeric monoclonal antibody that is approved for use in psoriasis (2006) and psoriatic arthritis (2005), and adalimumab (Humira, Abbott Laboratories), a fully human monoclonal antibody, is approved for use in psoriatic arthritis (2005). While data regarding the efficacy and safety of these therapies is abundant, it proves nearly impossible to objectively compare and contrast agents as there are no head-to-head trials. Clinical experience and post-marketing reporting has allowed dermatologists to identify the relative strengths and limitations of each agent. The well-founded enthusiasm for these agents, because of their excellent initial efficacy and safety profile, is reasonably tempered by concerns about declining efficacy over time, the risk of infection, lymphoma and demyelinating disorders, and cost. The distinct and targeted mechanism of action of the TNF inhibitors allows dermatologists to customize therapy to match the individual needs and characteristics of patients who are candidates for systemic or phototherapy.

Systemic treatment for moderate to severe psoriasis: estimates of failure rates and direct medical costs in a north-eastern US managed care plan.

BACKGROUND: Estimates of US medical costs related to psoriasis treatment are limited and tend to understate the economic burden of moderate to severe psoriasis, which often requires the use of systemic agents, phototherapy or both. OBJECTIVE: To estimate treatment failure rates and direct medical costs associated with the use of systemic agents and phototherapy in US patients with psoriasis. METHODS: Claims records from a large New England-based health insurer were used to obtain patient-level data. Eligible patients with at least one claim listing an ICD-9-CM code for psoriasis (696.0; 696.1) were identified. Patients not receiving systemic treatments (methotrexate, cyclosporine, acitretin) or phototherapy (ultraviolet B with or without tar or petrolatum, psoralen and ultraviolet A [PUVA]) were excluded. Treatment failure was defined as a switch in therapy, augmentation with non-topical therapies, discontinuation following uptitration of dose or discontinuation following hospitalization. Medical costs included those related to pharmacy (over-the-counter medication excluded), institutional services (inpatient and outpatient) and professional services. RESULTS: A total of 2068 patients with moderate to severe psoriasis were included in the analysis. Over a 1-year period, approximately 20% of patients experienced treatment failure. The mean time to failure among patients who switched therapy ranged from 3 to 6 months. Mean annual pharmacy costs in the various treatment groups (categorized according to initial therapy received) ranged from 257 dollars to 1992 dollars per patient. Mean annual costs for institutional and professional services ranged from 156 dollars to 799 dollars and 183 dollars to 481 dollars per patient, respectively. The 99th percentile annual pharmacy and institutional costs exceeded 10,000 dollars and 18,000 dollars, respectively. CONCLUSION: Treatment of moderate to severe psoriasis with traditional systemic agents or phototherapy is associated with a high likelihood of treatment failure and a considerable economic burden.

Class I topical corticosteroid use by psoriasis patients in an academic practice.

BACKGROUND: Psoriasis is a chronic skin disorder that can have a profound impact on the quality of life of patients. The treatment of psoriasis is complicated by the availability of numerous topical agents, systemic agents, and phototherapy. Of the topical preparations available, the ultra-high potency, or Class I steroids, have an important role in treating psoriasis. Their use is most appropriate for the treatment of plaques in regions excluding the face, axilla, groin and genitals. OBJECTIVE: The purpose of this study was to examine the prescribing patterns of Class I topical corticosteroids within a large academic dermatology practice for patients with all types of psoriasis. METHODS: A retrospective chart review of 650 patients with psoriasis from an academic dermatology practice was performed. Class I steroid use was defined as those patients who were observed to be currently using clobetasol propionate, halobetasol propionate, diflorasone, or augmented betamethasone dipropionate. RESULTS: A total of 79% of patients were prescribed topical steroids of any class while 46% of patients were prescribed a Class I steroid. In all, 58% of patients who received topical steroid therapy received a Class I agent; 11% of patients prescribed Class I steroids also received systemic therapy for their psoriasis. Conversely, 35% of patients who received systemic therapy were also receiving Class I topical therapy. DISCUSSION: In our department, Class I topical steroids are commonly used in the treatment of psoriasis. The superpotent topicals are often used as an adjunct to systemic therapy and will likely remain a mainstay of psoriasis therapy.

Electrical stimulation of the dorsal hippocampus caused a long lasting inhibition of ACTH and adrenocortical responses to photic stimuli in freely moving rats.

The effect of a single train of electrical hippocampal stimulation on ACTH and corticosterone (CS) responses to subsequent photic stimulation was studied in freely moving male rats. The hippocampal stimulation inhibited the stress-induced rise [corrected] in serum CS levels up to 150 h when compared to sham stimulated animals. This effect did not exist at 300 h following stimulation. This sustained hippocampal inhibitory effect on the adrenocortical response, which was not reported previously, was partially abolished by section of the dorsal fornix. The present data demonstrate that dorsal hippocampal stimulation has a long lasting inhibitory effect on pituitary adrenocortical secretion following neural stimuli and this is partially mediated by the dorsal fornix.

Clinical management of psoriasis: principles and practice.

A chronic condition that compromises many patients' quality of life, psoriasis is treatable with a range of agents, either alone or in combination. Clinical management strategies using these therapies can be organized as a stepped-care approach. For mild disease, corticosteroids and other topical therapies (step 1) are often appropriate. When lesions are more pronounced or extensive, phototherapy (step 2) is often the treatment of choice, and topical treatments or the step 3 agent acitretin can be added to enhance or accelerate therapeutic responses. Step 3 agents, which also include cyclosporine and methotrexate, may be contemplated when psoriasis is moderate or severe. Acitretin may cause acute adverse effects, including mucocutaneous effects, which can be avoided by reducing dosage. Methotrexate treatment can lead to bone marrow suppression and hepatotoxicity, and cyclosporine can cause nephrotoxicity. The clinical uses of these agents are illustrated in part through case presentations drawn from the authors' practices, and the supportive role of the National Psoriasis Foundation is reviewed.

The efficacy of 308nm laser treatment of psoriasis compared to historical controls.

UVB treatment with a 308nm excimer laser has shown promise in the treatment of localized psoriasis. There is no placebo or comparison treatment controlled trial studying efficacy of the laser, however. The purpose of this report is to compare the results of a study of 308nm laser treatment of psoriasis to published results of other psoriasis treatments. Data on the efficacy of 308nm laser treatment of psoriasis were obtained from a previously published case series, supplemented by reanalysis of the data to estimate the median time to success using Kaplan-Meier methods. These results were compared to those from other studies identified by a Medline search. Treatment success was measured by estimating the percentage of patients who achieve 75% improvement in the severity of psoriasis. Patients treated in the 308nm laser study had similar disease severity as those in topical treatment studies and less severe disease than those treated in studies using standard phototherapy or systemic therapy. A greater percentage of patients achieved 75% improvement with the UVB laser treatments than was reported for other forms of phototherapy or systemic therapy with acitretin or low dose cyclosporine, and did so more rapidly. The UVB laser study patients achieved the 75% improvement endpoint in an average of 46% fewer treatments than was observed in other phototherapy studies. Laser treatment and topical calcipotriene had similar efficacies, and both were more effective than topical tazarotene or topical fluocinonide. As compared to topical therapies, the time to achieve 75% improvement favored the UVB laser. 308nm laser treatments for psoriasis are clearly more effective than placebo and are comparable to or more effective than many other standard treatments for psoriasis.

Use of clotrimazole/betamethasone diproprionate by family physicians.

BACKGROUND AND OBJECTIVES: Clotrimazole/betamethasone diproprionate contains a fluorinated, high-potency topical corticosteroid and is the most frequently prescribed topical agent in the United States. Family physicians are more likely than pediatricians and dermatologists to use this product when faced with a common fungal infection. To better understand the settings in which US family physicians recommend the use of clotrimazole/betamethasone diproprionate, we determined the diagnoses and characteristics of patients for whom family physicians prescribe this drug. METHODS: Data from the National Ambulatory Medical Care Survey were used to determine the demographic characteristics of patients who were given a prescription for clotrimazole/betamethasone diproprionate, the diagnoses of patients treated with the drug, and the potency of other topical corticosteroids by family physicians. Wholesale costs of drugs were used to estimate potential drug cost savings obtainable by switching to specific monotherapy agents. RESULTS: Clotrimazole/betamethasone diproprionate was prescribed at 3.1% of visits to family physicians but at only .6% of visits to dermatologists for either inflammatory or fungal/candidal conditions. Family physicians frequently prescribed clotrimazole/betamethasone diproprionate to children under age 5 and for use on genital skin disorders. Dermatologists rarely used clotrimazole/betamethasone diproprionate in these settings. CONCLUSIONS: The frequent use by family physicians of clotrimazole/betamethasone diproprionate in high-risk settings is of concern. Use of alternative agents with anti-inflammatory and antifungal properties without the risks associated with the use of high-potency topical corticosteroids may be the most practical approach to replacing use of clotrimazole/betamethasone diproprionate.

Clearance is not a realistic expectation of psoriasis treatment.

BACKGROUND: Psoriasis is a disease with many manifestations for which numerous treatments are available. OBJECTIVE: The purpose of this article is to assess whether complete clearance is a realistic expectation given the currently available treatments for psoriasis. METHODS: Clinical trials of the treatment of psoriasis were identified from the medical literature, and the reported rates of clearance were compared. RESULTS: The percentage of patients who experienced complete clearing of their psoriasis varied with the different monotherapy treatments from 2% with tazarotene gel to a maximum of 86% with narrow-band UVB. Combinations of systemic retinoids (etretinate, acitretin) and photochemotherapy (PUVA) attained the maximum reported clearance rate as combination therapy. CONCLUSION: The new treatments available for psoriasis give physicians new opportunity to control the severity of psoriasis. Despite the availability of novel treatments for psoriasis, complete clearing of psoriasis is obviously not a realistic expectation of topical treatment. Phototherapy and systemic therapy provide greater improvement, but studies rarely report complete clearing of the disease as an endpoint. At this time, optimal therapy consists of using combinations of different treatments to obtain short-term improvement and long-term control of the disease.

Treatment of psoriasis: an algorithm-based approach for primary care physicians.

Psoriasis is characterized by red, thickened plaques with a silvery scale. The lesions vary in size and degree of inflammation. Psoriasis is categorized as localized or generalized, based on the severity of the disease and its overall impact on the patient's quality of life and well-being. Patient education about the disease and the treatment options is important. Medical treatment for localized psoriasis begins with a combination of topical corticosteroids and coal tar or calcipotriene. For lesions that are difficult to control with initial therapy, anthralin or tazarotene may be tried. The primary goal of therapy is to maintain control of the lesions. Cure is seldom achieved. If control becomes difficult or if psoriasis is generalized, the patient may benefit from phototherapy, systemic therapy and referral to a physician who specializes in the treatment of psoriasis.

Sex-specific differences in the treatment of severe psoriasis.

BACKGROUND: Psoriasis treatment requires consideration of patient-specific concerns in addition to the severity of skin involvement. There may be sex-specific differences in the treatment of severe psoriasis. OBJECTIVE: The purpose of this study was to determine whether there are sex-specific differences in the treatment of severe psoriasis. METHODS: We analyzed the medications prescribed to patients with a primary and only diagnosis of psoriasis recorded in the 1990-1994 National Ambulatory Medical Care Survey. RESULTS: There were 8.5 million visits to physicians for the treatment of psoriasis in the years 1990-1994. These visits were made by approximately 4.3 million women and 4.1 million men. Only 39% of patients receiving systemic treatments were women. Women received less methotrexate (23% women) and etretinate (35% women) than men, but more psoralen photochemotherapy (PUVA) (63% women) and isotretinoin (100% women) than men. In contrast, there was no notable difference by sex in the potency of topical corticosteroid agents prescribed. CONCLUSION: For mild disease treated with topical agents alone, there is no notable difference in the treatment of men and women. Men are more likely than women to receive intensive treatments for severe psoriasis, at least in part because of the teratogenic potential of these treatments. There is a need for development of new treatments for severe psoriasis that are safe for women of childbearing potential.

New topical treatments change the pattern of treatment of psoriasis: dermatologists remain the primary providers of this care.

BACKGROUND: Psoriasis is a common chronic skin disorder that can be debilitating both physically and psychologically. The treatment of psoriasis is complicated by the many manifestations of the disease, different patients' subjective impression of the disease, and the availability of numerous topical agents, systemic agents, and phototherapy options for the disease. Purpose The purpose of this study was to characterize how topical psoriasis treatment is changing in the USA. Methods Data from the National Ambulatory Medical Care Survey (1990-1996) were used to characterize the use of medication at physician office visits for psoriasis vulgaris. Corticosteroid agents in the years 1990-1994 were classified by relative potency. Results There were 1.0 million yearly visits for psoriasis. Dermatologists were responsible for 95% of these office visits. Topical corticosteroids were the only medication listed at 50% of psoriasis visits, and were used in combination with another medication in an additional 26% of visits. High and superpotent corticosteroid agents accounted for 55% of all topical corticosteroid agents listed. Topical calcipotriene was the most commonly used noncorticosteroid treatment, and its use in combination with corticosteroids increased from 17% to 84% between 1994 and 1996. CONCLUSION: s 80% or more of people with psoriasis do not see a physician for the disease in any given year. A combination of different topical medications is commonly used to treat psoriasis. Patients should be aware of the availability of new therapeutic options and the special expertise of dermatologists in managing complex treatment regimens for psoriasis.