Baseline Characteristics of Canadian Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

Pregnancy Outcomes in Women With Moderate-to-Severe Psoriasis From the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

Importance: Prospective data are limited on pregnancy outcomes among women with psoriasis who may be receiving biologic or conventional systemic therapy. Objective: To report pregnancy outcomes observed in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Design, Setting, and Participants: This cohort study used data from PSOLAR, a multicenter, disease-based, observational registry evaluating long-term safety and clinical outcomes for patients receiving or eligible to receive treatment for psoriasis with biologics and/or conventional systemic therapies. Of 12 090 enrollees, 5456 were women (45.1%), and 2224 women were of childbearing age (18-45 years). Participants had a total of 12 929 patient-years of follow-up (median, 7.2 [range, 3.3-8.0] years per patient). Data were collected from June 20, 2007, to August 23, 2019, and analyzed from April 23 to June 23, 2020. Exposures: Exposure to biologics within the prenatal period (≤1 year before birth or ≤6 months before spontaneous abortion) or at any other time. Main Outcomes and Measures: Descriptive summaries of pregnancies and pregnancy-related outcomes were self-reported in PSOLAR, including births, stillbirths, spontaneous abortions, and elective terminations. Live birth characteristics collected in PSOLAR include whether a birth was full-term (≥37 weeks) or premature (<37 weeks) and whether neonatal adverse events or congenital anomalies occurred. Results: A total of 298 pregnancies occurred among 220 women (mean [SD] age, 27.8 [5.2] years), and the general fertility rate was 18.9 per 1000 women aged 18 to 45 years. Of the 298 pregnancies, 244 (81.9%) resulted in birth, 41 (13.8%) ended in spontaneous abortion, and 13 (4.4%) were electively terminated. Gestational age was available for 243 births; 221 infants (90.9%) were full-term, and 22 (9.1%) were born prematurely. Birth outcomes included 231 healthy newborns, 10 infants with a neonatal problem, 2 infants with a congenital anomaly, and 1 stillbirth. Of the 298 pregnancies, 252 were associated with biologic exposure before or during pregnancy. Pregnancy outcomes for women exposed to biologics were similar to those for women exposed to nonbiologics. Among women who became pregnant, mean (SD) age at the time of pregnancy outcome was 30.9 (4.8) years; at enrollment into the registry, 74 of 219 (33.8%) had obesity, and 121 of 220 (55.0%) were past or current smokers. Conclusions and Relevance: The findings of this cohort study suggest that pregnancy outcomes in PSOLAR have remained consistent with previous reports. Overall and live birth outcomes were similar to those for the general population.

Radiation dermatitis assessment tools used in breast cancer: A systematic review of measurement properties.

PURPOSE: This review aimed to assess the quality and efficacy of tools currently used in breast cancer patients to score radiation dermatitis (RD), a common debilitating side effect of radiotherapy (RT). METHODS: A search was conducted through Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials databases on 14 February 2020. English articles that evaluated an instrument's use in assessing RD among breast cancer patients receiving external beam RT were included. Studies that reported on the reliability, validity, or concordance of items between assessment tools were included in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria. RESULTS: Twelve studies were included in this review, with a total of 13 skin toxicity assessment tools discussed. Tools that assessed clinician-reported outcomes (CROs) mostly reported moderate correlation with biophysical parameter (BP) measurements and low correlation with patient-reported outcomes (PROs). Traditionally used CRO scoring tools demonstrated moderate inter-rater reliability between clinicians, likely due to the subjective nature of items on the grading scales. Most commonly used tools were found to be either insufficient or indeterminate in their measurement properties. CONCLUSIONS: Current standardized tools that measure CROs are subject to clinician interpretation and fail to represent the patient experience. Tools designed to assess PROs are promising in their assessments of the impact of RT on patient quality of life; however, most PRO tools are generic to all skin conditions and require further validation for use in breast cancer. Among tools that measure CROs, PROs, and BPs, there is insufficient evidence on their measurement properties to establish a "gold standard" for the assessment of RD in breast cancer patients.

A network meta-analysis on the efficacy and safety of monotherapies for tinea capitis, and an assessment of evidence quality.

Various monotherapies exist for tinea capitis; however, their relative efficacies have never been determined using a statistical approach which compares treatments' efficacy simultaneously. The goal of this study was to determine the relative efficacy (mycologic and complete cure rates) of monotherapies for the treatment of tinea capitis. On October 5, 2019, searches were performed in Scopus, PubMed, EMBASE, MEDLINE (Ovid), and CINAHL; there were no date restrictions. For the main network meta-analysis, eligible studies were randomized trials that investigated the effect of tinea capitis monotherapies on subjects' mycological and complete cure rates. Network meta-analyses were conducted in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for network meta-analyses. Mycological cure rate was the primary outcome; complete cure rate and adverse events were secondary outcomes. Twelve studies met the eligibility criteria for the main network; five systemic monotherapies were identified, griseofulvin, ketoconazole, terbinafine, itraconazole, and fluconazole. When the causative species was of the Microsporum genus, griseofulvin was most efficacious in terms of mycological cure (SUCRA = 66.1%) and complete cure (SUCRA = 80.6%). For tinea capitis caused by the Trichophyton species, terbinafine was the most efficacious in terms of both mycological and complete cure (SUCRA values of 75.2% and 78.2%, respectively). Risk of adverse events did not significantly differ across the interventions. Our results are congruent with those of previous pairwise meta-analyses; our findings also corroborate clinical experience and anecdotal evidence.

SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.

Correction to: Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

The correct name of the 9th Author is David J. Margolis. The original article was corrected.

Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

PURPOSE: Establishment of causality between drug exposure and adverse drug reactions (ADR) is challenging even for serious ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several causality assessment tools (CAT) exist, but the reliability and validity of such tools is variable. The objective of this study was to compare the reliability and validity of existing ADR CATs on SJS/TEN cases. METHODS: Seven investigators completed three CAT (ALDEN, Naranjo, Liverpool) for 10 SJS/TEN cases. Each CAT categorized the causality of 30 potential drugs as definite/very probable, probable, possible, or doubtful/unlikely. An additional reviewer provided expert opinion by designating the implicated drug(s) for each case. A Kappa score was generated to compare CAT responses both by method (reliability of all 7 reviewers, by CATs) and by reviewer (reliability of the 3 CAT, by reviewer). A c statistic was calculated to assess validity. RESULTS: Inter-rater reliability by CAT was poor to fair: ALDEN 0.22, Naranjo 0.11, and Liverpool 0.12. Reliability was highest when causality classification was definite/very probable (0.16-0.41). Similarly, intra-rater reliability by reviewer was poor. When comparing the validity of the overall CAT to expert reviewer, area under the curve was highest for ALDEN (c statistic 0.65) as compared to Liverpool (0.55) or Naranjo (0.54). CONCLUSION: Available CAT have poor reliability and validity for drug-induced SJS/TEN. Due to the importance of determining ADR causality for research, industry, and regulatory purposes, development of an enhanced tool that can incorporate data from immunological testing and pharmacogenetic results may strengthen CAT usefulness and applicability for drug-induced SJS/TEN.

Global perspectives for the management of onychomycosis.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophyte molds, and yeasts. This difficult-to-treat chronic infection has a tendency to relapse despite treatment. This paper aims to offer a global perspective on onychomycosis management from expert physicians from around the world. Overall, the majority of experts surveyed used systemic, topical, and combination treatments approved in their countries and monitored patients based on the product insert or government recommendations. Although the basics of treating onychomycosis were similar between countries, slight differences in onychomycosis management between countries were found. These differences were mainly due to different approaches to adjunctive therapy, rating the severity of disease and use of prophylaxis treatment. A global perspective on the treatment of onychomycosis provides a framework of success for the committed clinician with appreciation of how onychomycosis is managed worldwide.

Effect of Age of Onset of Psoriasis on Clinical Outcomes with Systemic Treatment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

OBJECTIVE: Our objective was to compare therapeutic response among patients with early-onset psoriasis (EOP) and late-onset psoriasis (LOP) receiving adalimumab, etanercept, infliximab, ustekinumab, or methotrexate in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Patients were grouped by age of onset: EOP (age ≤ 40 years) or LOP (age > 40 years). Repeated-measures analysis with logistic regression was used to calculate the adjusted odds ratio (AOR; adjusted for baseline characteristics) for achieving a Physician's Global Assessment score of cleared/minimal (PGA 0/1) or a percentage of body surface area involved with psoriasis < 3% (%BSA < 3) or %BSA < 1 for all patients; similar sensitivity analyses were performed for each treatment group. RESULTS: Of 7511 patients, 5479 (72.9%) had EOP. The LOP group had a higher likelihood of achieving PGA 0/1 after treatment than did the EOP group in all patients (AOR 1.14 [95% confidence interval (CI) 1.05-1.25]; p = 0.0019); the same was true in subgroups of etanercept-treated (AOR 1.38 [95% CI 1.14-1.66]; p = 0.0010) and methotrexate-treated (AOR 1.62 [95% CI 1.16-2.26]; p = 0.0049) patients. No significant difference was found between the EOP and LOP groups with regard to the likelihood of achieving %BSA < 3 or %BSA < 1 among all patients. However, LOP patients were more likely than EOP patients to achieve %BSA < 3 or %BSA < 1 in subgroups treated with infliximab (AOR 1.45 [95% CI 1.09-1.93; p = 0.0103] and AOR 1.36 [95% CI 1.03-1.78; p = 0.0290], respectively) and etanercept (AOR 1.30 [95% CI 1.06-1.61; p = 0.0123] and AOR 1.34 [95% CI 1.09-1.64; p = 0.0053], respectively). CONCLUSION: Our real-world data from PSOLAR indicate that there are differences in some patient characteristics between EOP and LOP and that patients with EOP are less likely than those with LOP to respond to certain systemic treatments. (ClinicalTrials.gov identifier: NCT00508547).

Confirmatory Testing Prior to Initiating Onychomycosis Therapy Is Cost-Effective.

BACKGROUND: Onychomycosis can be investigated by sampling. Information gleaned includes nail bed involvement, nail plate penetration, fungal viability, and species identification. Testing samples can confirm a diagnosis. While diagnostic testing is considered useful in directing therapy, a substantial number of clinicians do not confirm diagnosis prior to treatment. OBJECTIVES: The aim of this study is to quantify the benefit of confirmatory testing prior to treating toenail onychomycosis. METHODS: The cost of mycological cure (negative potassium hydroxide and negative culture) and the cost-effectiveness of confirmatory testing were determined using the average cost of potassium hydroxide (KOH), culture, periodic acid-Schiff (PAS), efinaconazole, ciclopirox, terbinafine, and itraconazole. Costs were obtained through literature searches, public domain websites, and telephone surveys to local pharmacies and laboratories. To represent the potential risks of prescribing onychomycosis treatment, the costs associated with liver monitoring, potential life-threatening adverse events, and drug-drug interactions were obtained through public domain websites, published studies, and product inserts. RESULTS: PAS was determined to be the most sensitive confirmatory test and KOH the least expensive. The overall cost of an incorrect diagnosis (no confirmatory test used) ranged between $350 and $1175 CAD per patient for treatment of 3 infected toenails. Comparatively, performing confirmatory testing prior to treatment decreases the overall cost to $320 to $930, depending on the therapy, physician, and test. CONCLUSIONS: It is preferred to diagnose onychomycosis prior to treatment. Furthermore, there are cost savings when confirmatory testing is performed before initiating treatment with both topical and oral antifungals in Canada.

Onychomycosis in the 21st Century: An Update on Diagnosis, Epidemiology, and Treatment.

Onychomycosis accounts for 50% of all nail disease cases and is commonly caused by dermatophytes. Diabetes, human immunodeficiency virus, immunosuppression, obesity, smoking, and advancing age are predisposing factors of this fungal infection. Potassium hydroxide and culture are considered the current standard for diagnosing onychomycosis, revealing both fungal viability and species identification. Other diagnostic tests currently available include periodic acid-Schiff staining, polymerase chain reaction techniques, and fluorescent staining. Across 6 recently published epidemiology studies, the global prevalence of onychomycosis was estimated to be 5.5%, falling within the range of previously reported estimates (2%-8%). Newly approved onychomycosis treatments include efinaconazole, tavaborole, and laser therapy with lasers only approved to temporarily increase the amount of clear nail. Additional onychomycosis treatments being investigated include iontophoresis and photodynamic therapy with small open-label studies reported thus far. Preventative strategies, to help decrease recurrence and reinfection rates, include sanitisation of footwear and prophylactic topical antifungal agents.

Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]).

BACKGROUND: Comparing effectiveness of biologics in real-world settings will help inform treatment decisions. OBJECTIVES: We sought to compare therapeutic responses among patients initiating infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness. RESULTS: Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab [odds ratio {OR} 0.396, P < .0001], adalimumab [OR 0.686, P = .0012], etanercept [OR 0.554, P = .0003] at 6 months and infliximab [OR 0.449, P = .0040] at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months. LIMITATIONS: Treatment selection bias and limited data for doing adjustments are limitations. CONCLUSIONS: In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.

Cost and Resource Use of Pemphigus and Pemphigoid Disorders Pre- and Post-Rituximab.

BACKGROUND: Rituximab (RTX) is increasingly used for the treatment of pemphigus and pemphigoid disorders. The high cost of RTX frequently limits its use and access. OBJECTIVE: To determine the health system resources and costs associated with RTX treatment of pemphigus and pemphigoid. METHODS: Health system resources and costs attributed to a convenience sample of 89 patients with either pemphigus or pemphigoid were identified, quantified, and valued 6 months prior to and following RTX initiation between May 2006 and August 2012. Overall cohort costs and costs per patient were calculated (2013 Can$). RESULTS: The overall cohort cost for 6 months pre-RTX was $3.8 million and for 6 months post-RTX was $2.6 million. The average cost per patient decreased from $42,231 to $29,423 (30.3% decrease). The main cost driver was intravenous immunoglobulin. CONCLUSIONS: Our findings suggest that RTX is effective in reducing health system resources and the costs associated with the treatment of pemphigus and pemphigoid.

Cost utility analysis based on a head-to-head Phase 3 trial comparing ustekinumab and etanercept in patients with moderate-to-severe plaque psoriasis: a Canadian perspective.

OBJECTIVE: A head-to-head comparator study has shown that the clinical efficacy of ustekinumab is superior to that of etanercept over a 12-week period in patients with psoriasis. Economic models are often hindered by the lack of trials directly comparing outcomes between relevant alternative therapies. The aim of this analysis was to evaluate the cost-effectiveness of ustekinumab versus etanercept among adults with moderate-to-severe plaque psoriasis based on a Phase 3 head-to-head trial. METHODS: The Markov model incorporates trial data from the Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial study (ustekinumab 45 mg at Weeks 0 and 4; etanercept 50 mg biweekly) to follow patient response to initial treatment using the modeling approach developed by the Centre for Reviews and Dissemination, University of York, and often cited by others conducting economic analyses of psoriasis. Beyond the initial trial period, the Canadian model extrapolates results up to 10 years. RESULTS: Over the 10-year time horizon of the model, the mean annual costs were $16,807 for ustekinumab (45 mg) and $19,525 for etanercept (50 mg). The incremental difference in costs and utilities remained in favour of ustekinumab across a range of sensitivity analyses. CONCLUSIONS: This model highlights the advantage of having head-to-head comparative trial data relevant to the at-risk population. Our model shows that ustekinumab is more cost-effective than etanercept for patients with moderate-to-severe plaque psoriasis.

Canadian hand dermatitis management guidelines.

BACKGROUND: Hand dermatitis (HD) is one of the most common skin conditions; however, it is not a homogeneous disease entity. The severity of HD may range from very mild cases to severe chronic forms, which may result in prolonged disability and, occasionally, refractory HD. Chronic hand dermatitis (CHD) is associated with a high health- economic burden and significant loss of quality of life. OBJECTIVE: Although numerous treatment options are available, the management of CHD is often difficult and unsatisfactory. There is a paucity of well-designed, randomized, controlled clinical trials in support of the efficacy of established treatment modalities. CONCLUSION: These guidelines cover the epidemiology, burden, quality of life, etiology, diagnosis, classification, and prevention of HD and provide guidance on management using an approach that is as evidence based as possible.

Clinical risk management of Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.

Clinical risk management concedes that risk is inherent to all health-care processes. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life-threatening reactions to medications. Risk management should be considered prior to starting, during, and after therapy. Prior to starting therapy, risks that need to be assessed include any specific patient groups that may be at greater risk for the development of SJS/TEN. Gene testing is in place for Chinese and Thai patients who are going to be exposed to carbamazepine. During therapy, it is important to recognize SJS/TEN as a possible adverse drug reaction. Diagnostic criteria have changed, and more data exist on drugs with an increased risk. Although there is no standardized treatment for all patients with SJS/TEN, options that have been used include cyclosporine, corticosteroids, and intravenous immunoglobulin. Standards of care are usually defined locally, but new treatments, such as amniotic membrane support for ocular damage, may need to be considered. Good communication skills are needed to allow practitioners to show empathy and to provide disclosure. Risk management after a reaction includes skills in acknowledging bad outcomes or error; freedom to say "sorry" as defined by "apology laws," and knowing the rights provided by "Quality Assurance Conferences," where the information discussed is protected. In other words, the patient is best supported after an event like SJS/TEN if the practitioner is knowledgeable about optimal care standards and their legal rights and obligations.

Socioeconomic status influences care of patients with acne in Ontario, Canada.

BACKGROUND: Canada's universal health care system is designed to ensure equitable access to medical care based on need rather than socioeconomic status, although a number of studies indicate a preferential access and greater use of specialist services for those patients in higher socioeconomic groups. OBJECTIVES: The primary objective of this study was to determine whether socioeconomic status influences access to specialist care by a dermatologist for the management of acne in Ontario, Canada. A secondary objective was to determine whether the urban-rural dwelling status of patients affects access to specialty care. METHODS: We conducted a population-based cohort study using administrative health care databases covering more than 12 million residents of Ontario. Individuals age 12 to 27 years with a new diagnosis of acne by a general practitioner were identified as belonging to 1 of 5 socioeconomic groups based on median annual neighborhood household income. Patients were then observed for 2 years after the index visit to identify visits to a dermatologist. The main outcome measure was visitation to a dermatologist within 2 years of an initial diagnosis of acne. RESULTS: The study cohort consisted of 295,469 patients given a diagnosis of acne by their primary care physician of which 59,799 (20%) were subsequently referred to a dermatologist. Of those in the lowest income group of less than Can dollars 20,000, 17% were referred to a dermatologist, as compared with 24% in the highest income group of greater than Can dollars 80,000 (P value for trend < .001). Furthermore, patients living in an urban area had a 43% greater likelihood of being referred to a dermatologist (odds ratio 1.43, 95% confidence interval 1.39-1.48) as compared with patients in a rural location. LIMITATIONS: Limitations of our study include imputing socioeconomic status of patients on the basis of median income at the neighborhood level rather than on the basis of data on individual patients. Furthermore, our use of administrative databases did not allow us to characterize the severity of acne in our population cohort and whether that would affect referral patterns. CONCLUSION: Within Canada's universal health care system, those likely to be in lower socioeconomic groups are significantly less likely to visit a dermatologist for specialist consultation.

Objective psychological measurement and clinical assessment of anxiety in adverse drug reactions.

BACKGROUND: A confounding factor in the diagnosis of adverse drug reactions (ADRs) is the psychological state of the patient. Patients with underlying anxiety and related disorders may present with psychogenic reactions, which involve physiologic responses originating from psychological, rather than organic factors. OBJECTIVE: To examine the contribution of anxiety and related disorders to adverse drug events. METHODS: Participants from an adverse drug reaction clinic completed the Trauma Symptom Checklist-40 (TSC-40), a 40-item questionnaire consisting of six subscales: anxiety, depression, dissociation, sexual abuse trauma index (SATI), sexual problems, and sleep disturbance. Physicians assessed the likelihood that adverse events were due to anxiety or drug(s) by providing an anxiety score (0 to 10) and an ADR score (0 to 10), respectively, for each participant. RESULTS: Patients clinically assessed as having "high anxiety" (anxiety score 7-10 and ADR score 0-3; n = 11) scored higher than patients clinically assessed as having a "true ADR" (anxiety score 0-3 and ADR score 7-10; n = 19) on the TSC-40 total (P = 0.006) as well as anxiety (P = 0.012), depression (P = 0.007), and SATI subscales (P = 0.016). CONCLUSION: This study is the first to use a validated psychological measurement to indicate that a substantial percentage of reported adverse drug events may in fact be a manifestation of underlying anxiety and/or related disorders. We suggest that mechanisms of symptom generation may be analogous to those operative in idiopathic environmental intolerance.