Examining the association between pruritus and quality of life in patients with atopic dermatitis treated with crisaborole.

BACKGROUND: Pruritus is a leading cause of reduced health-related quality of life (QoL) in atopic dermatitis (AD). Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In identical Phase 3 studies (NCT02118766, NCT02118792), crisaborole reduced disease and pruritus severity versus vehicle. OBJECTIVE: Quantify the relationship between pruritus and QoL using data from these studies. METHODS: Patients aged ≥2 years were randomly assigned 2 : 1 to receive crisaborole:vehicle twice daily for 28 days. QoL was measured at baseline and day 29 using the Dermatology Life Quality Index (DLQI; patients aged ≥16 years), the Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years) and the Dermatitis Family Impact (DFI; caregivers of patients aged 2-17 years). Pruritus was measured using the Severity of Pruritus Scale (SPS), a 4-point scale from 0 ('no itching') to 3 ('bothersome itching/scratching that disturbs sleep'), and captured morning and evening via electronic diary. Data from crisaborole and vehicle arms were pooled for this analysis. A repeated-measures longitudinal model was used to estimate relationships between pruritus (SPS) and QoL (DLQI, CDLQI and DFI in separate analyses). RESULTS: One thousand five hundred and twenty two patients received crisaborole or vehicle. A linearity assumption for the relationship between SPS and DLQI (n = 294), CDLQI (n = 1200), and DFI (n = 1293) was appropriate. For DLQI, SPS score of 0 was associated with 'no negative effect on patient QoL'; SPS score of 1 was associated with 'small effect on patient QoL'; SPS score of 2 was associated with 'moderate effect on patient QoL'; and SPS score of 3 was associated with 'very large effect on patient QoL'. The pattern of relationships between SPS and CDLQI and DFI was similar. CONCLUSIONS: The relationships between SPS and DLQI, CDLQI and DFI substantiate the significant link between pruritus and patient/caregiver QoL in AD.

Safety and tolerability of collagenase Clostridium histolyticum and fasciectomy for Dupuytren's contracture.

Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature review of 48 European studies (N = 7727) for treatment of Dupuytren's contracture. Incidence of adverse events was numerically lower with CCH vs. equivalent complications from fasciectomy (median [range] incidence), including nerve injury (0% vs. 3.8% [0%-50+%]), neurapraxia (4.4% vs. 9.4% [0%-51.3%]), complex regional pain syndrome (0.1% vs. 4.5% [1.3%-18.5%]) and arterial injury (0% vs. 5.5% [0.8%-16.5%]). Tendon injury (0.3% vs. 0.1% [0%-0.2%]), skin injury (16.2% vs. 2.8% [0%-25.9%]) and haematoma (77.7% vs. 2.0% [0%-25%]) occurred at a numerically higher incidence with CCH than surgery. Adverse events in CCH trials not reported after fasciectomy included peripheral oedema; extremity pain; injection site pain, haemorrhage and swelling; tenderness; pruritus and lymphadenopathy. CCH-related adverse events were reported as predominantly injection-related and transient. These results may support clinical decision-making for treatment of Dupuytren's contracture.

Collagenase clostridium histolyticum in patients with Dupuytren's contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes.

In POINT X, a study designed to reflect clinical practice and patient treatment choices, 254 European patients received open-label collagenase for Dupuytren's contracture. The most severely affected joint was treated first in 74% of patients. In total, 52%, 41%, 7%, and 1% of patients selected the little, ring, middle, and index finger, respectively; 79% had one or two joints treated. Only 9% of patients (n = 24) received 4 or 5 injections. The mean improvement in total passive extension deficit (TPED) was 34° on day 1, improving further by day 7 to 42°. This secondary improvement was maintained by day 90 and month 6. The mean number of injections/joint was 1.2 for the metacarpophalangeal joint and 1.25 for the proximal interphalangeal joint. Median time to recovery was 4 days; the mean improvement in hand function was clinically relevant as measured by the Unité Rhumatologique des Affections de la Main (URAM) score. In total, 87% and 86% of patients and physicians, respectively, were very satisfied or satisfied with treatment at month 6, although correlation between TPED and patient satisfaction was weak (Spearman -0.18, 95% CI -0.32 to -0.06). Collagenase was well tolerated, with 10 (3.9%) patients experiencing severe adverse events. As a real-world study, the POINT X findings can be generalized to the at-large population.

Dupuytren's disease presentation, referral pathways and resource utilisation in Europe: regional analysis of a surgeon survey and patient chart review.

AIM: We explored the management of Dupuytren's disease (DD) using a surgeon survey and patient chart review. METHODS: Twelve countries participated: Denmark, Finland, Sweden (Nordic region); Czech Republic, Hungary, Poland (East); France, Germany, the Netherlands, United Kingdom (West); Italy, Spain (Mediterranean). A random sample of orthopaedic/plastic surgeons (N = 687) with 3-30 years' experience was asked about Dupuytren's contracture procedures performed during the previous 12 months. Information ≤ 5 consecutive patients per surgeon was extracted from patient charts (N = 3357). RESULTS: Overall, 84% of participants were orthopaedic surgeons; 56% of surgeons were hand specialists. Deciding factors for fasciectomy and dermofasciectomy were consistent across regions: metacarpophalangeal (MP) or proximal interphalangeal contracture > 45°, recurrent contracture, and high expectations for success. Deciding factors for percutaneous needle fasciotomy were less consistent across regions, but the leading factor was MP flexion < 20°. Overall, 49% of diagnoses and 55% of referrals were made by a general practitioner (GP), with regional variation: 31-77% for GP diagnoses and 36-81% for GP referrals. There were also differences in admission status (e.g. 9% of Nordic patients and 80% of Eastern patients were treated as inpatients). Most patients were treated in public hospitals and most procedures were covered by public health insurance. CONCLUSIONS: We found regional variations in surgical practice, patient characteristics and referral patterns. Understanding current diagnosis and treatment patterns, in relation to regional differences in health economics, may improve physicians' diagnosis of DD and guide patients towards appropriate, customised management plans.

Surgical management of Dupuytren's contracture in Europe: regional analysis of a surgeon survey and patient chart review.

AIM: We explored regional variations in the surgical management of patients with Dupuytren's contracture (DC) in 12 European countries using a surgeon survey and patient chart review. METHODS: Twelve countries participated: Denmark, Finland, Sweden (Nordic region); Czech Republic, Hungary, Poland (East); France, Germany, the Netherlands, UK (West); Italy, Spain (Mediterranean). For the survey, a random sample of orthopaedic/plastic surgeons (n = 687) with 3-30 years' experience was asked about DC procedures performed during the previous 12 months. For the chart review (n = 3357), information from up to five consecutive patients was extracted. Descriptive statistics are reported. RESULTS: Ninety-five per cent of all surgeons used fasciectomy for DC, followed by fasciotomy (70%), dermofasciectomy (38%) and percutaneous needle fasciotomy (35%). Most surgeons were satisfied with fasciectomy over other procedures. Recommended time away from work and duration of physical therapy increased with the invasiveness of the procedure. The intra-operative complication rate was 4.0%; the postoperative complication rate was 34%. Overall, ≥ 97% of the procedures were rated by surgeons as having a positive outcome. Across all regions, 54% of patients had no nodules or contracture after the procedures. Only 2% of patients required retreatment within the first year of surgery. Important inter- and intraregional differences in these aspects of patient management are described. CONCLUSIONS: Understanding current regional treatment patterns and their relationships to country-specific health systems may facilitate earlier identification of, and intervention for, DD and help to optimise the overall treatment for patients with this chronic condition.

The efficacy and safety of fasciectomy and fasciotomy for Dupuytren's contracture in European patients: a structured review of published studies.

A structured review of published papers was done to assess the efficacy and safety of fasciectomy and fasciotomy in European patients with Dupuytren's contracture. The outcomes varied across 48 studies. For fasciectomy, outcomes and results were as follows: the proportions of patients with a 100% correction in contracture angle ranged from 61 to 97%, the mean improvement in contracture angle ranged from 58 to 79%, and cases judged excellent/good ranged from 63 to 90%. Fasciotomy had similar outcomes, with a mean improvement in contracture angle ranging from 46 to 88%. Immediate failures upon recovery were reported for both procedures. The average recurrence rates were 39% after a fasciectomy and 62% after a fasciotomy at a median time of about 4 years. Overall, about 20% of fasciectomy and fasciotomy patients experienced an adverse event. In summary, postoperative outcomes were successful, but surgical complications were common and recurrence of a contracture was likely within a few years.

Evaluating the Power of Food Scale in obese subjects and a general sample of individuals: development and measurement properties.

BACKGROUND: The Power of Food Scale (PFS) was developed to assess the psychological impact of today's food-abundant environments. OBJECTIVE: To evaluate the structure of the PFS in diverse populations of obese and nonobese individuals. DESIGN: Data were obtained from obese adults in a clinical trial for a weight management drug (n=1741), and overweight, obese and normal weight adults in a Web-based survey (n=1275). Exploratory and confirmatory factor analyses were used to investigate the PFS structure using the clinical data. The model developed was then tested using the Web-based data. Relationships between PFS domains and body mass index (BMI) were examined. Logistic regression was used in the Web-based survey to evaluate the association between obesity status and PFS scores. RESULTS: Clinical data indicated that the scale was best represented by a 15-item version with three subscale domains and an aggregate domain (average of three domains); this was confirmed with data from the Web-based survey (Comparative Fit Index: 0.95 and 0.94 for the clinical and Web-based studies, respectively). Cronbach's alpha for both data sets was high, ranging from 0.81 to 0.91. The relationships between BMI and each domain were weak (and approximately linear). A full category increase in PFS domain score (range 1-5) increased the odds of being obese 1.6-2.3 times. CONCLUSIONS: The 15-item PFS is best represented by three domains and an aggregate domain. The PFS may provide a useful tool to evaluate the effects of obesity treatments on feelings of being controlled by food in an obesogenic food environment.

Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants.

BACKGROUND: The 21-item Three-Factor Eating Questionnaire (TFEQ-R21) is a scale that measures three domains of eating behavior: cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE). OBJECTIVES: To assess the factor structure and reliability of TFEQ-R21 (and if necessary, refine the structure) in diverse populations of obese and non-obese individuals. DESIGN: Data were obtained from obese adults in a United States/Canadian clinical trial (n=1741), and overweight, obese and normal weight adults in a US web-based survey (n=1275). Confirmatory factor analyses were employed to investigate the structure of TFEQ-R21 using baseline data from the clinical trial. The model was refined to obtain adequate fit and internal consistency. The refined model was then tested using the web-based data. Relationships between TFEQ domains and body mass index (BMI) were examined in both populations. RESULTS: Clinical data indicated that TFEQ-R21 needed refinement. Three items were removed from the CR domain, producing the revised version TFEQ-R18V2 (Comparative Fit Index (CFI)=0.91). Testing TFEQ-R18V2 in the web-based sample supported the revised structure (CFI=0.96; Cronbach's coefficient alpha of 0.78-0.94). Associations with BMI were small. In the clinical study, the CR domain showed a significant and negative association with BMI. On the basis of the web-based survey, it was shown that the relationship between BMI and CR is population-dependent (obese versus non-obese, healthy versus diabetics). CONCLUSIONS: In two independent datasets, the TFEQ-R18V2 showed robust factor structure and good reliability. It may provide a useful tool for characterizing UE, CR and EE.

Does rapid transition to insulin therapy in subjects with newly diagnosed type 2 diabetes mellitus benefit glycaemic control and diabetes-related complications? A German population-based study.

OBJECTIVE: The aim of this study was to assess whether earlier transition to insulin in subjects with newly diagnosed type 2 diabetes improves glycaemic control and reduces diabetes-related complications. METHODS: Subjects with newly diagnosed type 2 diabetes, and 2 or more recorded glycosylated haemoglobin (HbA1c) values, were identified from the Mediplus Germany database between June 1993 and May 2001. Subjects were stratified by treatment group: diet and exercise, sulfonylurea drugs, antihyperglycaemic drugs, insulin, or insulin plus sulfonylurea or antihyperglycaemic drugs. Treatment modifications were tracked over time and a rapid transition to insulin recorded if insulin was the initial therapy administered or the immediate treatment after diet and exercise. The area under the curve (AUC) for HbA1c was calculated and a linear regression model used to explain AUC as a function of rapid transitioning to insulin. A Cox proportional hazard model assessed the relationship between the time to first complication and AUC, rapid transition to insulin, and the number of treatment modifications. RESULTS: Of the 3136 subjects who met the study entry criteria, just 151 (4.8%) were initiated on insulin; after 5 years only 811 (25.9%) subjects had received insulin therapy. In the regression model explaining AUC, rapid transition to insulin significantly improved glycaemic control (-0.20, p=0.03). The Cox proportional hazard model demonstrated that the time to first complication was negatively related to AUC (-0.05, p<0.01) and the rapid use of insulin (-0.27, p<0.01), and positively related to the number of treatment modifications (0.07, p<0.01). CONCLUSIONS: Using actual real world clinical practice data, the present study found that the immediate use of insulin in patients with type 2 diabetes improved blood glucose control as measured by the AUC for HbA1c readings. This, in turn, reduced the risk of diabetes-related complications. In contrast, we observed that a stepwise transition treatment pattern (switching from diet and exercise to sulfonylureas and then perhaps to antihyperglycaemic agents and finally insulin) increased the risk of diabetes-related complications. Greater effort is required to remove some of the barriers currently preventing earlier initiation of insulin therapy in patients with type 2 diabetes.

Treatment satisfaction with inhaled insulin in patients with type 1 diabetes: a randomized controlled trial.

OBJECTIVE: In patients with type 1 diabetes, glycemic control can be achieved as effectively with an inhaled insulin regimen, comprising preprandial inhaled intrapulmonary insulin plus a bedtime ultralente injection, as with a conventional subcutaneous insulin regimen involving two to three injections per day. Our objective was to compare patient satisfaction between inhaled insulin and subcutaneous insulin. RESEARCH DESIGN AND METHODS: Subjects with type 1 diabetes participated in a 12-week open-label trial and were randomized to either an inhaled insulin regimen or a subcutaneous insulin regimen. Subjects (n = 69) were asked to complete a 15-item self-administered satisfaction questionnaire, the Patient Satisfaction with Insulin Therapy (PSIT) Questionnaire, at baseline and week 12. Outcomes included mean percentage changes in global (overall) satisfaction and two subscales: convenience/ease of use and social comfort. RESULTS: The mean percentage improvement in overall satisfaction with inhaled insulin (35.1%, 95% CI 18.0-52.2) was greater than with subcutaneous insulin (10.6%, 4.7-16.5) (P < 0.01), as was the improvement in convenience/ease of use: inhaled insulin 41.3% (22.9-59.6) versus subcutaneous insulin 11.2% (4.1-18.3; P < 0.01). Improvement in social comfort was greater with inhaled insulin but was not statistically significant. The 12-week change in HbA(1c) was associated with improved overall satisfaction (r = -0.27, P = 0.04). CONCLUSIONS: Inhaled insulin may offer the first practical, noninvasive alternative to insulin injections. For patients with type 1 diabetes, inhaled insulin maintains glycemic control and provides greater overall satisfaction and convenience/ease of use than subcutaneous insulin.

Development and factor analysis of a questionnaire to measure patient satisfaction with injected and inhaled insulin for type 1 diabetes.

OBJECTIVE: To develop a self-administered questionnaire to address alternative delivery routes of insulin and to investigate aspects of patient satisfaction that may be useful for subsequent assessment and comparison of an inhaled insulin regimen and a subcutaneous insulin regimen. RESEARCH DESIGN AND METHODS: Attributes of patient treatment satisfaction with both inhaled and injected insulin therapy were derived from five qualitative research studies to arrive at a 15-item questionnaire. Each item was analyzed on a five-point Likert scale so that higher item scores indicated a more favorable attitude. There were 69 subjects with type 1 diabetes previously taking injected insulin therapy who were enrolled in a phase II clinical trial. Their baseline responses on the questionnaire were evaluated and subjected to an exploratory factor analysis. Meaningful factors were retained and interpreted based on their psychometric properties. RESULTS: Exploratory factor analysis suggested a two-factor solution accounting for 66 and 20% of the variance, respectively. The first factor contained 10 reliable items (Cronbach's alpha = 0.89) relating to convenience and ease of use, and the second contained 5 reliable items (Cronbach's alpha = 0.82) relating to social comfort. CONCLUSIONS: Among patients with type 1 diabetes, this analysis highlighted and quantified two key factors contributing to patient satisfaction: convenience/ease of use and social comfort. The questionnaire underwent rigorous development, had reliable properties, and an interpretable and rich factor structure. This report is intended to help advance, in subsequent investigations, the understanding and measurement of treatment satisfaction with novel and existing forms of insulin delivery.

Impact of pharmacist consultations provided to patients with diabetes on healthcare costs in a health maintenance organization.

We conducted a study to assess the impact on healthcare utilization and costs of pharmacist consultations provided to patients with diabetes. Data for this study were derived from a larger study conducted by Kaiser Permanente and the University of Southern California that evaluated three alternative models of pharmacist consultations (control, state, and Kaiser). Computerized data were available for patient demographic characteristics and healthcare utilization. We used medication data to classify patient cohorts as insulin only or oral antidiabetics +/- insulin. We estimated hospitalization costs based on diagnostic related group and medication costs based on average wholesale price; office visits were estimated at $70 each. In the insulin only cohort, total costs for patients who had their prescriptions filled at a state model pharmacy were 7.8% less than those for patients filling prescriptions at a control model pharmacy (P = 0.008). In the oral +/- insulin cohort, total costs for patients filling new prescriptions at a Kaiser model pharmacy were 21.9% less than those for patients using a control model pharmacy (P = 0.0001). The state model also was negatively correlated (beta coefficient, -0.0997) with total costs (P = 0.0001). These data suggest that pharmacist consultations provided to patients with diabetes can decrease total healthcare costs in a health maintenance organization.

Methodological issues in evaluating HIV prevention community planning.

To be effective, HIV prevention programs should be planned in partnership with affected communities and should be built on a solid scientific foundation. In 1994, the Centers for Disease Control and Prevention (CDC) and its prevention partners implemented HIV prevention community planning to achieve primarily these two objectives. In order to manage the community planning process effectively, extensive evaluation activities were employed at both the grantee and national level. This paper describes the first year evaluation goals and methods in detail. Throughout, reasons for collecting specific types of information and for using particular methodologies are highlighted.

Concurrent bilateral hypernephroma. Successful diagnosis and treatment of one patient.

Clinically unsuspected, bilateral concurrent clear cell cancers of each kidney were identified in a patient during evaluation for acute pancreatitis. A right renal lesion was demonstrated by computerized axial tomography (CAT) scan. Promptly thereafter percutaneous transfemoral aortography was performed, identifying separate, bilateral kidney neoplasms. The surgical outcome at nineteen months postoperatively has been satisfactory.