A Novel Qualitative Study Assessing Patient-Reported Outcome Measures Among People Living with Psoriatic Arthritis or Ankylosing Spondylitis.

INTRODUCTION: Patient-reported outcome measures (PROMs) are used to capture patient perspectives in disease assessment. The objective of this study was to capture feedback about commonly used PROMs for spondyloarthritis (SpA) through semi-structured group discussions with individuals diagnosed with psoriatic arthritis (PsA) or ankylosing spondylitis (AS). The goal was to identify PROM content that most resonated with patient experiences and is therefore suitable for implementation in SpA clinical practice. METHODS: Semi-structured tasks and probes were designed to elicit qualitative patient feedback on several general health and disease-specific PROMs. During a series of in-person and telephone meetings, participants with PsA or AS were asked to identify content that resonated with them and to identify items that may not have captured their personal experiences living with their disease. Both individualized and small group review and concept elicitation were captured after participant review of PROMs. RESULTS: Both PsA and AS participants identified concepts that reflected their experiences living with a chronic disease, including fatigue, isolation, depression, inter-personal relationships, and sexual intimacy. Constructs incorporated into existing PROMs, such as pain, physical function, ability to perform activities of daily living, and stiffness, were also identified as important to participants. There were a few qualitative differences in participant perceptions about what they would like to see addressed by PROMs. For example, AS participants said that they would like to see PROMs elicit feedback about their experiences with pelvic and chest pain (e.g., as a result of chest inflammation/tenderness and chest expansion). PsA participants felt that PROMs should include measures about the embarrassment and shame that they experience as well as the impact of PsA on their daily lives. CONCLUSION: Results of these qualitative assessments suggest that PROMs should be incorporated more frequently in outpatient settings to help improve the quality of decision-making conversations between patients and their healthcare providers. Participants indicated that constructs such as isolation, depression, fatigue, and relationships with others were critical to inform healthcare professionals about the patient experience of living with their disease.

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study.

Esketamine nasal spray (ESK) is indicated, in conjunction with an oral antidepressant (OAD), for the management of treatment-resistant depression (TRD) in adults. Select US-based patients from an open-label, long-term extension safety study of ESK (NCT02782104) participated in this study through semi-structured interviews. The study evaluated patient-reported early health changes related to emotional health, daily functioning, and social functioning in adults with TRD treated with ESK plus OAD. Eligible patients were responders to ESK who had begun initial ESK treatment ≤30 months before enrollment and were currently receiving ESK plus OAD. Results from 23 patients (9 men, 14 women; mean age, 46 years) were analyzed. Patients described the degree to which ESK treatment changed the effects of depression on aspects of health as either being much improved or improved (91.8%, 156/170). Key characteristics noted regarding treatment with ESK plus OAD included degree of effectiveness (n = 11), rapid onset of action (n = 7), and side-effect profile (n = 5). All patients reported being either satisfied (52%) or very satisfied (48%) with ESK plus OAD treatment. Adverse events were consistent with the known safety profile of ESK. Study insights may help prepare patients with TRD and their clinicians to anticipate potential health changes experienced with ESK.

Gastrointestinal Signs and Symptoms Related to Inflammatory Bowel Disease in Patients With Moderate-to-Severe Psoriasis

Background: Psoriasis (PsO) is a chronic inflammatory skin disorder that may be associated with comorbidities, including inflammatory bowel disease (IBD), given common immunopathogenic mechanisms. Whether PsO patients are more likely to suffer from gastrointestinal (GI) signs and symptoms has not been well-characterized. Understanding their prevalence in PsO patients may inform strategies to evaluate for GI signs and symptoms, screen for those at risk for IBD, and guide choice of therapy. Objective: To assess the prevalence of GI signs and symptoms in patients with moderate-to-severe PsO. Methods: An Internet-based survey was conducted to evaluate GI signs and symptoms in patients with self-reported moderate-to-severe PsO and non-PsO controls. The impact of PsO severity and presence of psoriatic arthritis (PsA) [self-reported and/or screened positive on the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire] on prevalence of GI signs and symptoms was also assessed. The survey included questions about PsO, comorbidities, demographics, and GI signs and symptoms. Questions related to GI signs and symptoms were used to calculate a modified CalproQuest* score to identify patients at increased risk for IBD. Results: Survey responses were collected from 740 PsO patients and 1411 non-PsO controls. With the exception of age, demographics were generally comparable between groups. All six GI signs and symptoms assessed (belly pain, feeling full/bloated, diarrhea, mucus in stool, blood in stool, and unintentional weight loss) were more prevalent in PsO patients compared with non-PsO controls, and a higher proportion of PsO patients also had a positive CalproQuest* result. In addition, both more severe PsO and concomitant PsA were associated with a higher prevalence of GI signs and symptoms and a positive CalproQuest*. Conclusions: This study suggests that PsO patients, including those with PsA, have a higher prevalence of GI signs and symptoms. Physicians should recognize and consider this concern in PsO patient management. J Drugs Dermatol. 2018;17(12):1298-1308.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality.

OBJECTIVE: To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. METHODS: We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. RESULTS: In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). CONCLUSION: Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials.

Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials. Study Design A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother-neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at ≥24 weeks' GA. Results Among 17,912 mother-neonate pairs, neonates were at a risk of numerous severe but infrequent morbidities. Clinically important, predominantly rare events were combined into a CE comprising neonatal mortality and morbidities, which decreased in frequency with increasing GA. The highest CE frequency occurred at <31 weeks. High frequency of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the CE. Median length of hospital stay was longer at all GAs in those with the CE compared with those without. Conclusions Descriptive epidemiological assessment and clinical input were used to develop a CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical data and CE allowed trials investigating tocolytics to be sized appropriately.

Adjunctive use of anticoagulants at the time of percutaneous coronary intervention in patients with an acute coronary syndrome treated with fondaparinux: a multinational retrospective review.

Aim: This retrospective chart review was designed to evaluate physician adherence to the prescribing information for fondaparinux regarding adjunctive anticoagulant use during percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome (ACS). Methods and results: Medical record abstractors at each site obtained information regarding the use of fondaparinux and adjunctive anticoagulants during PCI. Physician adherence to fondaparinux prescribing information regarding the administration of an adjunctive anticoagulant during PCI was estimated using generalized estimating equations. This retrospective study, conducted in 2008-2010, included a total of 1056 patient records from 27 sites across 6 countries (Canada, France, Germany, Greece, Poland, and Sweden). Over 98% of patients had been treated with fondaparinux at the recommended 2.5 mg dose. Use of adjunctive anticoagulant during PCI was 97.5%, giving an adjusted adherence rate of 98.8% (95% confidence interval: 0.97-0.99), with 86.3% of patients receiving unfractionated heparin. Although the sub-group of patients with ST-elevation myocardial infarction who underwent primary PCI was too small to make a definitive conclusion, 70.4% of the 159 patients did not receive fondaparinux immediately prior to (<24 h) or during primary PCI, suggesting that their treating physicians may have been adherent to the prescribing information. Conclusion: Physician adherence to the prescribing information for adjunctive anticoagulation during PCI in patients with an ACS receiving fondaparinux was high. The results were consistent in each of the six countries and across patient sub-groups.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.

Right answers, wrong questions in clinical research.

To ensure that clinical research arrives at the "right" answers to the right questions for patients, studies should be designed to more closely approximate real-world use of therapeutics and devices.

Clinical accuracy of a PLEX-ID flu device for simultaneous detection and identification of influenza viruses A and B.

Respiratory tract infections caused by influenza A and B viruses often present nonspecifically, and a rapid, high-throughput laboratory technique that can identify influenza viruses is clinically and epidemiologically desirable. The PLEX-ID Flu assay (Abbott Molecular Inc., Des Plaines, IL) incorporates multilocus PCR and electrospray ionization-mass spectrometry to detect and differentiate influenza A 2009 H1N1 (H1N1-p), seasonal H1N1 (H1N1-s), influenza A H3N2, and influenza B viruses in nasopharyngeal swab (NPS) specimens. The clinical performance characteristics of the PLEX-ID Flu assay in symptomatic patients were determined in this multicenter trial. A total of 2,617 prospectively and retrospectively collected NPS specimens from patients with influenza-like illness between February 2008 and 28 May 2010 were eligible for inclusion in the study. Each specimen was tested in parallel by the PLEX-ID Flu assay and by the Prodesse ProFLU+ assay (Prodesse Inc., Madison, WI), to detect influenza A and B viruses. Specimens testing positive for influenza A virus by ProFLU+ were subtyped as H1N1-p, H1N1-s, or H3N2 by using the ProFAST+ assay (Gen-Probe Prodesse Inc.). The reproducibility of the PLEX-ID Flu assay ranged from 98.3 to 100.0%, as determined by testing a nine-specimen panel at three clinical sites on each of 5 days. Positive percent agreements (PPAs) and negative percent agreements (NPAs) of the PLEX-ID Flu assay were 94.5% and 99.0% for influenza A virus and 96.0% and 99.9% for influenza B virus, respectively. For the influenza A virus subtyping characterization, the PLEX-ID Flu assay had PPAs and NPAs of 98.3% and 97.5% for H1N1-p, 88.6% and 100.0% for H1N1-s, and 98.0% and 99.9% for H3N2, respectively. The overall agreements between the PLEX-ID and Prodesse ProFLU+/ProFAST+ assays were 97.1 to 100.0%. Bidirectional Sanger sequencing analysis revealed that 87.5% of 96 discrepant results between the PLEX-ID Flu and ProFLU+/ProFAST+ assays were found upon influenza A virus detection and H1N1-p subtyping. The PLEX-ID Flu assay demonstrated a high level of accuracy for the simultaneous detection and identification of influenza A and B viruses in patient specimens, providing a new laboratory tool for the rapid diagnosis and management of influenza A and B virus infections.

Differences in cardiovascular disease mortality associated with body mass between Black and White persons.

We analyzed cardiovascular disease mortality risks associated with obesity using participant-level meta-analysis of data from the Black Pooling Project for Black and White individuals. The adjusted relative risks (ARRs) were stronger among White participants than among Black participants for coronary heart disease AAR=1.21 (95% confidence interval [CI]=1.07, 1.36) versus 0.87 (95% CI=0.69, 1.09), respectively, and cardiovascular disease ARR=1.18 (95% CI=1.07, 1.29) versus 0.91 (95% CI=0.77, 1.05), respectively. The results suggest that obesity is an independent risk factor in White people, and additional study of body size and disease progression is necessary in the assessment of racial disparities.

Age and race impact the association between BMI and CVD mortality in women.

OBJECTIVES: In previous studies, we have shown that obesity is associated with increased cardiovascular disease (CVD) mortality in white women but not in black women. Earlier research suggests that body mass index (BMI) has a greater effect on CVD mortality in younger white females than older white females, whereas this relationship in black women is not as clear. This study examines the effect of age on the association of BMI to CVD in black and white women. METHODS: The Black Pooling Project includes data on 2,843 black women with 50,464 person-years of follow-up, and 12,739 white women with 214,606 person-years of follow-up. A Cox proportional hazards model was used to examine the association between BMI and CVD mortality for specific age/race groups. The younger group was < 60 years of age and the older group was > 60 years of age. RESULTS: In younger white women, the relative risk (95% confidence interval [CI]) for CVD mortality was significant in obese women (BMI > 30 kg/m2) vs. women of normal weight (BMI 18.5-24.9 kg/m2) (1.59 [CI 1.20, 2.09]). Similarly, in older white women, the relative risk for CVD mortality in obese women vs. women of normal weight was significant (1.21 [CI 1.04, 1.41]). There were no such associations for black women. Overweight (BMI 25-29.9 kg/m2) was not associated with increased risk in black or white women. CONCLUSION: These findings indicate that obesity is associated with a significantly greater risk of CVD mortality among white women, with the strongest association among white women < 60 years of age.

Physical activity and health related quality of life among people with arthritis.

STUDY OBJECTIVE: To assess the association between physical activity and health related quality of life (HRQOL) among persons with arthritis or chronic joint symptoms (CJS). DESIGN: Cross sectional survey investigating the relation between physical activity level and HRQOL. HRQOL was estimated using the number of physically or mentally unhealthy days during the past 30 days. Physical activity was categorised as recommended, insufficient, or inactive according to federal activity recommendations. Persons with arthritis were defined as those with either self reported CJS or doctor diagnosed arthritis. SETTING: Community dwelling, US adults residing in all 50 states and the District of Columbia. PARTICIPANTS: Respondents (n = 212 000) in the 2001 behavioral risk factor surveillance system (BRFSS), an annual population based, telephone survey. MAIN RESULTS: The 33% of BRFSS respondents with arthritis had a mean of 6.7 physically and 4.9 mentally unhealthy days during the past 30 days, compared with 1.8 and 2.7 among those without arthritis. Inactive men and women were 1.2-2.4 times more likely to report impaired HRQOL compared with those who met physical activity recommendations. Men and women who engage in insufficient physical activity also report variably reduced HRQOL. CONCLUSIONS: Among people with arthritis, recommended levels of physical activity were associated with fewer mean physically and mentally unhealthy days and a decreased probability of having severely impaired physical or mental HRQOL.