Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis.

BACKGROUND: To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting. METHODS: Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI). RESULTS: ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were - 0.416 (- 0.796, - 0.060), - 0.195 (- 0.371, - 0.028), and - 0.196 (- 0.373, - 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab. CONCLUSION: Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188.

Lung adenocarcinoma patients with ROS1-rearranged tumors by sex and smoking intensity.

Background: ROS1 rearrangements (ROS1+) define a distinct molecular subset of lung adenocarcinomas. ROS1 + tumors are known to occur more in never-smokers, but the frequency and outcome of ROS1 positivity by sex and smoking intensity are not clearly documented. Patients and methods: This patient cohort study included all never- (<100 cigarettes lifetime) and light- (100 cigarettes-20 pack-years) smokers, and a sample of heavy-smokers. ROS1 + rates by sex and smoking intensity were compared within and beyond our study. Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards models. Results: Of the 571 total patients, ROS1 + was detected in 24 (4.2%): 6.4% in men and 3.0% in women; 5.1% in never-, 5.7% in light-, and 1.8% in heavy-smokers (P=0.05). Among the 209 stage IIIB-IV patients, men had much higher ROS1 + rate (11.1%) not only than women (1.7%, P=0.004) in our study, but also than men (0.4%-1.8%) in 8 published studies (Ps = 0.0019-0.0001). ROS1+ rates were similar between never- (9.3%) and light-smokers (8.1%) and significantly lower in heavy-smokers (1.2%, P=0.017), a finding confirmed by 6 published studies (Ps = 0.041-0.0001). Overall survival of ROS1 + patients were significantly better than the ROS1- (P=0.023) mainly due to targeted therapy. Among patients who exhibited resistance to crizotinib, follow-up treatment of entrectinib and lorlatinib showed remarkable survival benefits. Conclusions: The ROS1 + rates were higher in men than in women, and similar in never- and light-smokers, more pronounced in stage IIIB-IV patients. Newer-generation ALK/ROS1-targeted drugs showed efficacy in a cohort of crizotinib resistant ROS1 + patients. These results, when validated, could assist efficiently accruing ROS1 + patients.

A matching-adjusted indirect comparison of the efficacy of elranatamab versus teclistamab in patients with triple-class exposed/refractory multiple myeloma.

For patients with triple-class exposed/refractory multiple myeloma (TCE/RMM), where effective treatments options are limited, B-cell maturation antigen and CD3-directed bispecific antibodies offer a promising new approach. Teclistamab gained conditional approval in Europe and accelerated Food and Drug Administration (FDA) approval based on the MajesTEC-1 trial (NCT03145181). Elranatamab, approved by the FDA demonstrated its safety and efficacy in the MagnetisMM-3 trial (NCT04649359). Given the absence of head-to-head trials, an unanchored matching-adjusted indirect comparison (MAIC) was conducted to assess their relative efficacy. Key baseline characteristics were adjusted to be comparable between the two trials. In the MAIC, elranatamab demonstrated significantly better objective response rate and progression-free survival (PFS) than teclistamab, and numerically better complete response, duration of response, and overall survival (OS). These results suggest that elranatamab is an efficacious option for treating patients with TCE/R MM.

Effectiveness of BNT162b2 BA.4/5 Bivalent COVID-19 Vaccine against Long COVID Symptoms: A US Nationwide Study.

BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

From Qualitative Research to Quantitative Preference Elicitation: An Example in Invasive Meningococcal Disease.

BACKGROUND: Qualitative research is fundamental for designing discrete choice experiments (DCEs) but is often underreported in the preference literature. We developed a DCE to elicit preferences for vaccination against invasive meningococcal disease (IMD) among adolescents and young people (AYP) and parents and legal guardians (PLG) in the United States. This article reports the targeted literature review and qualitative interviews that informed the DCE design and demonstrates how to apply the recent reporting guidelines for qualitative developmental work in preference studies. METHODS: This study included two parts: a targeted literature review and qualitative interviews. The Medline and Embase databases were searched for quantitative and qualitative studies on IMD and immunization. The results of the targeted literature review informed a qualitative interview guide. Sixty-minute, online, semi-structured interviews with AYP and PLG were used to identify themes related to willingness to be vaccinated against IMD. Participants were recruited through a third-party recruiter's database and commercial online panels. Interviews included vignettes about IMD and vaccinations and three thresholding exercises examining the effect of incidence rate, disability rate, and fatality rate on vaccination preferences. Participant responses related to the themes were counted. RESULTS: The targeted literature review identified 31 concepts that were synthesized into six topics for the qualitative interviews. Twenty AYP aged 16-23 years and 20 PLG of adolescents aged 11-17 years were interviewed. Four themes related to willingness to be vaccinated emerged: attitudes towards vaccination, knowledge and information, perception of IMD, and vaccine attributes. Most participants were concerned about IMD (AYP 60%; PLG 85%) and had positive views of vaccination (AYP 80%; PLG 60%). Ninety percent of AYP and 75% of PLG always chose vaccination over no vaccination, independent of IMD incidence rate, disability rate, or fatality rate. CONCLUSION: Willingness to be vaccinated against IMD was affected by vaccine attributes but largely insensitive to IMD incidence and severity. This article provides an example of how to apply the recent reporting guidelines for qualitative developmental work in preference studies, with 21 out of 22 items in the guidelines being considered.

A comprehensive review and shiny application on the matching-adjusted indirect comparison.

Population-adjusted indirect comparison (PAIC) is an increasingly used technique for estimating the comparative effectiveness of different treatments for the health technology assessments when head-to-head trials are unavailable. Three commonly used PAIC methods include matching-adjusted indirect comparison (MAIC), simulated treatment comparison (STC), and multilevel network meta-regression (ML-NMR). MAIC enables researchers to achieve balanced covariate distribution across two independent trials when individual participant data are only available in one trial. In this article, we provide a comprehensive review of the MAIC methods, including their theoretical derivation, implicit assumptions, and connection to calibration estimation in survey sampling. We discuss the nuances between anchored and unanchored MAIC, as well as their required assumptions. Furthermore, we implement various MAIC methods in a user-friendly R Shiny application Shiny-MAIC. To our knowledge, it is the first Shiny application that implements various MAIC methods. The Shiny-MAIC application offers choice between anchored or unanchored MAIC, choice among different types of covariates and outcomes, and two variance estimators including bootstrap and robust standard errors. An example with simulated data is provided to demonstrate the utility of the Shiny-MAIC application, enabling a user-friendly approach conducting MAIC for healthcare decision-making. The Shiny-MAIC is freely available through the link: https://ziren.shinyapps.io/Shiny_MAIC/.

Appropriateness of conducting and reporting random-effects meta-analysis in oncology.

A random-effects model is often applied in meta-analysis when considerable heterogeneity among studies is observed due to the differences in patient characteristics, timeframe, treatment regimens, and other study characteristics. Since 2014, the journals Research Synthesis Methods and the Annals of Internal Medicine have published a few noteworthy papers that explained why the most widely used method for pooling heterogeneous studies-the DerSimonian-Laird (DL) estimator-can produce biased estimates with falsely high precision and recommended to use other several alternative methods. Nevertheless, more than half of studies (55.7%) published in top oncology-specific journals during 2015-2022 did not report any detailed method in the random-effects meta-analysis. Of the studies that did report the methodology used, the DL method was still the dominant one reported. Thus, while the authors recommend that Research Synthesis Methods and the Annals of Internal Medicine continue to increase the publication of its articles that report on specific methods for handling heterogeneity and use random-effects estimates that provide more accurate confidence limits than the DL estimator, other journals that publish meta-analyses in oncology (and presumably in other disease areas) are urged to do the same on a much larger scale than currently documented.

Patient experience and unmet needs in high-risk nonmuscle-invasive bladder cancer: Insights from qualitative interviews and a cross-sectional survey.

OBJECTIVES: To evaluate patient experience, unmet needs, and burden among patients with high-risk nonmuscle-invasive bladder cancer (HR-NMIBC) treated with Bacillus Calmette-Guérin (BCG). METHODS: This cross-sectional study included HR-NMIBC patients who received BCG treatment in the past 3 years. The study, preceded by a focused literature review, was conducted in 2 phases: 1) qualitative interviews with 32 patients in the United States (US), France, Germany, and United Kingdom (UK) and 2) quantitative survey of 150 patients in the US. Both phases of the study assessed patient characteristics, treatment history, experience, and perceptions, as well as side effects, pain, discomfort, and time burden associated with BCG treatment. The quantitative survey included additional items related to BCG treatment satisfaction, health-related quality of life (HRQoL), productivity, and healthcare resource utilization. Descriptive statistics and bivariate subgroup comparisons were reported. RESULTS: All patients in both study phases received transurethral resection of the bladder tumor (TURBT). Nearly all patients reported keeping their bladder/avoiding radical cystectomy (RC) was important (99%). Results from the quantitative survey reported a substantial impact to cancer-specific HRQoL of patients, with lower mean scores on physical (64.7), social (62.8), and role functioning (56.7) as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30). Most patients (69%) were satisfied overall with BCG treatment, although satisfaction declined with increased number of side effects, higher numbers of BCG administrations, and greater discomfort (all P < 0.05). CONCLUSIONS: Most HR-NMIBC patients were satisfied overall with BCG treatment. Approximately half of the patients had stopped BCG treatment, notably, most during the induction phase, suggesting nonadherence to guidelines which recommend maintenance treatment after induction. Future treatments should focus on delaying or avoiding recurrence and cystectomy while reducing patient discomfort and discontinuation prior to completing the recommended course of treatment.

Adult, adolescent, and caregiver preferences for attributes of topical treatments for mild-to-moderate atopic dermatitis: a discrete-choice experiment.

Purpose: Topical treatments for mild-to-moderate (MM) atopic dermatitis (AD) include emollients, corticosteroids, calcineurin inhibitors, a Janus kinase inhibitor, and a phosphodiesterase 4 inhibitor, which differ in multiple ways. This study aimed to quantify the conditional relative importance (CRI) of attributes of topical treatments for MM AD among adult and adolescent patients and caregivers of children with MM AD.Materials and methods: A discrete-choice experiment (DCE) survey was administered to US adults and adolescents with MM AD and caregivers of children with MM AD. Each choice task comprised 2 hypothetical topical treatments characterized by efficacy, adverse events, vehicle, and application frequency. Data were analyzed using a random-parameters logit model to calculate the CRI of each attribute.Results and conclusions: 300 adults, 331 adolescents, and 330 caregivers completed the DCE. Avoiding changes in skin color (CRI 29.0) and time until itch improves (26.6) were most important to adults, followed by time until clear/almost clear skin (17.8). Application frequency (3.0) did not have a statistically significant impact on adults' choices. Adolescents were less concerned about changes in skin color than adults or caregivers; caregivers were less concerned about time until clear/almost clear skin than patients. Physicians should consider age-relevant aspects of preferences in treatment discussions with patients and caregivers.

A matching-adjusted indirect comparison of the efficacy of elranatamab versus physician's choice of treatment in patients with triple-class exposed/refractory multiple myeloma.

INTRODUCTION: For patients with triple-class exposed/refractory multiple myeloma (TCE/R MM), prognosis is poor and effective treatment options are limited. Elranatamab is a novel B-cell maturation antigen (BCMA)- and CD3-directed bispecific antibody which was approved by the US Food and Drug Administration in August 2023 and demonstrated safety and efficacy in patients with TCE/R MM in the phase 2, single-arm MagnetisMM-3 trial (NCT04649359). To compare the effectiveness of elranatamab vs physician's choice of treatment (PCT) in the absence of head-to-head comparative data, a matching-adjusted indirect comparison (MAIC) was conducted. METHODS: Individual patient data from MagnetisMM-3 (Cohort A [BCMA-naïve] N = 123, 14.7 months of follow-up) were reweighted to match published summary data from two real-world studies of PCT in patients with TCE/R MM (LocoMMotion and MAMMOTH) using a propensity score-type logistic regression. Unanchored MAIC analyses were conducted according to National Institute for Health and Care Excellence (NICE) Decision Support Unit (DSU) 18 guidance. RESULTS: Compared with PCT in LocoMMotion, elranatamab was associated with a significantly higher objective response rate (ORR rate difference: 37.52; 95% CI 26.20-48.83; odds ratio: 4.85; 95% CI 2.85-8.23) and complete or stringent complete response rate (≥CR rate difference: 42.29; 95% CI 31.84-52.74; odds ratio: 184.01; 95% CI 24.66-1372.86), longer progression-free survival (PFS HR 0.32; 95% CI 0.20-0.49), and overall survival (OS HR 0.62; 95% CI 0.40-0.94). Compared with PCT in MAMMOTH, elranatamab was associated with significantly higher ORR (rate difference: 28.14; 95% CI 16.77-39.52; odds ratio: 3.24; 95% CI 1.98-5.32) and ≥ CR (rate difference: 26.22; 95% CI 16.40-36.05; odds ratio: 5.48; 95% CI 2.88-10.44), as well as longer PFS (HR 0.25; 95% CI 0.17-0.37) and OS (HR 0.49; 95% CI 0.33-0.71). Sensitivity analysis results were consistent with the base case. CONCLUSION: In the MAIC, elranatamab was consistently associated with improved rates and depth of response and significantly longer PFS and OS versus PCT in LocoMMotion and MAMMOTH.

Measures of functional status in older patients treated with palbociclib for advanced breast cancer.

INTRODUCTION: Limited data are available on the effects of treatment for advanced breast cancer (ABC) in older patients because this population has limited enrollment in clinical trials. Data generated from the prospective, noninterventional POLARIS study of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative ABC may help bridge the gap in our understanding of the tolerability and outcomes in this vulnerable population. MATERIALS AND METHODS: We evaluated measures of geriatric impairments and activities of daily living in patients with ABC aged ≥70 years in POLARIS to evaluate the change within six months of palbociclib initiation. Geriatric impairments and activities of daily living (functional) status were assessed using the Geriatric 8 (G8) and Activities of Daily Living (ADL) screening tools. The G8, ADL, and Eastern Cooperative Oncology Group performance status (ECOG PS) scores were assessed at baseline and month six through end of treatment with palbociclib. ECOG PS scores were also stratified by G8 and ADL score severity subgroups (G8: ≤14 = impaired subgroup; >14 = not at all impaired subgroup; ADL: <18 = dependent subgroup, 18 = independent subgroup). RESULTS: At data cutoff in November 2020, of 1282 POLARIS patients of all ages, 287 (22.4%) were ≥ 70 years old and completed ≥6 months of palbociclib therapy. At baseline, 117 (45%; n = 260) of these patients had an ECOG PS score of 0, 143 (55%; n = 260) had ECOG PS score > 0, 248 (86%) had G8 scores (mean [SD] 13.6 [2.14]), and 256 (89%) had ADL scores (17.7 [1.03]) among the available 287 patients. At six months, 102 (40%; n = 255) had an ECOG PS score of 0, 153 (60%; n = 255) had ECOG PS score > 0, 198 (69%) had G8 scores (13.6 [1.99]), and 211 (74%) had ADL scores (17.6 [1.22]) among the 287 available patients. There was no mean change (standard deviation) from baseline to 6 months in mean ECOG PS scores (0.0 [0.61], P = 0.24), G8 scores (0.0 [2.17], P = 0.89), or ADL scores (0.0 [1.00], P = 0.62). DISCUSSION: In this subgroup analysis of older patients with ABC from POLARIS, functional status and impairment outcomes were preserved in older patients receiving palbociclib. G8, ADL, and ECOG PS scores were generally maintained during the first six months of palbociclib therapy. CLINICALTRIALS: govidentification number. NCT03280303.

Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2.

BACKGROUND: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. METHODS: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. RESULTS: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. CONCLUSION: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. CLINICAL TRIAL REGISTRATION: NCT03575871.

Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib.

Outcomes of male patients with HR+/HER2- advanced breast cancer receiving palbociclib in the real-world POLARIS study.

PURPOSE: Data on treatments for male breast cancer patients are limited owing to rarity and underrepresentation in clinical trials. The real-world POLARIS study gathers data on palbociclib use for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in female and male patients. This sub-analysis describes real-world palbociclib treatment patterns, clinical outcomes, and quality of life (QoL) in male patients. METHODS: POLARIS is a prospective, noninterventional, multicenter, real-world study of patients with HR+/HER2- ABC receiving palbociclib. Assessments included medical record reviews, patient QoL questionnaires (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30), site characteristics questionnaires, and physician treatment selection surveys. Variables included demographics, disease history, global health status/QoL, clinical assessments and adverse events. Analyses were descriptive in nature. For clinical outcomes, real-world tumor responses and progression were determined by physician assessment in routine clinical practice. Real-world progression-free survival (rwPFS) was described using the Kaplan-Meier method. RESULTS: At data cutoff, 15 male patients were enrolled (median age, 66 years). Nine patients received palbociclib as a first-line treatment and 6 as a second-line or later treatment. Patients received a median of 20 cycles of palbociclib. Neutropenia was experienced by 2 patients and grade ≥ 3 adverse events were reported in 11 patients. Global health status/QoL scores remained generally consistent during the study. One patient (6.7%) achieved a complete tumor response, 4 (26.7%) a partial response, and 8 (53.3%) stable disease. Median rwPFS was 19.8 months (95% CI, 7.4-38.0). Median follow-up duration was 24.7 months (95% CI, 20.0-35.7). CONCLUSION: This real-world analysis showed that palbociclib was well tolerated and provides preliminary data on treatment patterns and outcomes with palbociclib in male patients with HR+/HER2- ABC, helping inform the use of palbociclib in this patient subgroup. TRIAL IDENTIFIER: NCT03280303.

Relationships of Work Productivity and Activity Impairment With Patient-Reported Outcomes in Ankylosing Spondylitis: Results From Two Trials.

OBJECTIVE: We examined the relationships of work productivity and activity impairment with key patient-reported outcomes (PROs) assessing pain, disease activity, and health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). METHODS: This post hoc analysis pooled available data from baseline to end of the double-blind phase of phase 2 and 3 placebo-controlled tofacitinib trials in patients with active AS. A repeated-measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5-Dimension 3-Level [EQ-5D-3L], and EQ-5D Visual Analog Scale [EQ-5D-VAS]) as predictors. RESULTS: Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%-23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. CONCLUSION: Evidence of linear relationships between work productivity and activity impairment with patient-reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS.

The Impact of the COVID-19 Pandemic on Patients with Ulcerative Colitis: Results from a Global Ulcerative Colitis Narrative Patient Survey.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created challenges related to disease management of patients with ulcerative colitis (UC). METHODS: The UC Narrative COVID-19 survey was conducted from August to December 2021 among adults with UC from the United States, Canada, Japan, France, and Finland. Patients were questioned on disease management, health care access and experience, and preferences for interactions with their doctor. Data were analyzed descriptively. RESULTS: In total, 584 patients qualified for and completed the survey. Compared with 2019, 25% experienced more flares during the pandemic (from early 2020). Most patients (88%) taking prescription medication were very/somewhat satisfied with their current treatment plan; 53% were hesitant to make changes during the pandemic. Factors that patients agreed helped control UC symptoms during the pandemic included fewer social outings (37%), working from home (29%), and less busy schedules (28%). Greater anxiety/stress (43%) and hesitancy to visit a hospital/office (34%) made the control of UC symptoms more difficult. Compared with 2019, more patients relied on certain alternative support systems during the pandemic. Patients who used in-person and virtual appointments were equally very satisfied/satisfied with the quality of care (both 81%). In-person appointments were preferred by 68% of patients when meeting a new doctor, 55% when experiencing a flare, and 52% for regular check-ups; 41% preferred virtual appointments for UC prescription refills. CONCLUSION: During the pandemic, most patients were satisfied with their current UC treatment plan and access to care; more patients relied on certain alternative UC management support systems, and many were impacted by anxiety/stress.

The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with ulcerative colitis. These challenges included managing symptoms, lifestyle changes, and access to health care. We asked patients with ulcerative colitis to answer questions about their experience during the pandemic to try to understand how the pandemic was affecting them. A total of 584 patients from the United States, Canada, Japan, France, and Finland took part. Patients were asked questions online. We asked them about their disease activity during the COVID-19 pandemic compared with before the pandemic and how their disease was managed, their access to health care, and their experience during the pandemic. We also asked them about their satisfaction with the types of appointments they had during the pandemic (for example, in-person or virtual meetings), and their interactions and preference for interactions with their doctors. We found that most patients were satisfied with their current treatment plan, their access to health care, and the quality of the care they received. However, many patients experienced greater stress or anxiety, and there was a negative impact on their emotional well-being. During the pandemic, more patients relied on alternative support systems such as online patient portals or virtual appointments, but patients preferred in-person appointments with their doctors in most cases except for refilling prescriptions. This information may help doctors understand the impact of the COVID-19 pandemic on patients with ulcerative colitis, and may help doctors and patients develop treatment plans that include both in-person and virtual appointments.

Reliability, validity, and change thresholds of the NCCN/FACT Bladder Symptom Index (NFBlSI-18) in patients with advanced urothelial cancer.

BACKGROUND: The NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) is a bladder cancer-specific instrument. We aimed to psychometrically evaluate the reliability and validity of NFBlSI-18 and estimate change thresholds for total, disease-related symptoms-physical (DRS-P), DRS-emotional (DRS-E), and function/well-being (F/WB) scales in patients with locally advanced/metastatic urothelial cancer (la/mUC). METHODS: JAVELIN Bladder 100 trial data were analyzed. Anchors to evaluate validity included: 5-level EuroQoL-5D utility index (EQ-5D-5L UI), visual analog scale (VAS), Eastern Cooperative Oncology Group (ECOG) performance status, and number of symptoms. Responsiveness to change was tested by anchoring to time to tumor progression (TTP), best overall response (BOR), and differences in means between ECOG categories to estimate meaningful between-group differences. Meaningful within-group change thresholds were estimated using receiver operating characteristic curve analysis, anchoring to change in EQ-5D-5L UI. Significant within-individual patient change thresholds were estimated with reliable and likely change indexes. RESULTS: Correlations with EQ-5D-5L UI and VAS ranged from 0.53 to 0.73. Standardized effect sizes were >0.20. Compared with patients with TTP of ≥6 months, patients with TTP of >0-2 and 3-5 months had larger declines; results for BOR were similar. Thresholds (points) for meaningful between-group differences were: total, 6-11; DRS-P, 3-6; and DRS-E and F/WB, 1. Thresholds (points) for meaningful within-group worsening were: total, 4; and DRS-P, 3, and for significant individual change they were: total, 3-9; DRS-P, 2-6; DRS-E, 1-3; and F/WB, 2-4. CONCLUSIONS: NFBlSI-18 exhibited evidence of reliability, validity, and responsiveness to assess quality of life in studies of la/mUC, and change thresholds are established for future studies. PLAIN LANGUAGE SUMMARY: The NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) is a questionnaire used to assess quality of life for people with advanced bladder cancer. People with advanced bladder cancer who took part in the JAVELIN Bladder 100 study completed the NFBlSI-18 when they joined the study and after each treatment with avelumab maintenance or best supportive care. This study showed that NFBlSI-18 is suitable for capturing bladder cancer symptoms and is able to detect important changes in a person's quality of life over time. This study also provides thresholds for changes in NFBlSI-18 scores, which will be useful for future studies.

Comorbidities in childhood atopic dermatitis: A population-based study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with allergic comorbidities. However, studies examining comorbidities in childhood AD are incomplete, which may contribute to suboptimal care. OBJECTIVE: The objective was to compare the risk of developing different allergic and non-allergic comorbidities among children with AD to that of a matched non-AD reference cohort in Sweden. METHODS: This was a nationwide population-based cohort study using longitudinal data from primary and specialist care registers. Patients with AD were identified by confirmed diagnosis in primary or specialist care. The non-AD reference cohort was randomly drawn from the general population and matched 1:1 with the AD patients. The risk of developing the following conditions was evaluated: hypersensitivity and allergic disorders, neurological disorders, psychiatric disorders, infections, immunological and inflammatory disorders, Type 1 diabetes (T1D), endocrine and metabolic disorders, skeletal disorders, ocular disorders and malignancies. RESULTS: This study included 165,145 patients with AD (mild-to-moderate [n = 126,681] and severe [n = 38,464]) and an equally sized reference cohort. Patients with AD displayed a higher risk of developing comorbid conditions for all investigated categories, except for T1D and skeletal disorders, compared with the reference cohort. The highest risk compared with the reference cohort was observed for hypersensitivity and allergic disorders (hazard ratio [HR]: 3.87), followed by malignancies (HR: 2.53) and immunological and inflammatory disorders (HR: 2.36). Patients with AD also had higher risk of developing multiple comorbidities (≥2). The risk of comorbidity onset increased alongside AD severity and patients with active AD were associated with increased risk of comorbidity onset compared with patients in remission. CONCLUSIONS: The clinical burden of AD is substantial for children with AD and patients are at an increased risk of developing several comorbid conditions extending beyond the atopic march. Our results also showed a positive association between worsening severity of AD and an increased risk of comorbidity onset.

Double-Negative Results Matter: A Reevaluation of Sensitivities for Detecting SARS-CoV-2 Infection Using Saliva Versus Nasopharyngeal Swabs.

In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.

Correction: The Patient Experience of Acute Lymphoblastic Leukemia and Its Treatment: Social Media Review.

[This corrects the article DOI: 10.2196/39852.].

Systematic Literature Review: Ability of the IBDQ-32 to Detect Meaningful Change in Ulcerative Colitis Health Indicators.

PURPOSE: Previous reviews produced weak evidence regarding the responsiveness of the Inflammatory Bowel Disease Questionnaire (IBDQ-32) to changes in ulcerative colitis (UC) health indicators. This systematic review and meta-analysis provide an updated synthesis on IBDQ-32 responsiveness. METHODS: A systematic literature review identified 11 articles reporting IBDQ-32 responder analyses in randomized control trials, which were included in a random effects meta-analysis, and 15 articles linking IBDQ-32 change to change in UC health indicators, which were summarized narratively. Meta-analysis compared differences between IBDQ-32 responder proportions in efficacious and nonefficacious treatment arms relative to placebo. Linear meta-regression examined the association of treatment efficacy and proportions of IBDQ-32 responders in active treatment compared with placebo. RESULTS: Meta-analysis showed larger differences in IBDQ-32 response proportions between active treatment and placebo for efficacious treatments (pooled OR, 2.19; 95% CI, 1.83-2.63) than nonefficacious treatments (pooled OR, 1.21; 95% CI, 0.84-1.74; Cochran's Q[df = 1] = 8.26, P = .004). Meta-regression showed that the magnitude of treatment efficacy positively predicted IBDQ-32 response in active treatments relative to placebo (ß = 0.21, P < .001). Moderate to strong correlations were found between change in IBDQ-32 and change in health indicators (eg, patient-reported measures, disease activity, endoscopic indices; correlations, 0.37-0.64 in absolute values). Patients achieving clinical response or remission showed greater change in IBDQ-32 total scores (range, 22.3-50.1 points) and more frequently met clinically meaningful thresholds on the IBDQ-32 than those not achieving clinical response or remission (all P < .05). CONCLUSIONS: The IBDQ-32 is responsive to changes in UC health indicators and disease activity, including in response to efficacious treatment (relative to placebo).

This article presents a review of evidence on the responsiveness of the 32-item Inflammatory Bowel Disease Questionnaire, a widely used patient-report measure of health-related quality of life. W found a generally good ability of the instrument to detect changes in ulcerative colitis health that are meaningful to patients and clinicians.