The Capio Prostate Cancer Center Model for Prostate Cancer Diagnostics-Real-world Evidence from 2018 to 2022.

Background: The Capio Prostate Cancer Center (Capio PCC) in Stockholm, Sweden, adopts a comprehensive diagnostic approach, utilizing prostate-specific antigen (PSA), Stockholm3, and magnetic resonance imaging (MRI) for prostate cancer risk assessment, followed by targeted and systematic biopsies for high-risk cases. Objective: This study aims to elucidate the clinical process and real-world outcomes of the Capio PCC model for prostate cancer diagnosis at Capio S:t Göran Hospital. Design setting and participants: Between 2018 and 2022, a cohort of 12 406 men aged 45-75 yr underwent prostate cancer testing, adhering to Capio PCC's structured diagnostic protocol. Outcome measurements and statistical analysis: We provide a comprehensive description of the Capio PCC model and present results from its implementation, including assessments of PSA, Stockholm3, MRI scans, and biopsies. A comparative analysis is conducted between the diagnostic outcomes obtained at Capio PCC and those obtained at other regions in Sweden. Results and limitations: The median participant age was 61 yr (interquartile range [IQR]: 55-67), with PSA levels at 1.6 ng/ml (IQR: 0.8-3.3) and Stockholm3 scores at 4 (IQR: 3-11). Among 1064 men (8.6%) undergoing biopsies, 611 (57% of biopsied) were diagnosed with International Society of Urological Pathology grade ≥ 2 cancer. Notably, employing a Stockholm3 ≥ 15 cutoff for biopsy, in lieu of PSA ≥ 3 ng/ml, reduced biopsy recommendations by 43%. For men with PSA levels between 1.5 and 2.9 ng/ml, 360 (12%) exhibited Stockholm3 scores of ≥ 15, with 72 (56% of biopsied) diagnosed with clinically significant prostate cancer. A comparative analysis with national Swedish prostate cancer detection data indicated that the Capio PCC model (vs Sweden) revealed a distribution of 14% (vs 25%) low-risk, 59% (vs 42%) intermediate-risk, and 26% (vs 30%) high-risk and advanced cancers. Conclusions: This study underscores the effectiveness of the protocol-driven diagnostic process at Capio PCC, enabling earlier detection of intermediate-risk prostate cancer and reducing the need for MRI assessments compared with standard prostate cancer care in Sweden. Patient summary: At the Capio Prostate Cancer Center, a novel diagnostic approach incorporating prostate-specific antigen, Stockholm3, magnetic resonance imaging, and targeted biopsies has been implemented to enhance prostate cancer testing and diagnosis in Stockholm, Sweden.

One-Year Medication Adherence and Persistence in Rheumatoid Arthritis in Clinical Practice: A Retrospective Analysis of Upadacitinib, Adalimumab, Baricitinib, and Tofacitinib.

INTRODUCTION: This study evaluated 12 months adherence and persistence among Janus kinase inhibitors (upadacitinib, baricitinib, tofacitinib) and adalimumab, a tumor necrosis factor inhibitor (TNFi), in patients with rheumatoid arthritis (RA). METHODS: This retrospective analysis used administrative claims data from the Merative™ MarketScan® Research Databases (2018-2022). Eligible adults had ≥ 1 RA diagnosis before the index date, ≥ 1 pharmacy claim for index medication, and ≥ 12 months of continuous insurance enrollment pre- and post-index. Adherence to treatment [defined as proportion of days covered (PDC) ≥ 80%], risk of treatment discontinuation, and mean time to discontinuation were assessed during the 12 months follow-up. Adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) were reported. RESULTS: In total, 6317 patients were included (683 upadacitinib, 3732 adalimumab, 132 baricitinib, 1770 tofacitinib). Compared with upadacitinib, patients initiating adalimumab [aOR (95% CI): 0.82 (0.69, 0.96)], baricitinib [0.46 (0.31, 0.68)], and tofacitinib [0.74 (0.62, 0.88)] were significantly less likely to achieve PDC ≥ 80%. Risk of treatment discontinuation was significantly higher in patients treated with adalimumab [aHR (95% CI): 1.14 (1.01, 1.29)], baricitinib [1.48 (1.16, 1.90)], and tofacitinib [1.22 (1.07, 1.38)] compared with upadacitinib. Mean time to discontinuation was 256 (upadacitinib), 249 (adalimumab), 221 (baricitinib), and 239 (tofacitinib) days. Similar results were observed in patients with prior TNFi use. CONCLUSIONS: Patients with RA, regardless of recent TNFi experience, initiating upadacitinib were significantly more likely to be adherent and less likely to discontinue therapy compared to adalimumab, baricitinib, and tofacitinib in the first 12 months of treatment.

[Improved prostate cancer diagnostics with a structured pathway including ¼Stockholm 3« test, MRI and targeted perineal biopsies]. / Strukturerad kedja vid test för prostatacancer kortar ledtider.

The Prostate Cancer Center at Capio S:t Göran hospital is located in Stockholm and offers testing for prostate cancer. The pathway applies task shifting from doctors to nurses and new and innovative test methods, and leverages digitalization opportunities to enable a cost-efficient pathway with high specificity and sensitivity. In this article, we describe our experiences of the Capio S:t Göran Model.

Clinical and Economic Benefit of Achieving Disease Control in Psoriatic Arthritis and Ankylosing Spondylitis: A Retrospective Analysis from the OM1 Registry.

BACKGROUND: There is limited evidence on the clinical and economic benefit of achieving disease control in psoriatic arthritis (PsA) and ankylosing spondylitis (AS), thus we aimed to assess the impact of disease control on healthcare resource use (HCRU) and direct medical costs among US patients with PsA or AS over 1 year. METHODS: Data were derived from the US OM1 PsA/AS registries (PsA: 1/2013-12/2020; AS: 01/2013-4/2021) and the Optum Insight Clinformatics® Data Mart to identify adult patients with PsA or AS. Two cohorts were created: with disease control and without disease control. Disease control was defined as modified Disease Activity Index for Psoriatic Arthritis (DAPSA28) ≤ 4 for PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4 for AS. Outcomes were all-cause inpatient, outpatient, and emergency department (ED) visits and associated costs over a 1-year follow-up period. Mean costs per person per year (PPPY) were assessed descriptively and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated for the likelihood of HCRU by logistic regression. RESULTS: The study included 1235 PsA (with disease control: N = 217; without: N = 1018) and 581 AS patients (with disease control: N = 342; without: N = 239). Patients without disease control were more likely to have an inpatient (aOR [95% CI]; PsA: 3.0 [0.9, 10.1]; AS: 7.7 [2.3, 25.1]) or ED (PsA: 1.6 [0.6, 4.2]; AS: 3.5 [1.5, 8.3]) visit than those with disease control. Those without disease control, vs. those with disease control, had greater PPPY costs associated with inpatient (PsA: $1550 vs. $443), outpatient (PsA: $1789 vs. $1327; AS: $2498 vs. $2023), and ED (PsA: $114 vs. $57; AS: $316 vs. $50) visits. CONCLUSIONS: Findings from this study demonstrate lower disease activity among patients with PsA and AS is associated with less HCRU and lower costs over the following year.

Media use and trust during the COVID-19 pandemic: evidence from eight cross-sectional surveys in Sweden.

BACKGROUND: While a lot has been written about Sweden's COVID-19 control strategy, less is known about Swedish residents' media use during the pandemic and trust in and perceived agreement among key stakeholders commenting in the media. METHODS: Eight online, nationwide surveys were fielded between March and August 2020, during the first wave of the coronavirus pandemic in Sweden, with 8146 responses. Questions were asked on media usage, perceived tone of media, trust in key pandemic stakeholder groups commenting in the media (politicians, journalists, government officials, doctors/healthcare professionals and researchers) and perceived agreement among these key stakeholders about how the pandemic was handled in Sweden. RESULTS: Using five or more information sources was associated with increased perceived alarmism in the media. Women and those with tertiary education were more likely to trust key pandemic actors. Trust in doctors/healthcare professionals and researchers remained high over the course of the study, trust in politicians and journalists was relatively low throughout the study period, with a slight increase in April 2020. Trust in key stakeholders was strongly associated with perceived agreement among the key stakeholders. CONCLUSIONS: Our results show that trust in stakeholders was strongly associated with perceived consistency of messages from those stakeholders. The inverse also holds: perceived conflicting messages among stakeholders was associated with low trust in them. Taken together, this could point to the importance of building trust before a crisis. Trust-building efforts could be targeted to men and those with lower educational attainment, as they had lower trust in key stakeholders.

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials.

INTRODUCTION: The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program. METHODS: This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients. RESULTS: A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32-52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19-28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001). CONCLUSIONS: Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA. TRIAL REGISTRATION: SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).

Rheumatoid arthritis (RA) is a disease that causes inflammation of the joints. Doctors have several ways of assessing how bad a patient's disease is, and these often use a combination of signs and symptoms to develop a 'score'. One method is called RAPID3, which is a score based on an overall assessment of the disease by the patient, the level of pain, and the amount of physical disability. An advantage of RAPID3 is that it is quick and easy to use, and since it uses only patient-reported symptoms, it can be measured easily via telemedicine, without the need for an in-person consultation. In this study, we decided to look into the effect of upadacitinib, a drug used for the treatment of RA, on RAPID3 score in patients with RA. We also investigated whether RAPID3 correlates with other ways of measuring RA severity, including scores that use physician-measured factors such as number of affected joints, as this can help show whether RAPID3 is a valid and useful tool. We found that upadacitinib led to long-term improvements in RAPID3 score, and that results were the same in different studies and patient groups, including patients who had not responded well to other treatments. We also found that RAPID3 correlated well with other measures, i.e., improvements in RAPID3 happened in parallel with improvements in other scores. Overall, these results suggest that RAPID3 can be a useful tool in patients with RA.

Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial.

BACKGROUND: In previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR). METHODS: Patients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient's assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests. RESULTS: Data from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores (P<0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05). CONCLUSIONS: At week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment. TRIAL REGISTRATION: NCT03086343 , March 22, 2017.

Baseline Disease Activity Predicts Achievement of cDAPSA Treatment Targets With Apremilast: Phase III Results in DMARD-naïve Patients With Psoriatic Arthritis.

OBJECTIVE: The probability of achieving Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) treatment targets (remission [REM], low disease activity [LDA]) was evaluated following apremilast monotherapy in disease-modifying antirheumatic drug (DMARD)-naïve patients with psoriatic arthritis (PsA) based on baseline disease activity. METHODS: This post hoc probability analysis of PALACE 4, a phase III, multicenter, randomized, placebo-controlled study, evaluated shifting across cDAPSA categories from baseline to week 52 and included DMARD-naïve patients receiving apremilast 30 mg BID with available baseline cDAPSA data. Changes in articular/extraarticular manifestations were evaluated in patients with week 52 cDAPSA components. cDAPSA treatment target achievement was assessed in a subgroup with baseline extraarticular PsA manifestations (skin involvement, enthesitis, dactylitis). RESULTS: Of 175 apremilast-treated patients in the probability analysis, 66.3% were in high disease activity (HDA) and 31.4% in moderate disease activity (ModDA) at baseline. Approximately twice as many patients in ModDA at baseline reached REM/LDA at week 52 vs those in HDA (61.7% vs 28.2%). Achieving cDAPSA treatment targets was associated with reductions in articular (swollen/tender joints) and extraarticular (skin involvement, enthesitis, dactylitis, functional disability) disease activity. Similar treatment target achievement rates were observed in the subgroup with ≥ 1 extraarticular PsA manifestation (n = 126; ModDA: 66.7%, HDA: 32.2%). CONCLUSION: Apremilast-treated patients with baseline ModDA had higher probability of achieving cDAPSA treatment targets than patients with HDA. Resolution and/or near resolution of articular and/or extraarticular PsA manifestations was achieved by patients in REM/LDA at week 52. Consistent treatment target achievement was observed in patients with 1 or multiple extraarticular manifestations of active PsA.

The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial.

BACKGROUND: The phase 3 FUTURE 5 trial (NCT02404350) showed the clinical and radiographical efficacy of secukinumab in patients with psoriatic arthritis. This analysis aimed to assess the effect of secukinumab on patient-reported outcomes (PROs). METHODS: FUTURE 5 was a phase 3, multicentre, parallel-group randomised trial in which patients who were 18 years old or older, met the classification criteria for psoriatic arthritis at screening, and had symptoms of moderate-to-severe psoriatic arthritis for at least 6 months were randomly assigned to receive secukinumab 300 mg, 150 mg, 150 mg no loading dose (NL), or placebo weekly from baseline to week 4 and every 4 weeks thereafter. The prespecified PROs of the FUTURE 5 trial were assessed first in the overall population. We report mean changes from baseline and the proportion of patients reporting improvements equal to or more than the minimum clinically important differences (MCIDs) and scores equal to or more than the normative values for patient global assessments (PtGA) of disease activity; psoriasis and arthritis visual analogue scale (VAS) scores; pain VAS; Health Assessment Questionnaire Disability Index (HAQ-DI); 36-item Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F); and quality of life questionnaires. Patients were then stratified and assessed according to their tumour necrosis factor (TNF) inhibitor status (TNF-naive and TNF-inadequate responder [TNF-IR] populations) as a post-hoc analysis. FINDINGS: Patients in all secukinumab groups reported significant least-squares mean changes from placebo at week 16 in all PROs except SF-36 mental component summary (MCS), irrespective of TNF inhibitor use. These included PtGA (300 mg difference vs placebo -12·2 [95% CI -16·3 to -8·1], 150 mg -8·22 [-12·4 to -4·1], 150 mg NL -8·3 [-12·5 to -4·2]; all p<0·0001), pain VAS (300 mg -14·3 [-18·3 to -10·2], 150 mg -11·5 [-15·6 to -7·5], 150 mg NL -11·3 [-15·3 to -7·2]; all p<0·0001), HAQ-DI (300 mg -0·33 [-0·42 to -0·24], 150 mg -0·23 [-0·32 to -0·14], 150 mg NL -0·24 [-0·33 to -0·15]; all p<0·0001), and FACIT-F (300 mg 4·8 [3·2 to 6·4], 150 mg 4·2 [2·6 to 5·8], 150 mg NL 3·5 [1·9 to 5·1]; all p<0·0001). Similarly, the proportion of patients with improvements equal to or better than MCID at week 16 was higher in the secukinumab group compared with the placebo group for most PROs except SF-36 (MCS), regardless of TNF inhibitor use. INTERPRETATION: Secukinumab resulted in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses compared with placebo in patients with active psoriatic arthritis. These improvements were seen irrespective of previous TNF inhibitor use, in a post-hoc analysis. These results indicate that secukinumab provides comprehensive improvement for patients with psoriatic arthritis, regardless of previous therapy. FUNDING: Novartis.

Guided therapy selection in rheumatoid arthritis using a molecular signature response classifier: an assessment of budget impact and clinical utility.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) can be treated with a range of targeted therapies following inadequate response to conventional synthetic disease-modifying antirheumatic drugs such as methotrexate. Whereas clinical practice guidelines provide no formal recommendations for initial targeted therapies, the tumor necrosis factor alpha inhibitor (TNFi) class is the prevalent first-line selection based on clinician experience, its safety profile, and/or formulary requirements, while also being the costliest. Most patients do not achieve adequate clinical response with a first-line TNFi, however. A molecular signature response classifier (MSRC) test that assesses RA-related biomarkers can identify patients who are unlikely to achieve adequate response to TNFi-class therapies. OBJECTIVE: To model cost-effectiveness of MSRC-guided, first-line targeted therapy selection compared with current standard care. METHODS: This budget impact analysis used data sourced from August to September 2020. The prevalence of each first-line targeted therapy was obtained using market intelligence from Datamonitor/Informa PLC Rheumatology Dashboard Forecast 2020, and the average first-year cost of treatment for each class was calculated using wholesale acquisition costs from IBM Micromedex RED BOOK Online. Average effectiveness for each class was based on manufacturer-reported ACR50 response rates (American College of Rheumatology adequate response criteria of 50% improvement at 6 months after therapy initiation). The impact of MSRC testing on first therapy selection was predicted based on a third party-generated decision-impact study that analyzed potential alterations in rheumatologist prescribing patterns after receiving MSRC test reports. Sensitivity analysis evaluated potential impacts of variation in first-year medication cost, adherence to MSRC report, and test price on the first-year cost of treatment. Cost for response (first-year therapy cost therapy divided by probability of achieving ACR50) was compared between standard care and MSRC-guided care. RESULTS: The estimated cost for first-year, standard-care treatment was $65,117, with 80% of patients initiating treatment with a TNFi. Cost for achieving ACR50 response was $177,046. After applying MSRC-guided patient stratification and therapy selection, the first-year cost was $56,543, net of test price, with 49.0% of patients initiating with a TNFi. First-year MSRC-guided care cost, including test price, was estimated at $117,103, a 33.9% improvement over standard care. Sensitivity analysis showed a net cost improvement for guided care vs standard care across all scenarios. Patients predicted to be inadequate TNFi responders, when modeled with lower-priced alternatives, were predicted to show increased ACR50 response rates. Those with MSRC test results indicating a first-line TNFi were predicted to show an ACR50 response rate superior to that for any other class. In this model, if implemented clinically, MSRC-guided care might save the US health care system more than $850 million annually and improve ACR50 by up to 31.3%. CONCLUSIONS: Precision medicine using MSRC-guided patient stratification and therapy selection may both decrease cost and improve efficacy of targeted RA therapies. DISCLOSURES: This work was funded in full by Scipher Medicine Corporation, which participated in data analysis and interpretation and drafting, reviewing, and approving the publication. All authors contributed to data analysis and interpretation and publication preparation, maintaining control over the final content. Arnell, Withers, and Connolly-Strong are employees of and have stock ownership in Scipher Medicine Corporation. Bergman has received consulting fees from AbbVie, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Sanofi, and Scipher Medicine and owns stock or stock options in Johnson & Johnson. Kenney, Logan, and Lim-Harashima are consultants for Scipher Medicine Corporation. Basu has nothing to disclose.

Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis.

INTRODUCTION: To compare the economic benefit of upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy from improvements in health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from two trials of upadacitinib (SELECT-NEXT and SELECT-MONOTHERAPY) and one trial of tofacitinib (ORAL-Standard) that collected HRQOL measurements using the Short Form 36 (SF-36) Health Survey in patients with RA. Direct medical costs per patient per month (PPPM) for patients receiving upadacitinib 15 mg once daily and methotrexate were derived from observed SF-36 Physical (PCS) and Mental Component Summary (MCS) scores in the SELECT trials using a regression algorithm. Direct medical costs PPPM for patients receiving tofacitinib 5 mg twice daily were obtained from a published analysis of SF-36 PCS and MCS scores observed in the ORAL-Standard trial. Short-term (12-14 weeks) and long-term (48 weeks) estimates of direct medical costs PPPM were compared between upadacitinib and tofacitinib and between upadacitinib and methotrexate. RESULTS: Over 12 weeks, direct medical costs PPPM were $252 lower (95% CI $72, $446) for upadacitinib-treated patients versus tofacitinib-treated patients. Medical costs PPPM at weeks 24 and 48 and cumulative costs over the entire 48-week period (difference $1759; 95% CI $1162, $2449) were significantly lower for upadacitinib than for tofacitinib. Over 14 weeks, direct medical costs PPPM were $399 lower (95% CI $158, $620) for patients treated with upadacitinib monotherapy compared with those treated with methotrexate alone. Direct medical costs at week 48 and cumulative costs over the entire 48-week period (difference $2044; 95% CI $1221, $2846) were significantly lower for upadacitinib monotherapy compared with methotrexate alone. CONCLUSION: In the short and long term, upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy were associated with significantly lower direct medical costs for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02675426, NCT02706951, and NCT00853385.

Seeing the world through the eyes of a butterfly: visual ecology of the territorial males of Pararge aegeria (Lepidoptera: Nymphalidae).

Combining studies of animal visual systems with exact imaging of their visual environment can get us a step closer to understand how animals see their "Umwelt". Here, we have combined both methods to better understand how males of the speckled wood butterfly, Pararge aegeria, see the surroundings of their perches. These males are well known to sit and wait for a chance to mate with a passing females, in sunspot territories in European forests. We provide a detailed description of the males' body and head posture, viewing direction, visual field and spatial resolution, as well as the visual environment. Pararge aegeria has sexually dimorphic eyes, the smallest interommatidial angles of males are around 1°, those of females 1.5°. Perching males face the antisolar direction with their retinal region of the highest resolution pointing at an angle of about 45° above the horizon; thus, looking at a rather even and dark background in front of which they likely have the best chance to detect a sunlit female passing through the sunspot.

Healthcare Resource Use in Patients with Immune-Mediated Conditions Treated with Targeted Immunomodulators During COVID-19 Pandemic: A Retrospective Claims Analysis.

INTRODUCTION: The impact of the COVID-19 pandemic on routine medical care may result in altered healthcare resource use in patients with immune-mediated conditions. The aim of this study was to determine the impact of treatment interruptions in patients with and without COVID-19 infections who were treated with targeted immunomodulators (TIMs) in the USA. METHODS: Data from the IBM® MarketScan® Research Databases were analyzed in patients with immune-mediated conditions from January 1, 2018, through December 31, 2020. Healthcare resource use (HCRU) including hospitalizations, emergency department (ED) visits, in-person outpatient visits, and respiratory outcomes was assessed in a cohort of patients without COVID-19 who had uninterrupted versus interrupted TIM use. The impact of treatment interruption on HCRU and respiratory outcomes was also evaluated in a cohort of patients with COVID-19. Results from adjusted logistic regression were reported as adjusted odds ratios (aORs) with 95% confidence intervals. RESULTS: Approximately 25% of patients in both the COVID-19 (N = 787) and non-COVID-19 cohorts (N = 77,178) experienced interruptions in TIM therapy. In the non-COVID-19 cohort, the likelihood of being hospitalized was 20% less in patients with uninterrupted versus interrupted TIM use (aOR = 0.80, 95% CI 0.71-0.90). Patients with uninterrupted TIM use had a similar likelihood of an ED visit (aOR = 0.99, 95% CI 0.91-1.08) and respiratory outcome (aOR = 0.97, 95% CI 0.71-1.31) versus patients with interrupted TIM use. The likelihood of having an in-person outpatient visit was 87% greater in patients with uninterrupted versus interrupted TIM use (aOR = 1.87, 95% CI 1.81-1.94). Similar findings were observed in the COVID-19 cohort. CONCLUSION: This analysis of real-world claims data showed that uninterrupted TIM use was not associated with an increased likelihood of hospitalizations, ED visits, or negative respiratory outcomes compared to interrupted TIM use among patients with immune-mediated conditions, regardless of COVID-19 diagnosis.

Identifying Prostate Cancer Among Men with Lower Urinary Tract Symptoms.

BACKGROUND: In men aged above 50 yr, lower urinary tract symptoms (LUTS), benign prostate hyperplasia, and prostate cancer are common urological conditions. Current guidelines for general practitioners frequently recommend prostate-specific antigen (PSA) testing in patients with LUTS for the detection of prostate cancer. OBJECTIVE: To assess the performance of PSA, PSA density, and the Stockholm3 blood test for identification of prostate cancer among men with LUTS. DESIGN SETTING AND PARTICIPANTS: In this post hoc analysis of a population-based diagnostic trial (STHLM3, n = 58 588), 4588 men aged 50-69 yr, without previous prostate cancer, with International Prostate Symptom Score (IPSS) data, and having PSA ≥ 3 ng/mL were identified. Men with at least moderate LUTS, defined as an IPSS score of ≥8, were included. PSA density and Stockholm3 scores were calculated. INTERVENTION: Participants underwent 10-12-core systematic prostate biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was significant prostate cancer (sPCa) defined as International Society of Urological Pathology (ISUP) grade ≥2. Logistic regression analysis adjusted for age and previous biopsy status was performed. The area under the receiver operating characteristic curve (AUC) was calculated, and decision curve analysis was performed. RESULTS AND LIMITATIONS: Out of 4588 men, 1544 (34%) reported at least moderate LUTS. The median age was 64 yr, and 11% had undergone a previous prostate biopsy. The Stockholm3 test showed superior discrimination for sPCa to PSA density, which in turn showed superior discrimination to PSA (AUC 0.77 vs 0.70 vs 0.61, p <  0.02). Calibration of the Stockholm3 test was adequate. Performing biopsy only in men with PSA ≥5 ng/mL saved 64% of biopsies, but resulted in missing 52% of detectable sPCa. Recommending biopsy for men with PSA density ≥0.07 resulted in sparing 26% of biopsy procedures and delaying the diagnosis of 12% of sPCa cases, with a 6.1% risk of sPCa among unbiopsied men. Recommending men with Stockholm3 ≥ 0.11 for biopsy resulted in sparing 53% of biopsy procedures and delaying the diagnosis of 20% of sPCa cases, with a 5.1% risk of finding sPCa in unbiopsied men. CONCLUSIONS: PSA density and the Stockholm3 blood test were superior to PSA for the identification of prostate cancer among men with LUTS. PATIENT SUMMARY: In this analysis of a large Swedish study, we find that the use of prostate-specific antigen (PSA) density or the Stockholm3 blood test instead of only PSA might improve the detection of prostate cancer among men with lower urinary tract symptoms.

Prostate cancer screening using a combination of risk-prediction, MRI, and targeted prostate biopsies (STHLM3-MRI): a prospective, population-based, randomised, open-label, non-inferiority trial.

BACKGROUND: Screening for prostate cancer using prostate-specific antigen (PSA) reduces prostate cancer mortality but can lead to adverse outcomes. We aimed to compare a traditional screening approach with a diagnostic strategy of blood-based risk prediction combined with MRI-targeted biopsies. METHODS: We did a prospective, population-based, randomised, open-label, non-inferiority trial (STHLM3-MRI) in Stockholm county, Sweden. Men aged 50-74 years were randomly selected by Statistics Sweden and invited by mail to participate in screening; those with an elevated risk of prostate cancer, defined as either a PSA of 3 ng/mL or higher or a Stockholm3 score of 0·11 or higher were eligible for randomisation. Men with a previous prostate cancer diagnosis, who had undergone a prostate biopsy within 60 days before the invitation to participate, with a contraindication for MRI, or with severe illness were excluded. Eligible participants were randomly assigned (2:3) using computer-generated blocks of five, stratified by clinically significant prostate cancer risk, to receive either systematic prostate biopsies (standard group) or biparametric MRI followed by MRI-targeted and systematic biopsy in MRI-positive participants (experimental group). The primary outcome was the detection of clinically significant prostate cancer at prostate biopsy, defined as a Gleason score of 3 + 4 or higher. We used a margin of 0·78 to assess non-inferiority for the primary outcome. Key secondary outcome measures included the proportion of men with clinically insignificant prostate cancer (defined as a Gleason score of 3 + 3), and the number of any prostate MRI and biopsy procedures done. We did two comparisons: Stockholm3 (using scores of 0·11 and 0·15 as cutoffs) versus PSA in the experimental group (paired analyses) and PSA plus standard biopsy versus Stockholm3 plus MRI-targeted and systematic biopsy (unpaired, randomised analyses). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT03377881. FINDINGS: Between Feb 5, 2018, and March 4, 2020, 49 118 men were invited to participate, of whom 12 750 were enrolled and provided blood specimens, and 2293 with elevated risk were randomly assigned to the experimental group (n=1372) or the standard group (n=921). The area under the receiver-operating characteristic curve for detection of clinically significant prostate cancer was 0·76 (95% CI 0·72-0·80) for Stockholm3 and 0·60 (0·54-0·65) for PSA. In the experimental group, a Stockholm3 of 0·11 or higher was non-inferior to a PSA of 3 ng/mL or higher for detection of clinically significant prostate cancer (227 vs 192; relative proportion [RP] 1·18 [95% CI 1·09-1·28], p<0·0001 for non-inferiority), and also detected a similar number of low-grade prostate cancers (50 vs 41; 1·22 [0·96-1·55], p=0·053 for superiority) and was associated with more MRIs and biopsies. Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures (545 vs 846; 0·64 [0·55-0·82]) and fewer biopsy procedures (311 vs 338; 0·92 (0·86-1·03). Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3·0%] men tested vs 106 [2·1%] men tested; RP 1·44 [95% CI 1·15-1·81]), lower detection of low-grade cancers (50 [0·7%] vs 73 [1·4%]; 0·46 [0·32-0·66]), and led to fewer biopsy procedures. Patients randomly assigned to the experimental group had a lower incidence of prescription of antibiotics for infection (25 [1·8%] of 1372 vs 41 [4·4%] of 921; p=0·0002) and a lower incidence of admission to hospital (16 [1·2%] vs 31 [3·4%]; p=0·0003) than those in the standard group. INTERPRETATION: The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer. FUNDING: The Swedish Cancer Society, the Swedish Research Council, and Stockholm City Council.

MRI-Targeted or Standard Biopsy in Prostate Cancer Screening.

BACKGROUND: High rates of overdiagnosis are a critical barrier to organized prostate cancer screening. Magnetic resonance imaging (MRI) with targeted biopsy has shown the potential to address this challenge, but the implications of its use in the context of organized prostate cancer screening are unknown. METHODS: We conducted a population-based noninferiority trial of prostate cancer screening in which men 50 to 74 years of age from the general population were invited by mail to participate; participants with prostate-specific antigen (PSA) levels of 3 ng per milliliter or higher were randomly assigned, in a 2:3 ratio, to undergo a standard biopsy (standard biopsy group) or to undergo MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer (experimental biopsy group). The primary outcome was the proportion of men in the intention-to-treat population in whom clinically significant cancer (Gleason score ≥7) was diagnosed. A key secondary outcome was the detection of clinically insignificant cancers (Gleason score 6). RESULTS: Of 12,750 men enrolled, 1532 had PSA levels of 3 ng per milliliter or higher and were randomly assigned to undergo biopsy: 603 were assigned to the standard biopsy group and 929 to the experimental biopsy group. In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21%) in the experimental biopsy group, as compared with 106 men (18%) in the standard biopsy group (difference, 3 percentage points; 95% confidence interval [CI], -1 to 7; P<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the experimental biopsy group than in the standard biopsy group (4% [41 participants] vs. 12% [73 participants]; difference, -8 percentage points; 95% CI, -11 to -5). CONCLUSIONS: MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer. (Funded by the Swedish Research Council and others; STHLM3-MRI ClinicalTrials.gov number, NCT03377881.).

Healthcare Costs of Not Achieving Remission in Patients with Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

INTRODUCTION: To compare all-cause and rheumatoid arthritis (RA)-related healthcare costs and resource use in patients with RA who do not achieve remission versus those who achieve remission, using clinical practice data. METHODS: Data were derived from Optum electronic health records linked to claims from commercial and Medicare Advantage health plans. Two cohorts were created: remission and non-remission. Remission was defined as Disease Activity Score 28-joint count with the C-reactive protein level or erythrocyte sedimentation rate (DAS28-CRP/ESR) < 2.6 or Routine Assessment of Patient Index Data 3 (RAPID3 ≤ 3.0). Outcomes were all-cause and RA-related costs and resource use during a 1-year follow-up period. A weighted generalized linear regression and negative binomial regression were used to estimate adjusted annual costs and resource use, respectively, controlling for confounding factors, including patient and socio-demographic characteristics. RESULTS: Data from 335 patients (remission: 125; non-remission: 210) were analyzed. Annual all-cause total costs were significantly less in the remission versus non-remission cohort ($30,427 vs. $38,645, respectively; cost ratio [CR] = 0.79; 95% CI 0.63, 0.99). All-cause resource use (mean number of visits) was less in the remission versus non-remission cohort: inpatient (0.23 vs. 0.63; visit ratio [VR] = 0.36; 95% CI 0.19, 0.70), emergency department (0.36 vs. 0.77; VR = 0.47; 95% CI 0.30, 0.74), and outpatient visits (20.7 vs. 28.5; VR = 0.73; 95% CI 0.62, 0.86). Annual RA-related total costs were similar in both cohorts; however, RA-related medical costs were numerically lower in the remission versus non-remission cohort ($8,594 vs. $10,002, respectively; CR = 0.86; 95% CI 0.59, 1.25). RA-related resource use was less in the remission versus non-remission cohort. CONCLUSIONS: Significant economic burden was associated with patients who did not achieve remission compared with those who did achieve remission.