The role of traditional NSAIDs and selective COX-2 inhibitors on COVID-19 outcomes: a real-world data study.

The relation between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and severity of COVID-19 has been the subject to debate since the outbreak of the pandemic. Despite speculations about the possible harmful or protective effects, the position currently most supported by the scientific community is that there is no association between use of NSAIDs and COVID-19 outcomes. With the aim of contributing to increase the body of evidence on this issue, we conducted a case-control study using real-world data to investigate the association between prior use of NSAIDs, by active ingredient and type (traditional NSAIDs and selective COX-2 inhibitors), and important COVID-19-related outcomes, including susceptibility, PCR + patient progression, and hospitalisation. Our findings suggest that, in general, the use of traditional NSAIDs is not associated with any adverse COVID-19 outcome. However, we observed a possible association between diclofenac and a higher risk of PCR + patient progression. Our results also suggest that selective COX-2 inhibitors might be related with a reduction in the risk of PCR + patient progression. These results suggest that, with the possible exception of diclofenac, the use of NSAIDs should not be advised against for relief of symptoms in patients with COVID-19. In addition, they support the importance of continue to investigate the treatment potential of selective COX-2 inhibitors in the management of COVID-19, something that could have significant implications for the treatment of this disease and other viral infections.

Metabolic-associated steatotic liver disease and risk of Alzheimer's disease: a real-world retrospective cohort study.

Objective: Alzheimer's Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver Disease (MASLD). This study aimed to assess the relative risk of AD in individuals with MASLD. Methods: In this retrospective cohort study, we analyzed data from individuals aged over 65 who underwent health check-ups between January 2018 and June 2023. MASLD was diagnosed based on ultrasound findings and cardiometabolic criteria. AD incidence was identified using ICD-10 codes and self-reports. Poisson regression models estimated the relative risk of AD in relation to MASLD, adjusting for age, BMI, sex, SBP, HbA1c, HDL-c, triglycerides, hs-CRP, GGT, and estimated GFR. Results: The study included 4,582 MASLD patients and 6,318 controls. MASLD patients showed a higher incidence of AD (127 cases) compared to controls (61 cases). The fully adjusted Poisson regression model indicated an increased AD risk in MASLD patients [RR: 2.80 (95% CI: 1.79-4.38)]. Conclusion: Our findings suggested MASLD as an independent risk factor for AD, underlining the role of metabolic dysfunctions in AD pathogenesis. The study emphasized the need for comprehensive metabolic health management in AD prevention strategies, particularly among high-risk groups.

Scalable and successful patient portal lifestyle coaching training for primary care clinical staff.

Maintaining a healthy weight postintentional weight loss is crucial for preventing chronic health conditions, yet many regain weight postintervention. Electronic health record (EHR) portals offer a promising avenue for weight management interventions, leveraging patient-primary care relationships. Our previous research demonstrated that coaching alongside self-monitoring improves weight maintenance compared to monitoring alone. Integrating weight management into routine clinical practice by training existing staff could enhance scalability and sustainability. However, challenges such as inconsistent staff qualifications and high coach turnover rates could affect intervention effectiveness. Standardizing services, training, and coaching continuity seem crucial for success. To report on developing, testing, and evaluating an EHR-based coaching training program for clinical staff, guided by an implementation tool for the MAINTAIN PRIME study. Conducted across 14 University of Utah primary care sites, we developed, tested, and evaluated a coaching training for clinical staff. Guided by a planning model and the Predisposing, Enabling, and Reinforcing (PER) tool, stakeholders actively participated in planning, ensuring alignment with clinic priorities. All clinical staff were invited to participate voluntarily. Evaluation measures included staff interest, training effectiveness, confidence, and readiness. Data collection utilized REDCap, with survey results analyzed using descriptive statistics. Despite increased clinical workload and reassignments posed by coronavirus disease 2019, we were able to train 39 clinical staff, with 34 successfully coaching patients. Feedback indicated high readiness and positive perceptions of coaching feasibility. Coaches reported satisfaction with training, support, and enjoyed establishing connections with patients. The PER strategies allowed us to implement a well-received training program found effective by primary care coaches.

This report describes a training program for medical staff like nurses and medical assistants. The goal is to teach them how to coach patients through an online portal to help them keep their weight off after making healthy lifestyle changes. We worked with different clinic groups and used a planning tool called PER worksheet (predisposing, enabling, and reinforcing) to set up the training program. From September 2021 to March 2023, we offered the training in 14 clinics, and most interested staff completed it. The results showed that the training worked well. People who took part felt they learned enough to coach patients and felt ready to coach. They liked the training and found it helpful. This study suggests that we can teach coaching skills in just four hours of training and that ongoing support and mentorship are important to the trained coaches. Furthermore, this training set-up allows new staff to be trained as they join, which is especially important in places where staff changes frequently. Overall, using the PER tool enabled us to create a training program that staff can use in outpatient clinics to help patients improve their weight management.

Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic.

BACKGROUND: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic. METHODS: Three independent cohorts (modelling [n = 991, 59.7% female], testing [n = 642, 56.2% female] and validation [n = 441, 55.1% female]) of real-world patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other dementias were included. Paired cerebrospinal fluid (CSF) and plasma samples were used to measure AT(N) CSF biomarkers and plasma pTau181. FINDINGS: CSF and plasma pTau181 showed correlation in all phenotypes except in SCD and other dementias. Age significantly influenced the biomarker's performance. The general Aß(+) vs Aß(-) ROC curve showed an AUC = 0.77 [0.74-0.80], whereas the specific ROC curve of MCI due to AD vs non-AD MCI showed an AUC = 0.89 [0.85-0.93]. A cut-off value of 1.30 pg/ml of plasma pTau181 exhibited a sensitivity of 93.57% [88.72-96.52], specificity of 72.38% [62.51-79.01], VPP of 77.85% [70.61-83.54], and 8.30% false negatives in the subjects with MCI of the testing cohort. The HR of cox regression showed that patients with MCI up to this cut-off value exhibited a HR = 1.84 [1.05-3.22] higher risk to convert to AD dementia than patients with MCI below the cut-off value. INTERPRETATION: Plasma pTau181 has the potential to be used in the memory clinics as a screening biomarker of AD pathology in subjects with MCI, presenting a valuable prognostic utility in predicting the MCI conversion to AD dementia. In the context of a real-world population, a confirmatory test employing gold-standard procedures is still advisable. FUNDING: This study has been mainly funded by Ace Alzheimer Center Barcelona, Instituto de Salud Carlos III (ISCIII), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Spanish Ministry of Science and Innovation, Fundación ADEY, Fundación Echevarne and Grífols S.A.

Current use of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors for hypertension in patients with chronic kidney disease with proteinuria: a cross-sectional study based on real-world data.

Japanese guidelines recommend angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) as first-line therapy in hypertensive patients with chronic kidney disease (CKD) and proteinuria, but calcium channel blockers in patients with stage G4-5 CKD aged ≥75 years; however, the implementation of these guidelines in clinical practice is unclear. We investigated the actual use of these agents in this patient population. We conducted a cross-sectional study using the DeSC database, which includes anonymous information from various health insurance systems in Japan. A total of 34,362 hypertensive patients aged <75 years with CKD stage G1-G5 with urinary protein ≥1+ or aged ≥75 years with CKD stage G1-G3 with urinary protein ≥1+, for whom Japanese guidelines recommend first-line ARBs/ACEIs, were included in the analysis. Prescription rates of ARBs and ACEIs were calculated overall and separately for each age group and glomerular filtration rate category. The mean participant age was 65.8 ± 14.8 years, including 24,585 patients (72%) <75 years and 9777 (28%) ≥75 years. Of these, 9529 were prescribed ARBs/ACEIs (prescription rate 28%). The prescription rate was lower in patients aged <75 years with CKD stage G1-G5 (prescription rate 23%) compared with patients aged ≥75 years old with CKD stage G1-G3 (prescription rate 41%) (p < 0.001). Patients with CKD stage G1 had the lowest prescription rates for ARBs/ACEIs in both age categories. These results indicate that, despite guideline recommendations, ARBs/ACEIs are insufficiently prescribed for patients with hypertension associated with CKD with proteinuria. ARBs and ACEIs were only used in 28% of hypertensive patients aged<75 years (CKD stage G1-G5) or aged ⩾75 years (CKD stage G1-G3), with urinary protein ⩾1+, for whom Japanese guidelines recommend ARBs/ACEIs. The prescription rate was lower in the younger compared with the older patients.

Real-world assessment of comprehensive genome profiling impact on clinical outcomes: A single-institution study in Japan.

INTRODUCTION: Comprehensive genome profiling (CGP) has revolutionized healthcare by offering personalized medicine opportunities. However, its real-world utility and impact remain incompletely understood. This study examined the extent to which CGP leads to genomically matched therapy and its effectiveness. METHODS: We analyzed data from advanced solid tumor patients who underwent CGP panel between December 2019 and May 2023 at the Osaka International Cancer Institute. Patient demographics, specimen details, and expert panel assessments were collected. Turnaround time (TAT) and genomically matched therapy outcomes were analyzed. Gene alterations and their co-occurrence patterns were also assessed. RESULTS: Among 1437 patients, 1096 results were available for analysis. The median TAT was 63 [28-182] days. There were 667 (60.9%) cases wherein recommended clinical trials were presented and there were 12 (1.1%) cases that could be enrolled in the trial and 25 (2.3%) cases that could lead to therapies under insurance reimbursement. The median progression free survival of the trial treatment was 1.58 months (95% CI: 0.66-4.37) in clinical trials and 3.66 months (95% CI: 2.14-7.13) in treatment under insurance. Pathologic germline variants were confirmed in 15 patients (1.3%). Co-alteration of CDKN2A, CDKN2B, and MTAP was significantly observed in overall population. CONCLUSION: The effectiveness of the genomically matched therapy based on the CGP panel was unsatisfactory. Expansion of clinical trials and utilization of remote clinical trials are required to ensure that the results of the CGP panel can be fully returned to patients.

Real-World Study of the Burden of Myelodysplastic Syndromes in Patients and Their Caregivers in Europe and the United States.

INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure, peripheral blood cytopenias and a high risk of progression to acute myeloid leukemia (AML), which is associated with a poor prognosis and low survival rates. This study combined surveys with patient chart reviews to document real-world clinical practice and burden of MDS, including perspectives of physicians, patients and caregivers and underlying discrepancies. METHODS: Physicians in major European countries and the US provided information on 1445 patients, stratified into lower- (LR) and higher-risk (HR) MDS. Patients had the opportunity to complete questionnaires describing the impact of MDS. Caregivers had the option to report on the burden of caring for a patient with MDS. RESULTS: While supportive treatment was common, mainly with erythropoietins (52%), anti-AML agents were more frequently used in HR than in LR patients (70% vs 20%), while HR patients generally received more transfusions (48% vs 36%). Symptoms with the largest discordance between patient vs physician reporting were excessive bruising (30% vs 14%), GI side effects (19% vs 6%) and feeling tired or fatigued (68% vs 56%). A bigger impact of fatigue was reported on the European Organization for the Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for HR vs LR patients (43.2 vs 36.5 on a scale from 0 to 100). There was discordance between caregivers vs physicians on reporting of weekly caregiver hours (45.4 vs 29.2) with a Zarit Burden Interview score (ZBI, score 0-88) of 25.4. CONCLUSIONS: Patients reported a higher frequency than their physicians of top symptoms, with MDS-related disruptions in daily life for both patients and caregivers. There is a need for new therapeutic strategies, along with shared understanding and decision making among patients, caregivers and physicians, to optimize disease management and improve quality of life in people living with MDS.

Prevalence of obesity and cardiovascular disease in adults with type 2 diabetes and use of diabetes medication in Germany: A claims data study.

AIMS: To identify the prevalence of cardiovascular disease (CVD) and obesity in patients with type 2 diabetes (T2D) in Germany and to evaluate if antidiabetic treatment patterns varied by comorbidity status. MATERIALS AND METHODS: Patients with T2D (aged ≥18 years) were identified during the study period (2014-2020) from medical claims of 4.5 million publicly insured German residents and divided into different cohorts based on CVD and/or obesity diagnosis. Annual prevalence and incidence were estimated for each study year, while characteristics and treatments were assessed in 2020. Data were extrapolated to the German population by age and sex. RESULTS: The prevalence of T2D in 2020 was 11.4%. Among patients with T2D, 53.0% had CVD, 39.3% had obesity, and 20.9% had CVD and obesity. Since 2014, CVD increased by 1.4%, obesity by 4.5%, and CVD with obesity by 2.7% in patients with T2D. The incidence of T2D in 2020 was 1.0% (42.9% had CVD, 37.9% had obesity, and 15.8% had CVD and obesity). Among the prevalent T2D population in 2020, 4.9% received glucagon-like peptide-1 receptor agonists (GLP-1RAs), 9.7% received sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 13.0% received GLP-1 RAs and/or SGLT2 inhibitors. Of those with CVD, 12.9% received GLP-1 RAs and/or SGLT2 inhibitors (without CVD, 13.2%). Of those with obesity, 19.4% received GLP-1RAs and/or SGLT2 inhibitors (without obesity, 9.0%). CONCLUSIONS: In this retrospective claims database study, more than two thirds of patients with T2D also had CVD, obesity, or both CVD and obesity. GLP-1 RA and SGLT2 inhibitor use remained low.

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: A report from the GLORIA-AF registry phase III.

AIMS: Atrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use. MATERIALS AND METHODS: Our analysis included individuals with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-year follow-up. Outcomes included all-cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE). RESULTS: A total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all-cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28-1.66), CV death (HR: 1.53 95% CI: 1.27-1.86), major bleeding (HR: 1.23, 95% CI: 1.01-1.48), MI (HR: 1.50, 95% CI: 1.17-1.94) and MACE (HR: 1.42, 95% CI: 1.23-1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all-cause death (HR: 2.16, 95% CI: 1.61-2.91), CV death (HR: 2.24, 95% CI: 1.45-3.47), major bleeding (HR: 1.89, 95% CI: 1. 21-2.95), MI (HR: 2.24, 95% CI: 1.31-3.82) and MACE (HR: 2.11, 95% CI: 1.54-2.88). CONCLUSIONS: DM was independently associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE.

Lower mortality risk associated with remdesivir + dexamethasone versus dexamethasone alone for the treatment of patients hospitalized for COVID-19.

BACKGROUND: Treatment guidelines were developed early in the pandemic when much about COVID-19 was unknown. Given the evolution of SARS-CoV-2, real-world data can provide clinicians with updated information. The objective of this analysis was to assess mortality risk in patients hospitalized for COVID-19 during the Omicron period receiving remdesivir+dexamethasone versus dexamethasone alone. METHODS: A large, multicenter US hospital database was used to identify hospitalized adult patients, with a primary discharge diagnosis of COVID-19 also flagged as "present on admission" treated with remdesivir+dexamethasone or dexamethasone alone from December 2021 to April 2023. Patients were matched 1:1 using propensity score matching and stratified by baseline oxygen requirements. Cox proportional hazards model was used to assess time to 14- and 28-day in-hospital all-cause mortality. RESULTS: A total of 33 037 patients were matched, with most patients ≥65 years old (72%), White (78%), and non-Hispanic (84%). Remdesivir+dexamethasone was associated with lower mortality risk versus dexamethasone alone across all baseline oxygen requirements at 14 days (no supplemental oxygen charges: adjusted hazard ratio [95% CI]: 0.79 [0.72-0.87], low flow oxygen: 0.70 [0.64-0.77], high flow oxygen/non-invasive ventilation: 0.69 [0.62-0.76], invasive mechanical ventilation/extracorporeal membrane oxygen (IMV/ECMO): 0.78 [0.64-0.94]), with similar results at 28 days. CONCLUSIONS: Remdesivir+dexamethasone was associated with a significant reduction in 14- and 28-day mortality compared to dexamethasone alone in patients hospitalized for COVID-19 across all levels of baseline respiratory support, including IMV/ECMO. However, the use of remdesivir+dexamethasone still has low clinical practice uptake. In addition, these data suggest a need to update the existing guidelines.

Sequential vs. concurrent systemic therapies in combination with FOLFOX-HAIC for locally advanced hepatocellular carcinoma: a single-center, real-world cohort study.

BACKGROUND: Tri-combination therapy based on hepatic arterial infusion chemotherapy (HAIC) of infusion fluorouracil, leucovorin, and oxaliplatin (FOLFOX-HAIC) plus immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the locally advanced hepatocellular carcinoma (HCC) patients have been proven effective. However, whether it was best for these HCC patients to start with the most potent therapeutic pattern was still under debate. This retrospective study evaluated the efficacy and safety of FOLFOX-HAIC combined with systemic therapies in the patterns of sequential and concurrent schedules. METHODS: This real-world study included 117 unresectable HCC patients who initially received either FOLFOX-HAIC monotherapy (HAIC group, n = 44) or concurrent ICIs and TKIs (ConHAIC group, n = 73) from March 2020 and June 2022, during the period of FOLFOX-HAIC monotherapy in HAIC group, patients in the HAIC group (n = 30) experienced progressive disease (PD) would have their treatment pattern converted from the FOLFOX-HAIC monotherapy to the combination of FOLFOX-HAIC plus ICIs and TKIs sequentially (SeqHAIC group). The progression-free survival (PFS) and overall survival (OS), as primary outcomes, were compared between patients in the SeqHAIC and ConHAIC groups. RESULTS: The median follow-up time of the SeqHAIC group was 24.92 months (95% CI, 12.74-37.09 months) and of the ConHAIC group was 17.87 months (95% CI, 16.85-18.89 months) and no significant difference was observed in both PFS (HR, 1.572; 95% CI, 0.848-2.916; p = 0.151) and OS (HR, 1.212; 95% CI, 0.574-2.561; p = 0.614) between the SeqHAIC and the ConHAIC groups. As for the tumor responses, there was no significant difference between the two groups regarding tumor responses, overall response rates (p = 0.658) and disease control rates (p = 0.641) were 50.0%, 45.2%, and 83.3%, 89.0% for the SeqHAIC and the ConHAIC groups, respectively. CONCLUSION: Our study revealed that sequential systemic ICIs and TKIs in combination with FOLFOX-HAIC provides similar long-term prognosis and better tolerability compared to concurrent therapy for locally advanced HCC patients. Prospective studies with a larger sample size and longer follow-up are required to validate these findings.

Real-world data to support post-market safety and performance of embolization coils: evidence generation from a medical device manufacturer and data institute partnership.

BACKGROUND: Recognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils. METHODS: Through a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils' use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana's largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints. RESULTS: A total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method. CONCLUSIONS: Generating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems.

Risk of antimuscarinic initiation with cholinesterase inhibitor use in Alzheimer's disease.

BACKGROUND: The use of cholinesterase inhibitors (CHEIs) is commonly associated with urinary incontinence in patients with Alzheimer's disease (AD). This study evaluated the risk of antimuscarinic initiation drugs with the use of CHEIs in AD patients. METHODS: The study used a nested case-control study design involving 2013-2015 Medicare data of AD patients 65 years and older without antimuscarinic use in 2013. Cases were defined as those who initiated antimuscarinic treatment in 2014-2015. Controls with no antimuscarinic use were selected through incidence density sampling and matched to cases on age using a variable-ratio method. The CHEI utilization pattern was classified as current (event-30 days), recent (event-31 to event-90 days), and past (event-91 to event-180 days). Conditional logistic regression was used to assess the association between CHEI use and the risk of antimuscarinic initiation. RESULTS: This study included 1,909 cases and 9,064 controls. The adjusted model found that overall CHEI (Adjusted Odds Ratio [aOR] = 1.90, 95 % Confidence Interval [CI]: 1.58-2.28) and current CHEI use (aOR = 1.62, 95 % CI: 1.18-2.21) were associated with an increase in the risk of antimuscarinic initiation compared to non-CHEI use. In addition, the current use of donepezil and rivastigmine significantly increased the risk of antimuscarinic initiation by 48 % (95 % CI: 1.03-2.12) and 171 % (95 % CI: 1.46-5.03), respectively. CONCLUSION: The study found an increased risk of antimuscarinic initiation with the current use of CHEIs, particularly with donepezil and rivastigmine. These findings underscore the need for careful medication management to minimize prescribing cascades and associated consequences in AD.

Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis.

INTRODUCTION: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria. METHODS: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk. RESULTS: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence. CONCLUSIONS: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain. PROTOCOL REGISTRATION: www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.

A Retrospective Cohort Study to Determine Real-World Treatment Patterns in Patients with Sézary Syndrome in the United States.

INTRODUCTION: Sézary syndrome (SS) is a rare leukemic cutaneous T cell lymphoma. This study was conducted to examine the real-world treatment patterns among patients with SS in the USA from 2018 to 2020. METHODS:  This was a retrospective cohort study using the Symphony Health Solutions claims database. Adult patients with ≥ 1 diagnosis code for SS were classified into three non-mutually exclusive cohorts: 2018, 2019, and 2020. Patient characteristics and treatment patterns were examined across the 3 years of study and reported descriptively for each year. Annual treatment patterns were also described for the five states with the highest proportions of SS patients in 2020. RESULTS: Overall, 869, 882, and 853 SS patients were identified in 2018, 2019, and 2020, respectively (median age: 70 years for each year; male: 54.4%, 54.8%, and 55.6%, respectively). The use of any systemic and parenteral systemic treatments increased over time. While utilization rates for many specific systemic therapies decreased over the study period, mogamulizumab use increased, making it the most commonly used systemic treatment in 2020 (29.2%) among patients with any systemic treatment. The five states with the highest proportions of SS patients in 2020 were Florida, New York, California, Texas, and Pennsylvania. Systemic treatment patterns varied considerably by state. CONCLUSION: Some systemic therapies showed decreased usage over time while a few showed increased utilization, with mogamulizumab showing the largest increase. Treatment patterns for SS varied by region. Further research is needed to examine the factors that drive treatment selection for patients with SS.

Emissions of gaseous nitrous acid (HONO) from diesel trucks: Insights from real-driving emission experiments.

Nitrous acid (HONO) serves as a substantial contributor in the atmospheric chemistry of hydroxyl radicals (·OH). Despite its significance, the primary sources of atmospheric HONO, particularly diesel truck emissions, have not been thoroughly examined. This study investigated the factors influencing HONO emissions via real-world road exhaust emission tests using a self-developed portable measurement system. The findings show that the HONO emissions measured during on-road testing are higher than those measured during chassis dynamometer testing, highlighting the need for on-road tests to capture HONO emissions. Emission standards and truck types greatly influence HONO emission factors (EFs), with stricter regulations leading to lower emissions. The average fuel consumption-based EFs for light-duty diesel trucks ranged from 0.93 g/kg for China III to 0.08 g/kg for China VI. For medium-duty diesel trucks, the EFs decrease from 1.43 g/kg for China III to 0.19 g/kg for China V. Moreover, the vehicle-specific power demonstrated a stronger correlation with HONO emissions. This research showed that HONO emissions were significantly higher without or before the optimal operation of the SCR device, and the device notably reduced HONO emissions. Future research should focus on the impact of various exhaust after-treatment systems and explore HONO conversion mechanisms.

Effect of a prescription digital therapeutic for chronic insomnia on post-treatment insomnia severity, depression, and anxiety symptoms: results from the real-world DREAM study.

Introduction: Chronic insomnia is a substantial public health burden that often presents with co-occurring depression and anxiety. Randomized clinical trials and preliminary real-world evidence have shown that digitally delivered cognitive-behavioral therapy for insomnia (dCBT-I) is associated with improvements in insomnia, but real-world evidence is needed to determine the true impact of digital CBT-I. This pragmatic study aimed to evaluate the benefits of treating chronic insomnia with a tailored prescription digital therapeutic in a real-world population. Methods: This prospective, single-arm clinical study involved adults aged 22-75 with chronic insomnia living in the US who had access to a mobile device. Participants accessed the FDA-cleared prescription digital therapeutic (PDT; Somryst®) over a 9-week intervention period. The PDT delivers cognitive-behavioral therapy for insomnia via six interactive treatment cores and daily sleep diaries used for tailoring treatment. Participants completed validated patient-reported instruments at baseline, before completing treatment cores, immediately post-intervention, and at 6-month and 1-year follow-ups. The Insomnia Severity Index [ISI], the 8-item Patient Health Questionnaire [PHQ-8], and the Generalized Anxiety Disorder-7 scale [GAD-7] were used to determine the effect of the PDT on insomnia, depression, and anxiety. Results: After screening, 1565 adults accessed the PDT. 58% of those who began the program completed Core 4, established as exposure to all mechanisms of action in the digital therapeutic. For those who completed assessments for all 6 cores (48.4%), the ISI was lowered from 18.8 to a mean of 9.9 (P <.001). These scores continued to be lower than baseline at immediate post (11.0), 6-month (11.6), and 1-year follow-ups (12.2) (P <.001). The results of the PHQ-8 and GAD-7 also show significant decreases at all measured timepoints from baseline (P <.001). Of the patients that began the program, 908 (58.0%) were considered adherent and 733 (46.8%) completed all 6 cores. Conclusion: Data from the DREAM study contributes to the growing body of clinical evidence of how patients are utilizing a PDT in the real world, outside of controlled settings, offering insights for clinicians who use these therapeutics in practice. Clinical trial registration: ClinicalTrials.gov, identifier NCT04325464.

Predictive factors of right heart catheterization to diagnose pulmonary arterial hypertension using least absolute shrinkage selection operator (LASSO) regression.

OBJECTIVE: This study involved an analysis of a real world, international survey where physicians provided cross-sectional, retrospective data for patients with pulmonary arterial hypertension (PAH) to determine predictive factors of right heart catheterization (RHC) to confirm their PAH diagnosis. METHODS: Data were sourced from the Adelphi PAH Disease Specific Programme (DSP) in the United States (US), France, Germany, Italy, Spain, United Kingdom, and Japan, between March and August 2022. RESULTS: Overall, 75% (n = 395) of patients with PAH (n = 529) underwent RHC at diagnosis; this varied by country, ranging from 64% in the US to 92% in France. RHC was more likely to be performed in patients with a higher New York Heart Association Functional Class, with key PAH symptoms (dyspnea, palpitations, and cyanosis), and diagnosed at PH specialist centers. CONCLUSION: By understanding the factors associated with RHC utilization at PAH diagnosis, more targeted approaches for improving the diagnosis for patients with suspected PAH may be pursued.