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Wensheng Lu,1 JianFeng Wang,2 YuanJing Zhang,1 Ruixue Chang,1 Jun Zhao3 1Department of Dermatology, The No. 1 Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Dermatology, The No. 1 Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Department of Dermatology, The Lu’an Hospital Affiliated to Anhui Medical University, Lu’an, Anhui, People’s Republic of ChinaCorrespondence: Wensheng Lu; Jun Zhao, Email 492051693@qq.com; 13085092159@163.comIntroduction: This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment.Methods: This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤ 1/3 and Physicians’ Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28.Results: A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P< 0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline.Conclusion: Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.Keywords: ustekinumab, plaque psoriasis, real-world effectiveness, LTBI, inactive HBV infection

Background: Acne is the most common skin disorder which is known as a chronic inflammatory disease with psychological burden and reduced quality of life. Objective: The objective of this study is to determine, in a real-world effectiveness and clinical experience in treating acne scars which includes evaluating reduction in depth, diameter, erythema and pigmentation, with an acne scar gel, and to evaluate the effect of the product on quality of life. Methods: Overall, 435 patients were assessed for 90 days. The acne scars were counted and classified as mild, moderate or severe and the type of acne scar was registered. The study participants had gone through both oral and topical treatment for a time range of 1 week to over a month depending on the severity of the scars. They had also gone through medical procedures as per the requirement. The results were assessed at an interval of 30 days to 90 days and were graded between 1-5. Results: Overall facial appearance of atrophic acne scars improved after treatment with acne scar gel. Clinical experience with acne scar gel (in terms of reduction of scar depth, diameter, erythema, and pigmentation), and subject satisfaction (happiness and confidence) score along with the sensation and perception of the skin improved in most subjects. Conclusions: Acne scar gel was effective and safe for treatment of moderate-to-severe acne scars. The acne scar gel can be used as topical treatment for acne scars, thereby reducing the need of procedural treatment for acne scars. [ABSTRACT FROM AUTHOR]

Introduction: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA. Methods: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events. Results: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4–71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports. Conclusion: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit–risk profile. Trial Registration: NCT04574492. [ABSTRACT FROM AUTHOR]

Background and Aims This study compares the effectiveness of different biologic therapies and sequences in patients with inflammatory bowel disease [IBD] using real-world data from a large cohort with long exposure. Methods Demographic, disease, treatment, and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan–Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups. Results In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [ p  = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [ p  < 0.001 and p  < 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn's disease [CD] we found significant differences between first-line treatments over 10 years [ p  = 0.045], with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first-line anti-TNF failure in CD [ p  = 0.035]. Patients with UC or CD experiencing TNF failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF. Conclusions We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF treatment. [ABSTRACT FROM AUTHOR]

The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from traditional oncology drug dosing practices. Historically, oncology drug dosing relies on identifying the maximum tolerated dose through phase 1 dose escalation methodology, favoring higher dosing for greater efficacy, often leading to higher toxicity. However, this approach is not universally applicable, especially for newer treatments like targeted therapies and immunotherapies. Patient-Centered Dosing Initiative challenges this "more is better" ethos, particularly as metastatic breast cancer patients themselves, as they not only seek longevity but also a high quality of life since most metastatic breast cancer patients stay on treatment for the rest of their lives. Surveying 1221 metastatic breast cancer patients and 119 oncologists revealed an evident need for flexible dosing strategies, advocating personalized care discussions based on patient attributes. The survey results also demonstrated an openness toward flexible dosing and a willingness from both patients and clinicians to discuss dosing as part of their care. Patient-centered dosing emphasizes dialogue between clinicians and patients, delving into treatment efficacy-toxicity trade-offs. Similarly, clinical trial advocacy for multiple dosing regimens encourages adaptive strategies, moving away from strict adherence to maximum tolerated dose, supported by recent research in optimizing drug dosages. Recognizing the efficacy-effectiveness gap between clinical trials and real-world practice, Patient-Centered Dosing Initiative underscores the necessity for patient-centered dosing strategies. A focus on individual patient attributes aligns with initiatives like Project Optimus and Project Renewal, aiming to optimize drug dosages for improved treatment outcomes at both the pre- and post-approval phases. Patient-Centered Dosing Initiative's efforts extend to patient education, providing tools to initiate dosage-related conversations with physicians. In addition, it emphasizes physician-patient dialogues and post-marketing studies as essential in determining optimal dosing and refining drug regimens. A dose-finding paradigm prioritizing drug safety, tolerability, and efficacy benefits all stakeholders, reducing emergency care needs and missed treatments for patients, aligning with oncologists' and patients' shared goals. Importantly, it represents a win-win scenario across healthcare sectors. In summary, the Patient-Centered Dosing Initiative drives transformative changes in cancer drug dosing, emphasizing patient well-being and personalized care, aiming to enhance treatment outcomes and optimize oncology drug delivery. [ABSTRACT FROM AUTHOR]

Abstract Introduction Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA. Methods Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP)

Partnership between early childhood development interventions and primary health care services can help catalyse health care uptake by socially vulnerable families. This study aimed to assess the real-life effects of a large-scale home visiting programme [Primeira Infância Melhor (PIM)] in Brazil on the use of preventive (prenatal visits, well child visits, dentist visits and vaccination) and recovery (emergency room visits and hospitalization) health services. A quasi-experiment nested in a population-based birth cohort study was conducted. The intervention group was firstly defined as all children enrolled in PIM up to age 6 months, and afterwards stratified between those enrolled during pregnancy or after birth up to 6 months. Children receiving PIM were matched with controls on propensity scores based on 27 confounders to estimate effects on health service use from prenatal to age 2 years. Double adjustment was applied in outcome Quasi-Poisson regressions. No evidence was found for effects of PIM starting anytime up to 6 months (262 pairs), or for the children enrolled only after birth (133 pairs), on outcomes occurring after age 6 months. When the programme started during pregnancy (129 pairs), there was a 13% higher prevalence of adequate prenatal visits (prevalence ratio = 1.13; 95% confidence interval 1.01–1.27), but no effect on use of any other health service. Sensitivity analyses suggested longer participation in the programme with reduced visitor turnover might improve its impact on prenatal visits. Integration between PIM and primary health care was not adequate to affect overall patterns of contacts with health services. Nevertheless, prenatal home visits showed potential to increase health service contact during a sensitive period of development, indicating the need to start such programmes before birth, when there is more time for maternal care, and family engagement in a network of services is facilitated. [ABSTRACT FROM AUTHOR]

Purpose: Lenvatinib was approved for the treatment of patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) in the United States (US) in 2015. The main objective of the current study was to assess real-world clinical effectiveness in RAI-R DTC patients treated with first line lenvatinib monotherapy in the US. Methods: A retrospective chart review was conducted in RAI-R DTC patients who initiated lenvatinib monotherapy as first line treatment between February 2015 and September 2020. Anonymized data were abstracted by prescribing physicians from individual patient's electronic health records. Clinical outcomes included provider-reported real-world best overall response (rwBOR), real-world progression-free survival (rwPFS), and overall survival (OS). Time-to-event endpoints were assessed using Kaplan–Meier methods. Results: Our study included 308 RAI-R DTC patients treated with first line lenvatinib. At lenvatinib initiation, patients' median age was 60 years, 51.6% were female, and 26.0% of patients had an ECOG performance score of ≥2. Over the follow-up period, 32.5% of patients discontinued first line lenvatinib permanently, with others remaining on treatment. The median duration of lenvatinib therapy was 17.5 months overall. Provider-reported rwBOR (complete or partial response) to lenvatinib was 72.4%. Median rwPFS was 49.0 months. Estimated rwPFS rates at 24 and 48 months were 68.5% and 55.0%, respectively. Estimated OS rates at 24 and 72 months were 78.4% and 57.0%, respectively; median OS was not reached. Conclusion: The current study reinforces the clinical effectiveness of first line lenvatinib as standard of care in patients with RAI-R DTC in real-world clinical practice in the US. [ABSTRACT FROM AUTHOR]

Monitoring the real-life effectiveness of respiratory syncytial virus (RSV) products is of major public health importance. This generic protocol for a test-negative design study aims to address currently envisioned approaches for RSV prevention (monoclonal antibodies and vaccines) to study effectiveness of these products among target groups: children, older adults, and pregnant women. The generic protocol approach was chosen to allow for flexibility in adapting the protocol to a specific setting. This protocol includes severe acute respiratory infection (SARI) and acute respiratory infection (ARI), both due to RSV, as end points. These end points can be applied to studies in hospitals, primarily targeting patients with more severe disease, but also to studies in general practitioner clinics targeting ARI. [ABSTRACT FROM AUTHOR]

Sir Archibald Cochrane and Sir Austin Bradford Hill requested 80 years ago answers to three questions (Can it work? Does it work? Is it worth it?) before a new intervention is implemented in day-to-day healthcare. A critical analysis of currently accepted answers identified a terminology conflict that inherits the risk of misleading interpretations and inappropriate decisions. For detection of the terminology problem and the development of the solutions was possible through three recommendations (the "Ulm heritage"): (1) Albert Einstein (*1879 in Ulm/Germany) predicted, "A problem cannot be solved with the way of thinking that caused it"; (2) The "hochschule für gestaltung ulm (Academy of Design, 1953–1968)" disseminated the rules of American designers and architects e.g., "Form Follows Function"; and (3) requested to "design not only individual but universally valid solutions with socio-political relevance". Our data confirms the power of the FFF rule, the pros and cons of value judgments, the complexity of healthcare decisions, the difference between scientific statements and political decisions, and the effects of interprofessional collaboration. "Efficacy" offers promising "Proofs of Principle (PoP)" while "effectiveness" describes "Real-World Effectiveness (RWE)". That is why the results obtained are always more important than hypotheses. [ABSTRACT FROM AUTHOR]

Abstract Background and aim Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. Methods This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. Results After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1–3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6–4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80–1.86, P = 0.43). Conclusion Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

IntroductionWhile the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch.MethodsFrom Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy).ResultsMore than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p

There are limited real‐world data on the effectiveness of tixagevimab‐cilgavimab as pre‐exposure prophylaxis of COVID‐19. We describe lessons learned when coordinating data collection and identifying breakthrough SARS‐CoV‐2 infections among patients across indications and institutions in a major US city. The Chicago Department of Public Health requested patient‐level tixagevimab‐cilgavimab administration data from all prescribing providers in Chicago, for treatments December 8, 2021 through June 30, 2022. Records were matched to COVID‐19 vaccinations and laboratory‐confirmed SARS‐CoV‐2 infections through December 31, 2022. Due to difficulty collecting data from all providers, targeted follow‐up was conducted to improve completeness on key variables (demographics, vaccination status, clinical indication for prophylaxis). Over half of reported tixagevimab‐cilgavimab administrations were to patients residing outside Chicago. Five hundred forty‐four Chicago residents who received at least one dose of tixagevimab‐cilgavimab were included in this analysis. Most were age 50 years or older (72%), Black non‐Latinx (33%) or White non‐Latinx (29%), and fully vaccinated (80%). Seventy‐five patients (14%) had laboratory‐confirmed COVID‐19. Patients with and without breakthrough infections were demographically similar. Clinical indication was missing for >95% of cases, improved to 64% after follow‐up; the most frequently specified was hematologic malignancy (10%). Severe outcomes were uncommon: 16% had documented COVID‐19‐related hospitalizations, one death was identified. Tixagevimab‐cilgavimab recipients in Chicago had a lower rate of severe SARS‐CoV‐2 infection than reported among other untreated high‐risk patients, including during predominance of non‐neutralizing variants. Improving stakeholder collaboration is essential for generation of real‐world effectiveness data, informing pandemic preparedness and optimizing use of medical countermeasures. [ABSTRACT FROM AUTHOR]

Background and aim: Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. Methods: This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. Results: After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1–3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6–4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80–1.86, P = 0.43). Conclusion: Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment. [ABSTRACT FROM AUTHOR]

Introduction: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). Methods: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1–4, 8, and 12. RAPID3 responses over time were assessed using Kaplan–Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. Results: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. Conclusions: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12. [ABSTRACT FROM AUTHOR]

Background: The MOVe-OUT (efficacy and safety of molnupiravir [MK-4482] in non-hospitalized adult participants with COVID-19 [MK-4482-002]) trial reported that the administration of molnupiravir in unvaccinated patients with coronavirus disease 2019 (COVID-19) before the Omicron epidemic showed a preventive effect of 31% against hospitalization and death. However, studies on the preventive effect of molnupiravir against progression to severe disease and death in patients with COVID-19 during the Omicron epidemic are limited. This study aimed to evaluate the preventive effect of molnupiravir against severe/critical illness or death and death in Korean patients with COVID-19 who were vaccinated mostly during the Omicron epidemic. Materials and Methods: This study used large-scale retrospective cohort data to select patients with COVID-19 who were either treated or not treated with molnupiravir, between August 2022 and March 2023, at a ratio of 1 : 4 using the propensity score matching method. In total, 762,768 patients comprised the non- administered group, and 190,692 patients comprised the molnupiravir-administered group. The preventive effect of molnupiravir against severe/ critical illness or death and death was analyzed using logistic regression analysis. Results: The preventive effect of molnupiravir against severe/critical illness or death and death, represented by the odds ratio (OR) and 95% confidence interval (CI), in the molnupiravir-administered and non-administered group was (OR: 0.714; CI: 0.667 - 0.764) and (OR: 0.749; CI: 0.682 - 0.823), respectively. As age increased, the preventive effect against severe/critical illness or death and death increased. The preventive effect against severe/critical illness or death at ≥60 years was (OR: 0.669; CI: 0.624 - 0.717), at ≥70 years was (OR: 0.614; CI: 0.570 - 0.661), and at ≥80 years was (OR: 0.563; CI: 0.515 - 0.615). The preventive effect against death at ≥60 years was (OR: 0.729; CI: 0.663 - 0.802), at ≥70 years was (OR: 0.676; CI: 0.612 - 0.747), and at ≥80 years was (OR: 0.622; CI: 0.554 - 0.698). Conclusion: Although molnupiravir showed a relatively weak preventive effect against severe/critical illness or death (29%) and death (25%) among patients with COVID-19, it exhibited a stronger protective effect in older patients than in younger patients. In particular, the preventive effect against severe/critical illness or death (44%) and death (38%) in those aged ≥80 years was pronounced. This study strongly suggests that molnupiravir administration can alleviate the burden on the medical system, and treat patients with COVID-19 effectively by reducing its progression to severe disease and death. [ABSTRACT FROM AUTHOR]

Selecting an appropriate oral contraceptive can be challenging for healthcare professionals due to the abundance of marketed contraceptive options with different clinical and real-world effectiveness and safety profiles. Nomegestrol acetate + 17β-estradiol (NOMAC/E2) is a combined oral contraceptive (COC) that inhibits ovulation by suppressing ovarian function by a 17-hydroxy-progesterone derivative and an estrogen identical to that endogenously produced by the ovaries. This narrative review examines clinical and real-world studies of NOMAC/E2 based on a background literature search using PubMed and Google Scholar. The review outlines the pharmacology of NOMAC/E2, including its progestational activity, pharmacokinetics, and effects on carbohydrate metabolism, lipid metabolism, and coagulation parameters, and summarizes key clinical efficacy and safety data that led to the approval of NOMAC/E2 in Europe, Brazil, and Australia. To help elucidate how NOMAC/E2 clinical trial data translate into a real-world setting, this review describes the effectiveness and safety of NOMAC/E2 in prospective studies that include over 90,000 users (half of whom received NOMAC/E2), outlining its effects on risk of thrombosis, menstrual bleeding patterns, weight, mood, acne, bone health, and patient quality of life. Non-contraceptive benefits of NOMAC/E2 for women with endometriosis, dysmenorrhea, or pre-menstrual dysphoric disorder are also discussed. These data demonstrate that NOMAC/E2 has a long half-life and rapid absorption, is effective at preventing unwanted pregnancies, and exhibits a favorable safety profile in both clinical trials and real-world settings. Importantly, NOMAC/E2 is not associated with increased risk of venous thromboembolism, a major safety concern of healthcare professionals for women receiving hormonal contraceptives. This review highlights NOMAC/E2 as a differentiated option among COCs and could help inform oral contraceptive choice to ultimately improve patient management and outcomes in real-world settings.

Background: There is a lack of real-world data on the use of cabozantinib in Asian patients with metastatic renal cell carcinoma. Methods: We conducted a retrospective study to investigate the toxicity and efficacy of cabozantinib in this patient population who progressed on tyrosine kinase inhibitors and/or immune-checkpoint inhibitors from six oncology centres in Hong Kong. The primary endpoint was the incidence of serious adverse events (AEs) attributed to cabozantinib. Secondary safety endpoints included dose reductions and AE-led treatment terminations. Secondary effectiveness endpoints included overall survival, progression-free survival, and objective response rate. Results: A total of 24 patients were included. Half received cabozantinib as a third-line or later-line treatment, whilst 50% received prior immune-checkpoint inhibitors, primarily nivolumab. Overall, 13 (54.2%) patients reported at least one cabozantinib-related AE of grades 3–4. The most commonly reported AEs were hand-foot skin reactions (9; 37.5%) and anaemia (4; 16.7%). Fifteen (65.2%) patients required dose reductions. Three patients discontinued treatment because of AEs. The median progression-free survival and overall survival were 10.3 months and 13.2 months, respectively; 6 (25%) patients achieved partial responses, and 8 (33.3%) achieved stable disease. Conclusion: Cabozantinib was generally well tolerated and efficacious in Asian patients with metastatic renal cell carcinoma who were heavily pretreated.

INTRODUCTION: There is minimal evidence regarding the comparative effectiveness of individual antibiotics in the treatment of pouchitis. We sought to evaluate the comparative effectiveness of ciprofloxacin monotherapy, metronidazolemonotherapy, and combination therapy (ciprofloxacin and metronidazole) in the treatment of an initial episode of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis (UC). METHODS: We performed a retrospective cohort study in TriNetX, a global federated research network of electronic health records. Primary outcomes were failure of initial antibiotic therapy and the development of recurrent pouchitis in the first 12 months after an initial episode of pouchitis. One-to-one propensity score matching was performed for age, sex, race, primary sclerosing cholangitis, nicotine dependence, obesity, and previous exposure to tumor necrosis factor inhibitors between the cohorts. RESULTS: Among 271 patients who developed pouchitis (mean age at ileal pouch-anal anastomosis 35.8 years, male sex57%) and were treated with ciprofloxacin, metronidazole, or combination therapy, 190 (70%) developed recurrent pouchitis. After propensity score matching, there was no significant difference in the odds of early relapse or nonresponse with ciprofloxacin compared with metronidazole monotherapy (adjusted odds ratio 0.56, 95% confidence interval 0.23-1.34) or when either monotherapy was compared with combination therapy. There was also no significant difference in odds of recurrent pouchitis when comparing patients treated with ciprofloxacin with metronidazole monotherapy (adjusted odds ratio 0.86, 95% confidence interval 0.40-1.84) or either monotherapy with combination therapy. DISCUSSION: In this retrospective cohort study, we demonstrated no significant difference in the real-world effectiveness of ciprofloxacin, metronidazole, or combination therapy for the initial episode of pouchitis. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the effectiveness of the 0.19-mg fluocinolone acetonide (FAc) implant by multimodal measurements in patients with non-infectious uveitis (NIU) in a real-world setting in Spain. Methods: A prospective study of patients who had NIU including uveitic macular oedema (UME) with ≥ 12 months follow-up was done. Exclusion criteria include infectious uveitis and uncontrolled glaucoma or ocular hypertension requiring more than 2 medications. Effectiveness was assessed using a multicomponent outcome measure that included nine outcomes. Effectiveness was defined as all components being met at every timepoint. Secondary outcome measures were onset or progression of glaucoma and investigator-reported adverse events. Results: Twenty-six eyes from 22 patients were included, with 96.2% having an indication including UME. During the 12-month study, the FAc implant was effective in 15 (57.7%) eyes, reaching effectiveness as soon as 2 weeks post-implantation. Mean best-corrected visual acuity and mean central macular thickness (CMT) were significantly improved vs. baseline at all timepoints (all comparisons p < 0.01). During the 12-month study, inflammation markers (anterior chamber cells and vitreous haze) had also significantly declined. Factors predicting effectiveness at month 12 were systemic corticosteroid dose pre-FAc, higher immunomodulatory therapy (IMT) load at baseline and thicker retinal nerve fibre layer (RNFL) at baseline (all p < 0.05). Factors predicting failure were male gender, thinner RNFL at baseline and treatment ineffectiveness at 1 month (all p < 0.05). In parallel, corticosteroid and IMT use also declined significantly. No significant increase in IOP was detected. Conclusion: The FAc implant is safe and effective at treating NIU over 12 months in a real-world setting in Spain. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advancedstage epidermal growth factor receptor (EGFR)+ non--small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). Materials and Methods In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. Results The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). Conclusion This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+. [ABSTRACT FROM AUTHOR]

Nivolumab is a human programmed death receptor-1 blocking antibody, used as treatment option in patients with advanced non-small-cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second-line (2L) or third-line (3L) therapy in patients with advanced NSCLC. This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as 2L or 3L treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) to treatment. OS and PFS were estimated with the Kaplan–Meier method and the differences were evaluated through the log-rank test. Data of 178 patients were included. The median follow-up was 26.8 months (interquartile range (IQR): 20.3–40.4). Nivolumab was commonly used as a 2L treatment (77.5%). The outcomes in this setting (2L) were as follows: ORR was 21.0%, and the median PFS and OS were 5.5 months (95% confidence interval (CI): 4.5–6.5) and 12.4 months (95% CI: 10.8–14.0), respectively. In 3L, the ORR with nivolumab was 15.0%, the median PFS and OS were 4.1 months (95% CI: 3.1–5.1) and 10.1 months (95% CI: 9.4–10.6), respectively. Three patients (1.7%) required discontinuation due to toxicity. Nivolumab effectiveness and safety in this scenario was consistent with that reported by previous trials and other real-world data. [ABSTRACT FROM AUTHOR]

Mindfulness is increasingly offered to parents of children presenting with behavioral problems, either as a stand-alone intervention, or integrated within existing behavioral parenting interventions. There is relatively modest support for mindful parenting, with small to medium effect size improvements demonstrated across child and parent outcome measures. Here we introduce a mindfulness and imagery enhanced behavioral parenting program. We argue blending mindfulness, imagery and behavioral skills could produce improved parenting engagement and perseverance, leading to stronger outcomes. Pilot data is presented from two contrasting real world clinical settings. Parents attending the 8-week Confident Carers Cooperative Kids (CCCK) group program in a university clinic setting were invited to be included in the study (n = 20). Permission was also gained to use archival data from a community organisation offering CCCK groups to parents who were at risk of child welfare involvement (n = 14). Pre- and post-intervention measures were completed across both groups on parent-reported child behavior, parent wellbeing, adaptive parenting, and mindful parenting. Parents from both groups achieved significant pre- to post-intervention improvements in child behavior problems, parent wellbeing, adaptive parenting, and mindful parenting, with large effect sizes. Larger improvements in child behavior problems were reported by parents from the community group compared with the university group. The CCCK intervention appears beneficial across child and parent outcomes, including for families most in need. A larger sample is required to replicate and extend these promising findings. Highlights: Mindfulness and imagery have potential to improve behavioral parent training outcomes. Mindfulness and imagery enhanced behavioral parenting group found large effect size pre-post intervention improvements. Improvements in child behavior greater for higher need community participants compared with university clinic participants. Improvements in parent wellbeing, adaptive and mindful parenting similar across community and university participants. [ABSTRACT FROM AUTHOR]

Abstract Introduction Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. Methods Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann–Whitney U test and Chi-square test. A logistic regression model was used to compare participants’ characteristics by treatment group. Kaplan–Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). Results 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3–5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).

Abstract Background Functional recovery is an important treatment goal in major depressive disorder (MDD). This study assessed the real-world effectiveness of vortioxetine in patients with MDD, with particular focus on functioning; dose–response was also assessed. Methods This was a non-interventional, prospective, multicenter study conducted in Greece. Adult outpatients with MDD (n = 336) initiating vortioxetine (5–20 mg/day flexible dosing) as treatment for a current major depressive episode were followed for 3 months. Analyses were stratified according to vortioxetine dosage at 3 months: 5–10 mg/day versus 15–20 mg/day. Functioning was assessed using the Sheehan Disability Scale (SDS). Results Mean ± standard error SDS total score decreased (improved) from 18.7 ± 0.3 at baseline to 12.9 ± 0.3 after 1 month of vortioxetine treatment and 7.8 ± 0.4 after 3 months (p

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. Methods This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway–targeted mAb [CGRP mAb]). Results Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were − 7.7 (77.0%) in EM patients, − 10.1 (68.7%) in CM patients, − 10.8 (80.6%) in the MO subgroup, − 9.9 (68.3%) in the MDD subgroup, − 9.5 (66.4%) in the GAD subgroup, and − 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. Conclusions In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

Abstract Background The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. Methods This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. Results This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were − 4.6 (36.2%) and − 4.7 (33.6%) at Month 1, − 6.7 (52.8%) and − 6.8 (48.6%) at Month 3, and − 9.2 (72.4%) and − 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from − 6.2 (21.6%) and − 8.4 (14.0%) at Month 1 to − 18.1 (63.1%) and − 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. Conclusions This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

Abstract Introduction: Multi-level dissemination strategies are needed to increase equitable access to effective treatment for high-risk outpatients with COVID-19, particularly among patients from disproportionately affected communities. Yet assessing population-level impact of such strategies can be challenging. Methods: In collaboration with key contributors in Colorado, we conducted a retrospective cohort study to evaluate a multi-level dissemination strategy for neutralizing monoclonal antibody (mAb) treatment. Real-world data included county-level, de-identified output from a statewide mAb referral registry linked with publicly available epidemiological data. Outcomes included weekly number of mAb referrals, unique referring clinicians, and COVID-19 hospitalization rates. We assessed weekly changes in outcomes after dissemination strategies launched in July 2021. Results: Overall, mAb referrals increased from a weekly average of 3.0 to 15.5, with an increase of 1.3 to 42.1 additional referrals per county in each post-period week (p < .05). Number of referring clinicians increased from a weekly average of 2.2 to 9.7, with an additional 1.5 to 22.2 unique referring clinicians observed per county per week beginning 5 weeks post-launch (p < .001). Larger effects were observed in communities specifically prioritized by the dissemination strategies. There were no observed differences in COVID-19 hospitalization rates between counties with and without mAb treatment sites. Conclusion: Real-world data can be used to estimate population impact of multi-level dissemination strategies. The launch of these strategies corresponded with increases in mAb referrals, but no apparent population-level effects on hospitalization outcomes. Strengths of this analytic approach include pragmatism and efficiency, whereas limitations include inability to control for other contemporaneous trends.

Background: Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting. Methods: We performed an observational multicentric study with a retrospective cohort. All consecutive patients with confirmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT. Results: Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD: 13.59) years. Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD: 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (− 8.5, 95% CI − 14.6, − 2.5) were associated with AMT response. Conclusions: This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea. [ABSTRACT FROM AUTHOR]

ObjectivesThis study compared transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in terms of short- and long-term effectiveness.MethodsThis retrospective cohort study based on nationwide National Health Insurance claims data and Cause of Death data focused on adult patients (n = 3,643) who received SAVR (79%) or TAVR (21%) between 2015 and 2019. Propensity score overlap weighting was applied to account for selection bias. Primary outcomes included all-cause mortality (ACM), hospitalization for heart failure, and a composite endpoint of major adverse cardiac events (MACE). Secondary outcomes included medical utilization, hospital stay, and total medical costs at index admission for the procedure and in various post-procedure periods. The Cox proportional-hazard model with competing risk was used to investigate survival and incidental health outcomes. Generalized estimation equation (GEE) models were used to estimate differences in the utilization of medical resources and overall costs.ResultsAfter weighting, the mean age of the patients was 77.98 ± 5.86 years in the TAVR group and 77.98 ± 2.55 years in the SAVR group. More than half of the patients were female (53.94%). The incidence of negative outcomes was lower in the TAVR group than in the SAVR group, including 1-year ACM (11.39 vs. 17.98%) and 3-year ACM (15.77 vs. 23.85%). The risk of ACM was lower in the TAVR group (HR [95% CI]: 0.61 [0.44–0.84]; P = 0.002) as was the risk of CV death (HR [95% CI]: 0.47 [0.30–0.74]; P = 0.001) or MACE (HR [95% CI]: 0.66 [0.46–0.96]; P = 0.0274). Total medical costs were significantly higher in the TAVR group than in the SAVR in the first year after the procedure ($1,271.89 ± 4,048.36 vs. $887.20 ± 978.51; P = 0.0266); however, costs were similar in the second and third years after the procedure. The cumulative total medical costs after the procedure were significantly higher in the TAVR group than in the SAVR group (adjusted difference: $420.49 ± 176.48; P = 0.0172).ConclusionIn this real-world cohort of patients with aortic stenosis, TAVR proved superior to SAVR in terms of clinical outcomes and survival with comparable medical utilization after the procedure.

Background: Functional recovery is an important treatment goal in major depressive disorder (MDD). This study assessed the real-world effectiveness of vortioxetine in patients with MDD, with particular focus on functioning; dose–response was also assessed. Methods: This was a non-interventional, prospective, multicenter study conducted in Greece. Adult outpatients with MDD (n = 336) initiating vortioxetine (5–20 mg/day flexible dosing) as treatment for a current major depressive episode were followed for 3 months. Analyses were stratified according to vortioxetine dosage at 3 months: 5–10 mg/day versus 15–20 mg/day. Functioning was assessed using the Sheehan Disability Scale (SDS). Results: Mean ± standard error SDS total score decreased (improved) from 18.7 ± 0.3 at baseline to 12.9 ± 0.3 after 1 month of vortioxetine treatment and 7.8 ± 0.4 after 3 months (p < 0.001 vs. baseline for all comparisons). Functional recovery (SDS score ≤ 6) was achieved in 14.6% of patients after 1 month of treatment and 48.4% of patients after 3 months. Improvement from baseline in SDS total and domain scores at 3 months was more pronounced in patients receiving vortioxetine 15–20 mg/day than in those receiving vortioxetine 5–10 mg/day. The mean ± standard error change in SDS total score from baseline was 9.2 ± 0.8 in the 5–10 mg/day group and 12.1 ± 0.4 in the 15–20 mg/day group (p < 0.001). Limitations of this study include its non-interventional study design and lack of a control group or active comparator. Conclusions: Statistically significant and clinically relevant improvements in functioning were seen in patients with MDD treated with vortioxetine in a real-world setting. Higher doses of vortioxetine were associated with significantly greater improvements in functioning. [ABSTRACT FROM AUTHOR]

Introduction: Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. Methods: Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann–Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan–Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). Results: 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3–5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). Conclusion: Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS). [ABSTRACT FROM AUTHOR]

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics' (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms. [ABSTRACT FROM AUTHOR]

Background: Nintedanib is an oral multitarget tyrosine kinase inhibitor approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Recent evidence demonstrated that nintedanib reduced functional disease progression also in subjects with non-IPF progressive fibrosing interstitial lung disease (PF-ILD). However, real-life data on the effectiveness of nintedanib in PF-ILD and familial pulmonary fibrosis (FPF) are lacking. Methods: this retrospective monocentric study enrolled 197 patients affected with IPF, PF-ILD and FPF treated with nintedanib at the Referral Centre of Siena from 2014 to 2021. Pulmonary functional tests and survival data were collected throughout the observation period for the evaluation of mortality and disease progression outcomes. Results: nintedanib treatment significantly reduced the FVC decline rate in IPF and PF-ILD subgroups, but not in FPF subjects. No significant differences were observed among the subgroups in terms of survival, which appeared to be influenced by gender and impaired lung function (FVC < 70% of predicted value). Concerning disease progression rate, a diagnosis of FPF is associated with more pronounced FVC decline despite nintedanib treatment. Conclusions: our research studies the effectiveness and safety of nintedanib in reducing functional disease progression of IPF and PF-ILD. FPF appeared to be less responsive to nintedanib, even though no differences were observed in terms of survival. [ABSTRACT FROM AUTHOR]

Meta-analysis of randomized controlled trials is generally considered the most reliable source of estimates of relative treatment effects. However, in the last few years, there has been interest in using non-randomized studies to complement evidence from randomized controlled trials. Several meta-analytical models have been proposed to this end. Such models mainly focussed on estimating the average relative effects of interventions. In real-life clinical practice, when deciding on how to treat a patient, it might be of great interest to have personalized predictions of absolute outcomes under several available treatment options. This paper describes a general framework for developing models that combine individual patient data from randomized controlled trials and non-randomized study when aiming to predict outcomes for a set of competing medical interventions applied in real-world clinical settings. We also discuss methods for measuring the models' performance to identify the optimal model to use in each setting. We focus on the case of continuous outcomes and illustrate our methods using a data set from rheumatoid arthritis, comprising patient-level data from three randomized controlled trials and two registries from Switzerland and Britain. [ABSTRACT FROM AUTHOR]

Despite the superior efficacy of topical therapies for the treatment of actinic keratoses in clinical trials, cryosurgery remains a frequent treatment modality in clinical practice. Little is known about patients' experience of real-world use of topical therapy. To determine the real-world effectiveness and tolerability of 5-fluorouracil and imiquimod in the treatment of actinic keratoses. A phone survey and chart review was conducted among 51 patients prescribed 5-fluorouracil (N = 27) or imiquimod (N = 24) for actinic keratoses. Six patients (22%) in the 5-fluorouracil group and five patients (21%) in the imiquimod group reported severe local skin reactions, and three patients in both groups (11% and 13%, respectively) were unwilling to use the respective topical therapies again. Patients in the 5-fluorouracil group had, on average, 3.3 fewer cryosurgery spot treatments following topical treatment. Patients in the imiquimod group averaged 2.0 fewer spot treatments. While this study provides information on real-world experiences, patients' responses were limited by the ability to recall treatment and potential adverse effects. High rates of skin reactions, prolonged discomfort, and the continued need for procedural treatments may make patients less willing to use topical 5-fluorouracil or imiquimod for actinic keratoses. [ABSTRACT FROM AUTHOR]

introduction While promising evidence from trials of social-media-based stop smoking support informs service-planning, there is a need for more prospective, observational studies of smoking cessation interventions to build 'real-world' evidence. Specifically, user experiences have been under-explored with qualitative methods to date. This mixed-method evaluation of a closed Facebook group-based behavioral stop smoking support program, which was conducted in Ireland in 2018, aimed to address these issues. methods Pre- and post-program surveys measured smoking abstinence (self-reported 7-day point prevalence), changes in smoking attitudes and behavior, and participant experiences. Engagement with Facebook was measured through counting 'likes' and comments, and was used to categorize groups as 'more active' and 'less active' over a 12-week period of support. Thematic content analysis of semi-structured participant interviews explored program experience in depth. results In total, 13 of 52 participants reported smoking abstinence post-program (25.0%, 95% CI: 14.0-39.0). Participant engagement with Facebook was variable and decreased over the program. Membership of a 'more active' group was associated with better reported participant experience (e.g. 90.9% agreeing 'Facebook group helped me to quit or reduce smoking', versus 33.3% in the 'less active' group, p<0.05). Qualitative analysis identified three over-arching themes: importance of social interactions; perception of health information; and appeal of online support. conclusions Facebook can be used to deliver group-based behavioral stop smoking support in the real world. In Ireland, the one-month post-program abstinence outcomes achieved by other stop smoking services is approximately 50%, and while the outcomes for this service was lower (25%), it is still better than outcomes estimated for unassisted quitting. Engagement and peer-to-peer interactivity should be maximized to support positive participant experience. [ABSTRACT FROM AUTHOR]

This retrospective longitudinal study compared the effectiveness of dexamethasone+lenalidomide (Rd)-based triplet regimens containing proteasome inhibitors (PIs) ixazomib (IRd), carfilzomib (KRd), and bortezomib (VRd) or monoclonal antibodies (MABs) elotuzumab (ERd) and daratumumab (DRd) in patients with relapsed/refractory multiple myeloma (RRMM)—including those with high cytogenetic risk—primarily treated at community oncology clinics in the United States. Electronic health records of adult RRMM patients in a deidentified real-world database (01/01/2014–09/30/2020) who initiated IRd, KRd, VRd, ERd, or DRd in the second or later line of therapy (LOT) were analyzed. The index date was the date of initiation of each LOT and baseline was the 6-month pre-index period. Duration of therapy (DOT), time to next therapy (TTNT), progression-free survival (PFS), and overall survival (OS) were compared across regimens with multivariable Cox proportional hazards models. Of the 1,185 patients contributing 1,332 LOTs, 985 had standard cytogenetic risk (median age, 71 years) and 180 had high risk (median age, 69 years). Compared with other regimens, DRd was associated with longer DOT overall (adjusted hazard ratio [95 % confidence interval]: 1.84 [1.42, 2.38] vs. KRd, 1.65 [1.20, 2.28] vs. ERd, 1.58 [1.23, 2.04] vs. IRd, and 1.54 [1.18, 2.00] vs. VRd), and longer TTNT and PFS. KRd was associated with shorter OS compared with DRd (1.45 [1.01, 2.08]) and VRd (1.32 [1.01, 1.73]). High-risk patients had similar outcomes with all triplet regimens. Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM. [ABSTRACT FROM AUTHOR]

Background: Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. Methods: This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway–targeted mAb [CGRP mAb]). Results: Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were − 7.7 (77.0%) in EM patients, − 10.1 (68.7%) in CM patients, − 10.8 (80.6%) in the MO subgroup, − 9.9 (68.3%) in the MDD subgroup, − 9.5 (66.4%) in the GAD subgroup, and − 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. Conclusions: In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb). [ABSTRACT FROM AUTHOR]

Background: The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. Methods: This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. Results: This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were − 4.6 (36.2%) and − 4.7 (33.6%) at Month 1, − 6.7 (52.8%) and − 6.8 (48.6%) at Month 3, and − 9.2 (72.4%) and − 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from − 6.2 (21.6%) and − 8.4 (14.0%) at Month 1 to − 18.1 (63.1%) and − 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. Conclusions: This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes. [ABSTRACT FROM AUTHOR]

Data on real-world experiences for patients treated with ixekizumab is currently limited. Describe characteristics of ixekizumab-treated psoriasis patients and provide evidence of clinical outcomes using disease severity scores Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) in the real world. Chart review was performed for adult patients treated with ixekizumab at a single Canadian dermatology clinic (February 2017–August 2018). The cohort was stratified into responders (patients who remained on ixekizumab) and non-responders (patients who discontinued ixekizumab). Subgroup analyses were performed for responders to assess clinical improvement stratified by previous biologic exposure. Thirty-eight patients were included (mean observational time 32 weeks). At baseline, mean PASI and BSA were 10.8 and 11.6%, respectively. Mean changes in PASI and BSA were –7.8 and –6.7%, respectively, at week 4. PASI 100 was achieved in 70% of patients. Significant differences in mean change of BSA were seen between bio-naïve and bio-experienced patients. This analysis represents the first investigation of early clinical outcomes in a small cohort of Canadian patients treated with ixekizumab. Overall, complete and rapid skin clearance was observed. Future studies including more patients and longer follow-up time are crucial to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effectiveness of secukinumab in patients with axSpA treated in routine clinical settings in 5 European countries. Methods: Retrospective analysis of a cross-sectional survey to assess real-world effectiveness of secukinumab in the management of axSpA and rheumatologist satisfaction with treatment in France, Germany, Italy, Spain and the UK from March to December 2018. Outcomes collected included patient demographics, clinical characteristics and rheumatologist- and patient-reported satisfaction with secukinumab treatment. Results: Five hundred thirty-five patients receiving secukinumab for more than 4 months were assessed, 359 of whom were diagnosed with AS and 178 with nr-axSpA. Rheumatologist assessment of disease status at treatment initiation indicated that 39 (7.3%) had stable/improving disease. Secukinumab treatment for 4 months or longer resulted in 515 (95.9%) patients judged as stable/improving. Treatment was associated with benefits from initiation to assessment in terms of BASDAI (6.2 vs 2.8), 44-joint count score (9.7 vs 6.6), rheumatologist global VAS score (56.9 vs 23.0) and patient global VAS scores (64.4 vs 25.5). These benefits for key clinical outcomes were sustained for periods of 12 months or longer. Patient-reported outcomes on health status using EQ-5D, global functioning using the ASAS health index and overall work impairment via WPAI were sustained over the treatment period, while patient and rheumatologist satisfaction with secukinumab treatment remained very high at 80.2 and 91.2%, respectively. Conclusion: Consistent benefits across multiple clinical and patient-reported outcomes were seen with secukinumab treatment in patients with AS and nr-axSpA treated in routine clinical settings across five European countries. Key Points • In routine clinical settings across five European countries, secukinumab treatment resulted in improvements in a wide range of clinical outcomes including physician-reported disease severity, disease status, pain, BASDAI, 44-joint count score and global VAS scores. • Key clinical and patient reported outcomes were sustained for a 12-month period or longer with secukinumab treatment. • Rheumatologist- and patient-reported treatment satisfaction was high with secukinumab. [ABSTRACT FROM AUTHOR]

Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives: To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study -demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods: The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged =12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results: Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion: Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

Background Direct-acting antivirals (DAAs) are becoming accessible in sub-Saharan Africa. This study examined the effectiveness of DAAs in patients treated through the Rwandan national health system and identified factors associated with treatment outcomes. Methods This retrospective study used data from the national hepatitis C virus (HCV) program for patients who initiated DAAs between November 2015 and March 2017. Sustained virological response at 12 weeks after treatment (SVR12) was the primary outcome. Logistic regression models were fit to estimate the relationship between patients' clinical and demographic characteristics and treatment outcome. Results 894 patients started treatment during the study period; 590 completed treatment and had SVR12 results. Among the 304 patients without SVR12 results, 48 were lost to follow-up and 256 had no SVR12 results but clinical data indicated they likely completed treatment; these patients were classified as nonvirological failure because viral clearance could not be determined. In a per-protocol analysis of 590 patients with SVR12 results, SVR12 was achieved in 540 (92%), and virological failure occurred in 50 (8%). Pretreatment HCV RNA above the median split was associated with virological failure. Intention-to-treat analyses including all patients showed that SVR12 was achieved in 540 (60%), with nonvirological failure in 304 (34%) and virological failure in 50 (6%). Patients in Western Province were more likely to experience nonvirological failure than patients in Kigali, likely owing to the 5–7-hour travel required to access testing and treatment. Conclusions DAAs were effective when implemented through the Rwandan national health system. Decentralization and enhanced financing are underway in Rwanda, which could improve access to treatment and follow-up as the country prepares for HCV elimination. [ABSTRACT FROM AUTHOR]

Aims: This study compared medication use, healthcare resource utilization (HRU), and exacerbations among individuals with chronic obstructive pulmonary disease (COPD) who initiated glycopyrrolate/eFlow Closed System nebulizer 25 mcg/mL glycopyrrolate (hereafter GLY) in a real-world setting before and after treatment initiation. Materials and methods: Retrospective claims and hospital charge master data were used to identify individuals ≥ 40 years of age diagnosed with COPD who initiated GLY between 1 April 2018 and 28 February 2019 (first prescription claim-index date). Patients were excluded if they had ≥1 asthma diagnosis in the 6-month pre-index period. The proportion of patients with COPD-related medications, other outpatient HRU, hospitalizations, and exacerbations were compared between the 6-month preindex and 6-month follow-up periods. Among patients utilizing the service, per-person utilization rates were compared between the two periods. Results: Among patients initiating GLY (n=767), the mean age was 71.4 years, 56.1% were female, and the mean Charlson Comorbidity Index score was 2.0. The mean number of GLY claims per person was 3.8 during the follow-up period. Compared to the pre-index period, a lower proportion of patients had claims for COPD medications including oral corticosteroids (62.1% vs. 69.1%, p=.0001) and fixeddose SAMA/SABA (26.1% vs. 33.0%, p<.0001) and a higher proportion of patients had claims for LABA (29.7% vs. 22.6%, p<.0001) during the follow-up period. Fewer patients had ≥1 COPD-related physician office visit (42.4% vs. 49.8%, p<.0001), radiology test (40.7% vs. 46.5%, p=.005), or moderate exacerbation (48.0% vs. 53.2%, p=.01) after initiating GLY. Among patients with linkage to inpatient data (n=316), fewer were hospitalized (7.9% vs. 13.0%, p=.037) and hospital length of stay was shorter (1.9 vs. 3.6 days, p=.017) after initiating GLY/eFlow. Conclusions: Among patients initiating GLY in a real-world setting, COPD medications, hospitalizations, other HRU, and exacerbations decreased after treatment initiation compared with the 6-month pre-index period. [ABSTRACT FROM AUTHOR]

Background and Aims This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn's disease [CD] patients. Methods This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting. Results A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28–0.62]) and SIs (HR = 0.40 [0.19–0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [ p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45–0.76]). Other outcomes did not significantly differ between groups. Conclusion In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile. [ABSTRACT FROM AUTHOR]

Background: There is limited data on the relative survival rate of first-line therapy of gefitinib, erlotinib (first-generation epidermal growth factor receptor-tyrosine kinase inhibitor [EGFR-TKI]), and afatinib (second-generation EGFR-TKI) in patients with EGFR-mutated advanced lung adenocarcinoma in real-world data, especially in the Asian population. This study aimed to compare the relative survival rate of gefitinib, erlotinib, and afatinib in patients with EGFR-mutated advanced lung adenocarcinoma by real-world data in Taiwan.Methods: This retrospective cohort population-based study included untreated adult patients diagnosed with advanced lung adenocarcinoma who were identified in the Taiwan National Health Insurance Research Database between 2014 and 2017. The date of EGFR-mutated advanced lung adenocarcinoma diagnosis was referred as index date. This outcome evaluated overall survival (OS) and time to treatment failure (TTF) between gefitinib, erlotinib, and afatinib. Switching EGFR-TKIs or chemotherapy and new development of brain metastases were proxies of TTF. Estimated relative treatment effects on OS and TTF among EGFR-TKIs were adjusted by inverse probability of treatment weighting (IPTW) in Cox proportional hazards model. Propensity score (PS) matched pair analyses were performed as sensitivity analyses.Results: The study cohort included 3,695 patients initiated with gefitinib, 3,310 with erlotinib, and 3,041 with afatinib. The mean age among the three treatment groups was 70.4 (±11.6), 66.8 (±11.6), and 64.3 (±11.4) years, and the female percentage was 70.4, 58.6, and 57.7%, respectively. Afatinib showed longer median OS than gefitinib (23.9 vs. 21.3 months; adjusted hazard ratio (aHR), 0.87; p < 0.001) and erlotinib (23.9 vs. 21.8 months; aHR, 0.87; p = 0.001). Consistent results were observed with TTF outcomes. For patients with brain metastases at diagnosis, afatinib showed similar OS with erlotinib (p = 0.917) but superior to gefitinib (p = 0.028). PS matching had similar results with IPTW adjustment in the study population.Conclusion: Afatinib as first-line therapy had better survival outcomes for EGFR-mutated advanced lung adenocarcinoma than gefitinib and erlotinib in the Taiwan population. Both erlotinib and afatinib demonstrated superior treatment effect in patients with initial brain metastases than gefitinib.

Background: There is limited data on the relative survival rate of first-line therapy of gefitinib, erlotinib (first-generation epidermal growth factor receptor-tyrosine kinase inhibitor [EGFR-TKI]), and afatinib (second-generation EGFR-TKI) in patients with EGFR-mutated advanced lung adenocarcinoma in real-world data, especially in the Asian population. This study aimed to compare the relative survival rate of gefitinib, erlotinib, and afatinib in patients with EGFR-mutated advanced lung adenocarcinoma by real-world data in Taiwan. Methods: This retrospective cohort population-based study included untreated adult patients diagnosed with advanced lung adenocarcinoma who were identified in the Taiwan National Health Insurance Research Database between 2014 and 2017. The date of EGFR-mutated advanced lung adenocarcinoma diagnosis was referred as index date. This outcome evaluated overall survival (OS) and time to treatment failure (TTF) between gefitinib, erlotinib, and afatinib. Switching EGFR-TKIs or chemotherapy and new development of brain metastases were proxies of TTF. Estimated relative treatment effects on OS and TTF among EGFR-TKIs were adjusted by inverse probability of treatment weighting (IPTW) in Cox proportional hazards model. Propensity score (PS) matched pair analyses were performed as sensitivity analyses. Results: The study cohort included 3,695 patients initiated with gefitinib, 3,310 with erlotinib, and 3,041 with afatinib. The mean age among the three treatment groups was 70.4 (±11.6), 66.8 (±11.6), and 64.3 (±11.4) years, and the female percentage was 70.4, 58.6, and 57.7%, respectively. Afatinib showed longer median OS than gefitinib (23.9 vs. 21.3 months; adjusted hazard ratio (aHR), 0.87; p < 0.001) and erlotinib (23.9 vs. 21.8 months; aHR, 0.87; p = 0.001). Consistent results were observed with TTF outcomes. For patients with brain metastases at diagnosis, afatinib showed similar OS with erlotinib (p = 0.917) but superior to gefitinib (p = 0.028). PS matching had similar results with IPTW adjustment in the study population. Conclusion: Afatinib as first-line therapy had better survival outcomes for EGFR-mutated advanced lung adenocarcinoma than gefitinib and erlotinib in the Taiwan population. Both erlotinib and afatinib demonstrated superior treatment effect in patients with initial brain metastases than gefitinib. [ABSTRACT FROM AUTHOR]