Cluster Analysis Identifies Patients With Severe Eosinophilic Asthma Who Achieve Super-Response and Remission With Mepolizumab.

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes.

BACKGROUND: The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). METHODS: We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. RESULTS: The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87-101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. CONCLUSION: A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

BACKGROUND: Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. OBJECTIVE: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. METHODS: We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. RESULTS: Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. CONCLUSIONS: Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

Plant cover and biomass change on extensive green roofs over a decade and ten lessons learned.

Green roofs are well studied for the environmental, social, and economic services these provide. As a result, green roofs are widespread and within the common vernacular of city residents. Green roof bylaws and construction standards are present in many cities in North America, rooting the presence of this green infrastructure within urban landscapes. Although examples of green roofs constructed decades ago exist, rarely are green roofs monitored over such long periods, and in ways that allow for experimentation, analysis, and conclusions about performance or function. In this study we present findings on plant cover and biomass from a green roof testing facility in Toronto, Canada that was monitored for over a decade. We examine the contributions of growing media, planting, and irrigation in the first seven years (2011-2021) of the eleven-year monitoring period. We found that during this maintenance phase period (2011-2017), plant cover and biomass was highest in modules planted with Sedum, included organic media, and were irrigated, whereas non-irrigated modules planted with forbs and grasses had the poorest performance regardless of media type. Following the stoppage of irrigation, and the post maintenance phase (2017-2021), modules initially planted with Sedum continued to sustain cover and biomass whereas planted forbs and grasses mostly disappeared, and these treatments were overtaken by Sedum. Our findings demonstrate that with irrigation, plantings of forbs and grasses can sustain plant cover and biomass. However, Sedum buffers against major changes to environmental conditions or abrupt changes to maintenance, adding insurance against failure of extensive green roofs.

The Longevity Improvement & Fair Evidence (LIFE) Study: Overview of the Study Design and Baseline Participant Profile.

BACKGROUND: The Longevity Improvement & Fair Evidence (LIFE) Study, which was launched in 2019, is a multi-region community-based database project that aims to generate evidence toward extending healthy life expectancy and reducing health disparities in Japan. Herein, we describe the LIFE Study's design and baseline participant profile. METHODS: Municipalities participating in the LIFE Study provide data from government-administered health insurance enrollees and public assistance recipients. These participants cover all disease types and age groups. Centered on healthcare claims data, the project also collects long-term care claims data, health checkup data, vaccination records, residence-related information, and income-related information. The different data types are converted into a common data model containing five modules (health care, long-term care, health checkup, socioeconomic status, and health services). We calculated the descriptive statistics of participants at baseline in 2018. RESULTS: The LIFE Study currently stores data from 1,420,437 residents of 18 municipalities. The health care module contains 1,280,756 participants (mean age: 65.2 years), the long-term care module contains 189,069 participants (mean age: 84.3 years), and the health checkup module contains 274,375 participants (mean age: 69.0 years). Although coverage and follow-up rates were lower among younger persons, the health care module includes 74,151 children (0-19 years), 273,157 working-age adults (20-59 years), and 933,448 older persons (≥60 years). CONCLUSION: The LIFE Study provides data from over 1 million participants and can facilitate a wide variety of life-course research and cohort studies. This project is expected to be a useful platform for generating real-world evidence from Japan.

Efficacy and safety of tocilizumab in Behçet's syndrome with refractory arterial lesions: a single-centre observational cohort study in China.

OBJECTIVE: The aim of this observational cohort study was to assess the effectiveness and safety of the IL-6-receptor inhibitor tocilizumab (TCZ) in Behçet's syndrome (BS) with refractory arterial involvement. METHODS: Ten patients admitted to the Rheumatology and Immunology Department of Peking University People's Hospital between January 2014 and December 2019 were enrolled. The enrolled patients met the BS international criteria and exhibited severe arterial impairments. Refractory arterio-BS was diagnosed based on objective vascular symptoms unexplainable by other known illnesses, and resistance to traditional immunosuppressants and glucocorticoids after 12 weeks. Patients received 8 mg/kg TCZ infusions every 4 weeks for ≥24 weeks, with simultaneous continuation of immunosuppressants and glucocorticoids. Clinical and imaging data were assessed before and after TCZ treatment. RESULTS: The enrolled patients were men aged 44.3 (10.5) years; the median disease duration was 186.5 (45.7) months, and the average age of arterial impairment onset was 38.7 (12.9) years. The following trends were observed: improvement and maintenance of symptoms after the 26.8 (7.2)-month follow-up, n = 9; complete remission, n = 6; partial response, n = 3; immunosuppressant dose reduction, n = 4; radiologic improvement of arterial lesions, n = 4; and TCZ discontinuation owing to enlarged abdominal aortic aneurysm relapse, n = 1. The average daily glucocorticoid dose reduced from 54.5 (20.6) to 8.3 (3.6) mg/d (P < 0.001), while the median ESR and CRP values reduced from 50 (2-82) mm/h and 32.9 (2.1-62.3) mg/dl to 4 (1-10) mm/h and 2.9 (0.2-12.1) mg/dl, respectively (P < 0.001). No TCZ-associated side effects were noted. CONCLUSION: TCZ proved to be safe and effective for refractory arterial lesions in BS, with a steroid- and immunosuppressant-sparing benefit.

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic.

BACKGROUND: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID-19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. METHODS: Visual analogue scale for quality of life (VAS-QoL), VAS for symptom scores (VAS-symptom), medication scores (MSs), and total symptom scores (TSS-6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre-pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2-month intervals (Group 3). RESULTS: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS-symptom, and TSS-6 scores of Group 3 patients during the pandemic were higher than the pre-pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS-QoL scores of Group 3 during the pandemic were lower than the pre-pandemic scores (p < 0.001). Median TSS-6 and VAS-symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). CONCLUSION: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.

Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data.

BACKGROUND: Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. METHODS: The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. RESULTS: A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/µL to 89/µL and 85/µL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. CONCLUSION: Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings.

Therapeutic management and outcome of patients with advanced systemic mastocytosis treated with midostaurin: A comprehensive real-life study in the French national healthcare database.

Advanced Systemic Mastocytosis (Adv-SM) is rare and has a poor prognosis. Midostaurin (Rydapt® ) is one of the few treatments for Adv-SM in Europe. The study aims were to describe the characteristics of patients treated with midostaurin, their treatment modalities, outcomes, and serious events requiring hospitalization. This retrospective observational study was conducted using the French National Healthcare Database (SNDS) and included adult Adv-SM patients treated with midostaurin between 01-01-2012 and 09-30-2018. Kaplan-Meier method was used to assess survival and treatment duration. Eighty-one patients were included: 37 with Aggressive Systemic Mastocytosis (SM) (46%), 31 with SM with an Associated Hematological Neoplasm (38%), and 4 with Mast Cell Leukemia (5%). The SM subtype was undetermined in 9 patients (11%). The median age was 67 years; 64% of patients were male. Over the mean follow-up of 11.4 months, median midostaurin treatment duration was 8.4 months and 28 patients (35%) were still under treatment at the end of the study. One-year and 5-year overall survival rates estimated since the time of diagnosis were 83% and 56%, respectively. Twelve serious events (among those frequently reported during clinical trials and compassionate use) requiring hospitalization were identified; a causal association with Adv-SM treatment could neither be excluded nor established. In this first real-life study on patients treated with midostaurin for Adv-SM, the patients' characteristics, their management, treatment discontinuation, and survival were in line with previous results (compassionate use and clinical trials).

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

The Ostomy Skin Tool 2.0: a new instrument for assessing peristomal skin changes.

BACKGROUND: Peristomal skin complications (PSCs) are frequently reported postoperative complications. PSCs can present visibly or as symptoms such as pain, itching or burning sensations. AIM: To develop a new tool that can capture a range of sensation symptoms together with visible complications and an objective assessment of discolouration in the peristomal area. METHOD: Consensus from qualitative interviews with health professionals and people with an ostomy, and input from expert panels, formed the basis of a patient-reported outcome (PRO) questionnaire. A decision tree model was used to define a combined score including PRO and objectively assessed discolouration area. FINDINGS: Six elements were included in the PRO questionnaire and four health states representing different severity levels of the peristomal skin were defined. CONCLUSION: The Ostomy Skin Tool 2.0 is a sensitive tool that can be used to follow changes in the peristomal skin on a regular basis and thereby help prevent severe PSCs.

Lacosamide as first add-on or conversion monotherapy: A retrospective real-life study.

PURPOSE: Lacosamide (LCM), the R-enantiomer of 2-acetamido-N-benzyl-3-methoxypropionamide, is a newer approved antiseizure medication characterized by a novel pharmacodynamic and favorable pharmacokinetic profile that was approved as adjunctive treatment for adults with focal onset and focal to bilateral tonic-clonic seizures in 2008, and recently also for monotherapy. The aim of this study was to evaluate the effectiveness and tolerability of LCM as first add-on or conversion monotherapy in adult subjects with focal epilepsy. METHODS: We retrospectively included all adult patients who received LCM as first add-on regimen or as substitution monotherapy at least 12 months before starting the chart review, with a historical baseline of 6 months prior to day of the first administration of LCM. The choice of treatment was made independently by the epilepstologists, according to routine clinical practice. Clinical data were obtained at 3, 6, and 12 months after subjects started LCM and then analyzed to assess retention rate, seizure freedom, and adverse events (AE). RESULTS: A total of 101 patients (58 men) with a mean age of 44 years and a median epilepsy duration of 6.6 years (range 1-53) were included in the study. At 12 months 72 patients retained LCM, 54 (75%) of them were seizure free, 44 (81.5%) in monotherapy and 10 (18.5%) in add-on LCM treatment. Among all subjects, 31 (57.4%) were free from seizure under LCM monotherapy throughout the entire observation period. Thirty one out of 72 (43%) PwE who retained LCM at 12 months, were free from seizures throughout the entire observation period. The maintenance median dosage of LCM was 200 mg/day. Ten (10%) subjects reported mild to moderate AE, most commonly drowsiness and dizziness. No serious AE were documented. CONCLUSIONS: This real-life study confirms that LCM is an effective and well tolerated treatment option as first add-on or conversion monotherapy for focal seizures.

DECISA Project (DErmatology Clinics in Italy: Survey on Alitretinoin): A real-life retrospective cohort multicenter study on 438 subjects with chronic hand eczema.

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Olfactory Training and Visual Stimulation Assisted by a Web Application for Patients With Persistent Olfactory Dysfunction After SARS-CoV-2 Infection: Observational Study.

BACKGROUND: Persistent olfactory dysfunction is a significant complication of SARS-CoV-2 infection. Olfactory training involving aromatic oils has been recommended to improve olfactory recovery, but quantitative data are missing. OBJECTIVE: We aimed to quantify the benefit of olfactory training and visual stimulation assisted by a dedicated web application for patients who experienced olfactory dysfunction for ≥1 month. METHODS: We performed an observational, real-life, data-based study on a cohort of patients who experienced at least 1 month of persistent olfactory dysfunction between January 30 and March 26, 2021. An analysis was performed after a mean olfactory training time of 4 weeks, and at least 500 patients were assessable for primary outcome assessment. Participants exposed themselves twice daily to odors from 4 high-concentration oils and visual stimulation assisted by a dedicated web application. Improvement was defined as a 2-point increase on a 10-point, self-assessed olfactory visual analogue scale. RESULTS: In total, 548 patients were assessable for primary outcome assessment. The mean baseline, self-assessed olfactory score was 1.9 (SD 1.7), and this increased to 4.6 (SD 2.8) after a mean olfactory training time of 27.7 days (SD 17.2). Olfactory training was associated with at least a 2-point increase in 64.2% (352/548) of patients. The rate of patients' olfactory improvement was higher for patients who trained for more than 28 days than that rate for patients who trained for less than 28 days (73.3% vs 59%; P=.002). The time to olfactory improvement was 8 days faster for patients with hyposmia compared to the time to improvement for patients with anosmia (P<.001). This benefit was observed regardless of the duration of the olfactory dysfunction. CONCLUSIONS: Olfactory training and visual stimulation assisted by a dedicated web application was associated with significant improvement in olfaction, especially after 28 days of olfactory training.

Multinational survey on living with an ostomy: prevalence and impact of peristomal skin complications.

BACKGROUND: Peristomal skin complications (PSCs) impair life for people with an ostomy. Visual signs of PSCs include discolouration, but sensation symptoms like pain, itching, and burning are equally important and underreported. AIM: To provide improved understanding of PSC prevalence and associated challenges in the communities of ostomy patients and ostomy care nurses. METHODS: The Ostomy Life Study 2019 encompassed a patient survey (completed by 5187 people with an ostomy) and a nurse survey (completed by 328 ostomy care nurses). FINDINGS: In total, 88% of patients experienced PSCs and 75% experienced PSC symptoms in the absence of discolouration. Eighty per cent of nurses considered ostomy-related issues to be the main reason for PSCs, and a correlation between PSC severity and number of nurse consultations was demonstrated. CONCLUSION: This study revealed a remarkably high PSC incidence in the absence of discolouration and highlighted direct consequences of having compromised skin and the health-economic consequences.

FOLFIRINOX De-Escalation in Advanced Pancreatic Cancer: A Multicenter Real-Life Study.

BACKGROUND: Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer. MATERIALS AND METHODS: This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity. RESULTS: Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7-20.3) and median PFS1 was 9.4 months (95% CI, 8.5-10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%) patients versus 5FU monotherapy in 52 (35%) and FOLFOX in 25 (17%) patients. Among 118 patients who received maintenance CT with FOLFIRI or 5FU, there was no difference in PFS1 (median, 9.0 vs. 10.1 months, respectively; p = .33) or OS (median, 16.6 vs. 18.7 months; p = .86) between the two maintenance regimens. Reintroduction of FOLFIRINOX was performed in 20.2% of patients, with a median PFS2 of 2.8 months (95% CI, 2.0-22.3). The rates of grade 3-4 toxicity were significantly higher with FOLFIRI maintenance CT than with 5FU (41% vs. 22%; p = .03), especially for neuropathy (73% vs. 9%). CONCLUSION: 5FU monotherapy maintenance appeared to be as effective as FOLFIRI, in a FOLFIRINOX de-escalation strategy, which is largely used in France. IMPLICATIONS FOR PRACTICE: FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.

Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis.

BACKGROUND: Dupilumab is an anti-IL-4Rα antibody used in the treatment of patients with moderate-to-severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. METHODS: This multicentric, prospective, observational, real-life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16 weeks. Safety was also assessed. RESULTS: We enrolled 123 patients with msAD. Between baseline and 16 weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient-Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n = 41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five-item Asthma Control Questionnaire scores) and disease-related QoL (measured using the Asthma QoL Questionnaire scores). Thirty-five patients (28.5%) developed conjunctivitis during the study period. CONCLUSION: These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD.

Short and long-term efficacy of adalimumab in ulcerative colitis: a real-life study.

Objective: Randomized controlled trials have shown the effectiveness of Adalimumab in ulcerative colitis. However, real-life data is scarce. We aimed to assess the effectiveness and predictive factors of effectiveness in a large Swedish cohort.Methods: Retrospective capture of data from local registries at five Swedish IBD centers. Clinical response and remission rates were assessed at three months after starting adalimumab treatment and patients were followed until colectomy or need for another biological. Bio-naive patients were compared to bio experienced patients. Factors associated with short term responses were assessed using logistic regression model. Failure on drug was assessed using a Cox proportional hazards regression model.Results: 118 patients (59 males, 59 females) with median age 34.4 years (IQR 27.0-51.4) were included. Median disease duration was 4.3 years (IQR 2.0-9.0) and follow-up 1.27 years (IQR 0.33-4.1). A clinical corticosteroid-free remission was achieved by 38/118 (32.2%) and response by 91/118 (77%) after three months. CRP >3 mg/l at baseline was predictive of short-term failure to reach corticosteroid-free remission. Factors associated with survival on the drug were male gender, CRP <3 mg/l and absence of primary sclerosing cholangitis. Patients >42 years of age at diagnosis were more likely to respond to adalimumab and remain on treatment compared to patients <20 years.Conclusions: An elevated CRP-level, primary sclerosing cholangitis and female gender were predictors of treatment failure. In contrast older age at diagnosis was a predictor of short-term clinical response and drug survival. Prior infliximab failure, regardless of cause, did not influence the outcome of adalimumab treatment.

Pornography and Relationship Quality: Establishing the Dominant Pattern by Examining Pornography Use and 31 Measures of Relationship Quality in 30 National Surveys.

Numerous studies have examined the association between pornography use and various measures of relationship quality. Yet scholars have also pointed out the limitations of many such studies, including inconsistent findings for men and women, non-representative samples, and negatively biased measures that could result in misleading findings. The purpose of this study was to establish a dominant pattern in the association between pornography use and relationship quality in a way that mitigated these issues. Data were taken from 30 nationally representative surveys, which together included 31 measures of relationship quality: 1973-2018 General Social Surveys (1 repeated measure); 2006 Portraits of American Life Study (13 measures); 2012 New Family Structures Study (12 measures); and 2014 Relationships in America Survey (5 measures). This allowed for 57 independent tests examining the association between pornography use and relationship outcomes for married Americans and 29 independent tests for unmarried Americans. Along with bivariate associations, full regression models were estimated with sociodemographic controls and interaction terms for gender. For married and unmarried Americans alike, pornography use was either unassociated or negatively associated with nearly all relationship outcomes. Significant associations were mostly small in magnitude. Conversely, except for one unclear exception, pornography use was never positively associated with relationship quality. Associations were only occasionally moderated by gender, but in inconsistent directions. While this study makes no claims about causality, findings clearly affirmed that, in instances where viewing pornography is associated with relationship quality at all, it is nearly always a signal of poorer relationship quality, for men and women.

Real-Life Data in the Treatment of Neovascular Age-Related Macular Degeneration: Results from the Imaculaweb Registry Evaluated in a Single Italian Medical Retina Center.

INTRODUCTION: The aim of this study is to assess and compare the long-term clinical efficacy of anti-VEGF drugs using the Imaculaweb registry. METHODS: In this observational study based on the Imaculaweb registry, outcome measures were the number of injections, the change in mean visual acuity (VA) and central macular thickness (CMT), and the time between diagnosis and the first injection. RESULTS: In total, 126 eyes of 109 patients were included in the study. The mean VA was 49.4 ± 21.4, 54.1 ± 22.2, 51.6 ± 24.9, and 48.3 ± 25.7 letters at baseline and at the 1-, 2-, and 3-year follow-ups, respectively. Significant VA increases (p = 0.0002 for the first year and p = 0.045 for the second year) were documented at years 1 and 2 but not at year 3 (p = 0.8). The mean number of injections was 5.2, 2.6, and 2.3 at the 1-, 2-, and 3-year follow-ups, respectively. In the first year, 30% of the patients received at least 7 injections, while only 6.4% received <3 injections. CMT decreased significantly during the overall follow-up period, and intra- and subretinal fluid decreased (p < 0.0001). CONCLUSION: Imaculaweb turned out to be an effective tool to collect and share clinical data as well as to monitor patient outcome.