Impact of Atopic Dermatitis on Adult Women's Lives: A Survey of 1,009 French Women.

Atopic dermatitis (AD) is one of the most common inflammatory diseases, and has a higher prevalence among females in adulthood. The aim of this observational, cross-sectional, survey-based study was to evaluate the impact of AD on the daily lives of adult women patients. A scientific committee composed exclusively of women constructed a specific questionnaire in partnership with the French Eczema Association. Severity of AD was evaluated with the Patient-Oriented Eczema Measure (POEM). A sample of 1,009 adult women (mean age ± standard deviation: 41.8 ± 14.2 years) with AD was identified from a representative sample of the French population (82% response rate 1,230 women surveyed). According to the POEM, 50.64% (n = 511) of subjects were identified as having mild AD, 39.35% (n = 397) moderate AD, and 10.01% (n = 101) severe AD. Overall, 67.7% (n = 682) reported that their eczema involved a visible area (face, neck or hands), and 19.6% (n = 198) a sensual area (breasts/chest, genital area or buttocks). Of the 720 women with menstrual cycles, exacerbations of AD were reported to occur mostly before (50.6%) and during (48.3%) menstruation. A small proportion of women, 7.3% (n = 74), reported being afraid of  becoming pregnant because of their eczema. If AD involvement was in a visible area it had a greater impact on romantic relationships, sexual relationships and occupation. If AD involvement was in a sensual area it had a greater influence on romantic relationships and sexuality. Particular attention should be given to patients with localization of AD on the face, neck or hands, as they have a higher risk of social exclusion. Moreover, these results should encourage health professionals to ask patients with AD about the possible involvement of sensual areas.

Impact of Baricitinib on Patients' Quality of Life after One Year of Treatment for Atopic Dermatitis in Real-World Practice: Results of the Observatory of Chronic Inflammatory Skin Diseases Registry.

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients' lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patient-reported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well.

Baseline Demographics, Comorbidities, Treatment Patterns and Burden of Atopic Dermatitis in Adults and Adolescents from the GLOBOSTAD Long-Term Observational Study.

INTRODUCTION: Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. METHODS: The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. RESULTS: Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. CONCLUSION: Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03992417. Video Abstract.

What should a surgeon know about hidradenitis suppurativa?

Otherwise known as Verneuil's disease, hidradenitis suppurative (HS) is a severe dermatosis of heterogeneous appearance affecting 1% of the population. Its pathophysiology is multifactorial, involving genetic predisposition, inflammatory disorder and environmental elements. Its diagnosis is based on the association of three clinical characteristics: characteristic lesions, typical localizations, and the chronic and recurrent nature of the lesions. Given its diversified aspects, diagnosis can be difficult to achieve. As its manifestations often include abscesses, it is important for the surgeon to know how to detect this pathology. The development of biologics has improved treatment of this disease, treatment that necessitates a multidisciplinary medical and surgical approach involving dermatologists and proctologists as well as surgeons. The objective of this report is to synthesize what a surgeon will need to know so as effectively treat HS patients.

Antibiotic Treatment for Hidradenitis Suppurativa in France: A Practice Survey.

Purpose: Antibiotics are used for hidradenitis suppurativa's management with limited evidence. Choice of antibiotics is based on small randomized controlled trial or open case-series. Patients and Methods: We performed a practice survey in Resoverneuil, a French network of physicians treating hidradenitis suppurativa, to identify the antibiotic strategy according to the Hurley stage. Online questionnaire was sent to all members of ResoVerneuil between January and February 2021. Results: In total, 108 physicians answered the survey: 37.6% were hospital based, 34.6% had a private practice and 27.8% a mixed practice, and 13.8% had a dedicated consultation for hidradenitis suppurativa. Sixty-three physicians reported seeing fewer than 5 patients with hidradenitis suppurativa per month; 29 seeing 5 to 15 patients per month; and 9 seeing more than 15 patients per month. More than 90% declared prescribing antibiotics for flares in Hurley 1 and 2 stages, and 83% in Hurley 3 stages, mostly amoxicillin-clavulanic acid and pristinamycin. Of these physicians, 29.7% declared prescribing a background antibiotic therapy for Hurley 1 stage with less than 4 flares per year, and more than 75% for Hurley 1 stage with more than 4 flares per year, Hurley 2 and Hurley 3 stages; mostly cyclins, combination of rifampicin and clindamycin and sulfamethoxazole-trimethoprim. Conclusion: This survey underlines the heterogeneity in antibiotic prescription for hidradenitis suppurativa in France, particularly as background therapy.

How to Define Mild to Severe Hidradenitis Suppurativa? A Simple New Tool Based on Latent Class Analysis of EPIVER Data Study.

Purpose: Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by recurrent or chronic painful and suppurating lesions in the apocrine gland-bearing regions. The lack of knowledge about HS and its extremely heterogeneous clinical presentation, in terms of both lesion appearance and sites of involvement, frequently delay its diagnosis for several years. Objectives: in this study, using the latent class analysis, it was demonstrated that severity of HS could be evaluated not only with clinical or surgical characteristics but also with gender specificities. Patients and Methods: Clinical and sociodemographic data of HS patients were retrospectively analysed with the latent class method in order to create a classification tool of disease severity. Results: From the study of 1428 HS patients (544 men and 884 women), two classification models, depending on gender, were developed. Each classification model was composed of three distinct latent classes clearly identified and defined from mild-to-severe cases of HS. These classification models of HS severity were not distorted by patient ages and were coherent with Hurley stages but were more clinically precise. Conclusion: In this study, a convenient classification tool, useful for facilitating decision support in routine practice, has been developed. This tool could be used to define clinical subgroups within a study population.

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Switching biologics in children with psoriasis: Results from the BiPe cohort.

BACKGROUND: There is currently little information on switching biologics in pediatric psoriasis. OBJECTIVE: To evaluate the real-world clinical practice and safety of switching biologics in the "Biological Treatments for Pediatric Psoriasis" (BiPe) cohort. METHODS: Data for all 134 patients included in the BiPe cohort were analyzed. A further evaluation of the subpopulation of patients who switched from a first-line biologic to a second-line biologic was then conducted. Drug survival rates were also compared between biologics given as first-line or second-line agents. RESULTS: Overall, 29 patients (female: 55%; mean age: 16.6 ± 3.0 years) switched between two biologics. Etanercept (ETN) was the first-line biologic used in 23 patients: 16 (69.6%) switched to adalimumab (ADA) and seven (30.4%) to ustekinumab (UST). Six patients received first-line ADA and switched to UST. Loss of efficacy (62.1%), primary inefficacy (20.7%), and parental choice (6.9%) were the main reasons for switching biologics. One (3.4%) of the switches was performed because of adverse events or intolerance. For UST and ADA, the 18-month drug survival rate did not differ according to whether the agent was given as a first-line or second-line biologic (UST: P = .24; ADA: P = .68). No significant differences in drug survival rates were observed between the three different switches (ADA to UST, ETN to ADA, and ETN to UST). CONCLUSION: Our study provided key insights into the real-life clinical practice of switching biologics in pediatric psoriasis patients. However, more information and guidance on switching biologics in pediatric psoriasis are needed to improve real-life practice and outcomes.

Biological Therapies or Apremilast in the Treatment of Psoriasis in Patients with a History of Hematologic Malignancy: Results from a Retrospective Study in 21 Patients.

BACKGROUND: Few studies addressing the safety and efficacy of biological therapy (BT) or apremilast (APR) in patients with psoriasis with a history of hematologic malignancy (HM) exist. AIM: To describe the tolerance and efficacy of BT and APR in moderate-to-severe psoriasis in patients with a history of in-remission or evolving HM. METHODOLOGY: A retrospective, multicenter chart review of the tolerance and efficacy of BT or APR in patients with moderate-to-severe psoriasis and a clinical history of in-remission or evolving HM. RESULTS: Twenty-one patients with severe psoriasis and a history of HM were included in France by the GEM Resopso study group. Of the 16 patients treated with one or more BT lines, none showed recurrence of their HM which was considered as stable or in remission, and only 2 patients showed an evolution of their HM which had been considered as stable at the beginning of treatment. In the 10 patients treated with APR, the HM of one patient who also received BT worsened. The 3 evolutions did not impact the treatment with BT or APR. Tolerance was very satisfactory, with a low occurrence of infections. Regarding efficacy, only one patient treated with APR did not achieve any notable clinical improvement. CONCLUSION: Despite supportive data regarding tolerance, the heterogeneity of the analyzed population and limited available data, BT and APR should be used with caution in this patient population and investigations on larger cohorts should be conducted to further assess their tolerance in this patient population.

Use of Methotrexate in the Treatment of Moderate to Severe Plaque Psoriasis in France: A Practice Survey.

PURPOSE: To evaluate the modalities of methotrexate prescription for moderate to severe psoriasis by dermatologists in France. PATIENTS AND METHODS: We performed a national online practice survey between October and December 2020. RESULTS: A total of 254 dermatologists responded, 237 reported prescribing methotrexate for moderate to severe psoriasis in adults, of which 57% as a first line systemic treatment. Nineteen percent reported performing a test dose at the initiation of treatment. Methotrexate was prescribed orally in 54.7% of cases, subcutaneously in 44.8% of cases and intramuscularly in 0.4% of cases. The initial weekly dose of methotrexate was <15 mg for 30% of the dermatologists and ≥15 mg for 70% of them. Two hundred and three dermatologists had already change the route of administration for methotrexate from the oral to injectable form due to poor tolerance (48.3%), lack of efficacy (35%) or lack of compliance (16.7%). Two hundred thirty-four dermatologists (98.7%) reported prescribing folic acid with methotrexate, and 79.3% reported prescribing tests evaluating the risk of hepatic fibrosis. Forty-three percent of dermatologists have not initiated or have reduced their prescriptions since the beginning of the pandemic of COVID-19. Prescribing patterns were different according to the type of practice (private practice versus hospital/mixed practice). CONCLUSION: Methotrexate is used by the majority of dermatologists interviewed for moderate to severe psoriasis in adults, with heterogeneity of practices.

Use of Systemic Medications for Treating Adult Atopic Dermatitis in France: Results of a Practice Survey.

PURPOSE: Recent studies have illustrated that systemic medications are underused for treating adult atopic dermatitis (AD) and that dermatologists have concerns regarding the safety profile of cyclosporine in AD. PATIENTS AND METHODS: We performed a national online practice survey between March and April 2020. RESULTS: A total of 305 dermatologists responded, 57% with hospital-based activity and 43% with private practice. Overall, 46.9% prescribed cyclosporine for adult AD. Before initiating treatment, 56.9% did not perform evaluation scoring. Reasons for not prescribing cyclosporine were no eligible patients (24.7%), lack of information (52.6%), need for hospital prescription (31.2%), and lack of experience (79.2%). Fifty-four percent of the dermatologists prescribed methotrexate for adult AD. Before initiating treatment, 50.5% did not perform evaluation scoring. Reasons for not prescribing methotrexate were no eligible patients (46.7%), lack of information (39.3%), lack of experience (25.2%), and not approved for AD (47.4%). A total of 2.1% dermatologists prescribed other systemic treatments for adult AD, 9.8% prescribed corticosteroids and 56.4% prescribed dupilumab. CONCLUSION: Systemic treatments for AD are used by half of dermatologists, although cyclosporine and dupilumab must be initiated in hospitals in France. Methotrexate is more frequently used than cyclosporine, although it is not approved for this indication in France. A vast majority of dermatologists do not perform any evaluation scoring before initiating systemic treatment for adult AD.

At the Dawn of a Therapeutic Revolution for Atopic Dermatitis: An Interview with Dr Anne-Claire Fougerousse.

Dr Anne-Claire Fougerousse is Head of Dermatology at the Bégin Hospital in Saint-Mandé, France, and scientific coordinator of a French network of dermatologists and allergists (ResoEczema). The focus of her work is to improve the care of adolescent and adult patients with atopic dermatitis (AD), a chronic, pruritic inflammatory skin disease that substantially impacts patient quality of life. In this interview, Dr Fougerousse provides an overview of the clinical presentation of adult patients with AD and describes available treatments. Today, topical agents like emollients and corticosteroids are the mainstay of AD therapy, and patients with lesions that are resistant to optimally administered topical treatment can also receive phototherapy or systemic therapy with ciclosporin. Dr Fougerousse discusses her hopes for the future of AD therapy with the recent development of biologicals like dupilumab, which may provide improvements in clinical outcomes and quality of life for patients with moderate-to-severe AD. In the next few years, the therapeutic arsenal for AD will likely expand to include more systemic therapies providing sustained symptom control. The real challenge will be to ensure that the maximum number of patients with AD achieve clinical benefits from these new treatments.

Impact of psoriatic disease on women aged 18 to 45: Results from a multinational survey across 11 European countries.

BACKGROUND: Plaque psoriasis (PSO) is a long-term inflammatory condition that can cause concomitant joint symptoms (psoriatic arthritis [PsA]) in up to 30% of patients. The impact of psoriatic disease on disease outcomes and quality of life is greater in women than men. OBJECTIVE: We evaluated the impact of psoriatic disease on women aged 18 to 45 years across Europe. METHODS: Women aged 18 to 45 years with moderate to severe PSO, PsA, or PSO + PsA (PSO with progression to PsA) and prior biologic experience were recruited from market research panels and patient association groups of the International Federation of Psoriasis Associations, European Federation of Psoriasis Patient Associations, and Arthritis Ireland and asked to complete a survey. Questions covered social and psychological wellbeing, employment, and family planning. Question types included 5- or 7-point agreement scales, where the highest/lowest two ratings were considered agreement/disagreement, respectively. The results are reported as proportions of those who selected the answer, divided by overall respondents for each question. Women were not required to answer all questions. RESULTS: Survey respondents (N = 573) had a diagnosis of PSO (n = 236), PsA (n = 173), or PSO + PsA (n = 164). Women self-reported similar mean scores for physical (57.0 of 100) and mental (59.0 of 100) health. A fifth (21%) had not achieved their desired career due to PSO/PsA; career dissatisfaction and increased sick leave were linked to poor mental health. Some women reported having a limited social life (33%), smaller families (34%), and being more likely to adopt children (27%) due to PSO/PsA. A quarter of women (27%) reported not understanding enough about PSO/PsA (nonmembers vs. members of patient association groups: 37% vs. 8%). CONCLUSION: Our findings highlight the considerable burden of psoriatic disease on women of childbearing age. Increased provision of information tailored to women, training for health care professionals, and shared decision-making between patients and health care professionals may help better support women with psoriatic disease.

Contraception, Sexuality and Pregnancy in Women with Psoriasis: Real-Life Experience of 235 Women.

BACKGROUND: Little is known about how women of childbearing age with psoriasis experience contraception, sexuality and pregnancies through the lens of their skin condition. OBJECTIVE: To evaluate the experiences and expectations in this group of patients. MATERIALS AND METHODS: In total, 235 women aged between 18 and 45 years old completed an online survey. We collected the characteristics of psoriasis, contraception and pregnancy history. Psoriasis severity was measured using the Simplified Psoriasis Index. Patient quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Short Form-12. RESULTS: Psoriasis was mild in 78% of cases. The mean DLQI score was 8.8, highlighting a moderate impact of psoriasis. In total, 28% of the women had no current follow-ups, while at least two distinct physicians followed 21% of these patients. In total, 31.5% of the women felt that they could discuss sexuality during their consultations. In addition, 63% of respondents had a contraceptive method, but more than half of the women reported that contraception was rarely or never discussed during the consultations. In total, 63% had at least one pregnancy, and 61.5% reported that the doctor managing their psoriasis did not discuss their pregnancy during consultations. Psoriasis worsened during pregnancy for 21% of the respondents but improved in 34%. Among women who were not pregnant, less than 15% reported that the doctor in charge of their psoriasis discussed family planning and pregnancy possibilities. CONCLUSION: Our study shows that the management of women of childbearing age with psoriasis must be improved with respect to sexuality, contraception and pregnancy planning.

Effectiveness and Safety of Anti-interleukin-17 Therapies in Elderly Patients with Psoriasis.

Anti-interleukin-17 agents have recently been developed for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practice. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including secukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stopped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injection site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years.

Impact of the COVID-19 Pandemic on Chronic Inflammatory Dermatoses: Mixed Messages Regarding the Dermatologist's Point of View and the Patient's Concerns.

is missing (Short communication).

Real-World Effectiveness and Safety of Apremilast in Older Patients with Psoriasis.

INTRODUCTION: Apremilast is a drug recently developed for psoriasis. Few data are available on its use in the elderly. We evaluated the tolerance and effectiveness of apremilast used in daily practice for psoriasis treatment in older patients. METHODS: We performed a multicenter, retrospective study involving patients aged ≥ 65 years who had received apremilast as a psoriasis treatment. Demographic data and details regarding psoriasis and adverse events (AEs) were collected from patient medical records. RESULTS: 135 patients were included (mean age: 73.5 years). Treatment was stopped in 74 patients (54.8%) for AEs (n = 43, 56.6%), primary failures (n = 18, 23.4%), and relapses (n = 7, 9.2%). When patients were stratified by age at treatment initiation, the main cause of discontinuation in patients ≥ 75 years was AEs, whereas in patients aged 65-74 years it was primary failures (28.3%). Sixty-one patients reported AEs, mainly digestive (n = 49). Regarding effectiveness, 45.2% of patients reached PGA 0/1 between 3 and 6 months after treatment initiation. One-year apremilast continuation rates were better in the 65-74 and 75-84 years subgroups than in the > 85 years subgroup (p = 0.01). CONCLUSION: Apremilast seems to be an effective and safe therapeutic option for psoriasis in the elderly. The main AEs reported by patients did not seem to differ from those reported previously in younger populations. However, AEs were more frequent in patients > 75 years old leading to more frequent discontinuation of apremilast compared with younger patients, suggesting a higher level of vigilance is needed in the elderly.

Individual Burden of Psoriasis (I-BOP): Building and Validation of a New Scoring Tool for Patients with Psoriasis.

BACKGROUND: Psoriasis impacts independently of its severity on patients' lifestyle and quality of life (QoL). AIM: To build a tool for assessing the patient-reported psoriasis burden. METHODS: An expert group created a questionnaire using a standardized methodology building questionnaires assessing quality of life issues. The questionnaire was translated from French into a cultural and linguistically validated US English version. RESULTS: A conceptual questionnaire of 54 questions was created. The confirmatory analyses resulted in a 10-feature questionnaire divided into 4 internally consistent domains with a Cronbach's alpha coefficient of 0.9. It was reproducible and highly reliable. It correlated well with the Dermatology Life Quality Index (DLQI), Perceived Stress Scale (PSS), and SF-12 mental and SF12 physical scores. CONCLUSION: This tool allows for the first time to assess the burden of psoriasis patients. Its use may allow improving medical and nonmedical patient care, thus improving their daily life.