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Remote work (REMOTE) causes an overlap between working and domestic demands. The study of the cardiac autonomic profile (CAP) by means of heart rate variability (HRV) provides information about the impact of REMOTE on workers’ health. The primary aim was to determine whether CAP, self-perceived stress, environmental and workstation comfort are modified during REMOTE. The secondary aim was to explore how these indices are influenced by individual and environmental work-related factors. Fifty healthy office employees alternating REMOTE and in-office (OFFICE) working were enrolled, rated self-perceived stress, environmental and workstation comfort using a visual analogue scale and performed a 24-h electrocardiogram during REMOTE and OFFICE. Stress was lower (5.6 ± 2.2 vs. 6.4 ± 1.8), environmental comfort higher (7.7 ± 1.9 vs. 7.0 ± 1.5), and the workstation comfort poorer (6.2 ± 1.8 vs. 7.5 ± 1.2) during REMOTE. CAP was similar during REMOTE and OFFICE. CAP was influenced by some work-related factors, including the presence of offspring, absence of a dedicated workspace during REMOTE and number of working hours. All these variables determined a decreased vagal modulation. The working setting seems to impact the levels of perceived stress and comfort, but not the CAP. However, individual and environmental work-related factors reduce cardiac vagal modulation during REMOTE, potentially increasing the risk of developing cardiovascular diseases.

Temporal asymmetry is a peculiar aspect of heart period (HP) variability (HPV). HPV asymmetry (HPVA) is reduced with aging and pathology, but its origin is not fully elucidated. Given the impact of respiration on HPV resulting in the respiratory sinus arrhythmia (RSA) and the asymmetric shape of the respiratory pattern, a possible link between HPVA and RSA might be expected. In this study we tested the hypothesis that HPVA is significantly associated with RSA and asymmetry of the respiratory rhythm. We studied 42 middle-aged healthy (H) subjects, and 56 chronic heart failure (CHF) patients of whom 26 assigned to the New York Heart Association (NYHA) class II (CHF-II) and 30 to NYHA class III (CHF-III). Electrocardiogram and lung volume were monitored for 8 minutes during spontaneous breathing (SB) and controlled breathing (CB) at 15 breaths/minute. The ratio of inspiratory (INSP) to expiratory (EXP) phases, namely the I/E ratio, and RSA were calculated. HPVA was estimated as the percentage of negative HP variations, traditionally measured via the Porta’s index (PI). Departures of PI from 50% indicated HPVA and its significance was tested via surrogate data. We found that RSA increased during CB and I/E ratio was smaller than 1 in all groups and experimental conditions. In H subjects the PI was about 50% during SB and it increased significantly during CB. In both CHF-II and CHF-III groups the PI was about 50% during SB and remained unmodified during CB. The PI was uncorrelated with RSA and I/E ratio regardless of the experimental condition and group. Pooling together data of different experimental conditions did not affect conclusions. Therefore, we conclude that the HPVA cannot be explained by RSA and/or I/E ratio, thus representing a peculiar feature of the cardiac control that can be aroused in middle-aged H individuals via CB.

Stressful physical or psychological events can trigger acute swelling attacks in patients with Hereditary Angioedema due to C1 Inhibitor deficiency (HAE-C1INH), although the stress-disease relationship remains unclear. The Socially Evaluated Cold Pressor Test (SECPT) reliably induces acute stress under controlled conditions. This study aimed to compare perceived stress, inflammatory markers, and cardiovascular responses to SECPT between HAE-C1INH patients and healthy controls (HC). Twenty HAE-C1INH patients (9 males, 44 ± 14 years) and age and sex matched HC underwent a 3-minute SECPT. Participants completed questionnaires assessing anxiety and depression (HADS), pain catastrophizing (PCS), and subjective stress (0-100 scale) before and after SECPT. Heart rate (HR) and arterial pressure (AP) were recorded. Blood samples for inflammatory cytokines (IL-6, IL-1ß, TNF-α) were collected at baseline, and 10 and 40 minutes after SECPT. Compared to HC, patients showed higher baseline HADS-A (7.3 ± 4.5 vs 4.7 ± 2.7), overall PCS (19.7 ± 12.6 vs 12.9 ± 8.7), and perceived stress during SECPT (60.6 ± 34.3 vs 34.6 ± 23.8). IL-6 levels were higher at baseline and 10 minutes post-test (2.63 ± 1.21 vs 1.84 ± 0.87; 2.78 ± 1.20 vs 1.91 ± 0.79 pg/ml), as were TNF-α levels across all phases (4.19 ± 1.38 vs 3.26 ± 1.55; 4.09 ± 1.39 vs 3.40 ± 1.48; 4.09 ± 1.28 vs 3.20 ± 1.57) while IL-1 ß remained unchanged. HR and AP variations were similar between groups. HAE-C1INH patients exhibited heightened perceived stress response to SECPT, and elevated baseline inflammation, despite comparable cardiovascular reactivity. These findings highlight a complex psychophysiological-inflammatory interplay in acute stress responses, suggesting the need to integrate psychological and biological frameworks in understanding HAE-C1INH triggers. NCT06414252.

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) features clinical heterogeneity and stress-triggered attacks. Behavioral tolerance to acute stress may reveal vulnerability profiles beyond standard clinical descriptors. This study aimed to characterize stress response patterns and compare groups based on behavioral tolerance. HAE-C1INH patients underwent the Socially Evaluated Cold Pressor Test (SECPT) and were stratified as Completers or Non-completers (early withdrawal). Stress appraisal, cardiovascular parameters (heart rate, HR; systolic/diastolic arterial pressure, SAP/DAP), and plasma cytokines (IL-1β, TNF-α, IL-6) were assessed. Disease control and quality of life were measured via Angioedema Control Test (AECT) and Angioedema Quality of life (AE-QoL) questionnaires. Twenty patients were enrolled (15 Completers and 5 Non-completers). Non-completers showed poorer disease control (10.6 ± 5.5 vs 14.5 ± 2.2; p ≤ 0.05) and worse AE-QoL, particularly in the Functioning (8.6 ± 4.3 vs 4.7 ± 1.7; p ≤ 0.05) and Fatigue/Mood (13.6 ± 7.1 vs 10.5 ± 3.5; p ≤ 0.05) domains. They reported higher stress (91 ± 8.9 vs 50.5 ± 33.7; p ≤ 0.05), pain (87.8 ± 12.8 vs 50.1 ± 31.3; p ≤ 0.05) and unpleasantness (83 ± 19.9 vs 49.5 ± 30.5; p ≤ 0.05) during the SECPT. Non-completers displayed an attenuated SAP response relative to Completers (128.3 ± 18.0 vs 148.9 ± 18.3 mmHg; p ≤ 0.05). Inflammatory profiles also diverged: Non-completers showed higher IL-6 levels at 40 minutes after SECPT (3.5 ± 1.1 vs 2.2 ± 0.7 pg/ml; p ≤ 0.05) and opposite TNF-α trajectories compared with Completers (0.9 ± 1.0 vs -0.5 ± 0.9 pg/ml; p ≤ 0.05). Early withdrawal during SECPT identifies a vulnerable HAE-C1INH subgroup with distinct psychological, cardiovascular, and inflammatory patterns.

A reduced nocturnal cardiac vagal modulation has been observed in working women with preschoolers. Whether this adaptation also occurs in men remains an open question. The aim of this study was to analyze the cardiac autonomic profile of two groups of healthcare male professionals, one with and one without preschoolers, to be compared to females. Twenty-five working men with preschoolers (M_KID, age 35.41 ± 4.01 years) and 25 without (M_NOKID, 34.48 ± 6.00 years) were compared with 25 working women with preschoolers (W_KID, 37.7 ± 5.6 years) and 25 without (W_NOKID, 35.4 ± 7.2 years). A 24-h Holter electrocardiogram was performed for time and frequency domain analysis of the beat-to-beat variations of RR interval (RR) variability, during daytime (DAY) and nighttime (NIGHT). The power of RR variability in the high frequency band (HF RR ) was considered as an index of cardiac vagal modulation. RR variability indices were similar in M_KID and M_NOKID during both DAY and NIGHT. In contrast, W_KID showed a reduced nocturnal HF RR compared to W_NOKID. The comparison of working men with and without preschoolers revealed no differences in the cardiac autonomic profile, in contrast with women. This suggests that sex and/or gender may represent a crucial factor in the cardiac neural control in the parental condition.

Background Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients’ quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals’ attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients’ and their caregivers’ interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas. Results We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants’ personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community. Conclusion A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation.

The conciliation between career and family is a relevant issue for working women, in particular during the first years of motherhood. Data about the state of the cardiac autonomic regulation in working women with preschoolers are lacking. Aim of this study was to compare the cardiac autonomic profile of female healthcare professionals with and without preschoolers via the analysis of the variability of the time distance between two consecutive R-wave peaks (RR) from standard 24-h Holter electrocardiogram (ECG). Fifty healthy active female healthcare professionals were enrolled: 25 with at least one preschooler (W_KID) and 25 without (W_NOKID). A standard Holter ECG was obtained during a regular working day. Segments of 5000 consecutive RRs were selected during daytime (DAY) and nighttime (NIGHT). Heart rate variability analysis was performed and the following parameters were considered for comparison between the two groups: mean (μ RR ), variance (σ 2 RR ), and the absolute power in high frequency component (HF) of RR (HF RR ) series. HF RR was considered as a marker of vagal cardiac modulation. Only µ RR significantly increased from DAY to NIGHT in both groups (699 ± 88 vs 887 ± 140 ms in W_KID and 728 ± 90 vs 942 ± 166 ms in W_NOKID). Instead, σ 2 RR and HF RR increased from DAY to NIGHT only in W_NOKID (from 3334 ± 2153 to 4816 ± 4063 ms 2 and from 356 ± 334 to 1397 ± 1629 ms 2 , respectively). W_KID showed lower σ 2 RR and HF RR during NIGHT, compared to W_NOKID (2336 ± 3170 vs 4816 ± 4063 ms 2  and 556 ± 950 vs 1397 ± 1629 ms 2 , respectively). The perceived stress according to the visual analogue scale was similar in the two groups (4.7 ± 2.1 in W_KID, 5.7 ± 2.1 in W_NOKID). The presence of preschoolers lowered nocturnal cardiac vagal modulation in female healthcare professionals. This might represent an adaptation with a finalistic purpose, scilicet the facilitation of a prompt reaction in case of a child’s need.

Despite the efficacy of the on-demand treatment for the control of acute attacks of Hereditary Angioedema due to C1-Inhibitor Deficiency (C1-INH-HAE), the number and severity of attacks and the impairment in the quality of life of the affected patients have led to the development of a new monoclonal antibody, lanadelumab, directly addressed to the blockage of bradykinin, the principal mediator of vasodilation during angioedema attacks. It is indicated for the prophylactic treatment, it is easy to administer, highly effective and with known limited side effects. The current review summarizes the development of the drug, its clinical background and its perspectives.

Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Methods Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. Results We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. Conclusions C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.

Danazol is regularly used as a prophylactic treatment in patients with Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). However, this drug is characterized by a risk of drug-drug interactions (DDIs). Berotralstat, the first oral kallikrein inhibitor, has been recently approved for the prevention of HAE attacks. Here, we sought to compare the risk of potential DDIs in real-life HAE patients hypothetically given Danazol or Berotralstat. Our clinic's database was retrospectively reviewed to identify patients diagnosed with HAE who were treated with at least one concomitant medication. The DDIs were assessed using three freely available drug interaction checkers and scored based on their severity. The agreement between the three drug checkers was evaluated using weighted Cohen's kappa coefficient. 75 HAE patients (64% female, mean age 56 ± 21 years) were considered. They were mainly treated with antihypertensives (37%), hypoglycemic (19%), and hypolipemic agents (17%). Significant discrepancies among the three-drug interaction checkers were found. The first checker identified 18 potential DDIs, all involving Danazol and a statin (simvastatin). The second checker identified, respectively, 66 and 14 DDIs for Danazol (20% severe, regarding Simvastatin and Rivaroxaban) and Berotralstat (0% severe). The third checker identified 49 and 43 DDIs for Danazol (22% severe, regarding Simvastatin) and Berotralstat (0%). Berotralstat was consistently associated with a reduced risk of DDIs compared with Danazol. A rational assessment of DDIs would help select the best prophylactic treatment for HAE.