Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Antibody response after one and two jabs of the BNT162b2 vaccine in nursing home residents: The CONsort-19 study.

BACKGROUND: The humoral immune response following COVID-19 vaccination in nursing home residents is poorly known. A longitudinal study compared levels of IgG antibodies against the spike protein (S-RBD IgG) (S-RDB protein IgG) after one and two BNT162b2/Pfizer jabs in residents with and without prior COVID-19. METHODS: In 22 French nursing homes, COVID-19 was diagnosed with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2. Blood S-RDB-protein IgG and nucleocapsid (N) IgG protein (N-protein IgG) were measured 21-24 days after the first jab (1,004 residents) and 6 weeks after the second (820 residents). RESULTS: In 735 residents without prior COVID-19, 41.7% remained seronegative for S-RDB-protein IgG after the first jab vs. 2.1% of the 270 RT-PCR-positive residents (p < 0.001). After the second jab, 3% of the 586 residents without prior COVID-19 remained seronegative. However, 26.5% had low S-RDB-protein IgG levels (50-1050 UA/ml) vs. 6.4% of the 222 residents with prior COVID-19. Residents with an older infection (first wave), or with N-protein IgG at the time of vaccination, had the highest S-RDB-protein IgG levels. Residents with a prior COVID-19 infection had higher S-RDB-protein IgG levels after one jab than those without after two jabs. INTERPRETATION: A single vaccine jab is sufficient to reach a high humoral immune response in residents with prior COVID-19. Most residents without prior COVID-19 are seropositive for S-RDB-protein IgG after the second jab, but around 30% have low levels. Whether residents with no or low post-vaccine S-RDB protein IgG are at higher risk of symptomatic COVID-19 requires further analysis.

Receptor binding domain-IgG levels correlate with protection in residents facing SARS-CoV-2 B.1.1.7 outbreaks.

BACKGROUND: Limited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS-CoV-2 and severe COVID-19, and its association with post-vaccine humoral response. METHODS: 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-qPCR). SARS-CoV-2 receptor-binding domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-qPCR-positive residents and serum neutralizing antibodies in vaccinated residents from one NH. RESULTS: The incidence of positive RT-qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non-vaccinated residents (21/48; 43.7%; p < .01). COVID-19-induced deaths were observed in 5 of the 48 non-vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses (p = .0007). Severe symptoms were more common in infected non-vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD-IgG (n = 325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1050 AU/ml. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe COVID-19. CONCLUSIONS: Two BNT162b2 doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. Post-vaccine RBD-IgG levels correlate with BNT162b2 protection against SARS-CoV-2 B.1.1.7.

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Zoledronic Acid Contraindications Prevalence among Hip-Fractured Patients Aged 75 Years or Over Hospitalized in an Orthogeriatric Unit.

OBJECTIVE: Zoledronic acid (ZA) is an antiosteoporotic drug that has been proven to reduce mortality after a hip fracture (HF). ZA is however underused with older HF patients. One possible cause may be the high prevalence of severe renal failure and hypocalcemia which contraindicate ZA administration. The aim of this study was to assess the prevalence of these 2 contraindications in patients aged 75 years or older admitted into an orthogeriatric (OG) unit after a low-energy HF. The secondary objective was to assess the prevalence of situations in which ZA must be used with caution. METHODS: Our retrospective descriptive monocentric study was performed in an OG unit on a cohort of elderly patients hospitalized for HF from August 2015 to August 2017. Prevalence of hypocalcemia lower than 2 mmol/L and Cockcroft creatinine clearance lower than 35 mL/min was recorded. RESULTS: Among the 194 patients admitted for HF, 136 patients (mean age 86 ± 5.6 years; 101 women) were included. The mean length of hospital stay was 15 ± 9 days. 111 (81.5%) had no contraindications to ZA administration. More than 80% presented situations in which ZA had to be used with caution, including 25(OH)D deficiency (20%). CONCLUSION: The majority of subjects aged 75 years or older admitted to hospital after an HF seem to have no contraindication for ZA administration during their immediate postoperative hospital stay. The hospitalization period after HF repair gives the opportunity to give most of them this treatment to improve their prognosis, taking into account situations in which ZA must be used with caution.

Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19.

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.

Spices to Control COVID-19 Symptoms: Yes, but Not Only .

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19.

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.

Atypical symptoms, SARS-CoV-2 test results and immunisation rates in 456 residents from eight nursing homes facing a COVID-19 outbreak.

BACKGROUND: Frail older persons may have an atypical presentation of coronavirus disease 2019 (COVID-19). The value of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nursing homes (NHs) residents is not known. OBJECTIVE: To determine whether (i) atypical symptoms may predict rRT-PCR results and (ii) rRT-PCR results may predict immunisation against SARS-CoV-2 in NH residents. DESIGN: A retrospective longitudinal study. SETTING: Eight NHs with at least 10 rRT-PCR-positive residents. SUBJECTS: A total of 456 residents. METHODS: Typical and atypical symptoms recorded in residents' files during the 14 days before and after rRT-PCR testing were analysed. Residents underwent blood testing for IgG-SARS-CoV-2 nucleocapsid protein 6 to 8 weeks after testing. Univariate and multivariate analyses compared symptoms and immunisation rates in rRT-PCR-positive and negative residents. RESULTS: A total of 161 residents had a positive rRT-PCR (35.3%), 17.4% of whom were asymptomatic before testing. Temperature >37.8°C, oxygen saturation <90%, unexplained anorexia, behavioural change, exhaustion, malaise and falls before testing were independent predictors of a further positive rRT-PCR. Among the rRT-PCR-positive residents, 95.2% developed SARS-CoV-2 antibodies vs 7.6% in the rRT-PCR-negative residents. Among the residents with a negative rRT-PCR, those who developed SARS-CoV-2 antibodies more often had typical or atypical symptoms (P = 0.02 and <0.01, respectively). CONCLUSION: This study supports a strategy based on (i) testing residents with typical or unexplained atypical symptoms for an early identification of the first SARS-CoV-2 cases, (ii) rT-PCR testing for identifying COVID-19 residents, (iii) repeated wide-facility testing (including asymptomatic cases) as soon as a resident is tested positive for SARS-CoV-2 and (iv) implementing SARS-CoV-2 infection control measures in rRT-PCR-negative residents when they have unexplained typical or atypical symptoms.

New horizons in falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.

Compliance with Prescription Guidelines for Glucose-Lowering Therapies According to Renal Function: Real-Life Study in Inpatients of Internal Medicine, Endocrinology and Cardiology Units.

Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods: This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results: In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m2 in 13.4% of these patients, 30-44 in 15.1%, 45-60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m2, respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions: We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.

Influence of repeated effort induced by a 6-min walk test on postural response in older sedentary women.

According to the latest recommendations, adults should exercise regularly at moderate intensity to improve aerobic fitness and body composition. However, it is unknown whether aerobic exercise at submaximal intensity has detrimental effects on balance in older sedentary adults. We explored the effects of two 6-min walk tests (6MWTs) on the postural responses in 49 sedentary women between 60 and 76 years old. We assumed that an increase in the center of pressure (COP) fluctuations or a loss in the complexity of the COP time series would be a sign of a deleterious effect on balance. We used kinematic stabilometric parameters, recurrence quantification analysis (RQA) and the central tendency measure (CTM). We refer to the measures obtained through RQA and CTM methods by dynamical measures. Repeated-measures analysis of variance showed no significant differences between the three sets of postural kinematic measures (before vs. after the first vs. after the second 6MWT). However, we observed significant differences between the three sets for the CTM measure in the antero-posterior direction (p < 0.002), RQA determinism in the medio-lateral (ML) direction (p < 0.0001), and RQA entropy in the ML direction (F = 5.93; p < 0.004).Our results indicate that the effects of moderate-intensity walking exercise on posture are not revealed by classical postural kinematic measures but only by dynamical measures. The loss of complexity in the COP time series observed after both the first and second 6MWTs may indicate presymptomatic deterioration in the postural adaptive capabilities of sedentary older women.

Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study.

Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-α, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1ß, IFN-γ) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy.

The impact of exercise on Alzheimer's disease progression.

INTRODUCTION: The preventive effects of chronic physical exercise (CPE) on Alzheimer's disease (AD) are now admitted by the scientific community. Curative effects of CPE are more disputed, but they deserve to be investigated, since CPE is a natural non-pharmacological alternative for the treatment of AD. AREAS COVERED: In this perspective, the authors discuss the impact of CPE on AD based on an exhaustive literature search using the electronic databases PubMed, ScienceDirect and Google Scholar. EXPERT OPINION: Aerobic exercise alone is probably not the unique solution and needs to be complemented by other exercises (physical activities) to optimize the slowing down of AD. Anaerobic, muscle strength and power, balance/coordination and meditative exercises may also help to slow down the AD progression. However, the scientific evidence does not allow a precise description of the best training program for patients with AD. Influential environmental conditions (e.g. social relations, outdoor or indoor exercise) should also be studied to optimize training programs aimed at slowing down the AD progression.

"Geriatric Team Health Care Pathways": An Organizational Innovation to Enhance Care Pathways of Long-Term Care Facilities' Residents in the French Region of Occitania.

Born out of the COVID crisis, an innovative disposal called "Geriatric Team Healthcare Pathways" (GTHPs) has been implemented in the Occitania area in the south of France. GTHPs can be considered as geriatric "hotlines" providing expertise and knowledge to long-term care facility (LTCF) professionals, pursuing the general objective to promote a simplified, direct, and fair access to geriatric care for residents. This article highlights the history of their creation and their current use cases and operating modes for the year 2023, which includes a "quality of care approach" on good practices at a regional level (820 LTCFs), on topics such as the prevention of malnutrition and falls.

Orthostatic hypotension and neurocognitive disorders in older women: Results from the EPIDOS cohort study.

BACKGROUND: Although it is well-admitted that cardiovascular health affects cognition, the association between orthostatic hypotension (OH) and cognition remains unclear. The objectives of the present study were i) to determine among the EPIDOS cohort (EPIdémiologie de l'OStéoporose) whether OH was cross-sectionally associated with cognitive impairment at baseline, and ii) whether baseline OH could predict incident cognitive decline after 7 years of follow-up. METHODS: Systolic and Diastolic Blood Pressure (SBP and DBP) changes while standing (ie, ΔSBP and ΔDBP, in %) were measured at baseline among 2,715 community-dwelling older women aged 75 years and older using no antihypertensive drugs from the French EPIDOS cohort. OH was defined as a decrease in SBP ≥20 mmHg and/or a decrease in DBP ≥10 mmHg within 3 min after standing. Cognitive impairment was defined as a Short Portable Mental Status Questionnaire (SPMSQ) score <8 (/10). Among those without cognitive impairment at baseline, a possible incident onset of cognitive decline was then sought after 7 years of follow-up among 257 participants. RESULTS: Baseline ΔSBP was associated with baseline cognitive impairment (adjusted OR = 1.01, p = 0.047), but not with incident onset of cognitive decline after 7 years (adjusted OR = 0.98, p = 0.371). Neither baseline OH nor baseline ΔDBP were associated with cognitive impairment neither at baseline (p = 0.426 and p = 0.325 respectively) nor after 7 years (p = 0.180 and p = 0.345 respectively). CONCLUSIONS: SBP drop while standing, but neither OH per se nor DBP drop while standing, was associated with baseline cognitive impairment in older women. The relationship between OH and cognitive impairment appears more complex than previously expected.