Adult Day Research Articles

Objective assessment of the association between frailty and sedentary behavior in older adults: a cross-sectional study

BackgroundGiven the inconsistent findings of the association between frailty and sedentary behavior in older adults, this cross-sectional study investigated the aforementioned association using four different frailty criteria and two sedentary behavior indices in older adults.MethodsData from older adults (age ≥ 65 y) who participated in health examinations or attended outpatient integrated clinics at a medical center in Taipei, Taiwan, were collected. Frailty was measured using the modified Fried Frailty Phenotype (mFFP), Clinical Frailty Scale in Chinese Translation (CFS-C), Study of Osteoporotic Fractures (SOF) index, and Clinical Frailty-Deficit Count (CF-DC) index; sedentary behavior was assessed with a waist-worn accelerometer. Adjusted linear regression ascertained the association between frailty and both sedentary behavior outcomes.ResultsAmong the 214 participants (mean age 80.82 ± 7.14 y), 116 were women. The average total sedentary time and number of sedentary bouts were 609.74 ± 79.29 min and 5.51 ± 2.09 times per day, respectively. Frail participants had a longer total sedentary time (odds ratio [OR]: 30.13, P = .01 and 39.43, P < .001) and more sedentary bouts (OR: 3.50 and 5.86, both P < .001) on mFFP and CFS-C assessments, respectively. The SOF index revealed more sedentary bouts among frail than in robust participants (OR: 2.06, P = .009), without a significant difference in the total sedentary time. Frail participants defined by the CF-DC index were more likely to have frequent sedentary bouts (OR: 2.03, P = .016), but did not have a longer total sedentary time.ConclusionsRegardless of the frailty criteria adopted, frailty was positively associated with the number of sedentary bouts per day in older adults. A significant correlation between frailty and total sedentary time was detected only with mFFP and CFS-C indices. Further research may target decreasing the sedentary bouts in older adults as a strategy to improve frailty.

Impact of discontinuing non-pharmacological interventions on cognitive impairment in dementia patients by COVID-19 lockdown. A pilot observational, longitudinal, retrospective study carried out in an adult day center in Spain during the COVID-19 pandemic.

The lockdown imposed during the COVID-19 pandemic led to social isolation and prevented patients with dementia from receiving a suite of non-pharmacological interventions (NPIs) that prevent cognitive decline. This discontinuation of NPIs could substantially affect the mental health status of people with dementia in social care settings, such as adult day care centers (ADCs). The study aimed to evaluate the effects of the COVID-19 lockdown on mental health and cognitive impairment in patients with dementia who could not attend their usual ADCs and did not receive our NPIs, based on World Health Organization (WHO) Guidelines. Observational, longitudinal, retrospective study carried out in an adult day center in Spain and reported it in accordance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement. Cognitive status was assessed using the Mini-Mental State Examination (MMSE) in 80 patients attending the ADC of the "Leonese Association of Dementia Patients" (León, Spain), who had been evaluated with this instrument before the COVID-19 lockdown. We observed a 0.4-point decrease in MMSE score/month (IQR = 1.4) during lockdown versus a 0.1-point decrease/month (IQR = 0.3) before this period (p = 0.038). Notably, this translated to >10-point decreases in MMSE score/year in 33.8% of participants during lockdown versus 5.5% earlier (p < 0.001). No statistically significant associations (p < 0.05) were found between the individual characteristics of the caregivers and the occurrence of the event. The reported declines in MMSE scores reveal a significant acceleration of cognitive decline during the period of inactivity. This could suggest that our NPIs, focused on slowing cognitive decline, are beneficial and, therefore, necessary in patients with dementia.

Do Home- and Community-Based Services Delay Frailty Onset in Older Adults With Low Care Needs?

ObjectivesTo assess whether using adult day services or personal assistance services can delay the onset of frailty among older adults with low care needs during a 5-year follow-up study. DesignThis prospective cohort study was conducted using long-term care and health insurance claims data. Setting and ParticipantsThis was a population-based study of 3 municipalities in Osaka, Japan. Initially, 655 nonfrail or prefrail individuals were included from a cohort of 790 population-based adults aged ≥65 years, who were newly certified as being on a support level of the long-term care insurance program from September 2012 to March 2013. MethodsUsing long-term care and health insurance claims data from the Southern Osaka Health and Aging Study, conducted between April 2012 and March 2017, monthly usage of adult day and personal assistance services was measured. Data were analyzed from December 2021 to January 2022. ResultsOf the 655 individuals (median age at baseline: 79 years), 436 (66.6%) were female, 388 (59.2%) were nonfrail, and 267 (40.8%) were prefrail, according to the Veterans Affairs Frailty Index. During the 5-year follow-up period, 222 individuals (33.9%) experienced the onset of frailty. The time-dependent Cox regression models showed that using adult day services lowered the risk of frailty when compared with not using such services [hazard ratio (HR) 0.60, 95% CI 0.42-0.86; P = .006], although personal assistance services usage was not associated with the onset of frailty (HR 0.70, 95% CI 0.48-1.03, P = .07). Conclusions and ImplicationsUsing adult day services lowered the risk of frailty in older adults with low care needs over the 5-year follow-up period. The findings support the value of providing adult day services to prevent frailty for those in need of long-term care.

EFFICACY AND SAFETY OF PYRONARIDINE TETRAPHOSPHATEARTESUNATE FOR TREATMENT OF UNCOMPLICATED Plasmodium falciparum MALARIA IN BINH PHUOC, GIA LAI AND PHU YEN PROVINCES, VIET NAM, IN 2021

From March to December 2021, this prospective, open-label, single-armobservational clinical trial, conducted in Binh Phuoc, Gia Lai and Phu Yen provinces,evaluated the safety and efficacy of oral Pyronaridine tetraphosphate-Artesunate oncedaily for three consecutive days in adults and children with microscopically confirmedP. falciparum malaria. Patients were treated as in-patients for Days 0–3, with followup visits on Days 7, 14, 21, 28, 35 and 42. The primary outcome was PCR-adjustedadequate clinical and parasitological response (ACPR) at Day 42. The results from 54P. falciparum patients has shown that: The efficacy of Pyronaridine tetraphosphate -Artesunate to P. falciparum has still high, with the rate of ACPR is 100%, the rate ofpositive parasitemia at day 3 is 50%, 54.5% and 54.8% in Binh Phuoc, Phu Yen andGia Lai, respectively. Pyronaridine-Artesunate is safety for the patients. None seriousadverd event are recorded.

Caregiving During the COVID-19 Pandemic: Factors Associated With Feelings of Caregiver Preparedness.

Examination of caregiver preparedness for the COVID-19 pandemic can inform efforts to support caregivers in future times of global crisis. Informal caregivers of adults with dementia or severe disabilities (n = 72, Mage = 62.82years, 90.28% female) were recruited through Adult Day Centers across the United States. Caregivers responding to an online survey regarding their experiences and preparedness reported an increase in burden, stress, and time spent caregiving since the onset of the pandemic. Caregivers reported feeling prepared for typical caregiving responsibilities but felt less prepared for someone else to assume the role of primary caregiver. Multiple regression modeling indicated that resilience accounted for significant variance in primary caregiver preparedness, over and above burden, but only caregiver age accounted for significant variability in a component representing feeling prepared to delegate caregiving to another person. These findings have implications for research and applied efforts to promote caregiver well-being and preparedness.

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

We assessed the efficacy and safety of the oral glucagon-like peptide-1 analogue, semaglutide 50 mg, taken once per day versus placebo for the treatment of overweight or obesity in adults without type 2 diabetes. This randomised, double-blind, placebo-controlled, phase 3, superiority trial enrolled adults with a BMI of at least 30 kg/m2, or at least 27 kg/m2 with bodyweight-related complications and comorbidities, without type 2 diabetes. The trial was done at 50 outpatient clinics in nine countries across Asia, Europe, and North America. Participants were randomly allocated (1:1) via an interactive web-response system to oral semaglutide escalated to 50 mg, or visually matching placebo, once per day for 68 weeks, plus lifestyle intervention. Group assignment was masked for participants, investigators, and those assessing outcomes. Coprimary endpoints were the percentage change in bodyweight and whether participants reached a bodyweight reduction of at least 5% at week 68 for oral semaglutide 50 mg versus placebo, assessed regardless of treatment discontinuation or use of other bodyweight-lowering therapies (an intention-to-treat analysis). Safety was assessed in participants who received at least one dose of trial drug. This trial, registered with ClinicalTrials.gov (NCT05035095), is now complete. From Sept 13 to Nov 22, 2021, 709 participants were screened, of whom 667 were randomly assigned to oral semaglutide 50 mg (n=334) or placebo (n=333). The estimated mean bodyweight change from baseline to week 68 was -15·1% (SE 0·5) with oral semaglutide 50 mg versus -2·4% (0·5) with placebo (estimated treatment difference -12·7 percentage points, 95% CI -14·2 to -11·3; p<0·0001). More participants reached bodyweight reductions of at least 5% (269 [85%] of 317 vs 76 [26%] of 295; odds ratio [OR] 12·6, 95% CI 8·5 to 18·7; p<0·0001), 10% (220 [69%] vs 35 [12%]; OR 14·7, 9·6 to 22·6), 15% (170 [54%] vs 17 [6%]; OR 17·9, 10·4 to 30·7), and 20% (107 [34%] vs 8 [3%]; OR 18·5, 8·8 to 38·9) at week 68 with oral semaglutide 50 mg versus placebo. Adverse events were more frequent with oral semaglutide 50 mg (307 [92%] of 334) than with placebo (285 [86%] of 333). Gastrointestinal adverse events (mostly mild to moderate) were reported in 268 (80%) participants with oral semaglutide 50 mg and 154 (46%) with placebo. In adults with overweight or obesity without type 2 diabetes, oral semaglutide 50 mg once per day led to a superior and clinically meaningful decrease in bodyweight compared with placebo. Novo Nordisk.

#3074 CHANGES IN THE CLINICAL CHARACTERISTICS AND MANAGEMENT OF PATIENTS WITH AHUS OVER 10 YEARS: TRENDS FROM THE GLOBAL AHUS REGISTRY

Abstract Background and Aims Atypical haemolytic uraemic syndrome (aHUS) is a rare disease predominantly caused by alternative complement pathway dysregulation. Prior to 2011, before the targeted complement inhibitor eculizumab became available, aHUS frequently led to end-stage kidney disease (ESKD) and early death. Treatment with eculizumab led to notable improvements in outcomes; whether patient characteristics and management has continued to change over time is unknown. Using data from the Global aHUS Registry, we assessed clinical characteristics and management of patients with aHUS over 10 years to identify any potential trends. Method All patients enrolled in the Global aHUS Registry from 2012–2022 were included. Patients were categorised according to age at aHUS onset (adult [≥18 years] vs paediatric [&amp;lt;18 years]); onset of aHUS was defined as the earliest of initial symptom presentation, aHUS diagnosis, or first recorded thrombotic microangiopathy (TMA). Patient characteristics were summarised using descriptive analysis. Results Of the 1994 patients enrolled in the registry between 2012 and 2022, 33 (1.7%) were missing data on age at aHUS onset. Of the remaining 1961 patients, 813 (41.5%) were paediatric and 1148 (58.5%) were adult. Changes in patient characteristics and management are presented in Fig. 1. Plasma exchange/plasma infusion (PE/PI) prior to and including the year of enrolment was less common in paediatric than adult patients (58.5% vs. 71.3%) between 2012–2013 and declined substantially in paediatric (19.6%) relative to adult (55.1%) patients by 2020–2022. Similar proportions of paediatric patients required dialysis at the time of enrolment between 2012–2013 (5.1%) and 2020–2022 (5.9%), while numerically lower proportions of adults required dialysis over time (2012–2013, 15.2%; 2020–2022, 6.5%). The rate of paediatric patients requiring a kidney transplant prior and up to enrolment dropped from 2012–2013 (28.4%) to 2020–2022 (5.9%); however, the rate among adult patients remained comparable (2012–2013, 29.2%; 2020–2022, 27.1%). A decrease in the proportion of patients with a reported identified pathogenic variant and/or anti-CFH antibodies was observed in paediatric and adult patients between 2012–2013 (paediatric, 59.1%; adult, 45.5%) and 2020–2022 (paediatric, 49.0%; adult, 30.8%). The proportion of patients with a reported triggering event increased from 2012–2013 (paediatric, 6.3%; adult, 12.4%) to 2020–2022 (paediatric, 9.8%; adult, 28.0%). In this cohort, a total of 1208 patients were treated with eculizumab/ravulizumab between 2012 and 2022 (paediatrics, 476; adults, 732). Between 2012–2013, the median time from aHUS onset to treatment initiation was 94.9 days for paediatric patients (blue) and 51.1 days for adult patients (orange); this fell to 13.1 days in paediatrics and 24.1 days in adults between 2020–2022 (Fig. 2). Conclusion Utilisation of PE/PI to treat aHUS has decreased more in paediatric than adult patients over time. A decreased requirement for transplant in paediatric patients was evident, suggesting more paediatrics are now being diagnosed and treated earlier, leading to better outcomes with fewer patients progressing to renal failure and requiring kidney transplant. The proportion of both paediatric and adult patients with reported pathogenic variants and/or anti-CFH antibodies decreased over time and may reflect the rate at which a clinical constellation consistent with aHUS is identified. Moreover, aHUS may be recognised more frequently in the presence of a triggering condition, or a lower barrier for clinicians to suspect aHUS in recent years. Patients were more rapidly treated with a complement inhibitor, likely due to better awareness in the clinical community around complement inhibitors and the importance of early treatment initiation. Although patients with aHUS are being treated more promptly in recent years than 10 years ago, more work is needed, especially in adults, to move towards optimal clinical practice.

Exposure to airborne nickel and phenol and features of the immune response mediated by E and G immunoglobulins

Ambient air pollution with potentially allergenic technogenic haptens facilitates occurrence of atopic reactions and creates favorable conditions for future development of allergic pathologies in exposed population. The aim of this study was to estimate formation of an IgE-mediated and IgG-mediated specific immune response to low-molecular chemical compounds introduced into the body by inhalation (nickel and phenol used as examples). The test groups were made of children (n = 99) and adults (n = 57) who lived under exposure to airborne nickel and phenol in levels not exceeding maximum permissible ones (up to 0.7 MPL). The reference groups included children (n = 95) and adults (n = 53) who lived on a conventionally clean territory. In the test groups, average daily exposure doses of airborne nickel and phenol varied between 0.7•10-6 and 9.3•10-6 mg/(kg•day) for children and between 3.5•10-6 and 5.0•10-5 mg/(kg•day) for adults (the doses were created by emissions from a non-ferrous metallurgy plant); this was 1.5–3.0 times higher than the same indicators in the reference groups. Levels of IgG specific to nickel were more than two times higher in the exposed groups; the exposed children had elevated levels of IgG specific to phenol in their blood, practically three times higher than in the reference group (р &lt; 0.05). By using logistic regression models, we established a significant probabilistic cause-effect relation between elevated nickel levels in children’s blood and elevated levels of IgE-specific to nickel (R2 = 0.87; F = 468.58; р &lt; 0.05). The assessment of the odds ratio made it possible to verify the relationship between nickel levels in blood and the increase in the level of IgE specific to nickel in children (OR = 8.96; 95% CI = 2.00–40.15) and in adults from the test group (OR = 3.12; 95 % CI = 1.10–9.40). The study results indicate that exposure to low levels of airborne nickel and phenol induces hypersensitivity to technogenic haptens in the exposed children and adults. Its distinctive features are an IgE-mediated reaction to nickel and IgG-mediated reaction to phenol. Hyperproduction of immunoglobulin E specific to nickel as well as IgG-antibodies specific to phenol in the exposed children and adults reflects levels of exposure to airborne nickel and phenol and is a peculiarity of a hyperactive immune response developing in the analyzed children on the test territory.

Аэрогенная экспозиция никелем и фенолом и особенности иммунного ответа, опосредованного иммуноглобулинами класса E и G

Ambient air pollution with potentially allergenic technogenic haptens facilitates occurrence of atopic reactions and creates favorable conditions for future development of allergic pathologies in exposed population. The aim of this study was to estimate formation of an IgE-mediated and IgG-mediated specific immune response to low-molecular chemical compounds introduced into the body by inhalation (nickel and phenol used as examples). The test groups were made of children (n = 99) and adults (n = 57) who lived under exposure to airborne nickel and phenol in levels not exceeding maximum permissible ones (up to 0.7 MPL). The reference groups included children (n = 95) and adults (n = 53) who lived on a conventionally clean territory. In the test groups, average daily exposure doses of airborne nickel and phenol varied between 0.7•10-6 and 9.3•10-6 mg/(kg•day) for children and between 3.5•10-6 and 5.0•10-5 mg/(kg•day) for adults (the doses were created by emissions from a non-ferrous metallurgy plant); this was 1.5–3.0 times higher than the same indicators in the reference groups. Levels of IgG specific to nickel were more than two times higher in the exposed groups; the exposed children had elevated levels of IgG specific to phenol in their blood, practically three times higher than in the reference group (р &lt; 0.05). By using logistic regression models, we established a significant probabilistic cause-effect relation between elevated nickel levels in children’s blood and elevated levels of IgE-specific to nickel (R2 = 0.87; F = 468.58; р &lt; 0.05). The assessment of the odds ratio made it possible to verify the relationship between nickel levels in blood and the increase in the level of IgE specific to nickel in children (OR = 8.96; 95% CI = 2.00–40.15) and in adults from the test group (OR = 3.12; 95 % CI = 1.10–9.40). The study results indicate that exposure to low levels of airborne nickel and phenol induces hypersensitivity to technogenic haptens in the exposed children and adults. Its distinctive features are an IgE-mediated reaction to nickel and IgG-mediated reaction to phenol. Hyperproduction of immunoglobulin E specific to nickel as well as IgG-antibodies specific to phenol in the exposed children and adults reflects levels of exposure to airborne nickel and phenol and is a peculiarity of a hyperactive immune response developing in the analyzed children on the test territory.

Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey

Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.

Teilstationäre Versorgung im Fokus – Entwicklung wissenschaftsgestützter Impulse zur Gestaltung von Tagespflegen für ältere Menschen

BackgroundDespite its important role in the elderly care system, day care in Germany has so far rather little attention paid to it. Keeping their patients’ health and self-reliance and facilitating relief and support for family caregivers are central tasks of day care, regulated by law. Nevertheless, there is not only a lack of findings about the working methods and effects of day care, but also of orientation in terms of how to configure high-quality care on a structural, process-related and conceptual level. The aim of the TpQ project (“Weiterentwicklung und Qualitätsverbesserung von Tagespflege in Nordrhein-Westfalen”, “further development of and quality improvement in day care facilities in Northrhine-Westphalia”) was to close this gap and to offer the institutions a catalogue of impulses that contains current national and international research findings as well as the perspectives of every stakeholder associated with day care. MethodIn an explorative sequential mixed-method design, we conducted a search for and a synthesis of the literature in the form of a scoping review, qualitative interviews with guests, relatives, non-users, employees and managers of day care, association representatives, nursing scientists and business consultants, a quantitative paper-based survey among guests, relatives, employees and managers of day care and an expert conference for result validation. The sample received study information either directly by mail or through the staff of the recruited adult day care facilities. The survey-area is the federal state of North Rhine-Westphalia. The analysis of the qualitative data was conducted according to the qualitative content analysis and was used for the development of the quantitative surveys. The quantitative data analysis was descriptive. Based on the comparison with literature analysis and qualitative findings, the impulses for the design of day care were finally formulated and validated during an expert workshop. ResultsFrom the literature (N=49) and the interviews (N=85), different expectations and wishes with regard to day care were generated. These included staff and structural requirements as well as concrete ideas of the conceptual orientation of day care. The quantitative survey (N=392) showed considerable agreement with the content-related and organizational requirements of the qualitative survey and allowed us to identify the relevant quality aspects from the point of view of guests, relatives and staff of day care facilities. In summary, 15 dimensions for the design of day care (conception/basic principles, quality management, nursing care, transport/driving service, opening hours, equipment, networking, staff, introduction of new guests, activity offers, health promotion and prevention, promotion of social participation, support of relatives, public work, counseling) were defined as relevant quality areas and explained with 81 impulses. Discussion and conclusionAddressing the perspective of users, family caregivers and other persons involved in adult day care reveals complex requirements and opportunities for the design of adult day care. In contrast to existing quality inspection guidelines, the impulses can be used to independently assess adult day care with the goal of contributing to the further development and sharpening of the profile of adult day care.

Alzheimer's Disease Services, Staffing, and Outcomes in Adult Day Health Centers.

Increasing rates of Alzheimer disease and related dementia (ADRD) has resulted in greater reliance on adult day health centers (ADHCs) and their skilled workforce. Little is known about staffing in ADHCs that provide ADRD services compared with ADHCs that do not. This study examines whether there are differences in staffing between ADHCs that offer ADRD services versus those that do not, and whether the percentage of ADHC participants with ADRD is associated with staffing levels. It also examines whether staffing levels and provision of ADRD services are associated with participant outcomes. Cross-sectional analysis of secondary survey data. We used facility-level data from the 2014 National Post-acute and Long-term Care Study Adult Day Services Center module. This survey is completed by administrators of ADHCs, who provide information about their ADHC's organization, services, participants, sources of payment, staffing, and participant outcomes. Bivariate comparisons and multivariate regressions were used to compare scope of services, staffing, and participant outcomes for ADHCs that offered ADRD programs compared with those that did not. ADHCs with ADRD programs had similar average daily attendance, less revenue from Medicaid and self-payment, and greater proportions of Black and female participants. ADHCs with ADRD programs had similar staff hours per participant day for all staff categories; licensed nurse staffing increased and social worker staffing decreased with the proportion of participants with ADRD. Staffing had significant associations with participant outcomes. ADHCs that have more participants with ADRD have greater staffing of licensed nurses but fewer social workers. Participant outcomes are associated with staffing, but the results suggest that there are unmeasured dimensions of participant risk that confound the relationship.

Cost effectiveness of non-drug interventions that reduce nursing home admissions for people living with dementia.

Six million Americans live with Alzheimer's disease and Alzheimer's disease and related dementias (AD/ADRD), a major health-care cost driver. We evaluated the cost effectiveness of non-pharmacologic interventions that reduce nursing home admissions for people living with AD/ADRD. We used a person-level microsimulation to model the hazard ratios (HR) on nursing home admission for four evidence-based interventions compared to usual care: Maximizing Independence at Home (MIND), NYU Caregiver (NYU); Alzheimer's and Dementia Care (ADC); and Adult Day Service Plus (ADS Plus). We evaluated societal costs, quality-adjusted life years and incremental cost-effectiveness ratios. All four interventions cost less and are more effective (i.e., cost savings) than usual care from a societal perspective. Results did not materially change in 1-way, 2-way, structural, and probabilistic sensitivity analyses. Dementia-care interventions that reduce nursing home admissions save societal costs compared to usual care. Policies should incentivize providers and health systems to implement non-pharmacologic interventions.

Physiologically-Based Pharmacokinetic Modelling to Predict the Pharmacokinetics and Pharmacodynamics of Linezolid in Adults and Children with Tuberculous Meningitis.

Linezolid is used off-label for treatment of central nervous system infections. However, its pharmacokinetics and target attainment in cranial cerebrospinal fluid (CSF) in tuberculous meningitis patients is unknown. This study aimed to predict linezolid cranial CSF concentrations and assess attainment of pharmacodynamic (PD) thresholds (AUC:MIC of >119) in plasma and cranial CSF of adults and children with tuberculous meningitis. A physiologically based pharmacokinetic (PBPK) model was developed to predict linezolid cranial CSF profiles based on reported plasma concentrations. Simulated steady-state PK curves in plasma and cranial CSF after linezolid doses of 300 mg BID, 600 mg BID, and 1200 mg QD in adults resulted in geometric mean AUC:MIC ratios in plasma of 118, 281, and 262 and mean cranial CSF AUC:MIC ratios of 74, 181, and 166, respectively. In children using ~10 mg/kg BID linezolid, AUC:MIC values at steady-state in plasma and cranial CSF were 202 and 135, respectively. Our model predicts that 1200 mg per day in adults, either 600 mg BID or 1200 mg QD, results in reasonable (87%) target attainment in cranial CSF. Target attainment in our simulated paediatric population was moderate (56% in cranial CSF). Our PBPK model can support linezolid dose optimization efforts by simulating target attainment close to the site of TBM disease.

Occurrence of 1,3-Diphenylguanidine, 1,3-Di-o-tolylguanidine, and 1,2,3-Triphenylguanidine in Indoor Dust from 11 Countries: Implications for Human Exposure.

1,3-Diphenylguanidine (DPG), 1,3-di-o-tolylguanidine (DTG), and 1,2,3-triphenylguanidine (TPG) are synthetic chemicals widely used in rubber and other polymers. Nevertheless, limited information is available on their occurrence in indoor dust. We measured these chemicals in 332 dust samples collected from 11 countries. DPG, DTG, and TPG were found in 100%, 62%, and 76% of the house dust samples, at median concentrations of 140, 2.3, and 0.9 ng/g, respectively. The sum concentrations of DPG and its analogues varied among the countries in the following decreasing order: Japan (median: 1300 ng/g) > Greece (940) > South Korea (560) > Saudi Arabia (440) > the United States (250) > Kuwait (160) > Romania (140) > Vietnam (120) > Colombia (100) > Pakistan (33) > India (26). DPG accounted for ≥87% of the sum concentrations of the three compounds in all countries. DPG, DTG, and TPG exhibited significant correlations (r: 0.35-0.73; p < 0.001). Elevated concentrations of DPG were found in dust from certain microenvironments (e.g., offices and cars). Human exposure to DPG through dust ingestion were in the ranges 0.07-4.40, 0.09-5.20, 0.03-1.70, 0.02-1.04, and 0.01-0.87 ng/kg body weight (BW)/day for infants, toddlers, children, teenagers, and adults, respectively.

Measuring spatial accessibility to adult day services for older adults using GIS

Adult day services (ADS) provide community-based long-term care for older adults with chronic medical, cognitive, or mental health conditions and/or disabilities that are at risk of needing institutional care. This study aims to (a) measure and compare the spatial accessibility to ADS across major racial and ethnic minority older adult groups, and to (b) identify underserved urban areas which have limited access to ADS. Using Geographic Information Systems (GIS), we found little variation across ethnic and racial groups in accessibility to ADS; instead, most differences are between rural and urban areas. Underserved areas with a high older adult population in Los Angeles County were identified. Future research should incorporate other factors such as the organization’s capability, culture compatibility, types of services, and quality of services which may impact on ADS use among older adults.

Views of Older Adults on Using Support to Prevent Overload in Informal Caregivers: Results of a Story Completion Study

Older care recipients living at home increasingly rely on support from informal caregivers. As informal caregivers often combine these caregiving tasks with other tasks, such as paid work, they are at risk of becoming overloaded. To decrease informal caregiver burden, different forms of support are available that also affect older care recipients’ lives, such as respite care, technology, or home care. The aim of this qualitative study was to obtain more insight into the perceptions, potential concerns and preferences of older informal care recipients about the use of support to relieve informal caregivers. We performed a story completion writing task among 23 informal care recipients aged 65 years or older, using hypothetical situations to let them reflect on different caregiver relief support options. The task was followed-up by a story-mediated interview. We used thematic analysis to inductively analyze story completions and interviews. We found that older informal care recipients were often willing to use support to relieve their caregivers, to ensure their wellbeing. However, they were also concerned about how the use of such support may conflict with their interests, preferences and values (e.g. respect for their autonomy, privacy, having a trusting relationship with a caretaker, paying attention to human aspects in care). Older adults were most hesitant to use adult day care facilities and technological support options. While these areas of tensions cannot always be completely resolved, it is important to jointly identify and discuss these, and work towards solutions to balance the respective interests, values and needs of older adults and caregivers. Health and social care professionals and older adults’ personal networks may help in overcoming hesitation to use support.

Transfusion of Adult, but Not Neonatal, Platelets Promotes Monocyte Trafficking in Neonatal Mice.

Thrombocytopenia is common in preterm neonates. Platelet transfusions are sometimes given to thrombocytopenic neonates with the hope of reducing the bleeding risk, however, there are little clinical data to support this practice, and platelet transfusions may increase the bleeding risk or lead to adverse complications. Our group previously reported that fetal platelets expressed lower levels of immune-related mRNA compared with adult platelets. In this study, we focused on the effects of adult versus neonatal platelets on monocyte immune functions that may have an impact on neonatal immune function and transfusion complications. Using RNA sequencing of postnatal day 7 and adult platelets, we determined age-dependent platelet gene expression. Platelets and naive bone marrow-isolated monocytes were cocultured and monocyte phenotypes determined by RNA sequencing and flow cytometry. An in vivo model of platelet transfusion in neonatal thrombocytopenic mice was used in which platelet-deficient TPOR (thrombopoietin receptor) mutant mice were transfused with adult or postnatal day 7 platelets and monocyte phenotypes and trafficking were determined. Adult and neonatal platelets had differential immune molecule expression, including Selp. Monocytes incubated with adult or neonatal mouse platelets had similar inflammatory (Ly6Chi) but different trafficking phenotypes, as defined by CCR2 and CCR5 mRNA and surface expression. Blocking P-sel (P-selectin) interactions with its PSGL-1 (P-sel glycoprotein ligand-1) receptor on monocytes limited the adult platelet-induced monocyte trafficking phenotype, as well as adult platelet-induced monocyte migration in vitro. Similar results were seen in vivo, when thrombocytopenic neonatal mice were transfused with adult or postnatal day 7 platelets; adult platelets increased monocyte CCR2 and CCR5, as well as monocyte chemokine migration, whereas postnatal day 7 platelets did not. These data provide comparative insights into adult and neonatal platelet transfusion-regulated monocyte functions. The transfusion of adult platelets to neonatal mice was associated with an acute inflammatory and trafficking monocyte phenotype that was platelet P-sel dependent and may have an impact on complications associated with neonatal platelet transfusions.

A Longitudinal Study in Turkiye of Host Ability to Produce Antibodies following a Third Homologous BNT162b2 Vaccination.

Obesity is a multifaceted, complex condition that has negative impacts on one's health. There are conflicting reports regarding the COVID-19 vaccine's ability to induce antibody formation in obese people. Our study aimed to determine anti-S-RBD IgG and surrogate neutralizing antibody (snAb) levels before and after the third Pfizer-BioNTech (BNT162b2) vaccination (at 15, 60, 90, and 120 days) in normal-weight adults, overweight, and obese individuals without any comorbidity or previous SARS-CoV-2 infection history, but it did not evaluate the response to the first two doses. In this longitudinal prospective study in Istanbul, Turkey, a total of 323 consecutive adult individuals (141 normal weight, 108 overweight, and 74 patients with obesity) were included. Peripheral blood samples were collected. Anti-S-RBD IgG and surrogate neutralizing antibody levels were detected using the ELISA method. After the third dose of BNT162b2 vaccination, obese patients had significantly lower levels of snAb against SARS-CoV-2 compared with normal-weight controls, but the levels otherwise did not differ between the study groups. Across all individuals in our cohort, titers peaked about a month after this third vaccination and then gradually faded. Anti-S-RBD IgG and snAb IH% levels against SARS-CoV-2 were not correlated with IL-6 and TNF-α levels. In conclusion, anti-S-RBD IgG titers and snAb IH% levels against SARS-CoV-2 were determined longitudinally for 120 days after the third homologous BNT162b2 vaccination. Although there were no significant differences in anti-S-RBD IgG, we found significant differences in the snAb IH% levels against SARS-CoV-2 between obese and healthy control subjects.

Efficacy and safety of the ghrelin-O-acyltransferase inhibitor BI 1356225 in overweight/obesity: Data from two Phase I, randomised, placebo-controlled studies

BackgroundObesity is a complex disease associated with multiple concurrent complications, and the coordinated targeting of multiple pathways in pharmacological treatment may improve weight loss outcomes. During synthesis, ghrelin is converted from the ‘inactive’ unacylated ghrelin (UAG) to the active acylated ghrelin (AG) by the enzyme ghrelin-O-acyltransferase (GOAT), stimulating appetite and food intake. AimsTo report the results of two Phase I studies investigating single rising doses (SRDs) or multiple rising doses (MRDs) of the novel oral GOAT inhibitor BI 1356225 versus placebo in male and postmenopausal/sterilised female subjects with overweight or obesity. MethodsThe SRD study investigated single doses of BI 1356225 (0.1–20.0 mg) in healthy male subjects with a BMI of 18.5–29.9 kg/m2 (SRD cohort) and assessed doses of 2.5 mg BI 1356225 under fed and fasted conditions (bioavailability [BA] cohort). The MRD study investigated multiple doses of BI 1356225 (0.2, 1.0, 2.5 or 10.0 mg) or 5.0 mg BI 1356225 with a single dose of midazolam and celecoxib (drug–drug interaction part) over 28 days in adults with a BMI of 27.0–39.9 kg/m2. ResultsSixty-five subjects were treated in the SRD study. Drug-related adverse events (AEs) were reported for five subjects (9.1 %) in the SRD cohort and two subjects (20.0 %) in the BA cohort, with the most frequent being headache (SRD: n = 4, 9.8 %; BA: n = 1, 10.0 %). In the MRD study, two (2.3 %) of the 87 subjects treated discontinued treatment because of AEs. Drug-related AEs were reported for 18 subjects (20.7 %), did not increase with dose and were most frequently reported as headache (n = 5, 5.7 %) and gastrointestinal disorders (n = 5, 5.7 %). In both studies, exposure parameters (area under the concentration–time curve [AUC] and maximum plasma concentration [Cmax]) of BI 1356225 increased across dose groups, although this was less than dose-proportional across the entire dose range. In the BA cohort of the SRD study, AUC0–∞ was slightly increased and Cmax slightly decreased in fed versus fasted conditions, with fed/fasted ratios (90 % CI) of 101.10 % (92.42, 110.60) and 91.67 % (78.50, 107.05), respectively. In both studies, AG concentrations and the AG/UAG ratio were dose-dependently decreased after BI 1356225 treatment from baseline versus placebo. In the MRD study, UAG concentrations were increased from baseline, but not dose-dependently. No differences were observed in bodyweight, appetite, food cravings, ad libitum food uptake or obesity-related biomarkers after 28 days of treatment with BI 1356225. ConclusionsTreatment with SRDs and MRDs of BI 1356225 was well tolerated by healthy males and subjects with overweight/obesity. BI 1356225 treatment over 28 days reduced AG concentrations and the AG/UAG ratio by >80 %, but no effect was seen on bodyweight, hunger/satiety, control of eating or energy intake. Although, at 4 weeks, the MRD study was fairly short, a reduction in bodyweight would be expected to be evident by this time, suggesting that a reduction of AG via a GOAT inhibitor is not sufficient to induce clinically relevant bodyweight loss.