Health Deficits Research Articles

Mitochondrial changes in fish cells in vitro in response to serum deprivation.

Mitochondria are critical to cellular activity that implicated in expansive networks to maintain organismal homeostasis under external stimuli of nutrient variability, a common and severe stress to fish performance during the intensive culture conditions. In the present study, zebrafish embryonic fibroblast cells were used to investigate the fish mitochondrial changes upon serum deprivation. Results showed that mitochondrial content and membrane potential were significantly reduced with increased intracellular ROS level in the serum deprivation treated fish cells. And the impaired mitochondria were characterized by rough and fracted outer membrane, and more fused mitochondria were frequently observed with the upregulated mRNA expressions of mitochondrial fusion genes (mfn1b, mfn2, and opa1). Besides, the mitochondrial DNA (mtDNA) copy numbers of mtatp6, mtcox1, mtcytb, mtnd4, and mtnd6 were overall showing the highly significant reduction, together with the mRNA expressions of these genes significantly increased, exhibiting the compensatory effects in mitochondria. Furthermore, the methyl-cytosine of whole mtDNA was compared and the methyl-reads numbers were distinctly increased in the treatment group, reflecting the instability of fish mtDNA with mitochondrial dysfunction under nutrient fluctuations. Collectively, current findings could facilitate the integrated research between fish mitochondrial response and external variables that indicates the potentially profound and durative deficits in fish health during the aquaculture processes.

Specific Learning Disorders and Special Educational Needs during COVID-19 Pandemic; Pilot Survey Study Performed in Local District Schools in Italy.

Specific Learning Disorders (SLD) are a group of heterogeneous health deficits frequently diagnosed in early childhood that cause difficulties in general intellectual functioning. In the last decades in Italy new laws have been developed to give practical guidelines for the best education plans for children with SLD. Background: The aim of our study was to determine the efficacy of the educational treatment on SLD in Primary and Secondary schools in the Italian city of Barletta. We acquired valuable data to evaluate Special Education Needs during COVID-19. Methods: Our study was conducted from April to June 2021, during the second “lockdown” period in Italy. A fact-finding survey was conducted to schools with a questionnaire provided to the teachers to acquire data on the SEN applied in the management of distance learning for children. Results: The study involved 15 male and 6 female pupils with SLD in Primary Schools and 18 male and 6 female in Secondary Schools. The schools participating in the study organized distance learning programs with a support teacher with a 1:1 ratio. Data showed that all children with SLD needed a support teacher. Conclusions: The findings of this pilot study suggest that distance learning programs are able to achieve adequate educational goals, despite the difficulties of the lockdown period.

Assessing Frailty Risk in Clinical Practice

Assessing Frailty Risk in Clinical Practice

Age-related health deficits and five-year mortality among older, long-term cancer survivors

IntroductionGeriatric assessment evaluates multiple domains of health that, together, are superior to using chronologic age for predicting outcomes, such as hospitalization and mortality among patients with cancer. Most studies have not included comparison groups of individuals without cancer and assessed domains around the time of initial cancer diagnosis. Further, the potential for brief, self-reported measures to capture deficits that similarly predict mortality has not been well examined. This study compared age-related health deficit prevalence between older, long-term cancer survivors and individuals without a cancer history, and estimated associations between deficits and mortality risk among survivors. Materials and methodsAnalyses included participants in the Cancer Prevention Study (CPS)-II Nutrition Cohort who were cancer-free at enrollment in 1992/1993 and completed the Patient Reported Outcome Measurement Information System® (PROMIS®) global health questionnaire in 2011. Age-related deficits in five domains (comorbidities, functional status, mental health, malnutrition/weight loss, and social support) were self-reported. Cancer information was self-reported and confirmed via medical records or state cancer registries. Vital status through 2016 and cause of death was ascertained by linkage with the National Death Index. ResultsAnalyses included 9979 participants (median age = 80) diagnosed with invasive cancer 5–20 years prior to completing the 2011 survey and 63,578 participants without a cancer history (median age = 79). Overall deficits in the five domains were similar among long-term cancer survivors and controls. However, survivors of specific cancer types — non-Hodgkin lymphoma (NHL), lung, and kidney cancer – were more likely to report deficits in mental health and functional status than the control group. Among all survivors, each domain was independently associated with all-cause mortality, particularly functional status (hazard ratio [HR] = 2.02; 95% confidence interval [CI]: 1.80–2.27) and mental health (HR = 1.84; 95% CI: 1.65–2.04). Mortality risk increased with the number of deficits. DiscussionThese results suggest that, several years after treatment, NHL, lung, and kidney cancer survivors are still more likely to experience age-related deficits compared to other similarly-aged individuals. Furthermore, results show that shorter, self-reported physical and mental health assessments, such as the PROMIS® global health questions, are predictive of mortality among older, long-term cancer survivors and, therefore, may be useful in clinical and research settings.

0159 Sleep-wake stability and variability in the middle-aged adult population: a UK Biobank study

Abstract Introduction Given the increasing use of consumer, wrist-worn devices with triaxial accelerometry (actigraphy), understanding whether 24-hr activity patterns are associated with specific mental and physical health deficits is of paramount importance. The UK Biobank, a community-based sample of adults in the United Kingdom, provides an opportunity to examine this question given its size (more than 100,000 actigraphy records) and scope (association health records). As a first step in understanding these relationships, understanding the impact of missing data, ways to interpolate missing data, and the general characteristics of 24-hr patterns is necessary. Methods A subset (n=70) of complete (i.e., no missing data) actigraphy records from individuals participating in the UK Biobank were used to examine the impact of missing data on intradaily variability (IV; rhythm fragmentation) and interdaily stability (IS; rhythm regularity). Data were intentionally removed and imputed and the impact of the manipulations was examined with Bland-Altman statistics. After determining the best imputation method and the limits of the method, it was applied to missing data in the full cohort, resulting in 82,840 actigraphy records. These were examined for IV and IS, as well as relative amplitude and the timing of L5 and M10. Data were categorized by age, gender, ethnicity, BMI and material deprivation. ANOVA with eta² effect sizes were used for comparisons. Data shown as median (interquartile range). Results Relative to IV and IS, median and mean imputation methods corrected for missing data of up to 24 hours. Linear imputation of long (>3 hours) missing data worsened IV and IS scores. Non-parametric patterns in the general population were within expected range, with IV=0.89(0.74-1.05), IS=0.55(0.46-0.63), RA=0.90(0.85-0.99), L5-timing=00:52 (00:07-01:37), and M10-timing=08:25(07:40-09:20). Stratifying by gender, age, ethnicity, BMI and material deprivation resulted in significant differences within all groups (p<0.0001), but small effect sizes (0.0019-0.00052). Conclusion Median imputation is useful for correcting for missing data (<24 hours) when examining IV and IS. Non-parametric analysis of the general population indicated values within the expected range. Even though there were significant differences in non-parametric outcomes between genders, age groups, ethnicities, body-mass index and material deprivation, none of these had significant effect sizes. Support (If Any) This research has been conducted using the UK Biobank Resource

Predictive Patient Characteristics and Surgical Variables That Influence Postoperative Complications following Bilateral Reduction Mammoplasty.

Background:Breast hypertrophy is known to be a source of both physical and psychosocial health deficits. Therefore, the ability to relieve these symptoms with surgical treatment is an important consideration for patients. The primary objective of this study was to assess the impact of patient body mass index (BMI) on postoperation complications. The secondary objective of this study was to assess patient demographics, surgical techniques, and patient comorbidities for their impact on specific postoperative complications.Methods:A retrospective chart review of all patients who received bilateral breast reduction surgery in Nova Scotia over the past 10 years was performed. A total of 1022 patients met the inclusion criteria of the study. Logistic regression modeling was performed to identify demographic factors, surgical techniques, and patient comorbidities that impact the risk of developing specific postoperative complications.Results:Our study population had a total complication incidence of 37.7%. BMI was not significantly different between patients who developed complications and those who did not. Logistic regression modeling showed a significant relationship that with each unit increase in BMI above the mean (25.9 kg/m2) the relative risk of patient-reported postoperative asymmetry increased by 6%.Conclusions:The findings of this study suggest that BMI has several nonsignificant relationships to postoperative complications following bilateral breast reduction. These trends do not translate to significantly increased complaints of asymmetry, scarring‚ or revision surgeries. This study also provides valuable information on the timeline of postoperative complications and when they can commonly be identified.

Does poor quality housing impact on child health? Evidence from the social housing sector in Avon, UK

The correlation between poor quality housing and children's physical health has been well documented. Yet a limitation of the literature is the prevalence of selection bias and comparatively little evidence on children's mental health outcomes. This study explored the role of housing (and neighbourhood) quality in explaining differences in childhood mental and physical health between those living in social-rented flats and houses. The social housing allocation process mitigated unobserved differences across the two groups addressing some of the issues of endogenous selection, although stopping short of representing causal identification. Poorer housing quality explained over 50% of the 0.18 standard deviation deficit in the mental health of children in flats compared with houses, with primary mediators being damp and mould, home temperature, and mother's perception of her own home, but played no role in explaining physical health deficits of children in flats. In contrast, neighbourhood quality did not account for any of the mental and physical health deficits observed. Taken together, the present study adds to the evidence that the home environment of children in social housing is related to their development, whilst taking us beyond the existing literature in terms of accounting for selection bias.

The Graying of the Cool Pose: Examining Active Care Strategies Among Older African-American Men With Type 2 Diabetes Mellitus.

The influence of masculinity norms on disparate health outcomes has been established in the literature. What is less understood are the specific ways in which African-American men "do health" by engaging in strategies promoting positive health outcomes. This article reframes what has been previously examined through a health deficit perspective by reporting the experiences and positive health maintenance strategies of older, African-American men with type 2 diabetes mellitus (diabetes). We employed an intersectional framework to thematically analyze qualitative interviews with African-American male participants (N = 15) in our National Institute on Aging-funded study of diabetes among older adults in Baltimore. Interviews consisted of a modified version of the McGill Illness Narrative Interview, which included discussions of diabetes experiences and self-management strategies. The majority of African-American men in our study link their successful diabetes management to purposeful self-care activities, despite structural and personal limitations. These activities include proactively seeking diabetes education, healthy eating, medication management, and engaging in supportive relationships. Active pursuit of a healthy lifestyle often requires redefining Black manhood, defying negative gender stereotypes of what it means to be a Black male. Results are described in the context of the "Cool Pose," a framework for understanding how African-American men and boys cope with systemic racial oppression and the unachievable dominant standards of masculinity in the United States. The results suggest that this framework may be less applicable for older African-American men who promote well-being in the wake of chronic disease as they age.

Frailty indices based on self-report, blood-based biomarkers and examination-based data in the Canadian Longitudinal Study on Aging.

Frailty can be operationalised using the deficit accumulation approach, which considers health deficits across multiple domains. We aimed to develop, validate and compare three different frailty indices (FI) constructed from self-reported health measures (FI-Self Report), blood-based biomarkers (FI-Blood) and examination-based assessments (FI-Examination). Up to 30,027 participants aged 45-85years from the baseline (2011-2015) comprehensive cohort of the Canadian Longitudinal Study on Aging were included in the analyses. Following standard criteria, three FIs were created: a 48-item FI-Self Report, a 23-item FI-Blood and a 47-item FI-Examination. In addition a 118-item FI-Combined was constructed. Mortality status was ascertained in July 2019. FI-Blood and FI-Examination demonstrated broader distributions than FI-Self Report. FI-Self Report and FI-Blood scores were higher in females, whereas FI-Examination scores were higher in males. All FI scores increased nonlinearly with age and were highest at lower education levels. In sex and age-adjusted models, a 0.01 increase in FI score was associated with a 1.08 [95% confidence interval (CI): 1.07,1.10], 1.05 (1.04,1.06), 1.07 (1.05,1.08) and a 1.13 (1.11,1.16) increased odds of mortality for FI-Self Report, FI-Blood, FI-Examination and FI-Combined, respectively. Inclusion of the three distinct FI types in a single model yielded the best prognostic accuracy and model fit, even compared to the FI-Combined, with all FIs remaining independently associated with mortality. Characteristics of all FIs were largely consistent with previously established FIs. To adequately capture frailty levels and to improve our understanding of the heterogeneity of ageing, FIs should consider multiple types of deficits including self-reported, blood and examination-based measures.

Effects of tooth loss on anxiety‐like behaviors in Heterocephalus glaber

Tooth loss is an ailment affecting a large percentage of the population, particularly individuals of lower socioeconomic status and the elderly. Extensive tooth loss is known to result in anatomical changes in the face, including atrophy of masticatory muscles and decreases in mandibular and maxillary bone density, as well as volumetric changes within the brain. Human studies have reported strong correlations between tooth loss and levels of both anxiety and depression. However, little has been reported to date regarding the effect of dental health on emotional states, with only sparse information available from animal models regarding the psychiatric effects of tooth loss.Our study investigated the short‐term effects of tooth loss on anxiety‐like behaviors using Heterocephalus glaber, an animal with extensive sensory dedication to and behavioral reliance on its incisors. Adult naked mole‐rats underwent either tooth extraction or sham surgeries, followed by testing in both an open field maze and elevated plus maze in the weeks following. As there are no known studies to date that have utilized this animal model in behavioral tests of anxiety, our study provides critical information about the methodologies and modifications necessary to ascertain these important translational behavioral states so that future researchers can apply similar tests in other fields such as neurodegeneration, aging, and oncology.We hypothesized that tooth extraction will result in greater anxiety‐like behaviors, manifesting in various ways: greater defecation in the mazes, more time spent in the outer regions of the open field maze, and less time in the open arms of the elevated plus maze. The study demonstrated a trend towards tooth extraction increasing anxiety‐like behaviors in naked mole‐rats when investigated using the open field maze paradigm. There is evidence that, with an increase in sample sizes, this research will make evident the causal relationship of tooth loss and anxiety. Future research will investigate the long‐term behavioral changes associated with extensive tooth loss and the neurocircuitry associated with these behavioral alterations. Uncovering these details will provide potential therapeutic targets for negating the mental health difficulties associated with deficits in dental health.

The self-assessed information security skills of the Finnish population: A regression analysis

Instead of traditional services, citizens are increasingly being offered e-services, which require information security skills. However, the majority of research on information security skills has been conducted in homogenous groups of people. The purpose of this study was to describe self-assessed information security skills of the population of Finland and factors associated with the skills. A population survey covering inhabitants aged 20 and upwards was conducted from September 2020 to February 2021. The cross-sectional dataset was weighted (n = 6023) to ensure it represented the population. Descriptive statistics were used to establish an initial understanding. Then a regression analysis was conducted to identify the variables that were associated with information security skills. The results demonstrate that 78% of the respondents assessed their information security skills as good. There was a strong positive association between Internet skills and information security skills. Other factors that demonstrated a statistically significant association were age, level of education, financial situation, e-service use, information security concerns, functional health deficits, and major depression. Even though the majority of people were confident in their information security skills in the online environment, there was evidence of a skills gap that affected people in all age groups, more often senior citizens. The findings of this study increase our understanding of information security skills at the population level. The results can be used to identify groups who are not confident in their information security skills and for designing safer e-services and education or guidelines on information security.

Alcohol consumption patterns and unhealthy aging among older lifetime drinkers from Spain

BackgroundThe protective health effects of light alcohol consumption are debated due to potential selection biases, reverse causation and confounding. We examined cross-sectional and prospective associations of alcohol consumption patterns with unhealthy aging among older drinkers addressing these methodological issues. Methods2081 lifetime drinkers aged 65 + years from the Seniors-ENRICA-2 cohort followed-up for 2.4 years were classified as occasional (average lifetime alcohol intake [g/day] ≤1.43), low-risk (men: >1.43–20; women: >1.43–10), moderate-risk (men: >20–40; women: >10–20) and high-risk drinkers (men: >40; women: >20; or binge drinkers). A Mediterranean drinking pattern (MDP) was defined as occasional/low-risk drinking, wine preference and drinking only with meals. Unhealthy aging was measured with a 52-item health deficit accumulation index (DAI), with higher values indicating more health deficits. ResultsA 10-g/day increment in lifetime average alcohol intake was cross-sectionally associated with a higher DAI among all drinkers (mean difference [95% confidence interval] = 0.35 [0.16, 0.53]) and moderate-/high-risk drinkers (0.41 [0.17, 0.65]), but not among occasional/low-risk drinkers. Also, the DAI was 1.35 (0.06, 2.65) points higher in high-risk versus low-risk drinkers and 2.07 (0.59, 3.60) points higher in non-adherers versus adherers to the MDP. Most associations strengthened when restricting analyses to individuals with lower disease burden and did not generally remain after 2.4 years. ConclusionsWe found no evidence of a beneficial association between low-risk alcohol consumption and unhealthy aging, but a detrimental one for high-risk drinking, which strengthened when accounting for reverse causation, although attenuated over the follow-up likely due to selective attrition of those less resilient to the harmful effects of alcohol.

Translation of the geriatric emergency department intervention into other emergency departments: a post implementation evaluation of outcomes for older adults

BackgroundIncreasing numbers of older adults with complex health deficits presenting to emergency departments has prompted the development of innovative models of care. One such model designed to reduce poor outcomes associated with acute healthcare, is the Geriatric Emergency Department Intervention. This intervention is a nurse-led, physician-championed, Emergency Department intervention that improves the health outcomes for frail older adults in the emergency department.MethodsThis quantitative cohort study aimed to evaluate the healthcare outcomes and costs associated with the implementation of the Geriatric Emergency Department Intervention (GEDI) for adults aged 70 years and over at two hospital sites that implemented the model using the integrated-Promoting Action on Research Implementation in Health Services (i-PARHIS) framework. Hospital A was large teaching hospital located in the tropical north of Australia. Hospital B was a medium sized teaching hospital near Brisbane, Queensland Australia.The effect of the intervention was examined in two ways. Outcomes were compared between: 1) all patients in the pre- and post- implementation periods, and 2) patients seen or not seen by the Geriatric Emergency Department Intervention team in the post-implementation period. The outcomes measured were disposition (discharged home, admitted); emergency department length of stay; hospital length of stay; all cause in-hospital mortality within 28 days; time to re-presentation up to 28 days post-discharge; emergency department and in-hospital costs.Survival analyses were used for the primary and secondary outcome variables and a Cox survival model was used to estimate the associations between variables and outcomes. Multiple regression models were used to examine other secondary outcomes whilst controlling for a range of confounders.ResultsThe Geriatric Emergency Department Intervention was successfully translated into two different emergency departments. Both demonstrated an increased likelihood of discharge, decreased emergency department length of stay, decreased hospital costs for those who were admitted, with an associated reduction in risk of mortality, for adults aged 70 years and over.ConclusionsThe Geriatric Emergency Department Intervention was successfully translated into new sites that adapted the model design. Improvement in healthcare outcomes for older adults presenting to the emergency department was demonstrated, although this was more subtle than in the original model setting.

Family Structure is Associated with Mental Health and Attention Deficit (Hyperactivity) Disorders in Adolescents with Type 1 Diabetes.

To analyze the cross-sectional associations of family structure with mental health and attention deficit (hyperactivity) disorders (AD(H)D) in 11- to 17-year-old adolescents with early-onset type 1 diabetes participating in one of three baseline surveys as part of an ongoing cohort study. Parents (n=1,631) completed the Strengths and Difficulties Questionnaire to screen for their child's mental health and answered questions about their child's diagnosis of AD(H)D. Associations between mental health or AD(H)D and family structure were analyzed using multivariable logistic regression analyses adjusted for various personal and diabetes-related variables. Compared to adolescents living with both parents, adolescents living with one parent and his/her partner had 2.35 (95% confidence interval 1.32; 4.21) higher odds of abnormal screening result and 2.08 (1.09; 3.95) higher odds of a borderline screening result while adolescents living with a single parent had 1.84 (1.07; 3.17)/1.08 (0.53; 2.21) higher odds of abnormal/borderline screening results. The odds ratios for diagnosed attention deficit (hyperactivity) disorder were 2.17 (0.98; 4.84) for adolescents living with one parent and his/her partner and 1.27 (0.54; 3.01) for those living with a single parent vs. both parents. Our results indicate higher odds of mental health problems and AD(H)D in adolescents with type 1 diabetes who do not live with both parents; this finding was most pronounced in individuals living with one parent and his/her partner vs. both parents. Longitudinal studies are needed to verify our results and elucidate the underlying mechanisms.

Variability and agreement of frailty measures and risk of falls, hospital admissions and mortality in TILDA

Little is known about the within-person variability of different frailty instruments, their agreement over time, and whether use of repeat assessments could improve the strength of associations with adverse health outcomes. Repeat measurements recorded in 2010–2011 (Wave 1) and 2012 (Wave 2) from The Irish Longitudinal Study on Ageing (TILDA) were used to classify individuals with frailty using the frailty phenotype (FP) and frailty index (FI). Within-person variability and agreement of frailty classifications were assessed using ANOVA and kappa (K) statistics, respectively. Associations of each frailty measure (wave 1, wave 2, or mean of both waves) with risk of falls, hospitalisations and all-cause mortality were assessed using logistic regression. Among 7455 individuals (mean age 64.7 [SD 9.9] years), within-person SD was 0.664 units (95% CI 0.654–0.671) for FP and 2 health deficits (SD 0.050 [0.048–0.051]) for FI. Agreement of frailty was modest for both measures, but higher for FI (K 0.600 [0.584–0.615]) than FP (K 0.370 [0.348–0.401]). The odds ratios (ORs) for all-cause mortality were higher for frailty assessed using the mean of two versus single measurements for FI (ORs for mortality 3.5 [2.6–4.9] vs. 2.7 [1.9–3.4], respectively) and FP (ORs for mortality 6.9 [4.6–10.3] vs. 4.0 [2.8–5.635], respectively). Frailty scores based on single measurements had substantial within-person variability, but the agreement in classification of frailty was higher for FI than FP. Frailty assessed using the mean of two or more measurements recorded at separate visits was more strongly associated with adverse health outcomes than those recorded at a single visit.

Occurrence and Timing of Advance Care Planning in Persons With Dementia in General Practice: Analysis of Linked Electronic Health Records and Administrative Data.

BackgroundAdvance care planning (ACP) is a process of communication in which patients and family caregivers discuss preferences for future care with the healthcare team. For persons with dementia, it is crucial to timely engage in ACP. Therefore, we study ACP in dementia using electronic health record data. This study aims to determine how often ACP conversations are recorded, analyze time from dementia diagnosis until the first recorded conversation and time from the first recorded conversation to death, and analyze which factors are associated with the timing of ACP.MethodsElectronic records of 15,493 persons with dementia in Dutch general practice between 2008 and 2016 were linked to national administrative databases. ACP conversations and indicators of health deficits to determine frailty were obtained from electronic records coded with the International Classification of Primary Care. Socio-demographic characteristics were derived from the national population registry managed by Statistics Netherlands. Date of death was derived from the Personal Records Database (2008–2018).ResultsACP was recorded as such as 22 (95% CI, 20–23) first conversations per 1,000 person-years of follow-up. The hazard ratio (HR) for the first conversation increased every year after dementia diagnosis, from 0.01 in the first year to 0.07 in the 7th and 8th year after diagnosis. Median time from a first conversation to death was 2.57 years (95% CI, 2.31–2.82). Migrant status [non-Western vs. Western (HR 0.31, 95% CI, 0.15–0.65)] was significantly associated with a longer time from dementia diagnosis to the first conversation. Being pre-frail (HR 2.06, 95% CI, 1.58–2.69) or frail (HR 1.40, 95% CI, 1.13–1.73) vs. non-frail was significantly associated with a shorter time from dementia diagnosis to the first ACP conversation.ConclusionACP conversations in Dutch general practice were rare for persons with dementia, or was rarely recorded as such. In particular among persons with a non-Western migration background and those who are non-frail, it started long after diagnosis. We advise further research into public health and practical strategies to engage persons with dementia with a non-Western migration background and non-frail persons early in the disease trajectory in ACP.

Using an Electronic Health Record and Deficit Accumulation to Pragmatically Identify Candidates for Optimal Prescribing in Patients With Type 2 Diabetes.

Despite guidelines recommending less stringent glycemic goals for older adults with type 2 diabetes, overtreatment is prevalent. Pragmatic approaches for prioritizing patients for optimal prescribing are lacking. We describe glycemic control and medication patterns for older adults with type 2 diabetes in a contemporary cohort, exploring variability by frailty status. This was a cross-sectional observational study based on electronic health record (EHR) data, within an accountable care organization (ACO) affiliated with an academic medical center/health system. Participants were ACO-enrolled adults with type 2 diabetes who were ≥65 years of age as of 1 November 2020. Frailty status was determined by an automated EHR-based frailty index (eFI). Diabetes management was described by the most recent A1C in the past 2 years and use of higher-risk medications (insulin and/or sulfonylurea). Among 16,973 older adults with type 2 diabetes (mean age 75.2 years, 9,154 women [53.9%], 77.8% White), 9,134 (53.8%) and 6,218 (36.6%) were classified as pre-frail (0.10 < eFI ≤0.21) or frail (eFI >0.21), respectively. The median A1C level was 6.7% (50 mmol/mol) with an interquartile range of 6.2-7.5%, and 74.1 and 38.3% of patients had an A1C <7.5% (58 mmol/mol) and <6.5% (48 mmol/mol), respectively. Frailty status was not associated with level of glycemic control (P = 0.08). A majority of frail patients had an A1C <7.5% (58 mmol/mol) (n = 4,544, 73.1%), and among these patients, 1,755 (38.6%) were taking insulin and/or a sulfonylurea. Treatment with insulin and/or a sulfonylurea to an A1C levels <7.5% is common in frail older adults. Tools such as the eFI may offer a scalable approach to targeting optimal prescribing interventions.

The clinical utility of three frailty measures in identifying HIV-associated neurocognitive disorders: a cross-sectional comparison of the Fried Phenotype, Rockwood Frailty Index, and Veterans Aging Cohort Study Index

BackgroundFrailty is associated with poorer cognitive functioning among people with HIV. Frailty measures vary widely and the optimal measure for predicting HIV-associated neurocognitive disorders (HAND) is unclear. MethodsParticipants were 289 people with HIV, aged 50 years or older (mean age 59·6 years, SD 7·3; 87% male, 13% female), enrolled in University of California San Diego's HIV Neurobehavioral Research Program from 2014 to 2020. Frailty measurements included the Fried Phenotype criteria (0–5 symptoms: weight loss, exhaustion, low physical activity, slowness, weakness), the Rockwood Frailty Index (proportion of general and HIV-specific health deficits ranging from 0 [no deficits] to 1 [all 34 deficits]), and the Veterans Aging Cohort Study (VACS) Index 1.0. HIV-associated Neurocognitive Disorders (HAND) was diagnosed according to the Frascati criteria using a seven-domain neuropsychological test. Separate ANOVAs (ie, one for each frailty measure) were used to examine differences in frailty severity between HAND subgroups, and receiver operating characteristic (ROC) analyses evaluated sensitivity and specificity of each frailty measure to detect symptomatic HAND (mild neurocognitive disorder and HIV-associated dementia) from cognitively normal cases. FindingsParticipants diagnosed with HIV-associated dementia had higher rates of frailty than participants without HAND among all three frailty measures (p<0·05; ds>0·41). Significant differences in frailty severity were observed between no HAND and mild neurocognitive disorder (p<0·05; ds>0·48) as well as asymptomatic HIV-associated neurocognitive impairment and HIV-associated dementia (p<0·05; ds>0·53) when using the Fried Phenotype or the Rockwood Frailty Index, but not with the VACS Index. To detect people who were symptomatic from individuals who were cognitively normal, an optimal cutoff of at least 3 was identified for the Fried Frailty index (area under the curve [AUC] 0·71), with sensitivity of 37% and specificity of 92%; an optimal cutoff of at least 0·206 was identified for the Rockwood Frailty index (AUC 0·66), with sensitivity of 85% and specificity of 43%; and an optimal cutoff of at least 29 was identified for the VACS index (AUC 0·59), with sensitivity of 58% and specificity of 65%. InterpretationFried and Rockwood outperformed VACS in predicting HAND; however, ROC analyses suggest none of the indices had adequate predictive validity in detecting HAND. Given the Rockwood Index's overly inclusiveness (high sensitivity), we proposed it be used as a screening tool. When combined with the Frailty Index, which has demonstrated to be a good exclusionary tool (high specificity), the two measure can be clinically useful together in detecting HAND. FundingNational Institute of Mental Health (R01 MH099987, P30 MH062512), the National Institute on Drug Abuse (T32 DA031098 and F31AG064989), and the National Institute on Alcohol Abuse and Alcoholism (F31 AA027198).

Under the regulatory radar: Unregulated rural healthcare in Bangladesh and Australia.

This study examines health regulation under conditions of geographical constraint in two strikingly different settings, one on a remote island in Bangladesh and the other in an impoverished rural region in Australia. Both suffer from an absence of medically qualified professionals, which means that in the resultant vacuum, patients access alternative healthcare. The concept of regulation (or lack of regulation) is explored in terms of unconventional new responses to rural health deficits. The two cases show unexpected commonality, with policymakers facing shared challenges beyond physical remoteness. The difference in the degree of enforcement of regulation offers the greatest point of difference. This comparative study revealed a weak health regulatory system in the remote Bangladesh area of Bhola Island where ‘alternatives’ to formal clinical approaches have become the default choice. Brazen stop‐gap servicing is commonplace on Bhola Island, but in The Gemfields such practices only occur in the shadows or as a last resort. Each isolated location, one in a developing country and the other in a developed setting, exemplifies how geographical remoteness can present an opportunity for innovations in supply to emerge. Surprisingly, it is the developing world case that better leverages a regulatory void to respond to local healthcare needs.

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults.

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.