Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries.

Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.

Performance of FRAX in older adults with frailty: the Framingham Heart Study.

We compared the performance of FRAX according to frailty status in 3554 individuals from the Framingham Study. During 10-year follow-up, 6.9% and 3.0% of participants with and without frailty experienced MOF. Discrimination profiles were lower in participants with frailty compared to those without, but they improved when FRAX included BMD. INTRODUCTION: Frailty increases fracture risk. FRAX was developed to predict fractures but never validated in individuals with frailty. We aimed to compare the predictive performance of FRAX (v4.3) in individuals with and without frailty. METHODS: We conducted a cohort study using the Framingham Heart Study. Frailty was defined by the Fried phenotype. Major osteoporotic fractures (MOF) were ascertained from medical records during 10-year follow-up. To evaluate discrimination and calibration of FRAX, we calculated the area-under-the-receiver-operating characteristics curves (AUC) using logistic regression models and observed-to-predicted fracture probabilities. Analyses were stratified by frailty status. RESULTS: Frailty was present in 550/3554 (15.5%) of participants. Participants with frailty were older (81.1 vs. 67.6 years), female (68.6% vs. 55.1%), and had greater mean FRAX scores (MOF: 15.9% vs. 10.1%) than participants without frailty. During follow-up, 38 participants with frailty (6.9%) and 91 without (3.0%) had MOFs. The AUC for FRAX (without BMD) was lower in participants with frailty (0.584; 95% CI 0.504-0.663) compared to those without (0.695; 95% CI 0.649-0.741); p value = 0.02. Among participants with frailty, the AUC improved when FRAX included BMD (AUC 0.658, p value < 0.01). FRAX overestimated MOF risk, with larger overestimations in individuals without frailty. Performance of FRAX for hip fracture was similar. CONCLUSION: FRAX may have been less able to identify frail individuals at risk for fracture, as compared with individuals without frailty, unless information on BMD is available. This suggests that BMD captures features important for fracture prediction in frail persons. Future fracture prediction models should be developed among persons with frailty.

Comparative safety and cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in nursing homes.

AIM: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents. MATERIALS AND METHODS: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates. RESULTS: The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference. CONCLUSIONS: SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA.

Snack quality and snack timing are associated with cardiometabolic blood markers: the ZOE PREDICT study.

BACKGROUND: Snacking is a common diet behaviour which accounts for a large proportion of daily energy intake, making it a key determinant of diet quality. However, the relationship between snacking frequency, quality and timing with cardiometabolic health remains unclear. DESIGN: Demography, diet, health (fasting and postprandial cardiometabolic blood and anthropometrics markers) and stool metagenomics data were assessed in the UK PREDICT 1 cohort (N = 1002) (NCT03479866). Snacks (foods or drinks consumed between main meals) were self-reported (weighed records) across 2-4 days. Average snacking frequency and quality [snack diet index (SDI)] were determined (N = 854 after exclusions). Associations between snacking frequency, quality and timing with cardiometabolic blood and anthropometric markers were assessed using regression models (adjusted for age, sex, BMI, education, physical activity level and main meal quality). RESULTS: Participants were aged (mean, SD) 46.1 ± 11.9 years, had a mean BMI of 25.6 ± 4.88 kg/m2 and were predominantly female (73%). 95% of participants were snackers (≥ 1 snack/day; n = 813); mean daily snack intake was 2.28 snacks/day (24 ± 16% of daily calories; 203 ± 170 kcal); and 44% of participants were discordant for meal and snack quality. In snackers, overall snacking frequency and quantity of snack energy were not associated with cardiometabolic risk markers. However, lower snack quality (SDI range 1-11) was associated with higher blood markers, including elevated fasting triglycerides (TG (mmol/L) ß; - 0.02, P = 0.02), postprandial TGs (6hiAUC (mmol/L.s); ß; - 400, P = 0.01), fasting insulin (mIU/L) (ß; - 0.15, P = 0.04), insulin resistance (HOMA-IR; ß; - 0.04, P = 0.04) and hunger (scale 0-100) (ß; - 0.52, P = 0.02) (P values non-significant after multiple testing adjustments). Late-evening snacking (≥ 9 pm; 31%) was associated with lower blood markers (HbA1c; 5.54 ± 0.42% vs 5.46 ± 0.28%, glucose 2hiAUC; 8212 ± 5559 vs 7321 ± 4928 mmol/L.s, P = 0.01 and TG 6hiAUC; 11,638 ± 8166 vs 9781 ± 6997 mmol/L.s, P = 0.01) compared to all other snacking times (HbA1c remained significant after multiple testing). CONCLUSION: Snack quality and timing of consumption are simple diet features which may be targeted to improve diet quality, with potential health benefits. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: NCT03479866, https://clinicaltrials.gov/ct2/show/NCT03479866?term=NCT03479866&draw=2&rank=1.

Prehospital Massive Transfusion for Resuscitation of an Entrapped Patient in a Rural Setting: A Case Report.

Resuscitation of injured patients suffering from hemorrhagic shock with blood products in the prehospital environment is becoming more commonplace. However, blood product utilization is typically restricted and can be exhausted in the event of a prolonged entrapment. Delivery of large amounts of blood products to a scene is rare, particularly in rural settings. We present the case of a 26-year-old male who was entrapped in a motor vehicle for 144 min. First responders assessed the entrapped patient to be in hemorrhagic shock from lower extremities injuries. The Helicopter Emergency Medical Services team exhausted their supply of blood products shortly after arrival on scene. The local trauma center's Surgical Emergency Response Team (SERT) was requested to the scene. The preplanned response included seven units of blood components to provide massive transfusion at the point of injury and released directly to field responders by the blood bank. During extrication, the patient was given two units of packed red blood cells by initial responders with three more units of blood components from the SERT supply. During transfer to the hospital, the patient received an additional three units, and four units were transfused on initial trauma resuscitation in the hospital. He was found to have severe lower extremities injuries as the cause of his hemorrhage. The patient survived to hospital discharge. Delivery of large volumes of blood products to an entrapped patient with prolonged extrication time may be a lifesaving intervention. We advocate for integration of blood bank services and on scene physician guided resuscitation for prolonged extrications.

Risk Assessment and Prevention of Falls in Older Community-Dwelling Adults: A Review.

Importance: Falls are reported by more than 14 million US adults aged 65 years or older annually and can result in substantial morbidity, mortality, and health care expenditures. Observations: Falls result from age-related physiologic changes compounded by multiple intrinsic and extrinsic risk factors. Major modifiable risk factors among community-dwelling older adults include gait and balance disorders, orthostatic hypotension, sensory impairment, medications, and environmental hazards. Guidelines recommend that individuals who report a fall in the prior year, have concerns about falling, or have gait speed less than 0.8 to 1 m/s should receive fall prevention interventions. In a meta-analysis of 59 randomized clinical trials (RCTs) in average-risk to high-risk populations, exercise interventions to reduce falls were associated with 655 falls per 1000 patient-years in intervention groups vs 850 falls per 1000 patient-years in nonexercise control groups (rate ratio [RR] for falls, 0.77; 95% CI, 0.71-0.83; risk ratio for number of people who fall, 0.85; 95% CI, 0.81-0.89; risk difference, 7.2%; 95% CI, 5.2%-9.1%), with most trials assessing balance and functional exercises. In a meta-analysis of 43 RCTs of interventions that systematically assessed and addressed multiple risk factors among individuals at high risk, multifactorial interventions were associated with 1784 falls per 1000 patient-years in intervention groups vs 2317 falls per 1000 patient-years in control groups (RR, 0.77; 95% CI, 0.67-0.87) without a significant difference in the number of individuals who fell. Other interventions associated with decreased falls in meta-analysis of RCTs and quasi-randomized trials include surgery to remove cataracts (8 studies with 1834 patients; risk ratio [RR], 0.68; 95% CI, 0.48-0.96), multicomponent podiatry interventions (3 studies with 1358 patients; RR, 0.77; 95% CI, 0.61-0.99), and environmental modifications for individuals at high risk (12 studies with 5293 patients; RR, 0.74; 95% CI, 0.61-0.91). Meta-analysis of RCTs of programs to stop medications associated with falls have not found a significant reduction, although deprescribing is a component of many successful multifactorial interventions. Conclusions and Relevance: More than 25% of older adults fall each year, and falls are the leading cause of injury-related death in persons aged 65 years or older. Functional exercises to improve leg strength and balance are recommended for fall prevention in average-risk to high-risk populations. Multifactorial risk reduction based on a systematic clinical assessment for modifiable risk factors may reduce fall rates among those at high risk.

Long-Term Care Pharmacy Market Shares and Differences in Skilled Nursing Facilities Served.

Medications and pharmacy services are critical to post-acute care (PAC) in skilled nursing facilities (SNFs), yet little is known about the long-term care (LTC) pharmacies that provide them. We estimated the market shares of LTC pharmacies and how SNFs differed between pharmacies. This cross-sectional study used data from SNFs that provided PAC services in Rhode Island (RI) in 2019. We applied the parametric g-formula to compare SNF pharmacy-related deficiencies and medication use measures between LTC pharmacies while standardizing for SNF membership in a chain and number of beds. Among 75 SNFs, 68 (91%) were served by either Omnicare (n = 32, 43%) or PharMerica (n = 36, 48%), and 7 (9%) by other LTC pharmacies. After covariate adjustment, PharMerica SNFs had the lowest prevalences of any pharmacy-related deficiency (PharMerica, 63.2%; Omnicare, 80.2%; other LTC pharmacy, 69.1%) and antianxiety medication use (PharMerica, 9.7%; Omnicare, 13.6%; other LTC pharmacy, 13.5%), but estimates were imprecise. The RI market is highly concentrated between LTC pharmacies. If similarly high LTC pharmacy market concentration exists nationally, there is enormous promise for efficiently delivering interventions to improve medication management in SNFs. However, it may also present a risk of harm if policies do not maintain sufficient competition and innovation is stifled.

Little is known about long-term care pharmacies serving skilled nursing facilitiesThese pharmacies may have a strong influence on quality of care and outcomesTwo pharmacies dominate 91% of the Rhode Island skilled nursing facility marketSkilled beds, pharmacy deficiencies, and medication use may differ by pharmacyPharmacy market concentration creates opportunities for both big benefits and harms.

Evaluation of post-acute care and one-year outcomes among Medicare beneficiaries with hip fractures: a retrospective cohort study.

BACKGROUND: Post-acute care (PAC) services after hospitalization for hip fracture are typically provided in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), or at home via home health care (HHC). Little is known about the clinical course following PAC for hip fracture. We examined the nationwide burden of adverse outcomes by PAC setting in the year following discharge from PAC for hip fracture. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries > 65 years who received PAC services in U.S. SNFs, IRFs, or HHC following hip fracture hospitalization between 2012 and 2018. Individuals who had a fall-related injury (FRI) during PAC or received PAC services in multiple settings were excluded. Primary outcomes included FRIs, all-cause hospital readmissions, and death in the year following discharge from PAC. Cumulative incidences and incidence rates for adverse outcomes were reported by PAC setting. Exploratory analyses examined risk ratios and hazard ratios between settings before and after inverse-probability-of-treatment-weighting, which accounted for 43 covariates. RESULTS: Among 624,631 participants (SNF, 67.78%; IRF, 16.08%; HHC, 16.15%), the mean (standard deviation) age was 82.70 (8.26) years, 74.96% were female, and 91.30% were non-Hispanic White. Crude incidence rates (95%CLs) per 1000 person-years were highest among individuals receiving SNF care for FRIs (SNF, 123 [121, 123]; IRF, 105 [102, 107]; HHC, 89 [87, 91]), hospital readmission (SNF, 623 [619, 626]; IRF, 538 [532, 544]; HHC, 418 [414, 423]), and death (SNF, 167 [165, 169]; IRF, 47 [46, 49]; HHC, 55 [53, 56]). Overall, rates of adverse outcomes generally remained higher among SNF care recipients after covariate adjustment. However, inferences about the group with greater adverse outcomes differed for FRIs and hospital readmissions based on risk ratio or hazard ratio estimates. CONCLUSIONS: In this retrospective cohort study of individuals hospitalized for hip fracture, rates of adverse outcomes in the year following PAC were common, especially among SNF care recipients. Understanding risks and rates of adverse events can inform future efforts to improve outcomes for older adults receiving PAC for hip fracture. Future work should consider calculating risk and rate measures to assess the influence of differential time under observation across PAC groups.

Plasma protein N-glycome composition associates with postprandial lipaemic response.

BACKGROUND: A dysregulated postprandial metabolic response is a risk factor for chronic diseases, including type 2 diabetes mellitus (T2DM). The plasma protein N-glycome is implicated in both lipid metabolism and T2DM risk. Hence, we first investigate the relationship between the N-glycome and postprandial metabolism and then explore the mediatory role of the plasma N-glycome in the relationship between postprandial lipaemia and T2DM. METHODS: We included 995 individuals from the ZOE-PREDICT 1 study with plasma N-glycans measured by ultra-performance liquid chromatography at fasting and triglyceride, insulin, and glucose levels measured at fasting and following a mixed-meal challenge. Linear mixed models were used to investigate the associations between plasma protein N-glycosylation and metabolic response (fasting, postprandial (Cmax), or change from fasting). A mediation analysis was used to further explore the relationship of the N-glycome in the prediabetes (HbA1c = 39-47 mmol/mol (5.7-6.5%))-postprandial lipaemia association. RESULTS: We identified 36 out of 55 glycans significantly associated with postprandial triglycerides (Cmax ß ranging from -0.28 for low-branched glycans to 0.30 for GP26) after adjusting for covariates and multiple testing (padjusted < 0.05). N-glycome composition explained 12.6% of the variance in postprandial triglycerides not already explained by traditional risk factors. Twenty-seven glycans were also associated with postprandial glucose and 12 with postprandial insulin. Additionally, 3 of the postprandial triglyceride-associated glycans (GP9, GP11, and GP32) also correlate with prediabetes and partially mediate the relationship between prediabetes and postprandial triglycerides. CONCLUSIONS: This study provides a comprehensive overview of the interconnections between plasma protein N-glycosylation and postprandial responses, demonstrating the incremental predictive benefit of N-glycans. We also suggest a considerable proportion of the effect of prediabetes on postprandial triglycerides is mediated by some plasma N-glycans.

The effect of exercise in a fasted state on plasma low-density lipoprotein cholesterol concentrations in males and females.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Physical activity interventions improve almost all modifiable CVD risk factors, but the effect of physical activity on low density lipoprotein cholesterol (LDL-C) is uncertain. This may be due to lack of research on the feeding status in which the physical activity is performed. The aim of this study is to investigate the effect of fasted versus fed exercise on LDL-C concentrations in males and females. One hundred healthy participants, equal males and females, aged between 25 and 60 years will be recruited and will undergo a home-based 12-week exercise intervention. After baseline testing, participants will be randomized to a fasted exercise (exercise after an 8-h fast) or fed exercise (exercise 90-180 min after ingestion of 1 g kg-1 CHO) group and will perform 50 min of moderate intensity exercise (e.g., 95% heart rate of lactate threshold 1) three times a week either before or after a high carbohydrate (1 g kg-1 ) meal. Participants will visit the laboratory again at week 4 and week 12 and measurements will be taken for body composition, resting blood pressure, fasting blood glucose, lipid profiles and systemic inflammation, lactate threshold, and 14-day blood glucose control.

PCSK9 Activity Is Potentiated Through HDL Binding.

Rationale: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and high-density lipoprotein (HDL) remains unexplored. Objective: This study sought to interrogate the novel relationship between PCSK9 and HDL in humans. Methods and Results: Comparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck (n=656) study revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein-C3, an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 times points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apolipoprotein-C3 from HDL and lower levels of small HDL as measured by nuclear magnetic resonance. Crosslinking mass spectrometry (XLMS) upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin and apolipoprotein-E within the HDL proteome, that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalisation and multimerisation. Conclusions: This study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipaemia as a driver of PCSK9 and apolipoprotein-C3 release from HDL.

Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort.

PURPOSE: In this study, we explore the relationship between social jetlag (SJL), a parameter of circadian misalignment, and gut microbial composition, diet and cardiometabolic health in the ZOE PREDICT 1 cohort (NCT03479866). METHODS: We assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures (n = 1002). We used self-reported habitual sleep (n = 934) to calculate SJL (difference in mid-sleep time point of ≥ 1.5 h on week versus weekend days). We tested group differences (SJL vs no-SJL) in cardiometabolic markers and diet (ANCOVA) adjusting for sex, age, BMI, ethnicity, and socio-economic status. We performed comparisons of gut microbial composition using machine learning and association analyses on the species level genome bins present in at least 20% of the samples. RESULTS: The SJL group (16%, n = 145) had a greater proportion of males (39% vs 25%), shorter sleepers (average sleep < 7 h; 5% vs 3%), and were younger (38.4 ± 11.3y vs 46.8 ± 11.7y) compared to the no-SJL group. SJL was associated with a higher relative abundance of 9 gut bacteria and lower abundance of 8 gut bacteria (q < 0.2 and absolute Cohen's effect size > 0.2), in part mediated by diet. SJL was associated with unfavourable diet quality (less healthful Plant-based Diet Index), higher intakes of potatoes and sugar-sweetened beverages, and lower intakes of fruits, and nuts, and slightly higher markers of inflammation (GlycA and IL-6) compared with no-SJL (P < 0.05 adjusted for covariates); rendered non-significant after multiple testing adjustments. CONCLUSIONS: Novel associations between SJL and a more disadvantageous gut microbiome in a cohort of predominantly adequate sleepers highlight the potential implications of SJL for health.

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.

PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Perspectives on Deprescribing in long-term care: qualitative findings from nurses, aides, residents, and proxies.

BACKGROUND: Deprescribing initiatives in the long-term care (LTC) setting are often unsuccessful or not sustained. Prior research has considered how physicians and pharmacists feel about deprescribing, yet little is known about the perspectives of frontline nursing staff and residents. Our aim was to elicit perspectives from LTC nursing staff, patients, and proxies regarding their experiences and preferences for deprescribing in order to inform future deprescribing efforts in LTC. METHODS: This study was a qualitative analysis of interviews with nurses, nurse aides, a nurse practitioner, residents, and proxies (family member and/or responsible party) from three LTC facilities. The research team used semi-structured interviews. Guides were designed to inform an injury prevention intervention. Interviews were recorded and transcribed. A qualitative framework analysis was used to summarize themes related to deprescribing. The full study team reviewed the summary to identify actionable, clinical implications. RESULTS: Twenty-six interviews with 28 participants were completed, including 11 nurse aides, three residents, seven proxies, one nurse practitioner, and six nurses. Three themes emerged that were consistent across facilities: 1) build trust with team members, including residents and proxies; 2) identify motivating factors that lead to resident, proxy, nurse practitioner, and staff acceptance of deprescribing; 3) standardize supportive processes to encourage deprescribing. These themes suggest several actionable steps to improve deprescribing initiatives including: 1) tell stories about successful deprescribing, 2) provide deprescribing education to frontline staff, 3) align medication risk/benefit discussions with what matters most to the resident, 4) standardize deprescribing monitoring protocols, 5) standardize interprofessional team huddles and care plan meetings to include deprescribing conversations, and 6) strengthen non-pharmacologic treatment programs. CONCLUSIONS: By interviewing LTC stakeholders, we identified three important themes regarding successful deprescribing: Trust, Motivating Factors, and Supportive Processes. These themes may translate into actionable steps for clinicians and researchers to improve and sustain person-centered deprescribing initiatives. TRIAL REGISTRATION: NCT04242186.

Evolution in Health and Medical Humanities education: a proposal for accreditation.

The growth of Health and Medical Humanities baccalaureate and master's degrees in recent decades makes the present moment ideal for initiating field-defining conversations among health humanities constituents about the boundaries of this transdisciplinary field. Focusing on accreditation at the programme level rather than the individual level, we explore four models with different advantages for Health and Medical Humanities: a certification for practice; a network (umbrella organisation); a programme of merit (POM) model; and consultancy. We conclude that for a young field like health humanities that is transdisciplinary, does not have an established canon and does not lead to entry to a specific professional path (ie, gatekeeping), the POM model is the best fit. In contrast to a full accreditation model, POM credentialling leaves room for creativity, expansiveness, and diversity of approaches and will not restrict programmes from calling themselves health humanities programmes; POM enhances visibility rather than decides who can teach in the field and what they must teach. To implement this model, we suggest the creation of a semi-independent Health and Medical Humanities Program Accreditation Commission (HMHPAC) that would be administered by the Health Humanities Consortium. The HMHPAC should have three goals: ensure that health humanities educational programmes are of the highest quality, assist programmes in acquiring the resources they need from their institutions and help programmes attract potential students.

Impact of insufficient sleep on dysregulated blood glucose control under standardised meal conditions.

AIMS/HYPOTHESIS: Sleep, diet and exercise are fundamental to metabolic homeostasis. In this secondary analysis of a repeated measures, nutritional intervention study, we tested whether an individual's sleep quality, duration and timing impact glycaemic response to a breakfast meal the following morning. METHODS: Healthy adults' data (N = 953 [41% twins]) were analysed from the PREDICT dietary intervention trial. Participants consumed isoenergetic standardised meals over 2 weeks in the clinic and at home. Actigraphy was used to assess sleep variables (duration, efficiency, timing) and continuous glucose monitors were used to measure glycaemic variation (>8000 meals). RESULTS: Sleep variables were significantly associated with postprandial glycaemic control (2 h incremental AUC), at both between- and within-person levels. Sleep period time interacted with meal type, with a smaller effect of poor sleep on postprandial blood glucose levels when high-carbohydrate (low fat/protein) (pinteraction = 0.02) and high-fat (pinteraction = 0.03) breakfasts were consumed compared with a reference 75 g OGTT. Within-person sleep period time had a similar interaction (high carbohydrate: pinteraction = 0.001, high fat: pinteraction = 0.02). Within- and between-person sleep efficiency were significantly associated with lower postprandial blood glucose levels irrespective of meal type (both p < 0.03). Later sleep midpoint (time deviation from midnight) was found to be significantly associated with higher postprandial glucose, in both between-person and within-person comparisons (p = 0.035 and p = 0.051, respectively). CONCLUSIONS/INTERPRETATION: Poor sleep efficiency and later bedtime routines are associated with more pronounced postprandial glycaemic responses to breakfast the following morning. A person's deviation from their usual sleep pattern was also associated with poorer postprandial glycaemic control. These findings underscore sleep as a modifiable, non-pharmacological therapeutic target for the optimal regulation of human metabolic health. Trial registration ClinicalTrials.gov NCT03479866.

Significant Reduction in Vaccine-Induced Antibody Levels and Neutralization Activity Among Healthcare Workers and Nursing Home Residents 6 Months Following Coronavirus Disease 2019 BNT162b2 mRNA Vaccination.

Antibody decline occurred from 2 weeks to 6 months post-BNT162b2 mRNA vaccination in nursing home (NH) residents and healthcare workers. Antispike, receptor-binding domain, and neutralization levels dropped >81% irrespective of prior infection. Notably, 69% of infection-naive NH residents had neutralizing antibodies at or below the assay's limit of detection.

COVID-19 Vaccine Uptake Among Nursing Home Staff via Statewide Policy: The Mississippi Vaccinate or Test Out Policy.

Objectives. To examine whether COVID-19 vaccine mandates that allow a test-out exemption for nursing home staff are associated with increased staff vaccination rates in nursing homes. Methods. Using the National Healthcare Safety Network data, we conducted analyses to test trends over time in statewide staff vaccination rates between June 1, 2021, and August 29, 2021, in Mississippi, 4 adjacent states, and the United States overall. Results. COVID-19 staff vaccination rates increased slowly following Mississippi enacting a vaccinate-or-test-out policy, achieving small, but statistically greater gains than most comparator states. Yet, staff vaccination rates in Mississippi remained well below the national average and similar numerically to surrounding states without mandates. Conclusions. Mississippi's COVID-19 vaccinate-or-test policy was ineffective in meaningfully increasing staff vaccination rates. For COVID-19 nursing home mandates to be effective while still balancing the staff turnover risks, facilities might consider a more stringent or hybrid approach (e.g., test-out option not offered to new staff). Public Health Implications. Statewide COVID-19 vaccine mandates, when given a test-out option, do not appear to be an effective strategy to meaningfully increase nursing home staff COVID-19 vaccination. (Am J Public Health. 2022;112(5):762-765. https://doi.org/10.2105/AJPH.2022.306800).

Effects of dipeptidyl peptidase-4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. MATERIALS AND METHODS: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models. RESULTS: The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise. CONCLUSIONS: Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.

Screening for phenotypic outliers identifies an unusually low concentration of a ß-lactoglobulin B protein isoform in bovine milk caused by a synonymous SNP.

BACKGROUND: Milk samples from 10,641 dairy cattle were screened by a mass spectrometry method for extreme concentrations of the A or B isoforms of the whey protein, ß-lactoglobulin (BLG), to identify causative genetic variation driving changes in BLG concentration. RESULTS: A cohort of cows, from a single sire family, was identified that produced milk containing a low concentration of the BLG B protein isoform. A genome-wide association study (GWAS) of BLG B protein isoform concentration in milk from AB heterozygous cows, detected a group of highly significant single nucleotide polymorphisms (SNPs) within or close to the BLG gene. Among these was a synonymous G/A variation at position + 78 bp in exon 1 of the BLG gene (chr11:103256256G > A). The effect of the A allele of this SNP (which we named B') on BLG expression was evaluated in a luciferase reporter assay in transfected CHO-K1 and MCF-7 cells. In both cell types, the presence of the B' allele in a plasmid containing the bovine BLG gene from -922 to + 898 bp (relative to the transcription initiation site) resulted in a 60% relative reduction in mRNA expression, compared to the plasmid containing the wild-type B sequence allele. Examination of a mammary RNAseq dataset (n = 391) identified 14 heterozygous carriers of the B' allele which were homozygous for the BLG B protein isoform (BB'). The level of expression of the BLG B' allele was 41.9 ± 1.0% of that of the wild-type BLG B allele. Milk samples from three cows, homozygous for the A allele at chr11:103,256,256 (B'B'), were analysed (HPLC) and showed BLG concentrations of 1.04, 1.26 and 1.83 g/L relative to a mean of 4.84 g/L in milk from 16 herd contemporaries of mixed (A and B) BLG genotypes. The mechanism by which B' downregulates milk BLG concentration remains to be determined. CONCLUSIONS: High-throughput screening and identification of outliers, enabled the discovery of a synonymous G > A mutation in exon 1 of the B allele of the BLG gene (B'), which reduced the milk concentration of ß-lactoglobulin B protein isoform, by more than 50%. Milk from cows carrying the B' allele is expected to have improved processing characteristics, particularly for cheese-making.