The Genetic Landscape and Epidemiology of Phenylketonuria.

Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A>G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C>T (p.Arg408Trp) (22.2%), c.1066-11G>A (IVS10-11G>A) (6.4%), and c.782G>A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G>A];[1066-11G>A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.

The treatment of biochemical genetic diseases: From substrate reduction to nucleic acid therapies.

Newborn screening (NBS) began a revolution in the management of biochemical genetic diseases, greatly increasing the number of patients for whom dietary therapy would be beneficial in preventing complications in phenylketonuria as well as in a few similar disorders. The advent of next generation sequencing and expansion of NBS have markedly increased the number of biochemical genetic diseases as well as the number of patients identified each year. With the avalanche of new and proposed therapies, a second wave of options for the treatment of biochemical genetic disorders has emerged. These therapies range from simple substrate reduction to enzyme replacement, and now ex vivo gene therapy with autologous cell transplantation. In some instances, it may be optimal to introduce nucleic acid therapy during the prenatal period to avoid fetopathy. However, as with any new therapy, complications may occur. It is important for physicians and other caregivers, along with ethicists, to determine what new therapies might be beneficial to the patient, and which therapies have to be avoided for those individuals who have less severe problems and for which standard treatments are available. The purpose of this review is to discuss the "Standard" treatment plans that have been in place for many years and to identify the newest and upcoming therapies, to assist the physician and other healthcare workers in making the right decisions regarding the initiation of both the "Standard" and new therapies. We have utilized several diseases to illustrate the applications of these different modalities and discussed for which disorders they may be suitable. The future is bright, but optimal care of the patient, including and especially the newborn infant, requires a deep knowledge of the disease process and careful consideration of the necessary treatment plan, not just based on the different genetic defects but also with regards to different variants within a gene itself.

Environmental Path-Entropy and Collective Motion.

Inspired by the swarming or flocking of animal systems we study groups of agents moving in unbounded 2D space. Individual trajectories derive from a "bottom-up" principle: individuals reorient to maximize their future path entropy over environmental states. This can be seen as a proxy for keeping options open, a principle that may confer evolutionary fitness in an uncertain world. We find an ordered (coaligned) state naturally emerges, as well as disordered states or rotating clusters; similar phenotypes are observed in birds, insects, and fish, respectively. The ordered state exhibits an order-disorder transition under two forms of noise: (i) standard additive orientational noise, applied to the postdecision orientations and (ii) "cognitive" noise, overlaid onto each individual's model of the future paths of other agents. Unusually, the order increases at low noise, before later decreasing through the order-disorder transition as the noise increases further.

Opioid toxicity deaths in Black persons who experienced provincial incarceration in Ontario, Canada 2015-2020: A population-based study.

OBJECTIVE: In the context of mass incarceration and the opioid toxicity crisis in North America, there is a lack of data on the burden of opioid toxicity deaths in Black persons who experience incarceration. We aimed to describe absolute and relative opioid toxicity mortality for Black persons who experienced incarceration in Ontario, Canada between 2015 and 2020. METHODS: We linked data for all persons incarcerated in provincial correctional facilities and all persons who died from opioid toxicity in Ontario between 2015 and 2020, and accessed public data on population sizes. We described the characteristics of Black persons who were incarcerated and died from opioid toxicity, and calculated absolute mortality rates, as well as age-standardized mortality rates compared with all persons in Ontario not incarcerated during this period. RESULTS: Between 2015 and 2020, 0.9% (n = 137) of 16,177 Black persons who experienced incarceration died from opioid toxicity in custody or post-release, for an opioid toxicity death rate of 0.207 per 100 person years. In the two weeks post-release, the opioid toxicity death rate was 1.34 per 100 person years. Standardized for age and compared with persons not incarcerated, the mortality ratio (SMR) was 17.8 (95%CI 16.4-23.1) for Black persons who experienced incarceration. CONCLUSIONS: We identified a large, inequitable burden of opioid toxicity death for Black persons who experience incarceration in Ontario, Canada. Work is needed to support access to culturally appropriate prevention and treatment in custody and post-release for persons who are Black, and to prevent incarceration and improve determinants of health.

Early and intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): description of the intervention.

STUDY DESIGN: Descriptive. OBJECTIVES: The primary objective is to describe the intervention that will be provided in a large multi-centre randomised controlled trial titled: Early and Intensive Motor Training for people with Spinal Cord Injuries (the SCI-MT Trial). The secondary objective is to describe the strategies that will be used to operationalise and standardise the Motor Training provided to participants while keeping the intervention person-centred. METHODS: The paper focuses on the rationale and principles of Motor Training for people with spinal cord injuries (SCI). The description of the intervention is based on the Template for Intervention Description and Replication (TIDieR) checklist. Specifically, it addresses the following 6 criteria of the TIDieR checklist: why the effectiveness of Motor Training is being examined; what, how, where and when the Motor Training will be administered; and how much Motor Training will be provided. RESULTS: A detailed intervention manual has been developed to help standardise the delivery of the intervention. CONCLUSIONS: This paper describes the details of a complex intervention administered as part of a large randomised controlled trial. It will facilitate the subsequent interpretation of the trial results and enable the intervention to be reproduced in clinical practice and future trials.

Charles Scriver: Epitome of the physician scientist.

Charles Scriver is a towering figure in the medical genetics community. At 92 he can look back upon a remarkable career that established the field of biochemical genetics, a subsection of medical genetics that is translating the developments in basic genetics into the diagnoses and treatments of inherited biochemical diseases. This biographical sketch summarizes the key achievements of Dr. Scriver in research and medicine, integrating the different components of medical genetics into comprehensive provincial programs, teaching a generation of physicians and researchers, and developing worldwide collaborations. Charles has been a mighty figure in so many ways. He began his career by bringing amino acid chromatography from London to North America, thereby greatly enlarging the scope of metabolic disorders. Subsequently, his editorship of the classic Metabolic and Molecular Bases of Inherited Disease brought metabolism into genetics and established the field of biochemical genetics. He discovered a number of new diseases and was the first to recognize shared mediated amino acid transporters in the kidney, a medical breakthrough that has become a basic concept of amino acid homeostasis. He led the formation of the Quebec Network of Genetic Medicine, incorporating screening, diagnosis, counseling, treatment and research of genetic diseases, which to this day serves as a model for collaborative and comprehensive medical genetic programs internationally. He initiated the development of sapropterin (Kuvan®), the first non-dietary treatment for phenylketonuria (PKU) and helped identify the mechanism of this cofactor's action on phenylalanine hydroxylase in variants of PKU. His laboratory also led the development of phenylalanine ammonia lyase (Palynziq®), an enzyme substitution therapy that now serves as an alternative to dietary treatment for PKU. The ecosystem that Charles generated at the deBelle laboratory was collegial and highly fruitful. With the input and support of his remarkable wife Zipper, he found a way to integrate the concept of family into his work environment. Bustling with an endless series of evolving activities, he generated an inclusive setting which drew on the talents of brilliant clinical and research staff, as well as the input of patients and their families. In all these efforts, Charles managed to answer his own musings summarized in the following three questions: Who do we serve? How do we serve? Why do we serve? Charles Scriver's life is one well lived. An extraordinary physician scientist whose accomplishments are cause for pause and wonder; generating volumes of contribution which will forever seem impossible for one individual to deliver.

Perceived discrimination and mental health among African American and Caribbean Black adolescents: ethnic differences in processes and effects.

Objectives: Although the relationship between perceived discrimination and mental health among Black youth is well-documented, the mechanisms underlying this association remain unclear. Drawing from the stress process model, this study examines two psychosocial mediators - self-esteem and self-efficacy - in the association between perceived discrimination and mental health among African American and Caribbean Black adolescents. This research addresses three primary research questions: First, how is perceived discrimination associated with mental health? Second, to what extent do self-esteem and self-efficacy mediate the relationship between perceived discrimination and mental health? Finally, do these relationships and processes differ between African American and Caribbean Black adolescents?Design: Data for these analyses come from the National Survey of American Life - Adolescent Supplement. We use generalized structural equation modeling to examine relationships among perceived discrimination, psychosocial resources, and mental health.Results: For both African American and Caribbean Black adolescents, more frequent perceptions of discriminatory events were associated with greater depressive symptoms and a higher likelihood of having an anxiety disorder diagnosis. However, the association between perceived discrimination and depressive symptoms was significantly stronger for Caribbean Black adolescents. Generally, self-esteem and self-efficacy were found to be significant mediators in the association between perceived discrimination and mental health, although mechanisms varied between African American and Caribbean Black youth.Conclusion: African American and Caribbean Black adolescents are highly susceptible to experiences of discrimination that negatively affect their mental health. Heterogeneity among Black youth populations must be considered when developing interventions to reduce exposure to and the effects of discrimination among these adolescents.

Examining the Relationship between Discrimination and Prescription Drug Misuse: Findings from a National Survey of Black Americans.

Background: Research shows that substance use may be a way individuals cope with psychosocial stressors. Less is known about whether discrimination contributes to prescription drug misuse. Methods: Using a national sample of Black Americans, we examined whether two psychosocial stressors (i.e., everyday and lifetime major discrimination) were associated with lifetime prescription drug misuse (i.e., opioids, tranquilizers, sedatives, or stimulants). Results: Our logistic regression models separately examining the influence of everyday and major discrimination controlling for relevant demographic, health, and other drug use variables showed that only everyday discrimination was associated with higher odds of prescription drug misuse. In the model simultaneously considering both types of discrimination, only unit increases in everyday discrimination were associated with higher odds of prescription drug misuse. Conclusions: Encounters with everyday discrimination may be an important psychosocial stressor linked to prescription drug misuse in Black adults and possibly other racial-ethnic minorities. Intervention strategies aiming to reduce prescription drug misuse should consider developing ways to curb the negative health-related consequences of discriminatory experiences. Strategies to combat discrimination-related prescription drug misuse and limitations of this study are discussed.

Impact of an Antibiotic Side-Chain-Based Cross-reactivity Chart Combined With Enhanced Allergy Assessment Processes for Surgical Prophylaxis Antimicrobials in Patients With ß-Lactam Allergies.

BACKGROUND: ß-Lactam antibiotics are first-line therapy for perioperative prophylaxis; however, patient-reported allergies often lead to increased prescribing of alternative antibiotics that may increase the incidence of surgical site infections. The R-group side chain of the ß-lactam ring is responsible for allergic cross-reactivity and experts recommend the use of ß-lactams that are structurally dissimilar. METHODS: An internally developed, antibiotic side-chain-based cross-reactivity chart was developed and implemented alongside enhanced allergy assessment processes. This single-center, quasi-experimental study analyzed antibiotic prescribing in all adult patients with a documented ß-lactam allergy undergoing an inpatient surgical procedure between quartile (Q) 1 (2012)-Q3 (2014) (historical group) and Q3 (2016)-Q3 (2018) (intervention group). Propensity-weighted scoring analyses compared categorical and continuous outcomes. Interrupted time-series analysis further analyzed key outcomes. RESULTS: A total of 1119 and 1089 patients were included in the historical and intervention cohorts, respectively. There was a significant difference in patients receiving a ß-lactam alternative antibiotic between cohorts (84.9% vs 15.1%; P < .001). There was a decrease in 30-day readmissions in the intervention cohort (7.9% vs 6.3%; P = .035); however, there was no difference in the incidence of SSIs in patients readmitted (14.8% vs 13%; P = .765). No significant differences were observed in allergic reactions (0.5% vs 0.3%; P = .323), surgical site infections, in-hospital and 30-day mortality, healthcare facility-onset Clostridiodes difficile infection, acute kidney injury, or hospital costs. CONCLUSIONS: Implementation of an antibiotic cross-reactivity chart combined with enhanced allergy assessment processes significantly improved the prescribing of ß-lactam antibiotics for surgical prophylaxis.

Common and Rare Genetic Variants That Could Contribute to Severe Otitis Media in an Australian Aboriginal Population.

BACKGROUND: Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians. METHODS: Illumina® Omni2.5 BeadChip and imputed data were compared between 21 children with severe OM (multiple episodes chronic suppurative OM and/or perforations or tympanic sclerosis) and 370 individuals without this phenotype, followed by FUnctional Mapping and Annotation (FUMA). Exome data filtered for common (EXaC_all ≥ 0.1) putative deleterious variants influencing protein coding (CADD-scaled scores ≥15] were used to compare 15 severe OM cases with 9 mild cases (single episode of acute OM recorded over ≥3 consecutive years). Rare (ExAC_all ≤ 0.01) such variants were filtered for those present only in severe OM. Enrichr was used to determine enrichment of genes contributing to pathways/processes relevant to OM. RESULTS: FUMA analysis identified 2 plausible genetic risk loci for severe OM: NR3C1 (Pimputed_1000G = 3.62 × 10-6) encoding the glucocorticoid receptor, and NREP (Pimputed_1000G = 3.67 × 10-6) encoding neuronal regeneration-related protein. Exome analysis showed: (i) association of severe OM with variants influencing protein coding (CADD-scaled ≥ 15) in a gene-set (GRXCR1, CDH23, LRP2, FAT4, ARSA, EYA4) enriched for Mammalian Phenotype Level 4 abnormal hair cell stereociliary bundle morphology and related phenotypes; (ii) rare variants influencing protein coding only seen in severe OM provided gene-sets enriched for "abnormal ear" (LMNA, CDH23, LRP2, MYO7A, FGFR1), integrin interactions, transforming growth factor signaling, and cell projection phenotypes including hair cell stereociliary bundles and cilium assembly. CONCLUSIONS: This study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children.

Prescription Drug Misuse among African Americans and Afro Caribbeans: Results from the National Survey of American Life.

BACKGROUND: The misuse of prescription medications is an understudied topic among the non-Hispanic Black population in the U.S. Even less is known about the prevalence and correlates of misuse among African Americans and Afro-Caribbeans, despite documented differences in their substance use behaviors. OBJECTIVES: We aimed to examine the prevalence and correlates of lifetime prescription drug misuse among African Americans and Afro Caribbeans using data from the National Survey of American Life. METHODS: A national household probability sample of non-institutionalized African Americans and Afro Caribbeans from the Collaborative Psychiatric Epidemiology Surveys was used. Pooled and ethnicity-stratified logistic regressions were estimated. RESULTS: Findings showed no significant differences between African Americans (6.36%) and Afro-Caribbeans (5.71%) in lifetime prescription drug misuse. Several correlates were found to be associated with misuse among only African American or Afro-Caribbean respondents. CONCLUSIONS: While research has shown prescription drug misuse is an issue among Blacks overall, our results show that the role of ethnicity must not be overlooked, especially when tailoring prevention and intervention programs. Limitations of this study are discussed.

An 11-year review of hip fracture hospitalisations, health outcomes, and predictors of access to in-hospital rehabilitation for adults ≥ 65 years living with and without dementia: a population-based cohort study.

This study examined hip fracture hospitalisation trends and predictors of access to rehabilitation for adults aged ≥ 65 years living with and without dementia. The hospitalisation rate was 2.5 times higher for adults living with dementia and adults who lived in aged care were between 4.8 and 9.3 times less likely to receive rehabilitation. INTRODUCTION: To examine hip fracture hospitalisation temporal trends, health outcomes, and predictors of access to in-hospital rehabilitation for older adults living with and without dementia. METHODS: A population-based retrospective cohort study of adults aged ≥ 65 years hospitalised with a hip fracture during 2007-2017 in New South Wales, Australia. RESULTS: Of the 69,370 hip fracture hospitalisations, 27.1% were adults living with dementia. The hip fracture hospitalisation rate was 2.5 times higher for adults living with dementia compared with adults with no dementia (1186.6 vs 492.9 per 100,000 population). The rate declined by 6.1% per year (95%CI - 6.6 to - 5.5) for adults living with dementia and increased by 1.0% per year (95%CI 0.5-1.5) for adults with no dementia. Multivariable associations identified that adults living with dementia who experienced high frailty and increasing age were between 1.6 and 1.8 times less likely to receive in-hospital rehabilitation. Adults who were living in long-term aged care facilities were between 4.8 and 9.3 times less likely to receive in-hospital rehabilitation which varied by the presence of dementia or delirium. CONCLUSION: Consistent criteria should be applied to determine rehabilitation access, and rehabilitation services designed for older adults living with dementia or in aged care are needed. HIGHLIGHTS: • Adults living with dementia were able to make functional gains following hip fracture rehabilitation. • Need to determine consistent criteria to determine access to hip fracture rehabilitation. • Rehabilitation services specifically designed for adults living with dementia or in aged care are needed.

Rethinking electric vehicle subsidies, rediscovering energy efficiency.

Existing regulations regarding fuel energy intensity (MJ/km, litres/100 km, or its inverse, miles per gallon) of light-duty vehicles (LDVs: cars, SUVs, and pickup trucks) for 2025 or 2030 either fall short of the longterm technical potential, or contain numerous loopholes that undermine their effectiveness. At the same time, governments are subsidizing the purchase of electric vehicles (EVs) while the market share of SUVs and pickup trucks grows. This paper reviews the feasible fuel and/or electricity energy intensity of LDVs, and argues that the severity of impending anthropogenic global warming merits a strong policy approach that (i) prescribes significant improvements in the energy intensity of non-electric LDVs and plugin hybrid EVs (PHEVs) when running on fuel, (ii) is independent of the number of electric vehicles sold, and (iii) is accompanied by an overall limit on fleet-average CO2 emissions that applies to all manufacturers irrespective of the average size and mass of vehicles sold. Subsidies for EVs should be scaled back or eliminated, relying instead in the near term on deep across-the-board improvements in the fuel efficiency of LDVs that will have beneficial spillover effects on the eventual energy intensity of EVs and mineral requirements following a delayed market scale-up.

Revising the Psychiatric Phenotype of Homocystinuria.

PURPOSE: Associations of psychiatric and psychological symptoms with homocystinuria (HCU) have been described in multiple reports. This retrospective study was undertaken to refine the psychological phenotype among HCU patients and identify biomedical markers that could be used for prediction of those psychiatric or psychological symptoms. METHODS: This study examines the prevalence of psychological symptoms within a sample of 25 patients with classical homocystinuria. RESULTS: Psychological symptoms were noted in 16 of the 25 patients in the sample (64%), including a high prevalence of both anxiety (32%) and depression (32%) and correlated with IQ < 85. There was no difference in the type or the number of psychological symptoms between those diagnosed from newborn screening and early treated and those treated after 2 years of age. CONCLUSION: The results support the possible role of homocysteine as a risk factor for psychological and psychiatric problems and cognitive deficits and suggest that earlier diagnosis and treatment may reduce risk of their occurrences. Although early treatment clearly prevented serious medical complications, psychological and psychiatric symptoms were not associated with medical complications, highlighting the need for continued investigation.

Phenylalanine hydroxylase genotype-phenotype associations in the United States: A single center study.

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by pathogenic variants in the phenylalanine hydroxylase gene (PAH). The correlation between genotype and phenotype can be complex and sometimes variable but often very useful for categorizing and predicting dietary tolerance and potential outcome. We reviewed medical records for 367 patients diagnosed with PKU or persistent mild hyperphenylalaninemia (MHP) between 1950 and 2015 who had PAH genotyping. In 351 we had the full PAH genotype as well as phenotypic characteristics such as phenylalanine (Phe) concentrations (at newborn screening, confirmation, and highest known), and dietary Phe tolerance. On 716 mutant chromosomes, including 14 in genotypes with only one identified variant, we identified 114 different pathogenic variants. The most frequent, p.R408W, was present in 15.4% of the alleles; other frequent variants were c.1315 + 1G > A (6.1%), p.I65T (5.7%), and p.R261Q (5.7%). Three variants, c.142 T > G (p.L48 V), c.615G > C (p.E205D), and c.1342_1345delCTCC, were novel. We used the phenotypic parameters of variants paired with null alleles (functional hemizygotes) to assign the variants as classic PKU, moderate PKU, mild PKU, MHP-gray zone, or MHP. We also included the phenotype association(s) for all of the full genotypes. In 103 patients, we also could assign sapropterin dihydrochloride responsiveness, which is a synthetic form of the tetrahydrobiopterin (BH4) PAH cofactor. This compilation from a single metabolic center provides further information on PAH variants in the United States and the correlations between genotype and phenotype.

The ability of an LC-MS/MS-based erythrocyte GALT enzyme assay to predict the phenotype in subjects with GALT deficiency.

BACKGROUND: GALT deficiency is a rare genetic disorder of carbohydrate metabolism. Due to the decreased activity or absence of the enzyme galactose-1-phosphate uridylyltransferase (GALT), cells from affected individuals are unable to metabolize galactose normally. Lactose consumption in the newborn period could potentially lead to a lethal disease process with multi-organ involvement. In contrast to the newborn-stage disease, however, a galactose-restricted diet does not prevent long-term complications such as central nervous system (CNS) dysfunction with speech defects, learning disability and neurological disease in addition to hypergonadotropic hypogonadism or primary ovarian insufficiency (POI) in females. As the literature suggests an association between GALT enzyme activity and the long-term complications, it is of importance to have a highly sensitive assay to quantify the GALT enzyme activity. To that end, we had developed a sensitive and accurate LC-MS/MS method to measure GALT enzyme activity. Its ability to predict outcome is the subject of this report. MATERIALS AND METHODS: The GALT enzyme activity in erythrocytes from 160 individuals, in which 135 with classic, clinical variant or biochemical variant galactosemia, was quantified by LC-MS/MS. Individuals with GALT deficiency were evaluated for the long-term complications of speech defects, dysarthria, ataxia, dystonia, tremor, POI, as well as intellectual functioning (full scale IQ). The LC-MS/MS results were compared to a variety of assays: radioactive, [14C]-galactose-1-phosphate, paper chromatography with scintillation counting, enzyme-coupled assays with spectrophotometric or fluorometric readout or high-pressure liquid chromatography with UV detection of UDP-galactose. RESULTS: The LC-MS/MS method measured GALT activity as low as 0.2%, whereas other methods showed no detectable activity. Largely due to GALT activities that were over 1%, the LC-MS/MS measurements were not significantly different than values obtained in other laboratories using other methodologies. Severe long-term complications were less frequently noted in subjects with >1% activity. Patients with a p.Q188R/p.Q188R genotype have no residual enzyme activity in erythrocytes. CONCLUSION: Our LC-MS/MS assay may be necessary to accurately quantify residual GALT activities below 5%. The data suggest that patients with >1% residual activity are less likely to develop diet-independent long-term complications. However, much larger sample sizes are needed to properly assess the clinical phenotype in patients with residual enzyme activities between 0.1 and 5%.

Comparison of hospitalised trends, treatment cost and health outcomes of fall-related hip fracture for people aged ≥ 65 years living in residential aged care and the community.

This study compared hip fracture rates and health outcomes of older people living in residential aged care facilities (RACFs) to the community. The RACF resident age-standardised hospitalisation rate was five times higher than the community rate and declining. RACF residents experience overall worse health outcomes and survival post-hip fracture. INTRODUCTION: To compare hospitalisation trends, characteristics and health outcomes following a fall-related hip fracture of older people living in residential aged care facilities (RACFs) to older people living in the community. METHODS: A retrospective analysis of fall-related hip fracture hospitalisations of people aged ≥ 65 years during 1 July 2008 and 30 June 2013 in New South Wales (NSW), Australia's largest populated state. Linked hospitalisation, RACF and Aged Care Assessment Appraisal data collections were examined. Negative binomial regression examined the significance of hospitalisation temporal trends. RESULTS: There were 28,897 hip fracture hospitalisations. One-third were of older people living in RACFs. The hospitalisation rate was 2180 per 100,000 (95%CI: 2097.0-2263.7) for RACF residents and 390 per 100,000 (95%CI 384.8-395.8) for older people living in the community. The hospitalisation rate for RACF residents was estimated to decline by 2.9% annually (95%CI: - 4.3 to - 1.5). Hospital treatment cost for hip fractures was AUD$958.5 million. Compared to older people living in the community, a higher proportion of RACF residents were aged ≥ 90 years (36.1% vs 17.2%), were female (75.3% vs 71.8%), had > 1 Charlson comorbidity (37.6% vs 35.6%) and 58.2% had dementia (vs 14.4%). RACF residents had fewer in-hospital rehabilitation episodes (18.7% vs 60.9%) and a higher proportion of unplanned readmissions (10.6% vs 9.1%) and in-hospital mortality (5.9% vs 3.3%) compared to older people living in the community. CONCLUSIONS: RACF residents are a vulnerable cohort of older people who experience worse health outcomes and survival post-hip fracture than older people living in the community. Whether access to individualised hip fracture rehabilitation for RACF residents could improve their health outcomes should be examined.

Future hospital service utilisation in older adults living in long-term residential aged care or the community hospitalised with a fall-related injury.

This study identified group-based trajectories of hospitalisation for older adults who were living in residential aged care facilities (RACF) or the community for up to 4 years after an index fall injury hospitalisation. Greater than 3 subsequent fall injury hospitalisations and time until move to a RACF were key predictors of RACF and community-living trajectory group memberships, respectively. INTRODUCTION: To examine hospital service use trajectories of people aged ≥ 65 years who had a fall injury hospitalisation and were either living in a residential aged care facility (RACF) or the community at the time of the index fall and to identify factors predictive of their trajectory group membership. METHOD: A group-based trajectory analysis of hospitalisations of people aged ≥ 65 years who had a fall injury hospitalisation during 2008-2009 in New South Wales, Australia, was conducted. Linked hospitalisation and RACF data were examined for a 5-year period. Group-based trajectory models were derived based on number of subsequent hospital admissions following the index fall injury hospitalisation. Multinominal logistic regression examined predictors of trajectory group membership. RESULTS: There were 24,729 fall injury hospitalisations; 78.8% of fallers were living in the community and 21.2% in a RACF. Five distinct trajectory groups were identified for community-living and four trajectory groups for RACF residents. Key predictors of trajectory group membership for both community-living and RACF residents were age group, number of comorbidities and dementia status. For RACF residents, depression, assistance with activities of daily living and number of subsequent fall injury admissions were also predictors of group membership, with time to move to a RACF a predictor of group membership for community living. CONCLUSIONS: Identifying trajectories of ongoing hospital use informs targeting of strategies to reduce hospital admissions and design of services to allow community-living individuals to remain as long as possible within their own residence.

Identifying sources of measurement error in assessing dietary intakes - Results of a multi-country ring-trial.

BACKGROUND AND AIMS: Epidemiological investigations include dietary intakes as primary exposures or potential confounders. To reduce bias, data collection protocols include the administration of questionnaires together with measurements of biomarkers. Some error, however, remains and needs to be considered in the analysis and interpretation of results. The European Food Safety Authority supported a ring-trial to compare the precision and reproducibility of dietary assessment methods applied in Europe. METHODS AND RESULTS: Software applications used to collect 24-hour recalls and food records in six countries (Estonia, Italy, Latvia, Portugal, Spain, and Sweden) were assessed. The intake of 256 foods was identically reported to each method. Experienced interviewers participated and were instructed to repeat national protocols closely. The error in recording quantities, compared with reference values, was variable but in about 60% of recorded quantities was in the range of ±20%. Errors were however unsystematic and independent of the food type or quantification method used - although food pictures performed better. The reproducibility of some tools was limited. The methods generally captured additional ingredients (usually flavoring agents), but not sweetening agents or fortification and failed to record packaging information in about 60% of the cases. CONCLUSION: In a design that eliminated respondent bias, this study indicates that softwares, supporting databases and interviewers generally introduce random error in dietary assessments. The inclusion of large sample sizes and food pictures to quantify portions, together with enhanced attention on interviewers' training, standardisation of procedures and regular tool upgrades are essential in assuring a study's quality and comparability.

Gender Differences in Prescription Opioid Misuse Among U.S. Black Adults.

BACKGROUND: Prescription opioid misuse (POM) is a significant problem among U.S. adults, including Blacks, as indicated by past research. Despite potential gender differences in POM among Black adults, previous research has yet to examine this possibility. OBJECTIVES: This study identified the prevalence and unique correlates of POM among both Black men and Black women. Results were compared to those of Whites. METHODS: We used data from 2015-2016 National Survey on Drug Use and Health (N = 60,133). Weighted logistic regression models stratified by race and gender were estimated. One model was stratified by gender only, with race serving as the primary predictor. RESULTS: Findings revealed 3.4% of Black women, 4.9% of Black men, 4.1% of White women, and 5.4% of White men reported past-year POM; although, no significant differences were found. Among Black women only, lower socioeconomic status increased odds of POM. Higher educational attainment, residence in rural areas and older age lowered odds of POM. Encounters with drug dealers, illicit drug, marijuana, and tobacco use, other prescription drug misuse, and poor health were associated with increased odds of POM among Black men. In the gender stratified models, White men were more likely to report POM than Black men. However, White women were not more likely to report POM compared to Black women. CONCLUSIONS: Clear gender differences exist in the prevalence and correlates of POM among Black adults. Prevention and intervention strategies must be cognizant of these differences when developing programs to decrease POM.