Adipokines measured during pregnancy and at birth are associated with infant negative affect.

BACKGROUND: Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect. METHODS: Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines. RESULTS: Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect. CONCLUSIONS: This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect.

Prediction of long-term functional outcome following different rehabilitation pathways after stroke unit discharge.

OBJECTIVE: To investigate whether referral for different types of rehabilitation on discharge from Swedish stroke units can predict functional outcomes at 1 and 5 years after a stroke. DESIGN: A longitudinal and registry-based study. SUBJECTS/PATIENTS: A total of 5,118 participants with index stroke in 2011 were followed-up at 1 and 5 years after the stroke. METHODS: Ordinal logistic regression models were developed to predict the category of functional outcome: independent, dependent, or dead. The primary predictors were planned rehabilitation in a home setting, inpatient rehabilitation, and outpatient rehabilitation, with no planned rehabilitation as the reference category. RESULTS: Planned outpatient rehabilitation predicted independence (compared with death) at 1 year. Planned rehabilitation in the home setting predicted independence (compared with death) at 1 and 5 years. Compared with other planned pathways, participants planned for inpatient rehabilitation had more severe conditions, and planned inpatient rehabilitation did not predict independence. CONCLUSION: Planning for outpatient or home-based rehabilitation appeared to lead more effectively to participants achieving independence over the course of 1-5 years. This may have been due to the less severe nature of these participants' conditions, compared with those requiring inpatient rehabilitation.

The "Can Do, Do Do" Framework Applied to Assess the Association between Physical Capacity, Physical Activity and Prospective Falls, Subsequent Fractures, and Mortality in Patients Visiting the Fracture Liaison Service.

The "can do, do do" framework combines measures of poor and normal physical capacity (PC, measured by a 6 min walking test, can do/can't do) and physical activity (PA, measured by accelerometer, do do/don't do) into four domains and is able to categorize patient subgroups with distinct clinical characteristics, including fall and fracture risk factors. This study aims to explore the association between domain categorization and prospective fall, fracture, and mortality outcomes. This 6-year prospective study included patients visiting a Fracture Liaison Service with a recent fracture. Outcomes were first fall (at 3 years of follow-up, measured by fall diaries), first subsequent fracture, and mortality (at 6 years). Cumulative incidences of all three outcomes were calculated. The association between domain categorization and time to the three outcomes was assessed by uni- and multivariate Cox proportional hazard analysis with the "can do, do do" group as reference. The physical performance of 400 patients with a recent fracture was assessed (mean age: 64 years; 70.8% female), of whom 61.5%, 20.3%, and 4.9% sustained a first fall, sustained a subsequent fracture, or had died. Domain categorization using the "can do, do do" framework was not associated with time to first fall, subsequent fracture, or mortality in the multivariate Cox regression analysis for all groups. "Can't do, don't do" group: hazard ratio [HR] for first fall: 0.75 (95% confidence interval [CI]: 0.45-1.23), first fracture HR: 0.58 (95% CI: 0.24-1.41), and mortality HR: 1.19 (95% CI: 0.54-6.95). Categorizing patients into a two-dimensional framework seems inadequate to study complex, multifactorial outcomes. A personalized approach based on known fall and fracture risk factors might be preferable.

Shared decision-making for non-operative management versus operative management of hip fractures in selected frail older adults with a limited life expectancy: a protocol for a nationwide implementation study.

BACKGROUND AND PURPOSE: Recent research has highlighted non-operative management (NOM) as a viable alternative for frail older adults with hip fractures in the final phase of life. This study aims to guide Dutch physicians and hospitals nationwide in a standardised implementation of shared decision-making regarding surgery or NOM in selected frail older adults with a hip fracture. METHODS AND ANALYSIS: The patient population for implementation includes frail older adults aged ≥70 years with an acute proximal femoral fracture, nursing home care or a similar level of care elsewhere and at least one additional criterion (ie, malnutrition, severe mobility impairment or ASA≥4). The 2-year implementation study will be conducted in four phases. In phases 1 and 2, barriers and facilitators for implementation will be identified and an implementation protocol, educational materials and patient information will be developed. Phase 3 will involve an implementation pilot in 14 hospitals across the Netherlands. The protocol and educational material will be improved based on healthcare provider and patient experiences gathered through interviews. Phase 4 will focus on upscaling to nationwide implementation and the effect of the implementation on NOM rate will be measured using data from the Dutch Hip Fracture Audit. ETHICS AND DISSEMINATION: The study was exempted by the local Medical Research Ethics Committee (MEC-2023-0270, 10 May 2023) and Medical Ethics Committee United (W23.083, 26 April 2023). The study's results will be submitted to an open access international peer-reviewed journal. Its protocols, tools and results will be presented at several national and international academic conferences of relevant orthogeriatric (scientific) associations. TRIAL REGISTRATION NUMBER: NCT06079905 .

Low dose of propyl-pyrazole-triol, an agonist of estrogen receptor alpha, administration stimulates the Coolidge effect in fadrozole-treated male rats.

Estrogen receptor (ER) α is involved in male sexual function. Here, we aim to investigate how ERα activation influences sexual satiety and the Coolidge effect (i.e., when a rat, that has reached sexual satiety, experiences an increased arousal after exposure to a novel sexual partner) in estrogen-deprived male rats. Male rats (8 per group) were treated daily for 29 days with either saline (Control group) or fadrozole dissolved in saline (1 mg/kg/day) 1 h before mating. On Days 13 and 29, rats treated with fadrozole received either no additional treatment (fadrozole group) or a single injection of propyl-pyrazole-triol (ERα-agonist group, dissolved in sesame oil, 1 mg/kg). Rats mated until reaching sexual satiety on Days 13 and 29. In these sessions, the Control group displayed higher frequency of intromission and ejaculation than the other groups. The ERα-agonist group mounted more frequently but reached sexual satiety sooner than the Control group. On Day 29, when exposed to a new sexual partner, the fadrozole-treated rats were less likely to display intromission than the other groups, or ejaculation than the Control group, or mounting than the ERα-agonist group. The Control group showed more ejaculatory behavior and shorter ejaculation latency than the other groups. Body weights, testosterone levels, estradiol levels, and ERα-immunoreactive cell counts in brain regions for sexual behavior were comparable between groups after 29 days of treatments. Our data suggest that estrogen helps regulate sexual satiety and the Coolidge effect in male rats.

Visualizing threat and trustworthiness prior beliefs in face perception in high versus low paranoia.

Predictive processing accounts of psychosis conceptualize delusions as overly strong learned expectations (prior beliefs) that shape cognition and perception. Paranoia, the most prevalent form of delusions, involves threat prior beliefs that are inherently social. Here, we investigated whether paranoia is related to overly strong threat prior beliefs in face perception. Participants with subclinical levels of high (n = 109) versus low (n = 111) paranoia viewed face stimuli paired with written descriptions of threatening versus trustworthy behaviors, thereby activating their threat versus trustworthiness prior beliefs. Subsequently, they completed an established social-psychological reverse correlation image classification (RCIC) paradigm. This paradigm used participants' responses to randomly varying face stimuli to generate individual classification images (ICIs) that intend to visualize either facial prior belief (threat vs. trust). An independent sample (n = 76) rated these ICIs as more threatening in the threat compared to the trust condition, validating the causal effect of prior beliefs on face perception. Contrary to expectations derived from predictive processing accounts, there was no evidence for a main effect of paranoia. This finding suggests that paranoia was not related to stronger threat prior beliefs that directly affected face perception, challenging the assumption that paranoid beliefs operate on a perceptual level.

The value of preoperative diagnostic testing and geriatric assessment in frail institutionalized elderly with a hip fracture; a secondary analysis of the FRAIL-HIP study.

PURPOSE: The aim of this study was to provide a comprehensive overview of (preoperative and geriatric) diagnostic testing, abnormal diagnostic tests and their subsequent interventions, and clinical relevance in frail older adults with a hip fracture. METHODS: Data on clinical consultations, radiological, laboratory, and microbiological diagnostics were extracted from the medical files of all patients included in the FRAIL-HIP study (inclusion criteria: hip fracture, > 70 years, living in a nursing home with malnourishment/cachexia and/or impaired mobility and/or severe co-morbidity). Data were evaluated until hospital discharge in nonoperatively treated patients and until surgery in operatively treated patients. RESULTS: A total of 172 patients (88 nonoperative and 84 operative) were included, of whom 156 (91%) underwent laboratory diagnostics, 126 (73%) chest X-rays, and 23 (13%) CT-scans. In 153/156 (98%) patients at least one abnormal result was found in laboratory diagnostics. In 82/153 (50%) patients this did not result in any additional diagnostics or (pharmacological) intervention. Abnormal test results were mentioned as one of the deciding arguments for operative delay (> 24 h) for 10/84 (12%) patients and as a factor in the decision between nonoperative and operative treatment in 7/172 (4%) patients. CONCLUSION: A large number and variety of diagnostics were performed in this patient population. Abnormal test results in laboratory diagnostics were found for almost all patients and, in majority, appear to have no direct clinical consequences. To prevent unnecessary diagnostics, prospective research is required to evaluate the clinical consequences and added value of the separate elements of preoperative diagnostic testing and geriatric assessment in frail hip fracture patients.

Characteristics and Outcomes of Nonoperatively Managed Patients With Hip Fracture Using the Dutch Hip Fracture Audit.

OBJECTIVES: To identify and compare characteristics of patients with hip fracture treated nonoperatively versus those treated operatively. DESIGN: Retrospective cohort study. SETTING: Hip fracture population-based study. PATIENT SELECTION CRITERIA: All adult patients with hip fractures (OTA/AO 31A and 31B) were included. Patients with pathological or periprosthetic hip fractures were excluded. OUTCOME MEASURES AND COMPARISONS: Patients were categorized according to the type of management (operative vs. nonoperative) and type of fracture (nondisplaced vs. other). Patient and fracture characteristics associated with nonoperative management (NOM) were analyzed. RESULTS: A total of 94,930 patients with hip fracture were included. Of these, 3.2% were treated nonoperatively. Patients receiving NOM were older [86 years (interquartile range, 79-91 years) vs. 81 years (interquartile range, 72-87 years); P < 0.001], more frequently institutionalized (42.4% vs. 17.6%), and were more dependent in activities of daily living (22.2% vs. 55.0%). Various clinical characteristics, including dementia [odds ratio (OR) 1.31 (95% confidence interval, CI, 1.18-1.45) P < 0.001], no functional mobility [OR 4.39 (95% CI, 3.14-3.68) P < 0.001], and activities of daily living (ADL) measured as KATZ-6-ADL [OR 1.17 (95% CI, 1.14-1.20) P < 0.001] were independently associated with NOM. Seven-day mortality was 37.6%, and 30-day mortality was 57.1% in patients treated nonoperatively. CONCLUSIONS: The first step in understanding patients who potentially benefit from NOM is evaluating the current standard of care. This study provides insight into the current hip fracture population treated nonoperatively. These patients are older, have higher percentage of dementia, more dependent, and show higher short-term mortality rates. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sick leave one year after COVID-19 infection: a nationwide cohort study during the first wave in Sweden.

This study aimed to investigate the patterns of sick leave, as well as factors associated with sick leave due to COVID-19 during one year after the COVID-19 diagnosis, and sex-related aspects on sick leave. This nationwide study involved 11,902 individuals who received sickness benefits for COVID-19 during the first wave of the pandemic. Data from three Swedish registries were analyzed for sick leave that commenced between March 1 and August 31, 2020, with a follow-up period of 12 months. Sick leave due to COVID-19 was counted as the number of days with sickness benefits and required to include at least one registered COVID-19 diagnosis. The median duration of sick leave was 35 days, and 347 (2.9%) individuals continued their sick leave during the entire follow-up period. Furthermore, 1 year later, the cumulative incidence of sick leave was slightly higher in males (3.5%) compared to females (2.7%). Older age, being single with no children, diagnosed with the virus, medium income level, history of sick leave, and need for inpatient care were significantly associated with a higher duration of sick leave due to COVID-19, both in the total population and when stratified by sex. These results indicated that three out of 100 (3%) patients were still on sick leave 1 year after their COVID-19 diagnosis. Aspects regarding the importance of sick leave duration differed between males and females and comprised sociodemographic characteristics and need for inpatient care. The results indicated the complexity of sick leave due to COVID-19.

Posterolateral or Direct Lateral Surgical Approach for Hemiarthroplasty After a Hip Fracture: A Randomized Clinical Trial Alongside a Natural Experiment.

Importance: Hip fractures in older adults are serious injuries that result in disability, higher rates of illness and death, and a substantial strain on health care resources. High-quality evidence to improve hip fracture care regarding the surgical approach of hemiarthroplasty is lacking. Objective: To compare 6-month outcomes of the posterolateral approach (PLA) and direct lateral approach (DLA) for hemiarthroplasty in patients with acute femoral neck fracture. Design, Setting, and Participants: This multicenter, randomized clinical trial (RCT) comparing DLA and PLA was performed alongside a natural experiment (NE) at 14 centers in the Netherlands. Patients aged 18 years or older with an acute femoral neck fracture were included, with or without dementia. Secondary surgery of the hip, pathological fractures, or patients with multitrauma were excluded. Recruitment took place between February 2018 and January 2022. Treatment allocation was random or pseudorandom based on geographical location and surgeon preference. Statistical analysis was performed from July 2022 to September 2022. Exposure: Hemiarthroplasty using PLA or DLA. Main Outcome and Measures: The primary outcome was health-related quality of life 6 months after surgery, quantified with the EuroQol Group 5-Dimension questionnaire (EQ-5D-5L). Secondary outcomes included dislocations, fear of falling and falls, activities of daily living, pain, and reoperations. To improve generalizability, a novel technique was used for data fusion of the RCT and NE. Results: A total of 843 patients (542 [64.3%] female; mean [SD] age, 82.2 [7.5] years) participated, with 555 patients in the RCT (283 patients in the DLA group; 272 patients in the PLA group) and 288 patients in the NE (172 patients in the DLA group; 116 patients in the PLA group). In the RCT, mean EQ-5D-5L utility scores at 6 months were 0.50 (95% CI, 0.45-0.55) after DLA and 0.49 (95% CI, 0.44-0.54) after PLA, with 77% completeness. The between-group difference (-0.04 [95% CI, -0.11 to 0.04]) was not statistically significant nor clinically meaningful. Most secondary outcomes were comparable between groups, but PLA was associated with more dislocations than DLA (RCT: 15 of 272 patients [5.5%] in PLA vs 1 of 283 patients [0.4%] in DLA; NE: 6 of 113 patients [5.3%]) in PLA vs 2 of 175 patients [1.1%] in DLA). Data fusion resulted in an effect size of 0.00 (95% CI, -0.04 to 0.05) for the EQ-5D-5L and an odds ratio of 12.31 (95% CI, 2.77 to 54.70) for experiencing a dislocation after PLA. Conclusions and Relevance: This combined RCT and NE found that among patients treated with a cemented hemiarthroplasty after an acute femoral neck fracture, PLA was not associated with a better quality of life than DLA. Rates of dislocation and reoperation were higher after PLA. Randomized and pseudorandomized data yielded similar outcomes, which suggests a strengthening of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04438226.

Variations in respiratory and functional symptoms at four months after hospitalisation due to COVID-19: a cross-sectional study.

BACKGROUND: Much remains unknown about complex respiratory symptoms after COVID-19. Here we aimed to describe and analyse patients' various respiratory symptoms 4 months after discharge from hospitalisation for COVID-19, focusing on sex, previous pulmonary disease, and prolonged mechanical ventilation. METHODS: This cross-sectional study involved five hospitals and included 52 patients with self-assessed respiratory dysfunction at 4 months after discharge from hospitalisation for severe COVID-19. Their average age was 63 years, 38% were women, 15 had a previous diagnosed pulmonary disease, and 29 were current or previous smokers. Additionally, 31 had required intensive care-among whom 21 were intubated and 11 needed mechanical ventilation for ≥20 days. Respiratory function was tested concerning lung volumes, expiratory flow, muscle strength, physical capacity (including concurrent oxygen saturation), thoracic expansion, and respiratory movements. RESULTS: Among 52 patients, 47 (90%) had one or several objectively measured respiratory function abnormalities. Decreased thoracic expansion was observed in 32 patients (62%), abnormal respiratory movements in 30 (58%), decreased vital capacity in 21 (40%), low physical function in 13 (26%), and desaturation during the test in 9 (17%). Respiratory inspiratory muscle strength was more commonly diminished than expiratory strength (27% vs. 8%). We did not observe differences between men and women, or between patients with versus without diagnosed pulmonary disease, except that those with pulmonary disease had significantly lower physical capacity assessed with 6MWD (70% vs. 88% predicted, p = 0.013). Compared to those who did not, patients who required ≥20 days of mechanical ventilation performed similarly on most tests, except that all thoracic breathing movements were significantly smaller (p < 0.05). The numbers and combinations of abnormal findings varied widely, without clear patterns. CONCLUSION: Patients with remaining respiratory symptoms 4 months after discharge from hospitalization due to COVID-19 may suffer from various abnormal breathing functions, and dysfunctional breathing that is not detected using traditional measurements. These patients may benefit from multidimensional measuring of breathing movement, thoracic expansion, and respiratory muscle strength, along with traditional measurements, to assess their symptoms and enable prescription of optimal treatment interventions and rehabilitation. TRIAL REGISTRATION: FoU i Sverige (Research & Development in Sweden, Registration number: 274476, registered 2020-05-28).

Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens.

This review article compiles critical pre-analytical factors for sample collection and extraction of eight uncommon or underexplored biological specimens (human breast milk, ocular fluids, sebum, seminal plasma, sweat, hair, saliva, and cerebrospinal fluid) under the perspective of clinical metabolomics. These samples are interesting for metabolomics studies as they reflect the status of living organisms and can be applied for diagnostic purposes and biomarker discovery. Pre-collection and collection procedures are critical, requiring protocols to be standardized to avoid contamination and bias. Such procedures must consider cleaning the collection area, sample stimulation, diet, and food and drug intake, among other factors that impact the lack of homogeneity of the sample group. Precipitation of proteins and removal of salts and cell debris are the most used sample preparation procedures. This review intends to provide a global view of the practical aspects that most impact results, serving as a starting point for the designing of metabolomic experiments.

The Quality of Dying in Frail Institutionalized Older Patients After Nonoperative and Operative Management of a Proximal Femoral Fracture: An In-Depth Analysis.

Proximal femoral fractures in frail patients have a poor prognosis. Despite the high mortality, little is known about the quality of dying (QoD) while this is an integral part of palliative care and could influence decision making on nonoperative- (NOM) or operative management (OM). To identify the QoD in frail patients with a proximal femoral fracture. Data from the prospective FRAIL-HIP study, that studied the outcomes of NOM and OM in institutionalized older patients ≥70 years with a limited life expectancy who sustained a proximal femoral fracture, was analyzed. This study included patients who died within the 6-month study period and whose proxies evaluated the QoD. The QoD was evaluated with the Quality of Dying and Death (QODD) questionnaire resulting in an overall score and 4 subcategory scores (Symptom control, Preparation, Connectedness, and Transcendence). In total 52 (64% of NOM) and 21 (53% of OM) of the proxies responded to the QODD. The overall QODD score was 6.8 (P25-P75 5.7-7.7) (intermediate), with 34 (47%) of the proxies rating the QODD 'good to almost perfect'. Significant differences in the QODD scores between groups were not noted (NOM; 7.0 (P25-P75 5.7-7.8) vs OM; 6.6 (P25-P75 6.1-7.2), P = .73). Symptom control was the lowest rated subcategory in both groups. The QoD in frail older nursing home patients with a proximal femoral fracture is good and humane. QODD scores after NOM are at least as good as OM. Improving symptom control would further increase the QoD.

Investigating the Effectiveness of Care Delivery at an Acute Geriatric Community Hospital for Older Adults in the Netherlands: A Prospective Controlled Observational Study.

OBJECTIVES: Hospital admission in older adults is associated with unwanted outcomes such as readmission, institutionalization, and functional decline. To reduce these outcomes, the Netherlands introduced an alternative to hospital-based care: the Acute Geriatric Community Hospital (AGCH). The AGCH is an acute care unit situated outside of a hospital focusing on early rehabilitation and comprehensive geriatric assessment. The objective of this study was to evaluate if AGCH care is associated with decreasing unplanned readmissions or death compared with hospital-based care. DESIGN: Prospective cohort study controlled with a historic cohort. SETTING AND PARTICIPANTS: A (sub)acute care unit (AGCH) and 6 hospitals in the Netherlands; participants were acutely ill older adults. METHODS: We used inverse propensity score weighting to account for baseline differences. The primary outcome was 90-day readmission or death. Secondary outcomes included 30-day readmission or death, time to death, admission to long-term residential care, occurrence of falls and functioning over time. Generalized logistic regression models and multilevel regression analyses were used to estimate effects. RESULTS: AGCH patients (n = 206) had lower 90-day readmission or death rates [odds ratio (OR) 0.39, 95% CI 0.23-0.67] compared to patients treated in hospital (n = 401). AGCH patients had a lower risk of 90-day readmission (OR 0.38, 95% CI 0.21-0.67) but did not differ on all-cause mortality (OR 0.89, 95% CI 0.44-1.79) compared with the hospital control group. AGCH patients had lower 30-day readmission or death rates. Secondary outcomes did not differ. CONCLUSIONS AND IMPLICATIONS: AGCH patients had lower rates of readmission and/or death than patients treated in a hospital. Our results support further research on the implementation and cost-effectiveness of AGCH in the Netherlands and other countries seeking alternatives to hospital-based care.

Figuring Out Life After Covid-19: a Qualitative Study From Sweden.

OBJECTIVE: To obtain a deeper understanding of the daily life experiences of working aged people during the year following hospitalization due to SARS-CoV-2 (COVID-19), with a focus on function-ing in daily life and return to work. DESIGN: An explorative qualitative study using individual interviews. SUBJECTS: A purposive sample was selected of persons who had received inpatient hospital care, had been discharged approximately 1 year previously and were of working age. METHODS: Semi-structured interviews were conducted with 11 participants (9 men, 2 women). The interviews were transcribed and analysed with inductive thematic analysis. RESULTS: Four themes were identified. Navigating health, with or without support from healthcare, was described as challenging when managing consequences of COVID-19. Participants struggled with a lack of energy that interfered with daily life. It was a trial-and-error process trying to use familiar strategies in new ways to manage. The return to work process was facilitated by own strategies and support. CONCLUSION: This study contributes increased knowledge of everyday life experiences of people 1 year following hospitalization due to COVID-19. The lack of energy and a struggle to manage health while navigating the healthcare system emphasize the importance of strengthening personal and organizational health literacy to facilitate the recovery process after severe COVID-19.

Delirium in older patients with COVID-19: Prevalence, risk factors and clinical outcomes across the first three waves of the pandemic.

OBJECTIVES: Delirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic. METHODS: This study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models. RESULTS: 1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves. CONCLUSION: Delirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave.

Imminent fall risk after fracture.

RATIONALE: Adults with a recent fracture have a high imminent risk of a subsequent fracture. We hypothesise that, like subsequent fracture risk, fall risk is also highest immediately after a fracture. This study aims to assess if fall risk is time-dependent in subjects with a recent fracture compared to subjects without a fracture. METHODS: This retrospective matched cohort study used data from the UK Clinical Practice Research Datalink GOLD. All subjects ≥50 years with a fracture between 1993 and 2015 were identified and matched one-to-one to fracture-free controls based on year of birth, sex and practice. The cumulative incidence and relative risk (RR) of a first fall was calculated at various time intervals, with mortality as competing risk. Subsequently, analyses were stratified according to age, sex and type of index fracture. RESULTS: A total of 624,460 subjects were included; 312,230 subjects with an index fracture, matched to 312,230 fracture-free controls (71% females, mean age 70 ± 12, mean follow-up 6.5 ± 5 years). The RR of falls was highest in the first year after fracture compared to fracture-free controls; males had a 3-fold and females a 2-fold higher risk. This imminent fall risk was present in all age and fracture types and declined over time. A concurrent imminent fracture and mortality risk were confirmed. CONCLUSION/DISCUSSION: This study demonstrates an imminent fall risk in the first years after a fracture in all age and fracture types. This underlines the need for early fall risk assessment and prevention strategies in 50+ adults with a recent fracture.

Pelvic Ring Fractures in Older Adult Patients-Assessing Physician Practice Variation among (Orthopedic) Trauma Surgeons.

PURPOSE: Pelvic fractures in older adults are a major public health problem and socioeconomic burden. The standard of care has changed over the past years, and there is limited consensus on which patients benefit from surgical fixation. There is currently no nationwide treatment protocol to guide the decision-making process. Therefore, the aim of this survey was to provide more insight into if, when, and why patients with a fragility fracture of the pelvis (FFPs) would be considered for additional imaging and surgical fixation by treating physicians. METHODS: An online clinical vignette-based survey of hypothetical scenarios was sent out to all orthopedic and trauma surgeons in the Netherlands. The questionnaire comprised multiple-choice questions and radiographic images. Differences between subgroups were calculated using the X2 test or the Fisher exact test. RESULTS: 169 surgeons responded to the survey, with varying levels of experience and working in different types of hospitals. In a patient with a simple pubic ramus fracture and ASA 2 or ASA 4, 32% and 18% of the respondents would always advise a CT scan for further analysis. In the same patients, 11% and 31% of the respondents would not advise a CT scan, respectively. When presented with three cases of increasing severity of co-morbidity (ASA) and/or increasing age and/or different clinical presentation of an FFP type 3c on a CT scan, an increasing number of respondents would not consider surgical fixation. There was significant variation in practice patterns between the respondents who do not work in a hospital performing pelvic and acetabular (P&A) fracture surgery and those who do work in a P&A referral hospital. Most respondents (77%) refer patients 1-5 times a year to an expert center for surgical fixation. CONCLUSION: There is currently a wide variety of clinical practices regarding the imaging and management of FFPs, which seems to be influenced by the type of hospital the patients are presented to. A regional or national evidence-based treatment protocol should be implemented to ensure a more uniform approach.

Sample Preparation in Microbial Metabolomics: Advances and Challenges.

Microbial metabolomics has gained significant interest as it reflects the physiological state of microorganisms. Due to the great variability of biological organisms, in terms of physicochemical characteristics and variable range of concentration of metabolites, the choice of sample preparation methods is a crucial step in the metabolomics workflow and will reflect on the quality and reliability of the results generated. The procedures applied to the preparation of microbial samples will vary according to the type of microorganism studied, the metabolomics approach (untargeted or targeted), and the analytical platform of choice. This chapter aims to provide an overview of the sample preparation workflow for microbial metabolomics, highlighting the pre-analytical factors associated with cultivation, harvesting, metabolic quenching, and extraction. Discussions focus on obtaining intracellular and extracellular metabolites. Finally, we introduced advanced sample preparation methods based on automated systems.

Delineating early developmental pathways to ADHD: Setting an international research agenda.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent, impairing, and highly heritable condition typically diagnosed in middle childhood. However, it is now recognized that symptoms emerge much earlier in development. Research focused on understanding-using multiple units of analysis-the cascade of early-life (i.e., prenatal-infant-toddler) developmental changes that will later emerge as ADHD has the potential to transform early identification, prevention, and intervention. To this end, we introduce the recently established Early ADHD Consortium, an international network of investigators engaged in prospective, longitudinal studies of risk for ADHD beginning early in life, conducted within a developmental framework, and which incorporate multimethod approaches. This network seeks to harmonize measures and methodological approaches to increase the potential for data sharing and subsequent impact. Methods: This perspective paper highlights the importance of investigating pre-diagnostic markers of ADHD, and potential models and mechanisms of ADHD risk and development, with the long-term objective of facilitating development of preemptive interventions that will minimize the impact of ADHD symptoms on everyday functioning and maximize health and developmental outcomes. Results: We selectively describe key challenges and questions for this field related to theoretical models and developmental mechanisms in ADHD and recommend next steps for the science, including methodological, measurement, and study design considerations. We then describe potential implications for preemptive intervention development. We conclude by considering other issues including ethical concerns and the critical value of incorporating stakeholder input. Conclusions: It is hoped that this perspective puts forth a research agenda that will enhance collaborative efforts and accelerate progress in understanding developmental mechanisms and the early ADHD phenotype, with implications for early intervention enhancement of healthy development for infants, young children, and their families.