Top-down control of flight by a non-canonical cortico-amygdala pathway.

Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder1. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA)2; however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.

Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.

Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, L-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in L-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.

Infantile hypercalcemia type 1 (HCINF1): a rare disease resulting in nephrolithiasis and nephrocalcinosis caused by mutations in the vitamin D catabolic enzyme, CYP24A1.

Infantile hypercalcemia type 1 (HCINF1), formerly known as Lightwood syndrome, is a subtype of hypercalcemia caused by loss-of-function biallelic mutations in the vitamin D catabolic enzyme, CYP24A1, which 24-hydroxylates the hormone 1,25-(OH)2D3. This short review focuses on the main features of the HCINF1 disease; emerging knowledge of the structure and function of the cytochrome P450, CYP24A1 and the location of inactivating mutations; the development of a rapid LC-MS/MS-based laboratory test for defective 24-hydroxylation; and future implications for bioanalytical assay and treatment of all types of vitamin D-related hypercalcemic conditions.

Ageing of juvenile coral grouper (Plectropomus maculatus) reveals year-round spawning and recruitment: implications for seasonal closures.

Temporal patterns in spawning and juvenile recruitment can have major effects on population size and the demographic structure of coral reef fishes. For harvested species, these patterns are crucial in determining stock size and optimizing management strategies such as seasonal closures. For the commercially important coral grouper (Plectropomus spp.) on the Great Barrier Reef, histological studies indicate peak spawning around the summer new moons. Here we examine the timing of spawning activity for P. maculatus in the southern Great Barrier Reef by deriving age in days for 761 juvenile fish collected between 2007 and 2022, and back-calculating settlement and spawning dates. Age-length relationships were used to estimate spawning and settlement times for a further 1002 juveniles collected over this period. Unexpectedly, our findings indicate year-round spawning activity generates distinct recruitment cohorts that span several weeks to months. Peak spawning varied between years with no clear association with environmental cues, and little to no alignment with existing seasonal fisheries closures around the new moon. Given the variability and uncertainty in peak spawning times, this fishery may benefit from additional and longer seasonal closures, or alternative fisheries management strategies, to maximize the recruitment contribution from periods of greatest reproductive success.

Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis: a sub-study from the DISCUSS project.

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.

Neural ensemble dynamics underlying a long-term associative memory.

The brain's ability to associate different stimuli is vital for long-term memory, but how neural ensembles encode associative memories is unknown. Here we studied how cell ensembles in the basal and lateral amygdala encode associations between conditioned and unconditioned stimuli (CS and US, respectively). Using a miniature fluorescence microscope, we tracked the Ca2+ dynamics of ensembles of amygdalar neurons during fear learning and extinction over 6 days in behaving mice. Fear conditioning induced both up- and down-regulation of individual cells' CS-evoked responses. This bi-directional plasticity mainly occurred after conditioning, and reshaped the neural ensemble representation of the CS to become more similar to the US representation. During extinction training with repetitive CS presentations, the CS representation became more distinctive without reverting to its original form. Throughout the experiments, the strength of the ensemble-encoded CS-US association predicted the level of behavioural conditioning in each mouse. These findings support a supervised learning model in which activation of the US representation guides the transformation of the CS representation.

Patients' and clinicians' perspectives towards primary care consultations for shoulder pain: qualitative findings from the Prognostic and Diagnostic Assessment of the Shoulder (PANDA-S) programme.

BACKGROUND: Clinical management of musculoskeletal shoulder pain can be challenging due to diagnostic uncertainty, variable prognosis and limited evidence for long-term treatment benefits. The UK-based PANDA-S programme (Prognostic And Diagnostic Assessment of the Shoulder) is investigating short and long-term shoulder pain outcomes. This paper reports linked qualitative research exploring patients' and clinicians' views towards primary care consultations for shoulder pain. METHODS: Semi-structured interviews were conducted with 24 patients and 15 primary care clinicians. Twenty-two interviews (11 patients, 11 clinicians) were conducted as matched patient-clinician 'dyads'. Data were analysed thematically. RESULTS: Clinicians reported attempts to involve patients in management decisions; however, there was variation in whether patients preferred treatment choice, or for decisions to be clinician-led. Some patients felt uncertain about the decisions made, due to a lack of discussion about available management options. Many General Practitioners expressed a lack of confidence in diagnosing the underlying cause of shoulder pain. Patients reported either not being given a diagnosis, or receiving different diagnoses from different professionals, resulting in confusion. Whilst clinicians reported routinely discussing prognosis of shoulder pain, patients reported that prognosis was not raised. Patients also expressed concern that their shoulder pain could be caused by serious pathology; however, clinicians felt that this was not a common concern for patients. CONCLUSIONS: Findings showed disparities between patients' and clinicians' views towards shoulder pain consultations, indicating a need for improved patient-clinician communication. Findings will inform the design of an intervention to support treatment and referral decisions for shoulder pain that will be tested in a randomised controlled trial.

Advice to remain active with arm pain reduces disability.

BACKGROUND: Arm pain is common amongst working-aged adults and causes substantial work disability. The results of a population-based randomized controlled trial (the ARM trial) suggested that advice to remain active reduced disability after 6 months. AIMS: To verify ARM trial results amongst people in paid employment. METHODS: The ARM trial recruited adults with distal arm pain referred for physiotherapy and randomized equally to three groups: wait-listed for physiotherapy (advised to rest); wait-listed for physiotherapy (advised to remain active) or early physiotherapy. The primary outcome was absence of disability at 26 weeks. Secondary analyses were undertaken amongst participants in paid employment. RESULTS: Amongst 538 trial participants, 347 (64%) were in paid employment, mean age 46.1 years and 47% in manual work. Employed participants were randomized equally to the three arms. Amongst the 271 (78% workers with 26-week data), 43% of those advised to remain active were free from disability, as compared with 37% of those advised to rest. Forty per cent of those who waited for physiotherapy were disability-free as compared with 35% of those treated rapidly. Advice to rest was associated with lower chances of recovery amongst workers who lift/carry weights and those who believed work had caused their symptoms (P = 0.023). CONCLUSIONS: Although not powered as a trial for workers only, our findings suggest that advising activity was as beneficial for people currently in paid work and may be superior to advice to rest in reducing disability. Addressing harmful beliefs about causation of symptoms has the potential to reduce disability.

Early experience of a local pathway on the waiting time for MRI in patients presenting to a UK district general hospital with suspected cauda equina syndrome.

AIM: This study evaluated the impact of the Salisbury Protocol for Assessment of Cauda Equina Syndrome (SPACES) on the waiting time for MRI in patients presenting with suspected Cauda Equina Syndrome (sCES) within a UK district general hospital. PATIENTS AND METHODS: All consecutive patients undergoing an MRI scan in our hospital, for sCES, over a 12 month period, prior to and following the introduction of SPACES, were identified. Patient's gender, age, MRI diagnosis, time from MRI request to imaging and outcome were recorded. RESULTS: In the year prior to the introduction of SPACES, 66 patients underwent MRI for sCES, out of which 10.6% had cauda equina compression (CEC), 63.5% had other spinal pathology and 25% had a normal scan. In the year after introduction of SPACES, 160 patients underwent MRI for sCES out of which 6.2% had CEC, 70.7% had other spinal pathology and 23% had a normal scan. Despite the referrals for sCES increasing by more than 2-fold following the introduction of SPACES, the median time from MRI request to scan decreased from 9.1 to 4.2 hours (p = 0.106, Mann-Whitney-U) and the number of patients transferred to the regional hub hospital decreased from 7 to 3. CONCLUSION: Implementation of SPACES for patients with sCES resulted in a substantial reduction in waiting time for MRI and decreased the number of transfers to the regional hub hospital. Based on our early experience, we encourage other centres within the UK to introduce such a pathway locally, to improve the management of patients with sCES.

Association between osteoarthritis-related serum biochemical markers over 11 years and knee MRI-based imaging biomarkers in middle-aged adults.

OBJECTIVE: To describe the associations between osteoarthritis (OA)-related biochemical markers (COMP, MMP-3, HA) and MRI-based imaging biomarkers in middle-aged adults over 10-13 years. METHODS: Blood serum samples collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-06; n = 156) and 10-13 year follow-up at CDAH-3 (n = 167) were analysed for COMP, MMP-3, and HA using non-isotopic ELISA. Knee MRI scans obtained during the CDAH-knee study (year:2008-10; n = 313) were assessed for cartilage volume and thickness, subchondral bone area, cartilage defects, and BML. RESULTS: In a multivariable linear regression model describing the association of baseline biochemical markers with MRI-markers (assessed after 4-years), we found a significant negative association of standardised COMP with medial femorotibial compartment cartilage thickness (ß:-0.070; 95%CI:-0.138,-0.001), and standardised MMP-3 with patellar cartilage volume (ß:-141.548; 95%CI:-254.917,-28.179) and total bone area (ß:-0.729; 95%CI:-1.340,-0.118). In multivariable Tobit regression model, there was a significant association of MRI-markers with biochemical markers (assessed after 6-9 years); a significant negative association of patellar cartilage volume (ß:-0.001; 95%CI:-0.002,-0.00004), and total bone area (ß:-0.158; 95%CI-0.307,-0.010) with MMP-3, and total cartilage volume (ß:-0.001; 95%CI:-0.001,-0.0001) and total bone area (ß:-0.373; 95%CI:-0.636,-0.111) with COMP. No significant associations were observed between MRI-based imaging biomarkers and HA. CONCLUSION: COMP and MMP-3 levels were negatively associated with knee cartilage thickness and volume assessed 4-years later, respectively. Knee cartilage volume and bone area were negatively associated with COMP and MMP-3 levels assessed 6-9 years later. These results suggest that OA-related biochemical markers and MRI-markers are interrelated in early OA.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Electrically Controllable Kondo Correlation in Spin-Orbit-Coupled Quantum Point Contacts.

Integrating the Kondo correlation and spin-orbit interactions, each of which have individually offered unprecedented means to manipulate electron spins, in a controllable way can open up new possibilities for spintronics. We demonstrate electrical control of the Kondo correlation by coupling the bound spin to leads with tunable Rashba spin-orbit interactions, realized in semiconductor quantum point contacts. We observe a transition from single to double peak zero-bias anomalies in nonequilibrium transport-the manifestation of the Kondo effect-indicating a controlled Kondo spin reversal using only spin-orbit interactions. Universal scaling of the Kondo conductance is demonstrated, implying that the spin-orbit interactions could enhance the Kondo temperature. A theoretical model based on quantum master equations is also developed to calculate the nonequilibrium quantum transport.

Use of Prothrombin Complex Concentrate in Oral Anticoagulant-Associated Major Bleeding.

Severe bleeding remains the most significant adverse effect associated with both warfarin and the direct oral anticoagulant agents. Due to the life-threatening nature of these bleeds, knowledge and understanding of agents that are able to rapidly overcome the anticoagulation effects of these medications is paramount to their use. Worldwide, the most commonly used agent for this indication is prothrombin complex concentrate (PCC). This review summarizes the evidence on the use of PCC in this population and provides practical information regarding patient-specific administration considerations.

Safety of early antiplatelet administration in patients with acute ischemic stroke treated with alteplase (SEAPT-24).

OBJECTIVES: Alteplase, a tissue-type plasminogen activator, is recommended for ischemic stroke patients presenting within 4.5 h. Due to bleeding risks, current guidelines advise delaying antiplatelet therapy for 24 h after alteplase. However, specific scenarios may require antiplatelet therapy to be given within the 24 h window. This study aimed to examine the safety of early antiplatelet therapy administration within the first 24 h after alteplase. MATERIALS AND METHODS: This study is a retrospective, observational study of adult patients with acute ischemic stroke who received alteplase across a multi-hospital system. Patients were grouped based on early antiplatelet therapy (within 24 h window) or as recommended per guidelines. The occurrence of bleeding events, including symptomatic intracranial hemorrhage and/or gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes (modified Rankin score 3-6), and hospital length of stay, were compared between groups. RESULTS: Patients were predominantly African American (72%) and female (53%) with a median age of 62 years. Median baseline NIHSS scores were higher in the early group (5 vs. 7; p = 0.04), and patients in the early group were more likely to undergo endovascular therapy (26% vs. 8%, p < 0.0001). In patients treated with alteplase only and who did not undergo endovascular therapy, there was no difference in symptomatic intracranial hemorrhage (1.4% vs. 0%, p = 0.1), gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes, or length of stay. CONCLUSIONS: In our retrospective analysis, early administration of antiplatelet therapy (< 24 h post-alteplase) did not increase the risk of symptomatic intracranial hemorrhage, gastrointestinal bleeding, or unfavorable outcomes in patients who received alteplase alone for management of acute ischemic stroke. Prospective studies are needed to validate these findings.

Acute paediatric mastoiditis in the UK before and during the COVID-19 pandemic: A national observational study.

OBJECTIVES: To explore the impact of COVID-19 on the management and outcomes of acute paediatric mastoiditis across the UK. DESIGN: National retrospective and prospective audit. SETTING: 48 UK secondary care ENT departments. PARTICIPANTS: Consecutive children aged 18 years or under, referred to ENT with a clinical diagnosis of mastoiditis. MAIN OUTCOME MEASURES: Cases were divided into Period 1 (01/11/19-15/03/20), before the UK population were instructed to reduce social contact, and Period 2 (16/03/20-30/04/21), following this. Periods 1 and 2 were compared for population variables, management and outcomes. Secondary analyses compared outcomes by primary treatment (medical/needle aspiration/surgical). RESULTS: 286 cases met criteria (median 4 per site, range 0-24). 9.4 cases were recorded per week in period 1 versus 2.0 in period 2, with no winter increase in cases in December 2020-Febraury 2021. Patient age differed between periods 1 and 2 (3.2 vs 4.7 years respectively, p < 0.001). 85% of children in period 2 were tested for COVID-19 with a single positive test. In period, 2 cases associated with P. aeruginosa significantly increased. 48.6% of children were scanned in period 1 vs 41.1% in period 2. Surgical management was used more frequently in period 1 (43.0% vs 24.3%, p = 0.001). Treatment success was high, with failure of initial management in 6.3%, and 30-day re-admission for recurrence in 2.1%. The adverse event rate (15.7% overall) did not vary by treatment modality or between periods 1& 2. CONCLUSION: The COVID-19 pandemic led to a significant change in the presentation and case mix of acute paediatric mastoiditis in the UK.

Safety of Propofol When Used for Rapid Sequence Intubation in Septic Patients: A Multicenter Cohort Study.

Purpose: Septic patients are at risk for hypotension, and this risk may increase during rapid sequence intubation (RSI). Sedatives such as propofol must be used carefully due to its ability to reduce vascular sympathetic tone. Since the safety of propofol for RSI is not well described in sepsis, this was a study evaluating propofol and its effects on hemodynamics when used for RSI in a septic population. Materials and methods: We conducted a multicenter, retrospective, cohort study of patients with sepsis or severe sepsis requiring sedation for RSI. Patients receiving a propofol bolus for RSI were compared to patients undergoing RSI without a propofol bolus. The safety profile of propofol was evaluated according to the rates of post-intubation hypotension and vasopressor utilization between groups. Results: A total of 179 patients (79 propofol, 100 non-propofol) were evaluated. There were no differences in hypotension (81% vs 78%; P = .62) or vasopressor utilization between the propofol and non-propofol groups (43% vs 49%; P = .43). Patients in the non-propofol group had increased APACHE II scores and healthcare-associated infections. Conclusions: In this cohort study, administration of propofol for RSI in patients with sepsis and severe sepsis did not increase incidence of hypotension or vasopressor use, but acute illness may have introduced provider selection bias causing less propofol use in the non-propofol group. Larger prospective studies are needed to better characterize the adverse hemodynamic effects of propofol, before propofol bolus doses for RSI can be considered for safe use in this population.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Predictors of total hip replacement in community based older adults: a cohort study.

OBJECTIVE: The purpose of this study is to describe predictors of total hip replacement (THR) in community dwelling older adults. A better understanding of predictors of THR can aid in triaging patients and researching preventative strategies. DESIGN: At baseline, participants had assessment of radiographic OA and cam morphology (from pelvic radiographs), shape mode scores and hip bone mineral density (BMD; from dual energy X-ray absorptiometry (DXA)). After 2.6 and 5 years, participants reported hip pain using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), and had hip structural changes assessed using magnetic resonance imaging (MRI). Risk of THR was analysed using mixed-effect Poisson regression. RESULTS: Incidence of THR for OA over 14 years was 4.6% (37/801). As expected, WOMAC hip pain and hip radiographic OA both predicted risk of THR. Additionally, shape mode 2 score (decreasing acetabular coverage) (RR 1.83/SD; 95% CI 1.1-3.04), shape mode 4 score (non-spherical femoral head) (RR 0.59/SD; 95% CI 0.36-0.96), cam morphology (α > 60°) (RR 2.2/SD; 95% CI 1.33-3.36), neck of femur BMD (RR 2.09/SD, 95% CI 1.48-2.94) and bone marrow lesions (BMLs) increased risk of THR (RR 7.10/unit; 95% CI 1.09-46.29). CONCLUSION: In addition to hip pain and radiographic hip OA, measures of hip shape, cam morphology, BMD and BMLs independently predict risk of THR. This supports the role of hip bone geometry and structure in the pathogenesis of end stage hip OA and has identified factors that can be used to improve prediction models for THR.

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review.

OBJECTIVE: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. DESIGN: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. RESULTS: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). CONCLUSIONS: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.