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The experience of stress is often utilised in models of emerging mental illness and neurobiological systems are implicated as the intermediary link between the experience of psychological stress and the development of a mental disorder. Chronic stress and prolonged glucocorticoid exposure have potent effects on neuronal architecture particularly in regions that modulate the hypothalamic-pituitary-adrenal (HPA) axis and are commonly associated with psychiatric disorders. This review provides an overview of stress modulating neurobiological and neurochemical systems which underpin stress-related structural and functional brain changes. These changes are thought to contribute not only to the development of disorders, but also to the treatment resistance and chronicity seen in some of our most challenging mental disorders. Reports to date suggest that stress-related psychopathology is the aetiological mechanism of these disorders and thus we review the rapid acting antidepressant ketamine as an effective emerging treatment. Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, is shown to induce a robust treatment effect in mental disorders via enhanced synaptic strength and connectivity in key brain regions. Whilst ketamine's glutamatergic effect has been previously examined, we further consider ketamine's capacity to modulate the HPA axis and associated pathways.

Advocating for anesthesiology is a professional responsibility. We need to make the public aware of the role we play in assuring their safety and comfort; and we must also ensure that payment models are fair and commensurate with the quality of our work.

Background: Malnutrition (excess or defect) and sedentariness act as an accelerator in the older people frailty process. A systemic solution has been developed to engage older people in a healthier lifestyle using serious games and food monitoring. The study aimed to evaluate protocol influence on variables related to unhealthy behaviors improving dietary habits through a remote nutritional coaching approach and stimulating the population to increase physical activity through Exergames. Methods: Thirty-two subjects (25 Treatments and 7 Controls, aging 65-80 years), of which 15 (11 Treatments and 4 Controls) living in the UK (ACCORD and ExtraCare Villages placed in Shenley Wood (Milton Keynes), St. Crispin (Northampton), and Showell Court (Wolverhampton)) and 17 (14 Treatments and 3 Controls) in Italy (Genoa, Liguria), were recruited and characterized in terms of nutritional status, physical, somatometric, hemodynamic and biochemical measurements, and body composition. Participants were stimulated to adopt the Mediterranean dietary pattern, by a food diary diet-app, and perform regular physical activity, by the Exergame app, for three months. At the end of the trial, users underwent the same test battery. Data were tested for normality of distribution by the Shapiro-Wilk test. Comparisons between groups were performed at baseline by unpaired Student's t-test for continuous variables, chi-square test, or Fisher's exact test for categorical variables. Analysis of Variance (ANOVA) for repeated measures was used to analyze the significance of changes over time between groups. Results: At the end of the trial, significant reductions of systolic (15 mmHg, P = 0.001), diastolic (5 mmHg, P = 0.025), mean (10 mmHg, P = 0.001) blood pressure, and rate-pressure product (RPP) (1,105 mmHg*bpm, P = 0.017) values were observed in DOREMI users. A trend of improvement of physical performance by the short physical performance battery (SPPB) was observed for balance and walk subtests. A significant decrease (0.91 kg, P = 0.043) in Body Mass Index (BMI) was observed in overweight subjects (BMI >25 kg/m) after DOREMI intervention in the entire population. The Mini Nutritional Assessment (MNA) score (1, P = 0.004) significantly increased after intervention, while waist measure (3 cm, P

Peripheral nerve injuries associated with reverse total shoulder arthroplasty (rTSA) are rarely reported and are often dismissed as neuropraxias, particularly in the setting of perioperative nerve blocks. The purpose of this study was to evaluate nerve injuries following rTSA to determine if there is a pattern of injury and to evaluate outcomes of patients who sustain an intraoperative nerve injury.A retrospective review was performed identifying patients who underwent rTSA and had a concomitant major nerve injury who were referred to a multidisciplinary peripheral nerve injury clinic. Demographic data, preoperative nerve block use, physical examination, electrodiagnostic studies, injury pattern, and time from injury to referral was collected. Radiographs, Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) score, and outcomes surveys were obtained at final follow-up.Twenty-two patients were identified with postoperative nerve injuries. Average time from injury to referral was 9.0 months, with 18.8 months' follow-up. Eight patients had undergone prior shoulder surgery, and 11 patients had prior shoulder trauma. Injury patterns were variable and involved diffuse pan-plexopathies with severity localized to the posterior and medial cords (11), the upper trunk (5), lateral cord (2), and axillary nerve (4). The average postoperative acromiohumeral distance (AHD) was 3.7 cm, with an average change of 2.9 cm. The average postoperative lateral humeral offset (LHO) was 1.1 cm, with an average change of 0.2 cm. Seventeen patients were confirmed to have undergone preoperative nerve blocks, which were initially attributed as the etiology of nerve injury. Eighteen patients were initially treated with observation: 11 experienced residual debilitating neuropathic pain and/or disability, and 7 had substantial improvement. One patient underwent nerve transfers, whereas the others underwent procedures for hand dysfunction improvement. The average QuickDASH score was 53.5 at average of 4 years post rTSA.Although uncommon, permanent peripheral nerve injuries following rTSA do occur with debilitating effects. Preoperative regional blocks were used in most cases, but none of the blocks could be directly attributed to the nerve injuries. Nerve injuries were likely secondary to traction at the time of arthroplasty and/or substantial distalization and lateralization of the implants. Patients with medial cord injuries had the most debilitating loss of hand function. Surgeons should be cognizant of these injuries and make a timely referral to a peripheral nerve specialist.

Background Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of hormone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. Methods The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40–65 years, for whom 1–10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12–15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. Findings From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63–92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0·50 [95% CI 0·25–0·75]). The trial met the prespecified criteria for progression to a full trial. Interpretation This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Funding Research for Patient Benefit programme, National Institute for Health Research.

Prior work shows that ads related to abortion services often feature crisis pregnancy centers instead of abortion providers. We investigated whether a change in Google's advertising policy that required advertisers to disclose whether they provided abortion services increased the proportion of ads facilitating abortion self-referral.We used a standardized protocol to search online for abortion services before, during, and after the policy change; we performed searches in August 2016 to June 2017, June 2019, and October 2019, respectively, using Google, Bing, and Yahoo search engines. We performed searches for the 25 most populous U.S. cities and the 43 state capitals not already included. We classified up to the first 5 ads as facilitating abortion referral, hindering abortion referral, or providing neutral content. We compared search engine results using a chi-square test.Among ads returned by Google, those shown after the policy change were significantly more likely to facilitate abortion self-referral (66.7% vs. 44.2%; p = 0.003) and slightly less likely to hinder abortion self-referral (33.3% vs. 40.6%; p = 0.33) compared to before the change. These findings were reversed for ads shown by Bing and Yahoo; ads returned after the change were significantly less likely to facilitate abortion self-referral (24.6% vs. 32.8%; p = 0.01) and significantly more likely to hinder self-referral (28.3% vs. 21.6%; p = 0.03) compared to before the change.A policy requiring advertisers to disclose whether they provide abortion services was associated with increasing the proportion of ads facilitating self-referral. Similar policies should be considered by all search engines.While the internet is a convenient source of information that individuals often use to locate abortion providers, the information may not actually lead searchers to services. Search engines should consider restricting abortion-related advertising to organizations that provide abortion services in order to ensure that individuals searching online for abortion services are able to locate services in a direct and timely manner.

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.

Background: Torus (buckle) fractures of the wrist are the most common fractures in children, involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up, or would equally recover by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, school absences and NHS costs. Objectives: To establish whether treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (“offer of bandage”), provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (“rigid immobilisation”). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: 23 UK Emergency Departments. Participants: 965 children (4-15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online encrypted randomisation service. Exclusion criteria included presentation >36 hours after injury, multiple injuries and inability to complete follow-up. Interventions: Offer of bandage (n= 489) of whom the bandage was applied in 458, versus rigid immobilisation (n= 476). Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: Pain at 3-days post-randomisation measured using the WongBaker FACES Pain Rating Scale. Secondary outcomes were the PROMIS Upper Extremity score for children, health related quality of life (QoL), complications, school absence, analgesia use and resource use collected up to 6 weeks post-randomisation. Results: 94% of participants provided primary outcome data. Pain was equivalent at the 3 day primary outcome for both groups. With reference to the pre-specified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was -0.10; 95% CI -0.37 to 0.17 and the per-protocol population was -0.06; 95% CI -0.34 to 0.21. There was equivalence in pain for both age subgroups (4-7 and 8–15 years). There was no difference in the rate of complications, with five (1.0%) in the offer of bandage group and three (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, QoL or school absence at any point during follow-up. Analgesia use was marginally higher at Day 1 in the offer of bandage group (83% vs 78% participants), though was no different at other times. The offer of bandage significantly reduced the cost of treatment, and had a high probability of cost-effectiveness. Limitations: Families had a strong pre-existing preference for rigid immobilisation. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of bandage in children with a distal radius torus fracture.

Multiple ocean sectors compete for space and resources, creating conflicts but also opportunities to plan for synergistic outcomes that benefit multiple sectors. Planning and management are increasingly informed by qualitative and quantitative methods for assessing multi-sector interactions to identify trade-offs and synergies among sectors and with the environment, but there is a need to critically review the alignment of these tools with the requirements of Blue Economy stakeholders. Through a systematic literature review, an operational maturity analysis, and a survey of Blue Economy stakeholders, we found that the most well-developed tools for assessing interactions between multiple Blue Economy industries, and with the environment, are spatial prioritization tools, such as Marxan and multi-criteria decision support tools; and spatial static tools, such as cumulative effect mapping. More complex process/dynamic tools such as ecosystem and oceanographic models are well developed for single sectors, particularly water quality assessments and commercial fisheries, but have been less commonly applied in multi-sector contexts. Our review and stakeholder survey highlighted that assessing the environmental and operational suitability of sites for Blue Economy infrastructure in conjunction with operational impacts, trade-offs and decommissioning considerations requires: 1) a toolbox of approaches that covers a range of spatial, temporal and ecological scales; 2) tools that capture interactions and feedbacks among sectors, and with the environment, without being unnecessarily complicated (i.e., tractable to use and allow for effective communication of findings); and 3) continued synthesis of approaches and tools used across sectors such as commercial fishing, aquaculture, offshore renewable energy, and offshore engineering.

Black participants often lose less weight than White participants in response to behavioral weight-loss interventions. Many participants experience significant pretreatment weight fluctuations (between baseline measurement and treatment initiation), which have been associated with treatment outcomes. Pretreatment weight gain has been shown to be more prevalent among Black participants and may contribute to racial differences in treatment responses. The purpose of this study was to (1) examine the associations between pretreatment weight change and treatment outcomes and (2) examine racial differences in pretreatment weight change and weight loss among Black and White participants.Participants were Black and White women (n=153, 60% Black) enrolled in a 4-month weight loss program. Weight changes occurring during the pretreatment period (41 ± 14 days) were categorized as weight stable (±1.15% of baseline weight), weight gain (≥+1.15%), or weight loss (≤-1.15%). Recruitment and data collection occurred from 2011 to 2015; statistical analyses were performed in 2021.During the pretreatment period, most participants (56%) remained weight stable. Pretreatment weight trajectories did not differ by race (p=0.481). At 4-months, those who lost weight before treatment experienced 2.63% greater weight loss than those who were weight stable (p0.005), whereas those who gained weight before treatment experienced 1.91% less weight loss (p0.01).Pretreatment weight changes can impact weight outcomes after initial treatment, although no differences between Black and White participants were observed. Future studies should consider the influence of pretreatment weight change on long-term outcomes (e.g., weight loss maintenance) along with potential racial differences in these associations. This study is registered (retrospectively registered) at ClinicalTrials.gov (NCT02487121) on June 26, 2015.

Acute thrombotic thrombocytopenic purpura (TTP) is a life-threatening emergency and plasma exchange (PEX) is the initial treatment shown to reduce acute mortality.To compare current practice in the United Kingdom (UK) against the standards set out in the 2012 British Society of Haematology guideline, and to better understand the issues affecting prompt initiation of PEX.The trainee research network HaemSTAR conducted a retrospective nationwide review of adults presenting to UK hospitals with a first episode of acute TTP.Data on 148 patients treated at 80 UK hospitals between 2014 and 2019 demonstrated that 64.8% of patients received PEX within 24 h. Diagnostic uncertainty was the most commonly cited reason for delayed treatment. Conversely, a shorter time to PEX occurred in patients who had red cell fragments or severe thrombocytopenia identified on their first complete blood count. Availability of on-site PEX was associated with a greater proportion of patients receiving PEX within 8 h compared to patients transferred, but by 24 h there was no difference between the two groups and two-thirds of all patients had received their first PEX. The mortality rate for patients that received PEX was 9.2%, with 27.8% of deaths linked to delayed treatment initiation.This is the first multi-center evaluation of treatment delays in acute TTP and it will inform targeted pathways to improve prompt access to life-saving intervention.