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We report the case of a 46-year-old male with long-standing low back pain who presented with a deterioration of symptoms characterised by back and right leg pain corresponding to the L4 and L5 dermatomes. An MRI scan revealed severe central and lateral recess stenosis at L4/5 secondary to a large central disc protrusion. We remotely monitored activity and general health metrics over a time-period exceeding two years. This is the first study to monitor these metrics remotely and continuously in the surgical spine patient. Over this time, he received several interventions including a spinal cord stimulator implant, and an L4/5 microdiscectomy. We tracked his fluctuating health status using the Oura Ring [objectively measuring metrics including step count, sleep patterns, heart rate (HR), heart-rate variability (HRV), and respiratory rate (RR)] and with daily self-reported scores on the Visual Analogue Scale. The Oura Ring is a convenient and lightweight wearable device that is worn on any finger. Taken together, metrics provided a comprehensive picture of deterioration and recovery, paralleling key events in the patient’s history. The use of wearable devices is feasible in enabling long-term remote continuous monitoring. This may assist surgeons and rehabilitation providers in identifying early deterioration and monitoring the post-intervention course of recovery.

The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P < .001) and unilateral (P < .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.

Objective To evaluate usability of a quality improvement tool that promotes guideline-based care for patients with peripheral arterial disease (PAD). Patients and Methods The study was conducted from July 19, 2018, to August 21, 2019. We compared the usability of a PAD cohort knowledge solution (CKS) with standard management supported by an electronic health record (EHR). Two scenarios were developed for usability evaluation; the first for the PAD-CKS while the second evaluated standard EHR workflow. Providers were asked to provide opinions about the PAD-CKS tool and to generate a System Usability Scale (SUS) score. Metrics analyzed included time required, number of mouse clicks, and number of keystrokes. Results Usability evaluations were completed by 11 providers. SUS for the PAD-CKS was excellent at 89.6. Time required to complete 21 tasks in the CKS was 4 minutes compared with 12 minutes for standard EHR workflow (median, P = .002). Completion of CKS tasks required 34 clicks compared with 148 clicks for the EHR (median, P = .002). Keystrokes for CKS task completion was 8 compared with 72 for EHR (median, P = .004). Providers indicated that overall they found the tool easy to use and the PAD mortality risk score useful. Conclusions Usability evaluation of the PAD-CKS tool demonstrated time savings, a high SUS score, and a reduction of mouse clicks and keystrokes for task completion compared to standard workflow using the EHR. Provider feedback regarding the strengths and weaknesses also created opportunities for iterative improvement of the PAD-CKS tool.

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia.

Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long-term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contractures, camptodactyly, widely spaced teeth, and constriction rings. We also propose novel occasional features including craniosynostosis, ocular pterygia, anterior chamber cleavage syndrome, early osteoporosis, increased pigmentation, recurrent haematomas, predisposition to cellulitis, nail dystrophy, carpal tunnel syndrome, recurrent hypoglycaemia in infancy, joint dislocation, and splenomegaly. Importantly, we report fusiform aneurysm of the basilar artery in two patients. Complications include thrombosis and stroke in the oldest reported patient and fatal rupture at the age of 21 in the patient with the novel variant. We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS-like disorders and suggest vascular imaging is indicated in these patients.

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Traumatic supra-hepatic inferior vena cava (IVC) injury is rare and nearly universally fatal. We report an excellent outcome from a case involving severe injury of the suprahepatic and intra-pericardial IVC utilizing emergency cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. The goal of this case report is to outline key factors that facilitated the patient's survival of extensive IVC injury. We conclude that aggressive prehospital fluid resuscitation, facile transfer to the operating room, early detection of anatomy and pathology of the injury, an early decision to call for perfusion and cardiothoracic surgery, and prompt blood transfusion were the key factors that allowed for the patient to survive without deficits.

Multiple summer events, including large indoor gatherings, in Provincetown, Massachusetts (MA), in July 2021 contributed to an outbreak of over one thousand COVID-19 cases among residents and visitors. Most cases were fully vaccinated, many of whom were also symptomatic, prompting a comprehensive public health response, motivating changes to national masking recommendations, and raising questions about infection and transmission among vaccinated individuals. To characterize the outbreak and the viral population underlying it, we combined genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of sequenced outbreak-associated cases. Phylogenetic analysis suggests over 40 sources of Delta in the dataset, with one responsible for a single cluster containing 83% of outbreak-associated genomes. This cluster was likely not the result of extensive spread at a single site, but rather transmission from a common source across multiple settings over a short time. Genomic and epidemiological data combined provide strong support for 25 transmission events from, including many between, fully vaccinated individuals; genomic data alone provides evidence for an additional 64. Together, genomic epidemiology provides a high-resolution picture of the Provincetown outbreak, revealing multiple cases of transmission of Delta from fully vaccinated individuals. However, despite its magnitude, the outbreak was restricted in its onward impact in MA and the US, likely due to high vaccination rates and a robust public health response.

Background Hypoglycaemia is a leading cause of admissions to neonatal units. A major risk factor for neonatal hypoglycaemia is maternal gestational diabetes mellitus (GDM). Since 2013, diagnosis of GDM in the UK has relied upon the oral glucose tolerance test (OGTT) at 28 weeks of pregnancy. In response to the COVID-19 pandemic, however, guidance released by the Royal College of Obstetricians and Gynaecologists [RCOG] (2020) advised replacing OGTT with alternative measures such as HbA1C and random blood glucose (RBG) measurement. Objectives 1. Compare the number of neonatal admissions for hypoglycaemia to a level two unit before and during the COVID-19 pandemic. 2. Detect differences in diagnostic modalities used for gestational diabetes in mothers of newborns admitted with hypoglycaemia before and during COVID-19. 3. Compare outcomes of neonates admitted with hypoglycaemia before and during COVID-19. Methods Neonates admitted with hypoglycaemia to our unit during two time periods - April to August 2019 and April to August 2020 - were identified using an online portal and formed the two groups for auditing. Maternal and neonatal health records were then retrospectively reviewed to determine: (1) the presence of risk factors for GDM during pregnancy among mothers of neonates in both groups, and (2) the diagnostic methods for GDM performed in mothers of neonates in each group. We further collected data on selected outcomes for neonates, including length of stay, IV glucose delivery, umbilical venous cannulation (UVC) and parenteral feeding, in both groups. Results The number of neonatal admissions with hypoglycaemia to the unit doubled during the COVID-19 pandemic (group 2 [n=32] vs group 1 [n=17]). Fewer newborns admitted during COVID-19 had a mother with a diagnosis of GDM (group 2 [15.6%] vs group 1 [23.5%]) despite mothers of newborns in this group being more likely to be at risk for GDM (group 2 [69.6%] vs group 1 [64.3%]). In all, less OGTTs were performed in mothers of neonates admitted with hypoglycaemia during COVID-19 than before (group 2 [31.3%] vs group 1 [35.3%]) and HbA1C and RBG measurements were more likely to be performed (group 2 [25%] vs group 1 [0%] and group 2 [15.6%] vs group 1 [11.8%], respectively). Nevertheless, median length of admission for newborns was shorter during the COVID- 19 pandemic (group 2 [4 days;IQR 2-16] vs group 1 [7 days;IQR 3-11.5]) and the proportion receiving treatments such as intravenous glucose did not increase [53.1% vs 58.8%]). Conclusions The number of admissions to NICU of newborns with hypoglycaemia increased considerably during the COVID- 19 pandemic. This rise is likely, at least in part, to reflect missed diagnoses of GDM in pregnancy, resulting in less access to treatment for mothers and delays in identification of newborns at risk for hypoglycaemia. As there exists some overlap among our COVID-19 group as to when changes to maternal screening for GDM were introduced and when OGTT was still in use, we have extended this study and further data collection is underway which may reveal greater differences between our groups.

In comparison to the general patient population, trauma patients show higher level detections of bloodborne infectious diseases, such as Hepatitis and Human Immunodeficiency Virus. In comparison to bloodborne pathogens, the prevalence of respiratory infections such as SARS-CoV-2 and how that relates with other variables, such as drug usage and trauma type, is currently unknown in trauma populations. Here, we evaluated SARS-CoV-2 seropositivity and antibody isotype profile in 2,542 trauma patients from six Level-1 trauma centers between April and October of 2020 during the first wave of the COVID-19 pandemic. We found that the seroprevalence in trauma victims 18-44 years old (9.79%, 95% confidence interval/CI: 8.33 11.47) was much higher in comparison to older patients (45-69 years old: 6.03%, 4.59-5.88; 70+ years old: 4.33%, 2.54 – 7.20). Black/African American (9.54%, 7.77 – 11.65) and Hispanic/Latino patients (14.95%, 11.80 – 18.75) also had higher seroprevalence in comparison, respectively, to White (5.72%, 4.62 7.05) and Non-Latino patients (6.55%, 5.57 – 7.69). More than half (55.54%) of those tested for drug toxicology had at least one drug present in their system. Those that tested positive for narcotics or sedatives had a significant negative correlation with seropositivity, while those on anti-depressants trended positive. These findings represent an important consideration for both the patients and first responders that treat trauma patients facing potential risk of respiratory infectious diseases like SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) reverse-transcription polymerase chain reaction employee testing was implemented across New York University Langone Health. Over 8 weeks, 14 764 employees were tested; 33% of symptomatic employees, 8% of asymptomatic employees reporting COVID-19 exposure, and 3% of employees returning to work were positive. Positivity rates declined over time, possibly reflecting the importance of community transmission and efficacy of personal protective equipment.

© 2019 The Author(s). Background: The purpose of this systematic review was to evaluate the accuracy and reliability of wearable devices for objective gait measurement of Lumbar Spinal Stenosis (LSS) patients, with a focus on relevant gait metrics. Methods: Systematic searches were conducted of five electronic databases to identify studies that assessed gait metrics by wearable or portable technology. Data was collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. Results: Four articles were identified for inclusion in this review. The objectives, methodology and quality of the studies varied. No single gait metric was investigated in all four studies, making comparison difficult. The most relevant metrics reported included gait cycle, gait velocity, step length and cadence, which were reported in two studies. Two studies explored gait symmetry. Differences between LSS patients and normal healthy subjects are demonstrable using wearable technology. Conclusions: The measurements of gait cycle, cadence, step length, gait velocity, and number of steps with wearable devices can be used in the gait measurement of LSS patients for initial assessment, and objective outcomes following interventions. However, data and analysis are limited, and further studies are necessary to comment on reliability.

Puberty is a critical period of development marked by sexual, immune, and neural maturation. Exposure to stress during this period can lead to enduring changes in brain functioning and in behavior; however, the underlying mechanisms and the programming effects of stress during puberty remain unknown. Therefore, the objective of this study was to investigate the programming effects of pubertal immune challenge in response to a homotypic stressor later in life in CD-1 mice. Age and sex differences in the peripheral and central cytokine levels, along with sickness behavior and telemetry data, were analyzed following the secondary treatment. The results showed that pretreatment with LPS attenuated the immune response to a second homotypic challenge. Males pretreated with LPS during puberty and in early adulthood displayed an attenuated hypothermic response following the second LPS treatment compared with saline-pretreated controls, which is consistent with the attenuated peripheral IL-6 and IFN-γ concentrations. Females pretreated with LPS during puberty displayed lower IL-1β, TNF-α, and IL-6 mRNA expression in the prefrontal cortex following the secondary immune challenge compared with saline controls. The results of this study show that exposure to LPS during puberty programs the peripheral and central immune responses, resulting in an attenuated immune response following a subsequent homotypic stressor. Thus, exposure to an immune challenge during puberty affects immune function later in life, which could permanently affect brain function and have implications on mental health.

Summary Guideline 1.1: Compression after thermal ablation or stripping of the saphenous veins. When possible, we suggest compression (elastic stockings or wraps) should be used after surgical or thermal procedures to eliminate varicose veins. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 1.2: Dose of compression after thermal ablation or stripping of the varicose veins. If compression dressings are to be used postprocedurally in patients undergoing ablation or surgical procedures on the saphenous veins, those providing pressures >20 mm Hg together with eccentric pads placed directly over the vein ablated or operated on provide the greatest reduction in postoperative pain. [GRADE - 2; LEVEL OF EVIDENCE - B] Guideline 2.1: Duration of compression therapy after thermal ablation or stripping of the saphenous veins. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after treatment. [BEST PRACTICE] Guideline 3.1: Compression therapy after sclerotherapy. We suggest compression therapy immediately after treatment of superficial veins with sclerotherapy to improve outcomes of sclerotherapy. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 3.2: Duration of compression therapy after sclerotherapy. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after sclerotherapy. [BEST PRACTICE] Guideline 4.1: Compression after superficial vein treatment in patients with a venous leg ulcer. In a patient with a venous leg ulcer, we recommend compression therapy over no compression therapy to increase venous leg ulcer healing rate and to decrease the risk of ulcer recurrence. [GRADE - 1; LEVEL OF EVIDENCE - B] Guideline 4.2: Compression after superficial vein treatment in patients with a mixed arterial and venous leg ulcer. In a patient with a venous leg ulcer and underlying arterial disease, we suggest limiting the use of compression to patients with ankle-brachial index exceeding 0.5 or if absolute ankle pressure is >60 mm Hg. [GRADE - 2; LEVEL OF EVIDENCE - C]

Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, R t, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the R t of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, R t fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.

The second SARS virus, SARS-CoV-2, emerged in December 2019, and within a month was globally distributed. It was first introduced into Scotland in February 2020 associated with returning travellers and visitors. By March it was circulating in communities across the UK, and to control COVID-19 cases, and prevent overwhelming of the National Health Service (NHS), a ‘lockdown’ was introduced on 23rd March 2020 with a restriction of people’s movements. To augment the public health efforts a large-scale genome epidemiology effort (as part of the COVID-19 Genomics UK (COG-UK) consortium) resulted in the sequencing of over 5000 SARS-CoV-2 genomes by 18th August 2020 from Scottish cases, about a quarter of the estimated number of cases at that time. Here we quantify the geographical origins of the first wave introductions into Scotland from abroad and other UK regions, the spread of these SARS-CoV-2 lineages to different regions within Scotland (defined at the level of NHS Health Board) and the effect of lockdown on virus ‘success’. We estimate that approximately 300 introductions seeded lineages in Scotland, with around 25% of these lineages composed of more than five viruses, but by June circulating lineages were reduced to low levels, in line with low numbers of recorded positive cases. Lockdown was, thus, associated with a dramatic reduction in infection numbers and the extinguishing of most virus lineages. Unfortunately since the summer cases have been rising in Scotland in a second wave, with >1000 people testing positive on a daily basis, and hospitalisation of COVID-19 cases on the rise again. Examining the available Scottish genome data from the second wave, and comparing it to the first wave, we find that while some UK lineages have persisted through the summer, the majority of lineages responsible for the second wave are new introductions from outside of Scotland and many from outside of the UK. This indicates that, while lockdown in Scotland is directly linked with the first wave case numbers being brought under control, travel-associated imports (mostly from Europe or other parts of the UK) following the easing of lockdown are responsible for seeding the current epidemic population. This demonstrates that the impact of stringent public health measures can be compromised if following this, movements from regions of high to low prevalence are not minimised.

Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is characterized by the expression of cytotoxic markers and shares clinical features with extranodal NK/T-cell lymphoma and primary cutaneous CD8+ aggressive epidermotropic T-cell lymphoma. γδ-Positive cases with panniculitis-like presentation should be called as PCGD-TCL with panniculitis-like presentation and not as subcutaneous panniculitis-like T-cell lymphoma with γδ expression. Those cases were shown to originate almost exceptionally from TCR-Vδ2 γδ T cells comprising the separate category. PCGD-TCL has a predilection for extremities and frequently ulcerates. Frequently, in clinical practice, the absence of β-F1 expression is considered to be an equivalent of γδ positivity. However, there is a small cohort of “TCR silent” cases with a lack of both markers. Therefore, TCRγ staining is still necessary. The absence of cytotoxic markers characterizes cases of MF with γδ expression. In the recent study, CCR4 expression was found to be useful in differential diagnosis of MF which are CCR4 positive from PCGD-TCL which are CCR4 negative. Clinically and prognostically, γδ-positive MF has no difference with classic counterparts. The cases with EBV+ CD56+ TCRγ+ presents a matter of active debate is that an extranodal NK/T-cell lymphoma with aberrant TCRγ expression or is that a case of EBV+ CD56+ primary cutaneous γδ T-cell lymphoma.

Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.

Background:\ud Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.\ud \ud Methods:\ud We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L (

Alcohol and substance misuse can cause a range of neurobiological disturbances. These may result from acute intoxication, following chronic misuse or drug withdrawal. This chapter will address these disturbances on a drug-by-drug basis. Relevant neurobiological mechanisms of drug action will also be described.

Background Simulation forms an integral part of medical training, but the modality is rarely accessed by nursing staff in our Trust. This abstract describes the development of a simulation course targeted at nurses working in the Nottingham Emergency General Surgery Service to improve confidence in non-technical skills and awareness of human factors on team function. Project Description The course was set up as an extended pilot with the Phase 1 running for 9 months. It ran one morning each month for 6 ward nurses drawn from a spectrum of experience and grades. Each course comprised 3 targeted scenarios and their debriefs using the PEARLS model (Eppich & Cheng, 2015). Scenarios were designed collaboratively by the simulation centre, ward’s clinical educator and ward management team. Themes were generated from clinical practice and clinical incidents. Scenarios were written with 3 key principles to facilitate a positive developmental experience for participants with no simulation experience; Maximize relevance – Scenarios designed around situations seen with regularity on the unit. Dieckmann, Jacobson and Rall (2019, p.287) recommend the potential of learning from successes in regular situations. No cardiac arrests – to decouple the experience from resuscitation training. Simulated patient instead of a manikin to facilitate the nuances of communication Summary of Results Participant free-text responses showed engagement with the simulations. Participants’ post-course mean confidence showed significant improvements in all categories despite high baseline (pre-course) scores. This positive impact of simulation training was most notable in participants improved reported confidence in their; … Clinical knowledge appropriate to their level … Skills and knowledge to assess and treat acutely unwell patients …Skills required for communicating information to the MPT Follow up surveys sent to participants approximately 6 months after the simulation course showed a slight drop off in some confidence ratings but in all but 1 category they remained above pre-training levels and in 3 categories they showed on-going improvements. (See table 1 below); Discussion and Conclusions Phase 1 of the pilot allowed almost the entire ward’s nursing staff to experience simulation based education for the first time. Phase 2 scenarios’ will be designed based on themes drawn from participant evaluations and current educational priorities from the senior ward team. Phase 3 would be to utilize the half day simulation course in other ward areas within the Trust maintaining transferable themes whilst tailoring the scenarios to the specific settings. References Dieckmann, P., Jacobson, R. & Rall, M. ( 2019) Key Issues in Scenario Design for Simulation. In Chiniara, G. (Ed). Clinical simulation:: education, operations and engineering (Second ed.) (pp. 285–313) London: Academic Press. Eppich, W., & Cheng, A. ( 2015). Promoting Excellence and Reflective Learning in Simulation (PEARLS): Development and Rationale for a Blended Approach to Health Care Simulation Debriefing. Simulation in Healthcare: The Journal of the Society for Simulation in Healthcare, 10(2), 106–115. https://doi.org/10.1097/SIH.0000000000000072

Following some methodological remarks the chapter briefly reviews the vocabulary of sickness used in the biblical Hebrew text. It then examines instances of sickness and healing that are described in the Hebrew Bible, in order to establish how sickness is understood and how ritual might therefore relate to it. Aspects considered include the relationship between sickness and sin; whether and how YHWH is involved in causing sickness; epidemics versus individual cases of sickness; and instances of ritual action, broadly understood, that are used to address sickness-related issues. Such instances of ritual action include consulting a functionary such as a priest or prophet, and performing ritual laments and prayers either at home or at a shrine. Two instances of concerns relating to childbearing are also considered, both of which are pictured in the context of ritual action at a shrine.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.

COPD is one of the top 10 causes of death worldwide. Omic technologies represent a “big-data” approach to more accurate describe key features of COPD and inform treatment strategies. Herein we explore metabolomic approaches to study biochemical changes in the sputum of COPD patients and volunteers (n=14) not diagnosed with a respiratory disease (CON). Sputum samples were assessed by high resolution - Direct infusion mass spectroscopy (DI-MS) based in the Q Exactive hybrid quadrupole-Orbitrap was used to assess the sample’s metabolomes. COPD samples were shown to be distinct using PLS-DA from CON and the sources of variation were identified. Five key metabolites allowed the discrimination between COPD and CON samples with an AUC value of 99% (CI 100%- 0.943 %). Three of the key metabolites were monoacylglycerides also stearic acid suggesting considerable changes in fatty processing in COPD. Other metabolites were involved in pathways involved in inflammatory mediation, bronchoconstriction and mucus secretion, known features of COPD. Ongoing working is assessing metabolomic changes at different GOLD stages, examining the impact of comorbidities and smoking status. We expect new insights that could improve the monitoring of COPD and its treatment.

SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China in December 2019 and spread rapidly throughout the world. Understanding the introductions of this new coronavirus in different settings may assist control efforts and the establishment of frameworks to support rapid response in future infectious disease outbreaks.We investigated the first four weeks of emergence of the SARS-CoV-2 virus in Scotland after the first case reported on the 1st March 2020. We obtained full genome sequences from 452 individuals with a laboratory-confirmed diagnosis of COVID-19, representing 20% of all cases until 1st April 2020 (n=2310). This permitted a genomic epidemiology approach to study the introductions and spread of the SARS-2 virus in Scotland.From combined phylogenetic and epidemiological analysis, we estimated at least 113 introductions of SARS-CoV-2 into Scotland during this period. Clusters containing multiple sequences suggestive of onward transmission occurred in 48/86 (56%). 42/86 (51%) clusters had no known international travel history indicating undetected introductions.The majority of viral sequences were most closely related to those circulating in other European countries, including Italy, Austria and Spain. Travel-associated introductions of SARS-CoV-2 into Scotland predated travel restrictions in the UK and other European countries. The first local transmission occurred three days after the first case. A shift from travel-associated to sustained community transmission was apparent after only 11 days. Undetected introductions occurred prior to the first known case of COVID-19. Earlier travel restrictions and quarantine measures might have resulted in fewer introductions into Scotland, thereby reducing the number of cases and the subsequent burden on health services. The high number of introductions and transmission rates were likely to have impacted on national contact tracing efforts. Our results also demonstrate that local real-time genomic epidemiology can be used to monitor transmission clusters and facilitate control efforts to restrict the spread of COVID-19.FundingMRC (MC UU 1201412), UKRI/Wellcome (COG-UK), Wellcome Trust Collaborator Award (206298/Z/17/Z – ARTIC Network; TCW Wellcome Trust Award 204802/Z/16/ZResearch in contextEvidence before this studyCoronavirus disease-2019 (COVID-19) was first diagnosed in Scotland on the 1st of March 2020 following the emergence of the causative severe acute respiratory system coronavirus 2 (SARS-CoV-2) virus in China in December 2019. During the first month of the outbreak in Scotland, 2310 positive cases of COVID-19 were detected, associated with 1832 hospital admissions, 207 intensive care admissions and 126 deaths. The number of introductions into Scotland and the source of those introductions was not known prior to this study.Added value of this studyUsing a combined phylogenetic and epidemiological approach following real-time next generation sequencing of 452 SARS-CoV-2 samples, it was estimated that the virus was introduced to Scotland on at least 113 occasions, mostly from other European countries, including Italy, Austria and Spain. Localised outbreaks occurred in the community across multiple Scottish health boards, within healthcare facilities and an international conference and community transmission was established rapidly, before local and international lockdown measures were introduced.

There are minimal data assessing the accuracy or use of continuous glucose monitoring (CGM) in hospitalized patients. Our group was interested in its use in the perioperative period, since we suspect we would identify more extremes and thus more dangerous blood glucose levels than seen with traditional bedside blood glucose monitoring. Given the lack of data for CGM use in hospitalized patients, and the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we felt this is a critical time to share our data. Use of CGM could potentially reduce the number of health care provider contacts and use of personal protective equipment. Eligible patients were adults (age ≥18 years) with diabetes who used intermittent home blood glucose monitoring and who were scheduled to undergo an elective general surgery at University of Washington Medical Center. The study protocol was approved by the University of Washington Institutional Review Board. The study was also registered as a clinical trial. Continuous intravenous insulin infusion was used per hospital algorithm (target blood glucose 100 mg/dL [5.6 mmol/L] to 180 mg/dL [10.0 mmol/L]) until oral consumption was resumed, at which time subcutaneous insulin was initiated. This …

Puberty is a critical developmental period that is characterized by significant brain development. Exposure to stress during this time can alter brain functioning setting the stage for long-lasting behavioural outcomes. The objective of this study was to investigate age and sex differences in the peripheral and central immune responses, along with sickness behaviour, following immune stress. The results showed that LPS treatment increased serum cytokine levels and sickness symptoms in all mice. Pubertal males displayed increased IL-1β concentrations at 2 h and increased IL-6 concentrations at 8 h post-treatment whereas increased concentrations of TNFα, IL-10, IL-12, IL-1β, IFNγ, and IL-6 persisted at 8 and 24 h in adult females. Consistent with peripheral cytokines, pubertal males displayed greater IL-1β, TNFα, and IL-6 mRNA expression in the prefrontal cortex at 2 h, whereas adult males expressed more of the aforementioned cytokines at 8 h compared to saline controls. Adult males also displayed greater IL-1β mRNA expression compared to their female counterparts, and adult females displayed greater TNFα mRNA expression compared to their male counterparts. These results not only provide a better understanding of the age and sex differences in acute immune response, but also show important region- and time-specific differences in the response to an immune challenge, and that the peripheral immune response differs from the central response. This highlights the need to examine immune markers in both the periphery and the central nervous system for an accurate depiction of acute immune response following an immune challenge.

Background and aims Cannabis withdrawal is thought to be a major contributor to relapse to cannabis use and is now included in the DSM-5. Aerobic exercise relieves withdrawal symptoms from tobacco and other drugs, but has yet to be tested in cannabis users. Methods A prospective, single blind, parallel-group RCT comparing daily aerobic exercise to a control stretching intervention. Setting A seven-day inpatient hospital admission, with follow-up at 28 days’ post-discharge. Participants The study population will be 80 cannabis dependent adults seeking assistance with cannabis withdrawal. Intervention and comparator Participants in the Intervention group will undergo 35 min of aerobic exercise daily, at 60% of their VO2 Max, on an exercise bicycle. The Control group will participate in a structured non-aerobic daily stretching routine for 35 min daily. Both groups receive treatment as usual in the withdrawal management unit of the hospital. Measurements The primary outcome measure is the severity of cannabis withdrawal symptoms assessed daily using the Cannabis Withdrawal Scale and the Marijuana Cravings Questionnaire – pre and post exercise, across the week. Mechanisms by which exercise may affect cannabis withdrawal will be assessed by analysis of endogenous cannabinoids, and plasma and urine cannabinoid levels. Discussion This is the first RCT of aerobic exercise for cannabis dependence that has a valid control group to aid in interpretation of findings. Should the intervention prove effective, it would give empirical support to an inexpensive and accessible treatment approach for drug withdrawal management.

Previous studies have shown brief online self-help interventions to be a useful method of treating cannabis use and related problems; however, no studies have compared the effects of brief versus extended feedback for online brief intervention programs. Objectives The current study was a two arm randomised trial aimed at testing the short term effectiveness of a brief and extended feedback version of Grassessment , a brief online intervention for cannabis users that provides individualised feedback regarding use, motives, and harms. Methods Participants ( n =287) reporting at least one symptom of DSM IV cannabis abuse or dependence were recruited using online and offline advertising methods. Participants were randomised to receive either a brief or extended feedback version of the Grassessment program and were required to complete a one month follow up questionnaire. Results One hundred and ninety four participants completed the one month follow up. Wilcoxon analyses showed a significant decrease in past month quantity and frequency of cannabis use ( ps r =−0.41 and −0.40 respectively) and lower severity of dependence scores ( p =0.002; r =−0.31) among those in the brief feedback condition. Participants in the extended feedback group also demonstrated significant decreases in patterns of use ( ps r =−0.39 and −0.33) but not severity of dependence ( p =0.09; r =0.18). A Generalized Estimating Equation (GEE) analysis showed no significant interaction between length of feedback received and past month cannabis use frequency ( p =0.78), quantity ( p =0.73), or severity of dependence ( p =0.47). Conclusion This study adds support for the use of brief online self-complete interventions to reduce cannabis use and related problems in the short term. The findings suggest that in the case of the brief online screening and feedback program Grassessment , extended feedback does not lead to superior outcomes over brief feedback.

This study investigated the effects of environmental manipulation on female Wistar Kyoto (WKY), an animal model of depression, and female Wistar rats. It explored the function of the hypothalamic-pituitary-adrenal axis (HPA) and immune system, as they have both been implicated in the pathophysiology of depression. A further goal was to characterize the immune cytokine concentrations of female WKY rats as this has, to our knowledge, never been documented. Animals were assigned to enriched, standard, or impoverished housing for four consecutive weeks. Following this, serum was collected at baseline and post-stress periods to measure the concentration of corticosterone, TNF-α, IL-1β, and IL-10. WKY animals had significantly higher corticosterone levels at the post-stress time-point than their Wistar counterparts. WKY females in isolation tended to have the lowest corticosterone levels which may indicate that they prefer a solitary environment, a symptom of depression. We observed a significant decrease in TNF-α after enrichment in the Wistar strain. A similar decrease in TNF-α was found in the WKY strain, but there was no difference between environmental conditions. There was a significant increase in pre- to post-stress IL-10 level in both Wistar and WKY animals. WKY females had a significantly lower level of IL-1β as compared to the Wistar animals at both pre- and post-stress time points. Given this strain difference, it is likely that the WKY rats had a dysregulated HPA axis which further influenced their circulating cytokine levels. Further studies are needed to examine how this pattern of findings plays a role in the pathophysiology of depression.

Background: Venous return from the lower extremities is pumped upwards to the right side of the heart in a process that is facilitated by one-way valves and the venous muscle pump, of which the calf muscle pump is a major contributor1-3. Venous plethysmography can quantitatively assess calf pump function (CPF). The association between the CPF and venous thromboembolism (VTE) has not been investigated. Methods: Venous plethysmography (VP) data (strain gauge or air plethysmography) from the Mayo Clinic Vascular Lab database (1998-2015) of CPF (bilaterally reduced, unilaterally reduced, and bilateral normal) were examined in Olmsted County Residents. The Rochester Epidemiology Project (REP) captures the population of Olmsted County and contains demographic information, medical diagnoses, hospital admissions, and surgical procedures as well as validated VTE events and death. Patients with signs of obstructed outflow in either extremity on the venous plethysmography (a possible sign of acute or chronic deep vein thrombosis) study were excluded. Patients with a history of VTE diagnosed before the physiologic study were also excluded. If more than one measurement of calf muscle pump function was performed, only the first measurement was used. The primary outcome was a composite of any VTE, including proximal and distal deep vein thrombosis (DVT) and pulmonary embolism (PE). Results: 1703 Olmsted County residents had venous plethysmography studies performed. MN research authorization was denied in 64 patients and 107 were excluded for any documented VTE preceding index VP study. 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were studied: 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral reduced CPF (rCPF), and 588 (38.3%) had bilateral rCPF. The mean age was 64.4 (SD 18.4), 68.9% were female, and the mean BMI was 29.5 (SD 6.4). Any VTE occurred in 87 patients (5.7%) after a mean follow up of 10.9 years (range 0-22.0 years). Isolated lower extremity DVT (excluding concurrent PE) occurred in 49 patients and PE+/-DVT occurred in 38 patients. Death occurred in 352 patients (23%). Bilateral rCPF compared to bilateral normal CPF was associated with VTE (p=0.007), DVT only (p=0.02) and death (p0.1 for each comparison). Conclusion: In this population-based study of Olmsted County residents with no prior VTE, rCPF function as measured by venous plethysmography is associated with increased risk for VTE, particularly lower extremity proximal DVT. More research is required to understand what additional measures of venous physiology influence these findings and whether CPF could be used in VTE risk stratification. Disclosures No relevant conflicts of interest to declare.

Background Fatigue is a major problem in rheumatoid arthritis (RA). There is evidence for the clinical effectiveness of cognitive–behavioural therapy (CBT) delivered by clinical psychologists, but few rheumatology units have psychologists. Objectives To compare the clinical effectiveness and cost-effectiveness of a group CBT programme for RA fatigue [named RAFT, i.e. Reducing Arthritis Fatigue by clinical Teams using cognitive–behavioural (CB) approaches], delivered by the rheumatology team in addition to usual care (intervention), with usual care alone (control); and to evaluate tutors’ experiences of the RAFT programme. Design A randomised controlled trial. Central trials unit computerised randomisation in four consecutive cohorts within each of the seven centres. A nested qualitative evaluation was undertaken. Setting Seven hospital rheumatology units in England and Wales. Participants Adults with RA and fatigue severity of ≥ 6 [out of 10, as measured by the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS)] who had no recent changes in major RA medication/glucocorticoids. Interventions RAFT – group CBT programme delivered by rheumatology tutor pairs (nurses/occupational therapists). Usual care – brief discussion of a RA fatigue self-management booklet with the research nurse. Main outcome measures Primary – fatigue impact (as measured by the BRAF-NRS) at 26 weeks. Secondary – fatigue severity/coping (as measured by the BRAF-NRS); broader fatigue impact [as measured by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ)]; self-reported clinical status; quality of life; mood; self-efficacy; and satisfaction. All data were collected at weeks 0, 6, 26, 52, 78 and 104. In addition, fatigue data were collected at weeks 10 and 18. The intention-to-treat analysis conducted was blind to treatment allocation, and adjusted for baseline scores and centre. Cost-effectiveness was explored through the intervention and RA-related health and social care costs, allowing the calculation of quality-adjusted life-years (QALYs) with the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). Tutor and focus group interviews were analysed using inductive thematic analysis. Results A total of 308 out of 333 patients completed 26 weeks (RAFT, n/N = 156/175; control, n/N = 152/158). At 26 weeks, the mean BRAF-NRS impact was reduced for the RAFT programme (–1.36 units; p p p = 0.03, effect size 0.36], and this was sustained over 2 years (–0.49 units, 95% CI –0.83 to –0.14 units; p = 0.01). At 26 weeks, further fatigue differences favoured the RAFT programme (BRAF-MDQ fatigue impact: adjusted mean difference –3.42 units, 95% CI –6.44 to – 0.39 units, p = 0.03; living with fatigue: adjusted mean difference –1.19 units, 95% CI –2.17 to –0.21 units, p = 0.02; and emotional fatigue: adjusted mean difference –0.91 units, 95% CI –1.58 to –0.23 units, p = 0.01), and these fatigue differences were sustained over 2 years. Self-efficacy favoured the RAFT programme at 26 weeks (Rheumatoid Arthritis Self-Efficacy Scale: adjusted mean difference 3.05 units, 95% CI 0.43 to 5.6 units; p = 0.02), as did BRAF-NRS coping over 2 years (adjusted mean difference 0.42 units, 95% CI 0.08 to 0.77 units; p = 0.02). Fatigue severity and other clinical outcomes were not different between trial arms and no harms were reported. Satisfaction with the RAFT programme was high, with 89% of patients scoring ≥ 8 out of 10, compared with 54% of patients in the control arm rating the booklet (p p Limitations Primary outcome data were missing for 25 patients; the EQ-5D-5L might not capture fatigue change; and 30% of the 2-year economic data were missing. Conclusions The RAFT programme improves RA fatigue impact beyond usual care alone; this was sustained for 2 years with high patient satisfaction, enhanced team skills and no harms. The RAFT programme is Future work Given the paucity of RA fatigue interventions, rheumatology teams might investigate the pragmatic implementation of the RAFT programme, which is low cost. Trial registration Current Controlled Trials ISRCTN52709998. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 57. See the NIHR Journals Library website for further project information.

Background Smartphone applications (apps) offer a promising alternative to face-to-face treatment due to their ease of access and convenience. However, there is a lack of evidence-based apps for cannabis users wishing to reduce their use. Objectives The current study evaluated the feasibility and acceptability of a smartphone app intervention (called Assess, Plan, Track, and Tips [APTT]) for cannabis users wanting to reduce their use. Method The current study included 111 cannabis users (68% male, aged 18–50 yrs) who had used cannabis in the past month, were not currently in treatment, and who wanted to reduce/quit their use. Participants were given access to APTT for 1 month. Participants reported on their cannabis use and related problems, confidence in resisting use, severity of dependence, and stage of change at baseline, post-intervention (4 weeks), and at 1-month follow-up. At post-intervention, participants also reported on their usage and satisfaction with the app. Results The current study found that APTT was acceptable, with over 40% of participants using the app over 20 times over the course of a month. Participants showed a reduction in dependence and cannabis related problems over the course of the study. Further, participants’ stage of change at baseline predicted changes in cannabis use. Conclusions/importance These findings support the feasibility and acceptability of APTT as an engaging app for cannabis users wishing to better manage their use and support the need for future RCTs to assess the efficacy of mobile-based interventions for cannabis users. Electronic supplementary material The online version of this article (10.1186/s42238-019-0009-6) contains supplementary material, which is available to authorized users.

ObjectivesTo see if a group course delivered by rheumatology teams using cognitive-behavioural approaches, plus usual care, reduced RA fatigue impact more than usual care alone.MethodsMulticentre, 2-year randomised controlled trial in RA adults (fatigue severity>6/10, no recent major medication changes). RAFT (Reducing Arthritis Fatigue: clinical Teams using CB approaches) comprises seven sessions, codelivered by pairs of trained rheumatology occupational therapists/nurses. Usual care was Arthritis Research UK fatigue booklet. Primary 26-week outcome fatigue impact (Bristol RA Fatigue Effect Numerical Rating Scale, BRAF-NRS 0–10). Intention-to-treat regression analysis adjusted for baseline scores and centre.Results308/333 randomised patients completed 26 week data (156/175 RAFT, 152/158 Control). Mean baseline variables were similar. At 26 weeks, the adjusted difference between arms for fatigue impact change favoured RAFT (BRAF-NRS Effect −0.59, 95% CI –1.11 to -0.06), BRAF Multidimensional Questionnaire (MDQ) Total −3.42 (95% CI –6.44 to -0.39), Living with Fatigue −1.19 (95% CI –2.17 to -0.21), Emotional Fatigue −0.91 (95% CI –1.58 to -0.23); RA Self-Efficacy (RASE, +3.05, 95% CI 0.43 to 5.66) (14 secondary outcomes unchanged). Effects persisted at 2 years: BRAF-NRS Effect −0.49 (95% CI −0.83 to -0.14), BRAF MDQ Total −2.98 (95% CI −5.39 to -0.57), Living with Fatigue −0.93 (95% CI −1.75 to -0.10), Emotional Fatigue −0.90 (95% CI −1.44, to -0.37); BRAF-NRS Coping +0.42 (95% CI 0.08 to 0.77) (relevance of fatigue impact improvement uncertain). RAFT satisfaction: 89% scored > 8/10 vs 54% controls rating usual care booklet (pConclusionMultiple RA fatigue impacts can be improved for 2 years by rheumatology teams delivering a group programme using cognitive behavioural approaches.Trial registration numberISRCTN52709998.

CASE We report the case of a pediatric terrible triad injury of the elbow consisting of an ulnohumeral dislocation, a radial neck fracture, and a coronoid chondral injury, which was diagnosed at 14 days following injury. We describe our surgical technique and provide details of the postoperative course, including the development of a rotational contracture following heterotopic ossification. CONCLUSION We describe a rare and challenging injury that should be recognized early and managed surgically to maintain acceptable elbow function.

We report a case of a 39-year-old male with sciatica who underwent an L5/S1 microdiscectomy with objective physical activity measurements performed preoperatively and continually postoperatively up to 3-month using wireless accelerometer technology linked to the surgical practice; collecting distance travelled, daily step count (DSC) and Gait Velocity (GV). Preoperative, the patient was walking with a GV of 0.97 m/s and a DSC of less than 2,500. After the first month following surgery, the patient had increased mobility, with a GV of 1.58 m/s, and taking an average of over 4,500 steps per day. At day 57 postop, the patient experienced a recurrence of pain with reduction of GV, DSC and walking distance. Magnetic resonance imaging (MRI) was performed and revealed a recurrent disc herniation with further surgery on day 63, with a rapid return of function post 2nd surgery. The use of wireless accelerometers is practical in obtaining objective physical activity measurements before and after lumbar microdiscectomy, and will assist the surgeon and rehabilitation provider to monitor outcomes, complications and assist in clinical decision making.

A Correction to this paper has been published: https://doi.org/10.1038/s41564-021-00869-0 .

Background In every field of medicine, comprehensive education should be delivered at the graduate level. Currently, no single specialty routinely provides a standardized comprehensive curriculum in venous and lymphatic disease. Method The American Board of Venous & Lymphatic Medicine formed a task force, made up of experts from the specialties of dermatology, family practice, interventional radiology, interventional cardiology, phlebology, vascular medicine, and vascular surgery, to develop a consensus document describing the program requirements for fellowship medical education in venous and lymphatic medicine. Result The Program Requirements for Fellowship Education in Venous and Lymphatic Medicine identify the knowledge and skills that physicians must master through the course of fellowship training in venous and lymphatic medicine. They also specify the requirements for venous and lymphatic training programs. The document is based on the Core Content for Training in Venous and Lymphatic Medicine and follows the ACGME format that all subspecialties in the United States use to specify the requirements for training program accreditation. The American Board of Venous & Lymphatic Medicine Board of Directors approved this document in May 2016. Conclusion The pathway to a vein practice is diverse, and there is no standardized format available for physician education and training. The Program Requirements for Fellowship Education in Venous and Lymphatic Medicine establishes educational standards for teaching programs in venous and lymphatic medicine and will facilitate graduation of physicians who have had comprehensive training in the field.

Key Clinical PointsPeripheral Artery Disease Atherosclerotic peripheral artery disease affects more than 200 million persons worldwide, including at least 8.5 million persons in the United States, and is associated with high rates of cardiovascular events and death. Smoking and diabetes are the strongest risk factors. Noninvasive vascular testing provides information on the presence, severity, and location of peripheral artery disease. Exercise testing can uncover mild disease and quantify functional capacity. In the treatment of peripheral artery disease, the main goals are to reduce cardiovascular risk and improve functional capacity. Supervised exercise increases walking distance. Cilostazol can be used as an adjunct to an exercise program. Conventional angiography is typically performed when revascularization is being considered. Computed tomography or magnetic resonance angiography can also be useful in planning for revascularization. Revascularization, endovascular or surgical, is indicated for symp...

The Optimal Health and Wellness Clinic of Morehouse Healthcare seeks to advance health equity by providing lifestyle medicine services to its predominantly African American patient population. Health equity means eliminating health disparities by providing services that meet the needs of the population served. African Americans have a higher burden of cardiovascular disease and diabetes than other American ethnic groups. Recent evidence indicates that eating a plant-based diet may eliminate disparities in cardiovascular disease and diabetes. The clinic provides lifestyle intervention services such as stress and sleep management, but the focus is on helping patients to adopt and maintain a plant-based diet. A range of encounter options that include shared medical appointments and cooking classes are offered. The clinic is an example of a lifestyle medicine specialty practice within the multispecialty practice arm of a medical school. The shared mission to promote health equity provides substantial resources to the clinic and allows for collaborative efforts to improve the health of the community.

Frailty is an age-related, multi-dimensional state of decreased physiologic reserve that results in diminished resiliency and increased vulnerability to stressors. It has proven to be an excellent predictor of unfavorable health outcomes in the older surgical population. There is agreement in recommending that a frailty evaluation should be part of the preoperative assessment in the elderly. However, the consensus is still building with regards to how it should affect perioperative care. The Society for Perioperative Assessment and Quality Improvement (SPAQI) convened experts in the fields of gerontology, anesthesiology and preoperative assessment to outline practical steps for clinicians to assess and address frailty in elderly patients who require elective intermediate or high risk surgery. These recommendations summarize evidence-based principles of measuring and screening for frailty, as well as basic interventions that can help improve patient outcomes.

The inverse relationship between age and dose requirement for potent volatile anesthetics is well established, but the question of whether anesthetic providers consider this relationship in practice remains unanswered. We sought to determine whether there is an association between patient age and the mean dose of volatile anesthetic delivered during maintenance of anesthesia.This was a retrospective cross-sectional study of patients receiving a single potent volatile anesthetic at 2 academic hospitals using data recorded in an anesthesia information management system. Multivariate linear models were constructed at each hospital to examine the relationship between age and mean minimum alveolar concentration (MAC) fraction delivered during the maintenance of anesthesia.A total of 7878 cases at the 2 hospitals were included for analysis. For patients aged65 years, we observed decreasing doses of volatile anesthetics as age increased. Per decade, mean delivered MAC fraction decreased by an estimated 1.8% (95% confidence interval, 1.5-2.2, P0.0001), smaller than the 6.7% decrease suggested by previous studies of human anesthetic requirements. At age65 years, the magnitude of the inverse association between age and MAC fraction was higher (3.8% decrease per decade; 95% confidence interval, 2.9-4.7).Increasing age is associated with decreased absolute doses of potent volatile anesthetics, an association that seems to strengthen as patients enter the geriatric age range. The observed decreases in absolute anesthetic dose were less than those predicted by previous research and therefore represent an overall increase in "age-adjusted dose" as patients grow older.

Creation of the American Society of Anesthesiologists Committee on Geriatric Anesthesia provided an opportunity for individuals to interact, strategize, and work with medical organizations outside of anesthesiology. These opportunities expanded with creation of the Society for the Advancement of Geriatric Anesthesia. The American Geriatrics Society provided a major boost when they realized it was important for surgical and related specialties to take an active role in the care of older patients. From this have come educational grants to improve residency training and establishment of a major research grant program now managed by the National Institutes of Health. Nevertheless, for improved care of the older patient, the level of involvement has to increase.