Strategic placement of automated external defibrillators (AEDs) for cardiac arrests in public locations and private residences.

Aim: The aim of our study was to determine whether businesses can be identified that rank highly for their potential to improve coverage of out-of-hospital cardiac arrests (OHCAs) by automated external defibrillators (AEDs), both in public locations and private residences. Methods: The cohort comprised 10,422 non-traumatic OHCAs from 2014 to 2020 in Perth, Western Australia. We ranked 115 business brands (across 5,006 facilities) for their potential to supplement coverage by the 3,068 registered public-access AEDs in Perth, while accounting for AED access hours. Results: Registered public-access AEDs provided 100 m coverage of 23% of public-location arrests, and 4% of arrests in private residences. Of the 10 business brands ranked highest for increasing the coverage of public OHCAs, six brands were ranked in the top 10 for increased coverage of OHCAs in private residences. A public phone brand stood out clearly as the highest-ranked of all brands, with more than double the coverage-increase of the second-ranked brand. If all 115 business brands hosted AEDs with 24-7 access, 57% of OHCAs would remain without 100 m coverage for public arrests, and 92% without 100 m coverage for arrests in private residences. Conclusion: Many businesses that ranked highly for increased coverage of arrests in public locations also rank well for increasing coverage of arrests in private residences. However, even if the business landscape was highly saturated with AEDs, large gaps in coverage of OHCAs would remain, highlighting the importance of considering other modes of AED delivery in metropolitan landscapes.

Electronic prescribing systems as tools to improve patient care: a learning health systems approach to increase guideline concordant prescribing for venous thromboembolism prevention.

BACKGROUND: Venous thromboembolism (VTE) causes significant mortality and morbidity in hospitalised patients. Risk factors for VTE are well known and there are validated risk assessment tools to support the use of prophylactic therapies. In England, reporting the percentage of patients with a completed VTE risk assessment is mandated, but this does not include whether that risk assessment resulted in appropriate prescribing. Full guideline compliance, defined as an assessment which led to an appropriate action-here prescribing prophylactic low molecular weight heparin where indicated, is rarely reported. Education, audit and feedback enhance guideline compliance but electronic prescribing systems (EPS) can mandate guideline-compliant actions. We hypothesised that a systems-based EPS intervention (prescribing rules which mandate approval or rejection of a proposed prescription of prophylactic low molecular weight heparin based on the mandated VTE assessment) would increase full VTE guideline compliance more than interventions which focused on targeting individual prescribers. METHODS: All admitted patients within University Hospitals Birmingham NHS Foundation Trust were included for analysis between 2011 and 2020. The proportion of patients who received a fully compliant risk assessment and action was assessed over time. Interventions included teaching sessions and face-to-face feedback based on measured performance (an approach targeting individual prescribers) and mandatory risk assessment and prescribing rules into an EPS (a systems approach). RESULTS: Data from all 235,005 admissions and all 5503 prescribers were included in the analysis. Risk assessments were completed in > 90-95% of all patients at all times, but full guideline compliance was lower (70% at the start of this study). Face-to-face feedback improved full VTE guideline compliance from 70 to 77% (p ≤ 0.001). Changes to the EPS to mandate assessment with prescribing rules increased full VTE compliance to 95% (p ≤ 0.001). Further amendments to the EPS system to reduce erroneous VTE assessments slightly reduced full compliance to 92% (p < 0.001), but this was then maintained including during changes to the low molecular weight heparin used for VTE prophylaxis. DISCUSSION: An EPS-systems approach was more effective in improving sustained guideline-compliant VTE prevention over time. Non-compliance remained at 8-5% despite this mandated system. Further research is needed to assess the potential reasons for this.

Is the Management of Rectal Cancer Using a Watch and Wait Approach Feasible, Safe and Effective in a Publicly Funded General Hospital?

AIMS: Although there is emerging evidence to suggest equivalent oncological outcomes using a watch and wait approach compared with primary total mesorectal excision surgery, there is a paucity of evidence about the safety and efficacy of this approach in routine clinical practice. Here we report the long-term outcomes and quality of life from patients managed with watch and wait following a clinical complete response (cCR) to neoadjuvant therapy. MATERIALS AND METHODS: Patients with adenocarcinoma of the rectum with cCR following neoadjuvant therapy managed using watch and wait were retrospectively identified. Demographic data, performance status, pretreatment staging information, oncological and surgical outcomes were obtained from routinely collected clinical data. Quality of life was measured by trained clinicians during telephone interviews. RESULTS: Over a 7-year period, 506 patients were treated for rectal cancer, 276 had neoadjuvant therapy and 72 had a cCR (26.1%). Sixty-three were managed with watch and wait. Thirteen patients had mucosal regrowth. There was no significant difference in the incidence of metastatic disease between the surgical and watch and wait cohorts (P = 0.38). The 13 patients with mucosal regrowth underwent salvage surgery. Eleven of the patients who underwent surgical resection had R0 resections. There was also a statistically and clinically significant improvement in the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) trial outcome index (P = 0.022). CONCLUSION: This study shows that watch and wait is safe and effective outside of tertiary referral centres. It suggests that an opportunistic cCR is durable and when mucosal regrowth occurs it can be salvaged. Finally, we have shown that quality of life is probably improved if a watch and wait approach is adopted.

Critical limb ischaemia in the time of COVID-19: establishing ambulatory service provision.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic enforced changes to healthcare services at a pace and extent not seen previously in the NHS. The Royal Devon and Exeter provides regional vascular surgery services. A consultant-led urgent 'hot clinic' was established, providing patients with ambulatory care. We aim to describe the service for critical limb ischaemia (CLI) before and during the COVID-19 pandemic, and evaluate this against recommended best practice. METHODS: Retrospective review of electronic databases and records of patients with CLI during a non-COVID vs COVID-19 period. Primary outcome measures were those established by guidance from the Vascular Society of Great Britain and Ireland. RESULTS: Non-COVID vs COVID-19: total patients n=97 vs 96, of which CLI patients n=29 vs 21. Median length of stay 15 vs 0 days (p<0.001); median time from referral to specialist review 0 vs 3 days (p<0.001); multidisciplinary team meeting (MDT) recorded 3% vs 29%; median time to intervention 6 vs 8 days; conservative management 52% vs 67%; endovascular 28% vs 10%; open surgery 21% vs 24%; 30-day survival 79% vs 76%. CONCLUSION: COVID-19 imposed a major change to the service for patients with CLI with a focus on ambulatory care pathways for diagnosis and intervention. We observe a significant reduction in overall length of stay with no clinically significant change in time to consultant review, time to imaging, overall management strategy or outcomes. The results of this study show that patients with CLI can be managed safely and effectively on an ambulatory basis in accordance with established best practice.

The changing characteristics of COVID-19 presentations. A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave.

BACKGROUND: This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus. METHODS: All patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days. RESULTS: Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions. CONCLUSION: Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.

The longitudinal relationship between child emotional disorder and parental mental health in the British Child and Adolescent Mental Health surveys 1999 and 2004.

BACKGROUND: Research suggests parental psychopathology has an adverse effect on child mental health. However, due to the interactional nature of parent-child relationships and with a high rate of emotional disorders reported in school-age children, it is important to know whether the effect is reciprocal. METHODS: We explored the longitudinal relationship between child and parent mental health in the British Child and Adolescent Mental Health Surveys (N=7,100 child-parent dyads) and their three-year follow-ups. The Development and Well-Being Assessment with DSM-IV diagnostic criteria was used to measure child psychiatric diagnoses, while parental mental health was assessed using the General Health Questionnaire. Multivariable logistic regression was used to explore the longitudinal association between child emotional disorder and parent mental health. RESULTS: Parents of children who had an emotional disorder at baseline were more likely to have poor mental health three years later compared with parents whose children had no psychiatric diagnosis (33.3% versus 16.7%; crude odds ratio=2.52; adjusted odds ratio=2.19, 95% CI=1.58 to 3.05, p<0.001). Children of parents with poor mental health at baseline were more likely to develop an emotional disorder three years later compared with children whose parents had good mental health (5.2% versus 2.5%; crude odds ratio=2.08; adjusted odds ratio=1.63, 95% CI=1.18 to 2.25, p=0.003). LIMITATIONS: The findings of this research are limited by the survey data collected, the measures used and survey dropout. CONCLUSIONS: We detected a bi-directional relationship between child and parent mental health, suggesting that effective intervention for one individual may benefit other family members.

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial.

BACKGROUND: Baricitinib is an oral, selective, reversible Janus kinase 1/2 inhibitor approved in the European Union and Japan and under investigation in the United States for treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the impact of baricitinib plus background topical corticosteroids (TCS) on health-related quality of life (HRQoL), how AD symptoms impact work productivity and life functioning, and treatment benefit using patient-reported outcome (PRO) assessments in patients with moderate-to-severe AD previously experiencing inadequate response to TCS. METHODS: Adult patients with AD in BREEZE-AD7, a Phase 3, multicentre, double-blind trial, were randomised 1 : 1 : 1 to daily oral placebo (control) or baricitinib 4- or 2-mg plus TCS. PROs reported Week 1 through Week 16: Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-AD (WPAI-AD); Patient-Reported Outcomes Measurement Information System (PROMIS) Itch and Sleep measures, and Patient Benefit Index (PBI). Data were analysed using logistic regression (categorical) and mixed model repeated measures (continuous). PBI scores were analysed using analysis of variance. RESULTS: A total of 329 patients were randomised. Treatment with baricitinib 4-mg (N = 111) or 2 mg (N = 109) plus TCS led to rapid, statistically significant improvements [vs. TCS plus placebo (N = 109)] in DLQI ≥4-point improvement starting at Week 2 (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05), change from baseline in WPAI-AD presenteeism at Week 1 (4-mg plus TCS, P ≤ 0.01; 2-mg plus TCS P ≤ 0.05) and PROMIS itch interference at Week 2 (4-mg plus TCS P ≤ 0.01). Improvements were sustained through Week 16 for baricitinib 4-mg. Statistically significant improvements were observed at Week 16 for PBI global score (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05). CONCLUSIONS: Baricitinib plus TCS vs. placebo plus TCS showed significant improvements in treatment benefit at Week 16 and rapid significant improvements in HRQoL and impact of AD symptoms on work productivity and functioning through 16 weeks.

Applying a COVID Virtual Ward model, assessing patient outcomes and staff workload.

A COVID virtual ward (CVW) is recommended by NHS England, but 'usual care' outcomes have not been reported. A retrospective study of all adults with COVID-19 attending Queen Elizabeth Hospital Birmingham between 01/06/2020-31/01/2021, assessed against CVW criteria and followed for 28 days. Of 2301 COVID-19 patients, 571(25%) would have met CVW criteria. Of these, 325(57%) were discharged after review and 246(43%) admitted. Of admitted patients who met CVW criteria, 81% required hospital-supported therapies; 11% died. Of the 325 discharged, 13% re-presented, 9% with COVID-related symptoms, 2% required intensive care admission, and one died (0.3%). In this comparison, discharging patients without a CVW did not lead to more re-presentations, re-admissions, ITU escalations or deaths compared to published outcomes for hospitals with a CVW.

Associations between interpregnancy interval and preterm birth by previous preterm birth status in four high-income countries: a cohort study.

OBJECTIVE: To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term. DESIGN: Cohort study. SETTING: USA (California), Australia, Finland, Norway (1980-2017). POPULATION: Women who gave birth to first and second (n = 3 213 855) singleton livebirths. METHODS: Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random effects meta-analysis. OUTCOME MEASURE: PTB (gestational age <37 weeks). RESULTS: Absolute risk of PTB for each IPI was 3-6% after a previous term birth and 17-22% after previous PTB. ORs for PTB differed between previous term and preterm births in all countries (P-for-interaction ≤ 0.001). For women with a previous term birth, pooled ORs were increased for IPI <6 months (OR 1.50, 95% CI 1.43-1.58); 6-11 months (OR 1.10, 95% CI 1.04-1.16); 24-59 months (OR 1.16, 95% CI 1.13-1.18); and ≥ 60 months (OR 1.72, 95%CI 1.60-1.86), compared with 18-23 months. For previous PTB, ORs were increased for <6 months (OR 1.30, 95% CI 1.18-1.42) and ≥60 months (OR 1.29, 95% CI 1.17-1.42), but were less than ORs among women with a previous term birth (P < 0.05). CONCLUSIONS: Associations between IPI and PTB are modified by whether or not the previous pregnancy was preterm. ORs for short and long IPIs were higher among women with a previous term birth than a previous PTB, which for short IPI is consistent with the maternal depletion hypothesis. Given the high risk of recurrence and assuming a causal association between IPI and PTB, IPI remains a potentially modifiable risk factor for women with previous PTB. TWEETABLE ABSTRACT: Short versus long interpregnancy intervals associated with higher ORs for preterm birth (PTB) after a previous PTB.

The bone attachments of the medial collateral and posterior oblique ligaments are defined anatomically and radiographically.

PURPOSE: To define the bony attachments of the medial ligaments relative to anatomical and radiographic bony landmarks, providing information for medial collateral ligament (MCL) surgery. METHOD: The femoral and tibial attachments of the superficial MCL (sMCL), deep MCL (dMCL) and posterior oblique ligament (POL), plus the medial epicondyle (ME) were defined by radiopaque staples in 22 knees. These were measured radiographically and optically; the precision was calculated and data normalised to the sizes of the condyles. Femoral locations were referenced to the ME and to Blumensaat's line and the posterior cortex. RESULTS: The femoral sMCL attachment enveloped the ME, centred 1 mm proximal to it, at 37 ± 2 mm (normalised at 53 ± 2%) posterior to the most-anterior condyle border. The femoral dMCL attachment was 6 mm (8%) distal and 5 mm (7%) posterior to the ME. The femoral POL attachment was 4 mm (5%) proximal and 11 mm (15%) posterior to the ME. The tibial sMCL attachment spread from 42 to 71 mm (81-137% of A-P plateau width) below the tibial plateau. The dMCL fanned out anterodistally to a wide tibial attachment 8 mm below the plateau and between 17 and 39 mm (33-76%) A-P. The POL attached 5 mm below the plateau, posterior to the dMCL. The 95% CI intra-observer was ± 0.6 mm, inter-observer ± 1.3 mm for digitisation. The inter-observer ICC for radiographs was 0.922. CONCLUSION: The bone attachments of the medial knee ligaments are located in relation to knee dimensions and osseous landmarks. These data facilitate repairs and reconstructions that can restore physiological laxity and stability patterns across the arc of knee flexion.

Microarray analysis of primary epithelial and fibroblast cells in chronic rhinosinusitis without nasal polyps.

BACKGROUND: Chronic rhinosinusitis is an inflammatory condition with an as yet unknown pathophysiology. We aimed to detect clusters of differentially regulated genes in the epithelial and fibroblast cells of patients with Chronic Rhinosinusitis without nasal polyposis (CRSsNP) and healthy controls. METHODOLOGY: Carefully phenotyped CRSsNP and healthy control participants were recruited. Primary cultures of isolated epithelial and fibroblast cells were established. Whole transcriptome analysis of the cells was performed using microarrays and replicated with quantitative RT-PCR and immunohistochemistry. RESULTS: Fibroblast cells from CRSsNP patients showed a significant upregulation (more than 2x) of the transcription factor NFE2L3 when compared to healthy controls by microarray with multiple hypothesis testing correction, qRT-PCR and immunohistochemistry. CONCLUSIONS: Here we have utilized microarray analysis to search for differentially expressed genes in isolated patient derived epithelial and fibroblast cells. The transcription factor NFE2L3 has been shown to be upregulated in fibroblast cells consistent with increasing evidence that fibroblasts play a key role in tissue specific inflammation within the paranasal sinuses.

The medial ligaments and the ACL restrain anteromedial laxity of the knee.

PURPOSE: The purpose of this study was to determine the contribution of each of the ACL and medial ligament structures in resisting anteromedial rotatory instability (AMRI) loads applied in vitro. METHODS: Twelve knees were tested using a robotic system. It imposed loads simulating clinical laxity tests at 0° to 90° flexion: ±90 N anterior-posterior force, ±8 Nm varus-valgus moment, and ±5 Nm internal-external rotation, and the tibial displacements were measured in the intact knee. The ACL and individual medial structures-retinaculum, superficial and deep medial collateral ligament (sMCL and dMCL), and posteromedial capsule with oblique ligament (POL + PMC)-were sectioned sequentially. The tibial displacements were reapplied after each cut and the reduced loads required allowed the contribution of each structure to be calculated. RESULTS: For anterior translation, the ACL was the primary restraint, resisting 63-77% of the drawer force across 0° to 90°, the sMCL contributing 4-7%. For posterior translation, the POL + PMC contributed 10% of the restraint in extension; other structures were not significant. For valgus load, the sMCL was the primary restraint (40-54%) across 0° to 90°, the dMCL 12%, and POL + PMC 16% in extension. For external rotation, the dMCL resisted 23-13% across 0° to 90°, the sMCL 13-22%, and the ACL 6-9%. CONCLUSION: The dMCL is the largest medial restraint to tibial external rotation in extension. Therefore, following a combined ACL + MCL injury, AMRI may persist if there is inadequate healing of both the sMCL and dMCL, and MCL deficiency increases the risk of ACL graft failure.

Understanding student radiographer attrition: Risk factors and strategies.

INTRODUCTION: Diagnostic student radiographer attrition is reported at 14%, 6% higher than the average for higher education, however, little research has been undertaken on this subject. This study explored risk factors for attrition and strategies that enabled these to be overcome. METHODS: A two-phase study was undertaken. Phase one: data for 579 former student diagnostic radiographers (468 completers and 111 non-completers) from 3 English universities were analysed. Logistic regression was used to estimate odds ratios and 95% confidence intervals for completion based on individual characteristics. Phase two: content analysis of data from an online survey of 186 current UK student diagnostic radiographers exploring their experiences was undertaken. RESULTS: Phase one: Attrition was 19%. Increased age, non A-level entry qualifications and poor academic performance were predictors of attrition (p < 0.005). Phase two: Challenges reported by groups identified as 'at risk' showed that for mature students and those with non-traditional entry qualifications, external responsibilities/pressures and financial pressures were likely to be the greatest cause of attrition and for younger students with traditional qualifications, academic difficulty and excessive workload were most significant. Scientific learning and academic writing were identified as the most common academic difficulties by all groups. Poor mental health may also be a risk factor. CONCLUSION: Although characteristics were identified that increased the chance of attrition, the study concluded that attrition is most likely to be multi-factorial. Academic and personal support were identified as key in students continuing their studies when they considered leaving. Clinical placement experience is likely to influence continuation decisions. IMPLICATIONS FOR PRACTICE: Transparency around course expectations and academic requirements together with ensuring high quality clinical placements may assist in reducing attrition.

Functional symptoms in dermatology: Part 2.

Functional disorders within dermatology present as various constellations of skin symptoms, but without evidence of organic pathology. Examples can include mucocutaneous pain syndromes, functional pruritus, somatoform pain disorder and rarer entities, such as undifferentiated somatoform idiopathic anaphylaxis and multiple chemical sensitivity syndrome. These conditions can have a significant impact on a patient's quality of life, and can present challenges in communication, investigation and management. The aetiology of functional disorders is not fully understood, but with an effective collaborative approach, a psychological explanation for these symptoms is often found. A structured approach to assessment can lead to a confident diagnosis, and understanding a patient's belief system and the impact of symptoms on their functioning can give better grounding for successful management. Treatment is dependent on the level of the patient's engagement with healthcare professionals, and often takes a measured and rehabilitative approach. Psychological therapies have been shown to be effective, often alongside both psychopharmacological and topical medications.

Functional symptoms in dermatology: Part 1.

Functional - or somatoform - symptoms are those that arise with no proven organic pathology. Also known as 'medically unexplained' symptoms, they can present in any medical speciality, including dermatology. Mucocutaneous pain syndromes and functional pruritus are two examples of functional disorders encountered by dermatologists. Patients presenting with somatoform symptoms have paradoxically complex and often subjectively severe symptomatology, yet minimal abnormalities on clinical examination or investigation. Such disparity can be frustrating and distressing for patients and clinicians alike, and there are many pitfalls regarding overinvestigation and misleading communication. However, with an honest and open approach - sometimes requiring collaboration with psychological services - management of functional symptoms can be effective, and patients can be successfully rehabilitated.

Host-pathogen biotic interactions shaped vitamin K metabolism in Archaeplastida.

Menaquinone (vitamin K2) shuttles electrons between membrane-bound respiratory complexes under microaerophilic conditions. In photosynthetic eukaryotes and cyanobacteria, phylloquinone (vitamin K1) participates in photosystem I function. Here we elucidate the evolutionary history of vitamin K metabolism in algae and plants. We show that Chlamydiales intracellular pathogens made major genetic contributions to the synthesis of the naphthoyl ring core and the isoprenoid side-chain of these quinones. Production of the core in extremophilic red algae is under control of a menaquinone (Men) gene cluster consisting of 7 genes that putatively originated via lateral gene transfer (LGT) from a chlamydial donor to the plastid genome. In other green and red algae, functionally related nuclear genes also originated via LGT from a non-cyanobacterial, albeit unidentified source. In addition, we show that 3-4 of the 9 required steps for synthesis of the isoprenoid side chains are under control of genes of chlamydial origin. These results are discussed in the light of the hypoxic response experienced by the cyanobacterial endosymbiont when it gained access to the eukaryotic cytosol.

SOCIETY FOR ENDOCRINOLOGY CLINICAL GUIDANCE: Inpatient management of cranial diabetes insipidus.

Cranial diabetes insipidus (CDI) is a treatable chronic condition that can potentially develop into a life-threatening medical emergency. CDI is due to the relative or absolute lack of the posterior pituitary hormone vasopressin (AVP), also known as anti-diuretic hormone. AVP deficiency results in uncontrolled diuresis. Complete deficiency can lead to polyuria exceeding 10 L/24 h. Given a functioning thirst mechanism and free access to water, patients with CDI can normally maintain adequate fluid balance through increased drinking. Desmopressin (DDAVP, a synthetic AVP analogue) reduces uncontrolled water excretion in CDI and is commonly used in treatment. Critically, loss of thirst perception (through primary pathology or reduced consciousness) or limited access to water (through non-availability, disability or inter-current illness) in a patient with CDI can lead to life-threatening dehydration. This position can be further exacerbated through the omission of DDAVP. Recent data have highlighted serious adverse events (including deaths) in patients with CDI. These adverse outcomes and deaths have occurred through a combination of lack of knowledge and treatment failures by health professionals. Here, with our guideline, we recommend treatment pathways for patients with known CDI admitted to hospital. Following these guidelines is essential for the safe management of patients with CDI.