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Background: The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort., Methods: All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes., Results: Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%)., Conclusions: Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality.

Purpose: Short and long sleep durations have adverse effects on physical and mental health. However, most studies are based on self-reported sleep duration and health status. Therefore, this longitudinal study aims to investigate objectively measured sleep duration and subsequent primary health care records in older adults to investigate the impact of sleep duration and fragmentation on physical and mental health., Methods: Data on objective sleep duration were measured using accelerometry. Primary care health records were then obtained from the UK Biobank (n=84,404). Participants (mean age, 62.4 years) were divided into five groups according to their sleep duration derived from the accelerometry data: <5 hours, 5-6 hours, 6-7 hours, 7-8 hours and >8 hours. ICD-10 codes were used for the analysis of primary care data. Wake after sleep onset, activity level during the least active 5 hours and episodes of movement during sleep were analysed as an indication for sleep fragmentation. Binary regression models were adjusted for age, gender and Townsend deprivation score., Results: A "U-shaped" relationship was found between sleep duration and diseases including diabetes, hypertension and heart disease and depression. Short and long sleep durations and fragmented sleep were associated with increased odds of disease., Conclusion: Six to eight hours of sleep, as well as less fragmented sleep, predicted better long-term metabolic and mental health., Competing Interests: This work is supported by UK Research and Innovation/Biotechnology and Biological Sciences Research Council (UKRI/BBSRC, BB/P504397/1, awarded to Mark Birch-Machin as principal investigator) in collaboration with Unilever. Dr David A Gunn is an employee of Unilever during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2021 Zhu et al.)

Venous thromboembolism (VTE) remains an important consideration within surgery, with recent evidence looking to refine clinical guidance. This review provides a contemporary update of existing clinical evidence for antithrombotic regimens for surgical patients, providing future directions for prophylaxis regimens and research. For moderate to high VTE risk patients, existing evidence supports the use of heparins for prophylaxis. Direct oral anticoagulants (DOACs) have been validated within orthopaedic surgery, although there remain few completed randomised controlled trials in other surgical specialties. Recent trials have also cast doubt on the efficacy of mechanical prophylaxis, especially when adjuvant to pharmacological prophylaxis. Despite the ongoing uncertainty in higher VTE risk patients, there remains a lack of evidence for mechanical prophylaxis in low VTE risk patients, with a recent systematic search failing to identify high-quality evidence. Future research on rigorously developed and validated risk assessment models will allow the better stratification of patients for clinical and academic use. Mechanical prophylaxis' role in modern practice remains uncertain, requiring high-quality trials to investigate select populations in which it may hold benefit and to explore whether intermittent pneumatic compression is more effective. The validation of DOACs and aspirin in wider specialties may permit pharmacological thromboprophylactic regimens that are easier to administer.

Objective: To encompass the needs of all stakeholders and allow effective data synthesis from trials, registries, and other studies; a core outcome set for infrarenal abdominal aortic aneurysm (AAA) repair is needed. In this first stage, the aim was to report the range, frequency, and time of pre-specified outcomes reported following AAA repair., Data Sources: Medline, Embase, and CENTRAL databases 2010 - 2019 were searched using ProQuest Dialog™., Review Methods: The systematic review was reported to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), PROSPERO registration CRD42019130119. Outcomes were coded using Core Outcome Measures in Effectiveness Trials (COMET) taxonomy and presented separately for intact and rupture repairs, endovascular aneurysm repair (EVAR) and open repair, and time from repair (acute < 90 days vs. ≥ 1 year) (COMET Initiative 1582)., Results: For intact AAA and rupture repair, a total of 231 and 70 reports with 589 255 and 177 465 patients respectively were included: only 98 and 19 respectively provided ≥ 1 year outcomes. Most studies were retrospective, with 13 randomised trials of intact AAA repair and five randomised trials of ruptured AAA repair. For intact AAA, the most common pre-specified COMET taxonomy outcomes were mortality (181), vascular complications (137), and re-intervention (52). EVAR studies dominated the vascular outcomes in acute and later time periods: excluding 47 reports from device registries, reduced vascular outcomes to 83. For ruptured AAA, the three most common outcomes were mortality (64), vascular (11), and hospital stay (10). The range of outcomes reported was wide with functioning outcomes reported from most randomised trials but few retrospective studies., Conclusion: This review identifies the paucity of long term data and the disproportionate attention paid to vascular complications vs. patient functioning outcomes, this skew being accentuated by reporting from EVAR device registries. These data will inform focus groups, prior to a pan-European Delphi consensus, involving clinicians, patients, carers and providers, for developing core outcomes for repair of intact and ruptured AAA., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: COVID-19 was declared a worldwide pandemic on 11 March 2020. Imperial College Healthcare NHS Trust provides 1412 inpatient beds staffed by 1200 junior doctors and faced a large burden of COVID-19 admissions., Local Problem: A survey of doctors revealed only 20% felt confident that they would know to whom they could raise concerns and that most were getting information from a combination of informal work discussions, trust emails, social media and medical literature., Methods: This quality improvement project was undertaken aligning with Standards for Quality Improvement Reporting Excellence 2.0 guidelines. Through an iterative process, a digital network (Imperial Covid cOmmunications Network; ICON) using existing smartphone technologies was developed. Concerns were collated from the junior body and conveyed to the leadership team (vertical-bottom-up using Google Form) and responses were conveyed from leadership to the junior body (vertical-top-down using WhatsApp and Zoom). Quantitative analysis on engagement with the network (members of the group and number of issues raised) and qualitative assessment (thematic analysis on issues) were undertaken., Results: Membership of the ICON WhatsApp group peaked at 780 on 17 May 2020. 197 concerns were recorded via the Google Form system between 20 March and 14 June 2020. There were five overarching themes: organisational and logistics; clinical strategy concerns; staff safety and well-being; clinical (COVID-19) and patient care; and facilities. 94.4% of members agreed ICON was helpful in receiving updates and 88.9% agreed ICON improved collaboration., Conclusions: This work demonstrates that a coordinated network using existing smartphone technologies and a novel communications structure can improve collaboration between senior leadership and junior doctors. Such a network could play an important role during times of pressure in a healthcare system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The incidence of flap failure is significantly higher in the lower extremity compared to free tissue transfer in the head, neck and breast. The most common cause of flap failure is venous thrombosis. The aim of this study was to assess the reliability of venous thromboembolism (VTE) risk assessment tools in this high-risk cohort and to assess the ability of such tools to identify patients at risk of developing microvascular venous thrombosis and venous thromboembolism following lower extremity free flap reconstruction., Methods: A single centre retrospective cohort study was conducted between August 2012-August 2019. Adult patients who had undergone free tissue transfer following open lower extremity fractures were eligible for inclusion. All patients were retrospectively risk assessed using the Department of Health (DoH), Modified Caprini and Padua VTE risk assessment tools., Results: Fifty-eight patients were included; all were at high risk of DVT according to the DoH (mean score ± SD, 3.7 ± 0.93), Caprini (10.2 ± 1.64) and Padua (5.4 ± 0.86) risk assessment tools. All patients received appropriate thromboprophylaxis; the incidence of symptomatic hospital acquired VTE was 3.5%. Micro-anastomotic venous thrombosis occurred in 4 patients resulting in one amputation. Partial flap necrosis occurred in 7 patients. There were no significant differences in scaled Caprini (median score, 10 vs 9, z  = 1.289, p  = 0.09), DoH (3 vs 3, z  = 0.344, p  = 0.36), and Padua (5 vs 5.5, z = -0.944, p  = 0.17) scores between those with and without microvascular venous thrombosis., Conclusion: This data suggests that current VTE risk assessment tools do not predict risk of microvascular venous thrombosis following lower extremity reconstruction. Further prospective studies are required to optimise risk prediction models and thromboprophylaxis use in this cohort., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.)

Background: Sustained fuel excess triggers low-grade inflammation that can drive mitochondrial dysfunction, a pivotal defect in the pathogenesis of insulin resistance in skeletal muscle., Objectives: This study aimed to investigate whether inflammation in skeletal muscle can be prevented by EPA, and if this is associated with an improvement in mitochondrial fusion, membrane potential, and insulin signaling., Methods: Human primary myotubes were treated for 24 h with palmitic acid (PA, 500 μM) under hyperglycemic conditions (13 mM glucose), which represents nutrient overload, and in the presence or absence of EPA (100 μM). After the treatments, the expression of peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A) and IL6 was assessed by q-PCR. Western blot was used to measure the abundance of the inhibitor of NF-κB (IKBA), mitofusin-2 (MFN2), mitochondrial electron transport chain complex proteins, and insulin-dependent AKT (Ser473) and AKT substrate 160 (AS 160; Thr642) phosphorylation. Mitochondrial dynamics and membrane potential were evaluated using immunocytochemistry and the JC-1 (tetraethylbenzimidazolylcarbocyanine iodide) dye, respectively. Data were analyzed using 1-factor ANOVA followed by Tukey post hoc test., Results: Nutrient excess activated the proinflammatory NFκB signaling marked by a decrease in IKBA (40%; P < 0.05) and the upregulation of IL6 mRNA (12-fold; P < 0.001). It also promoted mitochondrial fragmentation (53%; P < 0.001). All these effects were counteracted by EPA. Furthermore, nutrient overload-induced drop in mitochondrial membrane potential (6%; P < 0.05) was prevented by EPA. Finally, EPA inhibited fuel surplus-induced impairment in insulin-mediated phosphorylation of AKT (235%; P < 0.01) and AS160 (49%; P < 0.05)., Conclusions: EPA inhibited NFκB signaling, which was associated with an attenuation of the deleterious effects of PA and hyperglycemia on both mitochondrial health and insulin signaling in human primary myotubes. Thus, EPA might preserve skeletal muscle metabolic health during sustained fuel excess but this requires confirmation in human clinical trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: The aim of this systematic review is to assess the performance of graduated compression stockings (GCS) in comparison to no venous thromboembolism (VTE) prophylaxis in the prevention of hospital-acquired thrombosis in low-risk surgical patients undergoing short-stay procedures., Methods: Aligning with PRISMA guidelines, online databases MEDLINE and EMBASE, Cochrane Library® and trial registries were searched. Eligible articles reported the VTE rate in low-risk surgical patients either receiving GCS or no VTE prophylaxis., Results: Narrative synthesis was performed on a single eligible article. The included study arm consisted of participants undergoing knee arthroscopy with the use of GCS alone reporting a total of 29 VTE events (4.4%), 16 of which were asymptomatic DVTs (2.4%)., Conclusion: There is a complete lack of evidence to support the use of GCS in the prevention of HAT for low-risk surgical patients. An adequately powered trial is required to provide level-IA evidence to support this practice.

Introduction : Post-thrombotic syndrome (PTS) is a common lifelong condition affecting up to 50% of those suffering from deep vein thrombosis (DVT). PTS compromises function and quality of life with subsequent venous ulceration in up to 29% of those affected. Areas covered : A literature review of surgical and non-surgical approaches in the prevention and treatment of PTS was undertaken. Notable areas include the use of percutaneous endovenous interventions and the use of graduated compression stockings (GCS) after acute proximal DVT. Expert opinion : In patients with acute iliofemoral DVT, we think it is important to have a frank conversation with the patient about catheter-directed thrombolysis, aiming to reduce the severity of PTS experienced. We advocate ultrasound-accelerated thrombolysis with adjunctive procedures, such as deep venous stenting for proximal iliofemoral DVT. For patients with isolated femoral DVT, we believe that anticoagulation and GCS should be recommended. In patients with established PTS, we recommend GCS for symptomatic relief. We recommend that patients engage in regular exercise where possible with the prospect of gaining symptomatic relief. For those with severe PTS that has a significant effect on quality of life, we discuss the patient's case at a multi-disciplinary team meeting to plan for endovenous intervention.

Background: Photoageing describes complex cutaneous changes which occur following chronic exposure to solar ultraviolet radiation (UVR). Amongst White Northern Europeans, facial photoageing appears as distinct clinical phenotypes: 'hypertrophic' photoageing (HP) and 'atrophic' photoageing (AP). Deep, coarse wrinkles predominate in individuals with HP, whereas those with AP have relatively smooth, unwrinkled skin with pronounced telangiectasia. AP individuals have an increased propensity for developing keratinocyte cancers., Objectives: To investigate whether histological differences underlie these distinct phenotypes of facial photoageing., Methods: Facial skin biopsies were obtained from participants with AP (10 M, 10 F; mean age: 78.7 years) or HP (10 M, 10 F; mean age: 74.5 years) and were assessed histologically and by immunohistochemistry., Results: Demographic characterization revealed 95% of AP subjects, as compared to 35% with HP, were Fitzpatrick skin type I/II; of these, 50% had a history of one or more keratinocyte cancers. There was no history of keratinocyte cancers in the HP cohort. Analysis of UVR-induced mitochondrial DNA damage confirmed that all volunteers had received similar lifetime cumulative doses of sun exposure. Histologically, male AP had a significantly thicker epidermis than did AP females or those of either sex with HP. HP facial skin exhibited severe solar elastosis, whereas in AP facial skin, solar elastosis was apparent only in females. Loss of papillary dermal fibrillin-rich microfibrils occurred in all HP and AP female subjects, but not in AP males. Furthermore, male AP had a significant reduction in collagen VII at the dermal-epidermal junction than did AP females or those of either sex with HP., Conclusions: This study provides further evidence that AP and HP represent distinct clinical and histological entities. Knowledge of these two phenotypes is clinically relevant due to the increased prevalence of keratinocyte cancers in those - particularly males - with the AP phenotype., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Aim: Ileoanal pouch-vaginal fistula (PVF) is a relatively common complication of restorative proctocolectomy with ileal pouch-anal anastomosis. There are several operative approaches in the management of PVF. There is currently no consensus as to which approach is the most effective or which should be attempted first., Method: A systematic review was undertaken following a publicly available protocol registered with PROSPERO (CRD42019133750) in accordance with PRISMA guidelines. Online searches of databases MEDLINE and Embase, Cochrane Library, ClinicalTrials.gov, EU Clinical Trials and ISRCTN registry were performed., Results: Twenty-seven articles met the criteria for inclusion in the study: 13 retrospective cohort studies, two prospective cohort studies, eight case series, three case reports and a case-control study. A narrative synthesis was performed due to heterogeneity between included articles. Our study included 577 PVFs, and the incidence rate was 2.1%-17.1%. Both local and abdominal approaches were used in the management of PVF. The overall success of local and abdominal procedures was 44.9% and 60.2% respectively. ROBINS-I assessment revealed a critical risk of bias. GRADE assessment indicated a very low certainty in effect size and evidence quality., Conclusion: Local interventions and abdominal approaches have a high failure rate. The results of this review will aid the counselling of patients with this condition. Furthermore, we provide an algorithm for discussion on the management of PVF based on experience at our local centre. The studies available on the management of PVF are low quality; a large prospective registry and Delphi consensus are required to further this area of research., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Background: Actissist is a smartphone app designed to deliver an intervention grounded in cognitive behavior therapy for early psychosis. Actissist was developed by a multidisciplinary team of academics, clinicians, experts by experience and software engineers. Actissist has been tested in two trials, the first a proof-of-concept trial where Actissist was safe, acceptable and feasible, the second, a powered randomized controlled trial. Objective: This article describes how our multidisciplinary team designed and developed Actissist. This article describes: (i) how Actissist was informed by initial qualitative interviews and focus groups and an expert reference group; (ii) refinements made to the app based on ongoing user feedback; (iii) successes and challenges encountered; and (iv) learning points and recommendations for involving stakeholders in digital health interventions. Methods: Expert reference group meetings informed the development of Actissist and design of subsequent trials, which included individuals with lived experience of psychosis, clinicians, academics, computer scientists and software engineers. Person-centered stakeholder involvement was promoted using focus groups and qualitative interviews prior to the development of the app, which informed version one of Actissist. Interviews were carried out with participants who had used Actissist. Two further versions of Actissist were developed following additional rounds of testing. Results: Multidisciplinary working throughout the Actissist project led to the development, inclusion and improvement of the app design and content. These changes and features included non-directive and compassionate content, co-designed recovery videos, relaxation exercises, psychoeducation material, ability to "favorite" areas of the app that users found helpful, and goal-setting. Challenges to collaborative working included discrepancies between what stakeholders want and what is technically possible to deliver, resource pressures, trying to deliver desired features within the boundaries of fundamental trial design considerations, and power imbalances associated with multidisciplinary working. Conclusions: The involvement of stakeholders in the design and development and delivery of Actissist has been fundamental to our development approach. Through this collaborative process, we have identified different perspectives and ideas that would have not been generated by the research team alone. Clinical Trial Registrations: Proof-of-concept trial: http://www.isrctn.com/ISRCTN34966555 Fully-powered randomized controlled trial: https://www.isrctn.com/ISRCTN76986679., Competing Interests: SB, JA and SL are directors of a not-for-profit community interest company spun out of the University of Manchester designed to make digital health apps commercially available in the UK National Health Service. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Berry, Machin, Ainsworth, Berry, Edge, Haddock, Lewis, Morris and Bucci.)

Background: Chronic exertional compartment syndrome (CECS) is an overuse injury typically seen in young and athletic patients. The five cardinal symptoms are pain, tightness, cramping, weakness, and paresthesia. These classically occur during exertion and disappear with cessation of the activity, with no permanent damage to tissues within the compartment; nonetheless, CECS presents a significant functional impairment to those affected. Regulating exercise has been shown to alleviate symptoms, but this may not be acceptable to some patients (eg, professional athletes). For patients who fail to respond to conservative management or where exercise reduction is unrealistic, fasciotomy can be considered. There are no established guidelines on the management of CECS, and it remains underdiagnosed. The aim of this systematic review was to compare the outcomes of patients suffering from CECS managed with either fasciotomy or nonoperative means by examining functional outcomes and resolution of symptoms., Methods: MEDLINE and Embase databases and clinical trial registries were searched comprehensively; 219 articles were identified, and 14 articles were included in the systematic review. Given the heterogeneity between the studies in terms of outcomes reported, a qualitative synthesis was performed., Results: The majority of included studies were retrospective cohort studies, with a single prospective cohort study. Studies included fasciotomies performed in the upper and lower limbs. The population of patients included military servicemen, motocross racers, and unselected patients. There is insufficient evidence in the literature to support conservative or surgical management over the other in the management of CECS. However, fasciotomy appears to be a safe approach, with satisfaction rates of 48% to 94%. Complications related to the fasciotomy included hematomas (2.7%-22.5%), nerve injuries (2.0%-18.6%), deep venous thrombosis (2.7%), and symptom recurrence (0.65%-8.4%). Up to 10.4% of patients required revision fasciotomy., Conclusions: There is no consensus on the optimal management of CECS and, as yet, no established international guidelines on treatment. This systematic review suggests that fasciotomy could be a safe and viable option in the management of patients suffering from CECS, with promising long-term results. Future research in the form of randomized controlled trials comparing conservative and surgical management would be beneficial., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Carotid artery stenosis causes significant morbidity and mortality accounting for approximately 8% of all ischaemic strokes. Carotid artery stenting (CAS) offers an endovascular alternative to carotid endarterectomy (CEA), suggested as a viable option in those deemed high-risk for open CEA due to comorbidities or operative technical considerations. A number of large randomised-controlled trials (RCTs) and meta-analysis comparing CAS vs. CEA in unselected patient populations support the conclusion that CAS is associated with a higher risk of stroke and CEA is associated with a higher risk of myocardial infraction. Initial promise for CAS in high-risk patients was demonstrated by The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial that reported CAS was non-inferior to CEA. However, there is evidence to suggest age-related adverse outcome in patients undergoing CAS. There is limited evidence to suggest that CEA could be suitable even in patients deemed high-risk for medical or technical reasons. Further contemporary research on the use of CAS and CEA in high-risk patients is required to re-evaluate current guidelines and high-risk criterion. It is common for a composite outcome of death, ipsilateral stroke and MI which should be questioned as subsequent quality of life is likely to differ after suffering a stroke in comparison to MI. This literature review will discuss the current evidence for CAS and CEA interventions in unselected populations and high-risk patients with carotid disease requiring intervention., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-19-4085). The series “Carotid Artery Stenosis and Stroke: Prevention and Treatment Part I” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: Improving recovery from acute symptoms and preventing relapse are two significant challenges in severe mental illness. We developed a personalized smartphone-based app to monitor symptoms in real time and validated its acceptance, reliability, and validity., Objective: To assess (i) acceptability of continuous monitoring to SMI patients and health professionals over 3 months; (ii) impact of active self-monitoring on positive psychotic symptoms assessed at 6 and 12 weeks; and (iii) the feasibility of detecting early warning signs of relapse., Methods: The active symptom monitoring smartphone app was built into an end-to-end system in two NHS Trusts to enable real-time symptom self-monitoring and detection by the clinical team of early signs of relapse in people with severe mental illness. We conducted an open randomized controlled trial of active symptom monitoring compared to usual management to assess: (i) acceptability and safety of continuous monitoring over 3 months; (ii) impact of active self-monitoring on positive psychotic symptoms assessed at 6 and 12 weeks; (iii) feasibility of detecting early warning signs of relapse communicated to the healthcare staff via an app streaming data to the electronic health record. Eligible participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of schizophrenia and related disorders, and a history of relapse within the previous two years were enrolled from an early intervention team and a community mental health team., Results: Of 181 eligible patients, 81 (45%) consented and were randomized to either active symptom monitoring or management as usual. At 12 weeks, 90% (33/36) of those in the active monitoring group continued to use the system and exhibited an adherence rate (defined as responding to >33% of alerts) of 84% (30/36}. Active symptom monitoring was associated with no difference on the empowerment scale in comparison to the usual management group at 12 weeks. The pre-planned intent-to-treat analysis of the primary outcome, a positive score on the Positive and Negative Syndrome Scale (PANSS) scale, showed a significant reduction in the active symptom monitoring group over 12 weeks in the early intervention center. Alerts for personalized early warning signs of relapse were built into the workflows of both NHS Trusts, and 100% of health professional staff used the system in a new digital workflow. Qualitative analyses supported the acceptability of the system to participants and staff., Conclusions: The active smartphone monitoring system is feasible and was accepted by users in a 3-month study of people with severe mental illness, with surprisingly high levels of adherence. App use was associated with psychotic symptom improvement in recent-onset participants, but not those with longstanding illness, supporting the notion of improved self-management. When built into clinical management workflows to enable personalized alerts of symptom deterioration, the app has demonstrated utility in promoting earlier intervention for relapse., Trial Registration: ISRCTN Registry ISRCTN88145142; http://www.isrctn.com/ISRCTN88145142., (©Shon Lewis, John Ainsworth, Caroline Sanders, Charlotte Stockton-Powdrell, Matthew Machin, Pauline Whelan, Richard Hopkins, Zhimin He, Eve Applegate, Richard Drake, Charlie Bamford, Chris Roberts, Til Wykes. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.08.2020.)

Background: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to < 8% 10-year) to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Despite the promise of systems such as BC-Predict, there are still too many uncertainties for a fully-powered definitive trial to be appropriate or ethical. The present research aims to identify these key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. Key objectives of the present research are to quantify important potential benefits and harms, and identify key drivers of the relative cost-effectiveness of embedding BC-Predict into NHSBSP., Methods: A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP., Discussion: We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict., Trial Registration: Retrospectively registered with clinicaltrials.gov (NCT04359420).

We discuss the preliminary safety analysis of a smartphone-based intervention for early detection of psychotic relapse. We briefly describe how we identified patient safety hazards associated with the system and how measures were defined to mitigate these hazards.

Aim: Synthetic rectal mesh erosion is a challenging complication following urogynaecological surgery. The aim of this study was to determine the optimal management of rectal mesh erosion following urogynaecological surgery., Method: A systematic review was undertaken following a pre-defined protocol registered with PROSPERO (CRD42018112425) in accordance with PRISMA guidelines. Searches of MEDLINE online database, Cochrane Library and clinical trial registries (ClinicalTrials.gov, EU Clinical Trials, ISRCTN registry) were performed. The included articles were heterogeneous - therefore a narrative synthesis was performed., Results: Fourteen studies were included in the review: 11 case reports, one case series, one retrospective cohort and one prospective multicentre trial. Fourteen rectal mesh erosions were identified. Eight (57%) of the rectal erosions underwent major abdominal surgery. In two of these cases, the abdominal approach was used only after failure of the transanal route. Five (36%) of the mesh erosions were managed using a transanal approach. In one case, the mesh passed without intervention., Conclusion: Synthetic rectal mesh erosion can be managed successfully via either a transanal or a transabdominal approach with a partial or complete excision of the mesh. An examination under anaesthetic with an attempted transanal removal of mesh should be considered the first step in the management of this condition before consideration of more invasive surgery., (Colorectal Disease © 2019 The Association of Coloproctology of Great Britain and Ireland.)

Objectives: To establish the acceptability and feasibility of collecting daily patient-generated health data (PGHD) using smartphones and integrating PGHD into the electronic health record, using the example of RA., Methods: The Remote Monitoring of RA smartphone app was co-designed with patients, clinicians and researchers using qualitative semi-structured interviews and focus groups, including selection of question sets for symptoms and disease impact. PGHD were integrated into the electronic health record of one hospital and available in graphical form during consultations. Acceptability and feasibility were assessed with 20 RA patients and two clinicians over 3 months. A qualitative evaluation included semi-structured interviews with patients and clinicians before and after using the app, and audio-recordings of consultations to explore impact on the consultation. PGHD completeness was summarized descriptively, and qualitative data were analysed thematically., Results: Patients submitted data on a median of 91% days over 3 months. Qualitative analysis generated three themes: RA as an invisible disease; providing the bigger picture of RA; and enabling person-centred consultations. The themes demonstrated that the system helped render patients' RA more visible by providing the 'bigger picture', identifying real-time changes in disease activity and capturing symptoms that would otherwise have been missed. Graphical summaries during consultations enabled a more person-centred approach whereby patients felt better able to participate in consultations and treatment plans., Conclusion: Remote Monitoring of RA has uniquely integrated daily PGHD from smartphones into the electronic health record. It has delivered proof-of-concept that such integrated remote monitoring systems are feasible and can transform consultations for clinician and patient benefit., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions., Objective: This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial., Methods: We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants' own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support., Results: Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation., Conclusions: The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial., Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262., International Registered Report Identifier (irrid): DERR1-10.2196/15058., (©Andrew Gumley, Simon Bradstreet, John Ainsworth, Stephanie Allan, Mario Alvarez-Jimenez, Louise Beattie, Imogen Bell, Max Birchwood, Andrew Briggs, Sandra Bucci, Emily Castagnini, Andrea Clark, Sue M Cotton, Lidia Engel, Paul French, Reeva Lederman, Shon Lewis, Matthew Machin, Graeme MacLennan, Claire Matrunola, Hamish McLeod, Nicola McMeekin, Cathrine Mihalopoulos, Emma Morton, John Norrie, Frank Reilly, Matthias Schwannauer, Swaran P Singh, Lesley Smith, Suresh Sundram, David Thomson, Andrew Thompson, Helen Whitehill, Alison Wilson-Kay, Christopher Williams, Alison Yung, John Farhall, John Gleeson. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.01.2020.)

Study Objectives: Normal timing and duration of sleep is vital for all physical and mental health. However, many sleep-related studies depend on self-reported sleep measurements, which have limitations. This study aims to investigate the association of physical activity and sociodemographic characteristics including age, gender, coffee intake and social status with objective sleep measurements., Methods: A cross-sectional analysis was carried out on 82995 participants within the UK Biobank cohort. Sociodemographic and lifestyle information were collected through touch-screen questionnaires in 2007-2010. Sleep and physical activity parameters were later measured objectively using wrist-worn accelerometers in 2013-2015 (participants were aged 43-79 years and wore watches for 7 days). Participants were divided into 5 groups based on their objective sleep duration per night (<5 hours, 5-6 hours, 6-7 hours, 7-8 hours and >8 hours). Binary logistic models were adjusted for age, gender and Townsend Deprivation Index., Results: Participants who slept 6-7 hours/night were the most frequent (33.5%). Females had longer objective sleep duration than males. Short objective sleep duration (<6 hours) correlated with older age, social deprivation and high coffee intake. Finally, those who slept 6-7 hours/night were most physically active., Conclusions: Objectively determined short sleep duration was associated with male gender, older age, low social status and high coffee intake. An inverse 'U-shaped' relationship between sleep duration and physical activity was also established. Optimal sleep duration for health in those over 60 may therefore be shorter than younger groups., Competing Interests: The authors have declared that no competing interests exist.

There is an important gap in scaling up psychosocial interventions for people with severe mental health problems so that these interventions are not only widely available but also delivered in a timely manner. We examined the feasability of adapting a psychological intervention traditionally delivered face-to-face onto a digital platform. We report both the clinical and technical processes used to adapt and develop the digital platform in a group of people in the early phase of psychosis. The digital platform prompts people to engage with the intervention multiple times a day over a 12-week period. Participants are also able to access a repository of multi-media content to support their mental health. The digital platform has been successfully validated by participants registered with early intervention for psychosis services in the Northwest of England, UK and is currently being tested in a powered efficacy trial.

Competing Interests: The authors report no conflicts of interest in this communication.

Skin ageing is the result of a loss of cellular function, which can be further accelerated by external factors. Mitochondria have important roles in skin function, and mitochondrial damage has been found to accumulate with age in skin cells, but also in response to solar light and pollution. There is increasing evidence that mitochondrial dysfunction and oxidative stress are key features in all ageing tissues, including skin. This is directly linked to skin ageing phenotypes: wrinkle formation, hair greying and loss, uneven pigmentation and decreased wound healing. The loss of barrier function during skin ageing increases susceptibility to infection and affects wound healing. Therefore, an understanding of the mechanisms involved is important clinically and also for the development of antiageing skin care products.

Anal cancer incidence is higher in persons living with HIV/AIDS (PLWHA) than in the general population. Participation of PLWHA in anal cancer clinical trials (CTs) is essential; Hispanic PLWHA are underrepresented in CTs. We conducted a behavioral CT among 305 PLWHA in Puerto Rico to measure the efficacy of an educational video in increasing calls and screening into an anal cancer CT. Participants received printed educational materials on anal cancer and CTs; the intervention group also received an educational video. Outcome assessment based on follow-up interviews showed that printed materials increased awareness about CTs and high-resolution anoscopy (HRA), and willingness to participate in an anal cancer CT in both groups. However, the addition of the video increased the likelihood of participants to call the CT for orientation (RR adjusted  = 1.66, 95% CI 1.00-2.76; p = 0.05) and pre-screening evaluation (RR adjusted  = 1.70, 95% CI 0.95-3.03; p = 0.07). This intervention could help increase participation of Hispanics into anal cancer-related CTs.

Banks v. Goodfellow [1870. LR 5 QB 549 (Eng.)] is almost 150 years old, yet still stands as authority for the principle that unsoundness of the mind will not rebut testamentary capacity where it does not affect the will itself. Readers of this journal would know that psychology has advanced greatly during this sesquicentenary, and yet the law relating to testamentary capacity has remained relatively stagnant. We review the present laws relating to decision-making for adults with impaired capacity, particularly in Queensland, and also review various models of gauging decision-making capacity in other jurisdictions. We argue that qualified experts should be enlisted to make determinations about testamentary capacity when questions of capacity arise. We also argue the case for the development of scientifically validated protocols to assess decision-making capacity in the testamentary context., Competing Interests: The authors have no conflict of interest., (© 2019 The Australian and New Zealand Association of Psychiatry, Psychology and Law.)

Surgical site infection (SSI) is associated with increased morbidity, length of stay, and cost. Cyanoacrylate glue is a low-cost, fluid-proof, antimicrobial barrier. The aim of this systematic review is to assess the use of cyanoacrylate glue after standard wound closure versus dressings in the reduction of SSI. Medline, Embase, Cochrane Library, and clinical trial registries were searched with no restrictions in accordance with PRISMA guidelines. Eligibility criteria were prospective studies comparing glue versus dressings after standardised wound closure. Two reviewers independently screened articles and utilised GRADE for quality assessment. Meta-analysis was not performed because of the heterogeneity of the data. Three articles were included in the review. Study quality was uniformly low. Incidence of SSI was low, between 0% and 4%. No significant differences were reported in the single randomised controlled trial. A single non-randomised parallel group trial reported a significant reduction in the incidence of SSI in the cyanoacrylate group. There was no consistent evidence demonstrating reduction in SSI as a result of the use of cyanoacrylate glue. Future studies should assess the use of cyanoacrylate in procedures with a higher rate of SSI, for example, lower limb bypass., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Schizophrenia relapses are common, have profound, adverse consequences for patients and are costly to health services. Early signs interventions aim to use warning signs of deterioration to prevent full relapse. Such interventions show promise but could be further developed. This study addresses 2 developments: adding basic symptoms to checklists of conventional early signs and using a mobile phone app ExPRESS to aid early signs monitoring., Objective: This study aimed to (1) design a pool of self-report items assessing basic symptoms (Basic Symptoms Checklist, BSC); (2) develop and beta test a mobile phone app (ExPRESS) for monitoring early signs, basic symptoms, and psychotic symptoms; and (3) evaluate the long-term acceptability of ExPRESS via qualitative feedback from participants in a 6-month feasibility study., Methods: The BSC items and ExPRESS were developed and then adjusted following feedback from beta testers (n=5) with a schizophrenia diagnosis. Individuals (n=18) experiencing a relapse of schizophrenia within the past year were asked to use ExPRESS for 6 months to answer weekly questions about experiences of early signs, basic symptoms, and psychotic symptoms. At the end of follow-up, face-to-face qualitative interviews (n=16; 2 were uncontactable) explored experiences of using ExPRESS. The topic guide sought participants' views on the following a priori themes regarding app acceptability: item content, layout, and wording; app appearance; length and frequency of assessments; worries about app use; how app use fitted with participants' routines; and the app's extra features. Interview transcripts were analyzed using the framework method, which allows examination of both a priori and a posteriori themes, enabling unanticipated aspects of app use experiences to be explored., Results: Participants' mean age was 38 years (range 22-57 years). Responses to a priori topics indicated that long-term use of ExPRESS was acceptable; small changes for future versions of ExPRESS were suggested. A posteriori themes gave further insight into individuals' experiences of using ExPRESS. Some reported finding it more accessible than visits from a clinician, as assessments were more frequent, more anonymous, and did not require the individual to explain their feelings in their own words. Nevertheless, barriers to app use (eg, unfamiliarity with smartphones) were also reported. Despite ExPRESS containing no overtly therapeutic components, some participants found that answering the weekly questions prompted self-reflection, which had therapeutic value for them., Conclusions: This study suggests that apps are acceptable for long-term symptom monitoring by individuals with a schizophrenia diagnosis across a wide age range. If the potential benefits are understood, patients are generally willing and motivated to use a weekly symptom-monitoring app; most participants in this study were prepared to do so for more than 6 months., Trial Registration: ClinicalTrials.gov NCT03558529; https://clinicaltrials.gov/ct2/show/NCT03558529 (Archived by WebCite at http://www.webcitation.org/70qvtRmZY)., (©Emily Eisner, Richard James Drake, Natalie Berry, Christine Barrowclough, Richard Emsley, Matthew Machin, Sandra Bucci. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 29.03.2019.)

Background: Human papillomavirus (HPV) causes 10% of cancers among human immunodeficiency virus (HIV)-infected people in the United States. Because Hispanics are disproportionally affected by the HIV epidemic and by infection-related cancers, this study compared incidence rates for HPV-related cancers and survival between Hispanics and non-Hispanic whites (NHWs) and non-Hispanic blacks (NHBs) in the HIV-infected US population., Methods: Based on data from the HIV/AIDS Cancer Match Study, standardized incidence ratios (SIRs) were used to estimate cancer risk in HIV-infected Hispanics and the general US Hispanic population. Among HIV-infected people, cancer rates were compared with incidence rate ratios (IRRs), and survival was compared with hazard ratios between Hispanics and NHWs and NHBs., Results: Five hundred two HPV-related cancers occurred in 864,067 person-years of follow-up among HIV-infected Hispanics. Except for oropharyngeal cancer, the risk of HPV-related cancers was higher among HIV-infected Hispanics than in the general population (SIR range, 3.59 [cervical cancer] to 18.7 [anal cancer in men]). Among HIV-infected females, Hispanics had higher cervical cancer rates than NHWs (IRR, 1.70; 95% confidence interval [CI], 1.19-2.43) but lower vulvar cancer rates than NHWs (IRR, 0.40; 95% CI, 0.24-0.67) and NHBs (IRR, 0.62; 95% CI, 0.41-0.95). Among HIV-infected males, Hispanics had higher penile cancer rates than NHWs (IRR, 2.60; 95% CI, 1.36-4.96) but lower anal cancer rates than NHWs (IRR, 0.54; 95% CI, 0.46-0.63) and NHBs (IRR, 0.65; 95% CI, 0.56-0.77). Among HIV-infected Hispanics, 5-year survival was greater than 50% across HPV-related cancer types, with no major differences by racial/ethnic group., Conclusions: HIV-infected Hispanics have an elevated risk for HPV-related cancers. Similarly to the general population, HIV-infected Hispanics have higher rates of cervical and penile cancer than NHWs and NHBs. HPV vaccination should be promoted among HIV-infected individuals to reduce the burden of HPV-related cancers., (© 2018 American Cancer Society.)

Background: Timely access to intervention for psychosis is crucial yet problematic. As such, health care providers are forming digital strategies for addressing mental health challenges. A theory-driven digital intervention that monitors distressing experiences and provides real-time active management strategies could improve the speed and quality of recovery in psychosis, over and above conventional treatments. This study assesses the feasibility and acceptability of Actissist, a digital health intervention grounded in the cognitive model of psychosis that targets key early psychosis domains., Methods: A proof-of-concept, single, blind, randomized controlled trial of Actissist, compared to a symptom-monitoring control. Thirty-six early psychosis patients were randomized on a 2:1 ratio to each arm of the trial. Actissist was delivered via a smartphone app over 12-weeks; clinical and functional assessment time-points were baseline, post-treatment and 22-weeks. Assessors' blind to treatment condition conducted the assessments. Acceptability was examined using qualitative methods., Results: Actissist was feasible (75% participants used Actissist at least once/day; uptake was high, 97% participants remained in the trial; high follow-up rates), acceptable (90% participants recommend Actissist), and safe (0 serious adverse events), with high levels of user satisfaction. Treatment effects were large on negative symptoms, general psychotic symptoms and mood. The addition of Actissist conferred benefit at post-treatment assessment over routine symptom-monitoring and treatment as usual., Conclusions: This is the first controlled proof-of-concept trial of a theory-driven digital health intervention for early psychosis. Actissist is feasible and acceptable to early psychosis patients, with a strong signal for treatment efficacy. Trial Registration: ISRCTN: 34966555.

Aneurysms of the inferior vena cava (IVC) are rare, with only 54 cases reported in the literature. They carry a significant morbidity and mortality risk. A case of an IVC aneurysm in a patient with Klippel-Trenaunay syndrome (KTS) is reported. Open aneurysmorrhaphy of the type III aneurysm was successfully performed. The patient's leg swelling, back pain, and exercise tolerance improved. IVC aneurysms are not known to be associated with KTS. However, clinicians should have a high index of suspicion for great vessel aneurysms in these patients as they are associated with greater thromboembolic risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We report that reactive oxygen species (ROS), as measured in capillary blood taken from the finger-tip, increased after a marathon (+128% P < 0.01; effect size = 1.17), indicating that this collection method might be useful for measuring ROS in field settings. However, mitochondrial DNA damage remained unchanged. Beetroot juice, taken before and after exercise, was unable to mitigate exercise-induced ROS production, questioning its use an antioxidant-rich food.

Background: Despite substantial advances in the era of highly active antiretroviral therapy, HIV-positive persons are at high risk of tobacco-related disease and mortality. This study describes the prevalence and sociodemographic factors associated with current tobacco use among HIV-positive men and women 18 years and older receiving HIV care in Puerto Rico., Methods: Data from the 2009 Medical Monitoring Project (MMP) was used. A three-stage sampling design was conducted to obtain annual cross-sectional probability samples of HIV-infected adults in care. Factors associated with current tobacco use were identified using logistic regression models. All analyses were performed using STATA version 11.0., Results: The estimated prevalence of current cigarette use among the population was 29.0% (95%CI: 23.5%-35.2%), daily smoking was reported in 76.7% of them. Multivariate logistic regression models, showed that male drug users (injected and noninjected) were up to nine times more likely to be current smokers (OR = 9.9; 95%CI = 3.1, 31.5) as compared to nonusers., Conclusion: Findings highlight the need for smoking cessation strategies in this population, particularly among male HIV+ drug users.

Purpose People with HIV infection have an elevated risk of anal cancer. However, recent calendar trends are incompletely described, and which population subgroups might benefit from cancer screening is unknown. Methods We used linked data from HIV and cancer registries in nine US areas (1996 to 2012). We calculated standardized incidence ratios to compare anal cancer incidence in people with HIV infection with the general population, used Poisson regression to evaluate anal cancer incidence among subgroups of people with HIV and to assess temporal trends, and estimated the cumulative incidence of anal cancer to measure absolute risk. Results Among 447,953 people with HIV infection, anal cancer incidence was much higher than in the general population (standardized incidence ratio, 19.1; 95% CI, 18.1 to 20.0). Anal cancer incidence was highest among men who have sex with men (MSM), increased with age, and was higher in people with AIDS than in those without AIDS (ie, HIV only; adjusted incidence rate ratio, 3.82; 95% CI, 3.27 to 4.46). Incidence among people with HIV increased steeply during 1996 to 2000 (annual percentage change, 32.8%; 95% CI, -1.0% to 78.2%), reached a plateau during 2001 to 2008, and declined during 2008 to 2012 (annual percentage change, -7.2%; 95% CI, -14.4% to 0.6%). Cumulative incidence after a 5-year period was high for MSM with HIV only age 45 to 59 or ≥ 60 years (0.32% to 0.33%) and MSM with AIDS age 30 to 44, 45 to 59, or ≥ 60 years (0.29% to 0.65%). Conclusion Anal cancer incidence is markedly elevated among people with HIV infection, especially in MSM, older individuals, and people with AIDS. Recent declines may reflect delayed benefits of HIV treatment. Groups with high cumulative incidence of anal cancer may benefit from screening.

Plain English Summary: There are a growing number of mobile phones, watches and electronic devices which can be worn on the body to track aspects of health and well-being, such as daily steps, sleep and exercise. Dementia researchers think that these devices could potentially be used as part of future research projects, for example to help spot changes in daily activity that may signal the early symptoms of dementia. We asked a range of older people, including people living with dementia and their carers, to participate in interactive discussions about how future participants might find using these devices as part of research projects. We also invited volunteers to borrow a range of devices to test at home, giving them further insights. Discussions revealed that people were generally supportive of this type of research, provided they gave informed consent and that devices were discreet, comfortable and easy to use. They also valued technical support and regular feedback on study progress to encourage ongoing participation. These findings were used to develop a pool of devices for researchers, with computer software and written guidance to help plan, design and support studies. Our work shows that when given the right opportunities, people who are affected by dementia can provide valuable insights that can enhance the design, delivery and quality of future research., Abstract: Background Increasingly, researchers are recognising the potential for connected health devices, including smartphones and smartwatches, to generate high resolution data about patterns of daily activity and health outcomes. One aim of the Dementias Platform UK (DPUK) project is to provide researchers with a secure means to collect, collate and link data generated by such devices, thereby accelerating this type of research in the field of dementia. We aimed to involve members of the public in discussions about the acceptability and feasibility of different devices and research designs to inform the development of a device pool, software platform and written guidance to support future studies. Methods Over 30 people attended a series of interactive workshops, drop-in sessions and meetings in Greater Manchester. This included people living with dementia and cognitive impairments, carers and people without memory problems. Discussions were tailored to suit different audiences and focused on the feasibility and acceptability of a range of different wearable devices and research designs. We also invited volunteers to borrow a device to test at home, enabling further insights from hands-on interactions with devices. Results Discussions revealed that people were supportive of connected health dementia research in principle, provided they gave informed consent and that devices were discreet, comfortable and easy to use. Moreover, they recommended technical support and regular feedback on study progress to encourage ongoing participation. Conclusion By using a range of discussion-based and practical activities, we found it was feasible to involve people affected by dementia and use their insights to shape the development of a software platform and device pool to support future connected health dementia research. We recommend that researchers planning such studies in future pay adequate attention to designing suitable participant information, technical support and mechanisms of providing study progress updates to support sustained engagement from participants.

Background: Epigenetic variations in peripheral blood have potential as biomarkers for disease. This systematic review assesses the association of lung function and chronic obstructive pulmonary disease (COPD) with DNA methylation profiles in peripheral blood from population-based studies., Methods: Online databases Medline, Embase, and Web of Science were searched. Google Scholar was searched to identify grey literature. After removing duplicate articles, 1155 articles were independently screened by two investigators. Peer reviewed reports on population-based studies that examined peripheral blood DNA methylation in participants with measured lung function (FEV1, FEV1/FVC ratio) or known COPD status were selected for full-text review. Six articles were suitable for inclusion. Information regarding study characteristics, designs, methodologies and conclusions was extracted. A narrative synthesis was performed based on published results., Results: Three of the six articles assessed the association of COPD with DNA methylation, and two of these also included associations with lung function. Overall, five reports examined the association of lung function with DNA methylation profiles. Five of the six articles reported 'significant' results. However, no consistent CpG sites were identified across studies for COPD status or lung function values., Conclusions: DNA methylation patterns in peripheral blood from individuals with reduced lung function or COPD may be different to those in people with normal lung function. However, this systematic review did not find any consistent associations of lung function or COPD with differentially methylated CpG sites. Large studies with a longitudinal design to address reverse causality may prove a more fruitful area of research., Trial Registration: PROSPERO 2016: CRD42016037352 .

Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0·015), but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0·008 and P = 0·001) and protein levels (P = 0·0006 and P = 0·005) of the SDHA and SDHB catalytic subunits of complex II respectively. In addition there was a significant decrease in complex II activity with age (P = 0·029) that was specific to senescent skin cells, our study being the first to investigate these differences with senescence and skin age. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. Our study provides a future potential biomarker for monitoring the progression of skin ageing., (© 2016 British Association of Dermatologists.)

Objective: Significant other responses to patients' symptoms are important for patient illness outcomes in chronic fatigue syndrome (CFS/ME); negative responses have been associated with increased patient depression, whilst increased disability and fatigue have been associated with solicitous significant other responses. The current study aimed to examine the relationship between significant other responses and patient outcomes within the context of daily life., Design: Experience Sampling Methodology (ESM)., Method: Twenty-three patients with CFS/ME and their significant others were recruited from specialist CFS/ME services. Sixty momentary assessments, delivered using individual San Francisco Android Smartphones, were conducted over a period of 6 days. All participants reported on affect, dyadic contact, and significant other responses to the patient. Patients reported on symptom severity, disability, and activity management strategies., Results: Negative significant other responses were associated with increased patient symptom severity and distress reported at the same momentary assessment; there was evidence of a potentially mediating role of concurrent distress on symptom severity. Patient-perceived solicitous responses were associated with reduced patient activity and disability reported at the same momentary assessment. Lagged analyses indicate that momentary associations between significant other responses and patient outcomes are largely transitory; significant other responses were not associated with any of the patient outcomes at the subsequent assessment., Conclusion: The results indicate that significant other responses are important influences on the day-to-day experience of CFS/ME. Further research examining patient outcomes in association with specific significant other behavioural responses is warranted and future interventions that target such significant other behaviours may be beneficial. Statement of contribution What is already known on this subject? The existing literature has identified that significant other responses are important with respect to patient outcomes in CFS/ME. In particular, when examined cross-sectionally and longitudinally, negative and solicitous significant other responses are associated with poorer illness outcomes. This study is the first to examine the momentary associations between negative and solicitous responses, as reported by the patient and significant other, and patient-reported outcomes. An ESM paradigm was used to assess these temporal relationships within the context of participants' daily life. What does this study add? Negative responses were associated with increased momentary patient distress and symptoms. Perceived solicitousness was associated with activity limitation but less perceived disability. The impact of significant other responses on patient outcomes was found to be transitory., (© 2015 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

We investigated changes in gene expression that occur in chronic obstructive pulmonary disease (COPD) after corticosteroid treatment and sought to identify the mechanisms that regulate these changes. Biopsy samples were taken from patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I to II) before and after treatment with fluticasone propionate (FP)/salmeterol (SM) (50/500, 4 wk). Gene expression was measured by microarray and was confirmed by real-time reverse transcription-quantitative PCR (RT-qPCR). The effect of FP on IgG expression and B-cell proliferation in the presence of oxidative stress was also studied. FP/SM significantly increased the expression of 180 genes while repressing 343 genes. The top 5 down-regulated genes were associated with immunoglobulin production, whereas the immunomodulatory FK506 binding protein (FK506BP) was up-regulated. Genes including IL6, IL8, and TBET-encoding TBX21 were unaffected. FP reduced IgG protein and mRNA expression and proliferation of human B cells through the dephosphorylation of ERK-1/2 via increased DUSP1 (dual-specificity protein phosphatase 1) expression. Consistent with in vivo data, oxidative stress did not prevent FP-induced suppression of IgG expression in human B cells in vitro Changes in expression were validated by RT-qPCR and by gene set enrichment analysis in distinct COPD cohorts. FP may reduce the adaptive immune response in COPD and may be more effective in patients with an increased B-cell/antibody response indicated by high autoantibody titers.-Lee, J., Machin, M., Russell, K. E., Pavlidis, S., Zhu, J., Barnes, P. J., Chung, K. F., Adcock, I. M., Durham, A. L. Corticosteroid modulation of immunoglobulin expression and B-cell function in COPD., (© FASEB.)

Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention., (© 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Background: Cognitive behaviour therapy (CBT) is recommended for the treatment of psychosis; however, only a small proportion of service users have access to this intervention. Smartphone technology using software applications (apps) could increase access to psychological approaches for psychosis. This paper reports the protocol development for a clinical trial of smartphone-based CBT., Methods/design: We present a study protocol that describes a single-blind randomised controlled trial comparing a cognitive behaviour therapy-informed software application (Actissist) plus Treatment As Usual (TAU) with a symptom monitoring software application (ClinTouch) plus TAU in early psychosis. The study consists of a 12-week intervention period. We aim to recruit and randomly assign 36 participants registered with early intervention services (EIS) across the North West of England, UK in a 2:1 ratio to each arm of the trial. Our primary objective is to determine whether in people with early psychosis the Actissist app is feasible to deliver and acceptable to use. Secondary aims are to determine whether Actissist impacts on predictors of first episode psychosis (FEP) relapse and enhances user empowerment, functioning and quality of life. Assessments will take place at baseline, 12 weeks (post-treatment) and 22-weeks (10 weeks post-treatment) by assessors blind to treatment condition. The trial will report on the feasibility and acceptability of Actissist and compare outcomes between the randomised arms. The study also incorporates semi-structured interviews about the experience of participating in the Actissist trial that will be qualitatively analysed to inform future developments of the Actissist protocol and app., Discussion: To our knowledge, this is the first controlled trial to test the feasibility, acceptability, uptake, attrition and potential efficacy of a CBT-informed smartphone app for early psychosis. Mobile applications designed to deliver a psychologically-informed intervention offer new possibilities to extend the reach of traditional mental health service delivery across a range of serious mental health problems and provide choice about available care., Trial Registration: ISRCTN34966555. Date of first registration: 12 June 2014.

Current approaches to the management of severe mental illness have four major limitations: 1) symptom reporting is intermittent and subject to problems with reliability; 2) service users report feelings of disengagement from their care planning; 3) late detection of symptoms delay interventions and increase the risk of relapse; and 4) care systems are held back by the costs of unscheduled hospital admissions that could have been avoided with earlier detection and intervention. The ClinTouch system was developed to close the loop between service users and health professionals. ClinTouch is an end-to-end secure platform, providing a validated mobile assessment technology, a web interface to view symptom data and a clinical algorithm to detect risk of relapse. ClinTouch integrates high-resolution, continuous longitudinal symptom data into mental health care services and presents it in a form that is easy to use for targeting care where it is needed. The architecture and methodology can be easily extended to other clinical domains, where the paradigm of targeted clinical interventions, triggered by the early detection of decline, can improve health outcomes.

The relationship between psychotic symptoms and self-injurious thoughts (SITs) remains unclear. The short-term temporal associations between psychotic symptoms and SITs were explored. A sample of 36 people with a diagnosis of a psychotic disorder or at-risk mental state completed mobile phone-based measures at multiple times each day for 1 week. Clustered regression with time-lagged variables supported a relationship between paranoia and subsequent SITs. Hallucinations did not predict these thoughts when controlling for paranoia. The role of specific psychotic symptoms in triggering SITs is highlighted and the importance of considering these factors in risk management is discussed., (© 2013 The American Association of Suicidology.)

The skin is regularly exposed to the harmful effects of sunlight, such as ultraviolet radiation (UVR), which leads to ageing effects as well as clinical precancerous lesions and skin cancer. The accumulation of mitochondrial DNA (mtDNA) damage has been strongly associated as an underlying cause of the general ageing process in tissues and mtDNA damage has been associated with cancer development in many tissues including human skin. This scenario is linked to the key roles of mitochondrial function and mtDNA both in terms of energy production and also oxidative stress production as well as a mediator of apoptosis. We and others have pioneered the use of mtDNA damage as a highly sensitive biomarker of UVR exposure and oxidative stress in human skin; furthermore, ageing-dependent mtDNA mutations can be accelerated by exposure to sunlight. In addition, this review will also highlight useful applications of mtDNA as a biomarker of UVR-induced oxidative stress including effects of antioxidants., (© 2013 The Authors. BJD © 2013 British Association of Dermatologists.)

Early-stage cutaneous squamous cell carcinoma (cSCC) has a favourable prognosis. Metastatic disease is probably associated with chemoresistance mediated through the activation of pro-survival phosphatidylinositol 3-kinase/AKT signalling. Inhibition of activated AKT partially increases chemosensitivity but induces autophagy, the principal lysosomal mechanism for the bulk degradation and recycling of proteins and damaged organelles. The aim of the current study was to test the hypothesis that combined inhibition of AKT signalling and autophagy by the lysosomal inhibitor chloroquine increases the susceptibility to docetaxel-induced apoptosis of cSCC cells isolated from a lymph-node metastasis. Combined AKT inhibition and chloroquine treatment of MET 4 cSCC cells resulted in significantly enhanced inhibition of cell viability and apoptosis induced by clinically achievable concentrations of docetaxel (P < 0.001). Inhibition of both autophagy and AKT thus represents an effective and viable therapeutic strategy to increase the cytotoxicity of docetaxel for the treatment of advanced cSCC., (© The Author(s) CED © 2013 British Association of Dermatologists.)

Background: Mobile phone-based assessment may represent a cost-effective and clinically effective method of monitoring psychotic symptoms in real-time. There are several software options, including the use of native smartphone applications and text messages (short message service, SMS). Little is known about the strengths and limitations of these two approaches in monitoring symptoms in individuals with serious mental illness., Objective: The objective of this study was to compare two different delivery modalities of the same diagnostic assessment for individuals with non-affective psychosis-a native smartphone application employing a graphical, touch user interface against an SMS text-only implementation. The overall hypothesis of the study was that patient participants with sewrious mental illness would find both delivery modalities feasible and acceptable to use, measured by the quantitative post-assessment feedback questionnaire scores, the number of data points completed, and the time taken to complete the assessment. It was also predicted that a native smartphone application would (1) yield a greater number of data points, (2) take less time, and (3) be more positively appraised by patient participant users than the text-based system., Methods: A randomized repeated measures crossover design was employed. Participants with currently treated Diagnostic and Statistical Manual (Fourth Edition) schizophrenia or related disorders (n=24) were randomly allocated to completing 6 days of assessment (four sets of questions per day) with a native smartphone application or the SMS text-only implementation. There was then a 1-week break before completing a further 6 days with the alternative delivery modality. Quantitative feedback questionnaires were administered at the end of each period of sampling., Results: A greater proportion of data points were completed with the native smartphone application in comparison to the SMS text-only implementation (β = -.25, SE=.11, P=.02), which also took significantly less time to complete (β =.78, SE= .09, P<.001). Although there were no significant differences in participants' quantitative feedback for the two delivery modalities, most participants reported preferring the native smartphone application (67%; n=16) and found it easier to use (71%; n=16). 33% of participants reported that they would be willing to complete mobile phone assessment for 5 weeks or longer., Conclusions: Native smartphone applications and SMS text are both valuable methods of delivering real-time assessment in individuals with schizophrenia. However, a more streamlined graphical user interface may lead to better compliance and shorter entry times. Further research is needed to test the efficacy of this technology within clinical services, to assess validity over longer periods of time and when delivered on patients' own phones.