An Updated Systematic Review and Meta-analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients.

OBJECTIVE: To compare the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCSs) versus pharmacological thromboprophylaxis alone. BACKGROUND: Surgical inpatients have elevated VTE risk; recent studies cast doubt on whether GCS confers additional protection against VTE, compared with pharmacological thromboprophylaxis alone. METHODS: The review followed "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched up to November 2022. Randomized trials reporting VTE rate after surgical procedures, utilizing pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism, and VTE-related mortality were pooled through fixed and random effects. RESULTS: In a head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI: 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI: 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of pulmonary embolism for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI: 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants). CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

Systematic Review and Meta-Analysis of Elective Open Conversion versus Fenestrated and Branched Endovascular Repair for Previous Non-Infected Failed Endovascular Aneurysm Repair.

OBJECTIVE: To evaluate outcomes of patients electively undergoing fenestrated and branched endovascular repair (F/B-EVAR) or open conversion for failed previous non-infected endovascular aneurysm repair (EVAR). DATA SOURCES: Embase, MEDLINE, Cochrane Library. REVIEW METHOD: The protocol was prospectively registered on PROSPERO (CRD42023404091). The review followed the PRISMA guidelines; certainty was assessed through the GRADE and quality through MINORS tools. Outcomes data were pooled separately for F/B-EVAR and open conversion. A random effects meta-analysis of proportions was conducted; heterogeneity was assessed with the I2 statistic. RESULTS: Thirty eight studies were included, for a total of 1 645 patients of whom 1 001 (60.9%) underwent an open conversion and 644 (39.1%) a F/B-EVAR. The quality of evidence was generally limited. GRADE certainty was judged low for 30 day death (in both groups) and F/B-EVAR technical success, and very low for the other outcomes. Pooled 30 day death was 2.3% (I2 33%) in the open conversion group and 2.4% (I2 0%) in the F/B-EVAR conversion group (p = .36). Technical success for F/B-EVAR was 94.1% (I2 23%). The pooled 30 day major systemic complications rate was higher in the open conversion (21.3%; I2 74%) than in the F/B-EVAR (15.7%; I2 78%) group (p = .52). At 18 months follow up, the pooled re-intervention rate was 4.5% (I2 58%) in the open conversion and 26% (I2 0%) in the F/B-EVAR group (p < .001), and overall survival was 92.5% (I2 59%) and 81.6% (I2 68%), respectively (p = .005). CONCLUSION: In the elective setting, and excluding infections, the early results of both open conversion and F/B-EVAR after failed EVAR appear satisfactory. Although open conversion presented with higher complication rates in the first 30 days after surgery, at follow up it seemed to be associated with fewer re-interventions and better survival compared with F/B-EVAR.

Editor's Choice - A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets (COS) has been developed. COS, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. METHODS: Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. RESULTS: The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents) 15 questions were eliminated, and 11 further questions were eliminated after round 2 (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: death at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, five year survival, and continued sac growth. CONCLUSION: Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and to define instruments for cognitive functioning is needed.

Quantifying the effects of risk-stratified breast cancer screening when delivered in real time as routine practice versus usual screening: the BC-Predict non-randomised controlled study (NCT04359420).

BACKGROUND: Risk stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) could provide a better balance of benefits and harms. We developed BC-Predict, to offer women when invited to the NHSBSP, which collects standard risk factor information; mammographic density; and in a sub-sample, a Polygenic Risk Score (PRS). METHODS: Risk prediction was estimated primarily from self-reported questionnaires and mammographic density using the Tyrer-Cuzick risk model. Women eligible for NHSBSP were recruited. BC-Predict produced risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5-<8% 10-year) to have appointments to discuss prevention and additional screening. RESULTS: Overall uptake of BC-Predict in screening attendees was 16.9% with 2472 consenting to the study; 76.8% of those received risk feedback within the 8-week timeframe. Recruitment was 63.2% with an onsite recruiter and paper questionnaire compared to <10% with BC-Predict only (P < 0.0001). Risk appointment attendance was highest for those at high risk (40.6%); 77.5% of those opted for preventive medication. DISCUSSION: We have shown that a real-time offer of breast cancer risk information (including both mammographic density and PRS) is feasible and can be delivered in reasonable time, although uptake requires personal contact. Preventive medication uptake in women newly identified at high risk is high and could improve the cost-effectiveness of risk stratification. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).

Systematic Review and Meta-analysis of the Additional Benefit of Pharmacological Thromboprophylaxis for Endovenous Varicose Vein Interventions.

OBJECTIVE: The primary objective of this systematic review and meta-analysis was to elucidate the rate of venous thromboembolism (VTE) after endovenous interventions for varicose veins in the presence of pharmacological and mechanical thromboprophylaxis versus mechanical thromboprophylaxis alone. BACKGROUND: The VTE rate after endovenous procedures for varicose veins is higher than other day-case procedures and could be reduced with pharmacological thromboprophylaxis. METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines with a registered protocol (PROSPERO: CRD42021274963). Studies of endovenous intervention for superficial venous incompetence reporting the predefined outcomes with at least 30 patients were eligible. Data were pooled with a fixed effects model. RESULTS: There were 221 trials included in the review (47 randomized trial arms, 105 prospective cohort studies, and 69 retrospective studies). In randomized trial arms, the rate of deep venous thrombosis with additional pharmacological thromboprophylaxis was 0.52% (95% CI, 0.23%-1.19%) (9 studies, 1095 patients, 2 events) versus 2.26% (95% CI, 1.81%-2.82%) (38 studies, 6951 patients, 69 events) with mechanical thromboprophylaxis alone. The rate of pulmonary embolism in randomized trial arms with additional pharmacological thromboprophylaxis was 0.45% (95% CI, 0.09-2.35) (5 studies, 460 participants, 1 event) versus 0.23% (95% CI, 0.1%-0.52%) (28 studies, 4834 participants, 3 events) for mechanical measures alone. The rate of EHIT grade III to IV was 0.35% (95% CI, 0.09-1.40) versus 0.88% (95% CI, 0.28%-2.70%). There was 1 VTE-related mortality and 1 instance of major bleeding, with low rates of minor bleeding. CONCLUSIONS: There is a significant reduction in the rate of DVT with additional pharmacological thromboprophylaxis and routine prescription of anticoagulation after endovenous varicose vein intervention should be considered. VTE risk for individual study participants is heterogeneous and risk stratification in future randomized interventional studies is critical to establish the clinical effectiveness and safety of additional pharmacological thromboprophylaxis.

Shared Decision Making and the Management of Intact Abdominal Aortic Aneurysm: A Scoping Review of the Literature.

OBJECTIVE: The aim of this study was to summarise the current knowledge of shared decision making (SDM) in patients facing a treatment decision about an intact abdominal aortic aneurysm (AAA), and to identify where further evidence is needed. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched on 18 July 2021. An updated search was run on 31 May 2022 for relevant studies published from 1 January 2000 to 31 May 2022. REVIEW METHODS: This scoping review was undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines following a pre-defined protocol, retrieving studies reporting on aspects of SDM in those with intact AAAs. Qualitative synthesis of the articles was performed, and the results grouped according to theme. RESULTS: Fifteen articles reporting on a total of 1 344 participants (age range 62-74 years) from hospital vascular surgery clinics with intact AAAs were included. Studies were observational (n = 9), non-randomised studies of an intervention (n = 3), and randomised clinical trials (n = 3). The first theme was the preferences and practice of SDM. The proportion of patients preferring SDM ranged from 58% to 95% (three studies), although objective rating of SDM practice was consistently < 50% (three studies). Clinician training improved SDM practice. The second theme was poor provision of information. Fewer than half of patients (0 - 46%) surveyed were informed about all available treatment options (three studies). Publicly available information sources were rated as poor. The third theme concerned the utility of decision making support tools (DSTs). Two randomised trials demonstrated that the provision of DSTs improves patient knowledge and agreement between patient preference and repair type received but not objective measures of SDM for patients with AAAs. CONCLUSION: SDM for patients with an intact AAA appears to be in its infancy. Most patients with an AAA want SDM, but this is not commonly applied. Most patients with an AAA do not receive adequate information for SDM, although the use of bespoke DSTs leaves patients better informed to facilitate SDM.

Systematic Review and Meta-Analysis of the Pooled Rate of Post-Thrombotic Syndrome After Isolated Distal Deep Venous Thrombosis.

OBJECTIVE: To identify the rate of post-thrombotic syndrome (PTS) after isolated distal deep venous thrombosis (IDDVT) by performing a meta-analysis of the rate of PTS across randomised and observational studies. DATA SOURCES: MEDLINE, Embase, the Cochrane Controlled Trials Register, Clinicaltrials.gov, European Union Clinical Trials, International Standard Randomised Controlled Trial Number, and the Australian and New-Zealand Trials Registries. REVIEW METHODS: This review followed PRISMA guidelines using a registered protocol (CRD42021282136). Databases were searched up to December 2021 and prospective studies reporting the development of post-thrombotic syndrome were included; these were pooled with the meta-analysis. RESULTS: The results showed a post-thrombotic rate of 17% (95% CI 11 - 26%) (seven studies, 217 cases, 1 105 participants). Heterogeneity was high (I2 = 89%). On meta-regression, the rate of post-thrombotic syndrome was not correlated with the length of follow up (p = .71). Three studies (302 participants) reported the severity of post-thrombotic syndrome: 78% were mild (Villalta score 5 - 9); 11% were moderate (Villalta score 10 - 14), and 11% were severe (Villalta score ≥ 15). CONCLUSION: The risk of post-thrombotic syndrome after IDDVT was one in five and the risk of severe clinical manifestations, including ulceration, was one in 50. There was significant clinical, methodological, and statistical heterogeneity between studies and a substantial risk of bias from pooled studies. Randomised trials to support interventions for prevention of post-thrombotic syndrome are urgently needed.

Exploring engagement with the CBT-informed Actissist smartphone application for early psychosis.

BACKGROUND: Individuals with psychosis report favourable attitudes towards psychological interventions delivered via smartphone apps. Evidence for acceptability, safety, feasibility and efficacy is promising but in-depth reporting of app engagement in trials is sparse. AIMS: To examine how people with psychosis engaged with the cognitive behaviour therapy (CBT)-informed Actissist app over a 12-week intervention period, and to examine factors associated with app engagement. METHODS: Secondary data from participants in the intervention arm (n = 24) of a proof-of-concept randomised controlled trial of the Actissist app were analysed. The app prompted participants to engage with app-based CBT-informed material in five domains (voices, socialization, cannabis use, paranoia, perceived criticism) at pseudo-random intervals (three notifications per day, six days per week). Participants could self-initiate use any time. App use was financially incentivised. RESULTS: Participants responded to 47% of app notifications. Most app engagements (87%) were app-initiated rather than self-initiated. Participants engaged most with the voices domain, then paranoia. Age and employment status were significantly associated with overall app engagement. CONCLUSION: Individuals with psychosis engaged well with Actissist, particularly with areas focussing on voice-hearing and paranoia. App-generated reminders successfully prompted app engagement. As financial incentives may have increased app engagement, future studies of non-incentivized engagement in larger samples are needed.

Global Epidemiology of Chronic Venous Disease: A Systematic Review With Pooled Prevalence Analysis.

OBJECTIVE: To provide an updated estimate of the global prevalence of CVD and to comprehensively evaluate risk factors associated with this condition. BACKGROUND: CVD is an important cause of morbidity internationally, but the global burden of this condition is poorly characterized. The burden of CVD must be better characterized to optimize service provision and permit workforce planning to care for patients with different stages of CVD. METHODS: A systematic search in Ovid MEDLINE and Embase (1946-2019) identified 1271 articles. Full-text, English language articles reporting on the epidemiology of CVD in a general adult population were included. Data extraction was performed by 2 independent reviewers, in accordance with a preregistered protocol (PROSPERO: CRD42019153656). STATA and Review Manager were used for quantitative analysis. A crude, unadjusted pooled prevalence was calculated for each Clinical (C) stage in the Clinical, Etiologic, Anatomic, Pathophysiologic classification and across different geographical regions. Qualitative analysis was performed to evaluate associated risk factors in CVD. RESULTS: Thirty-two articles across 6 continents were identified. Nineteen studies were included in the overall pooled prevalence for each Clinical (C) stage; pooled estimates were: C0 s: 9%, C1: 26%, C2: 19%, C3: 8%, C4: 4%, C5: 1%, C6: 0.42%. The prevalence of C2 disease was highest in Western Europe and lowest in the Middle East and Africa. Commonly reported risk factors for CVD included: female sex (OR 2.26, 95% confidence intervals 2.16-2.36, P < 0.001), increasing age, obesity, prolonged standing, positive family history, parity, and Caucasian ethnicity. There was significant heterogeneity across the included studies. CONCLUSIONS: CVD affects a significant proportion of the population globally; however, there is significant heterogeneity in existing epidemiological studies.

Towards a Core Outcome Set for Abdominal Aortic Aneurysm: Systematic Review of Outcomes Reported Following Intact and Ruptured Abdominal Aortic Aneurysm Repair.

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.

Providing 'the bigger picture': benefits and feasibility of integrating remote monitoring from smartphones into the electronic health record.

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.

A systematic review of fasciotomy in chronic exertional compartment syndrome.

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.

What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420).

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).

Smartphone-Enhanced Symptom Management In Psychosis: Open, Randomized Controlled Trial.

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.

Systematic review of the use of cyanoacrylate glue in addition to standard wound closure in the prevention of surgical site infection.

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.

An Inferior Vena Cava Aneurysm in a Patient with Klippel-Trenaunay Syndrome.

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.

Corticosteroid modulation of immunoglobulin expression and B-cell function in COPD.

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.

Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies.

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 .

Effects of Actissist, a digital health intervention for early psychosis: A randomized clinical trial.

Schizophrenia affects 24 million people worldwide. Digital health interventions drawing on psychological principles have been developed, but their effectiveness remains unclear. This parallel, assessor-blinded, randomized clinical trial aimed to investigate whether a cognitive behaviour therapy-informed digital health intervention (Actissist app) confers added benefit on psychotic symptoms over and above remote symptom monitoring (ClinTouch app). Participants recruited from UK community health services were randomized 1:1 to receive either Actissist plus treatment as usual (TAU) or ClinTouch plus TAU. Eligible participants were adults with schizophrenia-spectrum psychosis within five years of first episode onset meeting a criterion level of positive symptoms severity. The primary outcome was Positive and Negative Syndrome Scale (PANSS) symptoms total score at 12 weeks post-randomization. Intention-to-treat analysis included 172 participants, with 149 participants (86.6 %) providing primary outcome data. Actissist plus TAU was not associated with greater reduction than an active control remote symptom monitoring app (ClinTouch) in PANSS total score at post-randomization. There were no significant effects between groups across secondary measures. There were no serious adverse reactions. Both groups improved on the primary psychotic symptoms measure at primary end-point and on secondary measures over time. The Actissist app is safe but not superior to digital symptom monitoring.