BackgroundDue to regional shortages some health services have proposed using surgical masks manufactured from sterilisation wrap. However, there has been little assessment of the safety of this practice. Therefore, we developed our own prototypes and evaluated whether they met regulatory standards.MethodsSurgical mask prototypes were manufactured from two thickness grades of commercial sterilisation wrap. Safety was assessed in the context of regulatory standards. As it was not previously reported, we developed and performed differential pressure and synthetic blood penetration resistance experiments in accordance with official methodology.ResultsBacterial filtration efficiency was comparable between sterilisation wrap and commercial surgical masks. Both prototypes met regulatory standards for synthetic blood resistance, whilst only our thinner mask fulfilled acceptable differential pressure ('breathability') thresholds.ConclusionAcceptable barrier and breathability properties can be achieved with surgical masks produced from sterilisation wrap. Therefore, this may be a reasonable method to supplement stock if required. Unless there are shortages mandating alternatives, health-care workers should always use approved personal protective equipment.

Importance Atrial fibrillation (AF) affects more than 6 million people in the United States; however, much AF remains undiagnosed. Given that more than 265 million people in the United States own smartphones (>80% of the population), smartphone applications have been proposed for detecting AF, but the accuracy of these applications remains unclear. Objective To determine the accuracy of smartphone camera applications that diagnose AF. Data Sources and Study Selection MEDLINE and Embase were searched until January 2019 for studies that assessed the accuracy of any smartphone applications that use the smartphone's camera to measure the amplitude and frequency of the user's fingertip pulse to diagnose AF. Data Extraction and Synthesis Bivariate random-effects meta-analyses were constructed to synthesize data. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) of Diagnostic Test Accuracy Studies reporting guideline. Main Outcomes and Measures Sensitivity and specificity were measured with bivariate random-effects meta-analysis. To simulate the use of these applications as a screening tool, the positive predictive value (PPV) and negative predictive value (NPV) for different population groups (ie, age ≥65 years and age ≥65 years with hypertension) were modeled. Lastly, the association of methodological limitations with outcomes were analyzed with sensitivity analyses and metaregressions. Results A total of 10 primary diagnostic accuracy studies, with 3852 participants and 4 applications, were included. The oldest studies were published in 2016 (2 studies [20.0%]), while most studies (4 [40.0%]) were published in 2018. The applications analyzed the pulsewave signal for a mean (range) of 2 (1-5) minutes. The meta-analyzed sensitivity and specificity for all applications combined were 94.2% (95% CI, 92.2%-95.7%) and 95.8% (95% CI, 92.4%-97.7%), respectively. The PPV for smartphone camera applications detecting AF in an asymptomatic population aged 65 years and older was between 19.3% (95% CI, 19.2%-19.4%) and 37.5% (95% CI, 37.4%-37.6%), and the NPV was between 99.8% (95% CI, 99.83%-99.84%) and 99.9% (95% CI, 99.94%-99.95%). The PPV and NPV increased for individuals aged 65 years and older with hypertension (PPV, 20.5% [95% CI, 20.4%-20.6%] to 39.2% [95% CI, 39.1%-39.3%]; NPV, 99.8% [95% CI, 99.8%-99.8%] to 99.9% [95% CI, 99.9%-99.9%]). There were methodological limitations in a number of studies that did not appear to be associated with diagnostic performance, but this could not be definitively excluded given the sparsity of the data. Conclusions and Relevance In this study, all smartphone camera applications had relatively high sensitivity and specificity. The modeled NPV was high for all analyses, but the PPV was modest, suggesting that using these applications in an asymptomatic population may generate a higher number of false-positive than true-positive results. Future research should address the accuracy of these applications when screening other high-risk population groups, their ability to help monitor chronic AF, and, ultimately, their associations with patient-important outcomes.

Question What is the overall accuracy of smartphone camera applications that diagnose and screen for atrial fibrillation (AF)? Findings In this meta-analysis of 10 primary diagnostic accuracy studies with 3852 participants, all applications that used photoplethysmography signals to diagnose AF had high sensitivity and specificity. However, the modeled positive predictive value for screening an asymptomatic population aged 65 years and older with a history of hypertension was approximately 20% to 40%, although the negative predictive value was near 100%. Meaning In this study, smartphone camera applications had high sensitivity and specificity for diagnosing AF and appeared adequate for ruling out AF, but their modest positive predictive value suggests that these devices will generate a higher number of false-positive than true-positive results. This systematic review and meta-analysis assesses the accuracy of smartphone camera applications that diagnose atrial fibrillation among US adults aged 65 years and older. Importance Atrial fibrillation (AF) affects more than 6 million people in the United States; however, much AF remains undiagnosed. Given that more than 265 million people in the United States own smartphones (>80% of the population), smartphone applications have been proposed for detecting AF, but the accuracy of these applications remains unclear. Objective To determine the accuracy of smartphone camera applications that diagnose AF. Data Sources and Study Selection MEDLINE and Embase were searched until January 2019 for studies that assessed the accuracy of any smartphone applications that use the smartphone's camera to measure the amplitude and frequency of the user's fingertip pulse to diagnose AF. Data Extraction and Synthesis Bivariate random-effects meta-analyses were constructed to synthesize data. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) of Diagnostic Test Accuracy Studies reporting guideline. Main Outcomes and Measures Sensitivity and specificity were measured with bivariate random-effects meta-analysis. To simulate the use of these applications as a screening tool, the positive predictive value (PPV) and negative predictive value (NPV) for different population groups (ie, age >= 65 years and age >= 65 years with hypertension) were modeled. Lastly, the association of methodological limitations with outcomes were analyzed with sensitivity analyses and metaregressions. Results A total of 10 primary diagnostic accuracy studies, with 3852 participants and 4 applications, were included. The oldest studies were published in 2016 (2 studies [20.0%]), while most studies (4 [40.0%]) were published in 2018. The applications analyzed the pulsewave signal for a mean (range) of 2 (1-5) minutes. The meta-analyzed sensitivity and specificity for all applications combined were 94.2% (95% CI, 92.2%-95.7%) and 95.8% (95% CI, 92.4%-97.7%), respectively. The PPV for smartphone camera applications detecting AF in an asymptomatic population aged 65 years and older was between 19.3% (95% CI, 19.2%-19.4%) and 37.5% (95% CI, 37.4%-37.6%), and the NPV was between 99.8% (95% CI, 99.83%-99.84%) and 99.9% (95% CI, 99.94%-99.95%). The PPV and NPV increased for individuals aged 65 years and older with hypertension (PPV, 20.5% [95% CI, 20.4%-20.6%] to 39.2% [95% CI, 39.1%-39.3%]; NPV, 99.8% [95% CI, 99.8%-99.8%] to 99.9% [95% CI, 99.9%-99.9%]). There were methodological limitations in a number of studies that did not appear to be associated with diagnostic performance, but this could not be definitively excluded given the sparsity of the data. Conclusions and Relevance In this study, all smartphone camera applications had relatively high sensitivity and specificity. The modeled NPV was high for all analyses, but the PPV was modest, suggesting that using these applications in an asymptomatic population may generate a higher number of false-positive than true-positive results. Future research should address the accuracy of these applications when screening other high-risk population groups, their ability to help monitor chronic AF, and, ultimately, their associations with patient-important outcomes.

ObjectivesWe report on the key clinical predictors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and present a clinical decision rule that can risk stratify patients for COVID-19.Design, participants and settingA prospective cohort of patients assessed for COVID-19 at a screening clinic in Melbourne, Australia. The primary outcome was a positive COVID-19 test from nasopharyngeal swab. A backwards stepwise logistic regression was used to derive a model of clinical variables predictive of a positive COVID-19 test. Internal validation of the final model was performed using bootstrapped samples and the model scoring derived from the coefficients, with modelling performed for increasing prevalence.ResultsOf 4226 patients with suspected COVID-19 who were assessed, 2976 patients underwent SARS-CoV-2 testing (n = 108 SARS-CoV-2 positive) and were used to determine factors associated with a positive COVID-19 test. The 7 features associated with a positive COVID-19 test on multivariable analysis were: COVID-19 patient exposure or international travel, Myalgia/malaise, Anosmia or ageusia, Temperature, Coryza/sore throat, Hypoxia-oxygen saturation < 97%, 65 years or older-summarized in the mnemonic COVID-MATCH65. Internal validation showed an AUC of 0.836. A cut-off of >= 1.5 points was associated with a 92.6% sensitivity and 99.5% negative predictive value (NPV) for COVID-19.ConclusionsFrom the largest prospective outpatient cohort of suspected COVID-19 we define the clinical factors predictive of a positive SARS-CoV-2 test. The subsequent clinical decision rule, COVID-MATCH65, has a high sensitivity and NPV for SARS-CoV-2 and can be employed in the pandemic, adjusted for disease prevalence, to aid COVID-19 risk-assessment and vital testing resource allocation.

Due to the ongoing COVID-19 pandemic and increased pressure on testing resources, understanding the clinical and epidemiological features closely associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is vital at point of care to enable risk stratification. We demonstrate that an internally derived and validated clinical decision rule, COVID-MATCH65, has a high sensitivity (92.6%) and NPV (99.5%) for SARS-CoV-2 and could be used to aid COVID-19 risk-assessment and resource allocation for SARS-CoV-2 diagnostics.

The recent randomised trial PIONEER-HF (Comparison of Sacubitril–Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) investigates the safety and efficacy of in-hospital initiation of angiotensin–neprilysin inhibitors for acute decompensated heart failure. 1 The updated America and European College of Cardiology guidelines endorsed sacubitril–valsartan, an angiotensin–neprilysin inhibitor, as a new therapeutic agent for heart failure with reduced ejection fraction.2 3 These recommendations were based predominantly on the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, which demonstrated a significant reduction in death from cardiovascular causes or hospitalisation for heart failure with sacubitril–valsartan (21.8%) versus enalapril (26.5%).4 Despite this, there has been slow uptake of sacubitril–valsartan in clinical practice.5 This reluctance is partially explained by the trial design of PARADIGM-HF,4 which involved stable patients in the outpatient setting on an established dose of ACE inhibitors or angiotensin …

Background: Atrial Fibrillation (AF) affects more than 6 million people in the United States (US) and greatly increases one's risk of stroke. Despite its prevalence, much AF remains undiagnosed. Smartphone applications (apps) have been proposed to aid the detection of subclinical AF and to monitor chronic AF. However, the accuracy of these apps remains unclear. We set out to determine the accuracy of smartphone camera apps to diagnose AF and compare the accuracy of apps.Methods: We searched MEDLINE and EMBASE databases and grey literature for studies that assessed the accuracy of any smartphone camera app to diagnose AF. To synthesize data, we constructed bivariate random-effects meta-analyses to determine the meta-analyzed sensitivity and specificity. Furthermore, we modeled the positive predictive value (PPV) and negative predictive value (NPV) for different population groups (age ≥65 and age ≥65 with hypertension). Lastly, we explored the effect of methodological limitations with sensitivity analyses and meta-regressions.Findings: We analyzed data from 3852 participants across 10 primary diagnostic accuracy studies, which evaluated four different apps. The apps analyzed the pulsewave signal (PPG) for an average of 2 minutes (range: 1 to 5 mins). The meta-analyzed sensitivity and specificity for all apps combined was 94·2% (92·2% to 95·7%) and 95·8% (92·4% to 97·7%) respectively. We found the PPV and NPV for the detection of AF was between 19·3% to 37·5% and 99·8% to 99·9%, respectively, in an asymptomatic population aged ≥65. The PPV increased for people aged ≥65 year old and with hypertension (PPV: 20·5% to 39·2%, NPV: 99·8% to 99·9%)). We found methodological limitations in a number of studies that did not appear to impact diagnostic performance, but an effect could not be definitively excluded given data sparsity.Interpretation: All smartphone camera apps have a relatively high sensitivity and specificity. The modeled NPV was high for all analyses, but the PPV was modest, suggesting that using these apps in an asymptomatic population may generate more false, rather than true, positive results. Future research could address the accuracy of these apps to screen further highrisk population groups, and to monitor chronic AF.Funding Statement: The lead author (JOS) is supported by an unrestricted NIH Fellowship ( T32 post-doctoral Fellowship), however there was no specific funding for this study.Declaration of Interests: The authors stated: "None declared."Ethics Approval Statement: The protocol for this systematic review was developed and registered a priori (PROSPERO: CRD42019125253). This systematic review and meta-analysis were conducted in line with the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA).

Summary Background Calcineurin‐inhibitor immunosuppressants (tacrolimus and ciclosporin) have been associated with an exposure‐related increase in tumour recurrence following liver transplantation for hepatocellular carcinoma (HCC). Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. Aim To clarify the potential benefit of mTOR‐inhibitors in HCC transplant patients by comparing recurrence and survival outcomes with calcineurin‐inhibitor‐based immunosuppression. Methods A systematic review and meta‐analysis was performed. The inclusion criteria were observational or interventional studies reporting the effect of early‐initiated (<6 months post‐transplant) mTOR‐inhibitor‐based immunosuppression on survival or tumour recurrence in patients transplanted with HCC, compared to a control of calcineurin‐inhibitor‐based therapy. Results Meta‐analysis demonstrated that compared with calcineurin‐inhibitor controls, recurrence‐free‐survival was significantly increased with mTOR‐inhibitor‐based therapy at 1‐year (Risk‐Ratio (RR): 1.09, 95% CI: 1.01‐1.18) and 3‐years (RR: 1.1, 95% CI: 1.01‐1.21) post‐transplant, with a nonsignificant increase at 5‐years (RR: 1.15, 95% CI: 0.99‐1.35). Overall survival was improved at 1‐year (RR: 1.07, 95% CI: 1.02‐1.12), 3‐years (RR: 1.1, 95% CI: 1.02‐1.19), and 5‐years (RR: 1.18, 95% CI: 1.08‐1.29). Recurrence‐rate was lower in the mTOR‐inhibitor arm (RR: 0.67, 95% CI: 0.56‐0.82), with no significant increase in acute rejection (RR: 1.1, 95% CI: 0.94‐1.28). Conclusions mTOR‐inhibitor‐based immunosuppression may be a preferable option in patients transplanted with HCC. It improves recurrence‐free‐survival over at least three years and reduces the recurrence rate compared with standard calcineurin‐inhibitor‐based therapy, with no significant increase in the rate of acute rejection. Future research should clarify the effect in higher vs lower risk cohorts.

Objective To provide an overview of the evidence on prevalence and outcomes of incidental imaging findings. DESIGN Umbrella review of systematic reviews. DATA SOURCES Searches of MEDLINE, EMBASE up to August 2017; screening of references in included papers. ELIGIBILITY CRITERIA Criteria included systematic reviews and meta-analyses of observational studies that gave a prevalence of incidental abnormalities ("incidentalomas"). An incidental imaging finding was defined as an imaging abnormality in a healthy, asymptomatic patient or an imaging abnormality in a symptomatic patient, where the abnormality was not apparently related to the patient's symptoms. Primary studies that measured the prevalence of incidentalomas in patients with a history of malignancy were also considered in sensitivity analyses. RESULTS 20 systematic reviews (240 primary studies) were identified from 7098 references from the database search. Fifteen systematic reviews provided data to quantify the prevalence of incidentalomas, whereas 18 provided data to quantify the outcomes of incidentalomas (13 provided both). The prevalence of incidentalomas varied substantially between imaging tests; it was less than 5% for chest computed tomography for incidental pulmonary embolism in patients with and without cancer and whole body positron emission tomography (PET) or PET/computed tomography (for patients with and without cancer). Conversely, incidentalomas occurred in more than a third of images in cardiac magnetic resonance imaging (MRI), chest computed tomography (for incidentalomas of thorax, abdomen, spine, or heart), and computed tomography colonoscopy (for extracolonic incidentalomas). Intermediate rates occurred with MRI of the spine (22%) and brain (22%). The rate of malignancy in incidentalomas varied substantially between organs; the prevalence of malignancy was less than 5% in incidentalomas of the brain, parotid, and adrenal gland. Extra-colonic, prostatic, and colonic incidentalomas were malignant between 10% and 20% of the time, whereas renal, thyroid, and ovarian incidentalomas were malignant around a quarter of the time. Breast incidentalomas had the highest percentage of malignancy (42%, 95% confidence interval 31% to 54%). Many assessments had high between-study heterogeneity (15 of 20 meta- analyses with I-2 >50%). CONCLUSIONS There is large variability across different imaging techniques both in the prevalence of incidentalomas and in the prevalence of malignancy for specific organs. This umbrella review will aid clinicians and patients weigh up the pros and cons of requesting imaging scans and will help with management decisions after an incidentaloma diagnosis. Our results can underpin the creation of guidelines to assist these decisions.

In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines and medical devices, and monitors them to ensure they continue to meet quality and safety standards.1 However, recent controversies with both medicines2 and devices3–6 suggest the current system may be failing patients. In the UK, the 2000 Freedom of Information (FOI) Act provides public access to information held by public authorities, and can be used as one method to hold them accountable, and ensure they are promoting adequate patient safety.7 Under this Act, the MHRA must disclose information on request. Requests can come from any member of the public and relate to any process the MHRA is responsible for. These requests are important to facilitate independent assessment of the regulatory process the MHRA undertakes. There are two predominant ways a request can be made. First, it can be submitted by contacting the MHRA directly. Alternatively, it can be sent via the website WhatDoTheyKnow, which forwards requests to the MHRA, and subsequently publishes and archives the response.8 Section 10 of the FOI Act dictates that responses should be received within 20 working days.7 The FOI Act, however, has 24 provisions and sections that allow the MHRA to refuse particular requests.7 Given the importance of transparency and accountability, we set out to audit FOI requests made to the MHRA to determine the proportion of successful requests, evaluate the reasons for refusal and provide advice for those considering future requests. ### What did we do? A single author (SEG) identified all available FOI requests and responses to the MHRA listed on the ‘WhatDoTheyKnow’ website up until to 31 December 2017. We also contacted the MHRA on 21 November 2017 and asked them to supply a list of all FOI requests ever made to them, and the subsequent outcomes. We extracted the date …

"Sirolimus in Liver Transplant Recipients With Hepatocellular Carcinoma." Journal of Investigative Surgery, 33(4), pp. 389–390

Owing to wide‐spread use, low‐dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta‐analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy.

There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital.