Outcome Measures in Adult Vulvar Lichen Sclerosus: A Systematic Review.

OBJECTIVES: Core outcome domains (CODs) for treatment of adult vulvar lichen sclerosus (VLS) have recently been established through a Delphi study. A number of measuring tools are available for evaluating VLS. The aim of this study is to identify available standardized measurement tools for the major CODs for VLS that have recently been defined, namely, physical findings and quality of life (QoL) specific to VLS. MATERIALS AND METHODS: A systematic search through September 8, 2023, for measuring tools applicable to VLS regarding physical findings and QoL including sexual function or sexual well-being and self-image was performed. RESULTS: Thirty-five studies were included in the systematic review describing 26 tools covering the following 6 outcome domains: QoL-general health, QoL-lichen sclerosus specific, symptoms, clinical signs, emotional impact, and sexual functioning. CONCLUSIONS: In current research, there is no uniformity in use of measurement tools for evaluating VLS. The established CODs to evaluate treatment of VLS are applicable for evaluating disease course as well. A comprehensive study to reach consensus regarding measurement of physical findings, QoL-lichen sclerosus specific, sexuality, and self-image taking the predetermined CODs and other factors such as age into account is needed.

Imaging of the Lymphatic Vessels for Surgical Planning: A Systematic Review.

BACKGROUND: Secondary lymphedema is a common complication after surgical or radiotherapeutic cancer treatment. (Micro) surgical intervention such as lymphovenous bypass and vascularized lymph node transfer is a possible solution in patients who are refractory to conventional treatment. Adequate imaging is needed to identify functional lymphatic vessels and nearby veins for surgical planning. METHODS: A systematic literature search of the Embase, MEDLINE ALL via Ovid, Web of Science Core Collection and Cochrane CENTRAL Register of Trials databases was conducted in February 2022. Studies reporting on lymphatic vessel detection in healthy subjects or secondary lymphedema of the limbs or head and neck were analyzed. RESULTS: Overall, 129 lymphatic vessel imaging studies were included, and six imaging modalities were identified. The aim of the studies was diagnosis, severity staging, and/or surgical planning. CONCLUSION: Due to its utility in surgical planning, near-infrared fluorescence lymphangiography (NIRF-L) has gained prominence in recent years relative to lymphoscintigraphy, the current gold standard for diagnosis and severity staging. Magnetic resonance lymphography (MRL) gives three-dimensional detailed information on the location of both lymphatic vessels and veins and the extent of fat hypertrophy; however, MRL is less practical for routine presurgical implementation due to its limited availability and high cost. High frequency ultrasound imaging can provide high resolution imaging of lymphatic vessels but is highly operator-dependent and accurate identification of lymphatic vessels is difficult. Finally, photoacoustic imaging (PAI) is a novel technique for visualization of functional lymphatic vessels and veins. More evidence is needed to evaluate the utility of PAI in surgical planning.

The association of coagulation and atrial fibrillation: a systematic review and meta-analysis.

AIMS: While atrial fibrillation (AF) is suggested to induce a prothrombotic state, increasing thrombotic risk, it is also hypothesized that coagulation underlies AF onset. However, conclusive evidence is lacking. With this systematic review and meta-analysis, we aimed to summarize and combine the evidence on the associations between coagulation factors with AF in both longitudinal and cross-sectional studies. METHODS AND RESULTS: We systematically searched for longitudinal cohort and cross-sectional studies investigating AF and thrombosis. For longitudinal studies, pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. For cross-sectional studies, we determined pooled standardized mean differences (SMDs) and 95% CIs. A total of 17 longitudinal and 44 cross-sectional studies were included. In longitudinal studies, we found significant associations between fibrinogen (HR 1.05, 95% CI 1.00-1.10), plasminogen activator inhibitor 1 (PAI-1) (HR 1.06, 95% CI 1.00-1.12), and D-dimer (HR 1.10, 95% CI 1.02-1.19) and AF incidence. In cross-sectional studies, we found significantly increased levels of fibrinogen (SMD 0.47, 95% CI 0.20-0,74), von Willebrand factor (SMD 0.96, 95% CI 0.28-1.66), P-selectin (SMD 0.31, 95% CI 0.08-0.54), ß-thromboglobulin (SMD 0.82, 95% CI 0.61-1.04), Platelet Factor 4 (SMD 0.42, 95% CI 0.12-0.7), PAI-1 (1.73, 95% CI 0.26-3.19), and D-dimer (SMD 1.74, 95% CI 0.36-3.11) in AF patients, as opposed to controls. CONCLUSION: These findings suggest that higher levels of coagulation factors are associated with prevalent and incident AF. These associations are most pronounced with prevalent AF in cross-sectional studies. Limited evidence from longitudinal studies suggests a prothrombotic state underlying AF development.

Circulating lipoprotein (a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis.

AIMS: To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations. METHODS AND RESULTS: We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI ) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01-1.18, I2: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04-1.34, I2: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11-1.58, I2: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10-1.43, I2: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13-5.64, I2: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (Pnonlinearity > 0.05). CONCLUSION: This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person's lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality.

Needle-free pharmacological sedation techniques in paediatric patients for imaging procedures: a systematic review and meta-analysis.

BACKGROUND: Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques. METHODS: Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events. RESULTS: Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99). CONCLUSIONS: We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.

Updated guideline for closure of abdominal wall incisions from the European and American Hernia Societies.

BACKGROUND: Incisional hernia is a frequent complication of abdominal wall incision. Surgical technique is an important risk factor for the development of incisional hernia. The aim of these updated guidelines was to provide recommendations to decrease the incidence of incisional hernia. METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane CENTRAL was performed on 22 January 2022. The Scottish Intercollegiate Guidelines Network instrument was used to evaluate systematic reviews and meta-analyses, RCTs, and cohort studies. The GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) was used to appraise the certainty of the evidence. The guidelines group consisted of surgical specialists, a biomedical information specialist, certified guideline methodologist, and patient representative. RESULTS: Thirty-nine papers were included covering seven key questions, and weak recommendations were made for all of these. Laparoscopic surgery and non-midline incisions are suggested to be preferred when safe and feasible. In laparoscopic surgery, suturing the fascial defect of trocar sites of 10 mm and larger is advised, especially after single-incision laparoscopic surgery and at the umbilicus. For closure of an elective midline laparotomy, a continuous small-bites suturing technique with a slowly absorbable suture is suggested. Prophylactic mesh augmentation after elective midline laparotomy can be considered to reduce the risk of incisional hernia; a permanent synthetic mesh in either the onlay or retromuscular position is advised. CONCLUSION: These updated guidelines may help surgeons in selecting the optimal approach and location of abdominal wall incisions.

An incisional hernia results from a weakness of the abdominal wall muscles that allows fat from the inside or organs to bulge out. These hernias are quite common after abdominal surgery at the site of a previous incision. There is research that discusses different ways to close an incision and this may relate to the chance of hernia formation. The aim of this study was to review the latest research and to provide a guide for surgeons on how best to close incisions to decrease hernia rates. When possible, surgery through small incisions may decrease the risk of hernia formation. If small incisions are used, it may be better if they are placed away from areas that are already weak (such as the belly button). If the incision is larger than 1 cm, it should be closed with a deep muscle-fascia suture in addition to skin sutures. If there is a large incision in the middle of the abdomen, the muscle should be sutured using small stitches that are close together and a slowly absorbable suture should be used. For patients who are at higher risk of developing hernias, when closing the incision, the muscle layer can be strengthened by using a piece of (synthetic) mesh. There is no good research available on recovery after surgery and no clear guides on activity level or whether a binder will help prevent hernia formation.

Prediction Models for Future High-Need High-Cost Healthcare Use: a Systematic Review.

BACKGROUND: In an effort to improve both quality of care and cost-effectiveness, various care-management programmes have been developed for high-need high-cost (HNHC) patients. Early identification of patients at risk of becoming HNHC (i.e. case finding) is crucial to a programme's success. We aim to systematically identify prediction models predicting future HNHC healthcare use in adults, to describe their predictive performance and to assess their applicability. METHODS: Ovid MEDLINE® All, EMBASE, CINAHL, Web of Science and Google Scholar were systematically searched from inception through January 31, 2021. Risk of bias and methodological quality assessment was performed through the Prediction model Risk Of Bias Assessment Tool (PROBAST). RESULTS: Of 5890 studies, 60 studies met inclusion criteria. Within these studies, 313 unique models were presented using a median development cohort size of 20,248 patients (IQR 5601-174,242). Predictors were derived from a combination of data sources, most often claims data (n = 37; 62%) and patient survey data (n = 29; 48%). Most studies (n = 36; 60%) estimated patients' risk to become part of some top percentage of the cost distribution (top-1-20%) within a mean time horizon of 16 months (range 12-60). Five studies (8%) predicted HNHC persistence over multiple years. Model validation was performed in 45 studies (76%). Model performance in terms of both calibration and discrimination was reported in 14 studies (23%). Overall risk of bias was rated as 'high' in 40 studies (67%), mostly due to a 'high' risk of bias in the subdomain 'Analysis' (n = 37; 62%). DISCUSSION: This is the first systematic review (PROSPERO CRD42020164734) of non-proprietary prognostic models predicting HNHC healthcare use. Meta-analysis was not possible due to heterogeneity. Most identified models estimated a patient's risk to incur high healthcare expenditure during the subsequent year. However, case-finding strategies for HNHC care-management programmes are best informed by a model predicting HNHC persistence. Therefore, future studies should not only focus on validating and extending existing models, but also concentrate on clinical usefulness.

Perioperative Mortality in Pediatric Patients: A Systematic Review of Risk Assessment Tools for Use in the Preoperative Setting.

BACKGROUND: There are multiple preoperative risk scores for pediatric mortality. The aim of this study was to systematically describe and compare the existing studies of patient-specific multispecialty risk prediction scores for perioperative mortality in pediatric populations, with the goal of guiding clinicians on which may be most appropriate for use in the preoperative setting. METHODS: This study is a systematic literature review of published journal articles that presented the development, extension/updating, and/or validation of a risk core that predicted all-cause mortality (up to 30 days postoperatively) in pediatric patients undergoing a procedure in which anesthesia was used. Scores needed to be applicable to surgeries in more than one noncardiac surgical specialty and had to be able to be calculated by the anesthesiologist at the time of the preanesthetic assessment. Two investigators independently screened studies for inclusion and assessed study quality in the domains of clinical applicability, feasibility/ease of use in the clinical setting, and risk of bias. RESULTS: A total of 1,681 titles were retrieved. Of these, 10 studies met inclusion criteria: 9 reported the development and validation of scores, and 1 was an external validation of an existing score. Seven studies used varying years of multicenter data from the National Surgical Quality Improvement Program-Pediatric Participant Use File for development and/or validation. The unadjusted rate of mortality in the studies ranged from 0.3 to 3.6%. The preoperative predictors of mortality used in score development included patient demographics, preoperative therapies, and chronic conditions, among others. All models showed good discrimination upon validation (area under the receiver operating characteristics curve greater than 0.8). Most risk scores had high or unclear risks of bias. CONCLUSIONS: There are numerous scores available for the prediction of mortality in pediatric populations, all of which exhibited good performance. However, many have high or unclear risks of bias, and most have not undergone external validation.

Global infectious disease risks associated with occupational exposure among non-healthcare workers: a systematic review of the literature.

OBJECTIVES: Employees in non-healthcare occupations may be in several ways exposed to infectious agents. Improved knowledge about the risks is needed to identify opportunities to prevent work-related infectious diseases. The objective of the current study was to provide an updated overview of the published evidence on the exposure to pathogens among non-healthcare workers. Because of the recent SARS-CoV-2 outbreaks, we also aimed to gain more evidence about exposure to several respiratory tract pathogens. METHODS: Eligible studies were identified in MEDLINE, Embase and Cochrane between 2009 and 8 December 2020. The protocol was registered with International Prospective Register of Systematic Reviews (CRD42019107265). An additional quality assessment was applied according to the Equator network guidelines. RESULTS: The systematic literature search yielded 4620 papers of which 270 met the selection and quality criteria. Infectious disease risks were described in 37 occupational groups; 18 of them were not mentioned before. Armed forces (n=36 pathogens), livestock farm labourers (n=31), livestock/dairy producers (n=26), abattoir workers (n=22); animal carers and forestry workers (both n=16) seemed to have the highest risk. In total, 111 pathogen exposures were found. Many of these occupational groups (81.1%) were exposed to respiratory tract pathogens. CONCLUSION: Many of these respiratory tract pathogens were readily transmitted where employees congregate (workplace risk factors), while worker risk factors seemed to be of increasing importance. By analysing existing knowledge of these risk factors, identifying new risks and susceptible risk groups, this review aimed to raise awareness of the issue and provide reliable information to establish more effective preventive measures.

Evaluation of centers for information and support combining formal and informal care for patients with cancer: a systematic review of the literature.

PURPOSE: Clear information and supportive care are necessary for patients with cancer to effectively manage their condition. Traditionally, healthcare professionals offer information and support via the so-called formal care route. In addition, research has found favorable effects of informal care provided by volunteer programs and informal "walk-in support centers." Less research has been done on initiatives that combine formal and complementary informal supportive care for patients with cancer. This systematic literature study aimed to discover (1) which types of initiatives are described in the literature, (2) what type of care they offer, and (3). how they are evaluated in terms of outcome measures. METHODS: We performed a systematic literature search of MEDLINE, Embase, PsycINFO, and CINAHL. Studies were included if the collaboration between one type of formal care together with one type of informal care was explicitly mentioned in the article. The search was not restricted to a specific cancer type. RESULTS: A total of 4869 records were retrieved and 18 studies were included. In most studies, the care provided consisted of emotional support for, and/or providing information to, patients and their families. Initiatives were evaluated with interviews and questionnaires. Patients with cancer reported that they were satisfied with the care offered, including information, social and emotional support, help with activities of daily living, and family-related issues. Volunteers reported that visits they made were experienced positive and rewarding and the volunteers were confident about their contribution to general healthcare. Some negative experiences were reported by volunteers, e.g., interference of their own cancer diagnosis with volunteer work. The importance of proper training was stressed. CONCLUSIONS: Initiatives combining formal and informal supportive care hold the potential of added value in terms of providing emotional support for, and providing information to, patients with cancer. Support and specific training for volunteers can be viewed as success factors in the involvement of volunteers in formal care practices.

Guaiac-based faecal occult blood tests versus faecal immunochemical tests for colorectal cancer screening in average-risk individuals.

BACKGROUND: Worldwide, many countries have adopted colorectal cancer (CRC) screening programmes, often based on faecal occult blood tests (FOBTs). CRC screening aims to detect advanced neoplasia (AN), which is defined as CRC or advanced adenomas. FOBTs fall into two categories based on detection technique and the detected blood component: qualitative guaiac-based FOBTs (gFOBTs) and faecal immunochemical tests (FITs), which can be qualitative and quantitative. Screening with gFOBTs reduces CRC-related mortality. OBJECTIVES: To compare the diagnostic test accuracy of gFOBT and FIT screening for detecting advanced colorectal neoplasia in average-risk individuals. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS Citation Index, Science Citation Index Expanded, and Google Scholar. We searched the reference lists and PubMed-related articles of included studies to identify additional studies. SELECTION CRITERIA: We included prospective and retrospective studies that provided the number of true positives, false positives, false negatives, and true negatives for gFOBTs, FITs, or both, with colonoscopy as reference standard. We excluded case-control studies. We included studies in which all participants underwent both index test and reference standard ("reference standard: all"), and studies in which only participants with a positive index test underwent the reference standard while participants with a negative test were followed for at least one year for development of interval carcinomas ("reference standard: positive"). The target population consisted of asymptomatic, average-risk individuals undergoing CRC screening. The target conditions were CRC and advanced neoplasia (advanced adenomas and CRC combined). DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion. In case of disagreement, a third review author made the final decision. We used the Rutter and Gatsonis hierarchical summary receiver operating characteristic model to explore differences between tests and identify potential sources of heterogeneity, and the bivariate hierarchical model to estimate sensitivity and specificity at common thresholds: 10 µg haemoglobin (Hb)/g faeces and 20 µg Hb/g faeces. We performed indirect comparisons of the accuracy of the two tests and direct comparisons when both index tests were evaluated in the same population. MAIN RESULTS: We ran the initial search on 25 June 2019, which yielded 63 studies for inclusion. We ran a top-up search on 14 September 2021, which yielded one potentially eligible study, currently awaiting classification. We included a total of 33 "reference standard: all" published articles involving 104,640 participants. Six studies evaluated only gFOBTs, 23 studies evaluated only FITs, and four studies included both gFOBTs and FITs. The cut-off for positivity of FITs varied between 2.4 µg and 50 µg Hb/g faeces. For each Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability than gFOBTs for AN (P < 0.001) and CRC (P = 0.004). For the detection of AN, the summary sensitivity of gFOBTs was 15% (95% confidence interval (CI) 12% to 20%), which was significantly lower than FITs at both 10 µg and 20 µg Hb/g cut-offs with summary sensitivities of 33% (95% CI 27% to 40%; P < 0.001) and 26% (95% CI 21% to 31%, P = 0.002), respectively. Results were simulated in a hypothetical cohort of 10,000 screening participants with 1% CRC prevalence and 10% AN prevalence. Out of 1000 participants with AN, gFOBTs missed 850, while FITs missed 670 (10 µg Hb/g cut-off) and 740 (20 µg Hb/g cut-off). No significant differences in summary specificity for AN detection were found between gFOBTs (94%; 95% CI 92% to 96%), and FITs at 10 µg Hb/g cut-off (93%; 95% CI 90% to 95%) and at 20 µg Hb/g cut-off (97%; 95% CI 95% to 98%). So, among 9000 participants without AN, 540 were offered (unnecessary) colonoscopy with gFOBTs compared to 630 (10 µg Hb/g) and 270 (20 µg Hb/g) with FITs. Similarly, for the detection of CRC, the summary sensitivity of gFOBTs, 39% (95% CI 25% to 55%), was significantly lower than FITs at 10 µg and 20 µg Hb/g cut-offs: 76% (95% CI 57% to 88%: P = 0.001) and 65% (95% CI 46% to 80%; P = 0.035), respectively. So, out of 100 participants with CRC, gFOBTs missed 61, and FITs missed 24 (10 µg Hb/g) and 35 (20 µg Hb/g). No significant differences in summary specificity for CRC were found between gFOBTs (94%; 95% CI 91% to 96%), and FITs at the 10 µg Hb/g cut-off (94%; 95% CI 87% to 97%) and 20 µg Hb/g cut-off (96%; 95% CI 91% to 98%). So, out of 9900 participants without CRC, 594 were offered (unnecessary) colonoscopy with gFOBTs versus 594 (10 µg Hb/g) and 396 (20 µg Hb/g) with FITs. In five studies that compared FITs and gFOBTs in the same population, FITs showed a higher discriminative ability for AN than gFOBTs (P = 0.003). We included a total of 30 "reference standard: positive" studies involving 3,664,934 participants. Of these, eight were gFOBT-only studies, 18 were FIT-only studies, and four studies combined both gFOBTs and FITs. The cut-off for positivity of FITs varied between 5 µg to 250 µg Hb/g faeces. For each QUADAS-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability for detecting CRC than gFOBTs (P < 0.001). The summary sensitivity for CRC of gFOBTs, 59% (95% CI 55% to 64%), was significantly lower than FITs at the 10 µg Hb/g cut-off, 89% (95% CI 80% to 95%; P < 0.001) and the 20 µg Hb/g cut-off, 89% (95% CI 85% to 92%; P < 0.001). So, in the hypothetical cohort with 100 participants with CRC, gFOBTs missed 41, while FITs missed 11 (10 µg Hb/g) and 11 (20 µg Hb/g). The summary specificity of gFOBTs was 98% (95% CI 98% to 99%), which was higher than FITs at both 10 µg and 20 µg Hb/g cut-offs: 94% (95% CI 92% to 95%; P < 0.001) and 95% (95% CI 94% to 96%; P < 0.001), respectively. So, out of 9900 participants without CRC, 198 were offered (unnecessary) colonoscopy with gFOBTs compared to 594 (10 µg Hb/g) and 495 (20 µg Hb/g) with FITs. At a specificity of 90% and 95%, FITs had a higher sensitivity than gFOBTs. AUTHORS' CONCLUSIONS: FITs are superior to gFOBTs in detecting AN and CRC in average-risk individuals. Specificity of both tests was similar in "reference standard: all" studies, whereas specificity was significantly higher for gFOBTs than FITs in "reference standard: positive" studies. However, at pre-specified specificities, the sensitivity of FITs was significantly higher than gFOBTs.

Predicting inhospital admission at the emergency department: a systematic review.

BACKGROUND: ED crowding has potential detrimental consequences for both patient care and staff. Advancing disposition can reduce crowding. This may be achieved by using prediction models for admission. This systematic review aims to present an overview of prediction models for admission at the ED. Furthermore, we aimed to identify the best prediction tool based on its performance, validation, calibration and clinical usability. METHODS: We included observational studies published in Embase.com, Medline Ovid, Cochrane CENTRAL, Web of Science Core Collection or Google scholar, in which admission models were developed or validated in a general medical population in European EDs including the UK. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to assess quality of model development. Model performance was presented as discrimination and calibration. The search was performed on 11 October 2020. RESULTS: In total, 18 539 articles were identified. We included 11 studies, describing 16 different models, comprising the development of 9 models and 12 external validations of 11 models. The risk of bias of the development studies was considered low to medium. Discrimination, as represented by the area under the curve ranged from 0.630 to 0.878. Calibration was assessed in seven models and was strong. The best performing models are the models of Lucke et al and Cameron et al. These models combine clinical applicability, by inclusion of readily available parameters, and appropriate discrimination, calibration and validation. CONCLUSION: None of the models are yet implemented in EDs. Further research is needed to assess the applicability and implementation of the best performing models in the ED. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42017057975.

Accelerometer-Based Identification of Fatigue in the Lower Limbs during Cyclical Physical Exercise: A Systematic Review.

Physical exercise (PE) is beneficial for both physical and psychological health aspects. However, excessive training can lead to physical fatigue and an increased risk of lower limb injuries. In order to tailor training loads and durations to the needs and capacities of an individual, physical fatigue must be estimated. Different measurement devices and techniques (i.e., ergospirometers, electromyography, and motion capture systems) can be used to identify physical fatigue. The field of biomechanics has succeeded in capturing changes in human movement with optical systems, as well as with accelerometers or inertial measurement units (IMUs), the latter being more user-friendly and adaptable to real-world scenarios due to its wearable nature. There is, however, still a lack of consensus regarding the possibility of using biomechanical parameters measured with accelerometers to identify physical fatigue states in PE. Nowadays, the field of biomechanics is beginning to open towards the possibility of identifying fatigue state using machine learning algorithms. Here, we selected and summarized accelerometer-based articles that either (a) performed analyses of biomechanical parameters that change due to fatigue in the lower limbs or (b) performed fatigue identification based on features including biomechanical parameters. We performed a systematic literature search and analysed 39 articles on running, jumping, walking, stair climbing, and other gym exercises. Peak tibial and sacral acceleration were the most common measured variables and were found to significantly increase with fatigue (respectively, in 6/13 running articles and 2/4 jumping articles). Fatigue classification was performed with an accuracy between 78% and 96% and Pearson's correlation with an RPE (rate of perceived exertion) between r = 0.79 and r = 0.95. We recommend future effort toward the standardization of fatigue protocols and methods across articles in order to generalize fatigue identification results and increase the use of accelerometers to quantify physical fatigue in PE.

The Use of the FACE-Q Aesthetic: A Narrative Review.

INTRODUCTION: In the past decade there has been an increasing interest in the field of patient-reported outcome measures (PROMs) which are now commonly used alongside traditional outcome measures, such as morbidity and mortality. Since the FACE-Q Aesthetic development in 2010, it has been widely used in clinical practice and research, measuring the quality of life and patient satisfaction. It quantifies the impact and change across different aspects of cosmetic facial surgery and minimally invasive treatments. We review how researchers have utilized the FACE-Q Aesthetic module to date, and aim to understand better whether and how it has enhanced our understanding and practice of aesthetic facial procedures. METHODS: We performed a systematic search of the literature. Publications that used the FACE-Q Aesthetic module to evaluate patient outcomes were included. Publications about the development of PROMs or modifications of the FACE-Q Aesthetic, translation or validation studies of the FACE-Q Aesthetic scales, papers not published in English, reviews, comments/discussions, or letters to the editor were excluded. RESULTS: Our search produced 1189 different articles; 70 remained after applying in- and exclusion criteria. Significant findings and associations were further explored. The need for evidence-based patient-reported outcome caused a growing uptake of the FACE-Q Aesthetic in cosmetic surgery and dermatology an increasing amount of evidence concerning facelift surgery, botulinum toxin, rhinoplasty, soft tissue fillers, scar treatments, and experimental areas. DISCUSSION: The FACE-Q Aesthetic has been used to contribute substantial evidence about the outcome from the patient perspective in cosmetic facial surgery and minimally invasive treatments. The FACE-Q Aesthetic holds great potential to improve quality of care and may fundamentally change the way we measure success in plastic surgery and dermatology. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Deciphering the role of epigenetic modifications in fatty liver disease: A systematic review.

BACKGROUND: Fatty liver disease (FLD), primarily nonalcoholic fatty liver disease (NAFLD), is the most common liver disorder that affects a quarter of the global population. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis, which is associated with increased risk of developing liver cancer. Given that the pathogenic mechanisms of fatty liver remain largely elusive, it is important to further investigate potential underlying mechanisms including epigenetic modifications. Here, we performed a systematic review of human epigenetic studies on FLD presence. METHODS: Five bibliographic databases were screened until 28 August 2020. We included cross-sectional, case-control and cohort studies in humans that examined the association of epigenetic modifications including global, candidate or epigenome-wide methylation of DNA, noncoding RNAs and histone modifications with FLD. RESULTS: In total 36 articles, based on 33 unique studies, consisting of 12 112 participants met the inclusion criteria. Among these, two recent epigenome-wide association studies conducted among large population-based cohorts have reported the association between cg06690548 (SLC7A11) and FLD. Moreover, several studies have demonstrated the association between microRNAs (miRNAs) and FLD, in which miR-122, miR-34a and miR-192 were recognized as the most relevant miRNAs as biomarkers for FLD. We did not find any studies examining histone modifications in relation to FLD. CONCLUSIONS: Cumulative evidence suggests a link between epigenetic mechanisms, specifically DNA methylation and miRNAs, and FLD. Further efforts should investigate the molecular pathways by which these epigenetic markers may regulate FLD and also the potential role of histone modifications in FLD.

Asian patients' perspectives on advance care planning: A mixed-method systematic review and conceptual framework.

BACKGROUND: Asian healthcare professionals hold that patients' families play an essential role in advance care planning. AIM: To systematically synthesize evidence regarding Asian patients' perspectives on advance care planning and their underlying motives. DESIGN: Mixed-method systematic review and the development of a conceptual framework (PROSPERO: CRD42018099980). DATA SOURCES: EMBASE, MEDLINE, Web of Science, and Google Scholar were searched for studies published until July 27, 2020. We included studies concerning seriously-ill Asian patients' perspectives on advance care planning or their underlying motives for engaging or not engaging in it. RESULTS: Thirty-six articles were included; 22 were quantitative and 27 were from high-income countries. Thirty-nine to ninety percent of Asian patients were willing to engage in advance care planning. Our framework highlighted that this willingness was influenced not only by their knowledge of their disease and of advance care planning, but also by their beliefs regarding: (1) its consequences; (2) whether its concept was in accordance with their faith and their families' or physicians' wishes; and (3) the presence of its barriers. Essential considerations of patients' engagement were their preferences: (1) for being actively engaged or, alternatively, for delegating autonomy to others; (2) the timing, and (3) whether or not the conversations would be documented. CONCLUSION: The essential first step to engaging patients in advance care planning is to educate them on it and on their diseases. Asian patients' various beliefs about advance care planning should be accommodated, especially their preferences regarding their role in it, its timing, and its documentation.

Silent cerebral infarcts in patients with sickle cell disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Silent cerebral infarcts (SCIs) are the most common neurological complication in children and adults with sickle cell disease (SCD). In this systematic review, we provide an overview of studies that have detected SCIs in patients with SCD by cerebral magnetic resonance imaging (MRI). We focus on the frequency of SCIs, the risk factors involved in their development and their clinical consequences. METHODS: The databases of Embase, MEDLINE ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Trials via Wiley and Google Scholar were searched from inception to June 1, 2019. RESULTS: The search yielded 651 results of which 69 studies met the eligibility criteria. The prevalence of SCIs in patients with SCD ranges from 5.6 to 80.6% with most studies reported in the 20 to 50% range. The pooled prevalence of SCIs in HbSS and HbSß0 SCD patients is 29.5%. SCIs occur more often in patients with the HbSS and HbSß0 genotype in comparison with other SCD genotypes, as SCIs are found in 9.2% of HbSC and HbSß+ patients. Control subjects showed a mean pooled prevalence of SCIs of 9.8%. Data from included studies showed a statistically significant association between increasing mean age of the study population and mean SCI prevalence. Thirty-three studies examined the risk factors for SCIs. The majority of the risk factors show no clear association with prevalence, since more or less equal numbers of studies give evidence for and against the causal association. CONCLUSIONS: This systematic review and meta-analysis shows SCIs are common in patients with SCD. No clear risk factors for their development were identified. Larger, prospective and controlled clinical, neuropsychological and neuroimaging studies are needed to understand how SCD and SCIs affect cognition.

European Respiratory Society guideline on long-term management of children with bronchopulmonary dysplasia.

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and who have been discharged from the hospital, or who were >36 weeks of postmenstrual age. The guideline was based on predefined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the task force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence. We suggest monitoring with lung imaging using ionising radiation in a subgroup only, for example severe BPD or recurrent hospitalisations, and monitoring with lung function in all children. We suggest to give individual advice to parents regarding daycare attendance. With regards to treatment, we suggest the use of bronchodilators in a subgroup only, for example asthma-like symptoms, or reversibility in lung function; no treatment with inhaled or systemic corticosteroids; natural weaning of diuretics by the relative decrease in dose with increasing weight gain if diuretics are started in the neonatal period; and treatment with supplemental oxygen with a saturation target range of 90-95%. A multidisciplinary approach for children with established severe BPD after the neonatal period into adulthood is preferable. These recommendations should be considered until new and urgently needed evidence becomes available.

The global epidemiology of hepatitis E virus infection: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Hepatitis E virus (HEV), as an emerging zoonotic pathogen, is a leading cause of acute viral hepatitis worldwide, with a high risk of developing chronic infection in immunocompromised patients. However, the global epidemiology of HEV infection has not been comprehensively assessed. This study aims to map the global prevalence and identify the risk factors of HEV infection by performing a systematic review and meta-analysis. METHODS: A systematic searching of articles published in Medline, Embase, Web of science, Cochrane and Google scholar databases till July 2019 was conducted to identify studies with HEV prevalence data. Pooled prevalence among different countries and continents was estimated. HEV IgG seroprevalence of subgroups was compared and risk factors for HEV infection were evaluated using odd ratios (OR). RESULTS: We identified 419 related studies which comprised of 1 519 872 individuals. A total of 1 099 717 participants pooled from 287 studies of general population estimated a global anti-HEV IgG seroprevalence of 12.47% (95% CI 10.42-14.67; I2  = 100%). Notably, the use of ELISA kits from different manufacturers has a substantial impact on the global estimation of anti-HEV IgG seroprevalence. The pooled estimate of anti-HEV IgM seroprevalence based on 98 studies is 1.47% (95% CI 1.14-1.85; I2  = 99%). The overall estimate of HEV viral RNA-positive rate in general population is 0.20% (95% CI 0.15-0.25; I2  = 98%). Consumption of raw meat (P = .0001), exposure to soil (P < .0001), blood transfusion (P = .0138), travelling to endemic areas (P = .0244), contacting with dogs (P = .0416), living in rural areas (P = .0349) and receiving education less than elementary school (P < .0001) were identified as risk factors for anti-HEV IgG positivity. CONCLUSIONS: Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. 15-110 million individuals have recent or ongoing HEV infection. Our study highlights the substantial burden of HEV infection and calls for increasing routine screening and preventive measures.

The long-term clinical consequences of juvenile vulvar lichen sclerosus: A systematic review.

BACKGROUND: Vulvar lichen sclerosus (VLS) occurring in children and adolescents may have repercussions throughout life. OBJECTIVE: We sought to assess the evidence available on the long-term consequences of juvenile VLS. METHODS: Multiple databases were searched for studies containing long-term follow-up information on children or adolescents up to age 18 years with VLS. Articles were classified by level of evidence and the specific aspects of VLS studied. RESULTS: In all, 37 studies met the inclusion criteria, giving information on the long-term consequences of VLS, of which 13 were cohort studies and 24 were case reports or series. These publications show that signs and symptoms persist after puberty and beyond, scarring and permanent architectural changes occur, treatment is effective with regard to symptoms, and long-term quality of life is affected. Findings suggest a possible relationship with risk of malignancy. The included publications had low-level evidence. LIMITATIONS: Meta-analysis was not possible because the studies had different focuses. Very few patients were followed into adulthood. CONCLUSIONS: There is low-level evidence suggesting long-term repercussions of juvenile VLS. Studies following children and adolescents with VLS into adulthood are needed to better understand the course of this disease and its repercussions on adult vulvar health.