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.

A systematic review of midwives' training needs in perinatal mental health and related interventions.

Background: Midwives may be key stakeholders to improve perinatal mental healthcare (PMHC). Three systematic reviews considered midwives' educational needs in perinatal mental health (PMH) or related interventions with a focus on depression or anxiety. This systematic review aims to review: 1) midwives' educational/training needs in PMH; 2) the training programs in PMH and their effectiveness in improving PMHC. Methods: We searched six electronic databases using a search strategy designed by a biomedical information specialist. Inclusion criteria were: (1) focus on midwives; (2) reporting on training needs in PMH, perinatal mental health problems or related conditions or training programs; (3) using quantitative, qualitative or mixed-methods design. We used the Mixed Methods Appraisal Tool for study quality. Results: Of 4969 articles screened, 66 papers met eligibility criteria (47 on knowledge, skills or attitudes and 19 on training programs). Study quality was low to moderate in most studies. We found that midwives' understanding of their role in PMHC (e.g. finding meaning in opening discussions about PMH; perception that screening, referral and support is part of their routine clinical duties) is determinant. Training programs had positive effects on proximal outcomes (e.g. knowledge) and contrasted effects on distal outcomes (e.g. number of referrals). Conclusions: This review generated novel insights to inform initial and continuous education curriculums on PMH (e.g. focus on midwives' understanding on their role in PMHC or content on person-centered care). Registration details: The protocol is registered on PROSPERO (CRD42021285926).

How Do We Treat Children with Anterior Cutaneous Nerve Entrapment Syndrome and Is the Biopsychosocial Model Also Being Applied? A Scoping Review.

Background: Evidence-based guidelines for managing anterior cutaneous nerve entrapment syndrome (ACNES) in children are absent. The primary aim of this review was to scrutinize the evidence supporting currently used treatment interventions. In accordance with the World Health Organization (WHO) guidelines for managing chronic pain in children, these patients and their families and caregivers should be treated within the context of the biopsychosocial model; pain should not be treated purely as a biomedical problem. Therefore, our second aim was to evaluate whether these interventions are applied within the context of the biopsychosocial model, utilizing an inter- or multidisciplinary approach. Materials and Methods: A scoping review of the literature was conducted to explore treatment strategies for ACNES in children. To ensure a comprehensive overview of published literature on this topic, the search was not restricted based on study type. Two reviewers independently assessed titles and abstracts. After excluding records unrelated to children, full texts were screened for inclusion. Any discrepancies in judgement were resolved through discussion with a third reviewer. Results: Out of 35 relevant titles, 22 were included in this review. Only 4 articles provided information on long-term outcomes. The overall quality of the review was deemed low. The majority of reports did not address treatment or education within the psychological and social domains. A structural qualitative analysis was not feasible due to the substantial heterogeneity of the data. Conclusion: The evidence supporting current treatment strategies in children with ACNES is of low quality. More research is needed to establish an evidence-based treatment algorithm for patients with this challenging pain problem. In line with the WHO recommendation, greater emphasis should be placed on a biopsychosocial approach. The ultimate goal should be the development of a generic treatment algorithm outlining an approach to ACNES applicable to all professionals involved.

A Narrative Review of Patient-Reported Outcome Measures and Their Application in Recent Pediatric Surgical Research: Advancing Knowledge and Offering New Perspectives to the Field.

INTRODUCTION: Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This narrative review aims to describe PROM use in recent pediatric surgical research, identify and describe psychometrically robust PROMs, providing an overview of those derived from pediatric patient input, and make recommendations for future research. MATERIALS AND METHODS: A search was conducted to identify articles published from 2021 to August 2023 describing the availability and/or use of at least one valid or reliable PROM in children with conditions including anorectal malformations, biliary atresia, congenital diaphragmatic hernia, duodenal atresia, esophageal atresia, abdominal wall defects, Hirschsprung's disease, sacrococcygeal teratoma, and short bowel syndrome. Articles were categorized based on their objectives in applying PROMs. Psychometrically robust PROMs were identified and described. RESULTS: Out of the 345 articles identified, 49 met the inclusion criteria. Seventeen focused on esophageal atresia and 14 on Hirschsprung's disease. Twenty-nine PROMs were identified, with 12 deemed psychometrically robust. Seven psychometrically robust PROMs were developed using patient input in the primary item generation. Most PROMs were applied to advance understanding of conditions and/or treatment and fewer were developed or psychometrically evaluated. No PROMs were assessed for their impact or incorporated into an implementation study. CONCLUSIONS: This review reveals gaps in the application of PROMs in recent pediatric surgical research. Emphasis should be placed on the development and utilization of psychometrically robust PROMs, broadening the scope of covered diseases, conducting impact assessments, and evaluating implementation strategies.

Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and distressing endocrine disorder associated with lower quality of life, subfertility, diabetes, cardiovascular disease, depression, anxiety, and eating disorders. PCOS characteristics, its comorbidities, and its treatment can potentially influence sexual function. However, studies on sexual function in women with PCOS are limited and contradictory. OBJECTIVE AND RATIONALE: The aim was to perform a systematic review of the published literature on sexual function in women with PCOS and assess the quality of the research and certainty of outcomes, to inform the 2023 International Guidelines for the Assessment and Management of PCOS. SEARCH METHODS: Eight electronic databases were searched until 1 June 2023. Studies reporting on sexual function using validated sexuality questionnaires or visual analogue scales (VAS) in PCOS populations were included. Random-effects models were used for meta-analysis comparing PCOS and non-PCOS groups with Hedges' g as the standardized mean difference. Study quality and certainty of outcomes were assessed by risk of bias assessments and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method according to Cochrane. Funnel plots were visually inspected for publication bias. OUTCOMES: There were 32 articles included, of which 28 used validated questionnaires and four used VAS. Pooled Female Sexual Function Index (FSFI) scores in random-effects models showed worse sexual function across most subdomains in women with PCOS, including arousal (Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17], I2 = 82%, P < 0.001), lubrication (Hg [95% CI] = -0.54 [-0.79, -0.30], I2 = 90%, P < 0.001), orgasm (Hg [95% CI] = -0.37 [-0.56, -0.19], I2 = 83%, P < 0.001), and pain (Hg [95% CI] = -0.36 [-0.59, -0.13] I2 = 90%, P < 0.001), as well as total sexual function (Hg [95% CI] = -0.75 [-1.37, -0.12], I2 = 98%, P = 0.02) and sexual satisfaction (Hg [95% CI] = -0.31 [-0.45, -0.18], I2 = 68%, P < 0.001). Sensitivity and subgroup analyses based on fertility status and body mass index (BMI) did not alter the direction or significance of the results. Meta-analysis on the VAS studies demonstrated the negative impact of excess body hair on sexuality, lower sexual attractiveness, and lower sexual satisfaction in women with PCOS compared to controls, with no differences in the perceived importance of a satisfying sex life. No studies assessed sexual distress. GRADE assessments showed low certainty across all outcomes. WIDER IMPLICATIONS: Psychosexual function appears to be impaired in those with PCOS, but there is a lack of evidence on the related distress scores, which are required to meet the criteria for psychosexual dysfunction. Health care professionals should discuss sexual function and distress and be aware of the multifactorial influences on sexual function in PCOS. Future research needs to assess both psychosexual function and distress to aid in understanding the degree of psychosexual dysfunction in PCOS. Finally, more diverse populations (e.g. non-heterosexual and more ethnically diverse groups) should be included in future studies and the efficacy of treatments for sexual dysfunction should also be assessed (e.g. lifestyle and pharmacological interventions).

Health Policy for Prostate Cancer Early Detection in the European Union and the Impact of Opportunistic Screening: PRAISE-U Consortium.

With the new policy recommendation in 2022 to explore the possibilities of screening for prostate cancer by the European Commission, the landscape for prostate cancer early detection is evolving. In line with this recommendation, the PRAISE-U project aims to evaluate the early detection and diagnosis of prostate cancer through customised and risk-based screening programmes, with the goal to align protocols across European Union member states. This systematic review is part of the PRAISE-U project, with the goal to review the policy, medical guideline recommendations, and the current level of opportunistic screening presented in the scientific literature on prostate cancer early detection from 2016 to 2023 in European Union member states. An extensive literature search was performed on 1 June 2023 in a large number of databases, including Embase.com, Medline (Ovid), Web of Science Core Collection, Google Scholar, and Policy Commons. We identified 318 articles (qualitative, quantitative, and reviews), of which 41 were included in the full-text screening. Seventeen articles were ultimately identified as eligible for inclusion. The included articles revealed significant variations towards PSA-based early detection policies for prostate cancer in nine European countries. Despite official recommendations, opportunistic screening was prevalent across all nine countries regardless of recommendations for or against PSA-based early detection. This systematic review suggests that the current early detection policies are not fit for purpose. High levels of opportunistic screening and overdiagnosis persist, prompting policy recommendations for standardised guidelines, informed decision making, and increased awareness to improve efficiency and effectiveness in early detection.

Clinical outcomes of rifampicin combination therapy in implant-associated infections due to staphylococci and streptococci: A systematic review and meta-analysis.

OBJECTIVES: Adjunctive rifampicin for implant-associated infections is controversial. This study investigated the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating prosthetic joint infection (PJI) or prosthetic valve endocarditis (PVE) due to staphylococci and streptococci. METHODS: A systematic search was performed from inception to 13 June 2022 in Embase, MEDLINE, Cochrane and Web of Science to investigate the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating staphylococcal and streptococcal PJI or PVE. Randomised controlled trials (RCTs) and observational studies were included in the systematic review and meta-analysis. RESULTS: Fourteen studies were included. A moderate quality of evidence was found in favour of rifampicin in patients with staphylococcal PJI who underwent a debridement, antibiotics and implant retention (DAIR) procedure [odds ratio = 2.49, 95% confidence interval (CI) 1.93-3.23]. Including the two RCTs only, adding rifampicin to the antibiotic regimen after DAIR was also in favour of rifampicin, but this was not statistically significant (risk ratio = 1.27, 95% CI 0.79-2.04; n = 126). Pooling data for patients with staphylococcal PJI who underwent a two-stage procedure showed that adding rifampicin was not associated with therapeutic success. Limited evidence was found for the use of rifampicin for PVE caused by staphylococci. CONCLUSIONS: Adding rifampicin in the treatment of staphylococcal PJI treated by DAIR clearly increased the likelihood for therapeutic success. The clinical benefit of adjunctive rifampicin in the treatment of other staphylococci and streptococci implant-associated infections is still unclear.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

The efficacy and tolerability of latency-reversing agents in reactivating the HIV-1 reservoir in clinical studies: a systematic review.

Introduction: Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies. Methods: A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration. Results: After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed. Conclusion: This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Prevalence and radiological definitions of acetabular dysplasia after the age of 2 years: a systematic review.

Acetabular dysplasia is one of the most common causes of early hip osteoarthritis and hip replacement surgery. Recent literature suggests that acetabular dysplasia does not always originate at infancy, but can also develop later during childhood. This systematic review aims to appraise the literature on prevalence numbers of acetabular dysplasia in children after the age of 2 years. A systematic search was performed in several scientific databases. Publications were considered eligible for inclusion if they presented prevalence numbers on acetabular dysplasia in a general population of healthy children aged 2-18 years with description of the radiological examination. Quality assessment was done using the Newcastle-Ottawa score. Acetabular dysplasia was defined mild when: the center-edge angle of Wiberg (CEA-W) measured 15-20°, the CEA-W ranged between -1 to -2SD for age, or based on the acetabular index using thresholds from the Tönnis table. Severe dysplasia was defined by a CEA-W < 15°, <-2SD for age, or acetabular index according to Tönnis. Of the 1837 screened articles, four were included for review. Depending on radiological measurement, age and reference values used, prevalence numbers for mild acetabular dysplasia vary from 13.4 to 25.6% and for severe acetabular dysplasia from 2.2 to 10.9%. Limited literature is available on prevalence of acetabular dysplasia in children after the age of 2 years. Prevalence numbers suggest that acetabular dysplasia is not only a condition in infants but also highly prevalent later in childhood.

Mechanisms Linking Physical Activity with Psychiatric Symptoms Across the Lifespan: A Systematic Review.

BACKGROUND: Physical activity has been suggested as a protective factor against psychiatric symptoms. While numerous studies have focused on the magnitude of physical activity's effect on psychiatric symptoms, few have examined the potential mechanisms. OBJECTIVE: The current review aimed to synthesize scientific evidence of the mechanisms through which physical activity might reduce psychiatric symptoms across the lifespan. METHODS: We included articles that were published before March 2022 from five electronic databases (MEDLINE, Web of Science, PsycINFO, Embase, and Cochrane). A qualitative synthesis of studies was conducted. The risk of bias assessment was performed using The Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews. Studies were included if they explored the possible mechanisms through which physical activity influences psychiatric symptoms (i.e., internalizing and externalizing symptoms) across the lifespan. RESULTS: A total of 22 articles were included (three randomized controlled trials, four non-randomized controlled trials, three prospective longitudinal studies, and 12 cross-sectional studies). Overall, most of the studies focused on children, adolescents, and young adults. Our findings showed that self-esteem, self-concept, and self-efficacy were the only consistent paths through which physical activity influences psychiatric symptoms (specifically depressive and anxiety symptoms) across the lifespan. There were insufficient studies to determine the role of neurobiological mechanisms. CONCLUSIONS: Overall, future physical activity interventions with the purpose of improving mental health should consider these mechanisms (self-esteem, self-concept, self-efficacy) to develop more effective interventions. CLINICAL TRIAL REGISTRATION: The protocol of this study was registered in the PROSPERO database (registration number CRD42021239440) and published in April 2022.

Association of gestational thyroid function and thyroid peroxidase antibody positivity with postpartum depression: a prospective cohort study and systematic literature review with meta-analysis.

IMPORTANCE: Postpartum depression (PPD) has a major impact on maternal and offspring well-being, with multiple possible risk factors: Studies on the association of thyroid peroxidase antibody (TPOAb) positivity and thyroid function with PPD provide heterogeneous results. OBJECTIVE: To study the association of thyroid function and TPOAb positivity with PPD. DESIGN: We assessed the association of TPOAb and thyroid function with PPD in a population-based prospective cohort study and performed a systematic literature review and meta-analysis. METHODS: We measured thyroid stimulating hormone (TSH), free thyroxine (FT4), and TPOAb between 9- and 17-week gestation. Postpartum depression was assessed with Edinburgh Postpartum Depression Scale at 2-month postpartum and Brief Symptom Inventory at 2-, 6-, and 36-month postpartum. Additionally, we performed a systematic literature review and meta-analysis assessing this association. RESULTS: In the present study, there was no association of thyroid function with PPD (TSH: odds ratio [OR] 0.83, 95% CI 0.58-1.19, P = .32; FT4: OR 0.99, 95% CI 0.95-1.05, P = .86) or TPOAb positivity with PPD (OR 0.79, 95% CI 0.47-1.33, P = .37). An impaired thyroidal response to human chorionic gonadotropin (hCG), a surrogate marker for TPOAb positivity, was associated with a lower risk of PPD (P for interaction TSH = 0.04; FT4 = 0.06). Our systematic review and meta-analysis included 3 articles that were combined with the present study. There was no statistically significant association of TPOAb positivity with PPD (OR 1.93, 95% CI 0.91-4.10, P = .08), but the results were heterogeneous (I2 = 79%). CONCLUSIONS AND RELEVANCE: There was no significant association of TPOAb positivity, TSH, or FT4 with PPD. Our systematic review and meta-analysis revealed high heterogeneity of the current literature. Although TPOAb-positive women should be monitored for postpartum thyroiditis, our findings do not support routinely screening for PPD.

Diagnostic Accuracy of Portable, Handheld Point-of-Care Tests vs Laboratory-Based Bilirubin Quantification in Neonates: A Systematic Review and Meta-analysis.

Importance: Quantification of bilirubin in blood is essential for early diagnosis and timely treatment of neonatal hyperbilirubinemia. Handheld point-of-care (POC) devices may overcome the current issues with conventional laboratory-based bilirubin (LBB) quantification. Objective: To systematically evaluate the reported diagnostic accuracy of POC devices compared with LBB quantification. Data Sources: A systematic literature search was conducted in 6 electronic databases (Ovid MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) up to December 5, 2022. Study Selection: Studies were included in this systematic review and meta-analysis if they had a prospective cohort, retrospective cohort, or cross-sectional design and reported on the comparison between POC device(s) and LBB quantification in neonates aged 0 to 28 days. Point-of-care devices needed the following characteristics: portable, handheld, and able to provide a result within 30 minutes. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Data Extraction and Synthesis: Data extraction was performed by 2 independent reviewers into a prespecified, customized form. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was performed of multiple Bland-Altman studies using the Tipton and Shuster method for the main outcome. Main Outcomes and Measures: The main outcome was mean difference and limits of agreement in bilirubin levels between POC device and LBB quantification. Secondary outcomes were (1) turnaround time (TAT), (2) blood volumes, and (3) percentage of failed quantifications. Results: Ten studies met the inclusion criteria (9 cross-sectional studies and 1 prospective cohort study), representing 3122 neonates. Three studies were considered to have a high risk of bias. The Bilistick was evaluated as the index test in 8 studies and the BiliSpec in 2. A total of 3122 paired measurements showed a pooled mean difference in total bilirubin levels of -14 µmol/L, with pooled 95% CBs of -106 to 78 µmol/L. For the Bilistick, the pooled mean difference was -17 µmol/L (95% CBs, -114 to 80 µmol/L). Point-of-care devices were faster in returning results compared with LBB quantification, whereas blood volume needed was less. The Bilistick was more likely to have a failed quantification compared with LBB. Conclusions and Relevance: Despite the advantages that handheld POC devices offer, these findings suggest that the imprecision for measurement of neonatal bilirubin needs improvement to tailor neonatal jaundice management.

Evaluating associations between level of trauma care and outcomes of patients with specific severe injuries: A systematic review and meta-analysis.

BACKGROUND: Trauma networks have multiple designated levels of trauma care. This classification parallels concentration of major trauma care, creating innovations and improving outcome measures. OBJECTIVES: The objective of this study is to assess associations of level of trauma care with patient outcomes for populations with specific severe injuries. METHODS: A systematic literature search was conducted using six electronic databases up to April 19, 2022 (PROSPERO CRD42022327576). Studies comparing fatal, nonfatal clinical, or functional outcomes across different levels of trauma care for trauma populations with specific severe injuries or injured body region (Abbreviated Injury Scale score ≥3) were included. Two independent reviewers included studies, extracted data, and assessed quality. Unadjusted and adjusted pooled effect sizes were calculated with random-effects meta-analysis comparing Level I and Level II trauma centers. RESULTS: Thirty-five studies (1,100,888 patients) were included, of which 25 studies (n = 443,095) used for meta-analysis, suggesting a survival benefit for the severely injured admitted to a Level I trauma center compared with a Level II trauma center (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 1.06-1.25). Adjusted subgroup analysis on in-hospital mortality was done for patients with traumatic brain injuries (OR, 1.23; 95% CI, 1.01-1.50) and hemodynamically unstable patients (OR, 1.09; 95% CI, 0.98-1.22). Hospital and intensive care unit length of stay resulted in an unadjusted mean difference of -1.63 (95% CI, -2.89 to -0.36) and -0.21 (95% CI, -1.04 to 0.61), respectively, discharged home resulted in an unadjusted OR of 0.92 (95% CI, 0.78-1.09). CONCLUSION: Severely injured patients admitted to a Level I trauma center have a survival benefit. Nonfatal outcomes were indicative for a longer stay, more intensive care, and more frequently posthospital recovery trajectories after being admitted to top levels of trauma care. Trauma networks with designated levels of trauma care are beneficial to the multidisciplinary character of trauma care. LEVEL OF EVIDENCE: Systematic review and meta-analysis; Level III.

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%.

Systematic Review of the Content Validity of Patient Reported Outcome Measures of Transition to Parenthood.

This review aims to identify self-report instruments examining aspects of transition to parenthood for use in practice and research. After performing a literature search in Embase, Medline, Web of Science, Cochrane, PsycINFO and Google Scholar, the Patient Reported Outcome Measures (PROMs) measuring (aspects of) transition to parenthood during pregnancy or up to 1-year postpartum were identified. Following COSMIN guidelines for systematic reviews on PROMs, the quality of the PROM development and PROM content validity was evaluated. From the 129 included studies, 39 PROMs assessed aspects of transition to parenthood. A total of 32 PROMs were included in the evaluation. The development quality of 30/32 PROMS was mostly rated as inadequate and the quality of 15 content validity studies was mostly rated as doubtful. All PROMs received inadequate or doubtful ratings on content validity. Most of the PROMs measuring aspects of the transition to parenthood didn't include parents' points of view when developing them. Many PROMs are being used for a long time without reassessing relevance, comprehensiveness, and comprehensibility among parents and/or practitioners. It is recommended that researchers and healthcare professionals assess content validity of the PROM before use with the target population.

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.

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.