Rotator cuff repair: Sleep disturbance significantly improves after arthroscopic tendon repair.

PURPOSE: The aim of this study was to quantify sleep quality and define its evolution in patients treated for rotator cuff tears (RCTs) with arthroscopic rotator cuff repair (ARCR) and to understand its correlation with patients' depression and anxiety. METHODS: The patients were part of the 'ARCR_Pred cohort study', a prospective multicentre cohort of ARCR patients. INCLUSION CRITERIA: adult, RCT diagnosed by magnetic resonance imaging, treated by primary ARCR. EXCLUSION CRITERIA: irreparable tears, revision operations, open or mini-open reconstructions, pregnancy. Subjective sleep quality (prevalence and level of disturbance) was analysed. Psychological characteristics (PROMIS Sf questionnaire) and functional outcomes (Constant and Murley Score and Oxford Shoulder Score) were investigated. A gender-based analysis was performed as well. Patients were evaluated before the operation and prospectively at 6 and 12 months. RESULTS: Of the 973 patients, 611 (62.8%) were men, with the mean age being 57.3 ± 9.4 years (range, 21-84). A high prevalence of sleep disturbances was found before ARCR (88.4%), with 59% of the patients complaining of disturbance every night. Sleep disturbances progressively improved at 6 (37.2%) and 12 months (22.0%). Also, nocturnal pain (frequency of night disturbed by pain) progressively improved from 94.3% to 62.4% and then 37.9%. For depression and anxiety, a statistically significant difference (p < 0.05) was retrieved among every group (undisturbed, occasionally and always disturbed) at all follow-ups. On the other hand, the post-op improvement led to a decrease in anxiety and depression levels passing from 50.1 and 51.4 points at baseline to 45.0 and 45.4 at 12 months, respectively. Women had statistically worse sleep quality at 6 and 12 months (41% vs. 36% and 27% vs. 19%, respectively) (p < 0.05). CONCLUSIONS: RCTs cause a high prevalence of sleep disturbance and nocturnal pain, which progressively resolves after an arthroscopic tendon repair. Women have a higher risk than men of presenting disturbed sleep quality. LEVEL OF EVIDENCE: Level III, prognostic cohort study.

Virological impact of HIV drug-resistance testing in children, adolescents, and adults failing first-line ART in Tanzania.

BACKGROUND: Prospective data on the effectiveness of resistance testing in informing treatment decisions and outcomes in with first-line failure in these settings is limited. This study aimed to assess the virological impact of HIV drug-resistance testing in patients with virological failure in Tanzania. METHODS: Participants were randomly assigned to either the control or the experimental group. In addition to the standard of care, patients in the experimental group had access to genotypic drug-resistance testing, information used during treatment change, and were followed up at six-and 12-months to determine virological suppression. RESULTS: A total of 261 patients with a median age of 32 (14.7-44.7) years were enrolled. In the intention-to-treat analysis, at 6-months, suppression was achieved in 58 (42.3%; 95% CI, 34.1-50.1) experimental group patients versus 51 (41.1%; 95% CI, 32.5-49.8) control group patients, with a p-value of 0.4. At-12 months, suppression was achieved in 110 (80.3%; 95% CI, 73.6-87) experimental patients versus 99 (79.8%; 95% CI, 72.8-86.9) control patients, with a p-value of 0.5. In the per-protocol analysis, at 6-months, suppression was observed in 38.46% (95% CI, 27.6-49.3) experimental patients versus 38.6% (95% CI, 26.0-51.2) control patients, with a p-value of 0.5. At 12-months, suppression was observed in 79.49% (95% CI, 70.5-88.5) of experimental patients versus 75.44% (95% CI, 64.3-86.6) of control patients, with a p-value of 0.3. CONCLUSION: Conducting HIV drug-resistance testing, and switch to individualised second-line regimens did not significantly improve virological suppression in patients experiencing first-line ART failure in Tanzania.

Microbial cell-free DNA-sequencing as an addition to conventional diagnostics in neonatal sepsis.

BACKGROUND: Bloodstream infections remain a challenge for neonatologists, as traditional culture-based methods are time-consuming and rely on adequate blood volume. Next-generation sequencing (NGS) offers an alternative, as it can identify microbial cell-free DNA (mcfDNA) in a small blood sample, providing rapid pathogen detection. This study aimed to assess the diagnostic performance of DISQVER®-NGS compared to blood cultures in neonatal patients with suspected sepsis. METHODS: In neonates with suspected sepsis, blood cultures and samples for NGS were prospectively collected. Patients were divided into four categories: 1) sepsis, blood culture positive, 2) clinical sepsis, culture negative, 3) suspected sepsis, 4) validation cohort. RESULTS: NGS detected bacterial, viral or fungal mcfDNA in 24 of 82 samples. Blood cultures were collected in 46 of 84 patients (15/46 positive). DISQVER® correctly identified pathogens in 9/15 patients with a positive blood culture, two with intrinsic resistance to their antibiotic regimen. In seven samples NGS reported the mcfDNA of bacteria that could have theoretically grown in culture but did not. CONCLUSIONS: NGS may enhance sensitivity in sepsis diagnostics by detecting mcfDNA in neonates with suspected sepsis. Interpreting NGS results requires correlation with clinical data, laboratory values, and routine microbiological tests for a comprehensive understanding of the patient's condition. IMPACT: Conventional blood culture methods have limitations in accuracy and turnaround time. The study aimed to investigate the diagnostic performance of the Next-Generation Sequencing method DISQVER® compared to traditional blood cultures in neonatal patients with suspected sepsis. Our findings suggest that NGS has the potential to augment the precision of conventional diagnostic techniques, can lead to improved detection of pathogens and targeted treatment approaches in neonatal sepsis. It is emphasized that further validation and integration with clinical and microbiological data are required to ensure optimal clinical utility.

Early intermediates in bacterial RNA polymerase promoter melting visualized by time-resolved cryo-electron microscopy.

During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAPs), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, here we use time-resolved cryogenic electron microscopy (cryo-EM) to capture four intermediates populated 120 ms or 500 ms after mixing Escherichia coli σ70-RNAP and the λPR promoter. Cryo-EM snapshots revealed that the upstream edge of the transcription bubble unpairs rapidly, followed by stepwise insertion of two conserved nontemplate strand (nt-strand) bases into RNAP pockets. As the nt-strand 'read-out' extends, the RNAP clamp closes, expelling an inhibitory σ70 domain from the active-site cleft. The template strand is fully unpaired by 120 ms but remains dynamic, indicating that yet unknown conformational changes complete RPo formation in subsequent steps. Given that these events likely describe DNA opening at many bacterial promoters, this study provides insights into how DNA sequence regulates steps of RPo formation.

Parents-reported nutrition and feeding difficulties in infants with congenital diaphragmatic hernia after hospital discharge.

PURPOSE: Congenital diaphragmatic hernia (CDH) affects 1 in 3000-5000 newborns. In survivors, long-term complications include gastroesophageal reflux (GER), feeding difficulties, and failure to thrive. Data from the parents' perspective remain scarce. This study aims to report the prevalence and impact of feeding difficulties on CDH families after discharge. METHODS: National web-based survey amongst families with CDH infants in 2021. RESULTS: Caregivers of 112 CDH survivors participated. The baseline characteristics were representative with 54 % male, 83 % left-sided CDH, prenatal diagnosis in 83 %, and 34 % requiring extracorporeal membrane oxygenation. Most infants (81 %) were discharged within three months, with 62 % feeding by mouth, and 30 % requiring a feeding tube. Persisting feeding difficulties were experienced by 73 %, GER being the most common (66 %), followed by insufficient weight gain (64 %). After discharge, 41 % received medical support for failure to thrive. The primary-care pediatrician was consulted most frequently for information (61 %) and treatment of feeding difficulties (74 %). Therapeutic success was reported in 64 %. A cessation of symptoms was achieved in 89 % within three years. CONCLUSION: The majority of CDH infants had persistent feeding difficulties. This survey highlights the impact surrounding feeding problems on CDH families. Further studies and support systems are needed to raise the quality of life in CDH infants and their families.

The Impact of Time to Initiate Therapeutic Hypothermia on Short-Term Neurological Outcomes in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Therapeutic hypothermia is the standard treatment for neonates with hypoxic-ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. METHODS: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. RESULTS: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. CONCLUSION: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.

Approaches for delivery of refractive and optical care services in community and primary care settings.

BACKGROUND: Uncorrected refractive error is a leading cause of vision impairment which, in most cases, can be managed with the appropriate spectacle correction. In 2021, the World Health Assembly endorsed a global target of a 40-percentage-point increase in effective coverage of refractive error by 2030. To achieve this global target, equitable access to refractive and optical services within community and primary care settings needs to be strengthened. This review will inform the development of technical guidance to support improvements in the testing and correction of refractive error among World Health Organization (WHO) member states. OBJECTIVES: To determine the range of approaches for delivery of refractive and optical care services in community and primary care settings, and the methods employed for their evaluation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Global Health databases, grey literature, and annual reports and websites of relevant organizations involved in eye-care delivery from January 2002 to November 2022 to identify approaches for refractive and optical service delivery. SELECTION CRITERIA: We included observational and interventional studies, reviews, and reports from relevant organizations related to delivering refractive services and optical services for preschool and school-aged children and adults in community and primary care settings published between January 2002 and November 2022. We searched for studies and reports published within the last 20 years because vision impairment due to uncorrected refractive error has only recently become a public health and eye health priority, therefore we did not expect to find much relevant literature until after 2002. DATA COLLECTION AND ANALYSIS: Two review authors screened titles, abstracts and full texts, and extracted data. We resolved any discrepancies through discussion. We synthesized data, and presented results as tables, figures, and case studies. This project was led by the World Health Organization (WHO) Vision and Eye Care Programme. MAIN RESULTS: We identified 175 studies from searches of databases and grey literature, 146 records from company reports, and 81 records from website searches of relevant organizations that matched our inclusion criteria. Delivery approaches for refractive and optical services in community care included school-based, pharmacy, and outreach models, whereas primary care approaches comprised vision centre, health centre, and a combination of vision or health centre and door-to-door delivery. In community care, school-based and outreach approaches were predominant, while in primary care, a vision-centre approach was mainly used. In the WHO African region, the school-based and outreach approaches were mainly reported while, in the Americas, the outreach approach was mostly used. Very few approaches for service delivery were reported in the WHO Eastern Mediterranean region. Prominent gaps exist in the evaluation of the approaches, and few studies attempted to evaluate the approaches for delivery of refractive and optical care services. AUTHORS' CONCLUSIONS: We comprehensively describe a range of approaches for delivery of refractive and optical services in community and primary care. Further evaluation of their effectiveness will better inform the application of these service-delivery approaches. The study outcomes will help guide WHO member states in strengthening refractive and optical services at community and primary care levels. FUNDING: This scoping review was supported by the Vision and Eye care Programme, World Health Organization and ATscale Global Partnership. REGISTRATION: The protocol of this scoping review was published in the Open Source Framework.

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience.

OBJECTIVES: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. METHODOLOGY: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). RESULTS: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). CONCLUSION: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

Pre-Epiglottic Baton Plate in Newborns With Pierre Robin Sequence: Revisiting the Practical Workflow.

We demonstrate pre-epiglottic baton plate as non-invasive treatment modality for initial airway management in newborns with Pierre Robin Sequence. A case example illustrates management of upper airway obstruction and feeding using digital technology to facilitate customization. Laryngoscope, 2024.

Arterial hypertension in infants with congenital diaphragmatic hernia following surgical repair.

Pulmonary hypertension (PH) and cardiac dysfunction are established comorbidities of congenital diaphragmatic hernia (CDH). However, there is very little data focusing on arterial hypertension in CDH. This study aims to investigate the incidence of arterial hypertension in neonates with CDH at hospital discharge. Archived clinical data of 167 CDH infants who received surgical repair of the diaphragmatic defect and survived for > 60 days were retrospectively analyzed. Blood pressure (BP) values were averaged for the last 7 days before discharge and compared to standard BP values for sex, age, and height provided by the AHA in 2004. BP values reaching or extending the 95th percentile were defined as arterial hypertension. The use of antihypertensive medication was analyzed at discharge and during hospitalization. Arterial hypertension at discharge was observed in 19 of 167 infants (11.3%) of which 12 (63%) were not receiving antihypertensive medication. Eighty patients (47.9%) received antihypertensive medication at any point during hospitalization and 28.9% of 152 survivors (n = 44) received antihypertensive medication at discharge, although in 45.5% (n = 20) of patients receiving antihypertensive medication, the indication for antihypertensive medication was myocardial hypertrophy or frequency control. BP was significantly higher in ECMO compared to non-ECMO patients, despite a similar incidence of arterial hypertension in both groups (13.8% vs. 10.1%, p = 0.473). Non-isolated CDH, formula feeding, and minimal creatinine in the first week of life were significantly associated with arterial hypertension on univariate analysis. Following multivariate analysis, only minimal creatinine remained independently associated with arterial hypertension.   Conclusion: This study demonstrates a moderately high incidence of arterial hypertension in CDH infants at discharge and an independent association of creatinine values with arterial hypertension. Physicians should be aware of this risk and include regular BP measurements and test of renal function in CDH care and follow-up. What is Known: • Due to decreasing mortality, morbidity is increasing in surviving CDH patients. • Pulmonary hypertension and cardiac dysfunction are well-known cardiovascular comorbidities of CDH. What is New: • There is a moderately high incidence of arterial hypertension in CDH infants at discharge even in a population with frequent treatment with antihypertensive medication. • A more complicated hospital course (ECMO, higher degree of PH, larger defect size) was associated with a higher risk for arterial hypertension.

Association of preoperative beta-blocker use and cardiac complications after major noncardiac surgery: a prospective cohort study.

INTRODUCTION: Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. METHODS: In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. RESULTS: A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94-1.12, P=0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83-1.18, P=0.90) for patients on beta-blockers. CONCLUSION: Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. CLINICAL TRIAL REGISTRATION: NCT02573532.

Early intermediates in bacterial RNA polymerase promoter melting visualized by time-resolved cryo-electron microscopy.

During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAP), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, time-resolved cryo-electron microscopy (cryo-EM) was used to capture four intermediates populated 120 or 500 milliseconds (ms) after mixing Escherichia coli σ70-RNAP and the λPR promoter. Cryo-EM snapshots revealed the upstream edge of the transcription bubble unpairs rapidly, followed by stepwise insertion of two conserved nontemplate strand (nt-strand) bases into RNAP pockets. As nt-strand "read-out" extends, the RNAP clamp closes, expelling an inhibitory σ70 domain from the active-site cleft. The template strand is fully unpaired by 120 ms but remains dynamic, indicating yet unknown conformational changes load it in subsequent steps. Because these events likely describe DNA opening at many bacterial promoters, this study provides needed insights into how DNA sequence regulates steps of RPo formation.

Cleft lip and palate surgery simulator: Open source simulation model.

Objective: Cleft lip and palate is the most common craniofacial birth anomaly and requires surgery in the first year of life. However, craniofacial surgery training opportunities are limited. The aim of this study was to present and evaluate an open-source cleft lip and palate hybrid (casting and three-dimensional (3D) printing) simulation model which can be replicated at low cost to facilitate the teaching and training of cleft surgery anatomy and techniques. Design: The soft tissue component of the cleft surgery training model was casted using a 3D printed 5-component mold and silicone. The bony structure was designed to simulate the facial anatomy and to hold the silicone soft tissue. Setting: Two groups, one group of trainees and one group of expert surgeons, at University Hospital Basel in Switzerland and Pontifical Catholic University of Chile in Santiago, Chile, tested the cleft lip and palate simulation model. Participants completed a Likert-based face and content validity questionnaire to assess the realism of the model and its usefulness in surgical training. Results: More than 70 % of the participants agreed that the model accurately simulated human tissues found in patients with unilateral cleft lip and palate. Over 60 % of the participants also agreed that the model realistically replicated surgical procedures. In addition, 80-90 % of the participants found the model to be a useful and appropriate tool for teaching the anatomy and surgical techniques involved in performing unilateral cleft lip and palate repair. Conclusion: This open-source protocol provides a cost-effective solution for surgeons to introduce the cleft morphology and surgical techniques to trainees on a regular basis. It addresses the current financial barrier that limits access to commercially available models during the early stages of surgeon training prior to specialization in the field.

Is the collateral circulation pattern in the hard palate affected by cleft deformity?

OBJECTIVES: To evaluate the influence of collateral vascularization on surgical cleft palate closure and deformities. MATERIALS AND METHODS: Corrosion casting was performed using red-colored acrylic resin in twelve fresh adult cadavers with a normal hard palate. Additionally, white-colored barium sulfate was injected into a fetus with a unilateral complete cleft palate, and layer-by-layer tissue dissection was performed. Both substances were injected into the external carotid arteries. Corrosion casting involved dissolving the soft and hard tissues of the orofacial area utilizing an enzymatic solution. RESULTS: In normal palates, bilateral intraosseous infraorbital arteries formed a network in the premaxilla with the intraosseous nasopalatine- and greater palatine arteries (GPAs). The perforating GPAs anastomosed with the sphenopalatine artery sub-branches. Bilateral extraosseous GPA anastomoses penetrated the median palatine suture. Complex vascularization in the retrotuberal area was detected. In the cleft zone, anastomoses were omitted, whereas in the non-cleft zone, enlarged GPAs were distributed along the cleft edges and followed the anatomical course anteriorly to initiate the network with facial artery sub-branches. CONCLUSIONS: The anatomical subunits of the palate exhibited distinct anastomosis patterns. Despite omitted anastomoses with collateral circulation in the cleft zone, arteries maintained their anatomical pattern as seen in the normal specimen in the non-cleft zone. CLINICAL RELEVANCE: Based on the findings in normal- and cleft palates, surgeons may expect developed anastomosis patterns in the non-cleft zone. Due to the lack of microcirculation in the cleft zone, the existent anastomoses should be maintained as much as possible by the surgical technique. This applies anteriorly in the incisive canal territory, alveolar ridges, and posteriorly in the retrotuberal area.

Particle Dynamics in a Diblock-Copolymer-Based Dodecagonal Quasicrystal and Its Periodic Approximant by X-Ray Photon Correlation Spectroscopy.

Temperature-dependent x-ray photon correlation spectroscopy (XPCS) measurements are reported for a binary diblock-copolymer blend that self-assembles into an aperiodic dodecagonal quasicrystal and a periodic Frank-Kasper σ phase approximant. The measured structural relaxation times are Bragg scattering wavevector independent and are 5 times faster in the dodecagonal quasicrystal than the σ phase, with minimal temperature dependence. The underlying dynamical relaxations are ascribed to differences in particle motion at the grain boundaries within each of these tetrahedrally close-packed assemblies. These results identify unprecedented particle dynamics measurements of tetrahedrally coordinated micellar block polymers, thus expanding the application of XPCS to ordered soft materials.

Consensus definitions in imported human schistosomiasis: a GeoSentinel and TropNet Delphi study.

Terminology in schistosomiasis is not harmonised, generating misunderstanding in data interpretation and clinical descriptions. This study aimed to achieve consensus on definitions of clinical aspects of schistosomiasis in migrants and returning travellers. We applied the Delphi method. Experts from institutions affiliated with GeoSentinel and TropNet, identified through clinical and scientific criteria, were invited to participate. Five external reviewers revised and pilot-tested the statements. Statements focusing on the definitions of acute or chronic; possible, probable, or confirmed; active; and complicated schistosomiasis were managed through REDCap and replies managed in a blinded manner. Round 1 mapped the definitions used by experts; subsequent rounds were done to reach consensus, or quantify disagreement, on the proposed statements. Data were analysed with percentages, medians, and IQRs of a 5-point Likert scale. The study was terminated on the basis of consensus or stability-related and time-related criteria. 28 clinicians and scientists met the criteria for experts. 25 (89%) of 28 experts replied to Round 1, 18 (64%) of 28 to Round 2, 19 (68%) of 28 to Round 3, and 21 (75%) of 28 to at least two rounds. High-level consensus (79-100% agreement and IQRs ≤1) was reached for all definitions. Consensus definitions will foster harmonised scientific and clinical communication and support future research and development of management guidelines for schistosomiasis.

Comparative study on cleft palate morphology after passive presurgical plate therapy in unilateral cleft lip and palate.

BACKGROUND: Presurgical plate therapy has been widely accepted as a treatment prior to palatal cleft closure. The effects of passive presurgical plate therapy on cleft morphology prior to single-stage unilateral cleft lip and palate (UCLP) repair were quantified. PATIENTS AND METHODS: We compared the dimensions of cleft width and cleft area (true cleft and palatal cleft) measured preoperatively at 2 European cleft centers. Center A performed single-stage UCLP repair in 8-month-old infants without any presurgical orthopedic treatment. Center B initiated passive presurgical plate therapy immediately after the birth of the neonates, followed by single-stage UCLP repair at 8 months of age. RESULTS: We included 28 patients with complete UCLP from Center A and 12 patients from Center B. The average anterior width of the true cleft before surgery was significantly smaller in infants at Center B than that in Center A (p = 0.001) with 95% confidence interval of (1.8, 5.7) mm, but the average posterior width was similar in the 2 groups. The mean presurgical true cleft area amounted to 106.8 mm2 (SD = 42.4 mm2) at Center A and 71.9 mm2 (SD = 32.2 mm2) at Center B, with a confidence interval for the difference being (9.8, 60.1) mm2. This corresponded to a 32.7% reduction of the true cleft area when passive presurgical plate therapy was used for the first 8 months of the infants' life. CONCLUSION: Passive presurgical plate therapy in UCLP significantly reduced the cleft area. Implications for the subsequent surgical outcome might depend on the surgical technique used.

Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort.

AIMS: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment. METHODS: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment. RESULTS: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained. CONCLUSIONS: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.