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Economic Analysis and Policy Sep 2023This paper examines the effectiveness of four major COVID-19 social distancing policies, (i) shelter-in-place orders (SIPO), (ii) non-essential business closures, (iii)...
This paper examines the effectiveness of four major COVID-19 social distancing policies, (i) shelter-in-place orders (SIPO), (ii) non-essential business closures, (iii) mandatory quarantine for travelers, and (iv) bans on large gatherings, on both COVID cases and COVID deaths. Results indicate that states are highly ineffective in producing the fraction of the population that does not have COVID-19 or the fraction of the population that does not die from COVID-19. We find that having any form of social distancing policies increases the fraction of the population not considered a positive COVID-19 case by 23.5 percentage points. Results also show that having any of the four major social distancing policies reduces the fraction of the population who has died of COVID-19 by 1.3 percentage points between March 1, 2020 and September 1, 2020; during the first 100 days, effectiveness would improve by 2.1 percentage points. Evidence suggests that there is no effective uniform national COVID-19 social distancing policy. Furthermore, conditional efficiency regressions after 100 days suggest that behavioral noncompliance and premature expiration of social distancing policies both negatively impact effectiveness. Partial regression plots suggest that bans on large gatherings and the closure of non-essential businesses were the two most impactful COVID-19 social distancing policies.
PubMed: 37363405
DOI: 10.1016/j.eap.2023.06.026 -
Acta Orthopaedica Jun 2023Physeal fractures represent 15-20% of all pediatric fractures and may lead to premature physeal closure (PPC). The aim of our study was to determine the incidence rates...
BACKGROUND AND PURPOSE
Physeal fractures represent 15-20% of all pediatric fractures and may lead to premature physeal closure (PPC). The aim of our study was to determine the incidence rates of physeal fractures in the lower limb and the proportion of PPC that lead to limb length discrepancy (LLD), and/or angular deformity (AD).
PATIENTS AND METHODS
This retrospective study included 236 consecutive children with physeal fracture in the tibia, distal femur, or distal fibula. We estimated incidence rates and reviewed medical records and radiographs to obtain information regarding the development of PPC leading to LLD and AD. Of the 236 children, 100 had planned growth control or were referred for growth control due to symptoms of PPC.
RESULTS
The total incidence rate was 35 (95% CI 30-39) per 100,000 person-years, with 1.2 (CI 0.5-23) for distal femur, 5.7 (CI 3.1-7.8) for proximal tibia, 14 (CI 11-17) for distal tibia, and 14 (CI 11-17) for distal fibula. The overall prevalence of PPC was 9.7% (CI 6.3-14), while the prevalence was 38% (CI 8.5-76) for distal femur, 15% (CI 5.9-31) for proximal tibia, 14% (CI 7.4--22) for distal tibia, and 1.1% (CI 0.3--59) for distal fibula. We found a significant higher hazard of PPC in fractures with ≥ 3 mm displacement (hazard ratio: 12, CI 1.5-97).
CONCLUSION
10% of children with physeal fractures developed PPC that led to LLD or AD. The highest hazard ratio was in children who had an initial fracture displacement. This study highlights the importance of routine and uniform growth evaluation after a physeal fracture.
Topics: Humans; Child; Incidence; Cohort Studies; Retrospective Studies; Tibial Fractures; Growth Plate; Lower Extremity; Fractures, Multiple
PubMed: 37345369
DOI: 10.2340/17453674.2023.13429 -
Medicine Jun 2023The objective of this study was to evaluate the effect of maturing fetal lung on clinical efficacy of acetaminophen in the treatment of premature infants with patent... (Clinical Trial)
Clinical Trial
The objective of this study was to evaluate the effect of maturing fetal lung on clinical efficacy of acetaminophen in the treatment of premature infants with patent ductus arteriosus (PDA). A total of 441 premature infants admitted to our hospital from May 2020 to May 2021 were recruited, including 152 premature infants receiving fetal lung maturation (13 cases of PDA closure with drug use and 2 cases failed) and 289 cases without maturing fetal lung (17 cases of PDA closure and 8 cases failed). Finally, a total of 30 cases were enrolled in this clinical trial. All infants were divided into groups A and B according to whether fetal lung maturation was adopted before delivery. In group A, 13 infants received fetal lung maturation, and 17 in group B did not undergo fetal lung maturation. Infants in both groups were orally given with acetaminophen. After 3-day treatment, the second course of treatment was given immediately if PDA was not closed. The PDA closure rate and patency rate of PDA at the end of 2 treatment courses were statistically compared between 2 groups. The feeding intolerance, upper gastrointestinal bleeding, renal failure, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, the age at total enteral nutrition and the length of hospital stay were also compared between 2 groups. After the 1st and 2nd treatment courses, the PDA closure rate in group A was 84.61%, significantly higher than 52.94% in group B (P < .05), whereas there was no significant difference in the PDA patency rate between 2 groups (P > .05). No significant differences were observed regarding the feeding intolerance, renal failure, necrotizing enterocolitis, periventricular-intraventricular hemorrhage, bronchopulmonary dysplasia, the length of hospital stay and the age at total enteral nutrition between 2 groups (all P > .05). In addition, the incidence of upper gastrointestinal bleeding in group A was 7.69%, slightly lower than 5.88% in group B (P > .05). Compared with premature infants untreated with fetal lung maturation interventions before delivery, premature infants who receive fetal lung maturation interventions combined with acetaminophen for PDA are likely to obtain a higher PDA closure rate and a lower incidence rate of the upper gastrointestinal bleeding.
Topics: Humans; Infant, Newborn; Acetaminophen; Bronchopulmonary Dysplasia; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Gastrointestinal Hemorrhage; Infant, Premature; Lung
PubMed: 37327300
DOI: 10.1097/MD.0000000000034011 -
PharmacoEconomics Aug 2023Atrial fibrillation (AF) remains the most common form of cardiac arrhythmia. Management of AF aims to reduce the risk of stroke, heart failure and premature mortality...
BACKGROUND
Atrial fibrillation (AF) remains the most common form of cardiac arrhythmia. Management of AF aims to reduce the risk of stroke, heart failure and premature mortality via rate or rhythm control. This study aimed to review the literature on the cost effectiveness of treatment strategies to manage AF among adults living in low-, middle- and high-income countries.
METHODS
We searched MEDLINE (OvidSp), Embase, Web of Science, Cochrane Library, EconLit and Google Scholar for relevant studies between September 2022 and November 2022. The search strategy involved medical subject headings or related text words. Data management and selection was performed using EndNote library. The titles and abstracts were screened followed by eligibility assessment of full texts. Selection, assessment of the risk of bias within the studies, and data extraction were conducted by two independent reviewers. The cost-effectiveness results were synthesised narratively. The analysis was performed using Microsoft Excel 365. The incremental cost effectiveness ratio for each study was adjusted to 2021 USD values.
RESULTS
Fifty studies were included in the analysis after selection and risk of bias assessment. In high-income countries, apixaban was predominantly cost effective for stroke prevention in patients at low and moderate risk of stroke, while left atrial appendage closure (LAAC) was cost effective in patients at high risk of stroke. Propranolol was the cost-effective choice for rate control, while catheter ablation and the convergent procedure were cost-effective strategies in patients with paroxysmal and persistent AF, respectively. Among the anti-arrhythmic drugs, sotalol was the cost-effective strategy for rhythm control. In middle-income countries, apixaban was the cost-effective choice for stroke prevention in patients at low and moderate risk of stroke while high-dose edoxaban was cost effective in patients at high risk of stroke. Radiofrequency catheter ablation was the cost-effective option in rhythm control. No data were available for low-income countries.
CONCLUSION
This systematic review has shown that there are several cost-effective strategies to manage AF in different resource settings. However, the decision to use any strategy should be guided by objective clinical and economic evidence supported by sound clinical judgement.
REGISTRATION
CRD42022360590.
Topics: Adult; Humans; Atrial Fibrillation; Cost-Effectiveness Analysis; Developed Countries; Cost-Benefit Analysis; Stroke
PubMed: 37204698
DOI: 10.1007/s40273-023-01276-5 -
Journal of Perinatology : Official... Oct 2023Patent ductus arteriosus (PDA) is the most common cardiovascular condition diagnosed in premature infants. Acetaminophen was first proposed as a potential treatment for... (Review)
Review
Patent ductus arteriosus (PDA) is the most common cardiovascular condition diagnosed in premature infants. Acetaminophen was first proposed as a potential treatment for PDA in 2011. Since that time acetaminophen use among extremely preterm neonates has increased substantially. The limited available data demonstrate that acetaminophen reduces PDA without evident hepatotoxicity. These findings have led some to suggest that acetaminophen is a safe and effective therapy for PDA closure. However, the lack of apparent hepatoxicity is predictable. Acetaminophen induced cellular injury is due to CYP2E1 derived metabolites; and hepatocyte CYP2E1 expression is low in the fetal and neonatal period. Here, we review preclinical and clinical data that support the hypothesis that the lung, which expresses high levels of CYP2E1 during fetal and early postnatal development, may be particularly susceptible to acetaminophen induced toxicity. Despite these emerging data, the true potential pulmonary risks and benefits of acetaminophen for PDA closure are largely unknown. The available clinical studies in are marked by significant weakness including low sample sizes and minimal evaluation of extremely preterm infants who are typically at highest risk of pulmonary morbidity. We propose that studies interrogating mechanisms linking developmentally regulated, cell-specific CYP2E1 expression and acetaminophen-induced toxicity as well as robust assessment of pulmonary outcomes in large trials that evaluate the safety and efficacy of acetaminophen in extremely preterm infants are needed.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Acetaminophen; Indomethacin; Infant, Low Birth Weight; Ibuprofen; Cytochrome P-450 CYP2E1; Infant, Extremely Premature
PubMed: 37169914
DOI: 10.1038/s41372-023-01697-2 -
The Journal of Maternal-fetal &... Dec 2023To identify risk factors, maternal and neonatal adverse outcomes related to unintended lower segment uterine extension during cesarean delivery (CD).
OBJECTIVE
To identify risk factors, maternal and neonatal adverse outcomes related to unintended lower segment uterine extension during cesarean delivery (CD).
METHODS
A retrospective cohort analysis in a single, university-affiliated medical center between 1 January 2018 and 31 December 2019. All singleton pregnancies delivered by CD were included. Univariate and multivariate analyses were performed to identify maternal and obstetrical predictors for uterine extension during CD. For secondary outcomes, we assessed the correlation between uterine extension and any adverse maternal or neonatal outcome. Risk factors were analyzed using ROC statistics to measure their prediction performance for a uterine extension.
RESULTS
Overall, 1746 (19.3%) CDs were performed during the study period. Of them, 121 (6.9%) CDs were complicated by unintended uterine extension. There was no difference in maternal demographics and clinical data stratified by uterine extension at CD. Uterine extensions were significantly more common following induction of labor, intrapartum fever, premature rupture of membranes, a trial of labor after cesarean, advanced gestational age, emergent CD, and in particular CD during the second stage of labor (37.2% vs. 6.5%) and after failed vacuum extraction (6.6% vs. 1.1%), < .05 for all. The incidence of postpartum hemorrhage and re-laparotomy did not differ between the groups. Most of the extensions were caudal-directed (40.4%), and were closed by a two-layer closure (92%). Mean extension size was 4.5 ± 1.7 cm. Using multivariable analysis, the only factor that remained significant was CD at the second stage of labor (adjusted odds ratio (aOR) 54.2, 95% CI 4.5-648.9, = .002), with an area under the ROC curve 0.653 (95% CI 0.595-0.712, < .001). Emergent CD, body mass index, birth weight, failed vacuum attempt, and trial of labor after cesarean were not significant. For secondary outcomes, an unintended uterine extension was associated with longer operation time, higher estimated blood loss, greater pre- to post-CD hemoglobin difference, increased blood products transfusion, puerperal fever, and longer hospital stay. No clinically significant neonatal adverse outcomes were observed.
CONCLUSIONS
In our cohort, second-stage CD was the strongest predictor for an unintended uterine extension. Following uterine extension, women had increased infectious and blood-loss morbidity.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Retrospective Studies; Cesarean Section; Trial of Labor; Postpartum Hemorrhage; Risk Factors
PubMed: 37127602
DOI: 10.1080/14767058.2023.2204997 -
Current Problems in Cardiology Sep 2023This was a first-time evaluation that sought to analyze the cost-effectiveness of oral paracetamol and intravenous (IV) indomethacin as alternatives to ibuprofen for PDA...
This was a first-time evaluation that sought to analyze the cost-effectiveness of oral paracetamol and intravenous (IV) indomethacin as alternatives to ibuprofen for PDA in neonates. Decision-analytic, literature-based, economic simulation models were constructed, to follow up the use and consequences of oral/IV ibuprofen versus IV indomethacin, and oral/IV ibuprofen versus oral paracetamol, as first-line therapies for PDA closure. Model outcomes of interest were "success", defined as PDA closure with/without adverse events, or "failure" due to no response to the first course of treatment, death or premature discontinuation of therapy due to adverse events. Oral ibuprofen is dominant/cost-effective over IV indomethacin in 97.9% of simulated cases, but oral paracetamol was 75.2% dominant/cost-effective over oral ibuprofen. Against IV ibuprofen, IV indomethacin was 55.3% dominant/cost-effective, whereas oral paracetamol was dominant/cost-effective in 98.5% of the cases. Sensitivity analyses confirmed the robustness of the study results. For PDA closure, while IV indomethacin was cost-effective against IV ibuprofen, oral paracetamol was cost-effective against both oral and IV ibuprofen.
Topics: Infant, Newborn; Humans; Indomethacin; Ibuprofen; Ductus Arteriosus, Patent; Acetaminophen; Infant, Premature; Cyclooxygenase Inhibitors; Infant, Low Birth Weight; Cost-Effectiveness Analysis
PubMed: 37088173
DOI: 10.1016/j.cpcardiol.2023.101751 -
Frontiers in Pediatrics 2023Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the closure of ductus arteriosus in premature infants. We aimed to develop and validate an...
An interpretable machine-learning model for predicting the efficacy of nonsteroidal anti-inflammatory drugs for closing hemodynamically significant patent ductus arteriosus in preterm infants.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the closure of ductus arteriosus in premature infants. We aimed to develop and validate an interpretable machine-learning model for predicting the efficacy of NSAIDs for closing hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants.
METHODS
We assessed 182 preterm infants ≤ 30 weeks of gestational age first treated with NSAIDs to close hsPDA. According to the treatment outcome, patients were divided into a "success" group and "failure" group. Variables for analysis were demographic features, clinical features, as well as laboratory and echocardiographic parameters within 72 h before medication use. We developed the machine-learning model using random forests. Model performance was assessed by the area under the receiver operating characteristic curve (AUC). Variable-importance and marginal-effect plots were constructed to explain the predictive model. The model was validated using an external cohort of two preterm infants who received ibuprofen (p.o.) to treat hsPDA.
RESULTS
Eighty-three cases (45.6%) were in the success group and 99 (54.4%) in the failure group. Infants in the success group were associated with maternal chorioamnionitis ( = 0.002), multiple births ( = 0.007), gestational age at birth ( = 0.020), use of indometacin ( = 0.007), use of inotropic agents ( < 0.001), noninvasive ventilation ( = 0.001), plasma albumin level ( < 0.001), PDA size ( = 0.038) and Vmax ( = 0.013). Multivariable binary logistic regression analysis showed that maternal chorioamnionitis, multiple births, use of indomethacin, use of inotropic agents, plasma albumin level, and PDA size were independent risk factors influencing the efficacy of NSAIDs ( < 0.05). The AUC of the random forest model was 0.792. The top-three features contributing most to the model in the variable-importance plot were the plasma albumin level and platelet count 72 h before treatment and 24-h urine volume before treatment. In the external cohort, treatment succeeded in one case and failed in the other. The probabilities of success and failure predicted by the random forest model were 60.2% and 48.4%, respectively.
CONCLUSION
Based on clinical, laboratory, and echocardiographic features before first-time NSAIDs treatment, we constructed an interpretable machine-learning model, which has a certain reference value for predicting the closure of hsPDA in premature infants under 30 weeks of gestational age.
PubMed: 37082702
DOI: 10.3389/fped.2023.1097950 -
Orphanet Journal of Rare Diseases Apr 2023Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep...
BACKGROUND
Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome.
METHODS
A multimodal study was performed based on a paediatric cohort of 15 achondroplasia patients (mean age, 7.8 ± 3.3 years), including clinical and sleep study data, 2D cephalometrics, and 3D geometric morphometry analyses, based on CT-scans (mean age at CT-scan: patients, 4.9 ± 4.9 years; controls, 3.7 ± 4.2 years).
RESULTS
Craniofacial phenotype was characterized by maxillo-zygomatic retrusion, deep nasal root, and prominent forehead. 2D cephalometric studies showed constant maxillo-mandibular retrusion, with excessive vertical dimensions of the lower third of the face, and modifications of cranial base angles. All patients with available CT-scan had premature fusion of skull base synchondroses. 3D morphometric analyses showed more severe craniofacial phenotypes associated with increasing patient age, predominantly regarding the midface-with increased maxillary retrusion in older patients-and the skull base-with closure of the spheno-occipital angle. At the mandibular level, both the corpus and ramus showed shape modifications with age, with shortened anteroposterior mandibular length, as well as ramus and condylar region lengths. We report a significant correlation between the severity of maxillo-mandibular retrusion and obstructive sleep apnea syndrome (p < 0.01).
CONCLUSIONS
Our study shows more severe craniofacial phenotypes at older ages, with increased maxillomandibular retrusion, and demonstrates a significant anatomo-functional correlation between the severity of midface and mandible craniofacial features and obstructive sleep apnea syndrome.
Topics: Humans; Retrognathia; Cephalometry; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Achondroplasia
PubMed: 37072824
DOI: 10.1186/s13023-023-02664-y -
BMJ Open Apr 2023Premature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.
BACKGROUND
Premature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.
OBJECTIVES
To investigate trial completion and publication rate of cancer trials conducted within the Swiss Group for Clinical Cancer Research (SAKK).
DESIGN
Cohort study of clinical trials.
SETTING
Cohort of interventional cancer trials conducted in Switzerland with accrual closure between 1986 and 2021 identified from the SAKK trial management system.
OUTCOMES
Premature trial discontinuation and publication in peer-reviewed journal.
RESULTS
We included 261 trials; median number of recruited patients was 150.5 (range 1-8028). Most trials (67.0%) were randomised. Overall, 76 of 261 (29.1%) trials were prematurely closed for accrual. The three main reasons for premature closure were insufficient accrual in 28 trials, followed by stopping for futility in 17 or efficacy in 8 trials. We included 240 trials for the publication status (21 excluded, because 8 still in follow-up, for 10 the primary completion date was less than a year ago and for 3 the manuscript was submitted, but to accepted yet). 216 of 240 (90.0%) were published as a full article, 14 were published in other formats, leading to an overall publication rate of 95.8%. The rate of premature discontinuation declined over time, with 34.2%, 27.8% and 23.5% in trials activated before 2000, between 2000 and 2009, and since 2010, respectively. We observed an increasing publication rate in peer-reviewed journals over time: 79.2% (closed before 2000), 95.7% (closed between 2000 and 2009) and 93.2% (closed after 2010).
CONCLUSION
Insufficient patient recruitment is still the major reason for premature trial discontinuation. SAKK has continuously improved its quality management of trial conduct over time leading to increased successful trial completion and publication. However, there is still room for improvement to increase the number of trials reaching their target sample size.
Topics: Humans; Cohort Studies; Neoplasms; Research Design; Patient Selection; Ethnicity
PubMed: 37072360
DOI: 10.1136/bmjopen-2022-068490