CRISPR-Cas9-mediated barcode insertion into Bacillus thuringiensis for surrogate tracking.

The use of surrogate organisms can enable researchers to safely conduct research on pathogens and in a broader set of conditions. Being able to differentiate between the surrogates used in the experiments and background contamination as well as between different experiments will further improve research efforts. One effective approach is to introduce unique genetic barcodes into the surrogate genome and track their presence using the quantitative polymerase chain reaction (qPCR). In this report, we utilized the CRISPR-Cas9 methodology, which employs a single plasmid and a transformation step to insert five distinct barcodes into Bacillus thuringiensis, a well-established surrogate for Bacillus anthracis when Risk Group 1 organisms are needed. We subsequently developed qPCR assays for barcode detection and successfully demonstrated the stability of the barcodes within the genome through five cycles of sporulation and germination. Additionally, we conducted whole-genome sequencing on these modified strains and analyzed 187 potential Cas9 off-target sites. We found no correlation between the mutations observed in the engineered strains and the predicted off-target sites, suggesting this genome engineering strategy did not directly result in off-target mutations in the genome. This simple approach has the potential to streamline the creation of barcoded B. thuringiensis strains for use in future studies on surrogate genomes. IMPORTANCE: The use of Bacillus anthracis as a biothreat agent poses significant challenges for public health and national security. Bacillus anthracis surrogates, like Bacillus thuringiensis, are invaluable tools for safely understanding Bacillus anthracis properties without the safety concerns that would arise from using a virulent strain of Bacillus anthracis. We report a simple method for barcode insertion into Bacillus thuringiensis using the CRISPR-Cas9 methodology and subsequent tracking by quantitative polymerase chain reaction (qPCR). Moreover, whole-genome sequencing data and CRISPR-Cas9 off-target analyses in Bacillus thuringiensis suggest that this gene-editing method did not directly cause unwanted mutations in the genome. This study should assist in the facile development of barcoded Bacillus thuringiensis surrogate strains, among other biotechnological applications in Bacillus species.

Progression of brain injuries associated with methotrexate chemotherapy in childhood acute lymphoblastic leukemia.

BACKGROUND: Brain bases and progression of methotrexate-associated neurotoxicity and cognitive disturbances remain unknown. We tested whether brain abnormalities worsen in proportion to intrathecal methotrexate(IT-MTX) doses. METHODS: In this prospective, longitudinal study, we recruited 19 patients with newly diagnosed acute lymphoblastic leukemia 4-to-20 years of age and 20 matched controls. We collected MRI and neuropsychological assessments at a pre-methotrexate baseline and at week 9, week 22, and year 1 during treatment. RESULTS: Patients had baseline abnormalities in cortical and subcortical gray matter(GM), white matter(WM) volumes and microstructure, regional cerebral blood flow, and neuronal density. Abnormalities of GM, blood flow, and metabolites worsened in direct proportions to IT-MTX doses. WM abnormalities persisted until week 22 but normalized by year 1. Brain injuries were localized to dorsal and ventral attentional and frontoparietal cognitive networks. Patients had cognitive deficits at baseline that persisted at 1-year follow-up. CONCLUSIONS: Baseline abnormalities are likely a consequence of neuroinflammation and oxidative stress. Baseline abnormalities in WM microstructure and volumes, and blood flow persisted until week 22 but normalized by year 1, likely due to treatment and its effects on reducing inflammation. The cytotoxic effects of IT-MTX, however, likely contributed to continued, progressive cortical thinning and reductions in neuronal density, thereby contributing to enduring cognitive deficits. IMPACT: Brain abnormalities at a pre-methotrexate baseline likely are due to acute illness. The cytotoxic effects of intrathecal MTX contribute to progressive cortical thinning, reductions in neuronal density, and enduring cognitive deficits. Baseline white matter abnormalities may have normalized via methotrexate treatment and decreasing neuroinflammation. Corticosteroid and leucovorin conferred neuroprotective effects. Our findings suggest that the administration of neuroprotective and anti-inflammatory agents should be considered even earlier than they are currently administered. The neuroprotective effects of leucovorin suggest that strategies may be developed that extend the duration of this intervention or adapt it for use in standard risk patients.

Associations between COVID-19 therapies and outcomes in rural and urban America: A multisite, temporal analysis from the Alpha to Omicron SARS-CoV-2 variants.

PURPOSE: To investigate the enduring disparities in adverse COVID-19 events between urban and rural communities in the United States, focusing on the effects of SARS-CoV-2 vaccination and therapeutic advances on patient outcomes. METHODS: Using National COVID Cohort Collaborative (N3C) data from 2021 to 2023, this retrospective cohort study examined COVID-19 hospitalization, inpatient death, and other adverse events. Populations were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR). Adjustments included demographics, variant-dominant waves, comorbidities, region, and SARS-CoV-2 treatment and vaccination. Statistical methods included Kaplan-Meier survival estimates, multivariable logistic, and Cox regression. FINDINGS: The study included 3,018,646 patients, with rural residents constituting 506,204. These rural dwellers were older, had more comorbidities, and were less vaccinated than their urban counterparts. Adjusted analyses revealed higher hospitalization odds in UAR and NAR (aOR 1.07 [1.05-1.08] and 1.06 [1.03-1.08]), greater inpatient death hazard (aHR 1.30 [1.26-1.35] UAR and 1.37 [1.30-1.45] NAR), and greater risk of other adverse events compared to urban dwellers. Delta increased, while Omicron decreased, inpatient adverse events relative to pre-Delta, with rural disparities persisting throughout. Treatment effectiveness and vaccination were similarly protective across all cohorts, but dexamethasone post-ventilation was effective only in urban areas. Nirmatrelvir/ritonavir and molnupiravir better protected rural residents against hospitalization. CONCLUSIONS: Despite advancements in treatment and vaccinations, disparities in adverse COVID-19 outcomes persist between urban and rural communities. The effectiveness of some therapeutic agents appears to vary based on rurality, suggesting a nuanced relationship between treatment and geographic location while highlighting the need for targeted rural health care strategies.

Aortic Stiffness Is Associated With Higher Nighttime Ambulatory Blood Pressure in Middle-Aged and Older Adults.

PURPOSE: The objective of this study was to determine the relationship between aortic stiffening and brachial and central ambulatory blood pressure (AMBP) in a nonclinical sample of middle-aged and older adults (MA/O). We hypothesized aortic stiffness would be positively associated with 24-hr, daytime, and nighttime brachial and central AMBP. METHODS: Fifty-one participants aged ≥50 yr (21 males and 30 females, mean age 63.4 ± 9.0 yr) with a body mass index <35 kg/m2 who also had a resting brachial blood pressure (BP) <160/100 mmHg with or without BP medications were recruited for this cross-sectional analysis. All participants underwent measures of aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]) and 24-hr AMBP monitoring. Bivariate correlations assessed the relationship between cfPWV, brachial, and central AMBP. Partial correlations were used to independently adjust for traditional cardiovascular disease (CVD) risk factors including age, sex, waist circumference, glucose, and augmentation index normalized to heart rate 75 bpm, a surrogate measure of arterial stiffness, and in a multivariable combined model. RESULTS: Nighttime brachial systolic BP (r = 0.31) and central systolic BP (r = 0.30) were correlated with cfPWV in the multivariable combined model (P≤ .05). Nighttime brachial pulse pressure and central pulse pressure were correlated with cfPWV after independently adjusting for all CVD risk factors (P≤ .05, all) but not when combined in the multivariable model (P> .05). CONCLUSIONS: Higher nighttime brachial and central AMBP with older age are related, in part, to greater aortic stiffening. Therefore, interventions to lower or prevent aortic stiffening may also lower nighttime BP in MA/O adults to lower CVD risk.

Short-term aerobic exercise prevents development of glucocorticoid myopathic features in aged skeletal muscle in a sex-dependent manner.

Older adults are vulnerable to glucocorticoid-induced muscle atrophy and weakness, with sex potentially influencing their susceptibility to those effects. Aerobic exercise can reduce glucocorticoid-induced muscle atrophy in young rodents. However, it is unknown whether aerobic exercise can prevent glucocorticoid myopathy in aged muscle. The objectives of this study were to define the extent to which sex influences the development of glucocorticoid myopathy in aged muscle, and to determine the extent to which aerobic exercise training protects against myopathy development. Twenty-four-month-old female (n = 30) and male (n = 33) mice were randomized to either sedentary or aerobic exercise groups. Within their respective groups, mice were randomized to either daily treatment with dexamethasone (DEX) or saline. Upon completing treatments, the contractile properties of the triceps surae complex were assessed in situ. DEX marginally lowered muscle mass and soluble protein content in both sexes, which was attenuated by aerobic exercise only in females. DEX increased sub-tetanic force and rate of force development only in females, which was not influenced by aerobic exercise. Muscle fatigue was higher in both sexes following DEX, but aerobic exercise prevented fatigue induction only in females. The sex-specific differences to muscle function in response to DEX treatment coincided with sex-specific changes to the content of proteins related to calcium handling, mitochondrial quality control, reactive oxygen species production, and glucocorticoid receptor in muscle. These findings define several important sexually dimorphic changes to aged skeletal muscle physiology in response to glucocorticoid treatment and define the capacity of short-term aerobic exercise to protect against those changes. KEY POINTS: There are sexually dimorphic effects of glucocorticoids on aged skeletal muscle physiology. Glucocorticoid-induced changes to aged muscle contractile properties coincide with sex-specific differences in the content of calcium handling proteins. Aerobic exercise prevents glucocorticoid-induced fatigue only in aged females and coincides with differences in the content of mitochondrial quality control proteins and glucocorticoid receptors.

Targeting VEGF-mediated blood-brain barrier disruption in advanced cerebral leukodystrophy.

The earliest clinical manifestation of cerebral adrenoleukodystrophy (CALD) is adrenal insufficiency (AI) characterized by elevations in ACTH and loss of cortisol. We showed high (though physiologically achievable) levels of ACTH increases endothelial permeability, increases anisotropy, and increases VEGF secretion. An ACBD1 knockout endothelial cell line had increased sensitivity to ACTH and VEGF. Inhibition of VEGF via application of anti-VEGF (bevacizumab) improved permeability. Six boys with advanced CALD were treated with bevacizumab combined with dexamethasone and ruxolitinib as immune suppressants. Most boys had decreases in gadolinium enhancement on MRI indicating improvement in endothelial function, though all boys continued to progress symptomatically.

Challenging the Concept of Statistical Fragility: Is There Any Value Added?

ABSTRACT: Today, well-designed randomized clinical trials (RCTs) are considered the pinnacle of clinical research, and they inform many practices in orthopaedics. When designing these studies, researchers conduct a power analysis, which allows researchers to strike a balance between (1) enrolling enough patients to detect a clinically important treatment effect (i.e., researchers can be confident that the effect is unlikely due to chance) and (2) cost, time, and risk to patients, which come with enrolling an excessive number of patients. Because researchers will have a desire to conduct resource-efficient RCTs and protect patients from harm, many studies report a p value that is close to the threshold for significance. The concept of the fragility index (FI) was introduced as a simple way to interpret RCT findings, but it does not account for RCT design. The adoption of the FI conflicts with researchers' goals of designing efficient RCTs that conserve resources and limit ineffective or harmful treatments to patients. The use of the FI may reflect many clinicians' lack of familiarity with interpreting p values beyond "significant" or "nonsignificant." Instead of inventing new metrics to convey the same information provided by the p value, greater emphasis should be placed on educating clinicians on how to interpret p values and, more broadly, statistics, when reading scientific studies.

The Society of Thoracic Surgeons Clinical Practice Guidelines on the Management of Neonates and Infants with Coarctation.

BACKGROUND: Although coarctation of the aorta without concomitant intracardiac pathology is relatively common, there is lack of guidance regarding aspects of its management in neonates and infants. METHODS: A panel of experienced congenital cardiac surgeons, cardiologists, and intensivists was created, and key questions related to the management of isolated coarctation in neonates and infants were formed using the PICO (Patients/Population, Intervention, Comparison/Control, Outcome) Framework. A literature search was then performed for each question. Practice guidelines were developed with classification of recommendation and level of evidence using a modified Delphi method. RESULTS: For neonates and infants with isolated coarctation, surgery is indicated in the absence of obvious surgical contraindications. For patients with risk factors for surgery, medical management before intervention is reasonable. For those stable off prostaglandin E1, the threshold for intervention remains unclear. Thoracotomy is indicated when arch hypoplasia is not present. Sternotomy is preferable when arch hypoplasia is present that cannot be adequately addressed through a thoracotomy. Sternotomy may also be considered in the presence of a bovine aortic arch. Antegrade cerebral perfusion may be reasonable when the repair is performed through a sternotomy. Extended end-to-end, arch advancement, and patch augmentation are all reasonable techniques. CONCLUSIONS: Surgery remains the standard of care for the management of isolated coarctation in neonates and infants. Depending on degree and location, arch hypoplasia may require a sternotomy approach as opposed to a thoracotomy approach. Significant opportunities remain to better delineate management in these patients.

Lower Pregnancy and Live Birth Rates with Vaginal Endometrin Plus Intramuscular Progesterone Every Third Day Versus Intramuscular Progesterone Alone in Programmed Frozen Embryo Transfers: A Retrospective Case-control Study.

This study aimed to determine whether the use of vaginal Endometrin plus intramuscular progesterone on every third day (VIM) in programmed frozen embryo transfer (FET) is associated with lower pregnancy and live birth rates compared to daily intramuscular progesterone (IM). FET data from a single program were collected between November 2018 and December 2021. A total of 903 FETs were analyzed, including 504 FETs in the IM group, and 399 FETs in the VIM group. Inclusion criteria were women undergoing FETs with either 50 mg daily IM progesterone only (control) or 200 mg Endometrin twice daily plus 50 mg IM progesterone on every third day, with the transfer of a single day 5 or 6 frozen embryo. There were no significant differences in patient age at time of FETs, BMI, endometrial thickness, blastocyst quality, or infertility diagnosis between the groups. The VIM had significantly lower positive hCG and clinical pregnancy rates compared to the IM (60.2% vs 72.0% and 40.6% vs 56.7%, respectively, P = 0.0002 and P < 0.0001). The live birth rate was 36.1% in the VIM, compared to 49.4% in the IM (P < 0.0001). These findings also remained significant when excluding FETs with donor egg (35.9% vs 50.1%, P < 0.0001). This study demonstrated that VIM in FET cycles yields significantly lower pregnancy and live birth rates compared to IM along. IM progesterone alone may be preferable to combined Endometrin and IM progesterone in patients undergoing programmed frozen embryo transfers.

A multi-site 99mTc-HMPAO SPECT study of cerebral blood flow in a community sample of patients with major depression.

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.

Design and synthesis of a library of C8-substituted sulfamidoadenosines to probe bacterial permeability.

Gram-negative bacteria pose a major challenge in antibiotic drug discovery because their cell envelope presents a permeability barrier that affords high intrinsic resistance to small-molecule drugs. The identification of correlations between chemical structure and Gram-negative permeability would thus enable development of predictive tools to facilitate antibiotic discovery. Toward this end, have advanced a library design paradigm in which various chemical scaffolds are functionalized at different regioisomeric positions using a uniform reagent set. This design enables decoupling of scaffold, regiochemistry, and substituent effects upon Gram-negative permeability of these molecules. Building upon our recent synthesis of a library of C2-substituted sulfamidoadenosines, we have now developed an efficient synthetic route to an analogous library of regioisomeric C8-substituted congeners. The C8 library samples a region of antibiotic-relevant chemical space that is similar to that addressed by the C2 library, but distinct from that sampled by a library of analogously substituted oxazolidinones. Selected molecules were tested for accumulation in Escherichia coli in a pilot analysis, setting the stage for full comparative evaluation of these libraries in the future.

Methods for the discovery and characterization of octocoral terpene cyclases.

Octocorals are the most prolific source of terpenoids in the marine environment, with more than 4000 different compounds known from the phylum to date. However, the biochemical and genetic origin of their production remained elusive until recent studies showed that octocorals encode genes responsible for the biosynthesis of terpenoids in their own chromosomal DNA rather than from microbial symbionts as originally proposed. The identified coral genes include those encoding a new group of class I terpene cyclases (TCs) clustered among other candidate classes of tailoring enzymes. Phylogenetic analyses established octocoral TCs as a monophyletic clade, distinct from TCs of plants, bacteria, and other organisms. The newly discovered group of TCs appears to be ubiquitous in octocorals and is evolutionarily ancient. Given the recent discovery of octocoral terpenoid biochemistry and only limited genomic data presently available, there is substantial potential for discovering new biosynthetic pathways from octocorals for terpene production. The following chapter outlines practical experimental procedures for octocoral DNA and RNA extraction, genome and transcriptome assembly and mining, TC cloning and gene expression, protein purification, and in vitro analyses.

Corrigendum: A natural sustained-intestinal release formulation of red chili pepper extracted capsaicinoids (Capsifen®) safely modulates energy balance and endurance performance: a randomized, double-blind, placebo-controlled study.

[This corrects the article DOI: 10.3389/fnut.2024.1348328.].

A systematic review of social-validity assessments in the Journal of Applied Behavior Analysis: 2010-2020.

We conducted a systematic review of studies published in the Journal of Applied Behavior Analysis between 2010 and 2020 to identify reports of social validity. A total of 160 studies (17.60%) published during this time included a measure of social validity. For each study, we extracted data on (a) the dimensions of social validity, (b) the methods used for collecting social-validity data, (c) the respondents, and (d) when social-validity data were collected. Most social-validity assessments measured the acceptability of intervention procedures and outcomes, with fewer evaluating goals. The most common method for collecting social validity data was Likert-type rating scales, followed by non-Likert-type questionnaires. In most studies, the direct recipients of the intervention provided feedback on social validity. Social-validity assessment data were often collected at the conclusion of the study. We provide examples of social-validity measurement methods, discuss their strengths and limitations, and provide recommendations for improving the future collection and reporting of social-validity data.

Association between intravenous fluids during labor and primary postpartum hemorrhage: A retrospective cohort study.

INTRODUCTION: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high-volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labor (<2500 mL). MATERIAL AND METHODS: A retrospective cohort study was conducted at a tertiary referral hospital in Sydney, Australia between 1st September 2021 and 31st October 2022. Inclusion criteria were: women with a live singleton fetus in a cephalic presentation; planning a vaginal birth; and admitted for labor and birth care between 37 and 42 week gestation. The study factor was IV fluids during labor and the primary outcome was primary PPH ≥500 mL. Secondary outcomes included cesarean section and major perineal injury. Pregnancy, birth, and postnatal data were obtained from the hospital's electronic clinical database, electronic medical records, and paper fluid order documentation. Multivariable logistic regression and multiple imputation were used to explore the relationship between volume of IV fluids in labor and PPH. RESULTS: A total of 1023 participants were included of which 339 had a primary PPH (33.1%). There was no association between high-volume IV fluids and PPH after adjusting for demographic and clinical factors (adjusted odds ratio [ORadj]1.02 95% confidence interval [95%CI] 0.72, 1.44). However, there was a positive association between high-volume IV fluids and cesarean section (ORadj 1.99; 95%CI 1.4, 2.8). CONCLUSIONS: The findings of this research are important to further knowledge relating to the administration of IV fluids during labor. The findings emphasize the importance of accurately documenting IV fluids administration and identifies research priorities to enable us to better understand the broader implications of IV fluids administration on pregnancy and perinatal outcomes.

A randomised trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment.

BACKGROUND: Elevated markers of systemic and pulmonary inflammation are associated with failure to recover lung function following pulmonary exacerbations in people with cystic fibrosis (pwCF). Our aim was to determine whether adjuvant oral prednisone treatment would improve recovery of forced expiratory volume in 1 s (FEV1) % pred in CF pulmonary exacerbations not responding to antibiotic therapy. METHODS: This was a randomised, double-blind, placebo-controlled trial in pwCF treated with intravenous antibiotics for a pulmonary exacerbation. At day 7, those who had not returned to >90% baseline FEV1 % pred were randomised to adjuvant prednisone 1 mg·kg-1 twice daily (maximum 60 mg·day-1) or placebo for 7 days. The primary outcome was the difference in proportion of subjects who recovered >90% baseline FEV1 % pred at day 14 of i.v. antibiotic therapy. RESULTS: 173 subjects were enrolled, with 76 randomised. 50% of subjects in the prednisone group recovered baseline FEV1 on day 14 compared with 39% of subjects in the placebo group (difference of 11%, 95% CI -11-34%; p=0.34). The mean±sd change in FEV1 % pred from day 7 to day 14 was 6.8±8.8% predicted in the prednisone group and 4.6±6.9% predicted in the placebo group (mean difference 2.2% predicted, 95% CI -1.5-5.9%; p=0.24). Time to subsequent exacerbation was not prolonged in prednisone-treated subjects (hazard ratio 0.83, 95% CI 0.45-1.53; p=0.54). CONCLUSIONS: This study failed to detect a difference in FEV1 % pred recovery between adjuvant oral prednisone and placebo treatment in pwCF not responding at day 7 of i.v. antibiotic therapy for pulmonary exacerbations.

Chronic use of Antihypertensive Medications and Peak Exercise Blood Pressure in Adult Men and Women from the BALL ST Cohort.

PURPOSE: To determine if individuals chronically (>1 year) prescribed antihypertensive medications have a normal BP response to peak exercise compared to unmedicated individuals. METHODS: Participants included 2,555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 year were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the Amercian Heart Association. RESULTS: The unmedicated group had a greater prevalence (p < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence (p < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher (p < 0.01) in medicated compared to unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP (p = 0.613), risk factors (p = 0.104), or cardiorespiratory fitness (p = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP (p = 0.039), but not for men (p = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors and cardiorespiratory fitness (p = 0.022). CONCLUSIONS: Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension.

A Systematic Review of Patient Selection Criteria for Outpatient Total Shoulder Arthroplasty.

The utilization of total shoulder arthroplasty (TSA) is increasing, driving associated annual health care costs higher. Opting for outpatient over inpatient TSA may provide a solution by reducing costs. However, there is no single set of accepted patient selection criteria for outpatient TSA. Here, the authors identify and systematically review 14 articles to propose evidence-based criteria that merit postoperative admission. Together, the studies suggest that patients with limited ability to abmluate independently or a history of congestive heart failure may benefit from postoperative at least one night of hospital based monitoring and treatment.

Impact of Daily Growth Hormone Adherence on Height Velocity Among Children With Growth Hormone Deficiency (GHD).

OBJECTIVE: To describe adherence to daily somatropin treatment and impact on height velocity within 1 year of treatment start among patients with pediatric growth hormone deficiency in a real-world US population. METHODS: This retrospective cohort study included pediatric patients aged ≥3 years to <16 years with pediatric growth hormone deficiency prescribed somatropin by a pediatric endocrinologist at a US-based center of excellence between January 1, 2015 and December 31, 2020. Patient data were collected using hospital electronic health records linked to a specialty pharmacy patient prescription records. Adherence, evaluated over 12 months, was measured using the proportion of days covered metric and patients were categorized as adherent if their proportion of days covered ≥80%. Height velocity was annualized to compare across adherent and nonadherent patients. RESULTS: One hundred eighty-one patients were identified and included in this study, of which 70.2% were male,73.5% were white, and mean age (standard deviation [SD]) at index was 12.1 (2.8). In the height velocity analysis, 174 patients were included and the mean (SD) annualized change in height was 10.2 (5.7) cm/y in the adherent group (n = 108) and 9.8 (7.6) in the nonadherent group (n = 66). The difference in height velocity between the groups was not statistically significant. CONCLUSIONS: Minor improvements in average height velocity were observed in the patient group who were adherent to somatropin therapy, although not statistically significant. Lack of observed significance may be due to small sample sizes, short observation period, a likely heterogenous population in terms of growth hormone prescribing, data bias due to single-center origin, or potential patient misclassification.

Telehealth Visits have Lower Non-attendance than Traditional Orthopaedic Clinic Visits.

The use of telemedicine has rapidly expanded in the wake of the COVID pandemic, but its effect on patient attendance remains unknown for different clinicians. This study compared traditional in-clinic visits with telehealth visits by retrospectively reviewing all scheduled orthopaedic clinic visits. Results demonstrated lower rates of cancellations in patients scheduled for telehealth visits as compared to in-clinic visits, during the initial COVID pandemic. In general, physicians can expect a lower cancellation rate than non-physician practitioners.