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Principles for determining physician compensation in the provision of virtual care are discussed along with analysis of the virtual care components included in the 2022 Ontario Physician Services Agreement (SEAMO 2022). Ministries and medical associations should continue to discuss appropriate payment for virtual advice for patients who do not have a primary care provider. They should also determine methods for payment for physician engagement in apps designed to optimize treatment of chronic diseases.

As a brief, noninvasive, cost-effective, and technology-driven therapy, biofeedback is a promising and welcomed clinical intervention for children and adolescents with pediatric chronic pain conditions. The aim of this pilot study was to explore the application of a brief Heart Rate Variability (HRV) biofeedback intervention supplemented by at-home breathing practice as a tool for reducing symptomatology associated with chronic pain in a pediatric urban hospital setting.Twenty-one participants aged 10-17 years (M = 14.05, SD = 1.91; 76% female) and their caregivers completed the study. Participants were randomized to either 1) receive immediate biofeedback treatment including at-home breathing practice or 2) to be placed on a 4-week waitlist and then enrolled in the biofeedback treatment. Study outcomes included self-reported pain intensity, health-related quality of life (HRQOL), and anxiety sensitivity. HRV data were obtained from biofeedback sessions.Following biofeedback treatment, participants achieved significant reductions in self-reported pain intensity, higher levels of self-reported school functioning, and increased HRV, as measured by Blood Volume Pulse (BVP) amplitude. Participants in the waitlist group experienced an increase in pain intensity during the waitlist period.Further research is needed to understand the mechanisms underlying HRV biofeedback and its treatment of pediatric chronic pain.Nurses are ideal practitioners for biofeedback given their training in physiology and background in healthcare and should be encouraged to explore training in this area. Suggested biofeedback-related apps and mobile devices to share with patients at bedside are provided.

Lipid-lowering therapy with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition are effective strategies in reducing cardiovascular disease risk; however, concerns remain about potential long-term adverse neurocognitive effects.This genetics-based study aimed to evaluate the relationships of long-term PCSK9 inhibition and statin use on neurocognitive outcomes.We extracted single-nucleotide polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and PCSK9 from predominantly European ancestry-based genome-wide association studies summary-level statistics of low-density lipoprotein cholesterol and performed drug-target Mendelian randomization, proxying the potential neurocognitive impact of drug-based PCSK9 and HMGCR inhibition using a range of outcomes to capture the complex facets of cognition and dementia.Using data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area. Conversely, we observed several adverse associations for HMGCR inhibition with lowered cognitive performance (beta: -0.082; 95% CI: -0.16 to -0.0080; P = 0.03), reaction time (beta = 0.00064; 95% CI: 0.00030-0.00098; P = 0.0002), and cortical surface area (beta = -0.18; 95% CI: -0.35 to -0.014; P = 0.03). Neither PCSK9 nor HMGCR inhibition impacted biomarkers of Alzheimer's disease progression or Lewy body dementia risk. Consistency of findings across Mendelian randomization methods accommodating different assumptions about genetic pleiotropy strengthens causal inference.Using a wide range of cognitive function and dementia endpoints, we failed to find genetic evidence of an adverse PCSK9-related impact, suggesting a neutral cognitive profile. In contrast, we observed adverse neurocognitive effects related to HMGCR inhibition, which may well be outweighed by the cardiovascular benefits of statin use, but nonetheless may warrant pharmacovigilance.

Objectives Reduction in unnecessary services is one strategy for increasing the value of health care. Reference laboratory, or send-out, tests are associated with considerable costs. We investigated whether displaying cost and turnaround time (TAT), or time-to-result, for reference laboratory tests at the time of order entry in the electronic health record (EHR) system would impact provider ordering practices. Methods Reference laboratory test cost and TAT data were randomized prior to the study and only displayed for the intervention group. A 24-month dataset composed of 12 months each for baseline and study periods was extracted from the clinical data mart. A difference-in-differences (DID) analysis was conducted using a linear mixed-effects model to estimate the association between the intervention and changes in test-ordering patterns. Results In the inpatient setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.31 and p = 0.26, respectively). In the ambulatory setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.82 and p = 0.51, respectively). For both inpatient and ambulatory settings, no significant difference was observed in the DID of aggregate test-order costs and volumes calculated in respect to stratified relative cost and TAT groups (p > 0.05). Conclusion Lack of alternative tests, test orders placed at a late step in patient management, and orders facilitated by trainees or mid-level providers may have limited the efficacy of the intervention. Our randomized study demonstrated no significant association between the display of cost or TAT display and ordering frequency.

Contains fulltext : 283431.pdf (Publisher’s version ) (Closed access) Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression.

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are important therapeutic options for reducing cardiovascular disease risk; however, questions remain regarding potential differences in the neuropsychiatric impact of long‐term PCSK9 inhibition between men and women. Methods and Results Using PCSK9 gene single‐nucleotide polymorphisms from European ancestry–based genome‐wide association studies of low‐density lipoprotein cholesterol (N=1 320 016), circulating PCSK9 protein levels (N=10 186), tissue‐specific PCSK9 gene expression, sex‐specific genome‐wide association studies of anxiety, depression, cognition, insomnia, and dementia (ranging from 54 321 to 194 174), we used drug‐target inverse variance–weighted Mendelian randomization (MR) and complementary MR methods (MR Egger, weighted median, and weighted mode) to investigate potential neuropsychiatric consequences of genetically proxied PCSK9 inhibition in men and women. We failed to find evidence surpassing correction for multiple comparisons of relationships between genetically proxied PCSK9 inhibition and the risk for the 12 neuropsychiatric end points in either men or women. Drug‐target analyses were generally well‐powered to detect effect estimates at several hypothesized thresholds for both combined‐sex and sex‐specific end points, especially analyses using PCSK9 instruments derived from protein and expression quantitative trait loci. Further, MR estimates across complementary MR methods and additional models using genetic instruments derived from circulating PCSK9 protein levels and tissue‐specific PCSK9 expression were in alignment, strengthening causal inference. Conclusions Genetically proxied PCSK9 inhibition showed a neutral neuropsychiatric side effect profile with no major sex‐specific differences. Given statistical power considerations, replication with larger samples, as well as data from other ancestral populations, are necessary. These findings may have important clinical implications for lipid‐lowering drug‐prescribing practices and side effect monitoring of approved and future PCSK9 therapies.

Objectives To investigate frailty prevalence, cross-sectional associations, predictive validity, concurrent validity, and cross-cultural adaptations of the FRAIL-NH scale. Design Systematic review. Setting and Participants Frail residents living in nursing homes. Methods MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched from January 2015 to June 2021 for primary studies that used the FRAIL-NH scale, irrespective of study designs and publication language. Results Overall, 40 studies conducted across 20 countries utilized the FRAIL-NH scale; majority in Australia (n=14), followed by China (n=6), United States (n=3), and Spain (n=3). The scale has been translated and back-translated into Brazilian Portuguese, Chinese, and Japanese. Various cut-offs have been used, with ≥2 and ≥6 being the most common cut-offs for frail and most frail, respectively. When defined using these cut-offs, frailty prevalence varied from 15.1–79.5% (frail) to 28.5–75.0% (most frail). FRAIL-NH predicted falls (n=2), hospitalization or length of stay (n=4), functional or cognitive decline (n=4), and mortality (n=9) over a median follow-up of 12 months. FRAIL-NH has been compared to 16 other scales, and was correlated with Fried’s phenotype (FP), Frailty Index (FI), and FI-Lab. Four studies reported fair-to-moderate agreements between FRAIL-NH and FI, FP, and the Comprehensive Geriatric Assessment. Ten studies assessed the sensitivity and specificity of different FRAIL-NH cutoffs, with ≥8 having the highest sensitivity (94.1%) and specificity (82.8%) for classifying residents as frail based on FI, while two studies reported an optimal cut-off of ≥2 based on FI and FP, respectively. Conclusion In seven years, the FRAIL-NH scale has been applied in 20 countries and adapted into three languages. Despite being applied with a range of cut-offs, FRAIL-NH was associated with higher care needs and demonstrated good agreement with other well-established but more complex scales. FRAIL-NH was predictive of adverse outcomes across different settings, highlighting its value in guiding care for frail residents in nursing homes. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12603-021-1694-3 and is accessible for authorized users.

While pharmaceutical industry involvement in producing, interpreting, and regulating medical knowledge and practice is widely accepted and believed to promote medical innovation, industry-favouring biases may result in prioritizing corporate profit above public health. Using diabetes as our example, we review successive changes over forty years in screening, diagnosis, and treatment guidelines for type 2 diabetes and prediabetes, which have dramatically expanded the population prescribed diabetes drugs, generating a billion-dollar market. We argue that these guideline recommendations have emerged under pervasive industry influence and persisted, despite weak evidence for their health benefits and indications of serious adverse effects associated with many of the drugs they recommend. We consider pharmaceutical industry conflicts of interest in some of the research and publications supporting these revisions, and in related standard-setting committees and oversight panels. We raise concern over the long-term impact of these multifaceted involvements. Rather than accept industry conflicts of interest as normal, needing only to be monitored and managed, we suggest challenging that normalcy, and ask: what are the real costs of tolerating such industry participation? We urge the development of a broader focus to fully understand and curtail the systemic nature of industry's influence over medical knowledge and practice.

Experimental knowledge of human body decomposition in the deep ocean is very limited, partly due to the logistical challenges of deep-sea research. The literature on ecological responses to the arrival of naturally sunk and implanted whale carcasses on the seafloor represents a potential source of information relevant to questions of human body survival and recovery in the deep ocean. Whale falls trigger the formation of complex, localized, and dense biological communities that have become a point of interest for marine biologists for the past 2-3 decades. Researchers have documented whale falls by whale type, size, geographic location, water depth and water chemistry, and there have been some comparative analyses of decomposition rates and faunal presence on carcasses. We undertook a review and meta-analysis of the whale-fall literature to identify and statistically model trends relevant to human forensics. Results from studies using deep-sea cameras baited with pig carcasses and simulated carrion provided further validation of noted trends. The stages of whale carcass decomposition most relevant to human forensics are those characterised by mobile scavengers that strip the soft tissues from carcasses, and to a lesser degree, other biota that degrade skeletal material. Our statistical models used the number of faunal taxa attracted to the whale carcasses as a measure of the ecological response and the potential rate of decomposition. Negative binomial models identified significant influences of carcass age and dissolved oxygen concentration on the ecological response (taxon numbers). The strongest environmental effects were identified in data from experimental studies that implanted whale carcasses across a broad range of dissolved-oxygen conditions. We propose directions for further experimental research to refine models of environmental controls on decomposition in the deep sea. Our results also highlight the potential use of publicly available global databases on environmental conditions in the deep ocean for informing body scavenging activity and thus body survival. Applying a forensic lens to whale-fall studies provides a window into an otherwise unseen world from the standpoint of human forensic taphonomy.

Background Ongoing measures to improve pediatric continuous kidney replacement therapy (CKRT) have lowered mortality rates, shifting the focus to survivor functional status. While septic acute kidney injury generates new morbidity in pediatric critically ill patients, acquired morbidities and functional status of CKRT population are unknown. We predicted that CKRT survivors are at risk for new morbidity and would have worse functional status at PICU discharge compared to baseline, and aimed to describe associated factors. Methods Retrospective cohort study over 24 months of CKRT patients surviving to PICU discharge in a quaternary children’s hospital. Functional outcome was determined by Functional Status Scale (FSS). Results FSS scores were higher at PICU and hospital discharge compared to baseline. Of 45 CKRT survivors, 31 (69%) had worse FSS score at PICU discharge and 51% had new morbidity (≥3 increase in FSS); majority qualified as moderate to severe disability (FSS ≥10). Four patients (9%) had new tracheostomy, 3 (7%) were ventilator dependent, and 10 (22%) were dialysis dependent. Most (23/45, 51%) required outpatient rehabilitation. Cumulative days on sedation, controlled for illness severity, were independently associated with worse FSS at PICU discharge (aOR 25.18 (3.73, 169.92)). In adjusted analyses, duration of sedation was associated with new morbidity, while neurologic comorbidity, percent fluid overload at CKRT start, and nonrenal comorbidity were associated with moderate to severe disability at PICU discharge when controlled for baseline FSS. Conclusions CKRT survivors, with new morbidity and worse functional outcomes at PICU discharge, are a newly described vulnerable population requiring targeted follow-up. Deliberate decrease of sedation exposure in patients with decreased clearance due to organ dysfunction needs to be studied as a modifiable risk factor. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05177-7.

No physician can successfully deliver high-value patient care in the modern-day health care system in isolation. Delivery of effective patient care requires integrated and collaborative systems that depend on dynamic professional relationships among members of the health care team. An overview of the socioeconomic implications of professional relationships within modern care delivery systems and potential employment models is presented.

Background Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited. Objective To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery. Methods We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature. Results In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n = 27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7% vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4% vs 0.5%, P = .008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P = .005). Conclusion We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH.

Objective To utilize, in an individual and institutional privacy-preserving manner, electronic health record (EHR) data from 202 hospitals by analyzing answers to COVID-19-related questions and posting these answers online. Materials and Methods We developed a distributed, federated network of 12 health systems that harmonized their EHRs and submitted aggregate answers to consortia questions posted at https://www.covid19questions.org. Our consortium developed processes and implemented distributed algorithms to produce answers to a variety of questions. We were able to generate counts, descriptive statistics, and build a multivariate, iterative regression model without centralizing individual-level data. Results Our public website contains answers to various clinical questions, a web form for users to ask questions in natural language, and a list of items that are currently pending responses. The results show, for example, that patients who were taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, within the year before admission, had lower unadjusted in-hospital mortality rates. We also showed that, when adjusted for, age, sex, and ethnicity were not significantly associated with mortality. We demonstrated that it is possible to answer questions about COVID-19 using EHR data from systems that have different policies and must follow various regulations, without moving data out of their health systems. Discussion and Conclusions We present an alternative or a complement to centralized COVID-19 registries of EHR data. We can use multivariate distributed logistic regression on observations recorded in the process of care to generate results without transferring individual-level data outside the health systems.

Background: The six-month exclusive breastfeeding (EBF) rate almost halved between 2009 and 2013 in Northeast Thailand for no clear reason. Specific facilitators and barriers to six-month EBF have been identified for Thailand, but mothers’ views on these factors to continuing EBF breastfeeding until six months have not been explored in this region. Aim: This study aimed to prioritize mothers’ views on the identified facilitators and barriers of continuing six-month exclusive breastfeeding. Methods: Q-methodology was applied. This research was conducted at Well Baby Out-Patient Department of Khonkaen Hospital, Numphong Hospital and a private hospital. Thirty-four mothers, who had recently delivered infants aged between four and six months, were breastfeeding/had breastfed, were 20 to 40 years old, participated. Demographic data were analysed descriptively, and Q-method analysis was conducted using the PQ Method software 2.35. Results: There was consensus that having knowledge about the advantages of EBF was the most important facilitator of six-month EBF, and ‘not having any other responsibilities besides caring for her infant’ was the least important facilitator of six-month EBF. Three viewpoints emerged identifying different groups/clusters of mothers, namely, (1) caring for self, (2) requiring support and (3) breastfeeding knowledge. Conclusions: Despite some consensus among participants, three distinct viewpoints emerged regarding which facilitators and barriers were important to mothers. It is clear that a programme to improve the six-month EBF rate in Northeast Thailand would need to incorporate interventions or activities that address the different viewpoints identified.

To determine the effects of the COVID-19 pandemic on Adenotonsillectomies (TA), Tonsil Related Cases (TC), and Peritonsillar Abscess (PTA) Trends.Retrospective Cohort Study.This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 51 children's hospitals. Regions were defined according to PHIS rules with at least five children's hospitals per region. We compared monthly total TA, TC, TC as a proportion of all hospital visits, and PTA from all encounters at each hospital from January 1, 2019, through December 31, 2021.Compared to 2019, April 2020 saw mean TC drop significantly from 371.62 to 68.37 (p 0.001). Interestingly, June, September, and December 2020 had significantly higher mean TC compared to 2019. TC as a proportion of all hospital visits decreased significantly throughout the majority of 2021. Similarly, TA significantly decreased during 2020 and 2021 across all regions in the US, starting in March 2020 and this reduction in TA extended through the end of 2021 without any signs of recovery. PTA rates did not change significantly over the three years.The pandemic-plagued 2020 saw a noticeable decrease in overall TC and TA but then rebounded quickly to even higher than pre-pandemic levels. However, this rebound halted for the majority of 2021 and subsequently decreased to lower than pre-pandemic levels, which differs from other communicable pathologies such as otitis media which decreased initially then recovered to pre-pandemic levels by Summer of 2021.

Background Approximately 3.8% of adults worldwide have used cannabis in the past year. Understanding how cannabis use is associated with other health conditions is crucial for healthcare providers seeking to understand the needs of their patients, and for health policymakers. This paper analyzes the relationship between documented cannabis use disorders (CUD), cannabis use (CU) and other health diagnoses among primary care patients during a time when medical use of marijuana was permitted by state law in California, United States of America. Methods The study utilized primary care electronic health record (EHR) data from an academic health system, using a case–control design to compare diagnoses among individuals with CUD/CU to those of matched controls, and those of individuals with CUD diagnoses with individuals who had CU otherwise documented. Associations of documented CU and CUD with general medical conditions and health conditions associated with cannabis use (both medical and behavioral) were analyzed using conditional logistic regression. Results Of 1,047,463 patients with ambulatory encounters from 2013–2017, 729 (0.06%) had CUD diagnoses and 3,731 (0.36%) had CU documented in their EHR. Patients with documented CUD and CU patients had significantly (p Conclusion The prevalence of CUD and CU notation in EHR data from an academic health system was low, highlighting the need for improved screening in primary care. CUD and CU documentation were associated with increased risk for many health conditions, with the most elevated risk for behavioral health disorders and HIV/AIDS (among CUD-documented, but not CU-documented patients). Given the strong associations of CUD and CU documentation with health problems, it is important for healthcare providers to be prepared to identify CU and CUD, discuss the pros and cons of cannabis use with patients thoughtfully and empathically, and address cannabis-related comorbidities among these patients.

Introduction Bacterial sepsis is a life-threatening disease and a significant clinical problem caused by host responses to a microbial infection. Sepsis is a leading cause of death worldwide and, importantly, a significant cause of morbidity and mortality in combat settings, placing a considerable burden on military personnel and military health budgets. The current method of treating sepsis is restricted to pathogen identification, which can be prolonged, and antibiotic administration, which is, initially, often suboptimal. The clinical trials that have been performed to evaluate bacterial separation as a sepsis therapy have been unsuccessful, and new approaches are needed to address this unmet clinical need. Materials and Methods An inertial-based, scalable spiral microfluidic device has been created to overcome these previous deficiencies through successful separation of infection-causing pathogens from the bloodstream, serving as a proof of principle for future adaptations. Fluorescent imaging of fluorescent microspheres mimicking the sizes of bacteria cells and blood cells as well as fluorescently stained Acinetobacter baumannii were used to visualize flow within the spiral. The particles were imaged when flowing at a constant volumetric rate of 0.2 mL min−1 through the device. The same device was functionalized with colistin and exposed to flowing A. baumannii at 0.2 mL h−1. Results Fluorescent imaging within the channel under a constant volumetric flow rate demonstrated that smaller, bacteria-sized microspheres accumulated along the inner wall of the channel, whereas larger blood cell–sized microspheres accumulated within the center of the channel. Additionally, fluorescently stained A. baumannii displayed accumulation along the channel walls in agreement with calculated performance. Nearly 106 colony-forming units of A. baumannii were extracted with 100% capture efficiency from flowing phosphate-buffered saline at 0.2 mL h−1 in this device; this is at least one order of magnitude more bacteria than present in the blood of a human at the onset of sepsis. Conclusions This type of bacterial separation device potentially provides an ideal approach for treating soldiers in combat settings. It eliminates the need for immediate pathogen identification and determination of antimicrobial susceptibility, making it suitable for rapid use within low-resource environments. The overall simplicity and durability of this design also supports its broad translational potential to improve military mortality rates and overall patient outcomes.

Objectives Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin–twin transfusion syndrome (TTTS). Secondary aims were to create gestational‐age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS. Methods In the period 2015–2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four‐chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16–26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed‐effects multilevel regression. Inter‐rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within‐fetus variation was assessed in 16 such fetuses, in which multiple four‐chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as ‘pre‐TTTS’ when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the ‘non‐TTTS’ group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non‐TTTS and pre‐TTTS cases, matched for gestational age. Results Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre‐TTTS and 113 non‐TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28–220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2–26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non‐TTTS and 13/14 pre‐TTTS MCDA twin pregnancies 3.6% was found in eight of 13 pre‐TTTS pregnancies. In non‐TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P

Background Patients often seek medical treatment among different health care organizations, which can lead to redundant tests and treatments. One electronic health record (EHR) platform, Epic Systems, uses a patient linkage tool called Care Everywhere (CE), to match patients across institutions. To the extent that such linkages accurately identify shared patients across organizations, they would hold potential for improving care.Objective This study aimed to understand how accurate the CE tool with default settings is to identify identical patients between two neighboring academic health care systems in Southern California, The University of California Los Angeles (UCLA) and Cedars-Sinai Medical Center.Methods We studied CE patient linkage queries received at UCLA from Cedars-Sinai between November 1, 2016, and April 30, 2017. We constructed datasets comprised of linkages (“successful” queries), as well as nonlinkages (“unsuccessful” queries) during this time period. To identify false positive linkages, we screened the “successful” linkages for potential errors and then manually reviewed all that screened positive. To identify false-negative linkages, we applied our own patient matching algorithm to the “unsuccessful” queries and then manually reviewed a sample to identify missed patient linkages.Results During the 6-month study period, Cedars-Sinai attempted to link 181,567 unique patient identities to records at UCLA. CE made 22,923 “successful” linkages and returned 158,644 “unsuccessful” queries among these patients. Manual review of the screened “successful” linkages between the two institutions determined there were no false positives. Manual review of a sample of the “unsuccessful” queries (n = 623), demonstrated an extrapolated false-negative rate of 2.97% (95% confidence interval [CI]: 1.6–4.4%).Conclusion We found that CE provided very reliable patient matching across institutions. The system missed a few linkages, but the false-negative rate was low and there were no false-positive matches over 6 months of use between two nearby institutions.

Severe traumatic brain injury has historically been a non-survivable injury. Recent advances in neurosurgical care, however, have demonstrated that these patients not only can survive, but they also can recover functionally when they undergo appropriate cerebral decompression within hours of injury. At the present, general surgeons are deployed further forward than neurosurgeons (Role 2 compared to Role 3) and have been provided with guidelines that stipulate conditions where they may have to perform decompressive craniectomies. Unfortunately, Role 2 medical facilities do not have access to computed tomography imaging or intracranial pressure monitoring capabilities rendering the decision to proceed with craniectomy based solely on exam findings. Utilizing a case transferred from downrange to our institution, we demonstrate the utility of a small, highly portable quantitative pupillometer to obtain reliable and reproducible data about a patient’s intracranial pressures. Following the case presentation, the literature supporting quantitative pupillometry for surgical decision-making is reviewed.

BACKGROUND: Sepsis is the leading cause of in-hospital death. The SEP-1 sepsis bundle is a protocol for early sepsis care that requires providers to diagnose and treat sepsis quickly. Limited evidence suggests that adherence to the sepsis bundle is lower in cases of hospital-onset sepsis. OBJECTIVE: To compare sepsis bundle adherence in hospital-onset vs. community-onset sepsis. DESIGN: Retrospective cohort study using multivariable analysis of clinical data. PARTICIPANTS: A total of 4658 inpatients age 18 or older were identified by diagnosis codes consistent with sepsis or disseminated infection. SETTING: Four university hospitals in California between 2014 and 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was adherence to key components of the sepsis bundle defined by the Centers for Medicare and Medicaid Services in their core measure, SEP-1. Covariates included clinical characteristics related to the patient, infection, and pathogen. KEY RESULTS: Compared with community-onset, cases of hospital-onset sepsis were less likely to receive SEP-1 adherent care (relative risk 0.33, 95% confidence interval 0.29–0.38, p

IntroductionTraumatic brain injury (TBI) is the most common cause of death on the modern battlefield. In recent conflicts in Iraq and Afghanistan, the US typically deployed neurosurgeons to medical treatment facilities (MTFs), while the UK did not. Our aim was to compare the incidence, TBI and treatment in US and UK-led military MTF to ascertain if differences in deployed trauma systems affected outcomes.MethodsThe US and UK Combat Trauma Registries were scrutinised for patients with HI at deployed MTFs between March 2003 and October 2011. Registry datasets were adapted to stratify TBI using the Mayo Classification System for Traumatic Brain Injury Severity. An adjusted multiple logistic regression model was performed using fatality as the binomial dependent variable and treatment in a US-MTF or UK-MTF, surgical decompression, US military casualty and surgery performed by a neurosurgeon as independent variables.Results15 031 patients arrived alive at military MTF after TBI. Presence of a neurosurgeon was associated with increased odds of survival in casualties with moderate or severe TBI (p4, 95% CI 1.61×104 to 110.6×104, pConclusionsPresence of neurosurgeons increased the likelihood of survival after TBI. We therefore recommend that the UK should deploy neurosurgeons to forward military MTF whenever possible in line with their US counterparts.

The mechanical properties of connective tissues are tailored to their specific function, and changes can lead to dysfunction and pathology. In most mammalian tissues the mechanical environment is governed by the micro- and nano-scale structure of collagen and its interaction with other tissue components, however these hierarchical properties remain poorly understood. In this study we use the human cornea as a model system to characterise and quantify the dominant deformation mechanisms of connective tissue in response to cyclic loads of physiological magnitude. Synchronised biomechanical testing, x-ray scattering and 3D digital image correlation revealed the presence of two dominant mechanisms: collagen fibril elongation due to a largely elastic, spring-like straightening of tropocollagen supramolecular twist, and a more viscous straightening of fibril crimp that gradually increased over successive loading cycles. The distinct mechanical properties of the two mechanisms suggest they have separate roles in vivo. The elastic, spring-like mechanism is fast-acting and likely responds to stresses associated with the cardiac cycle, while the more viscous crimp mechanism will respond to slower processes, such as postural stresses. It is anticipated that these findings will have broad applicability to understanding the normal and pathological functioning of other connective tissues such as skin and blood vessels that exhibit both helical structures and crimp. Statement of significance: The tropocollagen spring mechanism allows collagen fibrils from some tissues to elongate significantly under small loads, and its recent discovery has the potential to change our fundamental understanding of how tissue deforms. This time-resolved study quantifies the contribution of the spring mechanism to the local strain in stretched tissue and compares it to the contribution associated with the straightening of fibril waviness, the widely accepted primary low-load strain mechanism. The spring mechanism contributed more to the local tissue strain than fibril straightening, and was found to be elastic while fibril straightening was more viscous. The results suggest that the viscoelastic behaviour of a biomaterial is controlled, at least in part, by the relative amount of fibril-scale crimp and tropocollagen supramolecular twist.

Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population.We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers.A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival.In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

This study aimed to develop and validate a predictive algorithm for unsatisfactory response to initial pulmonary arterial hypertension (PAH) therapy using health insurance claims. Adult patients with PAH initiated on a first PAH therapy (index date) were identified from Optum’s de-identified Clinformatics Data Mart Database (1/1/2010–12/31/2019). A random survival forest algorithm was developed using patient-month data and predicted the “survival function” (i.e. risk of not having unsatisfactory response) over time. For each patient-month observation, risk factors were assessed in the 12 months prior. Unsatisfactory response was defined as the first instance of (1) new PAH therapy, (2) PAH-related hospitalization or emergency room visit, (3) lung transplant or atrial septostomy, (4) PAH-related death or (5) chronic oxygen therapy initiation. To facilitate use in clinical practice, a simplified risk score was also developed based on a linear combination of the most important risk factors identified in the algorithm. In total, 4781 patients were included (median age = 69.0 years; 58.6% female). Over a median follow-up of 14.0 months, 3169 (66.3%) had an unsatisfactory response. The most important risk factors included in the algorithm were healthcare resource use (i.e. PAH-related outpatient visits, pulmonologist visits, cardiologist visits, all-cause hospitalizations), time since first PAH diagnosis, time since index date, Charlson Comorbidity Index, dyspnea, and age. Predictive accuracy was good for the full algorithm (C-statistic: 0.732) but was slightly lower for the simplified risk score (C-statistic: 0.668). The present claims-based algorithm performed well in predicting time to unsatisfactory response following initial PAH therapy.

Context Most methods for assessing dietary intake have considerable measurement error. Dietary biomarkers are objective tools for dietary assessment. Dietary biomarkers of dietary patterns have not been well described, despite modern dietary guidelines endorsing dietary patterns. Objective This systematic review sought to describe the dietary biomarkers commonly used to assess dietary patterns, and the novel biomarkers of dietary patterns identified by exploratory studies. Data Sources MEDLINE, Embase, Cochrane Central, PreMEDLINE, and CINAHL databases were searched. Data Extraction Data extraction and bias assessment were undertaken in duplicate. Data Analysis A qualitative approach was applied, without statistical analysis. Conclusion In controlled settings, dietary biomarkers of single nutrients or of individual foods or food groups are commonly used to assess compliance with dietary patterns. However, currently, there are no dietary biomarkers or biomarker profiles that are able to identify the specific dietary pattern that has been consumed by an individual. Future work should seek to validate novel dietary biomarkers and biomarker profiles that are indicative of specific dietary patterns and their characteristics. A dietary biomarker panel consisting of multiple biomarkers is almost certainly necessary to capture the complexity of dietary patterns. Systematic Review Registration PROSPERO registration no. CRD42019129839.

Purpose The pandemic related to the novel coronavirus (COVID-19) has led to a decrease in communicable diseases due to social distancing and mask-wearing. How have the prevalence of otitis media (OM) and its associated procedures changed during the pandemic? Study design Retrospective Cohort Study. Methods This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 48 children's hospitals. Regions were defined according to PHIS rules. We compared proportion of OM to total diagnoses codes, and collected mastoiditis, and MT placements from all encounters through January 1, 2019-June 31, 2021. Results In April 2020, there was a decrease in mean proportion of OM cases per 100 hospital visits (7 v. 2, p

Autophagy is a critical mechanism deployed by eukaryotic cells in response to stress, including viral infection, to boost the innate antimicrobial responses. However, an increasing number of pathogens hijack the autophagic machinery to facilitate their own replication. Influenza A virus (IAV), responsible for several global pandemics, has an intricate dependence on autophagy for successful replication in mammalian cells. To elucidate key chokepoints in the host stress responses facilitating IAV replication, we constructed a meta-transcriptome of IAV and host gene expression dynamics during early (1-3 hpi), mid (4-6 hpi), and late (8-12 hpi) stages of the viral replication cycle at two multiplicities of infection (MOI): 1 and 5. We supplemented the global transcriptome study with phosphoproteomic analysis of stress-activated protein kinase (SAPK/JNK) signaling in lung carcinoma (predominantly used as an in vitro model of IAV replication) and normal human bronchial epithelial cells. We report significant differences in the activation profiles of autophagy regulating genes upon IAV infection at the two MOI as well as divergent dependence on ULK1 signaling within the normal and cancer cells. Regardless of the cell model, JNK-Thr187 signaling was crucial for the production of infectious viral particles.

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice was associated with the failure in homeostasis restoration mediated by the cytokine interferon (IFN)-γ. Our findings show that diet composition calibrates host survival threshold by regulating adaptive homeostasis and highlights a pivotal role for extrinsic signals in host phenotype and outcome of host-pathogen interaction.

Objective Implementation of residency duty hour standards has led to adoption of different staffing models, such as the "holdover" model, whereby nighttime teams admit patients and transfer their care to daytime teams who provide ongoing care. In contrast, nonholdover teams at our institution are responsible for both admitting patients and providing ongoing care. We sought to determine whether patients admitted by holdover teams experience worse outcomes than those admitted by nonholdover teams. Methods This is a retrospective cohort study of patients admitted to the internal medicine hospital service at a quaternary care hospital from July 2013 to June 2015. Primary outcomes included hospital length of stay (LOS) and transfer to an intensive care unit within 72 hours of admission. Secondary outcomes were any transfer to an intensive care unit, in-hospital mortality, discharge to home (versus discharge to postacute care facility), and readmission to the health system within 30 days of discharge. Results We analyzed 5518 encounters, 64% of which were admitted by a holdover team. Outcomes were similar between study groups, except the LOS, which was 5.5 hours longer for holdover encounters in unadjusted analyses (5.18 versus 4.95 days, P = 0.04) but not significantly different in adjusted analyses. The mean discharge time was 4:00 P.M. for both groups, whereas the mean admission times were 12:00 A.M. and 4:00 P.M. for holdover and nonholdover encounters, respectively. Conclusions Holdover encounters at our institution were not associated with worse patient safety outcomes. A small increase in LOS may have been attributable to holdover patients having earlier admission and identical discharge times.

Deaf and hard of hearing (DHH) students experience unique stressors as a minority linguistic and cultural group that may contribute to problematic substance and alcohol use behavior. Proper coping strategies may be one protective factor to avoid reliance on alcohol as a means to reduce stress.The current study compared the endorsement of coping strategies by DHH students and hearing individuals and their relationship to drinking to cope behavior. Data was collected among DHH (n = 126) and hearing students (n = 349) at a large university.While these two groups did not differ in their levels of problematic drinking behavior, there were differences observed in drinking to cope motives as well as in the levels of coping styles used. DHH students were found to endorse greater levels of emotion-oriented and task-oriented coping than hearing students. Drinking to cope motivations were also higher for DHH students, particularly those who endorsed greater emotion focused coping.Interventions and educational efforts involving coping skills is a potentially important area of focus for the DHH student population. Further implications for understanding drinking behavior in this population are discussed.

Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs.PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. Primary outcome was the number of studies that reported p-values that differed in statistical significance (crossed p-value=0.05) from the reproduction analysis. Assuming an alpha of 0.05, a beta of 0.80, an estimated rate of statistical discordance of 5% for RCTs, a total of at least 568 studies were required.Overall, 572 RCTs were selected involving six specialties. Of these, 45% were positive (p0.05) studies. Eleven (2%) published results that differed from the reproduction analysis and crossed the p=0.05 threshold. All 11 studies were positive studies (while the reproduction analysis demonstrated p≥0.05).Less than 5% of published RCTs reported a discordant p-value that crossed the "p=0.05" threshold. Although the occurrence is uncommon, the existence of even one RCT publishing nonreproducible results is concerning. Future studies should seek to identify why some RCTs report discordant statistics and how to prevent this from occurring.

Stable isotope analysis of human tissues has become a valuable tool for mapping human geolocation. This study adds to the existing knowledge of the relationship between oxygen stable isotopes in human enamel and drinking water by presenting enamel oxygen values in clinic-extracted human dental enamel with known provenance. The results from this study indicate that the theoretical isotopic relationship between enamel and drinking water oxygen is weak at the city and country-level. Differences of up to 15‰ were observed between predicted drinking water oxygen values using existing models and observed values, highlighting the complexity of using water/enamel conversion equations. The lower isotopic boundary of enamel oxygen values is now understood for Metro Vancouver at δ18Oc(VPDB) = – 11.0‰ and presents the possibility of using stable isotope analysis as an exclusionary tool where individuals falling below threshold value can be identified as non-local. Overall, this study’s results support the development of geographical reference maps for human enamel oxygen.

Introduction: The Defense Health Agency has shifted focus of military medicine to operational readiness. As such, neurosurgery remains a critical wartime specialty. We investigate the factors impacting recruitment and retention of military neurosurgeons. Methods: Survey of military neurosurgeons was performed via the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Committee of Military Neurosurgeons and the Council of State Neurosurgical Societies. Retention and recruitment were queried. Results: 93/119 (78.2%) current or previously affiliated military neurosurgeons would recommend service as a military neurosurgeon to a colleague. Those who felt a sense of patriotism were 4.3 times more likely to recommend military service (P = 0.027, CI 1.19–16.82). Those who developed a sense of camaraderie showed a trend to recommending military neurosurgery (P = 0.058, CI 0.95–9.78). Those with a current military obligation were.28 times (P = 0.02, CI 0.09–0.85) as likely to recommend service. Military physicians who felt a need for reform to increase salary were 2.5 times less likely to be retained. Discussion: Service in the US military is a positive experience with camaraderie, patriotism, and unique military experiences predictive of recruitment. Meanwhile, focus on pay discrepancy can result in lost retention. These factors should be explored regarding recruitment and retention of military neurosurgeons.

As large corporations come to dominate U.S. health care, clinical medicine is increasingly market-driven and governed by business principles. We examine ways in which health insurers and health care systems are transforming the goals and means of clinical practice. Based on ethnographic research of diabetes management in a large health care system, we argue that together these organizations redefine clinical care in terms that prioritize financial goals and managerial logics, above the needs of individual patients. We demonstrate how emphasis on quality metrics reduces clinical work to quantifiable outcomes, redefining diabetes management to be the pursuit of narrowly defined goal numbers, despite often serious health consequences of treatment. As corporate employees, clinicians are compelled to pursue goal numbers by the heavy emphasis payers and health systems place on quality metrics, and accessing the required medications becomes the central focus of clinical practice. [diabetes mellitus, health insurance industry, health systems, clinical medicine, corporate influences]

While obtaining accurate estimates of tumor incidence volume is a difficult technical problem because it requires collating and analyzing data from dozens of world-wide sources curated under different conditions, our study aims to determine the global incidence of brain and spinal tumors. We analyzed 207 tumor registries on five continents, and calculated age-standardized rates to compare tumor incidence between geographic regions and income levels. Based on data available in current cancer registries, the apparent global incidence of malignant brain tumors was 4.25 cases per 100,000 person-years (95% CI [4.21-4.29]), and varied by region from 6.76 [6.71-6.80] in Europe to 2.81 [2.64-2.99] in Africa. Incidence also varied by World Bank income group, ranging from 6.29 [6.26-6.32] cases per 100,000 in high income countries (HICs), to 4.81 [4.77-4.86] in low and middle-income countries (LMICs). Malignant spinal tumors were much less frequent globally (0.098 [0.093-0.104]) and varied similarly by region and income group. The incidence of brain and spinal tumors varies by region and income group, although case ascertainment bias driven by limited resources in low income regions likely plays a role in variance. The burden of neurosurgical disease in LMICs is large, and similar in scale to HICs.

Background The opioid epidemic continues to worsen with a concomitant increase in opioid-related mortality. In response, the Department of Defense and Veterans Health Agency recommended against the use of long-acting opioids (LAOs) and concurrent use of opioids with benzodiazepines. Subsequently, we eliminated benzodiazepines and LAOs from our postoperative pain control regimen. Objective To evaluate the impact of removing benzodiazepines and LAOs on postoperative pain in single-level transforaminal lumbar interbody fusion (TLIF) patients. Methods A retrospective cohort study of single-level TLIF patients from February 2016-March 2018 was performed. Postoperative pain control in the + benzodiazepine cohort included scheduled diazepam with or without LAOs. These medications were replaced with nonbenzodiazepine, opioid-sparing adjuncts in the -benzodiazepine cohort. Pain scores, length of hospitalization, trigger medication use, and opioid use and duration were compared. Results Among 77 patients, there was no difference between inpatient pain scores, but the -benzodiazepine cohort experienced a faster rate of morphine equivalent reduction (-18.7%, 95% CI [-1.22%, -36.10%]), used less trigger medications (-1.55, 95% CI [-0.43, -2.67]), and discharged earlier (0.6 d; 95% CI [0.01, 1.11 d]). As outpatients, the -benzodiazepine cohort was less likely to receive opioid refills at 2 wk (29.2% vs 55.8%, P = .021) and 6 mo postoperatively (0% vs 13.2%, P = .039), and was less likely to be using opioids by 3 mo postoperatively (13.3% vs 34.2%, P = .048). Conclusion Replacement of benzodiazepines and LAOs in the pain control regimen for single-level TLIFs did not affect pain scores and was associated with decreased opioid use, a reduction in trigger medications, and shorter hospitalizations.

To evaluate the role of serial newborn screening of congenital hypothyroidism using thyroxine (T4) in the neonatal intensive care unit (NICU). Newborn screen results were reviewed from a single academic NICU during 2007–2016 (n = 6100). Thyroid function levels were reviewed in patients treated for hypothyroidism during that period. Duration of treatment was followed after discharge. Overall incidence of treated hypothyroidism was 1:103 with increasing incidence inversely related to birth weight. Among treated infants (n = 59), initial newborn screen demonstrated sensitivity and specificity of 74.1% and 84.9%, respectively; second screen demonstrated rates of 85.7% and 76.1%, respectively. Based on follow-up data, prevalence of permanent congenital hypothyroidism in our NICU population was 1:870 (n = 7); two patients would have been missed with a single screen. Abnormal T4 on newborn screening is common for preterm neonates. Higher rates of permanent congenital hypothyroidism highlight the need for screening beyond the newborn screen.

Background Body mass index does not indicate the distribution of adipose tissue. Central adiposity may be measured using ultrasound measurement of subcutaneous fat thickness. This study determined if the abdominal subcutaneous fat thickness measured correlated with skin-to-epidural space distance at delivery, and compared this with the booking body mass index. Methods We analysed a sub-set of participants from a single-centre, prospective cohort study that assessed the relationship between subcutaneous fat thickness and maternity outcomes. Abdominal subcutaneous fat thickness measurements were obtained during the routine fetal anomaly scan. The skin-to-epidural space distance was obtained in those having epidural or combined spinal-epidural analgesia. Linear regression was used to test for strength of association and adjusted R2 values calculated to determine if subcutaneous fat thickness or body mass index was more strongly associated with skin-to-epidural space distance. Results The 463 women had a median (IQR) booking body mass index of 25.0 kg/m2 (21.8–29.3) and subcutaneous fat thickness of 16.2 mm (13.0–21.0). The median (IQR) skin-to-epidural space distance was 5.0 cm (4.5–6.0). Both parameters significantly correlated with skin-to-epidural space distance (r=0.53 and 0.68 respectively, P Conclusions Booking body mass index had a stronger relationship with skin-to- epidural space distance at delivery than subcutaneous fat thickness, explaining 47% of the variation in the skin-to-epidural distance.

There is a large body of evidence suggesting that parasites could be a major preventable risk factor for epilepsy in low- and middle-income countries. We review potentially important substrates for epileptogenesis in parasitic diseases. Taenia solium is the most widely known parasite associated with epilepsy, and the risk seems determined mainly by the extent of cortical involvement and the evolution of the primary cortical lesion to gliosis or to a calcified granuloma. For most parasites, however, epileptogenesis is more complex, and other favorable host genetic factors and parasite-specific characteristics may be critical. In situations where cortical involvement by the parasite is either absent or minimal, parasite-induced epileptogenesis through an autoimmune process seems plausible. Further research to identify important markers of epileptogenesis in parasitic diseases will have huge implications for the development of trials to halt or delay onset of epilepsy.

Hypertension is a growing problem in children and adolescents, with primary hypertension becoming the most common etiology. In addition to demonstrating that high blood pressure in children and young adults is likely to remain elevated into adulthood, this review (1) addresses important aspects of measuring blood pressure in children and adolescents, (2) defines elevated blood pressure and hypertension in this age group, (3) describes the initial evaluation and workup of abnormally high blood pressure, and (4) introduces treatment strategies for youth with sustained hypertension.

Traumatic brain injury has been called the “signature injury” of the wars in Iraq and Afghanistan, and the management of severe and penetrating brain injury has evolved considerably based on the experiences of military neurosurgeons. Current guidelines recommend that decompressive hemicraniectomy be performed with large, frontotemporoparietal bone flaps, but practice patterns vary markedly. The following case is illustrative of potential clinical courses, complications, and efforts to salvage inadequately-sized decompressive craniectomies performed for combat-related severe and penetrating brain injury. The authors follow this with a review of the current literature pertaining to decompressive craniectomy, and finally provide their recommendations for some of the technical nuances of performing decompressive hemicraniectomy after severe or penetrating brain injury.

Background Acute kidney injury (AKI) is a recognised complication of coronavirus disease 2019 (COVID-19), yet the reported incidence varies widely and the associated risk factors are poorly understood. Methods Data was collected on all adult patients who returned a positive COVID-19 swab while hospitalised at a large UK teaching hospital between 1st March 2020 and 3rd June 2020. Patients were stratified into community- and hospital-acquired AKI based on the timing of AKI onset. Results Out of the 448 eligible patients with COVID-19, 118 (26.3 %) recorded an AKI during their admission. Significant independent risk factors for community-acquired AKI were chronic kidney disease (CKD), diabetes, clinical frailty score and admission C-reactive protein (CRP), systolic blood pressure and respiratory rate. Similar risk factors were significant for hospital-acquired AKI including CKD and trough systolic blood pressure, peak heart rate, peak CRP and trough lymphocytes during admission. In addition, invasive mechanical ventilation was the most significant risk factor for hospital-acquired AKI (adjusted odds ratio 9.1, p Conclusions AKI occurred in over a quarter of our hospitalised COVID-19 patients. Community- and hospital-acquired AKI have many shared risk factors which appear to converge on a pre-renal mechanism of injury. Hospital- but not community acquired AKI was a significant risk factor for death.

Surgeons rely on randomized controlled trials (RCT) to compare the effectiveness of treatments. RCTs require careful planning and substantial effort to complete. Because of the careful study design, statistics performed are often easy to reproduce such as Chi-squared or t-test. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon.RCTs pertaining to hernias were identified in PubMed using the search terms "hernia" and "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. Discordance between the obtained p-value from our analysis and the published p-value was assessed. Primary outcome was the number of studies that reported p-values that crossed the level of statistical significance (p-value = 0.05) but on reproduction analysis did not.Of the 100 included RCTs, five reported p-values that crossed the "p = 0.05" threshold that our team was unable to reproduce using the statistical test reported in the manuscript. An additional three studies reported p-values that crossed the "p = 0.05" threshold that our team was unable to reproduce using the appropriate statistical test (i.e., Fisher's exact test when all expected cell counts 5). All eight studies published p-values 0.05, whereas, our re-analysis demonstrated p ≥ 0.05.Eight percent of the RCTs analyzed in this study reported p-values 0.05 that on reproduction analysis was ≥ 0.05. The next steps should be to determine reasons for discordance and how to prevent this from happening.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Background: Medicine use is considered off-label when used for an indication, at a dose, via a route of administration or in a patient group not included in the approved product information. Off-label use varies according to therapeutic class and patient group, and often occurs in those who are vulnerable. Objective: The aim of this article is to discuss ethical, practice and policy considerations associated with off-label medicine use. Discussion: A number of professional organisations have issued guidance in relation to offlabel medicine use. Prescribers should inform patients and document consent when prescribing off-label, including an open discussion about known and unknown benefits and risks. It is important that the prescriber documents the reason for off-label use in the patient’s record and ensures that patients are aware of the intended duration and relevant monitoring. Australia’s new national health priority of Quality Use of Medicine and Medicine Safety should stimulate all stakeholders including consumers to work together to address off-label medicine use.

Globally, the conditions and time scales underlying coastal ecosystem recovery following disturbance remain poorly understood, and post-disturbance examples of resilience based on long-term studies are particularly rare. Here, we documented the recovery of a marine foundation species (turtlegrass) following a hypersalinity-associated die-off in Florida Bay, USA, one of the most spatially extensive mortality events for seagrass ecosystems on record. Based upon annual sampling over two decades, foundation species recovery across the landscape was demonstrated by two ecosystem responses: the range of turtlegrass biomass met or exceeded levels present prior to the die-off, and turtlegrass regained dominance of seagrass community structure. Unlike reports for most marine taxa, recovery followed without human intervention or reduction to anthropogenic impacts. Our long-term study revealed previously uncharted resilience in subtropical seagrass landscapes but warns that future persistence of the foundation species in this iconic ecosystem will depend upon the frequency and severity of drought-associated perturbation.

This population-based cross-sectional survey with a follow-up case-control study assessed the prevalence, incidence, and risk factors for epilepsy in a rural health district in the North-West Region of Cameroon. Community-based epilepsy screening targeted all inhabitants, six years and older, in all 16 health areas in the Batibo Health District. During door-to-door visits, trained fieldworkers used a validated questionnaire to interview consenting household heads to screen for epilepsy in eligible residents. Trained physicians subsequently assessed people with suspected seizures. After clinical assessment, they confirmed or refuted the diagnosis and estimated the date of epilepsy onset. A trained nurse interviewed people with epilepsy and randomly selected healthy individuals, obtaining relevant demographic details and information on exposure to risk factors for epilepsy. Out of 36,282 residents screened, 524 had active epilepsy. The age-standardized prevalence of active epilepsy was 33.9/1,000 (95% CI: 31.0-37.1/1,000). We estimated the one-year age-standardized epilepsy incidence at 171/100,000 (95%CI: 114.0-254.6). Active epilepsy prevalence varied widely between health areas, ranging between 12 and 75 per 1,000. The peak age-specific prevalence was in the 25-34 age group. In adults, multivariate analysis showed that having a relative with epilepsy was positively associated with epilepsy. Epilepsy characteristics in this population, geographical heterogeneity, and the age-specific prevalence pattern suggest that endemic neurocysticercosis and onchocerciasis may be implicated. Further investigations are warranted to establish the full range of risk factors for epilepsy in this population.

OBJECTIVE To examine the efficacy and safety of paliperidone palmitate once-monthly (PP1M) versus oral antipsychotics (OAPs) in Black/African American patients with schizophrenia and a history of criminal justice system involvement. METHODS This was a post hoc analysis of a 15-month prospective, randomized, open-label, parallel-group, multicenter US study conducted from May 2010 to December 2013 that examined a subpopulation of Black/African American patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria). The primary objective was to compare time to first treatment failure in patients treated with PP1M versus OAPs. Secondary objectives were to compare time to first institutionalization (psychiatric hospitalization or arrest/incarceration) and mean number of treatment failure events and institutionalizations over 15 months in PP1M-treated and OAP-treated patients. RESULTS The intention-to-treat population included 275 Black/African American patients (PP1M, n = 145; OAPs, n = 130). Median time to first treatment failure was not reached for PP1M-treated patients and was 270 days for OAP-treated patients; hazard ratio (HR) was 1.39 (95% CI, 0.97-1.99; P = .075). Median time to first institutionalization was not reached for PP1M-treated patients and was 304 days for OAP-treated patients; HR was 1.49 (95% CI, 1.01-2.19; P = .043). Mean numbers of treatment failure events and institutionalizations were lower with PP1M than OAPs. The safety profile of PP1M was consistent with that of previous PP1M studies. CONCLUSIONS In a Black/African American subpopulation of patients with schizophrenia and prior criminal justice system involvement, PP1M reduced the number of treatment failures, thereby reducing the number of psychiatric hospitalizations and/or arrests/incarcerations compared with daily OAPs. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01157351.

Aims Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores. Materials and methods Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan–Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression. Results Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36–4.63) for p16 negative versus p16 positive, 2.17 (1.34–3.5) for T3/4 versus T1/2, 2.42 (1.52–3.8) for males versus females and 3.30 (1.52–7.14) for TIL1 versus TIL3 (all P Conclusions We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282).