bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravascular Large B-cell Lymphoma Presenting as Sudden Death
Authors: Jackson Nicole R.
Published: April 2023

Intravascular large B-cell lymphoma is a rare subset of non-Hodgkin lymphoma composed of mature B lymphoma cells confined to the intravascular space. This disease remains elusive because it lacks a discrete tumor mass, can affect any part of the body, and has vague symptoms paired with heterogeneous clinical findings resulting in delayed or missed accurate diagnosis, even at postmortem examination. This is a case of a woman who died within hours of presenting to the emergency department with a diagnosis of intravascular large B-cell lymphoma made through autopsy examination, adding to the knowledge of this rare disease and bringing it to the attention of practicing autopsy and forensic pathologists.
National Trends in Acellular Dermal Matrix Utilization in Immediate Breast Reconstruction
Authors: Graziano Francis D. , Plotsker Ethan L. , Rubenstein Robyn N. , Haglich Kathryn , Stern Carrie S. , Matros Evan , Nelson Jonas A.
Published: April 2023

BACKGROUND:

Implant-based reconstruction is most common method of immediate breast reconstruction in the United States, with acellular dermal matrices(ADM) playing a significant role in implant support and coverage. This study evaluated recent national trends in ADM use in immediate breast reconstruction and assessed patient characteristics and 30-day complication rates.

METHODS:

We queried the American College of Surgeons(ACS) National Surgical Quality Improvement Program (NSQIP) database for all patients undergoing immediate breast reconstruction from 2015 to 2020. Primary outcomes were major surgical and medical complications, as well as ADM use per year. Subset analysis was performed to compare patients undergoing immediate breast reconstruction with ADM in 2015 versus 2020.

RESULTS:

In 39,800 immediate breast reconstructions, ADMs were used in 55.5%(n=22,087 cases). ADM usage increased annually from 2015–2020. Direct-to-implant (DTI) reconstruction was significantly associated with ADM use(p<0.001). Compared to the no ADM cohort, there was a significantly increased rate of return to the OR for any reason(p < 0.001). When comparing the 2015 and 2020 ADM cohorts, the 2020 ADM cohort had a significantly higher rate of superficial infections. Obesity, smoking history, and insulin-dependent diabetes were independent risk factors for superficial wounds in ADM patients.

CONCLUSIONS:

ADM use in immediate breast reconstruction increased significantly from 2015–2020, likely reflecting national trends in increasing DTI and prepectoral breast reconstruction. Obesity, smoking history, and insulin-dependent diabetes were independent risk factors for superficial wound infections in the ADM cohort. Patients with ADM had a slight increased incidence of return to the operating room.
Impact of one-piece fronto-orbital distraction osteogenesis on orbital morphology and the development of strabismus in patients with unilateral craniosynostosis
Authors: Park Hojin , Choi Jong Woo , Ra Young Shin
Published: April 2023

Background:

Unicoronal craniosynostosis (UCS) is associated with orbital dysmorphologies that underlie ophthalmologic dysfunctions, such as strabismus. This study aimed to assess orbital dysmorphology in patients with UCS and how it changes after fronto-orbital distraction osteogenesis (FODO), and to analyze the features of new-onset strabismus.

Methods:

A retrospective analysis was conducted on 19 patients with UCS who underwent FODO between May 2008 and November 2020. Ophthalmologic records and computed tomography were reviewed. Seven parameters, including width, height, volume, and 4-direction orbital angles were evaluated in patients with UCS and compared with those of age-matched control subjects.

Results:

The superolateral angle (SLA) and vertical angle (VA) of the ipsilateral orbit and the superomedial angle (SMA) of the contralateral orbit were more obtuse than those of the controls. Following FODO, the ipsilateral SLA was decreased from 69.2±5.4 degrees to 59.1±4.2 degrees (p=0.001), and the contralateral SMA was decreased from 64.8±5.8 degrees to 60.2±6.0 degrees (p=0.003). Four of the 17 patients without strabismus in the preoperative period developed strabismus, and the horizontal type was the most common. Logistic regression analysis demonstrated a significant association between new-onset strabismus and superomedial angle difference between both orbits (p=0.041, odds ratio: 1.39).

Conclusions:

Orbital dysmorphology in the UCS is bilateral, and the orbital roofs are dysmorphic. The bilateral orbital roofs are lifted toward the fused coronal suture and can be improved after FODO. Horizontal strabismus, such as esotropia and exotropia, is common after FODO, and superomedial orbital roof asymmetry may play a role in its development.
Spatial Fidelity of Microvascular Perforating Vessels as Perceived by Augmented Reality Virtual Projections
Authors: Cholok David J , Fischer Marc J , Leuze Christoph W , Januszyk Michael , Daniel Bruce L , Momeni Arash
Published: April 2023

Background:

Autologous breast reconstruction yields improved long-term aesthetic results but requires increased resources of practitioners and hospital systems. Innovations in radiographic imaging have been used increasingly to improve the efficiency and success of free-flap harvest. Augmented reality (AR) affords the opportunity to superimpose relevant imaging on a surgeon’s native field of view, potentially facilitating dissection of anatomically variable structures. To validate the spatial fidelity of AR projections of deep inferior epigastric perforator flap (DIEP) relevant anatomy, comparisons of 3D models and their virtual renderings were performed by four independent observers. Measured discrepancies between the real and holographic models were evaluated.

Methods:

3D-printed models of DIEP relevant anatomy were fabricated from CTA data from 19 de-identified patients. The corresponding CTA data was similarly formatted for the Microsoft Hololens to generate corresponding projections. Anatomic points were initially measured on 3D models, after which, the corresponding points were measured on the Hololens projections from two separate vantages. Statistical analyses, including Generalized Linear Modeling, were performed to characterize spatial fidelity regarding translation, rotation, and scale of holographic projections.

Results:

Amongst all participants, the median translational displacement at corresponding points was 9.0 mm, 12.1 mm, and 13.5 mm between the real 3D model and V1, 3D model and V2, and between V1 and V2, respectively.

Conclusion:

Corresponding points, including topography of perforating vessels for the purposes of breast reconstruction can be identified within millimeters, but there remain multiple independent contributors of error, most notably the participant and location at which the projection is perceived.
Classification of Health Information Technology Safety Events in a Pediatric Tertiary Care Hospital
Authors: Khan Amina , Karavite Dean J. , Muthu Naveen , Shelov Eric , Nawab Ursula , Desai Bimal , Luo Brooke
Published: April 2023

Objective

State agencies have developed reporting systems of safety events that include events related to health information technology (HIT). These data come from hospital reporting systems where staff submit safety reports and nurses, in the role of safety managers, review, and code events. Safety managers may have varying degrees of experience with identifying events related to HIT. Our objective was to review events potentially involving HIT and compare those with what was reported to the state.

Methods

We performed a structured review of 1 year of safety events from an academic pediatric healthcare system. We reviewed the free-text description of each event and applied a classification scheme derived from the AHRQ Health IT Hazard Manager and compared the results with events reported to the state as involving HIT.

Results

Of 33,218 safety events for a 1-year period, 1247 included key words related to HIT and/or were indicated by safety managers as involving HIT. Of the 1247 events, the structured review identified 769 as involving HIT. In comparison, safety managers only identified 194 of the 769 events (25%) as involving HIT. Most events, 353 (46%), not identified by safety managers were documentation issues. Of the 1247 events, the structured review identified 478 as not involving HIT while safety managers identified and reported 81 of these 478 events (17%) as involving HIT.

Conclusions

The current process of reporting safety events lacks standardization in identifying health technology contributions to safety events, which may minimize the effectiveness of safety initiatives.
Stress Testing the Cardiac Catheterization Laboratory
Authors: Jafri Farrukh Nadeem , Santana Felipes Rachel C. , Bliagos Dimitrios , Torres Rafael E. , Bellido Simon , Arif Amber , Elwell Diana , Mirante Doreen , Ellsworth Kelly , Cardasis John , Anastasian George , Pinto Hazel , Kochar Ajar
Published: April 2023

Introduction

Although uncommon, cardiac arrests in the cardiac catheterization laboratory (CCL) are often catastrophic and likely to increase with rising case complexity. In situ simulation (ISS) has been used to identify latent safety threats (LSTs) in inpatient units but has not yet been studied in the CCL.

Methods

Three Plan-Do-Study-Act (PDSA) cycles leveraging ISS were conducted focused on acute airway management. Data collected through debriefs focused on (1) airway management, (2) equipment availability, and (3) interdepartmental communication. The LSTs were subcategorized and plotted on the Survey Analysis for Evaluating Risk (SAFER)-Matrix. A SAFER score was calculated based on quantifying the likelihood of harm, scope, and the number of times a threat was identified during simulation. Time to definitive airway was collected as a secondary measure. Interventions were developed using cause and effect and driver diagrams between PDSA cycles.

Results

Eleven total simulations through 3 PDSA cycles were conducted between January and December 2021 (5 in PDSA 1, 4 in PDSA 2, and 2 in PDSA 3). One hundred one LSTs were identified with 14 total subcategories. The mean SAFER score decreased from 5.37 in PDSA 1, to 2.96 in PDSA 2, and to 1.00 in PDSA 3. Bivariate regression analysis showed a decrease in SAFER score of 2.19 for every PDSA cycle (P = 0.011). Ordinary least squares regression had a decrease of 1.65 in airway-related threats every PDSA cycle (P < 0.01) as well as an increase in intubation time of 35.0 seconds for every 1-unit increase in communication threat identified (P = 0.037).

Conclusions

This study successfully leveraged ISS and existing quality improvement initiatives in the CCL, resulting in a decrease in airway-related threats as measured through simulation.
ICTV Virus Taxonomy Profile: Simuloviridae 2023
Authors: Liu Ying , Du Shishen , Chen Xiangdong , Dyall-Smith Mike , Jalasvuori Matti , Oksanen Hanna M. ,   ICTV Report Consortium
Published: April 2023

The family Simuloviridae includes tailless icosahedral viruses with an internal lipid membrane. The capsid is constructed from two major capsid proteins, both with a single jelly-roll fold. The genome is a circular dsDNA molecule of 16–19 kb. All members infect halophilic archaea in the class Halobacteria (phylum Euryarchaeota) and are temperate viruses, their proviruses residing in host cells as extrachromosomal episomes. Once the lytic life cycle is triggered, production of virions causes cell lysis. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Simuloviridae, which is available at ictv.global/report/simuloviridae.
Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: a comparative cohort study
Authors: Slavova Nedelina , Münger Robin , Sanchez-Albisua Iciar , Regényi Maria , Oesch Gabriela , Fluss Joël , Hackenberg Annette , Lebon Sébastien , Maier Oliver , Datta Alexandre , Bigi Sandra , Grunt Sebastian , Steinlin Maja
Published: April 2023

Background

Inflammatory type Focal Cerebral Arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized and the FCA severity score (FCASS) reflects the severity of disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases.

Methods

Patients from the Swiss NeuroPaediatric Stroke Registry (SNPSR) with ischemic stroke in the PC and AC due to FCA-i and available neuroimaging were gathered. Comparison of data regarding Pediatric National Institutes of Health Stroke Scale (pedNIHSS) score and Pediatric Stroke Outcome Measure (PSOM) and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score (pedASPECTS) in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging (DWI) score in the PC.

Results

Thirty-six children with a median age of 6.3 years ([IQR 2.8,8.6; range 0.9,15.6], 21 males, 58.3%) with FCA-i were identified. The total incidence rate was 0.151/100 000/year (95%CI 0.109–0.209). Seven had PC FCA-i and 5 had FCA-i in both circulations. Time to final FCASS was longer in the PC compared to AC, evolution of FCASS did not differ. Initial pedNIHSS was highest in children with FCA-i in the PC with a median of 8.0 (IQR 5.0-18.0), compared to 4.5 (IQR 2.0-8.0) in those with AC FCA-i and 6.0 (IQR 6.0-6.0) with involvement of both AC and PC. Different to the anterior cases PC infarct volume did not correlate with higher discharge, maximum or final FCASS scores (R 0.25, 0.35, 0.54).

Conclusion

The PC is affected in up to one third of cases of FCA-i. These cases should be included in future investigations on FCA-i. Although it did not correlate with clinical outcome in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.
An approach to assess the patient benefit of demand management strategies
Authors: Yago Martín
Published: April 2023

Background

Much of the testing performed by clinical laboratories does not translate into benefit for patients. To reduce the number of these low-value tests, laboratories use different intervention strategies, trying to adapt the analytical demand to clinical needs. The effectiveness of these interventions is usually evaluated through indicators related to the activity or cost rather than the benefit they imply for patients.

Methods

We have derived expressions that relate the fraction of patients tested (Rt) and the abnormal result rate (Ra) obtained by the requesting physician with the net benefit that the use of the test represents for both tested and untested patients.

Results

The behavior of physicians regarding the use of a test in each healthcare context and the effect of an intervention on this behavior can be characterized by these two parameters:RaandRt. An increase in the value ofRaimplies a greater net benefit for all patients attended. When the physician is selective in the use of the test, an increase in the value ofRtimplies a greater benefit for untested patients but represents a limit to the increase inRa.

Conclusions

Interventions aimed at reducing the demand for tests should act primarily by increasing selectivity in the use of tests, increasing the benefit for the patients tested and compensating the harm that the reduction in testing entails for patients who are not.
Weather Shocks, Child Mortality, and Adaptation: Experimental Evidence from Uganda
Authors: Björkman Nyqvist Martina , von Carnap Tillmann , Guariso Andrea , Svensson Jakob
Published: April 2023

Background

Human-caused climate change is already increasing the intensity and frequency of extreme weather events, such as droughts. The health and economic consequences of these events are expected to be particularly severe for populations in low-income settings whose livelihoods rely on rain-fed agriculture. Within these populations, children are an especially vulnerable group, as undernutrition is linked to 45% of all child deaths across the globe. Despite progress, adaptation gaps exist. We still lack strong evidence on policies to effectively mitigate climate change’s most severe consequences for children. In this paper we ask whether adaptation investments in the form of improved community healthcare can build climate resilience in a low-income country setting.

Methods

We reanalyzed data from a clustered randomized controlled trial inducing spatial variation across 214 Ugandan villages in community-health program strengthening, and combined it with quasi-experimental data on locality-specific rainfall shocks. In the intervention clusters, financially incentivized community health workers (CHWs) were deployed over a three-year period to conduct home visits and provide integrated community case management and maternal, newborn, and child health treatment and preventive services. The trial followed 7,018 households with young children (3,790 in 115 intervention clusters and 3,228 in 99 control clusters) over three years. We estimated the effect of low rainfall in the growing season on infant mortality in the following (post-harvest and lean) period, conditional on CHW deployment, over six season-pairs in 2011-2013.

Findings

There were 134 infant deaths in the intervention clusters (38.6 deaths per 1000 infant-years) over the three-year trial period. 60 deaths (40.7 deaths per 1000 infant-years) occurred in periods following growing seasons with rainfall below the long-run detrended mean (rainfall deficit seasons), and 74 deaths (36.8 deaths per 1000 infant-years) occurred in periods following growing seasons rainfall above the long-run detrended mean (rainfall surplus seasons). There were 160 infant deaths in the comparison clusters (61.3 deaths per 1000 infant-years). 83 deaths (81.5 deaths per 1000 infant-years) occurred in periods following rainfall deficit seasons, and 77 deaths (46.3 deaths per 1000 infant-years) occurred in periods following rainfall surplus seasons. Adjusting only for the stratified random assignment of clusters, the mean difference corresponded to a 46% reduction in under-five mortality rate (p=.000; adjusted rate ratio 0.54, 95% CI 0.39-0.73) following rainfall deficit seasons. The risk of infant deaths in the comparison relative to the intervention group increased in the magnitude of the rainfall deficit.

Interpretation

Adaptation investments in a low-income context – here in the form of improved access to community health care – reduced the risk of infant mortality following adverse weather events.
Association Between Artificial Intelligence-Derived Tumor Volume and Oncologic Outcomes for Localized Prostate Cancer Treated with Radiation Therapy
Authors: Yang David D , Lee Leslie K , Tsui James MG , Leeman Jonathan E , Lee Katie N , McClure Heather M , Sudhyadhom Atchar , Guthier Christian V , Mouw Kent W , Martin Neil E , Orio Peter F , Nguyen Paul L , D’Amico Anthony V , King Martin T
Published: April 2023

Background

Although clinical features of multi-parametric magnetic resonance imaging (mpMRI) have been associated with biochemical recurrence in localized prostate cancer, such features are subject to inter-observer variability.

Objective

To evaluate whether the volume of the dominant intraprostatic lesion (DIL), as provided by a deep learning segmentation algorithm, could provide prognostic information for patients treated with definitive radiation therapy (RT).

Design, Setting, and Participants

Retrospective study of 438 patients with localized prostate cancer who underwent an endorectal coil, high B-value, 3-Tesla mpMRI and were treated with RT between 2010 and 2017.

Intervention

RT.

Outcome Measurements and Statistical Analysis

Biochemical recurrence and metastasis risk, assessed with a cause-specific Cox regression and time-dependent receiver operating characteristic analysis.

Results and Limitations

The artificial intelligence (AI) model identified DILs with an area under the receiver operating characteristic curve (AUROC) of 0.827 at the patient level. For the 233 patients with available PI-RADS scores, with a median follow-up of 5.6 years, AI-defined DIL volume was significantly associated with biochemical failure (adjusted hazard ratio 1.54, 95% confidence interval 1.09-2.17, p=0.014) after adjustment for PI-RADS score. Among all 438 patients with a median follow-up of 6.9 years, the AUROC for predicting 7-year biochemical failure for AI volume (0.790) was similar to that for an expanded National Comprehensive Cancer Network (NCCN+) category (p=0.17). The AUROC for predicting 7-year metastasis for AI volume trended towards being higher compared to NCCN+ categories (0.854 vs 0.769, p=0.06).

Conclusions

A deep learning algorithm could identify the DIL with good performance. AI-defined DIL volume may be able to provide prognostic information independent of the NCCN+ risk group or other radiologic factors for patients with localized prostate cancer treated with RT.
Effects of different cluster-set rest intervals during plyometric-jump training on measures of physical fitness: a randomized trial
Authors: Moghadam Behzad Taaty , Shirvani Hossein , Ramirez-Campillo Rodrigo , Martín Eduardo Báez-San , Abdolmohamadi Ali , Bazgir Behzad
Published: April 2023

The optimal intra-set rest in cluster sets (CLS) plyometric-jump training (PJT) to improve physical fitness remains unclear. Thus, this study compared the effects of PJT with traditional (TRS) vs. CLS structures using different intra-set rests on physical fitness components. Forty- seven recreationally active young men performed 3-5 sets of 10-12 repetitions of upper- and lower-body exercises twice a week for six weeks using different set configurations as the TRS group (no intra-set rest), and the CLS10, CLS20 and CLS30 groups with 10, 20 and 30 s intra-set rest, respectively, while the total rest period (i.e., 180 s) was equated. Testing was carried out 48 h before and after the intervention and the rating of fatigue (ROF) was also assessed 20 min after the first and last session. There was no significant difference in the mean energy intake between groups (p> 0.05). The ANCOVA revealed that all groups showed similar improvements (p< 0.05) in body mass, body mass index, fat-free mass, one repetition maximum (dynamic strength) and repetitions to failure (muscular endurance) in back squat and chest press, handgrip strength, standing long jump, 20 m sprint, and 9-m shuttle run (change of direction speed), whereas the ROF decreases were greater in the CLS20 and CLS30 groups (p< 0.05). Compared to the TRS structure, six weeks of PJT with an intra-set rest of 20 s, or 30 s induced similar improvements in the measures of physical fitness and anthropometrics, with lower exercise-induced fatigue perception.
Prospective phenotyping of CHAMP1 disorder indicates that coding mutations do not act through haploinsufficiency
Authors: Levy Tess , Pichardo Thariana , Silver Hailey , Lerman Bonnie , Zweifach Jessica , Halpern Danielle , Siper Paige M , Kolevzon Alexander , Buxbaum Joseph D
Published: April 2023

CHAMP1 disorder is a genetic neurodevelopmental condition caused by mutations in the CHAMP1 gene that result in premature termination codons. The disorder is associated with intellectual disability, medical comorbidities, and dysmorphic features. Deletions of theCHAMP1gene, as part of 13q3 deletion syndrome, have been briefly described with the suggestion of a milder clinical phenotype. To date, no studies have directly assessed differences between individuals with mutations inCHAMP1to those with deletions of the gene. We completed prospective clinical evaluations of 16 individuals with mutations and eight with deletions inCHAMP1. Analyses revealed significantly lower adaptive functioning across all domains assessed (i.e., communication, daily living skills, socialization, and motor skills) in the mutation group. Developmental milestones and medical features further showed difference between groups. The phenotypes associated with mutations, as compared to deletions, indicate likely difference in pathogenesis between groups, where deletions are acting through CHAMP1 haploinsufficiency and mutations are acting through dominant negative or gain of function mechanisms, leading to a more severe clinical phenotype. Understanding this pathogenesis is important to the future of novel therapies for CHAMP1 disorder and illustrates that mechanistic understanding of mutations must be carefully considered prior to treatment development.
Too much information? Asian Americans’ preferences for incidental brain MRI findings
Authors: Kota Karthik , Dawson Alice , Papas Julia , Sotelo Victor , Su Guibin , Li Mei-Ling , Lee Woowon , Estervil Jaunis , Marquez Melissa , Sarkar Shromona , Lopez Lisa Lanza , Hu William T.
Published: April 2023

INTRODUCTION

South Asian (SA) and East Asian (EA) older adults represent the fastest growing group of Americans at risk for dementia, but their participation in aging and dementia research has been limited. While recruiting healthy SA older adults into a brain health study, we encountered unexpected hesitancy towards structural brain MRI analysis along with some stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as one’s own MRI experience, perceived MRI safety, and concerns for one’s own risks for future dementia/stroke.

METHODS

We developed a brief cross-sectional survey to assess older adults’ MRI experiences and perceptions, desire to learn of six incidental findings of increasing health implications, and attitudes related to dementia as well as research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey, and modeled the proportional odds (P.O.) for pro-research attitudes.

RESULTS

77 SA and 84 EA respondents were analyzed with 95 non-Asian adults. White (P.O.=2.54, p=0.013) and EA (P.O.=2.14, p=0.019) respondents were both more likely than SA respondents to endorse healthy volunteers’ participation in research, and the difference between White and SA respondents was mediated by the latter’s greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p=0.006), but still shared SA respondents’ low desire to learn of incidental MRI findings.

DISCUSSION

SA and EA older adults had different attitudes towards future dementia/stroke risks, but shared a low desire to learn of incidental MRI findings. A culturally-appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research.

Color printing

Please have figure one and two be in color; figure three is in black and white
TB disease yield from household contact screening of tuberculosis index patients; a cohort study from Karachi, Pakistan
Authors: Jaswal Maria R. , Farooq Saira , Hussain Hamidah , Shah Jinsar , Nasir Kumail , Khalil Ahsan , Khan Hiba , Safdar Nauman , Malik Amyn A. , McQuaid Christopher F.
Published: April 2023

Nearly 40% of people affected by TB in Pakistan are not diagnosed each year. Guidelines recommend screening household contacts however, not all index patients or contacts are eligible. Therefore, many contacts who may have TB disease, remain unscreened.

We conducted a prospective cohort study under programmatic conditions in Karachi, Pakistan from January 2018 - December 2019, to screen all household contacts of all TB index patients. We disaggregated these according to guidelines into eligible (those with bacteriologically confirmed pulmonary TB or children <5 years) or ineligible (those with clinically diagnosed or extrapulmonary TB ≥5 years) index patients, and eligible (children <5 years or symptomatic individuals) or ineligible (asymptomatic individuals ≥5 years) contacts. We calculated TB disease yields for different groups of index patients and contacts.

Out of 39,168 household contacts from 6,362 index patients, 21,035 completed clinical assessments for TB disease, and 416 were diagnosed with all forms TB. Household contacts of clinically diagnosed pulmonary TB patients were 26% more likely to be diagnosed with TB compared to the household contacts of bacteriologically confirmed pulmonary TB (adjusted Odds Ratio 1.26 [1.01 – 1.59] p-value:0.03). The yield of TB disease among child contacts (3.4%) was significantly higher than the yield among adult contacts (0.5%) (p-value:<0.001).

Broadening TB contact screening guidelines to include clinically diagnosed and extrapulmonary index patients ≥5 years could double the number of patients detected at a similar level of effort.
YouDiagnose Predictive Model Pilot Study to Compare Expert Human vs. Machine Prediction Accuracy
Authors: Misro Aswini , Sharma Vikash , Kadoglou Naim
Published: April 2023

YouDiagnose carried out a pilot study that seeks to compare the accuracy of expert human predictions with those made by a predictive model. Specifically, this study will analyse the prediction of diseases, cancer risk and the care need of patients being admitted or referred to the specialist service. The doctor was provided with a set of patient data, e.g., patient ID 9001 to 9050. The pilot consisted of 2 parts 1. Clinical prediction and 2. Model validation. In the first part, the doctor had to read the information in the clinical vignette and had to select one of the predetermined choices for the best clinical prediction (DP-1, DP-2, DP-3). Afterwards, he/she was asked to validate the model’s predictions (MP-1, MP-2, MP-3) and recommendations (R-1, R-2, R-3) for the same case.

The study shows that MP has higher total accuracy (82.8%) compared to DP (50.6%). In predicting cancer, the MP method has higher sensitivity (100.0%) and positive predictive value (38.5%) compared to the DP method (90.0% sensitivity and 30.0% positive predictive value). The MP method also has higher specificity (78.9%) compared to the DP method (72.7%). Both methods have high negative predictive values (98.2% for DP and 100.0% for MP) with a p-value of 0.3705.

The results of the current pilot study demonstrate the model’s potential, while also highlighting areas where further testing is needed in order to increase user confidence and improve the accuracy of diagnosis. Such testing could provide invaluable insights into how to maximize the value of the system in offering better frontline screening solutions e.g., triaging, clinical decision support, risk-based clinic booking system etc.
Reanalysis of cluster randomised trial data to account for exposure misclassification using a per-protocol and complier-restricted approach
Authors: Dufault Suzanne M. , Tanamas Stephanie K. , Indriani Citra , Ahmad Riris Andono , Utarini Adi , Jewell Nicholas P. , Simmons Cameron P. , Anders Katherine L.
Published: April 2023

The intention-to-treat (ITT) analysis of the ApplyingWolbachiato Eliminate Dengue (AWED) trial estimated a protective efficacy of 77.1% for participants resident in areas randomised to receive releases ofwMel-infectedAedes aegyptimosquitoes, an emerging dengue preventive intervention. The limiting assumptions of ITT analyses in cluster randomised trials and the mobility of mosquitoes and humans across cluster boundaries indicate the primary analysis is likely to underestimate the full public health benefit. Using spatiotemporally-resolved data on the distribution ofWolbachiamosquitoes and on the mobility of AWED participants (n = 6,306), we perform complier-restricted and per-protocol re-examinations of the efficacy of theWolbachiaintervention. Increased intervention efficacy was estimated in all analyses by the refined exposure measures. The complier-restricted analysis returned an estimated efficacy of 80.7% (95% CI: 65.9, 89.0) and the per-protocol analysis estimated 82.7% (71.7, 88.4) efficacy when comparing participants with an estimatedwMel exposure of≥80% compared to those with<20%. These reanalyses demonstrate how human and mosquito movement can lead to underestimation of intervention effects in trials of vector interventions and indicate that the protective efficacy ofWolbachiais even higher than reported in the primary trial results.
Rheumatoid Arthritis and Sarcopenia - a Prospective Single Center Cohort Study of Postmenopausal Women
Authors: Schietzel Simeon , Moor Matthias B. , Roos Flurina , Stalder Odile , Aeberli Daniel
Published: April 2023

Objectives

The individual and socioeconomic burden of sarcopenia in rheumatoid arthritis (RA) is most relevant. However, longitudinal cohort data are scarce.

Methods

Prospective, single-center, controlled, observational cohort study of consecutive 124 postmenopausal women, 53 with RA, 71 healthy controls (HC). Low muscle mass and low muscle strengths was defined according to the European working group on sarcopenia in older people 2019 (appendicular lean mass index [ALMI] via dual-energy x-ray absorptiometry < 5.5 Kg/m2; handgrip strength via dynamometer < 16 Kg). Linear regression models were calculated including demographic and anthropometric data, comorbidities, and co-medication as confounders.

Results

Median age was 63 (IQR 56, 70), follow-up 2.1 (IQR 2.0, 5.3) years. At baseline, median ALMI was 6.2 (IQR 6.0, 6.5) Kg/m2in RA patients, 6.3 (IQR 5.6, 6.9) Kg/m2in HC (p = 0.64) with no difference in rates of low muscle mass (RA 16.2 % vs. HC 15.1 %). In the fully adjusted model, mean change in ALMI per year was -0.05 (95%CI -0.10 to -0.01) Kg/m2in RA patients and 0.00 (95%CI -0.02 to 0.03) Kg/m2in HC resulting in a differential loss of -0.06 (95%CI -0.11 to -0.01) Kg/m2per year (p = 0.027). For RA patients, the adjusted OR of experiencing any loss of muscle mass was 3.98 (95%CI 1.47 to 10.77) compared to HC (p = 0.007). On average, RA patients lost 0.78 % of muscle mass per year. At baseline, low grip strength was seen in 27.3 % of RA patients and in 2.9 % of HC (p = 0.002). In both groups, grip strength did not decline during study period. TNFα inhibitors were associated with less, T-cell inhibition with greater loss of muscle mass. Low mass at baseline, disease duration and disease activity were not associated with loss of muscle mass.

Conclusion

Postmenopausal women with RA have a significant risk of accelerated loss of muscle mass over time.
Antenatal care coverage in a low-resource setting: estimations from the Birhan Cohort
Authors: Pons-Duran Clara , Bekele Delayehu , Haneuse Sebastien , Hunegnaw Bezawit Mesfin , Alemu Kassahun , Kassa Munir , Berhan Yifru , Goddard Frederick G.B. , Taddesse Lisanu , Chan Grace J.
Published: April 2023

Antenatal care (ANC) coverage estimates commonly rely on self-reported data, which may carry biases. Leveraging prospectively collected longitudinal data, this study aimed to estimate the coverage of ANC, minimizing assumptions and biases due to self-reported information and describing retention patterns in ANC in rural Amhara, Ethiopia. This is a cohort study using data from the Birhan Health and Demographic Surveillance System and its nested pregnancy and birth cohort, the Birhan Cohort. The study population were women enrolled and followed during pregnancy between December 2018 and April 2020. ANC visits were measured by prospective facility chart abstraction and self-report at enrollment. The primary study outcomes were the total number of ANC visits attended during pregnancy and the coverage of at least one, four and eight ANC visits. Additionally, we estimated ANC retention patterns.We included 2069 women, of which 150 (7.2%) women enrolled <13 weeks of gestation with complete prospective facility reporting. Among 150 women, ANC coverage of at least one visit was 97.3%, whereas coverage of four visits or more was 34.0%. Among all women, coverage of one ANC visit was 92.3%, while coverage of four or more visits was 28.8%. No women were found to have attended eight or more ANC visits. On retention in care, 70.3% of participants who had an ANC visit between weeks 28 and <36 of gestation did not return for a subsequent visit. Despite the high proportion of pregnant women who accessed ANC at least once in our study area, the coverage of four visits remains low. Further efforts are needed to enhance access to more ANC visits, retain women in care, and adhere to the most recent National ANC guideline. It is essential to identify the factors that lead a large proportion of women to discontinue ANC follow-up.
Atrial fibrillation in adult congenital heart disease in Asia
Authors: Chiu Shuenn-Nan , Tseng Wei-Chieh , Lu Chun-Wei , Lin Ming-Tai , Chen Chun-An , Wang Jou-Kou , Wu Mei-Hwan
Published: April 2023

Introduction

With the improvement of long-term survival of patients with congenital heart disease (CHD), complications such as atrial fibrillation (AF) have become a concern. This study aimed to determine the epidemiology data and risk factors of AF in adult CHD (ACHD) patients and evaluate the impact of AF on late outcomes using a large ACHD cohort in Asia.

Method

This study enrolled all CHD patients older than 18 years of age diagnosed with CHD at National Taiwan University Hospital between 2007 and 2018. Data on patients’ clinical characteristics, electrocardiogram, Holter reports, and follow-up information were collected. AF status was classified as sustained AF, paroxysmal AF, or intra-atrial reentry tachycardia (IART). CHD was categorized as simple, severe, or complex CHD (single ventricle). Primary endpoint was defined as cerebrovascular accidents (CVA) or death.

Result

The study included 4403 patients (55.9% women), with 16.4% having severe and 2.9% having complex CHD. The cumulative incidence of AF was 6.9% (54.8% paroxysmal AF, 26.9% sustained AF, and 18.4% IART), which is comparable to the Western countries. The incidence increased with age and was higher in patients with pulmonary hypertension (PH, 27%), complex CHD (12.7%), and metabolic syndrome. The mean onset age of IART, paroxysmal, and sustained AF was 35.7±15.8, 48.4±19.3, and 56.9±14.2 years, respectively. Multivariate Cox regression analysis revealed that male sex, PH, and severe and complex CHD were the most critical risk factors for AF (odds ratio 1.67, 1.91, 3.55, and 12.6, respectively). The 70-year CVA-free survival rate was 67.1% in patients with AF (vs. 80.5% in those without AF, p<0.001). However, multivariate Cox regression analysis identified male sex, PH, severe and complex CHD, and genetic syndrome as the most significant risk factors of the primary endpoint (odds ratio 1.76, 3.38, 2.62 and 19.3, and 8.91, respectively).

Conclusions

This large ACHD cohort showed a high cumulative incidence of AF, similar to the Western countries, which increased with age, PH, and CHD severity. CVA-free survival was more closely associated with these factors than with AF.
International Classification of Diseases (ICD) Codes for Congenital Heart Defects (CHD) Have Variable and Limited Accuracy for Detecting CHD Cases
Authors: Ivey Lindsey C. , Rodriguez Fred H. , Shi Haoming , Chong Cohen , Chen Joy , Raskind-Hood Cheryl , Downing Karrie F. , Farr Sherry L. , Book Wendy M.
Published: April 2023

Background

Administrative data permits analysis of large cohorts but relies on International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD) codes that may not reflect true congenital heart defects (CHD).

Methods

1497 cases with at least one encounter between 1/1/2010 – 12/31/2019 in two healthcare systems (one adult, one pediatric) identified by at least one of 87 ICD CHD codes were validated through chart review for the presence of CHD and CHD anatomic group.

Results

Inter- and intra-observer reliability averaged > 95%. Positive predictive value (PPV) of ICD codes for CHD was 68.1% (1020/1497) overall, 94.6% (123/130) for cases identified in both healthcare systems, 95.8% (249/260) for severe codes, 52.6% (370/703) for shunt codes, 75.9% (243/320) for valve codes, 73.5% (119/162) for shunt and valve codes, and 75.0% (39/52) for “Other CHD” (7 ICD codes). PPV for cases with >1 unique CHD code was 85.4% (503/589) vs. 56.3% (498/884) for one CHD code. Of cases with secundum atrial septal defect ICD codes 745.5/Q21.1 in isolation, 30.9% (123/398) had a confirmed CHD. Patent foramen ovale was present in 66.2% (316/477) of false positives (FP). The median number of unique CHD-coded encounters was higher for true positives (TP) than FP (2.0; interquartile range [IQR]: 1.0-3.0 vs 1.0; IQR:1.0-1.0, respectively, p<0.0001). TP had younger mean age at first encounter with a CHD code than FP (22.4 years vs 26.3 years, p=0.0017).

Conclusion

PPV of CHD ICD codes varies by characteristics for detection of CHD by ICD code and anatomic grouping. While an ICD code for severe CHD and/or the presence of a case in more than one data source, regardless of anatomic group, is associated with higher PPV for CHD, most TP cases did not have these characteristics. The development of algorithms to improve accuracy may improve administrative data for CHD surveillance.
Analytical validation of the PROphet test for treatment decision-making guidance in metastatic non-small cell lung cancer
Authors: Yellin Ben , Lahav Coren , Sela Itamar , Yahalom Galit , Shoval Shani Raveh , Elon Yehonatan , Fuller James , Harel Michal
Published: April 2023

The blood proteome, consisting of thousands of proteins engaged in various biological processes, acts as a valuable source of potential biomarkers for various medical applications. PROphet is a plasma proteomics-based test that serves as a decision-support tool for non-small cell lung cancer (NSCLC) patients. PROphet combines proteomic profiling using the SomaScan technology and subsequent computational algorithm. PROphet was implemented as a laboratory developed test (LDT). Under the Clinical Laboratory Improvement Amendments (CLIA) and Commission on Office Laboratory Accreditation (COLA) regulations, prior to releasing patient test results, a clinical laboratory located in the United States that employs an LDT must examine the performance characteristics concerning analytical validity. This study describes the experimental and computational analytical validity of the PROphet test, as required by CLIA/COLA. Experimental precision analysis displayed a median coefficient of variation (CV) of 3.9% and 4.7% for intra-plate and inter-plate examination, respectively, and the median accuracy rate between sites was 88%. Computational precision exhibited a high accuracy rate, with 93% of samples displaying complete concordance in results. A cross-platform comparison between SomaScan and other proteomics platforms yielded a median Spearman correlation coefficient of 0.51, affirming the consistency and reliability of the SomaScan platform. Our study presents a robust framework for evaluating the analytical validity of a platform that combines an experimental assay with subsequent computational algorithms. When applied to the PROphet test, strong analytical performance of the test was demonstrated.
Hormone Receptor Expression and Disease Prognosis in High-Grade Serous Ovarian Cancer
Authors: Dodds Leah V. , Sanchez-Covarrubias Alex P , Sowamber Ramlogan , Milea Anca , Pinto Andre , Ban Yuguang , Schlumbrecht Matthew , Shaw Patricia A , George Sophia HL
Published: April 2023

ER and PR regulate growth and differentiation in normal ovaries and fallopian tubes and in HGSC transformation and progression. Higher PR expression was associated with improved survival outcomes, while high ER expression was associated with worse survival in patients with HGSC. Here, we show that patients with ER+PR+ tumors have longer overall survival and confirm the role of PR as a prognostic marker of survival and response to chemotherapy. Gene expression analysis demonstrated up-regulation of the ATM signaling pathway in the ER+PR+ subgroup when compared to ER+PR− tumors. Up-regulation of interferon alpha, beta and gamma signaling, and antigen presentation pathways were identified in ER+PR− compared to ER−PR+. In summary, this study elucidated that the genomic and transcriptomic signatures related to ER/PR status in HGSC have clinical prognostic value.
Efficacy of pharmacological and interventional treatment for resistant hypertension-a network meta-analysis
Authors: Tian Zhejia , Barbosa Clara Vollmer , Lang Hannah , Bauersachs Johann , Melk Anette , Schmidt Bernhard MW
Published: April 2023

Background

Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease and mortality. Yet, its management is challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis.

Methods

MEDLINE, Cochrane Register of Controlled Trials and Web of Science Core Collection were systematically searched in March 2022. Randomized controlled trials comparing treatment options for management of resistant hypertension were included. Outcomes were blood pressure changes, measured in the office and in 24h ambulatory blood pressure measurement. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator.

Results

From 4771 records, 24 studies met the inclusion criteria with 3458 included patients in total. 12 active treatment alternatives were analyzed. Among all comparators, spironolactone had the highest-ranking probability and was considered the most effective treatment to reduce office systolic blood pressure (−13.30 mmHg [−17.89; −8.72];P< 0.0001) and 24h systolic blood pressure (−8.46 mmHg [−12.54; −4.38]; P < 0.0001) in patients with resistant hypertension.

Conclusion

Among all pharmacologic and interventional treatments, spironolactone is the most effective in reducing office and 24h systolic blood pressure in patients with resistant hypertension. More comparative trials and especially trials with long-term follow up are needed.

Graphical Abstract
Learning from the expert: studyingSalicorniato understand salinity tolerance
Authors: Salazar Octavio R. , Chen Ke , Melino Vanessa J. , Reddy Muppala P. , Hřibová Eva , Čížková Jana , Beránková Denisa , Aranda Manuel , Jaremko Lukasz , Jaremko Mariusz , Fedoroff Nina V. , Tester Mark , Schmöckel Sandra M.
Published: April 2023

Salinity remains a major inhibitor of crop production in irrigated and marginal lands. The identification of genes involved in salinity tolerance has been predominantly limited to model plants and crop species. However, plants naturally adapted to highly saline environments can provide key insights into mechanisms of salinity tolerance. Plants of the genusSalicorniagrow in coastal salt marshes, and their growth is even stimulated by NaCl – much can be learnt from them. We generated genome sequences of twoSalicorniaspecies and studied the transcriptomic and proteomic responses ofSalicornia bigeloviito NaCl. Through the generation of subcellular membrane proteomes, we found that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, where it could be involved in mediating Na+translocation into the vacuole to prevent toxicity in the cytosol. We identified 11 proteins of interest which, when expressed in yeast, altered salinity tolerance. One of these proteins, SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR showed it to be an intrinsically disordered protein and to localize to the endoplasmic reticulumin planta, where it could interact with ribosomes and RNA, potentially stabilizing or protecting them during salt stress. The study and understanding of the molecular mechanisms providing high salinity tolerance inS. bigeloviiis likely to provide significant insights for improving salinity tolerance of crop plants.