bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis
Authors: Mikiashvili L , Kempker R R , Chakhaia T S , Bablishvili N , Avaliani Z , Lomtadze N , Schechter M C , Kipiani M
Published: November 2023

Background

There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones).

Methods

We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting.

Results

Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%).

Conclusions

Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.
Symptoms, Viral Loads, and Rebound Among COVID-19 Outpatients Treated With Nirmatrelvir/Ritonavir Compared With Propensity Score–Matched Untreated Individuals
Authors: Smith-Jeffcoat Sarah E , Biddle Jessica E , Talbot H Keipp , Morrissey Kerry Grace , Stockwell Melissa S , Maldonado Yvonne , McLean Huong Q , Ellingson Katherine D , Bowman Natalie M , Asturias Edwin , Mellis Alexandra M , Johnson Sheroi , Kirking Hannah L , Rolfes Melissa A R , Olivo Vanessa , Merrill Lori , Battan-Wraith Steph , Sano Ellen , McLaren Son H , Vargas Celibell Y , Goodman Sara , Sarnquist Clea C , Govindaranjan Prasanthi , Petrie Joshua G , Belongia Edward A , Ledezma Karla , Pryor Kathleen , Lutrick Karen , Bullock Ayla , Yang Amy , Haehnel Quenla , Rao Suchitra , Zhu Yuwei , Schmitz Jonathan , Hart Kimberly , Grijalva Carlos G , Salvatore Phillip P
Published: November 2023

Background

Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals.

Methods

We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2–positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022—May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated.

Results

Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7).

Conclusions

Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients.
Political Memoir, Celebrity, and the Reclamation of Feminism: Gendered Self-representation in Julia Gillard’sMy Storyand Hillary Clinton’sWhat Happened
Authors: Taylor Anthea
Published: November 2023

Offering a close textual analysis of My Story (2014), the memoir of Australia’s first woman Prime Minister, Julia Gillard, and What Happened (2017), by the 2016 US Democratic Presidential nominee, Hillary Clinton, this article explores their attempts—as is becoming common for celebrities—to use the memoir form to attempt to regain some control over their public personas and their feminisms. Focusing on the kind of feminist selves they seek to bring into being through these memoirs, this article examines the rhetorical strategies they each deploy to disrupt the dominant gendered narratives that came to circulate during their time in power and beyond.
Long-term outcomes of bioprosthetic valves in the mitral position a systematic review of studies published over the last 20 years
Authors: Koulouroudias Marinos , Di Mauro Michele , Lorusso Roberto
Published: November 2023

OBJECTIVES

Although the use of bioprostheses for mitral valve replacement (bMVR) is on the rise, their long-term durability is not well described. Defining bMVR durability will be instrumental in setting the standard against which the performance of transcatheter mitral replacement is to be judged against. The authors of this systematic review aimed to identify, assess the quality and review the outcomes in studies reporting on long-term outcomes after bMVR published over the last 20 years.

METHODS

Medline, Embase and Cochrane CENTRAL were searched for studies that have reported outcomes beyond a minimum of 5 years of follow-up after bMVR. Cohort characteristics, definitions of structural valve deterioration (SVD) and outcomes were summarized. The risk of bias in included studies was assessed using the Cochrane QUIPS tool.

RESULTS

Twenty-one studies, including 15 833 patients, were identified. Sixty-four percent of all implants were porcine and the remaining bovine pericardial. Freedom from SVD at 10 years ranged from 58.9% to 100% and at 15 years from 58.3% to 93%. Freedom from reoperation ranged from 65% to 98.7% at 10 years and 78.5% to 91% at 15 years. Information on native valve pathology or dominant haemodynamic lesion was missing in 25% and 66% of studies, respectively. Reports of postoperative echocardiography were lacking, despite the heavy reliance on echocardiography for SVD diagnosis.

CONCLUSIONS

There is considerable variability in reporting bMVR long-term outcomes. As such, it is difficult to generate an unbiased, generalizable understanding of long- term outcomes after bMVR across the spectrum of mitral disease phenotypes.
Rhizosphere microbial community structure differs between constant subzero and freeze-thaw temperature regimes in a subarctic soil
Authors: Doherty Stacey J , Busby Ryan R , Baker Christopher C M , Barbato Robyn A
Published: November 2023

In the Arctic and subarctic, climate change is causing reduced snowpack extent and earlier snowmelt. Shallower snowpack decreases the thermal insulation of underlying soil and results in more freeze-thaw conditions reflective of dynamic air temperatures. The aim of this study was to determine the effect of alternative temperature regimes on overall microbial community structure and rhizosphere recruitment across representatives of three subarctic plant functional groups. We hypothesized that temperature regime would influence rhizosphere community structure more than plant type. Planted microcosms were established using a tree, forb, grass, or no plant control and subjected to either freeze-thaw cycling or static subzero temperatures. Our results showed rhizosphere communities exhibited reduced diversity compared to bulk soils, and were influenced by temperature conditions and to a lesser extent plant type. We found that plants have a core microbiome that is persistent under different winter temperature scenarios but also have temperature regime-specific rhizosphere microbes. Freeze-thaw cycling resulted in greater community shifts from the pre-incubation soils when compared to constant subzero temperature. This finding suggests that wintertime snowpack conditions may be a significant factor for plant-microbe interactions upon spring thaw.
Diagnosis of gastrointestinal infections: comparison between traditional microbiology and a commercial syndromic molecular-based panel
Authors: Ligero-López Jorge , García-Rodríguez Julio , Ruiz-Carrascoso Guillermo
Published: November 2023

Traditional diagnosis of infectious gastroenteritis is based on culture, microscopy and antigen detection. The development of gastrointestinal syndromic panels based on molecular techniques have allowed rapid and simultaneous identification of multiple pathogens. The objective was to evaluate the implementation of Allplex™ Gastrointestinal Panel Assays (AGPA): Allplex™ GI-Virus, Allplex™ GI-Bacteria (I) and Allplex™ GI-Parasite by comparing with traditional diagnosis. A retrospective comparative study was conducted at Hospital Universitario La Paz, between the first year of implementation of the AGPA (April 1, 2018 to March 31, 2019) and the results obtained during the previous year with traditional methods (April 1, 2017 to March 31, 2018). With the implementation of AGPA we obtained an increase in the detection of rotavirus and adenovirus, being statistically significant for rotavirus ([CI95%:3.60–6.79]; P < 0.05) and an increase in the positivity rates of all the bacteria tested, with the exception of Salmonella spp. ([CI95%:3.60–6.79]; P < 0.05). Comparing the bacteria recovered by culture, we obtained an increase in the case of Shigella spp. cultivation during the AGPA period. Regarding protozoa, we achieved a significant increase in the positivity rates for Cryptosporidium spp. ([CI95%:1.98–3.01] P < 0.05), Giardia intestinalis ([CI95%:3.94–5.25]; P < 0.05) and Blastocystis spp. ([CI95%:9.44–11.36]; P < 0.05). There was an improvement in report turnaround time when comparing molecular diagnosis to bacterial culture and concentration plus microscopy for parasites; but not compared with antigen detection. The molecular diagnosis approach with AGPA were more sensitive and had a faster turnaround time for some targets, and in our setting, enabled an increased diagnostic capacity for viruses and protozoa.
Improved semantic segmentation network using normal vector guidance for LiDAR point clouds
Authors: Kim Minsung , Oh Inyoung , Yun Dongho , Ko Kwanghee
Published: November 2023

As Light Detection and Ranging (LiDAR) sensors become increasingly prevalent in the field of autonomous driving, the need for accurate semantic segmentation of three-dimensional points grows accordingly. To address this challenge, we propose a novel network model that enhances segmentation performance by utilizing normal vector information. Firstly, we present a method to improve the accuracy of normal estimation by using the intensity and reflection angles of the light emitted from the LiDAR sensor. Secondly, we introduce a novel local feature aggregation module that integrates normal vector information into the network to improve the performance of local feature extraction. The normal information is closely related to the local structure of the shape of an object, which helps the network to associate unique features with corresponding objects. We propose four different structures for local feature aggregation, evaluate them, and choose the one that shows the best performance. Experiments using the SemanticKITTI dataset demonstrate that the proposed architecture outperforms both the baseline models, RandLA-Net, and other existing methods, achieving mean intersection over union of 57.9%. Furthermore, it shows highly competitive performance compared with RandLA-Net for small and dynamic objects in a real road environment. For example, it yielded 95.2% for cars, 47.4% for bicycles, 41.0% for motorcycles, 57.4% for bicycles, and 53.2% for pedestrians.
PathBank 2.0—the pathway database for model organism metabolomics
Authors: Wishart David S , Kruger Ray , Sivakumaran Aadhavya , Harford Karxena , Sanford Selena , Doshi Rahil , Khetarpal Nitya , Fatokun Omolola , Doucet Daphnee , Zubkowski Ashley , Jackson Hayley , Sykes Gina , Ramirez-Gaona Miguel , Marcu Ana , Li Carin , Yee Kristen , Garros Christiana , Rayat Dorsa Yahya , Coleongco Jeanne , Nandyala Tharuni , Gautam Vasuk , Oler Eponine
Published: November 2023

PathBank (https://pathbank.org) and its predecessor database, the Small Molecule Pathway Database (SMPDB), have been providing comprehensive metabolite pathway information for the metabolomics community since 2010. Over the past 14 years, these pathway databases have grown and evolved significantly to meet the needs of the metabolomics community and respond to continuing changes in computing technology. This year's update, PathBank 2.0, brings a number of important improvements and upgrades that should make the database more useful and more appealing to a larger cross-section of users. In particular, these improvements include: (i) a significant increase in the number of primary or canonical pathways (from 1720 to 6951); (ii) a massive increase in the total number of pathways (from 110 234 to 605 359); (iii) significant improvements to the quality of pathway diagrams and pathway descriptions; (iv) a strong emphasis on drug metabolism and drug mechanism pathways; (v) making most pathway images more slide-compatible and manuscript-compatible; (vi) adding tools to support better pathway filtering and selecting through a more complete pathway taxonomy; (vii) adding pathway analysis tools for visualizing and calculating pathway enrichment. Many other minor improvements and updates to the content, the interface and general performance of the PathBank website have also been made. Overall, we believe these upgrades and updates should greatly enhance PathBank's ease of use and its potential applications for interpreting metabolomics data.
ELM—the Eukaryotic Linear Motif resource—2024 update
Authors: Kumar Manjeet , Michael Sushama , Alvarado-Valverde Jesús , Zeke András , Lazar Tamas , Glavina Juliana , Nagy-Kanta Eszter , Donagh Juan Mac , Kalman Zsofia E , Pascarelli Stefano , Palopoli Nicolas , Dobson László , Suarez Carmen Florencia , Van Roey Kim , Krystkowiak Izabella , Griffin Juan Esteban , Nagpal Anurag , Bhardwaj Rajesh , Diella Francesca , Mészáros Bálint , Dean Kellie , Davey Norman E , Pancsa Rita , Chemes Lucía B , Gibson Toby J
Published: November 2023

Short Linear Motifs (SLiMs) are the smallest structural and functional components of modular eukaryotic proteins. They are also the most abundant, especially when considering post-translational modifications. As well as being found throughout the cell as part of regulatory processes, SLiMs are extensively mimicked by intracellular pathogens. At the heart of the Eukaryotic Linear Motif (ELM) Resource is a representative (not comprehensive) database. The ELM entries are created by a growing community of skilled annotators and provide an introduction to linear motif functionality for biomedical researchers. The 2024 ELM update includes 346 novel motif instances in areas ranging from innate immunity to both protein and RNA degradation systems. In total, 39 classes of newly annotated motifs have been added, and another 17 existing entries have been updated in the database. The 2024 ELM release now includes 356 motif classes incorporating 4283 individual motif instances manually curated from 4274 scientific publications and including >700 links to experimentally determined 3D structures. In a recent development, the InterPro protein module resource now also includes ELM data. ELM is available at: http://elm.eu.org.
JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles
Authors: Rauluseviciute Ieva , Riudavets-Puig Rafael , Blanc-Mathieu Romain , Castro-Mondragon Jaime A , Ferenc Katalin , Kumar Vipin , Lemma Roza Berhanu , Lucas Jérémy , Chèneby Jeanne , Baranasic Damir , Khan Aziz , Fornes Oriol , Gundersen Sveinung , Johansen Morten , Hovig Eivind , Lenhard Boris , Sandelin Albin , Wasserman Wyeth W , Parcy François , Mathelier Anthony
Published: November 2023

JASPAR (https://jaspar.elixir.no/) is a widely-used open-access database presenting manually curated high-quality and non-redundant DNA-binding profiles for transcription factors (TFs) across taxa. In this 10th release and 20th-anniversary update, the CORE collection has expanded with 329 new profiles. We updated three existing profiles and provided orthogonal support for 72 profiles from the previous release's UNVALIDATED collection. Altogether, the JASPAR 2024 update provides a 20% increase in CORE profiles from the previous release. A trimming algorithm enhanced profiles by removing low information content flanking base pairs, which were likely uninformative (within the capacity of the PFM models) for TFBS predictions and modelling TF-DNA interactions. This release includes enhanced metadata, featuring a refined classification for plant TFs’ structural DNA-binding domains. The new JASPAR collections prompt updates to the genomic tracks of predicted TF binding sites (TFBSs) in 8 organisms, with human and mouse tracks available as native tracks in the UCSC Genome browser. All data are available through the JASPAR web interface and programmatically through its API and the updated Bioconductor and pyJASPAR packages. Finally, a new TFBS extraction tool enables users to retrieve predicted JASPAR TFBSs intersecting their genomic regions of interest.
Pan-cancer analysis of promoter activity quantitative trait loci
Authors: Li Ran , Wan Dongyi , Liang Junnan , Liang Huifang , Huang Haohao , Li Ganxun
Published: November 2023

Altered promoter activity has been generally observed in diverse biological processes, including tumorigenesis. Accumulating evidence suggests that employing a quantitative trait locus mapping approach is effective in comprehending the genetic basis of promoter activity. By utilizing genotype data from The Cancer Genome Atlas and calculating corresponding promoter activity values using proActiv, we systematically evaluated the impact of genetic variants on promoter activity and identified >1.0 million promoter activity quantitative trait loci (paQTLs) as both cis- and trans-acting. Additionally, leveraging data from the genome-wide association study (GWAS) catalog, we discovered >1.3 million paQTLs that overlap with known GWAS linkage disequilibrium regions. Remarkably, ∼9324 paQTLs exhibited significant associations with patient prognosis. Moreover, investigating the impact of promoter activity on >1000 imputed antitumor therapy responses among pan-cancer patients revealed >43 000 million significant associations. Furthermore, ∼25 000 significant associations were identified between promoter activity and immune cell abundance. Finally, a user-friendly data portal, Pancan-paQTL (https://www.hbpding.com/PancanPaQTL/), was constructed for users to browse, search and download data of interest. Pancan-paQTL serves as a comprehensive multidimensional database, enabling functional and clinical investigations into genetic variants associated with promoter activity, drug responses and immune infiltration across multiple cancer types.
MOS4-associated complex contributes to proper splicing and suppression of ER stress under long-term heat stress in Arabidopsis
Authors: Endo Naoya , Tsukimoto Ryo , Isono Kazuho , Hosoi Akito , Yamaguchi Ryo , Tanaka Keisuke , Iuchi Satoshi , Yotsui Izumi , Sakata Yoichi , Taji Teruaki
Published: November 2023

Plants are often exposed not only to short-term (S-) but also to long-term (L-)heat stress over several consecutive days. A few Arabidopsis mutants defective in L-heat tolerance have been identified, but the molecular mechanisms are less understood for this tolerance than for S-heat stress tolerance. To elucidate the mechanisms of the former, we used a forward genetic screen for sensitive to long-term heat (sloh) mutants and isolated sloh3 and sloh63. The mutants were hypersensitive to L- but not to S-heat stress, and sloh63 was also hypersensitive to salt stress. We identified the causal genes, SLOH3 and SLOH63, both of which encoded splicing-related components of the MOS4-associated complex (MAC). This complex is widely conserved in eukaryotes and has been suggested to interact with spliceosomes. Both genes were induced by L-heat stress in a time-dependent manner, and some abnormal splicing events were observed in both mutants under L-heat stress. In addition, endoplasmic reticulum (ER) stress and subsequent unfolded protein response occurred in both mutants under L-heat stress and were especially prominent in sloh63, suggesting that enhanced ER stress is due to the salt hypersensitivity of sloh63. Splicing inhibitor pladienolide B led to concentration-dependent disturbance of splicing, decreased L-heat tolerance, and enhanced ER stress. These findings suggest that maintenance of precise mRNA splicing under L-heat stress by the MAC is important for L-heat tolerance and suppressing ER stress in Arabidopsis.
Frequent asymmetric migrations suppress natural selection in spatially structured populations
Authors: Abbara Alia , Bitbol Anne-Florence
Published: November 2023

Natural microbial populations often have complex spatial structures. This can impact their evolution, in particular the ability of mutants to take over. While mutant fixation probabilities are known to be unaffected by sufficiently symmetric structures, evolutionary graph theory has shown that some graphs can amplify or suppress natural selection, in a way that depends on microscopic update rules. We propose a model of spatially structured populations on graphs directly inspired by batch culture experiments, alternating within-deme growth on nodes and migration-dilution steps, and yielding successive bottlenecks. This setting bridges models from evolutionary graph theory with Wright–Fisher models. Using a branching process approach, we show that spatial structure with frequent migrations can only yield suppression of natural selection. More precisely, in this regime, circulation graphs, where the total incoming migration flow equals the total outgoing one in each deme, do not impact fixation probability, while all other graphs strictly suppress selection. Suppression becomes stronger as the asymmetry between incoming and outgoing migrations grows. Amplification of natural selection can nevertheless exist in a restricted regime of rare migrations and very small fitness advantages, where we recover the predictions of evolutionary graph theory for the star graph.
Oleic acid stimulation of amino acid uptake in primary human trophoblast cells is mediated by phosphatidic acid and mTOR signaling
Authors: Silva Elena , Ferchaud‐Roucher Véronique , Kramer Anita , Madi Lana , Pantham Priyadarshini , Chassen Stephanie , Jansson Thomas , Powell Theresa L.
Published: November 2023

Normal fetal development is critically dependent on optimal nutrient supply by the placenta, and placental amino acid transport has been demonstrated to be positively associated with fetal growth. Mechanistic target of rapamycin (mTOR) is a positive regulator of placental amino acid transporters, such as System A. Oleic acid (OA) has been previously shown to have a stimulatory role on placental mTOR signaling and System A amino acid uptake in primary human trophoblast (PHT) cells. We investigated the mechanistic link between OA and System A activity in PHT. We found that inhibition of mTOR complex 1 or 2, using small interfering RNA to knock down raptor or rictor, prevented OA‐stimulated System A amino acid transport indicating the interaction of OA with mTOR. Phosphatidic acid (PA) is a key intermediary for phospholipid biosynthesis and a known regulator of the mTOR pathway; however, phospholipid biosynthetic pathways have not been extensively studied in placenta. We identified placental isoforms of acyl transferase enzymes involved in de novo phospholipid synthesis. Silencing of 1‐acylglycerol‐3‐phosphate‐O‐acyltransferase‐4, an enzyme in this pathway, prevented OA mediated stimulation of mTOR and System A amino acid transport. These data indicate that OA stimulates mTOR and amino acid transport in PHT cells mediated through de novo synthesis of PA. We speculate that fatty acids in the maternal circulation, such as OA, regulate placental functions critical for fetal growth by interaction with mTOR and that late pregnancy hyperlipidemia may be critical for increasing nutrient transfer to the fetus.
Gynecologic Care of Transgender and Gender-Diverse People
Authors: Ferrando Cecile A.
Published: November 2023

The visibility and care of transgender and gender-diverse (TGD) people is an important component of gynecology. Transmasculine individuals require routine gynecologic and preventative care. Guidelines can be extrapolated from the cisgender female population, and using affirming language, acknowledging the challenges patients face with pelvic examination, and discussing individual gynecologic needs are important components of care. Transmasculine patients may seek hysterectomy for gender affirmation from gynecologists. Unique nuances exist in the considerations needed when preparing for hysterectomy, and patients should be thoroughly counseled with regard to concurrent vaginectomy or oophorectomy or both. Transfeminine patients often seek gynecologic care after gender-affirming surgery, and, unlike transmasculine patients, the gynecology visit is often very affirming and welcomed by patients. Becoming familiar with the perioperative and delayed postoperative care needs of transfeminine patients undergoing vaginoplasty can help improve the care provided by gynecologists. In general, prospective data on the outcomes of gender-affirming care in large cohorts of TGD patients are limited, but the body of literature is growing. Gynecologists remain central to the care of TGD patients, the academic advancement of the field of transgender health, and the advocacy needed to support this vulnerable patient population.
Patient Removal of Urinary Catheters After Urogynecologic Surgery
Authors: Askew Amy L. , Margulies Samantha L. , Agu Ijeoma , LeCroy Katie M. , Geller Elizabeth , Wu Jennifer M.
Published: November 2023

OBJECTIVE:

To compare postoperative urinary retention rates in the early postoperative period between home and office catheter removal. Secondary outcomes included pain, difficulty, satisfaction, likelihood to use again, and health care utilization.

METHODS:

We conducted a nonblinded, randomized controlled, noninferiority trial of women undergoing surgery for stress incontinence and prolapse from March 2021 to June 2022. Exclusion criteria were preoperative voiding dysfunction (need for self-catheterization or postvoid residual [PVR] greater than 150 mL), urethral bulking, and need for prolonged postoperative catheterization. Participants discharged with indwelling catheters because of an initial failed void trial were randomized 1:1 to home compared with office removal on postoperative day 3–4. For home removal, participants were instructed to remove the catheter at 7 am and to drink two glasses of water. If they had difficulty voiding 5 hours after catheter removal, they came to the office for a void trial. For office removal, participants returned for a backfill void trial with PVR assessment. Our primary outcome was rate of early postoperative urinary retention, defined as confirmed retention (PVR greater than half the voided volume) after catheter removal. Secondary outcomes were assessed at a 2-week call. Health care utilization (telephone calls and office visits) related to catheter issues was also assessed. At 80% power and α=0.05, we needed 100 participants (50/group) to detect a noninferiority margin of 11%.

RESULTS:

Among 117 participants, the home (n=59) and office (n=58) removal groups were similar in mean age (60 years vs 61 years), mean body mass index (29 vs 30), pelvic organ prolapse quantification system stage 3 or 4, and proportion who underwent hysterectomy or apical suspension. Sling procedures were more common in the office group (45.8% vs 77.6%). For our primary outcome, the rate of early postoperative retention was 11.9% in the home group and 22.4% in the office group (P=.13). Our predetermined noninferiority margin was greater than the upper bound of our 95% CI; thus, we conclude noninferiority of home removal. For secondary outcomes, the home removal group was more likely to report “no pain” (P=.02) and “very likely” to use this method again (P=.004). There were no differences in difficulty or satisfaction between groups. Number of nursing calls was not different (P=.66); however, number of office visits was higher in the office group (median 0 [interquartile range 0–1] vs 1 [1–1], P<.001).

CONCLUSION:

Postoperative urinary catheter removal by the patient at home was noninferior to office removal when early urinary retention rates were compared. Participants in the home removal group had fewer office visits and reported low pain, low difficulty, and high satisfaction.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04783012.
Oral Nirmatrelvir–Ritonavir Use and Clinical Outcomes in Pregnant Patients With Coronavirus Disease 2019 (COVID-19)
Authors: Toure Bineta B. , Panakam Aisvarya , Johns Sarah L. , Butler Sharlay K. , Tuomala Ruth E. , Diouf Khady
Published: November 2023

We conducted a retrospective cohort study of pregnant patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RNA polymerase chain reaction test or home test who were counseled about taking nirmatrelvir–ritonavir if they were within 5 days of symptom onset. Obstetric and coronavirus disease 2019 (COVID-19) outcomes were compared between patients who did and did not take the medication. Overall, 114 individuals took nirmatrelvir–ritonavir and 323 did not. The cohorts were comparable, including high rates of vaccination in both groups. Nirmatrelvir–ritonavir was well-tolerated, with no patients discontinuing medication due to side effects. There were no intensive care unit admissions in either group. Most obstetric and medical outcomes were similar between those taking and not taking nirmatrelvir–ritonavir. Patients taking nirmatrelvir–ritonavir had significantly higher rates of surgical site infection (3 [2.7%] vs 0 [0%], P=.02) and preeclampsia (11 [9.6%] vs 12 [3.7%], P=.02). Outcome event numbers were too small for multivariable modeling. These preliminary data may be reassuring to clinicians and patients who would like to use nirmatrelvir–ritonavir in pregnancy.
Pharmacotherapy for Reducing RBC Transfusion for Patients in the ICU: A Systematic Review and Network Meta-Analysis
Authors: Yoshihiro Shodai , Hongo Takashi , Yamamoto Mariko , Taito Shunsuke , Kataoka Yuki
Published: November 2023

OBJECTIVES:

To determine optional therapeutic strategies by comparing monotherapies and combination therapies to reduce RBC transfusion requirement for patients in the ICU.

DATA SOURCES:

MEDLINE, CENTRAL, and Embase were searched for studies published from database inception until July 2023.

DATA EXTRACTION:

We included randomized controlled trials comparing erythropoiesis-stimulating agents (Epo), iron, combination therapy with iron and Epo, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), vitamin D3 (VD3), and placebo/no treatment. A frequentist network meta-analysis (NMA) was performed using a random effects model, and the confidence in NMA was rated.

DATA SYNTHESIS:

Of 117 eligible studies, 75 studies (15,091 patients) were included in the quantitative analysis. Compared with placebo/no treatment, the combination therapy reduces the requirement for RBC transfusion (risk ratio [RR]: 0.60; 95% CI, 0.49–0.74; confidence rating: moderate). The Epo or iron monotherapy may reduce the requirement for RBC transfusion (RR: 0.81; 95% CI, 0.63–1.04; confidence rating: low; RR: 0.83; 95% CI, 0.70–0.98; confidence rating: low, respectively). Combination therapy may not increase the prevalence of both venous thromboembolism (VTE) (RR: 0.73; 95% CI, 0.25–2.08; confidence rating: low) and infection. Epo monotherapy may not increase the prevalence of VTE but may increase that of infections (RR: 1.27; 95% CI, 0.94–1.73; confidence rating: low). Iron monotherapy may not increase the prevalence of both VTE and infection. Evidence for VD3 and HIF-PHI remains uncertain.

CONCLUSIONS:

Combination therapy with iron and Epo likely reduces the requirement for RBC transfusion and may be less harmful than other therapies.
Use of Lung Ultrasound in the New Definitions of Acute Respiratory Distress Syndrome Increases the Occurrence Rate of Acute Respiratory Distress Syndrome
Authors: Plantinga Coen , Klompmaker Peter , Haaksma Mark E. , Mousa Amne , Blok Siebe G. , Heldeweg Micah L.A. , Paulus Frederique , Schultz Marcus J. , Tuinman Pieter R.
Published: November 2023

OBJECTIVES:

To assess the effect of incorporating bilateral abnormalities as detected by lung ultrasound (LUS) in the Kigali modification and the New Global definition of acute respiratory distress syndrome (ARDS) on the occurrence rate of ARDS.

DESIGN:

Post hoc analysis of a previously published prospective cohort study.

SETTING:

An academic mixed medical-surgical ICU.

PATIENTS:

The original study included critically ill adults with any opacity on chest radiography in whom subsequent LUS was performed. Patients with ARDS according to the Berlin definition, COVID-19 patients and patients with major thorax trauma were excluded.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

LUS was performed within 24 hours of chest radiography and the presence of unilateral and bilateral abnormalities on LUS and chest radiograph (opacities) was scored. Subsequently, the Kigali modification and the New Global definition of ARDS were applied by two independent researchers on the patients with newly found bilateral opacities. Of 120 patients, 116 were included in this post hoc analysis. Thirty-three patients had bilateral opacities on LUS and unilateral opacities on chest radiograph. Fourteen of these patients had ARDS according to the Kigali modification and 12 had ARDS according to the New Global definition. The detected LUS patterns were significantly different between patients with and without ARDS (p= 0.004). An A-profile with a positive PosteroLateral Alveolar and/or Pleural Syndrome was most prevalent in patients without ARDS, whereas heterogeneous and mixed A, B, and C patterns were most prevalent in patients with ARDS.

CONCLUSION:

The addition of bilateral abnormalities as detected by LUS to the Kigali modification and the New Global definition increases the occurrence rate of the ARDS. The nomenclature for LUS needs to be better defined as LUS patterns differ between patients with and without ARDS. Incorporating well-defined LUS criteria can increase specificity and sensitivity of new ARDS definitions.
The Emerging Role of Reinforcement in the Clinician's Path from Continuing Education to Practice
Authors: Lucero Katie Stringer , Williams Betsy , Moore Donald E.
Published: November 2023

Continuing education (CE) activities may affect clinicians' knowledge, skills, self-efficacy, and/or performance. Studies have suggested that self-efficacy may moderate or mediate the relationship between knowledge/competence and performance. Some results have shown that increases in knowledge/competence contributed to increases in self-efficacy. However, clinicians do not always learn something “new” when they participate in CE activities; rather, their knowledge or skills may be reinforced. This study examined whether self-efficacy was greater when clinicians reinforced what they already knew compared with when they learned something new. Hierarchical linear modeling was conducted to examine the moderating role of status of knowledge/competence post-CE (reinforced/improved) in the relationship between post-CE knowledge/competence score and self-efficacy across 153 online continuing medical education- and/or CE-certified activities. The hierarchical linear modeling showed that learners with higher post-CE scores have higher post–self-efficacy ratings. Reinforced learners had higher post-CE–self-efficacy ratings than improved learners, controlling for post-CE score. This study contributes to an expanded understanding of the path from CE to practice. There was benefit to self-efficacy for learners who reinforced but did not improve their knowledge/competence. This study also suggests that pre-post questions can be considered part of the learning process.
Predicting 30-day mortality in intensive care unit patients with ischaemic stroke or intracerebral haemorrhage
Authors: van Valburg Mariëlle K. , Termorshuizen Fabian , Geerts Bart F. , Abdo Wilson F. , van den Bergh Walter M. , Brinkman Sylvia , Horn Janneke , van Mook Walther N.K.A. , Slooter Arjen J.C. , Wermer Marieke J.H. , Siegerink Bob , Arbous M. Sesmu
Published: November 2023

BACKGROUND

Stroke patients admitted to an intensive care unit (ICU) follow a particular survival pattern with a high short-term mortality, but if they survive the first 30 days, a relatively favourable subsequent survival is observed.

OBJECTIVES

The development and validation of two prognostic models predicting 30-day mortality for ICU patients with ischaemic stroke and for ICU patients with intracerebral haemorrhage (ICH), analysed separately, based on parameters readily available within 24 h after ICU admission, and with comparison with the existing Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) model.

DESIGN

Observational cohort study.

SETTING

All 85 ICUs participating in the Dutch National Intensive Care Evaluation database.

PATIENTS

All adult patients with ischaemic stroke or ICH admitted to these ICUs between 2010 and 2019.

MAIN OUTCOME MEASURES

Models were developed using logistic regressions and compared with the existing APACHE-IV model. Predictive performance was assessed using ROC curves, calibration plots and Brier scores.

RESULTS

We enrolled 14 303 patients with stroke admitted to ICU: 8422 with ischaemic stroke and 5881 with ICH. Thirty-day mortality was 27% in patients with ischaemic stroke and 41% in patients with ICH. Important factors predicting 30-day mortality in both ischaemic stroke and ICH were age, lowest Glasgow Coma Scale (GCS) score in the first 24 h, acute physiological disturbance (measured using the Acute Physiology Score) and the application of mechanical ventilation. Both prognostic models showed high discrimination with an AUC 0.85 [95% confidence interval (CI), 0.84 to 0.87] for patients with ischaemic stroke and 0.85 (0.83 to 0.86) in ICH. Calibration plots and Brier scores indicated an overall good fit and good predictive performance. The APACHE-IV model predicting 30-day mortality showed similar performance with an AUC of 0.86 (95% CI, 0.85 to 0.87) in ischaemic stroke and 0.87 (0.86 to 0.89) in ICH.

CONCLUSION

We developed and validated two prognostic models for patients with ischaemic stroke and ICH separately with a high discrimination and good calibration to predict 30-day mortality within 24 h after ICU admission.

TRIAL REGISTRATION

Trial registration: Dutch Trial Registry (https://www.trialregister.nl/); identifier: NTR7438.
CO2 laser, radiofrequency, and promestriene in the treatment of genitourinary syndrome of menopause in breast cancer survivors: a histomorphometric evaluation of the vulvar vestibule
Authors: Fernandes Marcela Furtado Roberto , Bianchi-Ferraro Ana Maria Homem de Mello , Sartori Marair Gracio Ferreira , Jármy Di Bella Zsuzsanna Ilona Katalin de , Cantarelli Gabriela Cruz , Dedonatto Chayanne , Vanzin Rafaela Brambatti , Dardes Rita de Cassia Maio ,   LARF Study Group, Logullo Ângela Flávia , Patriarca Marisa Teresinha
Published: November 2023

Objective

This study aimed to compare the efficacy of CO2 laser, radiofrequency, and promestriene in treating genitourinary syndrome of menopause in women with breast cancer receiving adjuvant therapy and to analyze the clinical and histological findings of the vulvar vestibule.

Methods

Women with moderate-to-severe symptoms of vulvar atrophy were enrolled. The participants were evaluated according to pretreatment and posttreatment protocols using the visual analog scale and clinical assessments, which included a gynecological examination and vestibular biopsy. Participants were randomly assigned into the laser, radiofrequency, or promestriene groups. Participants in the energy treatment groups underwent three consecutive monthly outpatient vulvovaginal treatment sessions, whereas those in the control group were administered promestriene for 4 months. During a follow-up visit 30 days posttreatment, the participant global posttreatment impression of improvement was evaluated using a Likert scale.

Results

Seventy women completed treatment. Histological vulvar atrophy was identified in four (5.7%) of the pretreatment vulvar samples. Postintervention, all histological parameters were normalized. Significant improvements in symptoms were observed, as all three groups showed a reduction in the visual analog scale score, with no statistically significant differences among them. A high level of satisfaction was reported posttreatment in all groups. No damage to the histological structure of the vulvar vestibule or relevant clinical adverse events were identified posttreatment.

Conclusions

Laser, radiofrequency, and promestriene delivered comparable, significant symptom improvements among women with breast cancer receiving adjuvant therapy. These treatments did not cause structural tissue damage or other clinical complications.
Threatened Periviable Delivery and Abortion: Clinical Considerations
Authors: Ohly Natalie Tanya , Khoury Rasha
Published: November 2023

Periviable delivery, or a pregnancy at risk of delivery between 20 0/7 and 25 6/7 weeks gestational, is an uncommon event with profound physical, psychological, and financial impact. Neonatal outcomes can be hard to predict and with the changing legal landscape around abortion access, management options may be compromised. Dynamic maternal and fetal factors make a cohesive and supportive care team critical for optimal care. Management of threatened periviable delivery in a post-Roe United States may prioritize fetal outcomes regardless of threat to maternal health due to legal restrictions.
Clinical and Laboratory Diagnosis of Exanthems Among Japanese Children Younger Than 6 Years Old in the Post–Measles-Rubella Vaccine Era
Authors: Yasuda Masato , Shoji Kensuke , Tomita Keiichi , Uchida Yoshiko , Uematsu Satoko , Yoshida Kazue , Kono Naoko , Funatsu Motoki , Miyairi Isao
Published: November 2023

Background:

Exanthems are a common reason for visits to the pediatric emergency department. However, epidemiological data in the post–measles-rubella vaccine era is limited.

Objective:

We sought to determine the recent causes of exanthems in children younger than 6 years old in the pediatric emergency department.

Methods:

A prospective single-center study was conducted in Japan from August 2019 to March 2020. Children younger than 6 years old with exanthems were enrolled. Exanthems were classified into 7 morphological patterns. Varicella, herpes zoster, impetigo, urticaria and Kawasaki disease were diagnosed clinically. Nasopharyngeal swab specimens were collected from patients with nonspecific exanthems and evaluated by polymerase chain reaction (PCR) assays capable of detecting 24 pathogens. The final diagnosis was made by discussion of 3 physicians based on clinical course and microbiology.

Results:

There were 9705 pediatric visits, of which 296 (3%) had exanthems and were younger than 6 years old. Clinical diagnosis was possible for 160 (54%), including urticaria in 110 (37%), Kawasaki disease in 29 (10%), impetigo in 10 (3%), varicella or herpes zoster in 7 (2%) and group A Streptococcus in 4 (1%). Among the remaining 136 (46%) children, 75 (25%) underwent testing by PCR. One or more pathogens were detected in 49 (65%), specifically enterovirus in 14 (19%), cytomegalovirus in 13 (17%), human herpesvirus type-6 in 12 (16%), adenovirus in 11 (15%) and human herpesvirus type-7 in 8 (11%). Final infectious disease diagnoses were roseola infantum in 11 (15%), enterovirus in 9 (12%), adenovirus in 6 (8%), mixed virus infection in 5 (7%), group A Streptococcus in 3 (4%), parechovirus-A in 3 (4%) and influenza in 3 (4%).

Conclusions:

The most common causes of pediatric exanthems were noninfectious diseases and viral exanthema. PCR assay was instrumental for etiological diagnosis of nonspecific exanthems.
Characteristics of early short-term traditional Chinese medicine in breast cancer patients: A population-based cohort study
Authors: Chan Pi-Wei , Yu Hung , Hsu Chung-Hua , Liu Chun-Yu
Published: November 2023

Background:

Traditional Chinese medicine (TCM) is frequently utilized as a complementary therapy for breast cancer patients. TCM primarily involves the use of Chinese herbal products (CHPs), which consist of single or multiherb formulas with diverse therapeutic effects documented in medical classics. The study aims to investigate the association between medication possession ratios to CHPs within 2-year post breast cancer diagnosis and 5-year survival, to explore the potential beneficial class effect of TCM.

Methods:

This retrospective population-based cohort study included newly diagnosed breast cancer patients between 2003 and 2006, identified from the National Health Insurance Research Database of Taiwan. Logistic regression and Cox proportional hazards analysis were utilized to assess the likelihood of medication possession ratios (MPRs) for CHPs and to examine the association of variables with 5-year survival.

Results:

A total of 3472 patients with breast cancer were included. Patients who had MPR of 1% to 9% and 10% to 19% for CHPs within 2 years after breast cancer diagnosis exhibited better 5-year survival rates compared with those who did not use CHPs (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.55-0.86, p = 0.001; aHR 0.50, 95% CI 0.28-0.88, p = 0.016). Furthermore, the use of TCM formulations specifically targeting insomnia, such as Tian-wang-bu-xin-dan and Suan-zao-ren-tang, demonstrated a significantly positive association with survival (aHR 0.71, 95% CI 0.52-0.98, p = 0.035) among patients who were short-term users of CHPs (MPR of 1% to 19%).

Conclusion:

Short-term use of TCM (ie, MPR to CHPs 1~19%) within 2-year post breast cancer diagnosis present positive association with survival outcome. Tian-wang-bu-xin-dan and Suan-zao-ren-tang may have benefits to 5-year survival, but their causality still need further investigation.