bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Insights: Severe Outcomes of Pneumocystis Pneumonia: A 10‐year Retrospective Cohort Study
Authors: Winichakoon Poramed , Solera Rallo Javier Tomas , Albasata Hanan , Poutanen Susan Marie , Hosseini‐Moghaddam Seyed M
Published: December 2024

Background

A considerable knowledge gap exists in predicting severe Pneumocystis pneumonia (PCP) outcomes following PCP diagnosis.

Methods

In this retrospective cohort, we studied immunocompromised patients with PCP admitted to 5 University Health Network centers in Canada (2011–2022). The study outcome included severe PCP, a composite of 21‐day ICU admission or 28‐day all‐cause mortality. Adjusted odds ratios (aOR) estimated the association between severe PCP and comorbidities as well as clinical and laboratory variables at diagnosis.

Results

A total of 44 out of 182 (24.2%) immunocompromised patients (19 [10.4%] HIV‐infected, 55 [30.2%] hematologic malignancies, 32 [17.6%] hematopoietic stem cell transplants, 32 [17.6% solid tumors, 26 solid organ transplants [14.3%], 12 (6.6%) autoimmune diseases, and 6 (3.3%) other immunosuppressive conditions) developed composite outcomes (40 ICU admissions [21.9%], 18 deaths [9.9%]). Patients with composite outcomes more often had acute‐onset PCP (< 7 days) (18/34 [52.9%] vs. 38/126 [30.1%], p = 0.013), shortness of breath (39/44 [88.6%] vs. 96/136 [70.6%], p = 0.002), chronic liver disease (15/44 [34.1%] vs. 9/138 [6.5%], p < 0.001), hypoalbuminemia (median [IQR] albumin (g/L): 27 [25–31] vs. 32 [29–35], p < 0.001), elevated lactate dehydrogenase (median [IQR] LDH (U/L): 537 [324–809] vs. 340 [237–475], p < 0.001), lymphopenia (median [IQR] absolute lymphocyte count [(10*9/L),]: 0.4 [0.2–0.6] vs. 0.7 [0.3–1.2], p < 0.001), or required supplemental oxygen (39/44 [88.6%] vs. 60/136 [44.1%], p < 0.001) than those without composite outcomes. In multivariable analysis, chronic liver disease (aOR: 11.6, 95% CI: 2.2–61.3) and requiring supplemental oxygen on admission (aOR: 19.7, 95% CI: 3.0–128.5) were significantly associated with severe PCP.

Conclusions

Alongside hypoxemia upon admission, chronic liver disease appears to significantly predict severe PCP in immunocompromised patients. This biologically plausible finding warrants further investigation.
Presentation and Outcomes of Histoplasmosis in Transplant Recipients: A Retrospective Single‐Centre Cohort Study
Authors: Rutjanawech Sasinuch , Zuniga‐Moya Julio C. , George Ige , Mazi Patrick B. , Osborn Matthew R. , Fallon Samuel M. , Spec Andrej , Rauseo Adriana M.
Published: December 2024

Background

Histoplasmosis is an important infection among transplant recipients. Few studies have described its epidemiology and outcomes in the modern era.

Methods

We conducted a retrospective analysis using medical records from a single center in the United States. We included patients 18 years or older with histoplasmosis. We divided the cohort into transplant recipients and immunocompetent groups to assess the outcomes in both groups. We utilized Cox hazard models to assess 90‐day all‐cause mortality.

Results

The study included 137 patients; with 28 (20%) transplant recipients. After the first year post‐transplant, patients with lung transplant (30%) had a diagnosis of histoplasmosis. Transplant recipients exhibited a significantly higher incidence of disseminated histoplasmosis than immunocompetent patients (64% vs. 34%, p = 0.001), higher admission to ICU (39% vs. 16%; p = 0.01) and higher but not significant 90‐day crude all‐cause mortality (14% vs. 11%, p = 0.71). Patients with transplants had a higher, but not significant hazard of all‐cause mortality at 90 days (hazard ratio: 1.5; 95% confidence interval: 0.4–3.9) when compared to immunocompetent patients.

Conclusion

Transplant recipients were more commonly diagnosed with histoplasmosis after the first year post‐transplantation, and although they exhibited a higher hazard for death at 90 days, this increase was not statistically significant.

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Electrochemically fabricated ultrafine nickel masks for the fabrication of MoS2-based devices
Authors: Zhong Jianwen , Sun Zhao , Li Han , Gan Zhuofei , Sun Chuying , Wan Yi , Li Lain-Jong , Li Wen-Di
Published: December 2024

Transition metal dichalcogenides (TMDs) are considered promising candidates for the next generation of electronic building blocks in integrated circuits due to their superior performance in mitigating various challenges such as short channel effects. Optical lithography and electron beam lithography are commonly employed for fabricating electrical contacts and patterning TMDs to create electronic devices. The atomic layer structure of TMDs is highly susceptible to external conditions, making conventional lithography methods, which often leave undesirable polymer residues and involve high-energy electron radiation, not ideal for achieving high device performance. Shadow mask lithography has been used to define electrodes and etch patterns on these sensitive materials, thereby avoiding the need for photoresists and electron irradiation. In this study, we introduce a novel, cost-effective electrochemical method for manufacturing reusable and flexible shadow masks with ultrafine feature sizes. By combining electroplating techniques with the dry transfer method, we successfully produced metal masks with ultrafine features, which were then utilized to evaporate metal electrodes with micron feature sizes onto nanostructured substrates. These metal masks, with specifically designed patterns, were employed as etching masks to pattern monolayer MoS2 (a type of TMD) materials without the need for photoresists or solution processes. Moreover, the resulting metal mask-evaporated electrodes, with smooth edges, were integrated with atomic layer transition metal dichalcogenides through van der Waals interactions to create devices based on MoS2.
Probing quantum geometry through optical conductivity and magnetic circular dichroism
Authors: Ghosh Barun , Onishi Yugo , Xu Su-Yang , Lin Hsin , Fu Liang , Bansil Arun
Published: December 2024

Probing ground-state quantum geometry and topology through optical responses is not only of fundamental interest, but it can also offer several practical advantages. Here, using first-principles calculations on thin films of the antiferromagnetic topological insulator MnBi
2
Te
4
, we demonstrate how the generalized optical weight arising from the absorptive part of the optical conductivity can be used to probe the ground-state quantum geometry and topology. We show that three-septuple-layer MnBi
2
Te
4
film exhibit an enhanced, almost-perfect magnetic circular dichroism for a narrow photon energy window in the infrared region. We calculate the quantum weight in this MnBi
2
Te
4
film and show that it far exceeds the lower bound provided by the Chern number. Our results suggest that the well-known optical methods are powerful tools for probing the ground-state quantum geometry and topology.
A neurocognitive pathway for engineering artificial touch
Authors: Nisky Ilana , Makin Tamar R.
Published: December 2024

Artificial haptics has the potential to revolutionize the way we integrate physical and virtual technologies in our daily lives, with implications for teleoperation, motor skill acquisition, rehabilitation, gaming, interpersonal communication, and beyond. Here, we delve into the intricate interplay between the somatosensory system and engineered haptic inputs for perception and action. We critically examine the sensory feedback’s fidelity and the cognitive demands of interfacing with these systems. We examine how artificial touch interfaces could be redesigned to better align with human sensory, motor, and cognitive systems, emphasizing the dynamic and context-dependent nature of sensory integration. We consider the various learning processes involved in adapting to artificial haptics, highlighting the need for interfaces that support both explicit and implicit learning mechanisms. We emphasize the need for technologies that are not only physiologically biomimetic but also behaviorally and cognitively congruent with the user, affording a range of alternative solutions to users’ needs.
Interfacial charge transfer and its impact on transport properties of LaNiO
3
/LaFeO
3
superlattices
Authors: Wang Le , Yang Zhifei , Koirala Krishna Prasad , Bowden Mark E. , Freeland John W. , Sushko Peter V. , Kuo Cheng-Tai , Chambers Scott A. , Wang Chongmin , Jalan Bharat , Du Yingge
Published: December 2024

Charge transfer or redistribution at oxide heterointerfaces is a critical phenomenon, often leading to remarkable properties such as two-dimensional electron gas and interfacial ferromagnetism. Despite studies on LaNiO
3
/LaFeO
3
superlattices and heterostructures, the direction and magnitude of the charge transfer remain debated, with some suggesting no charge transfer due to the high stability of Fe
3+
(3d
5
). Here, we synthesized a series of epitaxial LaNiO
3
/LaFeO
3
superlattices and demonstrated partial (up to ~0.5 e
−
/interface unit cell) charge transfer from Fe to Ni near the interface, supported by density functional theory simulations and spectroscopic evidence of changes in Ni and Fe oxidation states. The electron transfer from LaFeO
3
to LaNiO
3
and the subsequent rearrangement of the Fe 3d band create an unexpected metallic ground state within the LaFeO
3
layer, strongly influencing the in-plane transport properties across the superlattice. Moreover, we establish a direct correlation between interfacial charge transfer and in-plane electrical transport properties, providing insights for designing functional oxide heterostructures with emerging properties.
Mechanisms underlying modulation of human GlyRα3 by Zn
2+
and pH
Authors: Kindig Kayla , Gibbs Eric , Seiferth David , Biggin Philip C. , Chakrapani Sudha
Published: December 2024

Glycine receptors (GlyRs) regulate motor control and pain processing in the central nervous system through inhibitory synaptic signaling. The subtype GlyRα3 expressed in nociceptive sensory neurons of the spinal dorsal horn is a key regulator of physiological pain perception. Disruption of spinal glycinergic inhibition is associated with chronic inflammatory pain states, making GlyRα3 an attractive target for pain treatment. GlyRα3 activity is modulated by numerous endogenous and exogenous ligands that consequently affect pain sensitization. To understand the mechanism of two such endogenous modulators, Zn
2+
and protons, we have used cryo–electron microscopy to determine structures of full-length human GlyRα3 in various functional states. Whereas acidic pH reduces peak glycine response, Zn
2+
displays biphasic modulation in a concentration-dependent manner. Our findings reveal the effector sites and also capture intermediate conformations in the gating cycle. Combined with molecular dynamics simulations and electrophysiology, this work provides important insights into GlyRα3 activation and regulation.
Mechanosensitive nuclear uptake of chemotherapy
Authors: Scott Nicholas R. , Kang Sowon , Parekh Sapun H.
Published: December 2024

The nucleus is at the nexus of mechanotransduction and the final barrier for most first line chemotherapeutics. Here, we study the intersection between nuclear-cytoskeletal coupling and chemotherapy nuclear internalization. We find that chronic and acute modulation of intracellular filaments changes nuclear influx of doxorubicin (DOX). Rapid changes in cell strain by disruption of cytoskeletal and nuclear filaments sensitize nuclei to DOX, whereas chronic reduction of cell strain desensitize nuclei to DOX. Extracted nuclei from invasive cancer cells lines from different tissues have distinct nuclear permeability to DOX. Last, we show that mechano-priming of cells by paclitaxel markedly improves DOX nuclear internalization, rationalizing the observed drug synergies. Our findings reveal that nuclear uptake is a critical, previously unquantified aspect of drug resistance. With nuclear permeability to chemotherapy being tunable via modulation of nuclear mechanotransduction, mechano-priming may be useful to help overcome drug resistance in the future.
Counterfactual rewards promote collective transport using individually controlled swarm microrobots
Authors: Heuthe Veit-Lorenz , Panizon Emanuele , Gu Hongri , Bechinger Clemens
Published: December 2024

Swarm robots offer fascinating opportunities to perform complex tasks beyond the capabilities of individual machines. Just as a swarm of ants collectively moves large objects, similar functions can emerge within a group of robots through individual strategies based on local sensing. However, realizing collective functions with individually controlled microrobots is particularly challenging because of their micrometer size, large number of degrees of freedom, strong thermal noise relative to the propulsion speed, and complex physical coupling between neighboring microrobots. Here, we implemented multiagent reinforcement learning (MARL) to generate a control strategy for up to 200 microrobots whose motions are individually controlled by laser spots. During the learning process, we used so-called counterfactual rewards that automatically assign credit to the individual microrobots, which allows fast and unbiased training. With the help of this efficient reward scheme, swarm microrobots learn to collectively transport a large cargo object to an arbitrary position and orientation, similar to ant swarms. We show that this flexible and versatile swarm robotic system is robust to variations in group size, the presence of malfunctioning units, and environmental noise. In addition, we let the robot swarms manipulate multiple objects simultaneously in a demonstration experiment, highlighting the benefits of distributed control and independent microrobot motion. Control strategies such as ours can potentially enable complex and automated assembly of mobile micromachines, programmable drug delivery capsules, and other advanced lab-on-a-chip applications.
A call for diversity, equity, and inclusion in robotics
Authors: Yashinski Melisa
Published: December 2024

Robotics research is rooted in a diversity of ideas, so roboticists should embrace a diverse set of people.
Performance of a broth microdilution assay for routine minimum inhibitory concentration determination of 14 anti-tuberculous drugs against the
Mycobacterium tuberculosis
complex based on the EUCAST reference protocol
Authors: Mansjö Mikael , Espinosa-Gongora Carmen , Samanci Ishak , Groenheit Ramona , Werngren Jim
Published: December 2024

This comparative study aimed at qualifying a broth microdilution (BMD) assay for phenotypic drug susceptibility testing (pDST) of
Mycobacterium tuberculosis
complex (MTBC) strains for implementation in a routine DST workflow. The assay was developed based on the EUCAST (European Committee on Antimicrobial Susceptibility Testing) reference protocol for determination of the minimum inhibitory concentration (MIC) of 14 anti-tuberculous drugs (isoniazid [INH], rifampicin [RIF], ethambutol [EMB], amikacin [AMI], moxifloxacin [MFX], levofloxacin [LFX], bedaquiline [BDQ], clofazimine [CFZ], delamanid [DLM], pretomanid [PA], para-aminosalicylic acid [PAS], linezolid [LZD], ethionamide [ETH], and cycloserine [CS]). Forty MTBC strains with various drug resistance profiles were tested to determine the agreement between MIC results and genotypic drug susceptibility testing (gDST) results derived from whole-genome sequencing (WGS). The agreement between the BMD and gDST results was solid for the majority of the drugs (average agreement 98%, range 90%–100%), including key drugs such as INH, RIF, MFX, LFX, BDQ, DLM, and PA. Ten discrepancies were identified (corresponding to 1.8% of the total number of MIC determinations) and most (8/10) were characterized by MICs equal or close to the potential critical concentration (pCC) applied in the BMD assay. Importantly, the assay can be adjusted to new drug recommendations and concentrations, tailored to local needs. We conclude that the BMD assay provides reliable results, and its implementation in our MTBC routine workflow will produce valuable data that improve our understanding and management of MTBC drug resistance.
Population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation—an ASAP ECMO study
Authors: Abdul-Aziz Mohd H. , Diehl Arne , Liu Xin , Cheng Vesa , Corley Amanda , Gilder Eileen , Levkovich Bianca , McGuinness Shay , Ordonez Jenny , Parke Rachael , Pellegrino Vincent , Wallis Steven C. , Fraser John F. , Shekar Kiran , Roberts Jason A.
Published: December 2024

This study aimed to describe the population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) and to identify dosing regimens with a high likelihood of achieving effective exposures. Serial blood samples were collected over a single-dosing interval during ECMO. Total plasma concentrations were measured by a validated chromatographic assay. A population pharmacokinetic model was built and Monte Carlo dosing simulations were performed using Monolix. The probability of target attainment (PTA) and fractional target attainment (FTA) rates were simulated for various caspofungin dosing regimens against
Candida albicans
,
Candida glabrata
, and
Candida parapsilosis
. In all, 64 plasma concentration-time points were obtained from 8 critically ill patients receiving ECMO. Plasma concentration-time data for caspofungin were best described by a one-compartment model with first-order elimination. Lean body weight was identified as a significant covariate of volume of distribution. The typical volume of distribution and clearance of caspofungin in this cohort were 8.13 L and 0.55 L/h, respectively. The licensed caspofungin dosing regimen (a loading dose of 70 mg on day 1 followed by a maintenance dose of either 50 mg/day or 70 mg/day) demonstrated optimal PTA rates (≥90%) against
C. albicans
with an MIC of ≤0.064 mg/L,
C. glabrata
with an MIC of ≤0.125 mg/L, and
C. parapsilosis
with an MIC of ≤0.064 mg/L. The FTA analysis suggested that the licensed dosing regimen is only optimal (≥95%) against
Candida glabrata
, regardless of lean body weight. A higher-than-standard empirical dosing regimen (e.g., a loading dose of 100 mg on day 1, followed by a maintenance dose of 100 mg daily) is likely advantageous for critically ill patients receiving ECMO.
Cu- and Ag-mediated inactivation of
L. pneumophila
in bench- and pilot-scale drinking water systems
Authors: Hintz Chelsea L. , Morris Brian , Witt Sue , Sojda Nicole , Buse Helen Y.
Published: December 2024

Legionella pneumophila
(Lp) is an opportunistic drinking water pathogen that can cause infections through the inhalation of Lp-containing aerosols and can occur in premise plumbing systems. In this work, the use of copper (Cu) and silver (Ag) ions was evaluated at the bench and pilot scale to determine (i) the effective independent concentrations of copper and silver that are efficacious in inactivating Lp, (ii) the impact of various water quality parameters on the efficaciousness of copper and silver ions, and (iii) the effectiveness and practicality of using dissociation to produce ions at the pilot scale. At the bench scale, it was determined that 0.3 ppm and 0.03 ppm of Cu and Ag, respectively, achieved 6-log inactivation of Lp in 5 h in experimental buffer. But, in dechlorinated filter-sterilized tap water, the same concentrations of Cu were not effective, and the effectiveness of Ag was slower. pH and dissolved inorganic carbon content were found to be important parameters in determining if the use of Cu and Ag ions is appropriate. At the pilot scale, dissociation was successfully used to produce Cu and Ag ions. Target levels of ions were met at the pilot scale but were difficult to achieve, and no impact was observed on Lp concentrations. Results from this study suggest that there are important caveats in the application of this technology when applied in a drinking water matrix and prior understanding of a system’s water chemistry may be important to determine the effectiveness of Lp disinfection using Cu and Ag.

IMPORTANCE

This work sheds light on the effectiveness of using Cu and Ag ions to inactivate (or kill)
Legionella pneumophila. Legionella
is an opportunistic drinking water pathogen of public health concern. This work demonstrates that there are important caveats in the application of using Cu and Ag ions to inactivate
Legionella pneumophila
.
A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine
Authors: Haldar Risha , Halder Prolay , Koley Hemanta , Miyoshi Shin-ichi , Das Santasabuj
Published: December 2024

Shigella
infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl
3
) plus desferrioxamine intraperitoneally followed by oral infection with virulent
Shigella flexneri 2a
resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing
Shigella
invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against
Shigella
, indicating that the model is suitable for testing of vaccine candidates. To protect both
Shigella
and
Salmonella
, a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with
Salmonella
outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with
Shigella
(
S. flexneri 2a
,
Shigella dysenteriae
, and
Shigella sonnei
) using our present mouse model and
Salmonella
(
Salmonella
Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral S
higella
infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against
Shigella
.
DDO-adjuvanted influenza A virus nucleoprotein mRNA vaccine induces robust humoral and cellular type 1 immune responses and protects mice from challenge
Authors: Gnazzo Victoria , Saleh Hanaa , Castro Ítalo A. , Boon Adrianus C. M. , Pinto Amelia K. , Brien James D. , López Carolina B.
Published: December 2024

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8
+
T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA technology offers an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8
+
T-cells remains a challenge. Here, we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice. DDO268 when co-packaged with mRNA in lipid nanoparticles is sensed by RIG I-like receptors and safely induces local type I interferon (IFN) production followed by dendritic cells type 1 activation and migration to the draining lymph nodes. This early response triggered by DDO268 improved the generation of IgG2c antibodies and antigen-specific Th1 CD4
+
and CD8
+
T-cells (IFNγ
+
TNFα
+
IL2
+
) that provided enhanced protection against lethal IAV challenge. In addition, the inclusion of DDO268 reduced the antigen dose required to achieve protection. These results highlight the potential of DDO268 as an effective mRNA vaccine adjuvant and show that an IAV NP mRNA/DDO268 vaccine is a promising approach for generating protective immunity against conserved internal IAV epitopes.

IMPORTANCE

Vaccines that generate neutralizing antibodies and cytotoxic CD8
+
T-cells targeting conserved epitopes are ideal for effective protection against viruses. mRNA vaccines combined with the right adjuvant offer a promising solution to this challenge. We show that the virus-derived oligonucleotide DDO268 enhances antibody and T-cell responses to an influenza A virus (IAV) nucleoprotein mRNA vaccine in mice. DDO268 safely induces local type I interferon production and stimulates dendritic cell activation providing enhanced protection against IAV challenge. In addition, the adjuvant activity of DDO268 allows for the use of lower antigen doses during vaccination.
Supplemental Material: Neoproterozoic–early Paleozoic evolution of the southern Central Asian Orogenic Belt: Constraints from eclogites in the Beishan Orogenic Belt (NW China)
Authors: Wang Tingyi , Zhao Guochun , al. et
Published: December 2024

Table S1: Zircon U-Pb isotope data for the studied samples. Table S2: U-Pb isotope data for accessory minerals for the studied samples. Table S3: Whole-rock major and trace element contents of the Gubaoquan eclogite sample. Table S4: Zircon Lu-Hf isotope compositions for the Gubaoquan eclogite sample. Text S1: Analytical methods.
Bleb-related endophthalmitis during an epidemic of viral keratoconjunctivitis
Authors: Beri Nitika , Verma Saurabh , Sharma Namrata , Dada Tanuj
Published: December 2024

There is an annual epidemic of viral conjunctivitis at the onset of the monsoon (rainy) season in North India. This affects a large population, with many patients developing ocular symptoms and then getting better without any treatment as there is no specific therapy for adenoviral infections. However, this creates a dangerous situation for patients with operated trabeculectomy with a filtering bleb as conjunctivitis can lead to blebitis and bleb-related endophthalmitis with super-added bacterial/fungal infections. While the viral infection is self-limiting and most patients get well without treatment, urgent medical attention is required if patients with operated trabeculectomy develop this condition. It is important to educate all patients with operated glaucoma about the outbreak of conjunctivitis and explain the danger signs (like redness, sensitivity to light, vision decrease and pain, which require immediate medical attention and initiation of broad-spectrum antibiotics if a delay is anticipated in visiting the hospital.
Fresh osteochondral allograft transplantation of the medial femoral condyle in an elite football player
Authors: Oliveira João Pedro , Mendes João Castro , Fonseca Fernando
Published: December 2024

We present an elite footballer in his 20s with a large and symptomatic osteochondral lesion of the weight-bearing area of the medial femoral condyle, who was proposed for a single plug fresh osteochondral allograft transplantation. The lesion was due to repetitive micro traumas and had become highly symptomatic being responsible for making the football practice at a professional level almost impossible, reaching a point that keeping an elite sports career was compromised. Six months after surgery, the athlete returned to sports and, at a 3-year follow-up, still participated in elite high-level football, with a Tegner Activity Scale 10/10, IKDC 93.1, KOOS 97 and Lysholm Scoring 100.
Minocycline-induced lupus
Authors: Hasegawa Shinya , Craig Steven M , Suzuki Hiroyuki
Published: December 2024

Antibiotics are indicated for inappropriately prolonged durations not only for infectious diseases but also for non-infectious dermatologic conditions such as acne vulgaris, but inappropriate use is not uncommon. Inappropriate antibiotic prescription can contribute to the emergence of multidrug-resistant organisms, patient harm such as adverse drug events and increased healthcare costs. We experienced a case involving a late adolescent with acne vulgaris who had been treated with minocycline for more than 2 years, leading to the development of drug-induced lupus, attributed to minocycline. This resulted in multiple clinic and emergency department visits and extensive and expensive workups, including an invasive procedure. A collaboration between antibiotic stewardship activities and patient-centred medication reviews, followed by personalised deprescribing, could effectively mitigate inappropriate antibiotic prescriptions for non-infectious dermatologic conditions.
Intravenous thrombolysis in a stroke patient with a repaired aortic dissection
Authors: Ryan Dylan , Maher Michelle , Feng Wayne , Pawar Swaroop
Published: December 2024

Acute aortic dissection is considered a contraindication to the use of intravenous thrombolysis in patients presenting with acute ischaemic stroke, but less has been described about previously repaired dissections. We present a case of a woman in her 50s presenting with acute left hemiparesis with a known history of aortic dissection within the thrombolysis window. After multidisciplinary discussion with cardiothoracic surgery and discussion with the patient, she was treated with intravenous thrombolysis without complication. In patients with previously repaired aortic dissection without evidence of redissection, intravenous thrombolysis can be considered.
Effect of heated mittens on physical hand function in people with hand osteoarthritis: randomised controlled trial
Authors: Bartholdy Cecilie , Døssing Anna , Stisen Zara R , Nielsen Sabrina M , Christensen Robin , Danneskiold-Samsøe Bente , Bliddal Henning , Henriksen Marius , Ellegaard Karen
Published: December 2024

Objective

To assess the effect of electrically heated mittens on physical hand function in people with osteoarthritis of the hands compared with control mittens.

Design

Randomised controlled trial.

Setting

Osteoarthritis outpatient clinic, Copenhagen, Denmark.

Participants

200 people with hand osteoarthritis aged 42-90 years. 100 participants were assigned to the intervention group and 100 to the control group.

Interventions

Electrically heated mittens or control mittens (heating elements disconnected) worn for at least 15 minutes daily for six weeks.

Main outcome measures

The primary outcome was change in hand function measured on the function subscale of the Australian/Canadian hand osteoarthritis index (AUSCAN; score 0-100 points) at six weeks. Key secondary outcomes included changes in the AUSCAN hand pain subscale (score 0-100 points), global rating of hand osteoarthritis related problems (0-100 visual analogue scale), and grip strength (newtons) at six weeks. Analysis of secondary outcomes was performed using a hierarchical gatekeeping approach.

Results

91 participants in the intervention group and 95 in the control group completed the trial. The mean age of participants was 71 years, 87% (n=173) were women, and mean body mass index was 24.9 (SD 4.4). Median disease duration was 10 years (interquartile range 5-15 years). The between group difference for change in AUSCAN function at week 6 was 3.0 points (95% confidence interval (CI) −0.4 to 6.3; P=0.09) in favour of heated mittens. For the key secondary outcome, change in AUSCAN hand pain score from baseline, a group difference was observed of 5.9 points (95% CI 2.2 to 9.5) in favour of heated mittens. Changes in global rating of hand osteoarthritis related problems and grip strength did not differ between the groups with an observed difference between groups of 2.8 points (95% CI −3.7 to 9.2) and 2.3 newtons (95% CI −16.3 to 21.0) in favour of heated mittens, respectively.

Conclusion

Use of electrically heated mittens for six weeks was not related to a positive change in physical hand function compared with control mittens. Heated mittens provided no additional benefits on global rating of hand osteoarthritis related problems and grip strength. A small benefit was detected for hand pain, but this could have been overestimated.

Trial registration

ClinicalTrials.gov
NCT04576403
Net Zero is not enough: ratcheting ambition for sustainable health systems through Reduce and Support
Authors: Sue-Chue-Lam Colin , Bhopal Anand , Parker Joshua , Xie Edward C
Published: December 2024

Net Zero is the dominant framework for organising health system decarbonisation. Yet throughout Net Zero’s rise to prominence, greenhouse gas emissions have remained on a dangerous trajectory. In this analysis, we synthesise strands of Net Zero critique from the climate policy literature, examine their implications for health systems and briefly present an alternative framework for decarbonisation. We begin by reviewing three families of Net Zero critique which have, to date, received little attention in the sustainable healthcare space: unambitious and inequitable pledges, accounting failures, and structural problems with the framework itself. Together, these critiques challenge the idea that the Net Zero agenda is best positioned to deliver upon the Paris Agreement commitment to limit temperature rise to below 1.5°C–2°C. We then consider how each challenge manifests in the health sector with examples from state and non-state actors. Finally, we briefly introduce an alternative 'reduce and support' approach which aims to address some of Net Zero’s weaknesses. Reduce-and-support represents a conceptual pivot that would extend current best practices in science-based mitigation targets while exchanging the atomised trading of problematic carbon offsets for resource pooling towards collective efforts at deep decarbonisation. We discuss the moral, political and practical advantages of this framework and identify areas for future work. By considering the adoption of reduce-and-support, health systems can provide leadership for ratcheting climate ambition at this pivotal moment of accelerating climate breakdown.
Umbrella-Review, Evaluation, Analysis and Communication Hub (U-REACH):a novel living umbrella review knowledge translation approach
Authors: Gosling Corentin J , Cortese Samuele , Radua Joaquim , Moher David , Delorme Richard , Solmi Marco
Published: December 2024

Systematic reviews and meta-analyses have become crucial for evidence-based decision-making in recent decades. However, it is common for the results of multiple reviews on the same topic to be inconsistent, and it is widely recognised that the results of the reviews are not always effectively communicated to healthcare professionals and the lay public. This manuscript proposes a strategy to summarise and communicate the findings of previous systematic reviews and meta-analyses to wider audiences. The proposed approach couples the findings of umbrella reviews with the creation of open-access online platforms that present the results of these umbrella reviews in an accessible way to various stakeholders. The key potential methodological avenues of this approach are presented, and specific examples from the author’s own works and those from other teams are provided. An accompanying website (https://u-reach.org/) has been designed to present this Umbrella-Review, Evaluation, Analysis, and Communication Hub (U-REACH) approach and to overcome the technical challenges associated with this type of project (by sharing the code used to build existing U-REACH projects). The present document is intended to serve as a methodological and technical guide for the creation of large-scale projects designed to synthesise and disseminate scientific information to a broad audience.
Antigen-specific immune therapy (CNP-106) for treatment of generalised myasthenia gravis: rationale and design of first-in-human randomised controlled trial
Authors: G Brew Samantha , Frey Molly , P McCarthy Derrick , Elhofy Adam , Nowak Richard J
Published: December 2024

Introduction

Myasthenia gravis (MG) is a T cell-dependent B cell-mediated autoimmune disease with pathogenic antibodies directed against components of the acetylcholine receptor (AChR). Current therapies do not address the root cause of the disease (autoimmune recognition of AChR) and are associated with possible serious side effects. Therefore, new therapeutic options targeting antigen-specific autoimmunity are needed. COUR nanoparticle (CNP-106) is an antigen-specific immune tolerance therapy directed to the AChR to stop the pathogenic driver of MG. Data from experimental models suggest the potential benefit of CNP-106 to patients by reprogramming the immune system to AChR and stopping the progression of the disease. The aim of this study is to determine the safety and preliminary efficacy of CNP-106 in AChR antibody-positive generalised MG subjects.

Methods and analysis

The outlined study is a multicentre Phase 1b/2a double-blind, randomised, placebo-controlled trial with an enrolment target of 54 AChR antibody-positive generalised MG subjects. The primary endpoint is safety and tolerability. Exploratory and secondary endpoints include disease-specific clinical scores, measures of quality of life and activities of daily living, antigen-specific T cells and AChR antibodies. Trial enrolment is anticipated to start in 2024.

Ethics and dissemination

The trial has ethical approval from the Central Institutional Review Boards and has clinical trial authorisation from the Food and Drug Administration. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals.

Trial registration number

NCT06106672.
Patients' and clinicians’ perspectives on virtual phone consultation in vascular surgery
Authors: Yahya Muhammad Syafwan , Tang Lilian , Healy Donagh
Published: December 2024

Introduction

The pandemic limited our capacity for face-to-face (F2F) outpatient clinics and therefore we set up virtual phone consultation clinics (VPC). Our study evaluated patients' and clinicians’ perspectives on our VPC and identified areas for improvement.

Methods

We designed a questionnaire for patients and a questionnaire for clinicians. These included questions on satisfaction with VPC, practical aspects of VPC and suggestions for improvement. Between December 2021 and February 2022, one hundred patients and 11 clinicians completed these questionnaires.

Results

The average satisfaction score for the patients’ last VPC attendance was 4.42/5 (SD 0.90). The main benefits of VPC from the perspective of patients were: reduced risk of infection, the convenience of not needing to travel and increased efficiency. A large proportion of the patients were unaware that an F2F clinic attendance could be requested instead of a VPC. 3 patients suggested that we could do video calls. 52 patients indicated that they would prefer an F2F attendance for their next review.

The average satisfaction score for our clinicians was 4.19 (SD 0.98). Our clinicians believed that the advantages of VPC were increased efficiency, reduced risk of infection and lower cost. Clinicians felt that patients who needed to be told about normal scan results and patients who could not travel were most suitable for VPC. The most notable disadvantage of VPC was the inability to perform a physical examination and our clinicians felt that this could delay treatment. Some clinicians felt that giving patients a written summary of the VPC would be beneficial.

Conclusion

Our patients and staff were satisfied with our VPC programme and understand its advantages. Our study provided justification for the continued use of VPC.
Bundled de-implementation of recurring hospital orders with a novel electronic medical record order set
Authors: Murphy Caleb J , Narala Vanshika , Katiki Aishwarya , Martinez Maylyn S , Cerasale Matthew T , Nguyen Khanh T
Published: December 2024

Introduction

High-frequency recurring orders placed through the electronic medical record (EMR) may contribute to unnecessary care in hospitalised patients. This quality initiative sought to develop and pilot test a hospital order set for bundled review and de-implementation of common recurring orders.

Methods

A voluntary-use EMR order set was developed to display low-frequency order alternatives for common hospital care components. The order set was introduced to hospitalists at a large academic hospital from February to June 2023. Orders for overnight vital signs, tubes/tethers (a composite of telemetry, continuous pulse oximetry and Foley catheter) and daily labs (a composite of complete blood counts and metabolic panels) were monitored twice weekly in hospitalised patients at low risk for clinical decompensation from December 2022 through June 2023. Paired t-test was used to assess for differences in order frequency before and after order set introduction.

Results

The order set was used in 48 unique encounters to place 80 de-implementation orders, most commonly for discontinuation of overnight vital signs (n=37). Two or more de-implementation orders were placed during 44% of order set encounters. Mean (SD) total high-frequency orders decreased by 0.22 per patient day (95% CI −0.39 to −0.06; p=0.010) after order set introduction, driven by a reduction in overnight vital sign orders of 0.17 per patient day (95% CI −0.23 to −0.12; p<0.001). There was no statistically significant difference in orders for tubes/tethers or daily labs before and after order set introduction.

Discussion

Introduction of a novel order set for bundled review and de-implementation of recurring orders was associated with reduced high-frequency recurring orders in hospitalised patients, driven by a reduction in overnight vital signs. Nearly half of order set use was for two or more de-implementation orders, suggesting that bundling de-implementation orders may be an efficient way to reduce unnecessary orders.
Prevalence of anxiety and depression in former elite athletes: a systematic review and meta-analysis
Authors: Runacres Adam , Marshall Zoe A
Published: December 2024

Objectives

To summarise the evidence regarding the prevalence of anxiety and depression in former elite athletes compared with the general population.

Design

Systematic review and meta-analysis.

Data sources

Five electronic databases (Web of Science, PubMed, MEDLINE, Scopus and SPORTDiscus) were searched from 1970 to 2023.

Eligibility criteria

Studies were included in the meta-analysis if they: (1) were written in English; (2) included male or female elite athletes that had been retired ≥1 year; (3) included a control grouporpopulation reference values; (4) reported the time-point prevalence of anxiety and/or depression; and (5) were of a retrospective, longitudinal or prospective, methodological design. A modified version of the Downs and Black tool was used to determine risk of bias.

Results

37 unique studies including 24 732 former athletes (2% female) were included in the meta-analysis. The time-point prevalence of anxiety (prevalence ratio (PR): 2.08 (95% CI 1.57 to 2.60)) and depression (PR: 2.58 (95% CI 2.04 to 3.12)) in former athletes was over twice that of the general population. Subgroup analyses revealed former American football players and jockeys had the highest time-point prevalence of both anxiety and depression (PR: 2.24–2.88), whereas the time-point prevalence of depression and anxiety was not significantly different to the general population for former rugby players (PR: 1.13–1.30).

Conclusion

Our meta-analyses demonstrated the time-point prevalence of anxiety and depression in former elite athletes could be over twice that of the general population, with sport-specific differences evident.

PROSPERO registration number

CRD42022347359.
Impact of telehealth-based therapeutic exercise on pain, functional performance and dynamic knee valgus in young adult females with patellofemoral pain: a randomised controlled trial
Authors: Nilmart Patcharin , Vongsirinavarat Mantana , Khawsuwan Pimpaka , Chumthong Kiatrada , Tadein Russareeta , Komalasari Dwi Rosella
Published: December 2024

Objectives

This study aimed to evaluate the effectiveness of a telehealth-based therapeutic exercise (TTE) programme with real-time video conference supervision for young adult females with patellofemoral pain (PFP).

Methods

The study design was a randomised controlled trial. Forty-two participants with PFP were allocated to either the TTE group or the control (C) group. The TTE group received a 4-week telehealth-based exercise programme supervised through real-time video conferencing, while the C group followed a self-guided stretching exercise. Pain intensity was assessed using the Visual Analogue Scale, while functional performance was evaluated with hop tests and the step-down test. Dynamic knee valgus was measured by the frontal plane projection angle during a single-leg squat. In addition, the study used a specific health questionnaire which evaluated knee pain and function, including the self-administered Kujala Patellofemoral Questionnaire (KPQ). All outcomes were assessed both before and after the intervention.

Results

After the 4-week interventions, the results showed a significant interaction between the group and the time of pain intensity, functional performance and dynamic knee valgus (p<0.001). The TTE group demonstrated significant pain reduction (p<0.001) and improved KPQ score (p<0.001), while the C group showed no significant changes. TTE participants also exhibited improved functional performance in the hop and step-down tests. Additionally, dynamic knee valgus was significantly decreased in the TTE group.

Conclusion

The telehealth-based exercise programmes offer a convenient and effective alternative for managing PFP symptoms, providing remotely accessible and specialised care.
Outcomes of tricuspid valve surgery in patients with significant tricuspid regurgitation and low to intermediate risk
Authors: Gwak Seo-Yeon , Kim Kyu , Lee Hyun-Jung , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young
Published: December 2024

Background

In patients with tricuspid regurgitation (TR), delayed surgical intervention is associated with poor outcomes, particularly in advanced stages. This study aimed to assess whether earlier tricuspid valve (TV) surgery provides a survival benefit in patients with moderate to severe TR who are considered at low to intermediate risk of adverse clinical or surgical outcomes.

Methods

This retrospective cohort study included 10 016 patients diagnosed with moderate to severe TR between 2008 and 2020. Patients were stratified using the the Tricuspid Regurgitation Impact on Outcomes (TRIO) Score (for general health risk) and TRI-SCORE (for perioperative risk). We focused on patients deemed at low or intermediate risk by these scores, comparing the all-cause mortality of those who underwent TV surgery to those managed medically.

Results

Among 8874 patients categorised as low or intermediate risk, 871 (9.8%) underwent TV surgery. Patients in the surgical group were younger and had a higher prevalence of RV enlargement and RV dysfunction compared to those in the medical treatment group. During a mean follow-up of 5.2 years, surgical patients had a lower risk of death (HR 0.38, 95% CI 0.29 to 0.50) compared with medically managed patients after adjusting for confounders. This association persisted in patients who underwent isolated TV surgery. However, the potential for residual confounding in this non-randomised analysis should be considered.

Conclusions

TV surgery was associated with higher survival rates in patients with moderate to severe TR and low to intermediate prognostic risk. However, the observational nature of the study means that uncontrolled confounding cannot be excluded. These findings warrant further investigation in randomised studies.