bluuebunny/crossref_metadata_2025 huggingface dataset:
Contamination of platelet concentrates with Staphylococcus aureus induces significant modulations in platelet functionality
Authors: Yousuf Basit , Pasha Roya , Pineault Nicolas , Ramirez‐Arcos Sandra
Published: September 2022

Background and Objectives

Platelet concentrates (PCs) contaminated with Staphylococcus aureus can escape detection during PC screening, causing septic transfusion reactions. This study aimed to determine the impact of S. aureus contamination on platelet metabolism and functionality during PC storage.

Materials and Methods

Targeted metabolomics (N = 3) was performed on non‐spiked PCs and PCs inoculated with 10–20 colony‐forming units (CFU)/bag of S. aureus. Metabolites were quantified at 0, 48 and 144 h using high‐performance mass spectrometry (MS). Additionally, PCs spiked with approximately 20 CFU/bag of S. aureus were sampled every 24 h for up to 144 h to evaluate platelet functionality using flow cytometry (N = 2).

Results

Eight metabolites had significantly different levels in spiked PCs (log2 fold‐change ≤ or ≥±1) versus non‐spiked units at 48 and 144 h. Xanthine, uridine, serine, glutamine and threonine were increased, whereas orotic acid, dihydroorotic acid and aspartic acid were decreased. Flow cytometry showed a significant decrease in expression of GPIIb while P‐selectin expression was significantly increased in spiked PCs after 72 h of storage when S. aureus concentration was ≥10E+08 CFU/ml. Additionally, phosphatidylserine exposure was significantly increased after 48 h of PC storage, when S. aureus had reached a concentration of 2E+06.

Conclusion

Contamination with S. aureus exacerbates platelet storage lesions in contaminated PCs but only when the bacterium has reached clinically significant levels.
Use of O RhD‐negative red blood cells: A nationwide, prospective audit
Authors: Ilmakunnas Minna , Salmela Katja , Kivipuro Tiia , Sareneva Hannele , Sainio Susanna
Published: September 2022

Background and Objectives

Despite declining transfusion rates, overuse of O RhD‐negative red blood cells (RBCs) risks the secure supply of this limited resource. A nationwide prospective audit was performed in Finland to understand the clinical use and inventory management of O RhD‐negative units. Our aim was to identify areas where policy changes could help alleviate the shortage of O RhD‐negative RBCs.

Materials and Methods

The use of every O RhD‐negative unit in Finland during a period of 1 month was reviewed. For each issued unit (n = 1105), unit age, urgency of transfusion, hospital and patient demographics, and specific reasons for issuing O RhD‐negative units were recorded.

Results

Almost half of the O RhD‐negative units (n = 529, 47.9%) were issued to non‐O RhD‐negative patients. Only 22.3% (n = 118) were issued for females under the age of 50. Of the units for ABO‐nonidentical transfusion, one‐third (32.5%, n = 172) were issued for emergency transfusion, two‐thirds (67.5%, n = 357) for non‐urgent transfusions. The most common reason for issuing an O RhD‐negative unit was inventory management (n = 172, 48.2% of units issued for non‐urgent transfusion). Most of these units were issued close to the unit expiry date.

Conclusion

This nationwide audit revealed that a significant proportion of O RhD‐negative RBCs are used inappropriately. Clinicians should be educated on the appropriate use of O RhD‐negative RBCs, and blood banks should develop strategies for inventory management to avoid issuing O RhD‐negative units purely to prevent outdating.
Effectiveness of osteopathic manipulative treatment in cardiovascular function: a systematic review protocol
Authors: Vanier Cheryl , Johnston Kristine , DeArmond Megan , Salloum Liza , Arjmand Shadi , Toder Eric , Ioudina Marina
Published: September 2022

Objective:

The objective of this review is to investigate the short- and long-term effects of osteopathic manipulative treatment on cardiovascular function and its regulators in the nervous and endocrine systems.

Introduction:

A variety of pharmacological and lifestyle-based treatments are used to prevent or treat vascular diseases, yet vascular disease underpins the top 2 causes of death worldwide. There is a need for more preventative and therapeutic interventions in the management and prevention of vascular disease that are compatible with existing interventions. Osteopathic manipulative treatment has shown promise as a non-invasive approach to improve cardiovascular function, but it is currently utilized mostly for alleviating musculoskeletal symptoms. A comprehensive summary of the evidence on the effectiveness of osteopathic manipulative treatment in cardiovascular function will assist clinicians and guide future research directions.

Inclusion criteria:

This review will consider randomized controlled trials, non-randomized controlled trials, and crossover studies. Participants must have received osteopathic manipulative treatment intervention. Comparators will include passive or active controls, including controls for body position, touch, and other potential interventions for vascular disease. Cardiovascular, nervous-system, or endocrine-system outcome variables must be measured at least once after treatment. Adverse events will also be considered.

Methods:

Searches will be conducted in the following sources: MEDLINE, the Journal of Osteopathic Medicine, Embase, Scopus, ProQuest One Academic, MedNar, the International Journal of Osteopathic Medicine, and CINAHL. Studies available in English, without date restrictions, will be considered for inclusion. Relevant studies will be selected by 2 independent reviewers, critically appraised, and extracted using a tool customized for the details of the study. If meta-analysis is possible, evidence will be summarized using standard techniques with subgroup analyses providing more insight into particular osteopathic manipulative treatment techniques, time frame of the treatment, and duration of effects, among others. Certainty of findings will be presented using GRADE.

Systematic review registration number:

PROSPERO CRD42021225838
Barriers and facilitators for accessing and prescribing hormone therapy in primary care for transgender adults: a scoping review protocol
Authors: Ziegler Erin , Mills Christine M. , Lee Ji-Yoon Jessica , Carroll Benjamin
Published: September 2022

Objective:

The objective of this scoping review is to understand the extent and type of evidence in relation to barriers and facilitators experienced by transgender adults in accessing hormone therapy. It will also explore the experiences of primary care practitioners in prescribing hormone therapy in primary care.

Introduction:

Providing care to transgender patients is a rapidly growing area of primary care. Despite the existence of clinical practice guidelines that support the prescription of gender-affirming hormone therapy in primary care, only a small number of primary care providers are offering this care. This review will seek to advance research on this topic by examining the barriers and facilitators of hormone prescription for transgender adults in primary care.

Inclusion criteria:

This review will consider research on primary care practitioners who prescribe hormone therapy to transgender adults. It will also focus on transgender adults who seek hormone therapy in primary care. Only studies that examine barriers and facilitators in primary care will be included. The review will include qualitative, quantitative, and mixed methods studies, in addition to systematic reviews and meta-analyses.

Methods:

The search will include MEDLINE, CINAHL, EmCare, and Nursing and Allied Health Premium. No date limits will be applied to the search. Only articles written in English will be eligible for inclusion. Articles will be reviewed and data extracted by 2 independent reviewers. The results of the extracted data will be presented in a narrative summary with accompanying tables.
Investigation on Film Cooling Performance of a Novel Hole Arrangement Based on Combined-Hole Design
Authors: Zhu Rui , Zhu Huaitao , Xie Gongnan
Published: September 2022

Based on a combined-hole design, a novel hole arrangement was proposed and tested on a flat plate model by numerical simulation. Replacing one row in two rows of staggered holes with a row of smaller holes, the bigger holes in one row and smaller holes in the other row will form combined-hole units. The kidney–vortex pairs in the combined-hole unit will interact with each other and get weakened, finally enhancing film cooling performance. Compared to the original two rows of staggered holes, the coolant mass flowrate will be reduced by 25% for the new hole arrangements. Results show that the area-averaged film cooling effectiveness of the new arrangements is similar or even higher than that of the original one at different blowing ratios. Replacing the second row of holes with smaller holes provide better cooling performance than replacing the first row of holes. The overall film cooling performance is not sensitive to the row space. The highest improvement of film cooling effectiveness is 24% when the blowing ratio is 1. However, as the coolant accumulation and reattachment phenomenon is weakened by the new arrangements, the film cooling performance is not as good as the original one when the blowing ratio is 1.5.
A new species of Dolichotetranychus (Trombidiformes: Tenuipalpidae) damaging Dracaena trifasciata (Asparagaceae) in Iran
Authors: Mahdavi Sayed Mosayeb , Asadi Mahdieh , Paktinat-saeij Saeid , Ghanbarzadeh Mohammad Ali , Ziaei-Rad Hossein
Published: September 2022

A new species of the genus Dolichotetranychus Sayed, 1938 (Acari: Trombidiformes: Tenuipalpidae), Dolichotetranychus babolicus sp. nov. is described from Dracaena trifasciata (Asparagaceae) grown in greenhouses in northern Iran (Mazandaran province). All active life stages are described and illustrated and anomalous features noted. Photographs of its colonies and damage symptoms are presented. This is the first report of the family Tenuipalpidae on this plant genus. Additionally, some data of D. iranicus Khadem & Asadi in Safdarkhani et al. 2016 is corrected.
Genetic Load of SARS-CoV-2 in Aerosols Collected in Operating Theaters
Authors: Barberá-Riera María , Porru Simona , Barneo-Muñoz Manuela , Villasante Ferrer Andrea , Carrasco Paula , de Llanos Rosa , Llueca Antoni , Delgado-Saborit Juana María
Published: September 2022

Operating rooms are critical environments in which asepsis must be ensured. The COVID-19 pandemic entailed the implementation of additional preventative measures in health care settings, including operating theaters.
FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease
Authors: Camire Andrew C. , O’Bier Nathaniel S. , Patel Dhara T. , Cramer Nicholas A. , Straubinger Reinhard K. , Breitschwerdt Edward B. , Funk Rebecca A. , Marconi Richard T.
Published: September 2022

Lyme disease (LD) is a tick-transmitted bacterial infection caused by
Borreliella burgdorferi
and other closely related species collectively referred to as the LD spirochetes. The LD spirochetes encode an uncharacterized family of proteins originally designated
p
rotein
f
amily
t
welve (PF12).
Modulation of SOCS3 Levels via STAT3 and Estrogen-ERαp66 Signaling during Hepatitis E Virus Replication in Hepatocellular Carcinoma Cells
Authors: Sooryanarain Harini , Heffron C. Lynn , Mahsoub Hassan M. , Hassebroek Anna M. , Wang Bo , Tian Debin , Ahmed S. Ansar , Meng Xiang-Jin
Published: September 2022

Hepatitis E is usually a self-resolving acute disease; however, in pregnant women, HEV infection is associated with high mortality and fulminant hepatic failure. During pregnancy, estrogen levels are elevated, and in the liver, the estrogen receptor ERα is predominant and estrogen signaling is known to regulate hepatocyte metabolism and leptin-induced STAT3 levels.
Highly Pathogenic Avian Influenza A (H5N1) Virus in Swans, Central China, 2021
Authors: Ke Xianliang , Yao Zhongzi , Tang Yangyu , Yang Mengting , Li Yong , Yang Guoxiang , Chen Jing , Chen Guang , Feng Wei , Zheng Hesong , Chen Quanjiao
Published: September 2022

Here, we obtained the whole-genomes of six H5N1 viruses from dead or rescued wild birds in Hubei Province. These viruses were divided into two genotypes and had different evolutionary trajectories from previously reported H5N1 viruses in China.
Pyridostigmine-induced coronary artery spasm in early-onset myasthenia gravis: a case presentation and review of the literature
Authors: Chuapakdee Oranuch , Layangkool Tanit , Theerasuwipakorn Nonthikorn
Published: September 2022

We present a case of pyridostigmine-induced coronary artery spasm in a woman with early-onset myasthenia gravis (MG) who suffered from acute chest discomfort a few days after pyridostigmine dose up-titration. Twelve-lead ECG demonstrated ST-segment elevation in inferior limb leads together with sinus arrest. Sublingual nitrate was immediately given, which rapidly relieved her symptoms concomitantly with the resolution of abnormal ECG findings. Coronary angiography showed normal coronary arteries reflecting the transient nature of the disease. A small dose of pyridostigmine was rechallenged under close monitoring in the coronary care unit and reproduced her chest discomfort. After the substitution of pyridostigmine with immunosuppressive agents and prescription of long-acting nitrate, she had no recurrence of chest discomfort, as well as well-controlled MG symptoms.
Sino-orbital foreign body caused by a slingshot injury in a young boy
Authors: Lai Kenneth , Laycock Juliet , Bates Adam , Hamann Julian
Published: September 2022

Slingshots or hand catapults, historically used as a military or hunting weapon, are common toys among children and young teenagers. Their use can be dangerous as a strike to the eye or orbit can result in significant injuries including blindness. We describe a rare case of a sino-orbital foreign body caused by a slingshot injury in a young boy. The case was managed by a multidisciplinary team involving ear, nose and throat, ophthalmology and paediatrics, and the foreign body of a metal ball bearing was removed using an endoscopic transnasal approach. Although the patient made a good recovery, the case highlights the danger of slingshot devices misused by children.
Giant jelly bump deposits on therapeutic contact lens: an unusual finding following ptosis surgery
Authors: Agarwal Ayushi , Murthy Somasheila I , Bothra Nandini , Naik Milind N
Published: September 2022

The authors report two cases of unusually large deposits on their therapeutic bandage contact lens (BCL) following uneventful surgery for congenital ptosis. The first case presented at 6 weeks with decreased vision, large jelly-bump deposits over the contact lens and sterile corneal infiltrates. The infiltrates rapidly resolved with restoration of vision following contact lens removal and topical antibiotics. The second case presented 2 weeks after surgery with visual loss and similar deposits but with no corneal involvement. Following replacement of BCL and topical lubricants, her vision improved to 20/20. Studies on the role of BCL in ptosis surgery are scarce with literature supporting its use for ocular surface protection and minimising postoperative discomfort. The authors hypothesise impaired blink mechanism as the accelerating factor for this unusual occurrence in the early postoperative period and recommend frequent replacement of the contact lens and a closer follow-up in all these cases.
Associated factors for discontinuation of statin use one year after discharge in patients with acute coronary syndrome in China
Authors: Xie Gaoqiang , Myint Phyo Kyaw , Sun Yihong , Li Xian , Wu Tao , Gao Run-lin , Wu Yangfeng
Published: September 2022

Objectives

To determine the associated factors for discontinuation of statin use 1 year after discharge in patients who survived from acute coronary syndrome (ACS) in China.

Settings

75 hospitals across China.

Design

A cohort follow-up study.

Participants

The study included 10 337 patients with ACS hospitalised in 2007–2010 and discharged with statins from 75 hospitals in China in the Clinical Pathways for Acute Coronary Syndromes in China Study-Phase 2 (CPACS-2), who were followed-up at 6 and 12 months postdischarge.

Primary outcome measures

The primary outcome was the discontinuation of statin use defined as not in current use of statin at either 6-month or 12-month follow-up.

Results

Multivariable logistic regression model showed that patients who did not have cholesterol measurement (adjusted OR=1.29; 95% CI: 1.10 to 1.50) and patients with either higher (1.27; 1.13 to 1.43) or lower dose of statin (1.22; 1.07 to 1.40), compared with those with standard dose, were more likely to discontinue the use of statin. In addition, patients on the CPACS-2 intervention pathway (adjusted OR=0.83; 95% CI: 0.74 to 0.94), patients with medical insurance (0.75; 0.67 to 0.85), history of hypertension (0.83; 0.75 to 0.92), high low-density lipoprotein cholesterol (0.70; 0.57 to 0.87) at the baseline, prior statin use (0.73; 0.63 to 0.84), use of atorvastatin (0.78; 0.70 to 0.88) and those who underwent percutaneous coronary intervention or coronary artery bypass grafting during hospitalisation (0.47; 0.43 to 0.53) were less likely to discontinue statin use. The 1-year statin discontinuation rate decreased from 29.5% in 2007–2008 to 17.8% in 2010 (adjusted OR=0.60; 95% CI: 0.51 to 0.70).

Conclusion

Implementing clinical pathway, enhancing medical insurance coverage, strengthening health education in both physicians and patients, using statin at standard dosage may help improve the adherence to statin use after discharge in Chinese patients with ACS.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12609000491268).
Multi-Arm GlioblastoMa Australasia (MAGMA): protocol for a multiarm randomised clinical trial for people affected by glioblastoma
Authors: Kong Benjamin Y , Sim Hao-Wen , Barnes Elizabeth H , Nowak Anna K , Hovey Elizabeth J , Jeffree Rosalind , Harrup Rosemary , Parkinson Jonathon , Gan Hui K , Pinkham Mark B , Yip Sonia , Hall Merryn , Tu Emily , Carter Candace , Koh Eng-Siew , Lwin Zarnie , Dowling Anthony , Simes John S , Gedye Craig
Published: September 2022

Introduction

Glioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world setting to improve survival of people with GBM. Initial experimental arms are evaluating the effectiveness of interventions in newly diagnosed GBM (ndGBM). This study will compare maximal surgical resection followed by chemoradiotherapy plus adjuvant chemotherapy for 6 months with the addition of (1) ‘neoadjuvant’ chemotherapy beginning as soon as possible after surgery and/or (2) adjuvant chemotherapy continued until progression within the same study platform.

Methods and analysis

MAGMA will establish a platform for open-label, multiarm, multicentre randomised controlled testing of treatments for GBM. The study began recruiting in September 2020 and recruitment to the initial two interventions in MAGMA is expected to continue until September 2023.

Adults aged ≥18 years with ndGBM will be given the option of undergoing randomisation to each study intervention separately, thereby giving rise to a partial factorial design, with two separate randomisation time points, one for neoadjuvant therapy and one for extended therapy. Patients will have the option of being randomised at each time point or continuing on with standard treatment.

The primary outcome for the study is overall survival from the date of initial surgery until death from any cause. Secondary outcomes include progression-free survival, time to first non-temozolomide treatment, overall survival from each treatment randomisation, clinically significant toxicity as measured by grade 3 or 4 adverse events and health-related quality-of-life measures. Tertiary outcomes are predictive/prognostic biomarkers and health utilities and incremental cost-effectiveness ratio.

The primary analysis of overall survival will be performed separately for each study intervention according to the intention to treat principle on all patients randomised to each study intervention.

Ethics and dissemination

The study (Protocol version 2.0 dated 23 November 2020) was approved by a lead Human Research Ethics Committee (Sydney Local Health District: 2019/ETH13297). The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.

Trial registration number

ACTRN12620000048987.
Quickly identifying people at risk of opioid use disorder in emergency departments: trade-offs between a machine learning approach and a simple EHR flag strategy
Authors: Annis Izabela E , Jordan Robyn , Thomas Kathleen C
Published: September 2022

Objectives

Emergency departments (EDs) are an important point of contact for people with opioid use disorder (OUD). Universal screening for OUD is costly and often infeasible. Evidence on effective, selective screening is needed. We assessed the feasibility of using a risk factor-based machine learning model to identify OUD quickly among patients presenting in EDs.

Design/settings/participants

In this cohort study, all ED visits between January 2016 and March 2018 for patients aged 12 years and older were identified from electronic health records (EHRs) data from a large university health system. First, logistic regression modelling was used to describe and elucidate the associations between patient demographic and clinical characteristics and diagnosis of OUD. Second, a Gradient Boosting Classifier was applied to develop a predictive model to identify patients at risk of OUD. The predictive performance of the Gradient Boosting algorithm was assessed using F1 scores and area under the curve (AUC).

Outcome

The primary outcome was the diagnosis of OUD.

Results

Among 345 728 patient ED visits (mean (SD) patient age, 49.4 (21.0) years; 210 045 (60.8%) female), 1.16% had a diagnosis of OUD. Bivariate analyses indicated that history of OUD was the strongest predictor of current OUD (OR=13.4, CI: 11.8 to 15.1). When history of OUD was excluded in multivariate models, baseline use of medications for OUD (OR=3.4, CI: 2.9 to 4.0) and white race (OR=2.9, CI: 2.6 to 3.3) were the strongest predictors. The best Gradient Boosting model achieved an AUC of 0.71, accuracy of 0.96 but only 0.45 sensitivity.

Conclusions

Patients who present at the ED with OUD are high-need patients who are typically smokers with psychiatric, chronic pain and substance use disorders. A machine learning model did not improve predictive ability. A quick review of a patient’s EHR for history of OUD is an efficient strategy to identify those who are currently at greatest risk of OUD.
Late myocardial reperfusion in ST-elevation myocardial infarction: protocol for a systematic review and meta-analysis
Authors: Vargas-Fernández Rodrigo , Chacón-Diaz Manuel , Basualdo-Meléndez Gianfranco W , Barón-Lozada Francisco A , Visconti-Lopez Fabriccio J , Comandé Daniel , Hernández-Vásquez Akram
Published: September 2022

Introduction

ST-segment elevation myocardial infarction (STEMI) is the most severe clinical form of acute myocardial infarction, for which the current treatment consists of effective and timely myocardial reperfusion (within 12 hours of symptom onset). However, between 10% and 15% of patients with STEMI arrive at hospital facilities 12 hours after the onset of symptoms (late presentation). Therefore, the objective of the present study will be to determine if late revascularisation (12–72 hours after the onset of symptoms) affects the indicators of cardiovascular mortality, reinfarction, recurrent infarction, hospitalisation for heart failure and post infarction angina compared with no late revascularisation in patients with STEMI.

Methods and analysis

A systematic literature search of PubMed, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Scopus and Global Health will be conducted. Publications in English, Portuguese or Spanish that report the clinical results of primary percutaneous revascularisation (primary PCI) in adult patients with STEMI 12–72 hours after the onset of symptoms will be included. Studies with participants with a diagnosis other than STEMI or patients with STEMI of >12 hours complicated by heart failure, cardiogenic shock or ventricular arrhythmias, and studies of combined interventions (pharmacoinvasive strategy) were excluded. Two independent authors will identify the relevant publications, and discrepancies will be adjudicated by a third author. Data extraction will be performed by two independent authors and verified by a third author. Risk of bias of studies will be assessed using the Cochrane ‘risk of bias’ tool (RoB 2) or Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. If appropriate, a meta-analysis will be performed in order to examine the effect of late revascularisation in clinical outcomes of interest.

Ethics and discussion

This study will use published data only, thus, ethical approval will not be required. The results will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42021283429.
Efficacy of Lactococcus lactis strain plasma (LC-Plasma) in easing symptoms in patients with mild COVID-19: protocol for an exploratory, multicentre, double-blinded, randomised controlled trial (PLATEAU study)
Authors: Yamamoto Kazuko , Hosogaya Naoki , Inoue Tsuyoshi , Jounai Kenta , Tsuji Ryohei , Fujiwara Daisuke , Yanagihara Katsunori , Izumikawa Koichi , Mukae Hiroshi
Published: September 2022

Introduction

The COVID-19 pandemic has been a major concern worldwide; however, easily accessible treatment options for patients with mild COVID-19 remain limited. Since the oral intake of Lactococcus lactis strain plasma (LC-Plasma) enhances both the innate and acquired immune systems through the activation of plasmacytoid dendritic cells (pDCs), we hypothesised that the oral intake of LC-Plasma could aid the relief or prevention of symptoms in patients with asymptomatic or mild COVID-19.

Methods and analysis

This is an exploratory, multicentre, double-blinded, randomised, placebo-controlled trial. This study was initiated in December 2021 and concludes in April 2023. The planned number of enrolled subjects is 100 (50 subjects×2 groups); subject enrolment will be conducted until October 2022. Patients with asymptomatic or mild COVID-19 will be enrolled and randomly assigned in a 1:1 ratio to group A (oral intake of LC-Plasma-containing capsule, 200 mg/day, for 14 days) or group B (oral intake of placebo capsule, for 14 days). The primary endpoint is the change in subjective symptoms measured by the severity score. Secondary endpoints include SARS-CoV-2 viral loads, biomarkers for pDC activation, serum SARS-CoV-2-specific antibodies, serum cytokines, interferon and interferon-inducible antiviral effectors and the proportion of subjects with emergency room visits to medical institutions or who are hospitalised.

Ethics and dissemination

The study protocol was approved by the Clinical Research Review Board of Nagasaki University, in accordance with the Clinical Trials Act of Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported in journal publications.

Trial registration number

Japan Registry of Clinical Trials (registration number: jRCTs071210097).
Evaluating the impact of a sleep health education and a personalised smartphone application on sleep, productivity and healthcare utilisation among employees: results of a randomised clinical trial
Authors: Robbins Rebecca , Weaver Matthew D , Quan Stuart F , Sullivan Jason P , Qadri Salim , Glasner Laura , Cohen-Zion Mairav , Czeisler Charles A , Barger Laura K
Published: September 2022

Objectives

We evaluated an online Sleep Health and Wellness (SHAW) programme paired with dayzz, a personalised sleep training programme deployed via smartphone application (dayzz app) that promotes healthy sleep and treatment for sleep disorders, among employees at a large healthcare organisation.

Design

Open-label, randomised, parallel-group controlled trial.

Setting

A healthcare employer in the USA.

Participants

1355 daytime workers.

Intervention

Participants were randomised to intervention (n=794) or control (n=561) on consent. Intervention participants received the SHAW educational programme at baseline plus access to the personalised dayzz app for up to 9 months. The control condition received the intervention at month 10.

Primary and secondary outcome measures

Our primary outcome measures were sleep-related behavioural changes (eg, consistent sleep schedule); sleep behaviour tracked on an electronic sleep diary and sleep quality. Our secondary outcome measures included employee absenteeism, performance and productivity; stress, mood, alertness and energy; and adverse health and safety outcomes (eg, accidents).

Results

At follow-up, employees in the intervention condition were more likely to report increased sleep duration on work (7.20 vs 6.99, p=0.01) and on free (8.26 vs 8.04, p=0.03) nights. At follow-up, the prevalence of poor sleep quality was lower in the intervention (n=160 of 321, 50%) compared with control (n=184 of 327, 56%) (p=0.04). The mean total dollars lost per person per month due to reduced workplace performance (presenteeism) was less in the intervention condition (US$1090 vs US$1321, p=0.001). Employees in the intervention reported fewer mental health visits (RR 0.72, 95% CI 0.56 to 0.94, p=0.01) and lower healthcare utilisation over the study interval (RR 0.81, 95% CI 0.67 to 0.98, p=0.03). We did not observe differences in stress (4.7 (95% CI 4.6 to 4.8) vs 4.7 (95% CI 4.6 to 4.8)), mood (4.5 (95% CI 4.4 to 4.6) vs 4.6 (95% CI 4.5 to 4.7)), alertness (4.9 (95% CI 4.8 to 5.0) vs 5.0 (95% CI 4.9 to 5.1)) or adverse health and safety outcomes (motor vehicle crashes: OR 0.82 (95% CI 0.34 to 1.9); near-miss crashes: OR=0.89 (95% CI 0.5 to 1.5) and injuries: 0.9 (95% CI 0.6 to 1.3)); energy was higher at follow-up in the intervention group (4.3 vs 4.5; p=0.03).

Conclusions

Results from this trial demonstrate that a SHAW programme followed by access to the digital dayzz app can be beneficial to both the employee and employer.

Trial registration number

NCT04224285
Role of religious beliefs in adherence to antiretroviral therapy in the Cape Town metropole: a study protocol
Authors: Azia Ivo Nchendia , Carelse Shernaaz , Nyembezi Anam , Mukumbang Ferdinand C
Published: September 2022

Introduction

There are presently over four million people living with HIV (PLHIV) in the South African national antiretroviral therapy (ART) programme. However, some ART programmes are battling poor ART adherence emanating from patient-related factors, including their religious beliefs. In this paper, we outline a study protocol to understand the adherence behaviours of Pentecostal Christians living with HIV to ART and to develop guidelines that can be used to strengthen ART adherence.

Methods and analysis

We propose an exploratory multimethod research design. In phase 1, a scoping review will be conducted. The data captured in this phase will be put into charting forms, analysed qualitatively, and then collated and summarised to hypothesise the relationship between religious beliefs and ART adherence. In phase 2, an explanatory qualitative approach will be used. Semistructured interviews will be conducted with purposefully selected religious leaders, Pentecostal Christians living with HIV who are not adhering to ART and healthcare workers delivering ART at selected healthcare facilities in the Milnerton subhealth district. The qualitative data obtained in this phase will be transcribed verbatim and analysed thematically using the ATLAS.ti V.8 software program towards strengthening the hypothesised relationship between religious beliefs and ART adherence. In phase 3, intervention mapping and nominal group techniques will be applied with purposefully selected stakeholders to develop guidelines to strengthen ART adherence among PLHIV.

Ethics and dissemination

Phase 1 of the study will not require ethics approval. Ethics approval for phases 2 and 3 has been received from the University of the Western Cape Biomedical Research and Ethics Committee and the Western Cape Department of Health. Informed consent forms will be obtained from all participants at the different phases of the study. The study findings will be disseminated through publications in scientific journals, presentations at conferences and workshops aimed at improving ART adherence.
Outcomes of proximal humerus fractures in children: a study protocol for a retrospective cohort study
Authors: Abbot Samuel Richard , Proudman Susanna , Hall Kelly , Williams Nicole
Published: September 2022

Introduction

Proximal humerus fractures (PHFs) comprise <3% of all fractures in children and adolescents. While it is accepted that minimally displaced PHFs can be treated conservatively, the management of severely displaced PHFs remains controversial, especially in older children. This study will aim to analyse the functional and quality-of-life outcomes of children with PHFs, in order to inform their optimal management.

Methods and analysis

We will conduct a retrospective cohort study to evaluate the outcomes of patients who were diagnosed with a paediatric PHF at the Women’s and Children’s Hospital (WCH) in South Australia. The primary outcome will be each participant’s pain and quality-of-life outcome, determined by use of the Quick Disabilities of the Arm, Shoulder and Hand, Shoulder Pain and Disability Index and Paediatric Outcomes Data Collection Instrument. Secondary outcomes will include rates of non-union, persistent deformity and complications. The information for these variables will be acquired during a brief clinic appointment, and from the medical records and WCH radiology database. Multivariable logistic regression will be performed to determine the clinical variables associated with a worse clinical outcome.

Ethics and dissemination

The study has been approved by the Women’s and Children’s Health Network Human Research Ethics Committee (protocol number: 2021/HRE00250). The study findings will be submitted to peer-reviewed scientific journals for publication and disseminated at conference presentations.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12622000176763).
Diagnostic work-up of urinary tract infections in pregnancy: study protocol of a prospective cohort study
Authors: Werter Dominique Esmée , Kazemier Brenda M , van Leeuwen Elisabeth , de Rotte Maurits C F J , Kuil Sacha D , Pajkrt Eva , Schneeberger Caroline
Published: September 2022

Introduction

Symptoms of urinary tract infections in pregnant women are often less specific, in contrast to non-pregnant women where typical clinical symptoms of a urinary tract infection are sufficient to diagnose urinary tract infections. Moreover, symptoms of a urinary tract infection can mimic pregnancy-related symptoms, or symptoms of a threatened preterm birth, such as contractions. In order to diagnose or rule out a urinary tract infection, additional diagnostic testing is required.

The diagnostic accuracy of urine dipstick analysis and urine sediment in the diagnosis of urinary tract infections in pregnant women has not been ascertained nor validated.

Methods and analysis

In this single-centre prospective cohort study, pregnant women (≥16 years old) with a suspected urinary tract infection will be included. The women will be asked to complete a short questionnaire regarding complaints, risk factors for urinary tract infections and baseline characteristics. Their urine will be tested with a urine dipstick, urine sediment and urine culture. The different sensitivities and specificities per test will be assessed. Our aim is to evaluate and compare the diagnostic accuracy of urine dipstick analysis and urine sediment in comparison with urine culture (reference test) in pregnant women. In addition, we will compare these tests to a predefined ‘true urinary tract infection’, to distinguish between a urinary tract infection and asymptomatic bacteriuria.

Ethics and dissemination

Approval was requested from the Medical Ethics Review Committee of the Academic Medical Centre; an official approval of this study by the committee was not required. The outcomes of this study will be published in a peer-reviewed journal.
Exploring experiences with telehealth-delivered allied healthcare services for people with permanent and significant disabilities funded through a national insurance scheme: a qualitative study examining challenges and suggestions to improve services
Authors: Filbay Stephanie , Bennell Kim L , Morello Renata , Smith Lizzie , Hinman Rana S , Lawford Belinda J
Published: September 2022

Objectives

In people with a disability, or their caregivers, who reported suboptimal experiences, the objectives were to explore: (1) challenges with telehealth-delivered allied health services during the COVID-19 pandemic and (2) suggestions to improve such services.

Design

Qualitative study based on an interpretivist paradigm and a phenomenological approach.

Setting

Participants who accessed allied healthcare via telehealth during the pandemic.

Participants

Data saturation was achieved after 12 interviews. The sample comprised three people with permanent or significant disabilities, and nine carers/partners/family members of people with permanent or significant disabilities, who were funded by the Australian National Disability Insurance Scheme and had suboptimal experiences with telehealth. Semistructured one-on-one interviews explored experiences with telehealth and suggestions on how such services could be improved. An inductive thematic analysis was performed.

Results

Six themes relating to the first study objective (challenges with telehealth) were developed: (1) evoked behavioural issues in children; (2) reliant on caregiver facilitation; (3) inhibits clinician feedback; (4) difficulty building rapport and trust; (5) lack of access to resources and (6) children disengaged/distracted. Five themes relating to the second study objective (suggestions to improve telehealth services) were developed: (1) establish expectations; (2) increase exposure to telehealth; (3) assess suitability of specific services; (4) access to support workers and (5) prepare for telehealth sessions.

Conclusions

Some people with permanent and significant disabilities who accessed allied healthcare via telehealth during the pandemic experienced challenges, particularly children. These unique barriers to telehealth need customised solutions so that people with disabilities are not left behind when telehealth services become more mainstream. Increasing experience with telehealth, setting expectations before consultations, supplying resources for therapy and assessing the suitability of clients for telehealth may help overcome some of the challenges experienced.
Sex-based differences in atrial fibrillation ablation adverse events
Authors: Mszar Reed , Friedman Daniel J , Ong Emily , Du Chengan , Wang Yongfei , Zeitler Emily P , Cunningham Shayna D , Akar Joseph , Curtis Jeptha P , Freeman James V
Published: September 2022

Objective

Older, relatively small studies identified female sex as a risk factor for adverse events after catheter ablation for atrial fibrillation (AF). We aimed to assess contemporary sex-based differences in baseline and procedural characteristics, adverse events, and quality of life among adults undergoing catheter ablation for AF.

Methods

In this observational cohort study, we evaluated those enrolled in the National Cardiovascular Data Registry AFib Ablation Registry between January 2016 and September 2020. Using logistic regression, we analysed the association between patient sex and in-hospital adverse events.

Results

Among 58 960 adults (34.6% women) from 150 centres undergoing AF ablation by 706 physicians, women were older (68 vs 64 years, p<0.001), had more comorbidities, and had lower AF-related quality of life at the time of ablation (mean Atrial Fibrillation Effect on QualiTy-of-life Questionnaire) score: 51.8 vs 62.2, p<0.001). Women had a higher risk of hospitalisation >1 day (adjusted OR (aOR) 1.41 (95% CI 1.33 to 1.49)), major adverse event (aOR 1.60 (95% CI 1.33 to 1.92)) and any adverse event (aOR 1.57 (95% CI 1.41 to 1.75)). Women had a higher risk of bradycardia requiring pacemaker, phrenic nerve damage, pericardial effusion, bleeding and vascular injury, but had no differences in death or acute pulmonary vein isolation.

Conclusions

Among almost 60 000 patients in the largest prospective registry of AF ablation procedures, female sex was independently associated with a higher risk of hospitalisation >1 day, adverse events, and reduced quality of life, although there were no differences in death or acute pulmonary vein isolation.
Restoration of p53 activity via intracellular protein delivery sensitizes triple negative breast cancer to anti-PD-1 immunotherapy
Authors: Yang Zaofeng , Sun Jacquelyne Ka-Li , Lee Marianne M , Chan Michael K
Published: September 2022

Background

Although immune checkpoint inhibitors (ICIs) have been shown to yield promising therapeutic outcomes in a small subset of patients with triple negative breast cancer (TNBC), the majority of patients either do not respond or subsequently develop resistance. Recent studies have revealed the critical role ofTP53gene in cancer immunology. Loss or mutation of p53 in cancer cells has been found to promote their immune escape. Given the high mutation frequency ofTP53in TNBC cells, restoration of p53 function could be a potential strategy to overcome their resistance to anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy. Herein, we have assessed the use of Pos3Aa crystal-based platform to mediate the intracellular delivery of p53 protein to restore p53 activity in p53 null tumors and consequently augment anti-PD-1 activity.

Methods

The efficiency of Pos3Aa-p53 crystals in delivering p53 protein was evaluated using confocal imaging, immunofluorescence staining, flow cytometry and RNA-seq. The ability of Pos3Aa-p53 crystals to remodel tumor microenvironment was investigated by examining the markers of immunogenic cell death (ICD) and the expression of PD-L1, indoleamine 2,3-dioxygenase 1, tryptophan 2,3-dioxygenase 2 and type I interferon (IFN). Finally, both unilateral and bilateral 4T1 tumor mouse models were utilized to assess the efficacy of Pos3Aa-p53 crystal-mediated p53 restoration in enhancing the antitumor activity of ICIs. T cells in tumor tissues and spleens were analyzed, and the in vivo biosafety of the Pos3Aa-p53 crystal/anti-PD-1 antibody combination was also evaluated.

Results

Delivery of p53 protein into p53-null TNBC 4T1 cells via Pos3Aa-p53 crystals restored the p53 activity, and therefore led to the induction of ICD, activation of type I IFN signaling and upregulation of PD-L1 expression. Pos3Aa-p53 crystals significantly enhanced T cell infiltration and activation in 4T1 tumors, thereby sensitizing them to anti-PD-1 therapy. The combination of Pos3Aa-p53 crystals with anti-PD-1 antibody also induced a systemic antitumor immunity resulting in the inhibition of distal tumor growth with minimal toxicity.

Conclusion

This study validates that p53 restoration can be an effective approach to overcome ICI resistance and demonstrates that intracellular delivery of p53 protein can be an efficient, safe and potentially universal strategy to restore p53 activity in tumors carryingTP53mutation.
Extensive plasma proteomic profiling revealed receptor activator of nuclear factor kappa-Β ligand (RANKL) as emerging biomarker of nivolumab clinical benefit in patients with metastatic renal cell carcinoma
Authors: Simonetti Sonia , Iuliani Michele , Stellato Marco , Cavaliere Silvia , Vincenzi Bruno , Tonini Giuseppe , Santini Daniele , Pantano Francesco
Published: September 2022

Background

The advent of immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC), nevertheless, the benefit of treatment is confined to a limited proportion of patients. Therefore, the identification of predictive biomarkers for response to ICIs represents an unmet clinical need. Here, we performed a large-scale plasma proteomic profile of patients with mRCC, treated with nivolumab, to identify soluble molecules potentially associated with clinical benefit.

Methods

We analyzed the levels of 507 soluble molecules in the pretreatment plasma of 16 patients with mRCC (discovery set) who received nivolumab therapy as a single agent. The ELISA assay was performed to confirm the protein level of candidate biomarkers associated to clinical benefit in 15 patients with mRCC (validation set). Survival curves of complete cohort were estimated by the Kaplan-Meier method and compared with the log-rank test.

Results

Out of 507 screened molecules, 135 factors were selected as expressed above background and 12 of them were significantly overexpressed in patients who did not benefit from treatment (non-responders (NR)) compared with responders (R) group. After multiplicity adjustment, receptor activator of nuclear factor kappa-Β ligand (RANKL) was the only molecule that retained the statistical significance (false discovery rate: 0.023). RANKL overexpression in NR patients was confirmed both in discovery (median NR: 528 pg/mL vs median R: 288 pg/mL, p=0.011) and validation set (median NR: 440 pg/mL vs median R: 253 pg/mL, p<0.001). Considering the complete cohort of patients (discovery+validation set), significantly higher RANKL levels were found in patients who primarily progressed from treatment compared with those who had a partial response (p=0.003) or stable disease (p=0.006). Moreover, patients with low RANKL levels had significant improvements in progression-free survival (median 14.0 months vs 3.4 months, p=0.004) and overall survival (median not reached vs 30.1 months, p=0.003).

Conclusions

Our exploratory study suggests RANKL as a novel independent biomarker of response and survival in patients with mRCC treated with nivolumab.