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Laboratory testing and toxicity monitoring.
toxicity, Hepatitis, Toxicity
ADVERSE EVENT, ALLERGY, HEPATITIS
All patients underwent medical interview, physical exam, and laboratory testing at all visits to monitor for safety. Laboratory testing for toxicity monitoring (complete blood counts, serum chemistries, and quantitative immunoglobulins) was performed at each visit prior to OFC by the Johns Hopkins Core Pathology Labora...
PMC10425211
Statistics.
EVENT
All null hypothesis significance tests were 2-tailed. Normality testing was performed on all data using the Shapiro-Wilk test (α = 0.05). In the event that data did not demonstrate normal Gaussian distribution, nonparametric tests were utilized as described. For tests using multiple comparisons, corrections for multipl...
PMC10425211
Study approval.
This trial was conducted under the approval of a United States Food and Drug Administration (FDA) Investigational New Drug application (IND 142734) and the Johns Hopkins University IRB (IRB00223615). Written informed consent was obtained from all patients prior to participation in study procedures.
PMC10425211
Data availability.
The data that support the findings of this study including the supplemental materials are available in a separate supporting data file available online. Further study-related human subject data is available from the corresponding author upon request and will be deidentified before sharing.
PMC10425211
Author contributions
MCD
RECRUITMENT
The trial was conceived of and designed by MCD and BSB. RVS and MCD oversaw the conduct of the trial and took lead roles in all aspects of study visits and patient care. Patient recruitment and screening was done by RVS. RAW assisted in patient recruitment. Collection of data was performed by MCD, RVS, CD, and DWZM. Da...
PMC10425211
Supplementary Material
PMC10425211
Supplemental data
PMC10425211
ICMJE disclosure forms
PMC10425211
06/29/2023
In-Press Preview
PMC10425211
08/15/2023
Electronic publication
PMC10425211
Schematic representing study design and patient disposition.
Flow diagram summarizing the (
PMC10425211
Maximum tolerated peanut dose and symptom scores during OFC.
(
PMC10425211
Secondary outcomes.
(
PMC10425211
Baseline characteristics of patients
PMC10425211
Summary of adverse events
PMC10425211
Background
postoperative pulmonary complications
Minimising postoperative pulmonary complications (PPCs) after thoracic surgery is of utmost importance. A major factor contributing to PPCs is the driving pressure, which is determined by the ratio of tidal volume to lung compliance. Inhalation and intravenous administration of penehyclidine can improve lung compliance...
PMC10508004
Methods
A double-blind, prospective, randomised study involving 176 patients scheduled for elective thoracic surgery was conducted. These patients were randomly divided into two groups, namely the penehyclidine inhalation group and the intravenous group before their surgery. Driving pressure was assessed at T
PMC10508004
Results
All 167 participants, 83 from the intravenous group and 84 from the inhalation group, completed the trial. The AUC of driving pressure for the intravenous group was 39.50 ± 9.42, while the inhalation group showed a value of 41.50 ± 8.03 (
PMC10508004
Conclusions
Our study found that among patients undergoing thoracoscopic surgery, no significant differences were observed in the driving pressure and mechanical power during OLV between those who received an intravenous injection of penehyclidine and those who inhaled it. Moreover, no significant difference was observed in the in...
PMC10508004
Keywords
PMC10508004
Introduction
Postoperative pulmonary complications
Postoperative pulmonary complications (PPCs) are commonly observed during the first postoperative week and have been associated with a prolonged hospital stay [Strategies aimed at decreasing the incidence of PPCs include preoperative functional exercise [Airway driving pressure and mechanical power are two widely used ...
PMC10508004
Materials and methods
This prospective trial was conducted at affiliated hospital of Jiaxing University, China, from September 2022 to April 2023. The Institutional Review Board approved this study (2022-LY-164), and it was registered with the Chinese Clinical Trial Registry (
PMC10508004
Study population
liver dysfunction, tachyarrhythmia, respiratory tract infections, heart dysfunction, allergies, renal insufficiency, prostatic hypertrophy
MYOCARDIAL INFARCTION, RESPIRATORY TRACT INFECTIONS, NARROW-ANGLE GLAUCOMA, HEART DYSFUNCTION, ALLERGIES, RENAL INSUFFICIENCY, PROSTATIC HYPERTROPHY, HEART
The study included patients aged over 50 years who were undergoing thoracic surgery with OLV lasting expected to more than 45 min. Participants were required to have an American Society of Anaesthesiologists physical status of 1–3 and a postoperative hospital stay of at least 3 days to be eligible for participation. Pa...
PMC10508004
Blinding and randomisation
The anaesthesia was administered by an anaesthesiologist who was blinded to the patient grouping, and the postoperative assessment was conducted by a researcher who was also blinded to the patient grouping. All patients received a combination of inhalation and intravenous therapy. In both groups, the study drug, 0.5 mg...
PMC10508004
Procedures
The patient’s information was thoroughly reviewed by the surgeon and nurse before the start of the procedure. Intraoperative monitoring equipment, such as electrocardiogram, oxygen saturation, invasive arterial blood pressure, end-expiratory carbon dioxide, airway pressure, and entropy index, was also meticulously chec...
PMC10508004
Data collection and outcome assessment
For data collection, a standardised form was used, sourced from the clinical charts to obtain baseline characteristics. Baseline data included demographic and morphometric characteristics, preoperative comorbidities, and smoking and alcohol history, along with pulmonary function test results. These pulmonary function t...
PMC10508004
Sample size estimation
During the preliminary study, the driving pressure of 60 patients across T
PMC10508004
Statistical analysis
Categorical variables are presented as numbers and percentages. Continuous variables are presented as the mean ± standard deviation or median (interquartile). The chi-square test or Fisher’s exact test was used to compare categorical variables and Student’s t-test or Mann–Whitney U test was used for continuous variable...
PMC10508004
Results
From September 2022 to April 2023, 201 patients were initially assessed for eligibility, of which 176 patients were randomised. Nine patients were excluded after randomisation, resulting in 167 patients for per-protocol analysis. The final analysis encompassed 83 patients in the intravenous group and 84 patients in the...
PMC10508004
Driving pressure
(%)Adverse drug reactions
The AUC for driving pressure did not reveal any significant differences between the inhalation and intravenous groups (41.50 ± 8.03 vs. 39.50 ± 9.42, Driving pressure and mechanical power during OLV and PPCsIncidence of PPCs within 7 days,n (%)Adverse drug reactions associatedwith penehyclidine, n (%) Driving pressur...
PMC10508004
Mechanical power
No significant differences were observed between the inhalation and intravenous groups in terms of the AUC of mechanical power (24.00 [20.7–27.9] vs. 24.20 [19.7–27.1]; Mechanical power. According to generalised estimating equations, the mechanical power did not differ significantly in the intergroup comparison (
PMC10508004
Secondary outcomes
postoperative pulmonary complications
LUNG
Within 7 days postoperatively, PPCs, categorised according to the Clavien–Dindo classification were observed in 20 of the 84 patients (23.8%) in the inhalation group and 23 of the 83 (27.7%) patients in the intravenous group ( Incidence of postoperative pulmonary complications (PPCs) within 7 days. The incidence of PPC...
PMC10508004
Safety outcomes
ADVERSE REACTIONS
No significant differences were observed in terms of the adverse reactions associated with penehyclidine, and no serious adverse outcomes were attributed to the study drug (Table 
PMC10508004
Discussion
ADVERSE EFFECTS, COMPLICATIONS, POSTOPERATIVE COMPLICATIONS
In this randomised clinical trial involving adults undergoing thoracoscopic surgery, preoperative prophylactic inhalation of penehyclidine did not significantly reduce the driving pressure and mechanical power during OLV compared with intravenous administration. Moreover, there was no observed reduction in PPCs within ...
PMC10508004
Acknowledgements
We are grateful to the cardiothoracic surgeons of the Jiaxing University affiliated hospital for their assistance. Additionally, we would like to thank Zhiyun for their significant input in revising the wording of this paper.
PMC10508004
Authors' contributions
Ming-zi An and Qing-he Zhou were major contributors to this study. Te-sheng Gao, Qing-he Zhou and Ming-zi An contributed to the study conception and design. Data were collected by Cheng-yun Xu, Yue-ru Hou and Zhen-ping Li. The data analysis was performed by Ming-zi An and Qing-he Zhou. The first draft of the manuscript...
PMC10508004
Funding
This study was supported by Zhejiang medical and health science and technology plan project (2023KY341), Jiaxing Key Discipiline of Medcine --Anesthesiology (2023-ZC-001), the Key Discipline Established with Zhejiang Provincial Traditional Chinese Medical Innovation Team (No. 2022-19) and Zhejiang Provincial Key Clinic...
PMC10508004
Availability of data and materials
All the data and material generated during the current study are available from the corresponding author upon reasonable request (zqh10980@zjxu.edu.cn).
PMC10508004
Declarations
PMC10508004
Ethics approval and consent to participate
This trial was approved by the ethics committee of the Affiliated Hospital of Jiaxing University, China, on September 06, 2022 (2022-LY-164) before experiment was started and that has been conducted in accordance with the principles set forth in the Helsinki Declaration. Written informed consent was obtained from all p...
PMC10508004
Consent for publication
Not applicable.
PMC10508004
Competing interests
The authors declare no competing interests.
PMC10508004
References
PMC10508004
Background
sleep disorders, insomnia, sleep disorder
CHRONIC INSOMNIA
Shift workers are at high risk of developing sleep disorders such as shift worker sleep disorder or chronic insomnia. Cognitive behavioral therapy (CBT) is the first-line treatment for insomnia, and emerging evidence shows that internet-based CBT is highly effective with additional features such as continuous tracking ...
PMC10481224
Objective
sleep disorders
This study aimed to evaluate the impact of a 4-week, physician-assisted, internet-delivered CBT program incorporating machine learning–based well-being prediction on the sleep duration of shift workers at high risk of sleep disorders. We evaluated these outcomes using an internet-delivered CBT app and fitness trackers ...
PMC10481224
Methods
SYNDROME
A convenience sample of 61 shift workers (mean age 32.9, SD 8.3 years) from the intensive care unit or emergency department participated in the study. Eligible participants were on a 3-shift schedule and had a Pittsburgh Sleep Quality Index score ≥5. The study comprised a 1-week baseline period, followed by a 4-week in...
PMC10481224
Results
In the fourth week of intervention, the mean daily sleep duration for 7 days (6.06, SD 1.30 hours) showed a statistically significant increase compared with the baseline (5.54, SD 1.36 hours;
PMC10481224
Conclusions
sleep disorders
The physician-assisted internet-delivered CBT program targeting shift workers with a high risk of sleep disorders showed a statistically significant increase in sleep duration as measured by wearable sensors along with subjective sleep quality. This study shows that sleep improvement programs using an app and wearable ...
PMC10481224
International Registered Report Identifier (IRRID)
RR2-10.2196/24799.
PMC10481224
Introduction
PMC10481224
Interventions for Shift Work–Related Sleep Disorder
insomnia, SWSD
Shift work is common among the working population, with approximately 20% of individuals engaged in shift work [Cognitive behavioral therapy (CBT) is a treatment aimed at restructuring undesired thinking and modifying behavioral patterns through self-reflection and interactions with physicians. There are 4 fundamental ...
PMC10481224
Shift Workers’ Well-Being and Well-Being Prediction
Several studies have shown a correlation between poor sleep patterns resulting from shift work and an increased risk of burnout among various professional groups, including police officers [The second aim was to provide “well-being prediction” feedback to the participants. Previous studies have shown that self-monitori...
PMC10481224
Objectives
sleep disorders
This study aimed to evaluate the effect of a physician-assisted, internet-delivered CBT intervention with machine learning–based well-being prediction on sleep duration and well-being of shift workers at high risk of sleep disorders. The study followed a single-arm prospective design, with a baseline period of 1 week, ...
PMC10481224
Methods
PMC10481224
Study Design and Settings
sleep disorders
This prospective interventional study aimed to evaluate the effect of internet-delivered CBT on shift workers with a high risk of sleep disorders. This study involved shift workers, including physicians and nurses, employed in 2 ICUs in Japan. Participants were instructed to wear a wrist-worn fitness tracker 24 hours a...
PMC10481224
Inclusion and Exclusion Criteria
narcolepsy, psychiatric, sleep disorders
DISORDERS, SLEEP APNEA, NARCOLEPSY, RESTLESS LEG SYNDROME
Inclusion criteria were as follows: shift workers engaged in emergency and intensive care areas, working on a 3-shift schedule with 8-hour shifts, and a Pittsburgh Sleep Quality Index (PSQI) score ≥5. Exclusion criteria were as follows: diagnosis of sleep disorders such as sleep apnea, restless leg syndrome, and narcol...
PMC10481224
Study Measures and Outcomes
PMC10481224
Objective and Subjective Sleep Measurements
The primary outcome of this study was to evaluate the effect of the intervention on total sleep time. In this study, we used a consumer fitness tracker called Fitbit Charge 3 (Fitbit). It is widely used in sleep research under normal living conditions because of its easy obtainability, cost efficiency, and comparabilit...
PMC10481224
Subjective Well-Being and Mental Health State
calmness, Anxiety, PVT: psychomotor vigilance
SECONDARY
As a secondary outcome, we evaluated the effect of the intervention on subjective well-being. Participants scored their subjective well-being using 5 categories: alertness, happiness, energy, physical health, and calmness. Participants were asked to rate their subjective well-being on a scale of 0 to 100 as part of the...
PMC10481224
Sample Size and Power Calculation
Before this study, we collected data from 16 shift workers in a pilot study. The mean sleep duration was 334.68 (SD 135.1) minutes. On the basis of the pilot study data with a small sample, the mean sleep duration at week 4 of the intervention was assumed to be 30 minutes longer, with no change in SD. Assuming a 2-side...
PMC10481224
Intervention
sleep disorders
The smartphone app for the intervention was developed and made available as a Progressive Web Application so that it could be used on an iOS or Android device (Well-being prediction is an essential component of an app. On the basis of earlier studies on machine learning and subjective well-being [The second essential c...
PMC10481224
Statistical Analyses
Statistical analyses were performed using SPSS Statistics for Macintosh (version 25.0; IBM Corp). The baseline characteristics of the study population were expressed as mean and SD for quantitative variables. For the primary outcome of this study, the mean sleep duration at week 4 of the intervention and the means and ...
PMC10481224
Ethics Approval
MAY
This study was approved by the Clinical Research Ethics Review Committee of Mie University Hospital, Tsu, Japan (H2020-083). This study was approved by the ethics committee of the Suzuka General Hospital (review number 254). All procedures were performed in accordance with the ethical standards of the Institutional Res...
PMC10481224
Results
PMC10481224
Changes in Well-Being and Mental Health
There was no significant improvement in all 5 well-being scores (alertness, happiness, energy, health, and relaxation; all
PMC10481224
Postanalysis of Well-Being Prediction
After the study, the performance of the prediction model was evaluated. Postanalysis showed that the macroaveraged
PMC10481224
Discussion
PMC10481224
Principal Findings
sleep disorders, insomnia
DISORDERS
The main result of this study shows that physician-assisted internet-delivered CBT program in shift workers with a high risk of sleep disorders increased total sleep time, as measured using commercially available fitness trackers. After a 4-week intervention period, the mean daily sleep duration for 7 days (6.06 hours)...
PMC10481224
Limitations
anxiety
Our study has a few important limitations. First, this study does not provide any conclusion to the participants’ motivation for attribution and continuation, as the research incentives were financial rewards. We acknowledge that motivation and participation are crucial factors that affect the outcomes of internet-base...
PMC10481224
Conclusions
sleep disorders, Epilepsy
EPILEPSY
Physician-assisted, internet-delivered CBT for shift workers with a high risk of sleep disorders showed significant improvement in sleep duration, as measured by wearable sensors, and subjective sleep quality. This study implies that sleep improvement programs using an app and wearable sensors are feasible and may play...
PMC10481224
Abbreviations
Anxiety
DISORDER
cognitive behavioral therapyGeneral Health Questionnaireintensive care unitPittsburgh Sleep Quality Indexpsychomotor vigilance testState-Trait Anxiety Inventoryshift worker sleep disorder
PMC10481224
MATERIALS AND METHODS
PMC10071780
Population
RECURRENCE
This study was a prospective, open-label, randomized, 2-armed crossover study conducted in 6 study centers in France. Men who were at least 18 y old, who were diagnosed with PCa, and who had prior definitive therapy were considered for enrollment. Eligible patients presented with suspected PCa recurrence, defined as 3 ...
PMC10071780
Intervention
All men underwent both
PMC10071780
Image Reading and Standard of Truth
RECURRENCE
PET images were read on-site on the day of acquisition by investigators who were not masked regarding clinical data and were transferred to a core imaging laboratory where they were evaluated by 3 independent masked readers (supplemental materials). The composite standard of truth (recurrence, no recurrence, or undeter...
PMC10071780
Outcomes
The primary objective was to compare Secondary objectives were to compare the correct detection rates of the clinical investigators; to assess the correct detection rates of both radiotracers for PCa lesions in a region-based analysis; to report the impact on diagnostic thinking (impact of PET/CT result on posttest vs....
PMC10071780
Statistical Analysis
Analysis was performed using SAS 9.4 or higher (SAS Institute), detailed in the supplemental materials. A
PMC10071780
RESULTS
PMC10071780
Population
From March 5, 2019, to October 8, 2020, 200 patients consented to this study; 195 were randomized, and 189 completed all follow-up assessments (Trial chart.Patient Characteristics (Intention-to-Treat Population)Values in parentheses are ranges.Reported as numbers of patients, with percentages in parentheses.Reported as...
PMC10071780
Primary Objective
RECURRENCE, METASTASES, POSITIVE
Per-patient and per-region PET findings are detailed in the supplemental materials. At the patient level, the masked readers found evidence for PCa recurrence in 145–162 patients (76.3%–85.3%) with The overall proportion of patients with correct detection rates for PCa lesions with Patient-Level Overall Proportion of P...
PMC10071780
Secondary Objectives
PMC10071780
Comparison of Patient-Based Correct Detection Rates According to Investigator Findings
On the basis of the clinical investigators’ overall findings, the correct detection rates were 0.80 (95% CI, 0.74–0.86) for
PMC10071780
Comparison of Region-Based Correct Detection Rates According to Masked Readers’ Findings
In the 72 patients for whom 1 or more regions could be assessed by the expert panel, there were 78 regions with confirmed PCa lesions. The most common sites for PCa lesions were the pelvis (59 patients) and the spine (6 patients) (supplemental materials). In the patients considered to have a positive PET result, more s...
PMC10071780
Impact on Diagnostic Thinking, Therapeutic Decision Making, and Adequacy of Therapy Changes
The investigator assessments of the changes in diagnostic thinking after both PET/CT examinations and at the end of follow-up are summarized in Change in Diagnostic Thinking After Both PET/CT Scans (ITT Population) (Data are reported as numbers of patients, with percentages in parentheses.Change in Diagnostic Thinking ...
PMC10071780
Safety Profile of
toothache, diarrhea
ADVERSE EVENTS, EVENTS, ADVERSE EVENT, ARTERIAL HYPERTENSION
There were no serious adverse events. No patient discontinued study participation because of an adverse event. Four patients had 4 events (toothache, diarrhea, chest discomfort, and arterial hypertension) after the administration of
PMC10071780
DISCUSSION
prostate
RECURRENCE, PROSTATE
To our knowledge, the present study is the first multicenter, crossover randomized study to compare The investigator assessments after PET/CT and at the end of follow-up demonstrated the superiority of The strengths of our study are its prospective, multicenter, randomized crossover design. Limitations include the lack...
PMC10071780
CONCLUSION
This prospective, multicenter, open-label, crossover randomized study demonstrated that
PMC10071780
DISCLOSURE
This study was funded and supported by ABX Advanced Biochemical Compounds, Radeberg, Germany. Ines Rudolph and Alexander Hoepping work for ABX Advanced Biochemical Compounds. Charles Merlin has received personal fees and nonfinancial support from Curium Pharma and Novartis. Mathieu Gauthé has received personal fees and...
PMC10071780
ACKNOWLEDGMENTS
P.
We thank the following institutions and people for participating in this study: Hôpital Tenon—F. Montravers, C. Aveline, J.N. Talbot, T. Rusu, B. Mugnier, and N. Cailleux; HEGP—B. Clara, M. Bernardini, C. Smadja, H. Slimani, B. Truffault, and M. Homo Seban; CHRU Nancy—G. Karcher, P. Eschwege, M. Claudin, and D. Peiffer...
PMC10071780
REFERENCES
PMC10071780
Background
DRY EYE, DISORDER
Lifestyle modification is a newly recommended complementary treatment for dry eye (DE) disorder.
PMC10692261
Objective
hypertensive
OBESE
To investigate the effect of a 6-month high-intensity interval aerobic exercise (HIIAE) (conducted 30 min, 3 times weekly) alone or combined with a caloric-restriction approach, the Mediterranean diet (MD), on DE parameters in obese hypertensive elderly.
PMC10692261
The design, settings, participants, and intervention
hypertensive
OBESE, RECRUITMENT
This is a randomized controlled trial included sixty obese hypertensive elderly with DE based on university-based hospital recruitment. Elderly were randomly assigned to the experimental group (
PMC10692261
Results
Significant improvements in anthropometry, blood pressure, and DE parameters were higher in the experimental group than in the control group.
PMC10692261
Conclusion
DE disorder, hypertensive
OBESE
Aging-related DE symptoms and signs can be prevented and/or treated with HIIAE alone or combined with MD in obese hypertensive elderly with DE disorder.
PMC10692261
Keywords
Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).
PMC10692261
Introduction
obesity, ocular pain, redness, impairments of the lacrimal gland, itching, fatigue, inflammation, dry eye, Tear deficiency, atrophy, tear film disorder, diabetes
OBESITY, METAPLASIA, INFLAMMATION, DISEASE, ASSOCIATED DISEASE, DRY EYE, ATROPHY, METABOLIC SYNDROME, HYPERTENSION, COMPLICATIONS, DIABETES
Tear deficiency or excessive evaporation is the main descriptive definition of the tear film disorder, dry eye (DE). DE can damage the interpalpebral ocular surface with subsequent symptoms of ocular discomfort [The symptomatic discomfort expresses itself in DE as ocular pain, itching, scleral redness, light sensitivit...
PMC10692261
Materials and methods
PMC10692261
Study design
The design was as follows: single-blinded evaluation of DE parameters (conducted by an ophthalmologist who did not share in MD or HIIAE and both interventions were masked from him), the prospective registration of this lifestyle-modification study on clinicaltrials.gov (NCT05248698), and the randomized controlled follo...
PMC10692261
Setting
RECRUITMENT
DE patients’ recruitment was managed from the ophthalmology outpatient clinic of Cairo University hospitals. The exercise sessions were supervised by the two physiotherapy authors of this study in a physical therapy center (a private center located in Cairo) from 5th January to 30th December 2022.
PMC10692261