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European Respiratory Review : An... Jul 2024Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening conditions that can progress to death without... (Review)
Review
Medication adherence, related factors and outcomes among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: a systematic review.
INTRODUCTION
Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening conditions that can progress to death without treatment. Although strong medication adherence (MA) is known to enhance outcomes in chronic illnesses, its association with PAH and CTEPH was sporadically explored. This study aims to examine the MA of patients with PAH or CTEPH, identify factors associated with low adherence and explore the resulting outcomes.
METHODS
A systematic review was conducted by searching multiple databases (Medline, Embase, Cochrane Central, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar) from 6 March 1998 to 6 July 2023. We included studies reporting MA as primary or secondary end-points. Study selection, data extraction and methodological quality assessment were performed in duplicate.
RESULTS
20 studies involving 22 675 patients met the inclusion criteria. Heterogeneity was observed, particularly in the methods employed. MA means ranged from 0.62 to 0.96, with the proportion of patients exhibiting high MA varying from 40% (95% CI 35-45%) to 94% (95% CI 88-97%). Factors associated with low adherence included increased treatment frequency, time since diagnosis and co-payment. High MA seems to be associated with reduced hospitalisation rates, inpatient stays, outpatient visits and healthcare costs.
CONCLUSIONS
This systematic review underscores the heterogeneity of MA across studies. Nevertheless, the findings suggest that high MA could improve patients' clinical outcomes and alleviate the economic burden. Identifying factors consistently associated with poor MA could strengthen educational efforts for these patients, ultimately contributing to improved outcomes.
Topics: Humans; Medication Adherence; Antihypertensive Agents; Treatment Outcome; Chronic Disease; Risk Factors; Pulmonary Embolism; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Female; Male; Middle Aged
PubMed: 38960611
DOI: 10.1183/16000617.0006-2024 -
BMJ Open Jul 2024Previous studies demonstrated that wedge resection is sufficient for ground glass-dominant lung adenocarcinoma (LUAD) with tumour diameter ≤2 cm, however, the optimal...
INTRODUCTION
Previous studies demonstrated that wedge resection is sufficient for ground glass-dominant lung adenocarcinoma (LUAD) with tumour diameter ≤2 cm, however, the optimal surgical type for ground glass-dominant LUAD with tumour diameter of 2-3 cm remains unclear. The purpose of this trial is to investigate the safety and efficacy of segmentectomy for ground glass-dominant invasive LUAD with tumour size of 2-3 cm.
METHODS AND ANALYSIS
We initiated a phase III trial to investigate whether segmentectomy is suitable for ground glass-dominant invasive LUAD with tumour size of 2-3 cm. This trial plans to enrol 307 patients from multiple institutions including four general hospitals and two specialty cancer hospitals over a period of 5 years. The primary endpoint is 5 year disease-free survival. Secondary endpoints are lung function, 5 year overall survival, the site of tumour recurrence and metastasis, segmentectomy completion rate, radical segmentectomy (R0 resection) completion rate and surgery-related complications.
ETHICS AND DISSEMINATION
This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Centre (reference 2212267-18) and by the institutional review boards of each participating centre. Written informed consent is required from all participants. The study results will be published in a peer-reviewed international journal.
TRIAL REGISTRATION NUMBER
NCT05717803.
Topics: Humans; Lung Neoplasms; Pneumonectomy; Adenocarcinoma of Lung; Female; Male; Clinical Trials, Phase III as Topic; Disease-Free Survival; Multicenter Studies as Topic; Middle Aged; Adult; Neoplasm Recurrence, Local; China; Aged; Tumor Burden
PubMed: 38960464
DOI: 10.1136/bmjopen-2024-087088 -
BMJ Open Jul 2024Post-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Post-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex provides limited relief for symptoms of PTSD. This study will be conducted to validate the efficacy of MRI-guided rTMS in targeting the sites most closely associated with the amygdala for patients with PTSD. We hypothesise that the intervention will improve clinical symptoms by decreasing amygdala activity in patients.
METHODS AND ANALYSIS
A randomised, double-blind, sham-controlled trial will be conducted. Forty-eight eligible patients with PTSD will be randomly assigned to receive either active or sham MRI-guided rTMS for 10 consecutive days after the initial MRI scans. MRI scans will be recollected at the end of the intervention. Clinical assessments will be performed at baseline, treatment day 5, treatment day 10, and 2 weeks, 4 weeks, 8 weeks after completion of the intervention to monitor changes in clinical symptoms. The primary assessment outcome is the change in PTSD symptoms between baseline and treatment day 10, as measured by the PTSD Checklist for DSM-5. Repeated measures analysis of variance will be performed using statistical software SPSS V.26.0. The significance level will be set at 0.05.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Ethics Committee of Xijing Hospital in Xi'an, China (KY20222176-X-1), and the trial has been registered on ClinicalTrials.gov. The findings of this trial will be disseminated at academic conferences or published in peer-reviewed scientific journals.
TRIAL REGISTRATION NUMBER
NCT05544110.
Topics: Humans; Stress Disorders, Post-Traumatic; Transcranial Magnetic Stimulation; Magnetic Resonance Imaging; Double-Blind Method; Amygdala; Adult; Male; Randomized Controlled Trials as Topic; Middle Aged; Female; Treatment Outcome; Young Adult
PubMed: 38960463
DOI: 10.1136/bmjopen-2023-081751 -
BMJ Open Jul 2024Oocyte donation (OD) pregnancy is accompanied by a high incidence of hypertensive complications, with serious consequences for mother and child. Optimal care management,...
Development of the DONOR prediction model on the risk of hypertensive complications in oocyte donation pregnancy: study protocol for a multicentre cohort study in the Netherlands.
INTRODUCTION
Oocyte donation (OD) pregnancy is accompanied by a high incidence of hypertensive complications, with serious consequences for mother and child. Optimal care management, involving early recognition, optimisation of suitable treatment options and possibly eventually also prevention, is in high demand. Prediction of patient-specific risk factors for hypertensive complications in OD can provide the basis for this. The current project aims to establish the first prediction model on the risk of hypertensive complications in OD pregnancy.
METHODS AND ANALYSIS
The present study is conducted within the DONation of Oocytes in Reproduction project. For this multicentre cohort study, at least 541 OD pregnancies will be recruited. Baseline characteristics and obstetric data will be collected. Additionally, one sample of maternal peripheral blood and umbilical cord blood after delivery or a saliva sample from the child will be obtained, in order to determine the number of fetal-maternal human leucocyte antigen mismatches. Following data collection, a multivariate logistic regression model will be developed for the binary outcome hypertensive complication 'yes' and 'no'. The Prediction model Risk Of Bias ASsessment Tool will be used as guide to minimise the risk of bias. The study will be reported in line with the 'Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis' guideline. Discrimination and calibration will be determined to assess model performance. Internal validation will be performed using the bootstrapping method. External validation will be performed with the 'DONation of Oocytes in Reproduction individual participant data' dataset.
ETHICS AND DISSEMINATION
This study is approved by the Medical Ethics Committee LDD (Leiden, Den Haag, Delft), with protocol number P16.048 and general assessment registration (ABR) number NL56308.058.16. Further results will be shared through peer-reviewed journals and international conferences.
Topics: Humans; Female; Oocyte Donation; Pregnancy; Netherlands; Hypertension, Pregnancy-Induced; Risk Factors; Risk Assessment; Adult; Multicenter Studies as Topic; Cohort Studies; Logistic Models; Research Design
PubMed: 38960461
DOI: 10.1136/bmjopen-2023-079394 -
BMJ Open Jul 2024To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development.
Associations of air pollution exposures in preconception and pregnancy with birth outcomes and infant neurocognitive development: analysis of the Complex Lipids in Mothers and Babies (CLIMB) prospective cohort in Chongqing, China.
OBJECTIVES
To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development.
DESIGN
Cohort study.
SETTING
Eligible women attended six visits in the maternity clinics of two centres, the First Affiliated Hospital of Chongqing Medical University and Chongqing Health Centre for Women and Children.
PARTICIPANTS
Women who were between 20 and 40 years of age and were at 11-14 weeks gestation with a singleton pregnancy were eligible for participation. Women were excluded if they had a history of premature delivery before 32 weeks of gestation, maternal milk allergy or aversion or severe lactose intolerance. 1273 pregnant women enrolled in 2015-2016 and 1174 live births were included in this analysis.
EXPOSURES
Air pollution concentrations at their home addresses, including particulate matter with diameter ≤2.5 µm (PM) and nitrogen dioxide (NO), during pre-conception and each trimester period were estimated using land-use regression models.
OUTCOME MEASURES
Birth outcomes (ie, birth weight, birth length, preterm birth, low birth weight, large for gestational age and small for gestational age (SGA) status) and neurodevelopment outcomes measured by the Chinese version of Bayley Scales of Infant Development.
RESULTS
An association between SGA and per-IQR increases in NO was found in the first trimester (OR: 1.57, 95% CI: 1.06 to 2.32) and during the whole pregnancy (OR: 1.33, 99% CI: 1.01 to 1.75). Both PM and NO exposure in the 90 days prior to conception were associated with lower Psychomotor Development Index scores (β: -6.15, 95% CI: -8.84 to -3.46; β: -2.83, 95% CI: -4.27 to -1.39, respectively). Increased NO exposure was associated with an increased risk of psychomotor development delay during different trimesters of pregnancy.
CONCLUSIONS
Increased exposures to NO during pregnancy were associated with increased risks of SGA and psychomotor development delay, while increased exposures to both PM and NO pre-conception were associated with adverse psychomotor development outcomes at 12 months of age.
TRIAL REGISTRATION NUMBER
ChiCTR-IOR-16007700.
Topics: Humans; Female; Pregnancy; China; Adult; Infant, Newborn; Prospective Studies; Particulate Matter; Air Pollution; Child Development; Maternal Exposure; Pregnancy Outcome; Young Adult; Nitrogen Dioxide; Infant; Birth Weight; Air Pollutants; Prenatal Exposure Delayed Effects; Premature Birth; Male
PubMed: 38960456
DOI: 10.1136/bmjopen-2023-082475 -
BMJ Open Jul 2024The objective of the study was to assess the clinical predictive value of the dynamics of absolute lymphocyte count (ALC) for 90-day all-cause mortality in sepsis...
OBJECTIVES
The objective of the study was to assess the clinical predictive value of the dynamics of absolute lymphocyte count (ALC) for 90-day all-cause mortality in sepsis patients in intensive care unit (ICU).
DESIGN
Retrospective cohort study using big data.
SETTING
This study was conducted using the Medical Information Mart for Intensive Care IV database V.2.0 database.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome was 90-day all-cause mortality.
PARTICIPANTS
Patients were included if they were diagnosed with sepsis on the first day of ICU admission. Exclusion criteria were ICU stay under 24 hours; the absence of lymphocyte count on the first day; extremely high lymphocyte count (>10×10/L); history of haematolymphatic tumours, bone marrow or solid organ transplants; survival time under 72 hours and previous ICU admissions. The analysis ultimately included 17 329 sepsis patients.
RESULTS
The ALC in the non-survivors group was lower on days 1, 3, 5 and 7 after admission (p<0.001). The ALC on day 7 had the highest area under the curve (AUC) value for predicting 90-day mortality. The cut-off value of ALC on day 7 was 1.0×10/L. In the restricted cubic spline plot, after multivariate adjustments, patients with higher lymphocyte counts had a better prognosis. After correction, in the subgroups with Sequential Organ Failure Assessment score ≥6 or age ≥60 years, ALC on day 7 had the lowest HR value (0.79 and 0.81, respectively). On the training and testing set, adding the ALC on day 7 improved all prediction models' AUC and average precision values.
CONCLUSIONS
Dynamic changes of ALC are closely associated with 90-day all-cause mortality in sepsis patients. Furthermore, the ALC on day 7 after admission is a better independent predictor of 90-day mortality in sepsis patients, especially in severely ill or young sepsis patients.
Topics: Humans; Sepsis; Male; Female; Retrospective Studies; Intensive Care Units; Lymphocyte Count; Middle Aged; Aged; Big Data; Predictive Value of Tests; Hospital Mortality; Prognosis
PubMed: 38960455
DOI: 10.1136/bmjopen-2024-084562 -
BMJ Open Ophthalmology Jul 2024To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors.
METHODS
This prospective, multicentre, randomised, open-label clinical study examined open-angle glaucoma patients who underwent trabeculectomy or trabeculectomy combined with cataract surgery followed by 3-month postoperative ripasudil treatments. After randomly allocating patients to ripasudil-ROCK inhibitor (ripasudil) or without ripasudil (non-ripasudil) groups. Mean intraocular pressure (IOP) changes, success rate, and number of eyedrops were compared for both groups.
RESULTS
A total of 17 and 15 subjects dropped out in the ripasudil group and non-ripasudil group, respectively. At baseline, the mean IOP was 16.8±5.0 mm Hg in the ripasudil group (38 patients) and 16.2±4.4 in the non-ripasudil group (52 patients). The IOP decreased to 11.4±3.2 mm Hg, 10.9±3.9 mm Hg and 10.6±3.5 mm Hg at 12, 24 and 36 months in the ripasudil group, while it decreased to 11.2±4.1 mm Hg, 10.5±3.1 mm Hg and 10.9±3.2 mm Hg at 12, 24 and 36 months in the non-ripasudil group, respectively. There was a significant decrease in the number of IOP-lowering medications after trabeculectomy in the ripasudil group versus the non-ripasudil group at 24 (p=0.010) and 36 months (p=0.016). There was no statistically significant difference between the groups for the 3-year cumulative probability of success.
CONCLUSION
Although ripasudil application did not increase the primary trabeculectomy success rate, it did reduce IOP-lowering medications after trabeculectomy with mitomycin C.
Topics: Humans; Trabeculectomy; Male; Intraocular Pressure; Prospective Studies; Female; Glaucoma, Open-Angle; Isoquinolines; Aged; Sulfonamides; Mitomycin; Middle Aged; rho-Associated Kinases; Treatment Outcome; Alkylating Agents
PubMed: 38960415
DOI: 10.1136/bmjophth-2023-001449 -
The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway.Journal of Advanced Research Jul 2024Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular...
INTRODUCTION
Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated.
OBJECTIVES
This research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma.
METHODS
The amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules.
RESULTS
The upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4.
CONCLUSION
Our findings provide evidence for the role of VSIG4 as a cancer-promoting gene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.
PubMed: 38960279
DOI: 10.1016/j.jare.2024.06.023 -
Journal of Advanced Research Jul 2024Growing interest toward RNA modification in cancer has inspired the exploration of datasets related to multiple RNA modifications. However, a comprehensive elucidation...
INTRODUCTION
Growing interest toward RNA modification in cancer has inspired the exploration of datasets related to multiple RNA modifications. However, a comprehensive elucidation of the clinical value of various RNA modifications in breast cancer is still lacking.
OBJECTIVES
This study aimed to provide a strategy based on RNA modification-related genes for predicting therapy response and survival outcomes in breast cancer patients.
METHODS
Genes related to thirteen RNA modification patterns were integrated for establishing a nine-gene-containing signature-RMscore. Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. The biological function of key RMscore-related molecules was investigated by cellular experiments in vitro and in vivo, using flow cytometry, immunohistochemistry and immunofluorescence staining.
RESULTS
This study has raised an effective therapy strategy for breast cancer patients after a well-rounded investigation of RNA modification-related genes. With a great performance of predicting patient prognosis, high levels of the RMscore proposed in this study represented suppressive immune microenvironment and therapy resistance, including adjuvant chemotherapy and PD-L1 blockade treatment. As the key contributor of the RMscore, inhibition of WDR4 impaired breast cancer progression significantly in vitro and in vivo, as well as participated in regulating cell cycle and mTORC1 signaling pathway via m7G modification.
CONCLUSION
Briefly, this study has developed promising and effective tactics to achieve the prediction of survival probabilities and treatment response in breast cancer patients.
PubMed: 38960276
DOI: 10.1016/j.jare.2024.06.029 -
The Journal of Biological Chemistry Jul 2024Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial...
Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial injury. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that acts in combination with different receptors in the kidney. Here, we analyzed the tubular expression of TSP-1 and its receptor integrin β3 (ITGB3) in FSGS. Previously the renal interstitial chip analysis of FSGS patients with tubular interstitial injury showed that the expressions of TSP-1 and ITGB3 were up-regulated. We found that the level of TSP-1 and ITGB3 increased in the tubular cells of FSGS patients. The serum level of TSP-1 increased and was correlated to the degree of tubulointerstitial lesions in FSGS patients. THBS1/ITGB3 signaling induced renal tubular injury in HK-2 cells exposure to BSA and the ADR-induced nephropathy model. THBS1 knockout ameliorated tubular injury and renal fibrosis in ADR-treated mice. THBS1 knockdown decreased the expression of KIM-1 and caspase 3 in the HK-2 cells treated with BSA, while THBS1 overexpression could induce tubular injury. In vivo, we identified cyclo-RGDfK as an agent to block the binding of TSP-1 to ITGB3. Cyclo-RGDfK treatment could alleviate ADR-induced renal tubular injury and interstitial fibrosis in mice. Moreover, TSP-1 and ITGB3 were colocalized in tubular cells of FSGS patients and ADR-treated mice. Taken together, our data showed that TSP-1/ITGB3 signaling contributed to the development of renal tubulointerstitial injury in FSGS, potentially identifying a new therapeutic target for FSGS.
PubMed: 38960036
DOI: 10.1016/j.jbc.2024.107516