-
Health Technology Assessment... Apr 2024Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both...
BACKGROUND
Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice.
OBJECTIVES
1. Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. 2. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. 3. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities.
METHODS
The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: • Stage 1A - we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. • Stage 1B - we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. • Stage 2 - we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates.
RESULTS
Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting.
CONCLUSIONS
Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs.
FUTURE WORK
Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting.
LIMITATIONS
Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates.
TRIAL REGISTRATION
This trial is registered as ISRCTN10491361.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in ; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Diphosphonates; Alendronate; Zoledronic Acid; Osteoporotic Fractures; Osteoporosis
PubMed: 38634483
DOI: 10.3310/WYPF0472 -
Frontiers in Neurology 2024Epilepsy is one of the most common serious chronic neurological disorders, which can have a serious negative impact on individuals, families and society, and even death....
BACKGROUND
Epilepsy is one of the most common serious chronic neurological disorders, which can have a serious negative impact on individuals, families and society, and even death. With the increasing application of machine learning techniques in medicine in recent years, the integration of machine learning with epilepsy has received close attention, and machine learning has the potential to provide reliable and optimal performance for clinical diagnosis, prediction, and precision medicine in epilepsy through the use of various types of mathematical algorithms, and promises to make better parallel advances. However, no bibliometric assessment has been conducted to evaluate the scientific progress in this area. Therefore, this study aims to visually analyze the trend of the current state of research related to the application of machine learning in epilepsy through bibliometrics and visualization.
METHODS
Relevant articles and reviews were searched for 2004-2023 using Web of Science Core Collection database, and bibliometric analyses and visualizations were performed in VOSviewer, CiteSpace, and Bibliometrix (R-Tool of R-Studio).
RESULTS
A total of 1,284 papers related to machine learning in epilepsy were retrieved from the Wo SCC database. The number of papers shows an increasing trend year by year. These papers were mainly from 1,957 organizations in 87 countries/regions, with the majority from the United States and China. The journal with the highest number of published papers is EPILEPSIA. Acharya, U. Rajendra (Ngee Ann Polytechnic, Singapore) is the authoritative author in the field and his paper "Deep Convolutional Neural Networks for Automated Detection and Diagnosis of Epileptic Seizures Using EEG Signals" was the most cited. Literature and keyword analysis shows that seizure prediction, epilepsy management and epilepsy neuroimaging are current research hotspots and developments.
CONCLUSIONS
This study is the first to use bibliometric methods to visualize and analyze research in areas related to the application of machine learning in epilepsy, revealing research trends and frontiers in the field. This information will provide a useful reference for epilepsy researchers focusing on machine learning.
PubMed: 38628694
DOI: 10.3389/fneur.2024.1374443 -
BMC Pediatrics Apr 2024Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis.
METHODS
Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach.
RESULTS
Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects.
CONCLUSIONS
This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training.
TRIAL REGISTRATION
The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.
Topics: Child; Adolescent; Humans; Cystic Fibrosis; Quality of Life; Breathing Exercises; Chronic Disease; Respiratory Muscles
PubMed: 38622583
DOI: 10.1186/s12887-024-04726-x -
BMJ Open Apr 2024To compare the characteristics of patients with type 2 diabetes mellitus in general practice and those included in randomised controlled trials on which clinical...
OBJECTIVES
To compare the characteristics of patients with type 2 diabetes mellitus in general practice and those included in randomised controlled trials on which clinical practice guidelines are based.
DESIGN
Cross-sectional comparative study.
SETTING
We asked 45 general practitioners from three French Departments to identify the 15 patients with type 2 diabetes mellitus they most recently saw in consultation. In parallel, we selected randomised controlled trials included in the Cochrane systematic review on which the clinical practice guidelines for type 2 diabetes mellitus were based.
PARTICIPANTS
We included 675 patients with type 2 diabetes mellitus, and data were collected from 23 randomised controlled trials, corresponding to 36 059 patients.
OUTCOME MEASURES
Characteristics of general-practice patients were extracted from medical records by a unique observer. The same baseline characteristics of patients included in randomised controlled trials from the Cochrane systematic review were extracted and meta-analysed. We assessed standardised differences between these two series of baseline characteristics. A difference greater than 0.10 in absolute value was considered meaningful.
RESULTS
General-practice patients were older than randomised controlled trial patients (mean (SD) 68.8 (1.1) vs 59.9 years (standardised difference 0.8)) and had a higher body mass index (mean (SD) 31.5 (6.9) vs 28.2 kg/m (standardised difference 0.5)) but smoked less (11.0% vs 29.3% (standardised difference -0.6)). They more frequently used antihypertensive drugs (82.1% vs 37.5% (standardised difference 1.2)) but less frequently had a myocardial infarction (7.6% vs 23.1% (standardised difference -1.1)).
CONCLUSIONS
Patients with type 2 diabetes mellitus cared for in general practice differ in a number of important aspects from patients included in randomised controlled trials on which clinical practice guidelines are based. This situation hampers the applicability of these guidelines. Future randomised trials should include patients who better fit the 'average' general-practice patient with type 2 diabetes mellitus to help improve the translation of study findings in daily practice.
Topics: Humans; Diabetes Mellitus, Type 2; Cross-Sectional Studies; General Practice; Randomized Controlled Trials as Topic
PubMed: 38604640
DOI: 10.1136/bmjopen-2023-077582 -
Experimental Gerontology Jun 2024Large scale population norms for peak oxygen uptake (VO) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper... (Review)
Review
BACKGROUND
Large scale population norms for peak oxygen uptake (VO) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper body functional capacity has an important role in activities of daily living far less is known regarding the effect of age and sex on upper body functional capacity (i.e. arm crank ergometry; ACE). The aim of this review was to determine the effect of age and sex on VO obtained during ACE and CE in the same participants.
METHOD
The review was pre-registered with PROSEPERO (Ref: CRD42022349566). A database search using Academic Search Complete including CINAHL complete, CINHAL Ultimate, Medline, PubMed, SPORTDiscus was undertaken.
RESULTS
The initial search yielded 460 articles which was reduced to 243 articles following removal of duplicates. Twenty-five articles were subsequently excluded based on title resulting in 218 articles considered for retrieval. Following review of the abstracts, 78 further articles were excluded leaving 140 to be assessed for eligibility. Eighty-five articles were subsequently excluded, resulting in 55 articles being included. The decrease in VO with age during CE was consistent with previous studies. Decreases in VO during ACE with age, although paralleling those of CE, appeared to be of greater functional importance. When changes in VO were considered below the age of 50 years little change was observed for absolute VO during ACE and CE. In contrast, relative VO demonstrated decreases in VO for both ACE and CE likely reflecting increases in body mass and body fat percentage with age. After 50 years of age absolute and relative VO demonstrated more similar and subtle responses. Heterogeneity across studies for both absolute and relative VO between ACE and CE was large. Although strict inclusion criteria were applied, the inter-individual variation in sample populations was likely the main source of heterogeneity. There was a considerable lack data sets available for ages above 40 years of age.
CONCLUSIONS
These responses suggest that upper body VO decreases in line with that of the lower body but, due to the lower peak values achieved during ACE, decreases in VO may have more profound functional impact compared to that for the lower body. Using absolute and relative measures of VO results in different age-related profiles when considered below 50 years of age. To further our understanding of whole body ageing more data is required for participants in mid and later life. The association between VO and underlying physiological factors with age needs to be studied further, particularly in conjunction with activities of daily living and independent living.
Topics: Humans; Oxygen Consumption; Age Factors; Exercise; Female; Male; Sex Factors; Aging; Exercise Test; Aged; Middle Aged; Adult
PubMed: 38604251
DOI: 10.1016/j.exger.2024.112427 -
NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
International Journal of Biological... May 2024Corneal blindness is commonly treated through corneal replacement with allogeneic corneal donors, which may face shortage. Regarding this issue, xenogeneic alternatives... (Review)
Review
Corneal blindness is commonly treated through corneal replacement with allogeneic corneal donors, which may face shortage. Regarding this issue, xenogeneic alternatives are explored. Fish scale-derived scaffolds (FSSs) are among the alternatives due to the lower risk of infection and abundant sources of raw materials. Unfortunately, the information about mechanical, optical, chemical, and biological performances of FSSs for corneal replacements is still scattered, as well as about the fabrication techniques. This study aims to gather scattered pieces of information about the mentioned performances and fabrication techniques of FSSs for corneal replacements. Sorted from four scientific databases and using the PRISMA checklist, eleven relevant articles are collected. FSSs are commonly fabricated using decellularization and decalcification processes, generating FSSs with parallel multilayers or crossed fibers with topographic microchannels. In the collected studies, similar mechanical properties of FSSs to native tissues are discovered, as well as good transparency, light remittance, but poorer refractive indexes than native tissues. Biological evaluations mostly discuss histology, cell proliferations, and immune responses on FSSs, while only a few studies examine the vascularization. No studies completed comprehensive evaluations on the four properties. The current progress of FSS developments demonstrates the potential of FSS use for corneal replacements.
Topics: Animals; Tissue Scaffolds; Cornea; Humans; Corneal Transplantation; Animal Scales; Fishes; Tissue Engineering
PubMed: 38580016
DOI: 10.1016/j.ijbiomac.2024.131183 -
Frontiers in Oncology 2024Breast cancer is the leading cause of cancer-related fatalities among women worldwide. Conventional screening and risk prediction models primarily rely on demographic...
BACKGROUND
Breast cancer is the leading cause of cancer-related fatalities among women worldwide. Conventional screening and risk prediction models primarily rely on demographic and patient clinical history to devise policies and estimate likelihood. However, recent advancements in artificial intelligence (AI) techniques, particularly deep learning (DL), have shown promise in the development of personalized risk models. These models leverage individual patient information obtained from medical imaging and associated reports. In this systematic review, we thoroughly investigated the existing literature on the application of DL to digital mammography, radiomics, genomics, and clinical information for breast cancer risk assessment. We critically analyzed these studies and discussed their findings, highlighting the promising prospects of DL techniques for breast cancer risk prediction. Additionally, we explored ongoing research initiatives and potential future applications of AI-driven approaches to further improve breast cancer risk prediction, thereby facilitating more effective screening and personalized risk management strategies.
OBJECTIVE AND METHODS
This study presents a comprehensive overview of imaging and non-imaging features used in breast cancer risk prediction using traditional and AI models. The features reviewed in this study included imaging, radiomics, genomics, and clinical features. Furthermore, this survey systematically presented DL methods developed for breast cancer risk prediction, aiming to be useful for both beginners and advanced-level researchers.
RESULTS
A total of 600 articles were identified, 20 of which met the set criteria and were selected. Parallel benchmarking of DL models, along with natural language processing (NLP) applied to imaging and non-imaging features, could allow clinicians and researchers to gain greater awareness as they consider the clinical deployment or development of new models. This review provides a comprehensive guide for understanding the current status of breast cancer risk assessment using AI.
CONCLUSION
This study offers investigators a different perspective on the use of AI for breast cancer risk prediction, incorporating numerous imaging and non-imaging features.
PubMed: 38571502
DOI: 10.3389/fonc.2024.1343627 -
Medicina (Kaunas, Lithuania) Mar 2024: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA...
: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15-22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs-onto which the miRNAs hybridize-are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. : We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string "Endometrial Neoplasms AND Exosomes", and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. : Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls-relative expression ≥ 1 > 3 log2(ratio)-were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. : Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.
Topics: Female; Humans; Embryo Implantation; Endometrial Neoplasms; Endometrium; Epigenesis, Genetic; MicroRNAs; Tumor Microenvironment
PubMed: 38541212
DOI: 10.3390/medicina60030486 -
Gynecological Endocrinology : the... Dec 2024To synthesize the primary evidence on the efficacy and safety of visnadine on symptoms of sexual dysfunction (SD) in heterosexual women.
OBJECTIVE
To synthesize the primary evidence on the efficacy and safety of visnadine on symptoms of sexual dysfunction (SD) in heterosexual women.
METHODS
We conducted a systematic review of randomized clinical trials (RCTs) with a primary search without language restriction in PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, and international clinical trial registries. Trials reporting the use of visnadine by any route in women with SD were eligible. We performed screening, data extraction, and risk of bias assessment in a double-blind approach. The primary outcomes were the Female Sexual Function Index (FSFI) and its domains. Secondary outcomes were safety, arousal, lubrication, pleasure, orgasm, negative sensations, duration, and overall satisfaction.
RESULTS
Initially, 242 records were retrieved. We selected nine papers for full-text reading and finally included two RCTs: one with a parallel design and one with a crossover design with a total of 96 patients. One study compared visnadine aerosol with a placebo, while the other compared different frequencies of visnadine aerosol use. Visnadine use showed a statistically significant improvement ( < 0.05) in overall FSFI scores, regardless of the frequency of use. A meta-analysis was not possible due to the high clinical and methodological heterogeneity between available studies.
CONCLUSION
RCTs regarding the use of visnadine for the Female SD are scarce and methodologically limited. This preliminary evidence shows visnadine as a potentially effective and safe option to alleviate some of the clinical symptoms of SD in heterosexual women. However, future better-designed randomized studies with larger sample numbers are required.
Topics: Female; Humans; Heterosexuality; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Aerosols; Chromans
PubMed: 38528806
DOI: 10.1080/09513590.2024.2328619