Clinical Observational Studies Research Articles

Pregnancy-Associated Plasma Protein-A and Free β-Human Chorionic Gonadotrophin in Relation with Oxidative Stress in Obese Pregnant Women: A Clinical Cross-Sectional Study

Background: The pathophysiological mechanism underlying pregnancy complications is not entirely known. Although it is currently impossible to predict the occurrence of redox imbalance, it is possible to identify women with a high or medium risk of developing this disease prior to a negative outcome by non-invasive diagnostic methods. The Aim: This study aimed to examine the possible role of the parameter of oxidative stress (OS) measured in early pregnancy in the screening/treatment of obesity and its complications during pregnancy. Methods: This research was designed as a prospective observational cross-sectional clinical study which included 40 non-obese and 31 obese pregnant women between 11 and 13 g.w. who were managed in the Department of Obstetrics, University Clinical Center Kragujevac in Serbia. We collected anthropometric and clinical indicators, maternal and pregnancy factors, and measured prooxidative parameters from blood samples. Results: We observed significantly increased levels of the superoxide anion radical, hydrogen peroxide and the index of lipid peroxidation in the Obese group in comparison with the Non-Obese group and significantly decreased bioavailability of nitrites in the Obese group in comparison with the Non-Obese group. Conclusions: The determination of systemic parameters of OS in early pregnancy could be a good methodological approach in the screening/treatment of obesity during pregnancy and this approach should be followed for the screening of endothelial dysfunction in pregnancy which needs further monitoring and/or treatment.

The impact of sex on HIV immunopathogenesis and therapeutic interventions.

Globally, the majority of people living with HIV are women or girls, but they have been a minority of participants in clinical trials and observational studies of HIV. Despite this underrepresentation, differences in the pathogenesis of HIV have been observed between men and women, with contributions from both gender- and sex-based factors. These include differences in the risk of HIV acquisition, in viral load set point and immune activation in responses to viremia, and differences in HIV reservoir maintenance. These differences obligate adequate study in both males and females in order to optimize treatments, but also provide a powerful leverage point for delineating the mechanisms of HIV pathogenesis. The shifts in exposure to sex steroid hormones across a lifespan introduce additional complexity, which again can be used to focus on either genetic or hormonal influences as the driver of an outcome. In this Review, we discuss consistent and reproducible differences by sex across the spectrum of HIV, from acquisition through pathogenesis, treatment, and cure, and explore potential mechanisms and gaps in knowledge.

Less is more? A review of psilocybin microdosing.

The applications of psilocybin, derived from 'magic mushrooms,' are vast, including a burgeoning practice known as microdosing, which refers to the administration of sub-hallucinogenic doses of psychedelic substances to obtain benefits without experiencing significant cognitive and perceptual distortion. However, current research is fairly new with several limitations and gaps that hinder adequate conclusions on its efficacy. This semi-structured review aimed to identify and highlight research gaps in the field of psilocybin microdosing for future research. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses based strategy was employed, utilizing a chain of keywords and key phrases across multiple databases, augmented by a cross-sectional Google search for relevant grey literature in the form of the top 10 search results. A total of 40 studies and 8 unique websites were identified, summarized and tabulated into four distinct categories, namely non-clinical, clinical, observational and anecdotal evidence. The majority of available evidence originates from observational studies, while non-clinical and clinical study findings remain comparatively sparse and inconsistent. Web-based findings were consistent with current research findings. Key research gaps were highlighted: the imperative for more randomized placebo-controlled trials, exploration of dose-response ranges, psychological and personality testing of participants, utilization of active placebos, greater diversity in study populations, an increase in psilocybin-exclusive microdosing studies and the refinement of animal models. Definitive conclusions regarding the efficacy of psilocybin microdosing remain elusive, emphasizing the need for further study. Numerous research gaps necessitate consideration for future investigations.

Advancements in radiosurgery for the treatment of arteriovenous malformations

Arteriovenous malformations (AVMs) are complex vascular anomalies with high risks of hemorrhage and neurological deficits. The evolution of stereotactic radiosurgery (SRS) represents a significant advancement in their management, offering a less invasive alternative to traditional surgical approaches. This study aims to evaluate recent developments in SRS techniques for treating AVMs by conducting an integrative literature review. Utilizing the PICO strategy, a systematic search was performed across databases like LILACS, MEDLINE, and SCIELO, focusing on clinical trials, observational studies, meta-analyses, and systematic reviews. The analysis revealed that while microsurgical excision remains a definitive approach, SRS—particularly with advanced systems like Gamma Knife, Linac, CyberKnife, and Zap-X—has shown promising results in reducing hemorrhage rates and lesion volumes with lower complications. The findings indicate that SRS, bolstered by improved imaging and radiation precision, provides a viable alternative to invasive methods, though its effectiveness varies among different systems. This review underscores the need for a multidisciplinary approach in AVM management, emphasizing tailored treatment strategies based on lesion characteristics and patient-specific factors.

Which Interventions Are Effective in Treating Sleep Disturbances After THA or TKA? A Systematic Review.

Poor sleep quality is a common complaint after total joint arthroplasty (TJA), and it is associated with reports of higher pain and worse functional outcomes. Several interventions have been investigated with the intent to reduce the incidence of postoperative sleep disturbance with varying effectiveness. An aggregate of the best available evidence, along with an evaluation of the quality of those studies, is needed to provide valuable perspective to physicians and to direct future research. In this systematic review, we asked: (1) What is the reported efficacy of the most commonly studied medications and nonpharmacologic approaches, and (2) what are their side effects and reported complications? This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search using a combination of controlled vocabulary and keywords was performed utilizing Medline (Ovid), Embase (Ovid), Cochrane Central, and Web of Science databases from database inception to 2023, with the last search occurring October 24, 2023, to identify studies that evaluated a sleep intervention on the effect of patient-reported sleep quality after THA or TKA. Inclusion criteria were clinical trials, comparative studies, and observational studies on adult patients who underwent primary TKA or THA for osteoarthritis and who completed validated sleep questionnaires to assess sleep quality postoperatively. We excluded studies on patients younger than 18 years, patients with sleep apnea, TKA or THA because of trauma or conditions other than osteoarthritis, revision TJA, studies in languages other than English, and studies from nonindexed journals or preprint servers. Two investigators independently screened 1535 studies for inclusion and exclusion criteria and extracted data from the included studies. Ultimately, 14 studies were included in this systematic review, including 12 randomized controlled trials and 2 prospective comparative studies. A total of 2469 participants were included, with a mean ± SD age of 65 ± 7 years and 38% men in control groups and 65 ± 7 years and 39% men in intervention groups. Sleep quality questionnaires utilized included the Pittsburgh Sleep Quality Index, Self-Rating Scale of Sleep, 100-mm VAS - Sleep, Sleep Disturbance Numeric Rating Scale, Likert scales, and one institutionally designed questionnaire. Quality analysis was performed utilizing the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Randomized Controlled Trials, where higher scores of 13 indicated a more reliable study, and the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies, where higher scores of 9 indicated a more reliable study and scores < 5 represented a high risk of bias. Two of the randomized controlled trials scored a 12 of 13, and the remaining 10 met every criteria of the JBI checklist. Both comparative studies scored 5 of 9 possible points of the Newcastle-Ottawa Scale. Melatonin and selective cyclooxygenase-2 inhibitor rofecoxib were found to provide a clinically important benefit to sleep quality within the first postoperative week after TJA. However, rofecoxib was withdrawn from the market globally in 2004 over concerns about increased risk of cardiovascular events. Another cyclooxygenase-2 inhibitor, celecoxib, remains available. No other intervention demonstrated a clinical benefit. Side effects of melatonin include dizziness, headache, paresthesia, and nausea, and it is contraindicated in patients with liver failure, autoimmune conditions, or who are receiving warfarin. Long-term adverse effects of rofecoxib include hypertension, edema, and congestive heart failure, and it is contraindicated in patients with renal insufficiency or who are receiving warfarin. Melatonin is considered safe in older patients, but more caution should be taken with rofecoxib. Owing to limited evidence in support of most of the interventions we studied, none of these interventions can be recommended for routine use after TJA. Melatonin and rofecoxib may provide a benefit to sleep quality in some patients, but physicians need to understand the adverse effects and contraindications before recommending these interventions. Additionally, rofecoxib is no longer commercially available. Future investigation is warranted to evaluate the effectiveness of interventions with minimal side effect profiles for providers to be able to make an informed decision about interventions for sleep improvement after TJA. Level III, therapeutic study.

Assessment of treatment expectations in people with suspected endometriosis: A psychometric analysis

Background Treatment expectations influence clinical outcomes in various physical and psychological conditions; however, no studies have explored their role in endometriosis treatment. It is necessary to understand how these expectations can be measured to study treatment expectations and their effects in clinical practice. This study aimed to psychometrically analyze and compare different treatment expectation measurements and describe treatment expectations in women with suspected endometriosis. Method Analysis of cross-sectional baseline data of a mixed-method clinical observational study of N=699 patients undergoing laparoscopy in Germany. Descriptives, bivariate associations, convergent and discriminant validity of four expectation measurements (Treatment Expectation Questionnaire (TEX-Q); Generic rating scale for previous treatment experiences, treatment expectations, and treatment effects (GEEE); numerical rating scales (NRS) assessing improvement and worsening of endometriosis symptoms, expected Pain Disability Index (PDI); range: 0 to 10) were estimated. A cluster analysis was performed on the three GEEE items. Results Most participants expected high improvement (M=6.68 to 7.20, SD=1.90 to 2.09) and low worsening (M=1.09 to 2.52, SD=1.80 to 2.25) of disability from laparoscopy. Participants who expected greater worsening expected more side effects (r=.31 to .60, p&lt;.001). Associations between the positive and negative expectation dimensions, including side effects, were small to non-significant (r =|.24| to .00, p&lt;.001 to.978). Four distinct clusters, described as’positive’, ‘no pain, no gain’, ‘diminished’, and ‘uniform’ were found, with a total PVE of 62.2%. Conclusions Women with suspected endometriosis reported positive expectations concerning laparoscopy, but wide ranges indicated interindividual differences. Treatment expectations seem to be a multidimensional construct in this patient group. The investigated measurements did not correlate to the extent that they measured exactly the same construct. The selection of measurements should be carefully considered and adapted for the study purposes. Clusters provide initial indications for individualized interventions that target expectation manipulation. Trial Registration Number ID NCT05019612 (ClinicalTrials.gov)

Nanotechnology and Its Application in Dentistry: A Systematic Review of Recent Advances and Innovations.

Background: This study looks at the clinical applications of nanotechnology in dentistry, with an emphasis on implantology, preventive care, orthodontics, restorative dentistry, and endodontics. Methods: Following PRISMA criteria and registered in PROSPERO (ID: CRD 564245), a PubMed, Scopus, and Web of Science search was conducted for studies from January 2014 to April 2024. The criteria were English-language research on nanotechnology in dental coatings, with a focus on clinical trials and observational studies. The electronic database search yielded 8881 publications. Following the screening process, 17 records were selected for qualitative analysis. Results: Nanotechnology has revolutionized dentistry. In orthodontics, nanoparticles improve antibacterial characteristics, durability, and biocompatibility, lowering bacterial colonization and plaque. In preventative care, Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) combined with stannous fluoride (SnF2) and nano-sized sodium trimetaphosphate (TMPnano) substantially remineralizes enamel. Nanostructured surfaces in dental implants, particularly those containing calcium, improve osseointegration and stability. Nanoparticles in restorative dentistry improve composite and adhesive strength, aesthetics, and longevity. Conclusions: Nanotechnology improves dental materials and equipment, resulting in better treatment outcomes and increased patient comfort. Its integration provides more effective treatments, which improves dental care and patient outcomes. More research is needed to overcome present problems and expand nanotechnology's medicinal applications.

Hyperlipidemia negatively impacts implantation by dysregulating tight junction and Claudin-3 and Claudin-4 expression in the endometrium

Clinical observational studies have suggested hyperlipidemia may disturb embryo implantation through endometrium; however, the mechanism has been unclear. With its profound implications for reproductive health, the present study aims to investigate whether hyperlipidemia affects endometrial epithelial cell tight junctions for implantation failures. By constructing hyperlipidemia mice model, the number and distribution of embryo implantation status were investigated after both natural mating and in vitro fertilization and embryo transfer (IVF-ET). Transmission electron microscopy (TEM) was used to compare the ultrastructure of tight junctions in endometrial endothelial cells. Western blot and immunofluorescence were used to explore the expression and localization of tight junction proteins, such as Claudin (CDLN)3, CLDN4, occludin (OCLN), and zonula occludens-1 (ZO1). For women with reproductive failure, mid-luteal phase endometrial tissues were collected, and gene expression of tight junction proteins was investigated using RNA sequencing and qRT-PCR. In hyperlipidemic mice, the number of embryo implantation sites significantly decreased with uneven distribution after natural mating and IVF-ET. Disrupted tight junctions were found, characterized by a decreased number of tight junctions by TEM, downregulated expressions of CDLN4, OCLN, and ZO1, and an increased expression of CLDN3 by western blot. In hyperlipidemic women with reproductive failure, the dysregulated expression of CLDN3 and CLDN4 was also present in the luteal phase endometrium. In this study, evaluation of both animal models and infertile women in vivo demonstrated that hyperlipidemia reduced female fertility, accompanied by disruption of tight junction structures and dysregulation of CLDN3 and CLDN4 expression in the endothelial cells of luteal phase endometrium.

The causal association between gut microbiota and postpartum depression: a two-sample Mendelian randomization study.

An escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD. Summary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings. We identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD. The GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders. Based on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders.

The safety of a dolutegravir (DTG)-based antiretroviral treatment (ART) regimen for pregnancy and birth outcomes in Ethiopia: evidence from multicenter cohort study

BackgroundA dolutegravir (DTG)-based antiretroviral regimen has been rolled out for pregnant women in low- and middle-income countries since 2020. However, available safety data are limited to a few clinical trials and observational studies. Hence, we present real-world pregnancy and birth outcome safety data from a large sample multicenter cohort study in Ethiopia.MethodsA retrospective cohort study was conducted in fourteen hospitals across Ethiopia from 2017 to 2022. HIV-infected pregnant women were followed from the date of prevention of mother-to-child transmission (PMTCT) care enrolment until the infant was 6–8 weeks old. The primary safety outcome was a composite of adverse pregnancy events comprising spontaneous abortion, intrauterine fetal death (IUFD) before onset of labor, preterm birth, and maternal death. Additionally, a composite adverse birth outcome was assessed, comprising intrapartum fetal demise, low birth weight, and neonatal death. Finally, a composite of adverse pregnancy or birth outcome was also investigated. The exposure of interest was the antiretroviral treatment (ART) regimen used during pregnancy for PMTCT of HIV.ResultsDuring the study period, 2643 women were enrolled in routine PMTCT care. However, 2490 (92.2%) participants were eligible for the study. A total of 136/1724 (7.9%, 95% CI: 6.7–9.3%) women experienced adverse pregnancy outcomes. Fewer women in the DTG-based group (5.4%, 95% CI: 3.7–7.5%) had adverse pregnancy outcomes than in the Efavirenz (EFV)-based group (8.3%, 95% CI: 6.6–10.3%), P = 0.004. After controlling for baseline differences, the DTG group had a 43% lower risk of adverse pregnancy outcomes (adjusted odd ratio (AOR), 0.57; 95% CI, 0.32–0.96%) and a 53% lower risk of preterm birth (AOR, 0.47; 95% CI, 0.22–0.98%) compared to the EFV group. A total of 103/1616 (6.4%, 95% CI: 5.2–7.7%) women had adverse birth outcomes. Although the difference was not statistically significant, fewer women in the DTG group (30/548; 5.5%, 95% CI: 3.7–7.7%) than in the EFV group (57/830; 6.9%, 95% CI: 5.2–8.8%) had adverse birth outcomes.ConclusionsIn this study, we observed that DTG-based regimens were associated with better pregnancy and birth outcome safety profiles, reaffirming the WHO recommendation. However, a prospective study is recommended to assess uncaptured maternal and perinatal adverse outcomes, such as congenital abnormalities, and infant growth and neurocognitive development.

Effectiveness of dose-intensified salvage regimens versus standard-dose chemotherapy for progression-free survival in early progressed follicular lymphoma before autologous stem cell transplantation: a systematic review protocol.

This review will evaluate the effectiveness of dose-intensified versus standard-dose salvage regimens on progression-free survival in early progressed follicular lymphoma before high-dose chemotherapy and autologous stem cell transplantation. Despite the substantial advances in the management of follicular lymphoma, approximately 20% of patients experience progression of the disease within 2 years of induction therapy. These patients have worse outcomes, and autologous stem cell transplantation has been shown to improve outcomes in this context. Little is known about the optimal salvage regimen. Studies must include patients ≥18 years old with early progressed follicular lymphoma who were submitted to autologous stem cell transplantation in subsequent remission. Clinical trials and observational studies will be included. The search strategy will be carried out in MEDLINE (PubMed), Embase (Periódicos CAPES), Scopus, Web of Science, LiLACS, and the Cochrane Library. No date or language restrictions will be imposed. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis will be used. Studies should score at least 50% in accordance with the critical appraisal tool. Data will be pooled whenever possible using the random effects model. Heterogeneity will be assessed using the standard χ 2 and I2 tests. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in the meta-analysis. The GRADE approach will be used to rate certainty of evidence. PROSPERO CRD42022373345.

1373P Measuring PFS in clinical trials and observational studies of patients with NSCLC: A scoping review

1373P Measuring PFS in clinical trials and observational studies of patients with NSCLC: A scoping review

Early alterations of thalami- and hippocampi-cortical functional connectivity as biomarkers of seizures after traumatic brain injury

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx, project 3) is a prospective multicenter clinical observational study to identify early biomarkers of epileptogenesis after moderate-to-severe traumatic brain injury (TBI). We used a seed-based approach applied to acute (i.e., ≤14 days) fMRI imaging data, directly testing the hypothesis that the presence of seizures up to two years following brain trauma is associated with functional changes within hippocampi and thalami-cortical networks. Additionally, we hypothesized that the network connectivity involving thalami and hippocampi circuits underlying early and late-onset seizures would differ. Approximately 30% of the initial dataset was deemed unusable due to MRI issues. Approximately 50% of the enrolled sample was lost to a 2-year follow-up. After preprocessing the fMRI data, approximately 40% of the follow-up sample had to be excluded from the analysis due to excessive in-scanner movements, as assessed by state-of-the-art quality control protocols. Only 37 patients provided data that was suitable for the seed-based analysis. Despite these challenges, the remaining, high-quality data returned noteworthy findings. We identified specific hippocampi and thalami biomarkers associated with both early and late seizures following TBI (p < .05, FWE-corrected at the cluster level). The predictive capability for the development of late seizures after TBI, when adding fMRI data to demographic and clinical data, provided 88% accuracy — an additional 8% improvement compared to using demographic and clinical data alone. Our findings highlight the potential of fMRI for uncovering, in hippocampal and thalamic cortical networks, biomarkers of early and late seizures following TBI. However, they also highlight the important challenges that need to be overcome in order for fMRI to become an effective biomarker and prognostic tool in the intensive care context.

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.

Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

A Clinical Observational Case Series Study Performed to Find out How the Good Health of Mother Before and During Pregnancy Contribute in Giving Birth to a Healthier Baby with the Help of Homeopathic Anti-Miasmatic Medicines

A Clinical Observational Case Series Study Performed to Find out How the Good Health of Mother Before and During Pregnancy Contribute in Giving Birth to a Healthier Baby with the Help of Homeopathic Anti-Miasmatic Medicines

The association between ibuprofen administration in children and the risk of developing or exacerbating asthma: a systematic review and meta-analysis

BackgroundIbuprofen is one of the most commonly used analgesic and antipyretic drugs in children. However, its potential causal role in childhood asthma pathogenesis remains uncertain. In this systematic review, we assessed the association between ibuprofen administration in children and the risk of developing or exacerbating asthma.MethodsWe searched MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and Scopus from inception to May 2022, with no language limits; searched relevant reviews; and performed citation searching. We included studies of any design that were primary empirical peer-reviewed publications, where ibuprofen use in children 0–18 years was reported. Screening was performed in duplicate by blinded review. In total, 24 studies met our criteria. Data were extracted according to PRISMA guidelines, and the risk of bias was assessed using RoB2 and NOS tools. Quantitative data were pooled using fixed effect models, and qualitative data were pooled using narrative synthesis. Primary outcomes were asthma or asthma-like symptoms. The results were grouped according to population (general, asthmatic, and ibuprofen-hypersensitive), comparator type (active and non-active) and follow-up duration (short- and long-term).ResultsComparing ibuprofen with active comparators, there was no evidence of a higher risk associated with ibuprofen over both the short and long term in either the general or asthmatic population. Comparing ibuprofen use with no active alternative over a short-term follow-up, ibuprofen may provide protection against asthma-like symptoms in the general population when used to ease symptoms of fever or bronchiolitis. In contrast, it may cause asthma exacerbation for those with pre-existing asthma. However, in both populations, there were no clear long-term follow-up effects.ConclusionsIbuprofen use in children had no elevated risk relative to active comparators. However, use in children with asthma may lead to asthma exacerbation. The results are driven by a very small number of influential studies, and research in several key clinical contexts is limited to single studies. Both clinical trials and observational studies are needed to understand the potential role of ibuprofen in childhood asthma pathogenesis.

Exploring the etiology of dilated cardiomyopathy using Mendelian randomization.

Observational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach. To investigate the etiology of DCM through Mendelian randomization analysis. Data mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods. The IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744-0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010-1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085-1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference. Titin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet's disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.

Exploring the Efficacy of Homeopathic Medicines in Treating Uterine Fibroids: A Comprehensive Review

Abstract: Introduction: Uterine fibroids are a common gynaecological condition affecting women worldwide, often leading to significant morbidity and impacting quality of life. While conventional treatment options exist, there is growing interest in alternative therapies such as homeopathy. Objective: The objective of this review paper is to assess the effectiveness of homeopathic medicines in treating uterine fibroids through the analysis of recent clinical trials and observational studies, aiming to provide insights into the potential role of homeopathy as a complementary or alternative therapy for uterine fibroids. Methodology: A thorough search of databases such as PubMed, Google Scholar, Scopus, and pertinent medical journals was undertaken to locate recent studies on the efficacy of homeopathic medicines for uterine fibroids. Only studies meeting predefined inclusion criteria, including randomized controlled trials, prospective observational studies, and systematic reviews, were included in the review process. Result: Recent studies investigating the efficacy of homeopathic medicines in treating uterine fibroids consistently demonstrated positive outcomes, including symptom alleviation, reduction in fibroid size, and improved quality of life. Various remedies showed effectiveness across various potencies. Symptom severity scales, including the Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), and Verbal Multidimensional Scoring System (VMSS), were utilized to assess pelvic pain, menstrual bleeding, and discomfort. Quality of life measures like the WHOQOL-BREF scale provided insights into overall well-being. Conclusion: In conclusion, homeopathic medicines show promise as a safe and effective treatment option for uterine fibroids, offering personalized care and improving quality of life. However, more research, including larger trials and long-term studies, is needed to confirm these findings and understand the underlying mechanisms better.

Chronic pelvic pain syndrome in women of reproductive age: An observational cohort clinical ultrasound study

Background. The annual number of new cases of chronic pelvic pain syndrome in women of reproductive age is increasing worldwide. The high prevalence of this condition among the able-bodied female population leads to higher state expenditures on the treatment of this category of patients. New methods of diagnosis and early prophylaxis contribute to reducing economic burden associated with chronic pelvic pain syndrome in women and improving health of the female population as a fundamental demographic factor.Objectives. To determine somatic, obstetric-gynecological, anatomical, and psycho-emotional predictors of chronic pelvic pain syndrome.Methods. An observational cohort clinical and ultrasound study involved 60 patients of reproductive age. The study was conducted on the basis of the clinic for women, Voronezh City Outpatient Clinic No. 1 — clinical base of the Department of Obstetrics and Gynecology No. 2, Voronezh State Medical University named after N. N. Burdenko, Russia. According to clinical and laboratory data, the participants were divided into 2 groups. Group 1 (n = 30) included women of reproductive age without clinical manifestations of chronic pelvic pain syndrome; Group 2 (n = 30) enrolled women of reproductive age clinically diagnosed with chronic pelvic pain.Results. The mean age of the study participants in the main group comprised 27.4 ± 6.30 and 26.3 ± 7.25 years in the control group, p &gt; 0.05. Diseases of gastrointestinal tract, endocrine, cardiovascular, musculoskeletal and urinary systems, as well as neurocirculatory and vegetative disorders prevailed in the structure of somatic pathology in the main group, p &lt; 0.001. Analysis of obstetric and gynecologic anamnesis revealed no statistically significant differences in the incidence of gynecologic pathology in the study groups. However, according to the detailed analysis of the delivery history of the participants, 23 patients of the main group (76 %) and 3 patients (6.6 %) of the control group underwent episiotomy during labor, p &lt; 0.001. The evaluation of the comparison groups in terms of pain component in myofascial syndrome involved the pain rating index, number of selected descriptors, sensory index of the selected descriptors, emotional index of the selected descriptors, and pain intensity. Statistically significant differences were revealed for all of the above indicators, thereby confirming a reliable picture of pathopsychological changes in the compared groups of women. The analysis of the ultrasound parameters of topographic and anatomical relationships demonstrated the relevant change in the following parameters: urethral length, diameter of the external urethral sphincter, angle between the external urethra and the body of the bladder, direct and transverse dimensions of the levator hiatus in the studied groups under the muscle tension.Conclusion. An issue of early diagnosis and prophylaxis of chronic pelvic pain syndrome in women of reproductive age remains urgent and requires interdisciplinary participation of medical specialists. The development of new approaches to ultrasound evaluation of pelvic floor will increase the effectiveness of therapeutic and prophylactic measures and reduce the economic burden of this nosology in the morbidity structure of the able-bodied female population.

Long-Term Assessment (5 to 19-Year Follow-up) of the Incisal Level Changes in Single Implants Placed in the Anterior Maxillary Region. An Observational Clinical Study.

Long-Term Assessment (5 to 19-Year Follow-up) of the Incisal Level Changes in Single Implants Placed in the Anterior Maxillary Region. An Observational Clinical Study.