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The European Respiratory Journal Dec 2023There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS.
METHODS
We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo.
RESULTS
Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control.
CONCLUSIONS
Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.
Topics: Adolescent; Child; Humans; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Drug Therapy, Combination; Leukotriene Antagonists; Network Meta-Analysis; Systematic Reviews as Topic; Theophylline
PubMed: 37945034
DOI: 10.1183/13993003.01011-2023 -
Neuroscience and Biobehavioral Reviews Jan 2024Mothers exposed to infections during pregnancy disproportionally birth children who develop autism and schizophrenia, disorders associated with altered GABAergic... (Review)
Review
Mothers exposed to infections during pregnancy disproportionally birth children who develop autism and schizophrenia, disorders associated with altered GABAergic function. The maternal immune activation (MIA) model recapitulates this risk factor, with many studies also reporting disruptions to GABAergic interneuron expression, protein, cellular density and function. However, it is unclear if there are species, sex, age, region, or GABAergic subtype specific vulnerabilities to MIA. Furthermore, to fully comprehend the impact of MIA on the GABAergic system a synthesised account of molecular, cellular, electrophysiological and behavioural findings was required. To this end we conducted a systematic review of GABAergic interneuron changes in the MIA model, focusing on the prefrontal cortex and hippocampus. We reviewed 102 articles that revealed robust changes in a number of GABAergic markers that present as gestationally-specific, region-specific and sometimes sex-specific. Disruptions to GABAergic markers coincided with distinct behavioural phenotypes, including memory, sensorimotor gating, anxiety, and sociability. Findings suggest the MIA model is a valid tool for testing novel therapeutics designed to recover GABAergic function and associated behaviour.
Topics: Male; Pregnancy; Female; Animals; Child; Humans; Rodentia; Interneurons; Prefrontal Cortex; Mothers; Behavior, Animal; Disease Models, Animal; Prenatal Exposure Delayed Effects
PubMed: 38042358
DOI: 10.1016/j.neubiorev.2023.105488 -
Journal of Personalized Medicine Jul 2023COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a... (Review)
Review
COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR "deep gray matter" OR "cortical thickness" OR caudate OR striatum OR accumbens OR putamen OR "regions of interest" OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.
PubMed: 37511753
DOI: 10.3390/jpm13071140 -
Acta Otorhinolaryngologica Italica :... Apr 2024Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most... (Review)
Review
INTRODUCTION
Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated.
OBJECTIVE
To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability.
MATERIALS AND METHODS
Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed.
RESULTS
BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety.
CONCLUSIONS
BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.
Topics: Humans; Randomized Controlled Trials as Topic; Administration, Intranasal; Rhinitis; Sinusitis; Beclomethasone; Adrenal Cortex Hormones; Glucocorticoids; Chronic Disease
PubMed: 38651550
DOI: 10.14639/0392-100X-N2745 -
International Journal of Bipolar... May 2024Bipolar disorder (BD) is a severe psychiatric disorder characterized by changes in mood that alternate between (hypo) mania or depression and mixed states, often...
BACKGROUND
Bipolar disorder (BD) is a severe psychiatric disorder characterized by changes in mood that alternate between (hypo) mania or depression and mixed states, often associated with functional impairment and cognitive dysfunction. But little is known about biomarkers that contribute to the development and sustainment of cognitive deficits. The aim of this study was to review the association between neurocognition and biomarkers across different mood states.
METHOD
Search databases were Web of Science, Scopus and PubMed. A systematic review was carried out following the PRISMA guidelines. Risk of bias was assessed with the Newcastle-Ottawa Scale. Studies were selected that focused on the correlation between neuroimaging, physiological, genetic or peripheral biomarkers and cognition in at least two phases of BD: depression, (hypo)mania, euthymia or mixed. PROSPERO Registration No.: CRD42023410782.
RESULTS
A total of 1824 references were screened, identifying 1023 published articles, of which 336 were considered eligible. Only 16 provided information on the association between biomarkers and cognition in the different affective states of BD. The included studies found: (i) Differences in levels of total cholesterol and C reactive protein depending on mood state; (ii) There is no association found between cognition and peripheral biomarkers; (iii) Neuroimaging biomarkers highlighted hypoactivation of frontal areas as distinctive of acute state of BD; (iv) A deactivation failure has been reported in the ventromedial prefrontal cortex (vmPFC), potentially serving as a trait marker of BD.
CONCLUSION
Only a few recent articles have investigated biomarker-cognition associations in BD mood phases. Our findings underline that there appear to be central regions involved in BD that are observed in all mood states. However, there appear to be underlying mechanisms of cognitive dysfunction that may vary across different mood states in BD. This review highlights the importance of standardizing the data and the assessment of cognition, as well as the need for biomarkers to help prevent acute symptomatic phases of the disease, and the associated functional and cognitive impairment.
PubMed: 38758506
DOI: 10.1186/s40345-024-00340-z -
Psychiatry Research Jan 2024Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a... (Meta-Analysis)
Meta-Analysis
Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.
Topics: Humans; Transcranial Direct Current Stimulation; Craving; Prefrontal Cortex; Substance-Related Disorders; Methamphetamine; Cocaine; Double-Blind Method
PubMed: 38043411
DOI: 10.1016/j.psychres.2023.115621 -
Journal of Alzheimer's Disease : JAD 2024A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more strongly affected than postsynaptic proteins. However, it has also been reported that presynaptic protein loss is highly variable and shows region- and protein-specificity.
OBJECTIVE
The objective of this meta-analysis was to provide an update on the available literature and to further characterize patterns of presynaptic protein loss in AD.
METHODS
Systematic literature search was conducted for studies published between 2015-2022 which quantified presynaptic proteins in postmortem tissue from AD patients and healthy controls. Three-level random effects meta-analyses of twenty-two identified studies was performed to characterize overall presynaptic protein loss and changes in specific regions, proteins, protein families, and functional categories.
RESULTS
Meta-analysis confirmed overall loss of presynaptic proteins in AD patients. Subgroup analysis revealed region specificity of protein loss, with largest effects in temporal and frontal cortex. Results concerning different groups of proteins were also highly variable. Strongest and most consistently affected was the family of synaptosome associated proteins, especially SNAP25. Among the most severely affected were proteins regulating dense core vesicle exocytosis and the synaptic vesicle cycle.
CONCLUSIONS
Results confirm previous literature related to presynaptic protein loss in AD patients and provide further in-depth characterization of most affected proteins and presynaptic functions.
Topics: Humans; Alzheimer Disease; Proteins; Presynaptic Terminals
PubMed: 38073390
DOI: 10.3233/JAD-231034 -
Respiratory Medicine Jan 2024Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to...
Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting β-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.
INTRODUCTION
Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting β-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted.
METHODS
Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis.
RESULTS
The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs.
CONCLUSION
A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.
Topics: Humans; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Formoterol Fumarate; Randomized Controlled Trials as Topic; Meta-Analysis as Topic
PubMed: 38008385
DOI: 10.1016/j.rmed.2023.107478 -
Psychiatry and Clinical... Sep 2023Gray matter alterations play a role in the panic disorder's pathophysiology origin. However, the current literature seemed inadequate to reach a consistent conclusion....
BACKGROUND
Gray matter alterations play a role in the panic disorder's pathophysiology origin. However, the current literature seemed inadequate to reach a consistent conclusion. Therefore, we conducted this gray matter meta-analysis on panic disorder.
METHODS
A systematic review and a voxel-wise meta-analysis based on voxel-based morphometry were conducted for the gray matter studies in patients with panic disorder. The Seed-based d Mapping toolbox was applied for the voxel-wise meta-analysis. Fourteen gray matter studies (954 subjects) were enrolled in the current meta-analysis. The subgroup analysis of typical-onset versus late-onset patients was also performed. At last, the clinical severity was meta-regressed with gray matter alterations.
RESULTS
Significant gray matter alterations were found in the left para-cingulate gyrus and the right amygdala of panic disorder patients. The subgroup analysis of typical-onset panic disorder patients showed a similar pattern. However, gray matter alterations were demonstrated in the bilateral opercular cortex of late-onset panic disorder patients. A significant association between the clinical severity and the gray matter alterations was found in the fronto-cingulate regions of panic disorder patients.
CONCLUSION
Gray matter alterations might represent a significant pillar of panic disorder's neurobiology, especially for the amygdala, cingulate, and frontal regions. Future gray matter studies in panic disorder should be needed to reconfirm this pattern of gray matter alterations.
PubMed: 38765308
DOI: 10.5152/pcp.2023.23684 -
Systematic Reviews Jun 2024Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex,... (Meta-Analysis)
Meta-Analysis
Impact of sex and socioeconomic status on the likelihood of surgery, hospitalization, and use of medications in inflammatory bowel disease: a systematic review and meta-analysis.
BACKGROUND
Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the likelihood of bowel surgery, hospitalization, and use of corticosteroids and biologics among patients with IBD.
METHODS
We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on the likelihood of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn's disease or ulcerative colitis) and age. Finally, meta-regression was undertaken for the year of publication.
RESULTS
In total, 67 studies were included, of which 23 studies were eligible for meta-analysis. In the main meta-analysis, male sex was associated with an increased likelihood of bowel surgery (HR 1.42 (95% CI 1.13;1.78), which was consistent with the subgroup analysis for UC only (HR 1.78, 95% CI 1.16; 2.72). Sex did not impact the likelihood of hospitalization (OR 1.05 (95% CI 0.86;1.30), although the subgroup analysis revealed an increased likelihood of hospitalization in CD patients (OR 1.42, 95% CI 1.28;1.58). In 9 of 10 studies, no significant sex-based differences in the use of biologics were reported, although in 6 of 6 studies, female patients had lower adherence to biologics. In 11 of 13 studies, no significant sex-based difference in the use of corticosteroids was reported. The evidence of the impact of income and education on healthcare utilization was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type and age.
CONCLUSIONS
The results of this systematic review indicate that male patients with IBD are significantly more likely to have surgery than female patients with IBD but are not, overall, more likely to be hospitalized, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on healthcare utilization. Evidence for income- and education-based differences remains sparse.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022315788.
Topics: Humans; Hospitalization; Sex Factors; Inflammatory Bowel Diseases; Social Class; Adrenal Cortex Hormones; Male; Female; Colitis, Ulcerative
PubMed: 38915086
DOI: 10.1186/s13643-024-02584-3