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Molecular Psychiatry Nov 2023In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a...
In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a dramatic toll on western countries. OUD is a chronic relapsing disease associated with a lifetime struggle to control drug consumption, suggesting that opioids trigger long-lasting brain adaptations, notably through functional genomic and epigenomic mechanisms. Current understanding of these processes, however, remain scarce, and have not been previously reviewed systematically. To do so, the goal of the present work was to synthesize current knowledge on genome-wide transcriptomic and epigenetic mechanisms of opioid action, in primate and rodent species. Using a prospectively registered methodology, comprehensive literature searches were completed in PubMed, Embase, and Web of Science. Of the 2709 articles identified, 73 met our inclusion criteria and were considered for qualitative analysis. Focusing on the 5 most studied nervous system structures (nucleus accumbens, frontal cortex, whole striatum, dorsal striatum, spinal cord; 44 articles), we also conducted a quantitative analysis of differentially expressed genes, in an effort to identify a putative core transcriptional signature of opioids. Only one gene, Cdkn1a, was consistently identified in eleven studies, and globally, our results unveil surprisingly low consistency across published work, even when considering most recent single-cell approaches. Analysis of sources of variability detected significant contributions from species, brain structure, duration of opioid exposure, strain, time-point of analysis, and batch effects, but not type of opioid. To go beyond those limitations, we leveraged threshold-free methods to illustrate how genome-wide comparisons may generate new findings and hypotheses. Finally, we discuss current methodological development in the field, and their implication for future research and, ultimately, better care.
Topics: Animals; Humans; Analgesics, Opioid; Opioid-Related Disorders; Drug Overdose; Chronic Disease; Genomics; Models, Animal
PubMed: 37723284
DOI: 10.1038/s41380-023-02238-1 -
Frontiers in Neuroscience 2023Cerebral small vessel disease (cSVD) is associated with endothelial dysfunction but the pathophysiology is poorly understood. Low-frequency oscillations (LFOs) in the... (Review)
Review
BACKGROUND
Cerebral small vessel disease (cSVD) is associated with endothelial dysfunction but the pathophysiology is poorly understood. Low-frequency oscillations (LFOs) in the BOLD signal partly reflect cerebrovascular function and have the potential to identify endothelial dysfunction in cSVD. A systematic review was performed to assess the reported relationships between imaging markers of cSVD and LFOs.
METHODS
Medline and EMBASE were searched for original studies reporting an association between LFOs and STRIVE-defined imaging markers of cSVD, including: white matter hyperintensities (WMH), enlarged perivascular spaces, lacunes, CADASIL, and cerebral microbleeds, from inception to September 1, 2022. Variations in LFOs were extracted, where available, on a global, tissue-specific, or regional level, in addition to participant demographics, data acquisition, methods of analysis, and study quality. Where a formal meta-analysis was not possible, differences in the number of studies reporting LFO magnitude by presence or severity of cSVD were determined by sign test.
RESULTS
15 studies were included from 841 titles. Studies varied in quality, acquisition parameters, and in method of analysis. Amplitude of low-frequency fluctuation (ALFF) in resting state fMRI was most commonly assessed (12 studies). Across 15 studies with differing markers of cSVD (9 with WMH; 1 with cerebral microbleeds; 1 with lacunar infarcts; 1 with CADASIL; 3 with multiple markers), LFOs in patients with cSVD were decreased in the posterior cortex (22 of 32 occurrences across all studies, = 0.05), increased in the deep grey nuclei (7 of 7 occurrences across all studies, = 0.016), and potentially increased in the temporal lobes (9 of 11 occurrences across all studies, = 0.065).
CONCLUSION
Despite limited consensus on the optimal acquisition and analysis methods, there was reasonably consistent regional variation in LFO magnitude by severity of cSVD markers, supporting its potential as a novel index of endothelial dysfunction. We propose a consistent approach to measuring LFOs to characterise targetable mechanisms underlying cSVD.
PubMed: 37719157
DOI: 10.3389/fnins.2023.1254209 -
Experimental and Clinical... Aug 2023Although several studies have explored the connection between corticosteroids and renal transplant surgical complications, these studies have overlooked several factors.... (Review)
Review
OBJECTIVES
Although several studies have explored the connection between corticosteroids and renal transplant surgical complications, these studies have overlooked several factors. In addition, no review of the literature, to our knowledge, has been conducted to evaluate corticosteroid dose and incidence of posttransplant surgical complications in these patients. Thus, our objective was to carry out a systematic investigation ofthe correlationbetween corticosteroids and surgical complications in renaltransplant patients.
MATERIALS AND METHODS
A systematic search was conducted on the PubMed and Embase databases from their inception until April 2023. Retrospective and prospective cohort studies were included if they met the association between corticosteroids and surgical complications. The search strategy was performed using MeSH and non-MeSH key words. Terms used in the electronic search included kidney transplant* OR kidney transplant(mesh) AND steroid* OR steroids(mesh) AND complication* OR intraoperative complications(mesh).
RESULTS
From 3274 articles, 8 articles were included in the systematic review. Six studies were conducted as retrospective cohorts and 2 studies as prospective cohorts. The mean age of patients included in the studies was 42.1 years. The studies were conducted between 1981 and 2023. Findings suggested that decreasing the postoperative corticosteroid dosage was associated with a lower incidence of various postoperative surgical complications.
CONCLUSIONS
We investigated the potential benefits of reducing the dose of corticosteroids following kidney transplant. Findings suggested thatreducing the dose of corticosteroids following kidney transplant might be a viable strategy for minimizing the risk of surgical complications. However, it is essential to note that the optimal dosage and duration of corticosteroid therapy after kidney transplant may vary for each patient and should be carefully determined by the health care provider.
Topics: Humans; Adult; Kidney Transplantation; Prospective Studies; Retrospective Studies; Adrenal Cortex Hormones; Databases, Factual; Postoperative Complications
PubMed: 37698397
DOI: 10.6002/ect.2023.0198 -
Psychoneuroendocrinology Nov 2023Childhood adversity increases the risk of developing psychosis, but the biological mechanisms involved are unknown. Disaggregating early adverse experiences into core... (Review)
Review
Childhood adversity increases the risk of developing psychosis, but the biological mechanisms involved are unknown. Disaggregating early adverse experiences into core dimensions of deprivation and threat may help to elucidate these mechanisms. We therefore systematically searched the literature investigating associations between deprivation and threat, and neural, immune and stress hormone systems in individuals on the psychosis spectrum. Our search yielded 74 articles, from which we extracted and synthesized relevant findings. While study designs were heterogeneous and findings inconsistent, some trends emerged. In psychosis, deprivation tended to correlate with lower global cortical volume, and some evidence supported threat-related variation in prefrontal cortex morphology. Greater threat exposure was also associated with higher C-reactive protein, and higher and lower cortisol measures. When examined, associations in controls were less evident. Overall, findings indicate that deprivation and threat may associate with partially distinct biological mechanisms in the psychosis spectrum, and that associations may be stronger than in controls. Dimensional approaches may help disentangle the biological correlates of childhood adversity in psychosis, but more studies are needed.
Topics: Humans; Psychotic Disorders; Prefrontal Cortex; Hydrocortisone; Adult Survivors of Child Abuse
PubMed: 37651860
DOI: 10.1016/j.psyneuen.2023.106371 -
Journal of Perinatal Medicine Nov 2023Dexamethasone administration can reduce bronchopulmonary dysplasia, our objective was to identify long term adverse effects. (Review)
Review
BACKGROUND
Dexamethasone administration can reduce bronchopulmonary dysplasia, our objective was to identify long term adverse effects.
CONTENT
A systematic review was performed to determine the childhood and adolescent cardiopulmonary and cognitive effects of dexamethasone systemically administered to preterm infants during neonatal intensive care. Relevant studies were identified by searching two electronic health databases and the grey literature. Spirometry assessments were used as respiratory outcomes, blood pressure and echocardiography assessments as cardiovascular outcomes and cognitive and motor function as cognitive outcomes. From 1,479 articles initially identified, 18 studies (overall 1,609 patients) were included (respiratory n=8, cardiovascular n=2, cognitive n=10); all were observational cohort studies. Dexamethasone exposure was associated with worse pulmonary outcomes in children and adolescents (more abnormal FVC and FEV1:FVC z scores). Dexamethasone exposure was associated in one study with lower IQ scores compared to preterm controls (mean 78.2 [SD 15.0] vs. 84.4 [12.6], [p=0.008]) and in two others was associated with lower total and performance IQ when compared to term controls (p<0.001).
SUMMARY AND OUTLOOK
Postnatal dexamethasone exposure has a negative influence on pulmonary and cognitive outcomes in childhood and adolescence. Medications with a better benefit to risk profile need to be identified.
Topics: Adolescent; Child; Humans; Infant; Infant, Newborn; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Chronic Disease; Dexamethasone; Glucocorticoids; Infant, Premature
PubMed: 37606507
DOI: 10.1515/jpm-2023-0297 -
BMC Pulmonary Medicine Aug 2023The fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients.
METHODS
Two reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778).
RESULTS
Forty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture.
CONCLUSION
Inhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.
Topics: Humans; Adrenal Cortex Hormones; Budesonide; Duration of Therapy; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive
PubMed: 37592316
DOI: 10.1186/s12890-023-02602-5 -
BMJ Open Aug 2023To evaluate through a systematic review the effectiveness of electronic methods in monitoring adherence to regular inhaled corticosteroids (ICS) alone or in combination... (Review)
Review
Effect of monitoring adherence to regular inhaled corticosteroid (ICS) alone or in combination with a long-acting β2-agonist (LABA) using electronic methods on asthma outcomes: a narrative systematic review.
OBJECTIVES
To evaluate through a systematic review the effectiveness of electronic methods in monitoring adherence to regular inhaled corticosteroids (ICS) alone or in combination with long-acting β2-agonists (LABAs) and their effect on clinical outcomes.
DESIGN
A narrative systematic review.
DATA SOURCES
MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Web of Science were searched through up to 10 July 2022.
ELIGIBILITY CRITERIA
We included peer-reviewed studies of qualitative and quantitative outcomes that compared the effect of electronic methods to routine non-electronic monitoring intervention or placebo among children and adults with asthma on medication adherence rates to regular ICS alone or in combination with LABA, asthma control and asthma exacerbations.
DATA EXTRACTION AND SYNTHESIS
Data extraction was performed according to a predetermined sheet specific to the review objectives. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials and the Risk of Bias in Systematic Reviews tool for systematic reviews. Meta-analysis was not possible based on the findings of the scoping search; however, a narrative review was performed to allow for the grouping of results based on asthma inhaler adherence rates, asthma control and exacerbations.
RESULTS
Six articles comprising 98 studies published from 1998 to 2022 in the USA, Canada and the UK were included. Compared with the control, electronic monitoring devices (EMDs) showed a 23% adherence improvement, mean difference (MD) of 23%, 95% CI 10.84 to 34.16, p=0.0002. Asthmatic children were 1.5 times more likely to be adherent using EMDs compared with non-EMD users (RR=1.5, 95% CI 1.19 to 1.9) (p<0.001). Mobile devices and text message reminders (MHealth) showed a 12% adherence improvement (MD 12%, 95% CI 6.22 to 18.03) (p<0.0001), alongside a small to medium improvement in asthma control (standardised mean difference (SMD) 0.31, 95% CI 0.17 to 0.44), small improvement in asthma-related quality of life (SMD 0.26) (p=0.007) and variable risk reduction in asthma exacerbations for digital health (risk ratio 0.53, 95% CI 0.32 to 0.91) (p=0.02) compared with EMDs, which showed insignificant differences (risk ratio 0.89, 95% CI 0.45 to 1.75) (p=0.72). Technologies combined yielded variable adherence effects, with an SMD for eHealth of 0.41, 95% CI 0.02 to 0.79, and MD for digital health was 14.66% higher than the control, 95% CI 7.74 to 21.57. Heterogeneity between studies was significant (eHealth I=98%, digital I=94%).
CONCLUSION
Electronic methods improved adherence to inhaled medications in asthma. EMDs appear to be the most effective technology, followed by mHealth. The adherence improvement was associated with a small clinical improvement. There was inconsistent overlapping of terminology describing electronic methods that require standardisation. Data on the cost-effectiveness of electronic devices and their utilisation in severe asthma are lacking and require further research.
PROSPERO REGISTRATION NUMBER
CRD42022303069.
Topics: Adult; Child; Humans; Acceptance and Commitment Therapy; Adrenal Cortex Hormones; Asthma; Quality of Life
PubMed: 37586865
DOI: 10.1136/bmjopen-2023-074127 -
BMC Psychology Aug 2023Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple...
BACKGROUND
Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple pathologies. A phenomenon disrupted in several disorders is prepulse inhibition (PPI) of the startle response, in which startle to an intense sensory stimulus, or pulse, is reduced if a weak stimulus, or prepulse, is previously presented.
OBJECTIVE AND METHODS
The present systematic review analyzed the role of PPI deficit as a possible transdiagnostic process for four main groups of neuropsychiatric disorders: (1) trauma-, stress-, and anxiety-related disorders (2) mood-related disorders, (3) neurocognitive disorders, and (4) other disorders such as obsessive-compulsive, tic-related, and substance use disorders. We used Web of Science, PubMed and PsycInfo databases to search for experimental case-control articles that were analyzed both qualitatively and based on their potential risk of bias. A total of 64 studies were included in this systematic review. Protocol was submitted prospectively to PROSPERO 04/30/2022 (CRD42022322031).
RESULTS AND CONCLUSION
The results showed a general PPI deficit in the diagnostic groups mentioned, with associated deficits in the dopaminergic neurotransmission system, several areas implied such as the medial prefrontal cortex or the amygdala, and related variables such as cognitive deficits and anxiety symptoms. It can be concluded that the PPI deficit appears across most of the neuropsychiatric disorders examined, and it could be considered as a relevant measure in translational research for the early detection of such disorders.
Topics: Humans; Prepulse Inhibition; Reflex, Startle; Cognition Disorders; Mood Disorders; Anxiety Disorders; Acoustic Stimulation
PubMed: 37550772
DOI: 10.1186/s40359-023-01253-9 -
Frontiers in Behavioral Neuroscience 2023Conceptualizations and operational definitions of psychological resilience vary across resilience neuroimaging studies. Data on the neural features of resilience among... (Review)
Review
Conceptualizations and operational definitions of psychological resilience vary across resilience neuroimaging studies. Data on the neural features of resilience among healthy individuals has been scarce. Furthermore, findings from resting-state functional magnetic resonance imaging (fMRI) studies were inconsistent across studies. This systematic review summarized resting-state fMRI findings in different modalities from various operationally defined resilience in a mentally healthy population. The PubMed and MEDLINE databases were searched. Articles that focused on resting-state fMRI in relation to resilience, and published before 2022, were targeted. Orbitofrontal cortex, anterior cingulate cortex, insula and amygdala, were reported the most from the 19 included studies. Regions in emotional network was reported the most from the included studies. The involvement of regions like amygdala and orbitofrontal cortex indicated the relationships between emotional processing and resilience. No common brain regions or neural pathways were identified across studies. The emotional network appears to be studied the most in association with resilience. Matching fMRI modalities and operational definitions of resilience across studies are essential for meta-analysis.
PubMed: 37538200
DOI: 10.3389/fnbeh.2023.1175064 -
BMJ (Clinical Research Ed.) Aug 2023To systematically review the proportions of infants with early exposure to antenatal corticosteroids but born at term or late preterm, and short term and long term... (Meta-Analysis)
Meta-Analysis
The proportions of term or late preterm births after exposure to early antenatal corticosteroids, and outcomes: systematic review and meta-analysis of 1.6 million infants.
OBJECTIVE
To systematically review the proportions of infants with early exposure to antenatal corticosteroids but born at term or late preterm, and short term and long term outcomes.
DESIGN
Systematic review and meta-analyses.
DATA SOURCES
Eight databases searched from 1 January 2000 to 1 February 2023, reflecting recent perinatal care, and references of screened articles.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials and population based cohort studies with data on infants with early exposure to antenatal corticosteroids (<34 weeks) but born at term (≥37 weeks), late preterm (34-36 weeks), or term/late preterm combined.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened titles, abstracts, and full text articles and assessed risk of bias (Cochrane risk of bias tool for randomised controlled trials and Newcastle-Ottawa scale for population based studies). Reviewers extracted data on populations, exposure to antenatal corticosteroids, and outcomes. The authors analysed randomised and cohort data separately, using random effects meta-analyses.
MAIN OUTCOME MEASURES
The primary outcome was the proportion of infants with early exposure to antenatal corticosteroids but born at term. Secondary outcomes included the proportions of infants born late preterm or term/late preterm combined after early exposure to antenatal corticosteroids and short term and long term outcomes versus non-exposure for the three gestational time points (term, late preterm, term/late preterm combined).
RESULTS
Of 14 799 records, the reviewers screened 8815 non-duplicate titles and abstracts and assessed 713 full text articles. Seven randomised controlled trials and 10 population based cohort studies (1.6 million infants total) were included. In randomised controlled trials and population based data, ∼40% of infants with early exposure to antenatal corticosteroids were born at term (low or very low certainty). Among children born at term, early exposure to antenatal corticosteroids versus no exposure was associated with increased risks of admission to neonatal intensive care (adjusted odds ratio 1.49, 95% confidence interval 1.19 to 1.86, one study, 5330 infants, very low certainty; unadjusted relative risk 1.69, 95% confidence interval 1.51 to 1.89, three studies, 1 176 022 infants, I=58%, τ=0.01, low certainty), intubation (unadjusted relative risk 2.59, 1.39 to 4.81, absolute effect 7 more per 1000, 95% confidence interval from 2 more to 16 more, one study, 8076 infants, very low certainty, one study, 8076 infants, very low certainty), reduced head circumference (adjusted mean difference -0.21, 95% confidence interval -0.29 to -0.13, one study, 183 325 infants, low certainty), and any long term neurodevelopmental or behavioural disorder in population based studies (eg, any neurodevelopmental or behavioural disorder in children born at term, adjusted hazard ratio 1.47, 95% confidence interval 1.36 to 1.60, one study, 641 487 children, low certainty).
CONCLUSIONS
About 40% of infants exposed to early antenatal corticosteroids were born at term, with associated adverse short term and long term outcomes (low or very low certainty), highlighting the need for caution when considering antenatal corticosteroids.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022360079.
Topics: Child; Infant, Newborn; Infant; Humans; Female; Pregnancy; Premature Birth; Infant, Premature; Adrenal Cortex Hormones; Glucocorticoids; Parturition
PubMed: 37532269
DOI: 10.1136/bmj-2023-076035