Separate Meta-analyses Research Articles

Sleep-dependent memory consolidation in schizophrenia: A systematic review and meta-analysis

Sleep disturbances and cognitive impairment are both persistent and common features of schizophrenia. Accumulating evidence indicates that sleep-dependent memory consolidation might be impaired in patients with schizophrenia compared to healthy controls. The current systematic review was performed in accordance with PRISMA guidelines. A random-effects model was used to calculate effect sizes (Hedge's g). In the quantitative review, three separate meta-analyses were conducted for procedural memory in healthy controls, schizophrenia, and comparison between healthy controls and schizophrenia. Additionally, separate meta-analyses were conducted for the studies using finger tapping motor sequence task, as it is the most commonly used task. The current systematic review included 14 studies including 304 patients with schizophrenia and 209 healthy controls. The random-effects model analyses for sleep-dependent procedural memory consolidation resulted in a small effect size in schizophrenia (g=0.26), a large effect size in healthy controls (g=0.98), a moderate effect size in healthy controls vs schizophrenia (g=0.64). For the studies using finger tapping motor sequence task, meta-analyses resulted in a small effect size in schizophrenia (g=0.19), a large effect size in healthy controls (g=1.07), a moderate effect size in healthy controls vs schizophrenia (g=0.70). In the qualitative review, there was also impaired sleep-dependent declarative memory consolidation in schizophrenia compared to healthy controls. Current findings support that sleep improves memory consolidation in healthy adults, but there is a deficit in sleep-dependent memory consolidation in people with schizophrenia. Future studies investigating sleep-dependent consolidation of different memory subtypes with polysomnography in different stages of psychotic disorders are needed.

Prognostic value of perineural invasion in resected non-small cell lung cancer: A meta-analysis

ObjectiveThe prognostic role of perineural invasion (PNI) in resected non-small cell lung cancer (NSCLC) remains unclear. A meta-analysis was performed to compare the overall survival (OS) of patients with resected NSCLC with and without PNI. MethodsThe PubMed, EMBASE, and Web of Science databases were systematically searched to identify relevant studies investigating the effect of PNI on OS in patients with resected NSCLC. Pooled hazard ratio (HR) and 95% confidence intervals (CI) were estimated using a random-effects model. Separate meta-analyses using adjusted or unadjusted HR for OS were performed using Stata/SE 12.0. ResultsEleven studies comprising 2,279 patients were included. In total, PNI was identified in 9% (median, 4%–31%) of patients with resected NSCLC. The unadjusted pooled effect of the PNI was significantly associated with worse OS (HR, 2; 95% CI, 1.65–2.43). Adjusting for potential confounders yielded a similar result, with OS being significantly worse (HR, 2.13; 95% CI, 1.8–2.51) for patients exhibiting PNI. ConclusionThis meta-analysis indicates that the PNI is a strong prognostic factor for unfavorable outcomes in patients with resected NSCLC. Further large-scale prospective lung cancer trials are required to validate these results.

The Association between Early-Onset Diagnosis and Clinical Outcomes in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

Early-onset diagnosis, defined by age <40 years, has historically been associated with inferior outcomes in breast cancer. Recent evidence suggests that this association is modified by molecular subtype. We performed a systematic review and meta-analysis of the literature to synthesize evidence on the association between early-onset diagnosis and clinical outcomes in triple-negative breast cancer (TNBC). Studies comparing the risk of clinical outcomes in non-metastatic TNBC between early-onset patients and later-onset patients (≥40 years) were queried in Medline and EMBASE from inception to February 2023. Separate meta-analyses were performed for breast cancer specific survival (BCSS), overall survival (OS), and disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and pathological complete response (pCR). In total, 7581 unique records were identified, and 36 studies satisfied inclusion criteria. The pooled risk of any recurrence was significantly greater in early-onset patients compared to later-onset patients. Better BCSS and OS were observed in early-onset patients relative to later-onset patients aged >60 years. The pooled odds of achieving pCR were significantly higher in early-onset patients. Future studies should evaluate the role of locoregional management of TNBC and the implementation of novel therapies such as PARP inhibitors in real-world settings, and whether they improve outcomes.

Learned Nocebo Effects on Cutaneous Sensations of Pain and Itch: A Systematic Review and Meta-analysis of Experimental Behavioral Studies on Healthy Humans.

In past decades, the field of nocebo research has focused on studying how sensory perception can be shaped by learning. Nocebo effects refer to aggravated sensory experiences or increased sensitivity to sensations such as pain and itch resulting from treatment-related negative experiences. Behavioral conditioning and verbal suggestions of a negative treatment outcome may aggravate pain and itch perception. Gaining a comprehensive view of the magnitude of nocebo effects and contributing factors will help steer nocebo research toward fruitful directions for understanding complex sensory phenomena. We conducted a systematic review and meta-analysis of a total of 37 distinct experimental nocebo studies on healthy participants (all published in English between 2008 and 2021), with four separate meta-analyses for nocebo effects on pain or itch. We conducted subgroup analyses and meta-regression on factors such as type and intensity of sensory stimuli, and length of conditioning paradigms. This meta-analysis showed that, on average, effect sizes of nocebo effects were moderate to large (Hedges g between 0.26 and 0.71 for the four primary outcomes). The combination of conditioning and verbal suggestions yielded stronger nocebo responses on pain in particular. Subgroup analyses, including factors such as the type of sensory stimulation, did not explain the moderate heterogeneity in nocebo magnitudes between different studies. Risk of bias was generally low and was not related to nocebo magnitudes either. We discuss these results in relation to the role of conditioning and aversive learning, and we recommend more consistency in designing and reporting nocebo experiments.

The Effectiveness of Psychological Interventions for Rheumatoid Arthritis (RA): A Systematic Review and Meta-Analysis.

Rheumatoid arthritis (RA) is a long-term disorder that significantly impairs somatic, emotional, and psychological functioning. The objective of this review is to identify, appraise, and synthesize the effects of psychological interventions (e.g., cognitive behavioral therapy (CBT), emotional disclosure (ED), group therapy (GT), mindfulness (M), patient education (PE), and relaxation (R)) on biopsychosocial outcomes in the treatment of rheumatoid arthritis (RA). A systematic search of all relevant existing randomized clinical trials (RCTs) was conducted using the following online bibliographic databases: JSTOR, PubMed, PsycNET, and The Cochrane Library. Reference lists were searched for additional reports. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias in the included studies. After the selection process, 57 articles were included and 392 were excluded. Three separate meta-analyses were conducted involving psychological interventions as the main variables, showing: (1) significant positive medium effect sizes for average values (Hedges-g = 0.399, Z = 0.399, p = 0.009); (2) significant positive large effect sizes for maximum values (Hedges-g = 0.856, Z = 4.223, p < 0.001); and (3) non-significant results for minimum values (Hedges-g = -0.047, Z = -0.335, p = 0.738). These results demonstrate that, when grouped, psychological interventions are, on average, moderately effective in treating RA. Overall, this review shows consistent, supportive evidence that psychological interventions can significantly contribute to the standard medical care of RA patients. However, more high-quality, large-sample RCTs still need to confirm these findings.

Internet addiction-induced brain structure and function alterations: a systematic review and meta-analysis of voxel-based morphometry and resting-state functional connectivity studies.

Internet addiction (IA) is a growing social concern and has been intensively studied in recent years. Previous imaging studies have shown that IA may impair brain structure and function, but with no robust conclusions. We conducted a systematic review and meta-analysis of neuroimaging studies in IA. Two separate meta-analyses were conducted for voxel-based morphometry (VBM) studies and resting-state functional connectivity (rsFC) studies. All meta-analyses were performed using two analysis methods activation likelihood estimation (ALE) and seed-based d mapping with permutation of subject images (SDM-PSI). The ALE analysis of VBM studies revealed less gray matter volume (GMV) in the supplementary motor area (SMA) (1176 mm3), anterior cingulate cortex (ACC) (one cluster size is 744 mm3 and the other is 688 mm3), and orbitofrontal cortex (OFC) (624 mm3) in subjects with IA. The SDM-PSI analysis showed less GMV in the ACC (56 voxels). The ALE analysis of rsFC studies showed stronger rsFC from posterior cingulate cortex (PCC) (880 mm3) or insula (712 mm3) to the whole brain in subjects with IA; however, the SDM-PSI analysis revealed no obvious rsFC alteration. These changes may underlie the core symptoms of IA, which include emotional regulation disorder, distraction, and impaired executive control. Our results reflect the common features of neuroimaging studies related to IA in recent years and may potentially help inform the development of more effective diagnostic and treatment approaches.

Aging and Economic Preferences: Cumulative Meta-Analyses of Age Differences in Risk, Time, Social, and Effort Preferences.

Several theories predict changes in individuals' economic preferences across the life span. To test these theories and provide a historical overview of this literature, we conducted meta-analyses on age differences in risk, time, social, and effort preferences as assessed by behavioral measures. We conducted separate meta-analyses and cumulative meta-analyses on the association between age and risk, time, social, and effort preferences. We also conducted analyses of historical trends in sample sizes and citation patterns for each economic preference. The meta-analyses identified overall no significant effects of age for risk (r=-0.02, 95% CI [-0.06, 0.02], n=39,832) and effort preferences (r=0.24, 95% CI [-0.05, 0.52], n=571), but significant effects of age for time (r=-0.04, 95% CI [-0.07, -0.01], n=115,496) and social preferences (r=0.11, 95% CI [0.01, 0.21], n=2,997), suggesting increased patience and altruism with age, respectively. Equivalence tests, which compare these effects to practically important ones (i.e., r=|0.1|), however, suggest that all effects are of trivial significance. The analyses of temporal trends suggest that the magnitude of effects and sample sizes have not changed significantly over time, nor do they dramatically affect the extent that articles are cited. Overall, our results contrast with theories of aging that propose general age effects for risk and effort preferences, yet provide some but tenuous support for those suggesting age-related changes in time and social preferences. We discuss implications for theory development as well as future empirical work on economic preferences.

The prevalence of cyber dating abuse among adolescents and emerging adults: A meta-analysis

Numerous scholars have investigated the prevalence of cyber dating abuse (CDA) and recognize that CDA is a widespread phenomenon among adolescents and emerging adults. However, to date, there is no consensus on the extent to which adolescents and emerging adults perpetrate and experience CDA. Based on the PRISMA and MOOSE guidelines, the present work performed separate meta-analyses for studies involving adolescents and emerging adults. This study aims to estimate the pooled prevalence of CDA perpetration and victimization and try to explain discrepancies in the literature. In all, 69 publications (25 adolescent and 44 emerging adult studies) on CDA were identified through a systematic literature search, including 74 independent samples with a total of 62,376 participants. The results showed that the overall prevalence of CDA perpetration was 24.0% and victimization was 36.9% among adolescents, while 44.6% and 43.4% for CDA perpetration and victimization among emerging adults. Moderator analyses revealed that higher rates of CDA perpetration and victimization were found for older adolescents. In addition, control dimension had higher rates of CDA perpetration and victimization compared to direct aggression dimension among emerging adults. Finally, the assessed lifetime prevalence of CDA perpetration was higher than that assessed in the last year in emerging adults, whereas unpublished studies showed a higher prevalence of CDA victimization compared to published studies in adolescents. In sum, current evidence contributes to a better understanding of the prevalence and influencing factors for CDA among adolescents and emerging adults. Prevention and intervention programs are urgently required to reduce CDA behaviors in adolescents and emerging adults.

Dietary Patterns under the Influence of Rotational Shift Work Schedules: A Systematic Review and Meta-Analysis.

Workers employed in rotating shift schedules are at a higher metabolic risk compared with those in regular day and fixed shift schedules; however, the contribution of diet is unclear. This systematic review aimed to investigate how rotating shift work schedules affect dietary energy intake and dietary patterns compared with regular day and fixed shift schedules. In addition, intraperson energy intake and dietary pattern comparisons within rotating shift schedules were investigated. Database searches were conducted on MEDLINE, Cochrane, CINAHL, PSYCinfo, EMBASE, and Scopus, in addition to manual search of bibliographic references, to identify articles. Two separate meta-analyses compared dietary intake between day work and rotating shift work schedules and within the rotational shift work group (morning/day and night shifts). Differences in dietary patterns were synthesized narratively. Thirty-one studies (n = 18,196 participants) were included in the review, and meta-analyses were conducted with 24-hour mean energy intake data from 18 (n = 16,633 participants) and 7 (n = 327 participants) studies, respectively. The average 24-hour energy intake of rotating shift workers was significantly higher than that of workers in regular daytime schedules [weighted mean difference (WMD): 264 kJ; 95% confidence interval (CI): 70, 458 kJ; P < 0.008; I2 = 63%]. However, the mean difference in 24-hour energy intake between morning/day shifts compared with night shifts within rotational shift schedules was not statistically significant (WMD: 101 kJ; 95% CI: -651, 852 kJ; P = 0.79; I2 = 77%). Dietary patterns of rotating shift workers were different from those of day workers, showing irregular and more frequent meals, increased snacking/eating at night, consumption of fewer core foods, and more discretionary foods. This review highlights that dietary intake in rotational shift workers is potentially higher in calories and features different eating patterns as a consequence of rotating shift work schedules. This review was registered at PROSPERO as ID 182507.

A meta-analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder.

The capacity to anticipate and detect rewarding outcomes is fundamental for the development of adaptive decision-making and goal-oriented behavior. Delineating the neural correlates of different stages of reward processing is imperative for understanding the neurobiological mechanism underlying alcohol use disorder (AUD). To examine the neural correlates of monetary anticipation and outcome in AUD patients, we performed two separate voxel-wise meta-analyses of functional neuroimaging studies, including 12 studies investigating reward anticipation and 7 studies investigating reward outcome using the monetary incentive delay task. During the anticipation stage, AUD patients displayed decreased activation in response to monetary cues in mesocortical-limbic circuits and sensory areas, including the ventral striatum (VS), insula, hippocampus, inferior occipital gyrus, supramarginal gyrus, lingual gyrus and fusiform gyrus. During the outcome stage, AUD patients exhibited reduced activation in the dorsal striatum, VS and insula, and increased activation in the orbital frontal cortex and medial temporal area. Our findings suggest that different activation patterns are associated with nondrug rewards during different reward processing stages, potentially reflecting a changed sensitivity to monetary reward in AUD.

Outcomes of robotic nipple-sparing mastectomy versus conventional nipple-sparing mastectomy in women with breast cancer: a systematic review and meta-analysis.

The promising results of the robotic approach for multiple cancer operations has led to interest in the potential of robotic nipple-sparing mastectomy (R-NSM); however, further studies are required to compare the benefits and complications of this approach with those of conventional open nipple-sparing mastectomy (C-NSM). We performed a meta-analysis to compare surgical complications of R-NSM versus C-NSM. We performed a review of literature through June 2022 in PubMed, Scopus, and EMBASE. We included randomized controlled trials (RCTs), cohorts, case-control studies, and case series with > 50 patients comparing the two techniques. Separate meta-analyses were conducted according to study design. From 80 publications, we identified six studies. The sample size ranged from 63 to 311 mastectomies from 63 to 275 patients. The tumor size and disease stage were similar between groups. The positive margin rate was 0-4.6% in the R-NSM arm and 0-2.9% in the C-NSM arm. Four studies reported early recurrence data, which were similar between groups (R-NSM: 0%, C-NSM: 0-8%). The R-NSM group had a lower rate of overall complications compared to the C-NSM group in cohorts/RCTs (RR = 0.68, 95%CI 0.49-0.96). In case-control studies, rate of necrosis was lower with R-NSM. Operative time was significantly longer in the R-NSM group in cohort/RCTs. In early experience with R-NSM, R-NSM had a lower overall complication rate compared to C-NSM in cohorts/RCTs. While these data are promising, our results show variability and heterogeneity limiting definitive conclusions. Additional trials are needed to guide the role of R-NSM and its oncologic outcomes.

Prevalence of medication administration errors in hospitalized adults: A systematic review and meta-analysis up to 2017 to explore sources of heterogeneity.

Previous estimates to meta-analyze administration error rates were limited by the high statistical heterogeneity, restricting their use. This study aimed to investigate sources of heterogeneity in pooled administration error rates in hospitalized adults. We systematically searched scientific databases up to November 2017 for studies presenting error rates/relevant numerical data in hospitalized adults. We conducted separate meta-analyses for the numerators: One Medication Error (OME) (each dose can be correct or incorrect) and Total Number of Errors (TNE) (more than one error per dose could be counted), using the generic inverse variance with a 95% confidence interval. Heterogeneity was assessed using the I2 and Cochran's Q test. We meta-analyzed 33 studies. The global pooled analyses based on the OME and TNE numerators showed very high heterogeneity (I2 = 100%; p< 0.00001). For each meta-analysis, subgroup analyses based on study characteristics (countries, wards, population, routes of administration, error detection methods, and medications) yielded results with consistently elevated heterogeneity. Beyond these characteristics, we stratified the studies according to the mean error prevalence level as the threshold. Based on the OME numerator, we identified two subgroups of low (0.15[0.13-0.17]; I2 =0%; p= 0.43) and high (0.26[0.24-0.27]; I2 = 38%; p= 0.17) pooled prevalence rates, with controlled heterogeneity. Similarly, for the TNE numerator, we identified two subgroups of low (0.10[0.09-0.10]; I2 =0%; p= 0.76) and high (0.28[0.27-0.29]; I2 =0%; p= 0.89) pooled prevalence rates, with controlled heterogeneity. These subgroups differed regarding the denominators used: Total opportunities for errors versus others (doses, observations, administrations). Calculation methods, specifically the denominator, seem a primary factor in explaining heterogeneity in error rates. Standardizing numerators, denominators, and definitions is necessary.

Filgotinib for Treating Moderately to Severely Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited the manufacturer (Galapagos) of filgotinib (Jyseleca®), as part of the Single Technology Appraisal process, to submit evidence for the clinical effectiveness and cost effectiveness of filgotinib for treating moderately to severely active ulcerative colitis in adults who have had an inadequate response, loss of response or were intolerant to a previous biologic agent or conventional therapy. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group. This paper summarises the company submission, presents the Evidence Review Group's critical review on the clinical and cost-effectiveness evidence in the company submission, highlights the key methodological considerations and describes the development of the National Institute for Health and Care Excellence guidance by the Appraisal Committee. The company submission included one relevant study for the comparison of filgotinib versus placebo: the SELECTION trial. As there was no head-to-head evidence with any of the comparators, the company performed two separate network meta-analyses, one for the biologic-naïve population and one for the biologic-experienced population, and for both the induction and maintenance phases. The Evidence Review Group questioned the validity of the maintenance network meta-analysis because it assumed all active treatments to be comparators in this phase, which is not in line with clinical practice. The economic analysis used a number of assumptions that introduced substantial uncertainty, which could not be fully explored, for instance, the assumption that a risk of loss of response would be independent of health state and constant over time. Company and Evidence Review Group results indicate that at its current price, and disregarding confidential discounts for comparators and subsequent treatments, filgotinib dominates some comparators (golimumab and adalimumab in the company base case, all but intravenous and subcutaneous vedolizumab in the Evidence Review Group's base case) in the biologic-naïve population. In the biologic-experienced population, filgotinib dominates all comparators in both the company and the Evidence Review Group's base case. Results should be interpreted with caution as some important uncertainties were not included in the modelling. These uncertainties were mostly centred around the maintenance network meta-analysis, loss of response, health-related quality-of-life estimates and modelling of dose escalation. The National Institute for Health and Care Excellence recommended filgotinib within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional or biological treatment cannot be tolerated, or if the disease has not responded well enough or has stopped responding to these treatments, and if the company provides filgotinib according to the commercial arrangement.

Revisión sistemática y metaanálisis de intervenciones transdiagnósticas en línea de tercera generación

Existing meta-analyses on the effect of online psychological interventions (OPIs) have found small to medium effect sizes for the treatment of anxiety and depression. On the other hand, third-generation trans-diagnostic OPIs are very rare and, due to the large variability among disorders, symptoms or target populations, it is difficult to assess their overall effect. Other systematic reviews and meta-analyses have overly broad inclusion criteria that make the understanding of the findings more difficult. The current study aims to analyze the empirical evidence for third-wave trans-diagnostic OPIs designed to decrease symptoms and promote psychological flexibility, including studies that compare a OPI to some control condition ( e. g. , waiting list, treatment as usual or other that should not have any effect) and include a general symptomatology scale as dependent variable. A search without filters or timeframe was performed on Scopus and 1 408 articles were found, among which 21 were reviewed in depth and 6 were included for meta-analysis. Risk of bias was assessed by a quality and heterogeneity assessment. Separate meta-analyses were performed for general distress and psychological flexibility at post-treatment and last follow-up. Risk of bias analysis suggest low risk of threats to validity and attribute heterogeneity to between-study attrition rates. Additionally, meta-regression models for duration, attrition rate, and mean age are proposed for each time point. The results show significantly large effect sizes for both variables at both time points. According to the meta-regression models attrition rates are a mediating variable for the effect on general distress both at completion and at the last follow-up. On the other hand, duration, age and attrition rate are all mediating variables for the effect on psychological flexibility at the end of treatment. The findings suggest that the high attrition rates observed on tele-psychology need to be mitigated; if this is not possible, intention-to-treat approaches should be adopted for data analysis. https://doi.org/10.16888/interd.2023.40.2.5

Prevalence of Drug-Drug Interactions in Older Community-Dwelling Individuals: A Systematic Review and Meta-analysis.

Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults. PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥65 years. Nursing home and inpatient hospital studies were excluded. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analysis was performed using a random-effects model with logit transformation. Heterogeneity was evaluated using Cochran's Q and I2. DDI prevalence and 95% confidence intervals (CIs) are presented. All analyses were performed in R (version 4.1.2). There were 5144 unique articles identified. Thirty-three studies involving 17,011,291 community-dwelling individuals aged ≥65 years met inclusion criteria. Thirty-one studies reported DDI prevalence at the study-participant level, estimates ranged from 0.8% to 90.6%. The pooled DDI prevalence was 28.8% (95% CI 19.3-40.7), with significant heterogeneity (p < 0.10; I2 = 100%; tau2 = 2.13) largely explained by the different DDI identification methods. Therefore, 26 studies were qualitatively synthesised and seven studies were eligible for separate meta-analyses. In a meta-analysis of three studies (N = 1122) using Micromedex®, pooled DDI prevalence was 57.8% (95% CI 52.2-63.2; I2 = 69.6%, p < 0.01). In a meta-analysis of two studies (N = 809,113) using Lexi-Interact®, pooled DDI prevalence was 30.3% (95% CI 30.2-30.4; I2 = 6.8%). In a meta-analysis of two studies (N = 947) using the 2015 American Geriatrics Society Beers criteria®, pooled DDI prevalence was 16.6% (95% CI 5.6-40.2; I2 = 97.5%, p < 0.01). Common DDIs frequently involved cardiovascular drugs, including ACE inhibitor-potassium-sparing diuretic; amiodarone-digoxin; and amiodarone-warfarin. DDIs are prevalent among older community-dwelling individuals; however, the methodology used to estimate these events varies considerably. A standardised methodology is needed to allow meaningful measurement and comparison of DDI prevalence.

Reevaluating the role of the hippocampus in memory: A meta-analysis of neurotoxic lesion studies in nonhuman primates.

The hippocampus and perirhinal cortex are both broadly implicated in memory; nevertheless, their relative contributions to visual item recognition and location memory remain disputed. Neuropsychological studies in nonhuman primates that examine memory function after selective damage to medial temporal lobe structures report various levels of memory impairment-ranging from minor deficits to profound amnesia. The discrepancies in published findings have complicated efforts to determine the exact magnitude of visual item recognition and location memory impairments following damage to the hippocampus and/or perirhinal cortex. To provide the most accurate estimate to date of the overall effect size, we use meta-analytic techniques on data aggregated from 26 publications that assessed visual item recognition and/or location memory in nonhuman primates with and without selective neurotoxic lesions of the hippocampus or perirhinal cortex. We estimated the overall effect size, evaluated the relation between lesion extent and effect size, and investigated factors that may account for between-study variation. Grouping studies by lesion target and testing method, separate meta-analyses were conducted. One meta-analysis indicated that impairments on tests of visual item recognition were larger after lesions of perirhinal cortex than after lesions of the hippocampus. A separate meta-analysis showed that performance on tests of location memory was severely impaired by lesions of the hippocampus. For the most part, meta-regressions indicated that greater impairment corresponds with greater lesion extent; paradoxically, however, more extensive hippocampal lesions predicted smaller impairments on tests of visual item recognition. We conclude the perirhinal cortex makes a larger contribution than the hippocampus to visual item recognition, and the hippocampus predominately contributes to spatial navigation.

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis

Patients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient. To assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion. On August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised. Randomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled. The prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma. This systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]). These findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.

Inhaled Corticosteroid Exposure and Risk of Cataract in Patients with Asthma and COPD: A Systematic Review and Meta-Analysis.

Both systemic and inhaled corticosteroids may increase the risk of cataract in patients with both chronic obstructive pulmonary disease (COPD) and asthma. Our aim was to assess the degree of association between cataract and corticosteroid exposure in patients with asthma and COPD. A systematic literature review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The odds ratio estimates were extracted from each article. A random effects model was applied for estimate pooling in separate meta-analyses according to study design. Meta-regression was performed to assess the dose-response relationship between corticosteroid exposure and the risk of cataract development. A total of 19 studies met the criteria for inclusion in this review, of which 12 studies provided effect estimates for pooled analyses. All but one of the included observational studies reported a significant association between use of corticosteroids and cataract development in cohorts of asthma and/or COPD patients. Pooled analyses revealed on average a doubled risk of cataract in corticosteroid-exposed asthma and COPD patients. Studies have shown that daily high-dose inhaled corticosteroid (ICS) ≥ 1000 μg is associated with a significant risk of developing cataract and by that predispose to subsequent cataract surgery, although one study showed that systemic corticosteroids increase cataract risk more than ICS. ICS treatment in asthma and COPD patients is a risk factor for cataract development. Our results emphasize a previously underestimated potential long-term risk of treatment with ICS and underline the importance of targeting ICS treatment, and not least dosing, to improve the risk-benefit ratio of maintenance treatment in both asthma and COPD.

Impact of Methyl-Donor Micronutrient Supplementation on DNA Methylation Patterns: A Systematic Review and Meta-Analysis of in vitro, Animal, and Human Studies

Background: DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear. Objectives: The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation. Methods: A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation. Results: Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as “high risk” or “some concerns.” Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo. Conclusion: Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.

Sugar-free chewing gum versus conventional analgesic drugs for pain relief with fixed orthodontic appliances. A systematic review and meta-analysis.

To compare the effect of chewing sugar-free gum towards alleviating self-reported orthodontic treatment (OT) pain compared with conventional analgesic drugs (CADs). An unrestricted search of indexed databases and manual searching was performed up to September 2021. Randomised controlled trials (RCTs) comparing the impact of chewing gum and CADs on relieving self-reported orthodontic pain were included. Data screening, extraction and risk of bias (RoB) assessment were performed by two authors. Meta-analyses were performed using a random-effects model. The quality of available evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. Nine RCTs were included. Eight RCTs used the Visual Analogue Scale for self-reported pain assessment, while one RCT used the Numeric Rating Scale. Five RCTs had a high RoB and four RCTs had a moderate RoB. Power analysis for sample size estimation was performed in six RCTs. Separate meta-analyses were performed by pooling quantitative data from five RCTs that compared self-reported orthodontic pain between chewing gum and ibuprofen groups for the following timepoints: baseline; immediately; 2 hours; 6 hours; bedtime; 24 hours; 2 days; 3 days; 5 days; and 7 days after the placement of orthodontic appliances. None of the timepoints individually indicated a difference in self-reported pain scores between chewing sugar-free gum and ibuprofen groups. The overall level of evidence was very low. Chewing sugar-free gum is a potentially useful alternative to CADs towards pain alleviation during fixed OT.