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The Lancet. Oncology Aug 2022The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear.... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.
BACKGROUND
The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques.
METHODS
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508.
FINDINGS
7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44-0·79] and CKC: 0·63 [0·50-0·81]) and increased for laser ablation (1·69 [1·27-2·24]) and cryotherapy (1·84 [1·33-2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68-1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70-3·02]; laser conisation: 1·77 [1·29-2·43]; and LLETZ: 1·37 [1·16-1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78-1·41]; cryotherapy: 1·01 [0·35-2·92]; and cold coagulation: 0·67 [0·02-29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low.
INTERPRETATION
More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning.
FUNDING
National Institute for Health and Care Research: Research for Patient Benefit.
Topics: Conization; Female; Humans; Infant, Newborn; Network Meta-Analysis; Premature Birth; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 35835138
DOI: 10.1016/S1470-2045(22)00334-5 -
Molecular Psychiatry Sep 2022The wide range of psychosocial interventions designed to assist people with Autism Spectrum Disorder (ASD) makes it challenging to compile and hierarchize the scientific...
INTRODUCTION
The wide range of psychosocial interventions designed to assist people with Autism Spectrum Disorder (ASD) makes it challenging to compile and hierarchize the scientific evidence that supports the efficacy of these interventions. Thus, we performed an umbrella review of published meta-analyses of controlled clinical trials that investigated the efficacy of psychosocial interventions on both core and related ASD symptoms.
METHODS
Each meta-analysis that was identified was re-estimated using a random-effects model with a restricted maximum likelihood estimator. The methodological quality of included meta-analyses was critically appraised and the credibility of the evidence was assessed algorithmically according to criteria adapted for the purpose of this study.
RESULTS
We identified a total of 128 meta-analyses derived from 44 reports. More than half of the non-overlapping meta-analyses were nominally statistically significant and/or displayed a moderate-to-large pooled effect size that favored the psychosocial interventions. The assessment of the credibility of evidence pointed out that the efficacy of early intensive behavioral interventions, developmental interventions, naturalistic developmental behavioral interventions, and parent-mediated interventions was supported by suggestive evidence on at least one outcome in preschool children. Possible outcomes included social communication deficits, global cognitive abilities, and adaptive behaviors. Results also revealed highly suggestive indications that parent-mediated interventions improved disruptive behaviors in early school-aged children. The efficacy of social skills groups was supported by suggestive evidence for improving social communication deficits and overall ASD symptoms in school-aged children and adolescents. Only four meta-analyses had a statistically significant pooled effect size in a sensitivity analysis restricted to randomized controlled trials at low risk of detection bias.
DISCUSSION
This umbrella review confirmed that several psychosocial interventions show promise for improving symptoms related to ASD at different stages of life. However, additional well-designed randomized controlled trials are still required to produce a clearer picture of the efficacy of these interventions. To facilitate the dissemination of scientific knowledge about psychosocial interventions for individuals with ASD, we built an open-access and interactive website that shares the information collected and the results generated during this umbrella review.
PRE-REGISTRATION
PROSPERO ID CRD42020212630.
Topics: Adolescent; Child; Child, Preschool; Humans; Autism Spectrum Disorder; Behavior Therapy; Communication; Psychosocial Intervention; Meta-Analysis as Topic
PubMed: 35790873
DOI: 10.1038/s41380-022-01670-z -
Frontiers in Cellular Neuroscience 2022Neurodevelopmental impairment contributes to the hallmark cognitive disability in individuals with Down syndrome (DS, trisomy 21, T21). The appearance of cognitive...
Neurodevelopmental impairment contributes to the hallmark cognitive disability in individuals with Down syndrome (DS, trisomy 21, T21). The appearance of cognitive deficits in infancy suggests that alterations emerge during the earliest stages of neural development and continue throughout the lifespan in DS. Neural correlates of intellectual and language function include cortical structures, specifically temporal and frontal lobes that are smaller in DS. Yet, despite increased understanding of the DS cognitive-behavioral phenotype in childhood, there is very little structural and histological information to help explain the deficits. Consequently, attempts to effectively design therapeutic targets or interventions are limited. We present a systematic review of published research on cortical development in DS that reveals a paucity of studies that rigorously identify cellular features that may underlie the gross morphological deficits of the developing DS brain. We assessed 115 published reports retrieved through PubMed and other sources and found that only 23 reported histological and/or immunohistochemical data to define cell composition affected in DS post-mortem brain. Further, our analysis reveals that many reports have limited samples sizes and few DS samples, making it difficult to draw conclusions that are generally applicable to the DS population. Thus, the lack of replication and limited number of studies indicate that more developmentally focused research, ideally using equal numbers of age-matched samples in analyses, is needed to elucidate the cellular nature of smaller brain size in DS.
PubMed: 35769326
DOI: 10.3389/fncel.2022.915272 -
Frontiers in Oncology 2022The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are...
The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.
PubMed: 35756675
DOI: 10.3389/fonc.2022.889161 -
Annals of Medicine and Surgery (2012) Jun 2022Blount disease is a developmental abnormality characterized by abnormal ossification of proximal tibia, resulting in lower limb deformities with tibia vara. The... (Review)
Review
BACKGROUND
Blount disease is a developmental abnormality characterized by abnormal ossification of proximal tibia, resulting in lower limb deformities with tibia vara. The condition worsens into knee deformity, gait abnormalities, and premature medial compartment osteoarthritis if left untreated. Managements of those deformities have also advanced in line with the understanding of the deformities. Without proper care management, they could lead into residual and translational deformities, increase of recurrence, and complicate the revision surgery.
METHODS
This study aims to enrich our understanding about the recent advances of treatments for Blount disease by reviewing 15 articles published with osteotomy surgeries and fixation methods. We also highlight many aspects of pre-operative assessment and planning, post-operative complications and recurrence, patients' follow-up, and overall satisfaction from patients' self-assessment.
RESULTS
The scope of this review is considered small but still covers various efforts to manage Blount diseases, including single-stage double osteotomy, grafting fibular fragments into tibia, two comparison studies, two unique case study, and experimental techniques to manage special cases requiring novel procedures.
CONCLUSION
Careful surgical planning, acute or gradual correction options, and the use of fixator should be tailored to individual cases.
PubMed: 35734736
DOI: 10.1016/j.amsu.2022.103784 -
Brain and Behavior Jul 2022Numerous cortical and subcortical structures have been studied extensively concerning alterations of their integrity as well as their neurotransmitters in depression.... (Review)
Review
BACKGROUND
Numerous cortical and subcortical structures have been studied extensively concerning alterations of their integrity as well as their neurotransmitters in depression. However, connections between these structures have received considerably less attention.
OBJECTIVE
This systematic review presents results from recent neuroimaging as well as neuropathologic studies conducted on humans and other mammals. It aims to provide evidence for impaired white matter integrity in individuals expressing a depressive phenotype.
METHODS
A systematic database search in accordance with the PRISMA guidelines was conducted to identify imaging and postmortem studies conducted on humans with a diagnosis of major depressive disorder, as well as on rodents and primates subjected to an animal model of depression.
RESULTS
Alterations are especially apparent in frontal gyri, as well as in structures establishing interhemispheric connectivity between frontal regions. Translational neuropathological findings point to alterations in oligodendrocyte density and morphology, as well as to alterations in the expression of genes related to myelin synthesis. An important role of early life adversities in the development of depressive symptoms and white matter alterations across species is thereby revealed. Data indicating that stress can interfere with physiological myelination patterns is presented. Altered myelination is most notably present in regions that are subject to maturation during the developmental stage of exposure to adversities.
CONCLUSION
Translational studies point to replicable alterations in white matter integrity in subjects suffering from depression across multiple species. Impaired white matter integrity is apparent in imaging as well as neuropathological studies. Future studies should focus on determining to what extent influencing white matter integrity is able to improve symptoms of depression in animals as well as humans.
Topics: Anisotropy; Brain; Depression; Depressive Disorder, Major; Diffusion Tensor Imaging; Humans; White Matter
PubMed: 35652161
DOI: 10.1002/brb3.2629 -
Frontiers in Neuroscience 2022Adequate sleep especially during developmental stages of life, is considered essential for normal brain development and believed to play an important role in promoting...
Adequate sleep especially during developmental stages of life, is considered essential for normal brain development and believed to play an important role in promoting healthy cognitive and psychosocial development, while persistent sleep disturbances and/or sleep deprivation during early life are believed to trigger many mental ailments such as anxiety disorders, depression, and cognitive impairment. Initially it was suggested that adverse mental health conditions adversely affect sleep, however, it is now accepted that this association is bidirectional. In fact, sleep disturbances are listed as a symptom of many mental health disorders. Of special interest is the association between early life sleep deprivation and its negative mental health outcomes. Studies have linked persistent early life sleep deprivation with later life behavioral and cognitive disturbances. Neurobiological underpinnings responsible for the negative outcomes of early life sleep deprivation are not understood. This is a significant barrier for early therapeutic and/or behavioral intervention, which can be feasible only if biological underpinnings are well-understood. Animal studies have provided useful insights in this area. This article focusses on the knowledge gained from the research conducted in the area of early life sleep deprivation, brain development, and behavioral function studies.
PubMed: 35592259
DOI: 10.3389/fnins.2022.833786 -
International Journal of Environmental... May 2022Evidence indicates shared physiopathological mechanisms between autism and psychosis. In this regard, the endocannabinoid system has been suggested to modulate neural... (Review)
Review
Evidence indicates shared physiopathological mechanisms between autism and psychosis. In this regard, the endocannabinoid system has been suggested to modulate neural circuits during the early stage of neurodevelopment, with implications for both autism and psychosis. Nevertheless, such potential common markers of disease have been investigated in both autism and psychosis spectrum disorders, without considering the conundrum of differentiating the two groups of conditions in terms of diagnosis and treatment. Here, we systematically review all human and animal studies examining the endocannabinoid system and its biobehavioral correlates in the association between autism and psychosis. Studies indicate overlapping biobehavioral aberrancies between autism and schizophrenia, subject to correction by modulation of the endocannabinoid system. In addition, common cannabinoid-based pharmacological strategies have been identified, exerting epigenetic effects across genes controlling neural mechanisms shared between autism and schizophrenia. Interestingly, a developmental and transgenerational trajectory between autism and schizophrenia is supported by evidence that exogenous alteration of the endocannabinoid system promotes progression to inheritable psychosis phenotypes in the context of biobehavioral autism vulnerability. However, evidence for a diametral association between autism and psychosis is scant. Several clinical implications follow from evidence of a developmental continuum between autism and psychosis as a function of the endocannabinoid system dysregulation.
Topics: Animals; Autistic Disorder; Cannabinoids; Endocannabinoids; Psychotic Disorders; Schizophrenia
PubMed: 35565034
DOI: 10.3390/ijerph19095616 -
Psychological Medicine May 2022Psychomotor slowing is a key feature of depressive disorders. Despite its great clinical importance, the pathophysiology and prevalence across different diagnoses and... (Meta-Analysis)
Meta-Analysis Review
Psychomotor slowing is a key feature of depressive disorders. Despite its great clinical importance, the pathophysiology and prevalence across different diagnoses and mood states are still poorly understood. Actigraphy allows unbiased, objective, and naturalistic assessment of physical activity as a marker of psychomotor slowing. Yet, the true effect-sizes remain unclear as recent, large systematic reviews are missing. We conducted a novel meta-analysis on actigraphically measured slowing in depression with strict inclusion and exclusion criteria for diagnosis ascertainment and sample duplications. Medline/PubMed and Web-of-Science were searched with terms combining mood-keywords and actigraphy-keywords until September 2021. Original research measuring actigraphy for ⩾24 h in at least two groups of depressed, remitted, or healthy participants and applying operationalized diagnosis was included. Studies in somatically ill patients, N < 10 participants/group, and studies using consumer-devices were excluded. Activity-levels between groups were compared using random-effects models with standardized-mean-differences and several moderators were examined. In total, 34 studies (n = 1804 patients) were included. Patients had lower activity than controls [standardized mean difference (s.m.d.) = -0.78, 95% confidence interval (CI) -0.99 to -0.57]. Compared to controls, patients with unipolar and bipolar disorder had lower activity than controls whether in depressed (unipolar: s.m.d. = -0.82, 95% CI -1.07 to -0.56; bipolar: s.m.d. = -0.94, 95% CI -1.41 to -0.46), or remitted/euthymic mood (unipolar: s.m.d. = -0.28, 95% CI -0.56 to 0.0; bipolar: s.m.d. = -0.92, 95% CI -1.36 to -0.47). None of the examined moderators had any significant effect. To date, this is the largest meta-analysis on actigraphically measured slowing in mood disorders. They are associated with lower activity, even in the remitted/euthymic mood-state. Studying objective motor behavior via actigraphy holds promise for informing screening and staging of affective disorders.
Topics: Actigraphy; Bipolar Disorder; Depression; Humans; Mood Disorders
PubMed: 35550677
DOI: 10.1017/S0033291722000903 -
JCPP Advances Jun 2022Peer adversity and aggression are common experiences in childhood and adolescence which lead to poor mental health outcomes. To date, there has been no review conducted...
BACKGROUND
Peer adversity and aggression are common experiences in childhood and adolescence which lead to poor mental health outcomes. To date, there has been no review conducted on the neurobiological changes associated with relational peer-victimisation, bullying and cyberbullying.
METHODS
This systematic review assessed structural and functional brain changes associated with peer-victimisation, bullying, and cyberbullying from 1 January 2000 to April 2021. A systematic search of Psychoinfo, Pubmed, and Scopus was performed independently by two reviewers using predefined criteria. Twenty-six studies met the selection criteria and were considered for review.
RESULTS
The data collected shows altered brain activation of regions implicated in processing reward, social pain, and affect; and heightened sensitivity and more widespread activation of brain regions during acute social exclusion, most notably in the amygdala, left parahippocampal gyrus, and fusiform gyrus, associated with victimisation exposure. In addition, victimised youths also demonstrated greater risk-taking behaviours following acute social exclusion showing greater ventral striatum-inferior frontal gyrus coupling, activation in the bilateral amygdala, orbital frontal cortex (OFC), medial prefrontal cortex (MPFC), temporoparietal junction (TPJ), medial posterior parietal cortex (MPPC) and dorsomedial prefrontal cortex (dmPFC), suggesting greater social monitoring, seeking of inclusion, and more effortful cognitive control. The studies included participants from a very broad developmental age range, mostly using cross-sectional measure of peer-victimisation exposure, at varying developmental stages.
CONCLUSIONS
This review highlights the need for more neuroimaging studies in cyberbullying, as well as longitudinal studies across more diverse samples for investigating gender, age, and developmental interactions with peer-victimising. This also brings to attention the importance of addressing bullying victimisation particularly in adolescence, given the evidence for social stress in heightening developmentally sensitive processes which are associated with depression, anxiety, and externalising symptoms.
PubMed: 37431463
DOI: 10.1002/jcv2.12081