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BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331 -
Journal of Medical Education and... 2021Heralded as a teaching, assessment and reflective tool, and increasingly as a longitudinal and holistic perspective of the educator's development, medical educator's... (Review)
Review
BACKGROUND
Heralded as a teaching, assessment and reflective tool, and increasingly as a longitudinal and holistic perspective of the educator's development, medical educator's portfolios (MEP)s are increasingly employed to evaluate progress, assess for promotions and career switches, used as a reflective tool and as a means of curating educational activities. However, despite its blossoming role, there is significant dissonance in the content and structure of MEPs. As such, a systematic scoping review (SSR) is proposed to identify what is known of MEPs and its contents.
METHODS
Krishna's Systematic Evidenced Based Approach (SEBA) was adopted to structure this SSR in SEBA of MEPs. SEBA's constructivist approach and relativist lens allow data from a variety of sources to be considered to paint a holistic picture of available information on MEPs.
RESULTS
From the 12 360 abstracts reviewed, 768 full text articles were evaluated, and 79 articles were included. Concurrent thematic and content analysis revealed similar themes and categories including: (1) , (2) , (3) and (4) .
DISCUSSION
This SSR in SEBA proffers a novel 5-staged evidence-based approach to constructing MEPs which allows for consistent application and assessment of MEPs. This 5-stage approach pivots on assessing and verifying the achievement of developmental milestones or 'micro-competencies' that facilitate micro-credentialling and effective evaluation of a medical educator's development and entrust-ability. This allows MEPs to be used as a reflective and collaborative tool and a basis for career planning.
PubMed: 35187262
DOI: 10.1177/23821205211000356 -
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 -
The Journal of Clinical Endocrinology... Jan 2022Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian...
CONTEXT
Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients.
DESIGN AND RESULTS
A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. Thus, serum AMH has clinical utility as a marker of testicular tissue in males with differences in sexual development and cryptorchidism and in the evaluation of persistent Mullerian duct syndrome. In females, serum AMH has been used as a predictive marker of ovarian reserve and fertility, but prepubertal and adolescent AMH assessments need to be interpreted cautiously. AMH is also a marker of tumor burden, progression, and recurrence in germ cell tumors of the ovary.
CONCLUSIONS
AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child. Nonstandardized assays necessitate the need for assay-specific normative data. The recognition of the role of AMH beyond gonadal development and maturation may usher in novel diagnostic and therapeutic applications that would further expand its utility in pediatric care.
Topics: Anti-Mullerian Hormone; Child; Child Development; Cryptorchidism; Disorder of Sex Development, 46,XY; Female; Gonads; Humans; Male; Ovarian Reserve; Sexual Maturation
PubMed: 34537849
DOI: 10.1210/clinem/dgab687 -
Dialogues in Clinical Neuroscience 2021Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better... (Review)
Review
Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better understanding of brain function, both normal and abnormal, throughout developmental stages. The degree to which childhood epilepsies exert a significant effect on brain network organisation and cognition remains unclear. The hypothesis suggests that the formation of abnormal networks associated with epileptogenesis early in life causes a disruption in normal brain network development and cognition, reflecting abnormalities in later life. Neurological diseases with onset during critical stages of brain maturation, including childhood epilepsy, may threaten this orderly neurodevelopmental process. According to the hypothesis that the formation of abnormal networks associated with epileptogenesis in early life causes a disruption in normal brain network development, it is then mandatory to perform a proper examination of children with new-onset epilepsy early in the disease course and a deep study of their brain network organisation over time. In regards, graph theoretical analysis could add more information. In order to facilitate further development of graph theory in childhood, we performed a systematic review to describe its application in functional dynamic connectivity using electroencephalographic (EEG) analysis, focussing on paediatric epilepsy.
Topics: Brain; Brain Mapping; Child; Cognition; Electroencephalography; Epilepsy; Humans; Magnetic Resonance Imaging; Nerve Net; Neurodevelopmental Disorders
PubMed: 35860177
DOI: 10.1080/19585969.2022.2043128 -
International Journal of Environmental... Feb 2017Childhood and adolescence are important developmental phases which influence health and well-being across the life span. Social relationships are fundamental to child... (Review)
Review
Childhood and adolescence are important developmental phases which influence health and well-being across the life span. Social relationships are fundamental to child and adolescent development; yet studies have been limited to children's relationships with other humans. This paper provides an evidence review for the potential associations between pet ownership and emotional; behavioural; cognitive; educational and social developmental outcomes. As the field is in the early stages; a broad set of inclusion criteria was applied. A systematic search of databases and grey literature sources found twenty-two studies meeting selection criteria. The review found evidence for an association between pet ownership and a wide range of emotional health benefits from childhood pet ownership; particularly for self-esteem and loneliness. The findings regarding childhood anxiety and depression were inconclusive. Studies also showed evidence of an association between pet ownership and educational and cognitive benefits; for example, in perspective-taking abilities and intellectual development. Evidence on behavioural development was unclear due to a lack of high quality research. Studies on pet ownership and social development provided evidence for an association with increased social competence; social networks; social interaction and social play behaviour. Overall, pet ownership and the significance of children's bonds with companion animals have been underexplored; there is a shortage of high quality and longitudinal studies in all outcomes. Prospective studies that control for a wide range of confounders are required.
Topics: Adolescent; Adolescent Development; Animals; Anxiety; Child; Child Development; Depression; Humans; Loneliness; Mental Health; Pets; Self Concept
PubMed: 28264460
DOI: 10.3390/ijerph14030234 -
BMC Ophthalmology Apr 2018Retinopathy of prematurity (ROP) refers to the developmental disorder of the retina in premature infants and is one of the most serious and most dangerous complications... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Retinopathy of prematurity (ROP) refers to the developmental disorder of the retina in premature infants and is one of the most serious and most dangerous complications in premature infants. The prevalence of ROP in Iran is different in various parts of Iran and its prevalence is reported to be 1-70% in different regions. This study aims to determine the prevalence and risk factors of ROP in Iran.
METHODS
This review article was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. To find literature about ROP in Iran, a comprehensive search was done using MeSH keywords in several online databases such as PubMed, Ovid, Science Direct, EMBASE, Web of Science, CINAHL, EBSCO, Magiran, Iranmedex, SID, Medlib, IranDoc, as well as the Google Scholar search engine until May 2017. Comprehensive Meta-analysis Software (CMA) Version 2 was used for data analysis.
RESULTS
According to 42 studies including 18,000 premature infants, the prevalence of ROP was reported to be 23.5% (95% CI: 20.4-26.8) in Iran. The prevalence of ROP stages 1, 2, 3, 4 and 5 was 7.9% (95% CI: 5.3-11.5), 9.7% (95% CI: 6.1-15.3), 2.8% (95% CI: 1.6-4.9), 2.9% (95% CI: 1.9-4.5) and 3.6% (95% CI: 2.4-5.2), respectively. The prevalence of ROP in Iranian girls and boys premature infants was 18.3% (95% CI: 12.8-25.4) and 18.9% (95% CI: 11.9-28.5), respectively. The lowest prevalence of ROP was in the West of Iran (12.3% [95% CI: 7.6-19.1]), while the highest prevalence was associated with the Center of Iran (24.9% [95% CI: 21.8-28.4]). The prevalence of ROP is increasing according to the year of study, and this relationship is not significant (p = 0.181). The significant risk factors for ROP were small gestational age (p < 0.001), low birth weight (p < 0.001), septicemia (p = 0.021), respiratory distress syndrome (p = 0.036), intraventricular hemorrhage (p = 0.005), continuous positive pressure ventilation (p = 0.023), saturation above 50% (p = 0.023), apnea (p = 0.002), frequency and duration of blood transfusion, oxygen therapy and phototherapy (p < 0.05), whereas pre-eclampsia decreased the prevalence of ROP (p = 0.014).
CONCLUSION
Considering the high prevalence of ROP in Iran, screening and close supervision by experienced ophthalmologists to diagnose and treat the common complications of pre-maturity and prevent visual impairment or blindness is necessary.
Topics: Humans; Infant, Newborn; Iran; Prevalence; Retinopathy of Prematurity; Risk Factors
PubMed: 29606108
DOI: 10.1186/s12886-018-0732-3 -
Human Reproduction Open 2023What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as... (Review)
Review
STUDY QUESTION
What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards?
SUMMARY ANSWER
Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare.
WHAT IS KNOWN ALREADY
In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend.
STUDY DESIGN SIZE DURATION
The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: ('advanced parental age' OR 'advanced maternal age' OR 'advanced paternal age' OR 'advanced reproductive age' OR 'late parent*' OR 'late motherhood' OR 'late fatherhood') AND ('IVF' OR 'in vitro fertilization' OR 'in-vitro-fertilization' OR 'fertilization in vitro' OR 'ICSI' OR 'intracytoplasmic sperm injection' OR 'reproductive techn*' OR 'assisted reproductive technolog*' OR 'assisted reproduction' OR 'assisted conception' OR 'reproduction' OR 'conception' OR 'birth*' OR 'pregnan*') AND ('wellbeing' OR 'well-being' OR 'psycho-social' OR 'social' OR 'ethical' OR 'right to reproduce' OR 'justice' OR 'family functioning' OR 'parental competenc*' OR 'ageism' OR 'reproductive autonomy' OR 'outcome' OR 'risk*' OR 'benefit*').
PARTICIPANTS/MATERIALS SETTING METHODS
The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found.
MAIN RESULTS AND THE ROLE OF CHANCE
A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ultimately, 69 studies were included in the final sample. The key results concerned four aspects relevant to the research goals. (i) The studies showed discrepancies in defining who is an APA parent. (ii) There was an imbalance in the empirical evidence produced for different participant groups (mothers, fathers, and offspring), with offspring being the most studied study subjects. (iii) The research topics studied underlined the increased risks of neuro-developmental and psychotic disorders among offspring. (iv) The observed advantages and disadvantages were varied and could not be compared, especially for the offspring of APA parents.
LIMITATIONS REASONS FOR CAUTION
Only English-language studies, published between 2000 and 2021, found in the above-mentioned databases were considered for this review.
WIDER IMPLICATIONS OF THE FINDINGS
More research is necessary to understand the risks and benefits of building a family at an APA for the offspring when they reach adulthood. Furthermore, studies that explore the perspective of older fathers and older parents from non-Western societies would be highly informative.
STUDY FUNDING/COMPETING INTERESTS
The writing of this manuscript was permitted by financial support provided by the Swiss National Science Foundation (Weave/Lead Agency funding program, grant number 10001AL_197415/1, project title 'Family Building at Advanced Parental Age: An Interdisciplinary Approach'). The funder had no role in the drafting of this manuscript and the views expressed therein are those of the authors. The authors have no conflicts of interest.
REGISTRATION NUMBER
This systematic review is registered in Prospero: CRD42022304564.
PubMed: 38045093
DOI: 10.1093/hropen/hoad042 -
Frontiers in Systems Neuroscience 2022Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block...
Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block arose from the seminal experiments of Hubel and Wiesel who presented convincing evidence that there existed a critical period for plasticity during development after which the brain lost its ability to change in accordance to shifts in sensory input. Despite the zeitgeist that mature brain is relatively immutable to change, there were a number of examples of adult neural plasticity emerging in the scientific literature. Interestingly, some of the earliest of these studies involved visual plasticity in the adult cat. Even earlier, there were reports of what appeared to be functional reorganization in adult rat somatosensory thalamus after dorsal column lesions, a finding that was confirmed and extended with additional experimentation. To demonstrate that these findings reflected more than a response to central injury, and to gain greater control of the extent of the sensory loss, peripheral nerve injuries were used that eliminated ascending sensory information while leaving central pathways intact. Merzenich, Kaas, and colleagues used peripheral nerve transections to reveal unambiguous reorganization in primate somatosensory cortex. Moreover, these same researchers showed that this plasticity proceeded in no less than two stages, one immediate, and one more protracted. These findings were confirmed and extended to more expansive cortical deprivations, and further extended to the thalamus and brainstem. There then began a series of experiments to reveal the physiological, morphological and neurochemical mechanisms that permitted this plasticity. Ultimately, Mowery and colleagues conducted a series of experiments that carefully tracked the levels of expression of several subunits of glutamate (AMPA and NMDA) and GABA (GABAA and GABAB) receptor complexes in primate somatosensory cortex at several time points after peripheral nerve injury. These receptor subunit mapping experiments revealed that membrane expression levels came to reflect those seen in early phases of critical period development. This suggested that under conditions of prolonged sensory deprivation the adult cells were returning to critical period like plastic states, i.e., developmental recapitulation. Here we outline the heuristics that drive this phenomenon.
PubMed: 36762289
DOI: 10.3389/fnsys.2022.1086680 -
The Cochrane Database of Systematic... Oct 2018Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as diabetes is becoming more prevalent. PAD can cause pain in the limbs while walking, known as intermittent claudication, or can be more severe and cause pain while at rest, ulceration, and ultimately gangrene and limb loss. This more severe stage of PAD is known as 'critical limb ischaemia'. Treatments for PAD include medications that help to reduce the increased risk of cardiovascular events and help improve blood flow, as well as endovascular or surgical repair or bypass of the blocked arteries. However, many people are unresponsive to medications and are not suited to surgical or endovascular treatment, leaving amputation as the last option. Gene therapy is a novel approach in which genetic material encoding for proteins that may help increase revascularisation is injected into the affected limbs of patients. This type of treatment has been shown to be safe, but its efficacy, especially regarding ulcer healing, effects on quality of life, and other symptomatic outcomes remain unknown.
OBJECTIVES
To assess the effects of gene therapy for symptomatic peripheral arterial disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched Cochrane CENTRAL, the Cochrane Vascular Specialised Register, MEDLINE Ovid, Embase Ovid, CINAHL, and AMED, along with trials registries (all searched 27 November 2017). We also checked reference lists of included studies and systematic reviews for further studies.
SELECTION CRITERIA
We included randomised and quasi-randomised studies that evaluated gene therapy versus no gene therapy in people with PAD. We excluded studies that evaluated direct growth hormone treatment or cell-based treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, performed quality assessment, and extracted data from the included studies. We collected pertinent information on each study, as well as data for the outcomes of amputation-free survival, ulcer healing, quality of life, amputation, all-cause mortality, ankle brachial index, symptom scores, and claudication distance.
MAIN RESULTS
We included in this review a total of 17 studies with 1988 participants (evidence current until November 2017). Three studies limited their inclusion to people with intermittent claudication, 12 limited inclusion to people with varying levels of critical limb ischaemia, and two included people with either condition. Study investigators evaluated many different types of gene therapies, using different protocols. Most studies evaluated growth factor-encoding gene therapy, with six studies using vascular endothelial growth factor (VEGF)-encoding genes, four using hepatocyte growth factor (HGF)-encoding genes, and three using fibroblast growth factor (FGF)-encoded genes. Two studies evaluated hypoxia-inducible factor 1-alpha (HIF-1α) gene therapy, one study used a developmental endothelial locus-1 gene therapy, and the final study evaluated a stromal cell-derived factor-1 (SDF-1) gene therapy. Most studies reported outcomes after 12 months of follow-up, but follow-up ranged from three months to two years.Overall risk of bias varied between studies, with many studies not providing sufficient detail for adequate determination of low risk of bias for many domains. Two studies did not utilise a placebo control, leading to risk of performance bias. Several studies reported in previous protocols or in their Methods sections that they would report on certain outcomes for which no data were then reported, increasing risk of reporting bias. All included studies reported sponsorships from corporate entities that led to unclear risk of other bias. The overall quality of evidence ranged from moderate to very low, generally as the result of heterogeneity and imprecision, with few or no studies reporting on outcomes.Evidence suggests no clear differences for the outcomes of amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving this treatment (all moderate-quality evidence). Low-quality evidence suggests improvement in complete ulcer healing with gene therapy (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.02 to 4.59; P = 0.04). We could not combine data on quality of life and can draw no conclusions at this time regarding this outcome (very low-quality evidence). We included one study in the meta-analysis for ankle brachial index, which showed no clear differences between treatments, but we can draw no overall association (low-quality evidence). We combined in a meta-analysis pain symptom scores as assessed by visual analogue scales from two studies and found no clear differences between treatment groups (very low-quality evidence). We carried out extensive subgroup analyses by PAD classification, dosage schedule, vector type, and gene used but identified no substantial differences.
AUTHORS' CONCLUSIONS
Moderate-quality evidence shows no clear differences in amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving gene therapy. Some evidence suggests that gene therapy may lead to improved complete ulcer healing, but this outcome needs to be explored with improved reporting of the measure, such as decreased ulcer area in cm², and better description of ulcer types and healing. Further standardised data that are amenable to meta-analysis are needed to evaluate other outcomes such as quality of life, ankle brachial index, symptom scores, and claudication distance.
Topics: Amputation, Surgical; Chemokine CXCL12; Extremities; Fibroblast Growth Factors; Genetic Therapy; Hepatocyte Growth Factor; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intermittent Claudication; Ischemia; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 30380135
DOI: 10.1002/14651858.CD012058.pub2