-
Pathologica Apr 2022Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and... (Review)
Review
Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and 2.5% of all fibroepithelial breast tumors. PT are classified into benign, borderline and malignant based upon their stromal morphology with a distribution of 60%, 20%, and 20%, respectively. Malignant PT of the breast constitute an uncommon challenging group of fibroepithelial neoplasms. They have a relatively high tendency to recur, although distant metastasis is uncommon, and nearly exclusive to malignant PT. Adequate surgical resection remains the standard approach to achieve maximal local control. Giant malignant PT are rare and a pose a diagnostic dilemma for pathologists, especially when comprised of sarcomatous elements. This review highlights the morphological features of PT detected in cytology and histology specimens and discusses diagnostic pitfalls and differential diagnosis.
Topics: Breast; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Fibroepithelial; Phyllodes Tumor
PubMed: 35414723
DOI: 10.32074/1591-951X-754 -
Journal of the Neurological Sciences Nov 2021Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but... (Review)
Review
BACKGROUND
Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD.
OBJECTIVE
To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management.
METHODS
A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus.
RESULTS
The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed.
CONCLUSIONS
The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists.
Topics: Consensus; Deglutition Disorders; Humans; Italy; Parkinson Disease
PubMed: 34624796
DOI: 10.1016/j.jns.2021.120008 -
The Cochrane Database of Systematic... May 2018Childhood apraxia of speech (CAS) affects a child's ability to produce sounds and syllables precisely and consistently, and to produce words and sentences with accuracy... (Review)
Review
BACKGROUND
Childhood apraxia of speech (CAS) affects a child's ability to produce sounds and syllables precisely and consistently, and to produce words and sentences with accuracy and correct speech rhythm. It is a rare condition, affecting only 0.1% of the general population. Consensus has been reached that three core features have diagnostic validity: (1) inconsistent error production on both consonants and vowels across repeated productions of syllables or words; (2) lengthened and impaired coarticulatory transitions between sounds and syllables; and (3) inappropriate prosody (ASHA 2007). A deficit in motor programming or planning is thought to underlie the condition. This means that children know what they would like to say but there is a breakdown in the ability to programme or plan the fine and rapid movements required to accurately produce speech. Children with CAS may also have impairments in one or more of the following areas: non-speech oral motor function, dysarthria, language, phonological production impairment, phonemic awareness or metalinguistic skills and literacy, or combinations of these. High-quality evidence from randomised controlled trials (RCTs) is lacking on interventions for CAS.
OBJECTIVES
To assess the efficacy of interventions targeting speech and language in children and adolescents with CAS as delivered by speech and language pathologists/therapists.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, eight other databases and seven trial registers up to April 2017. We searched the reference lists of included reports and requested information on unpublished trials from authors of published studies and other experts as well as information groups in the areas of speech and language therapy/pathology and linguistics.
SELECTION CRITERIA
RCTs and quasi-RCTs of children aged 3 to 16 years with CAS diagnosed by a speech and language pathologist/therapist, grouped by treatment types.
DATA COLLECTION AND ANALYSIS
Two review authors (FL, AM) independently assessed titles and abstracts identified from the searches and obtained full-text reports of all potentially relevant articles and assessed these for eligibility. The same two authors extracted data and conducted the 'Risk of bias' and GRADE assessments. One review author (EM) tabulated findings from excluded observational studies (Table 1).
MAIN RESULTS
This review includes only one RCT, funded by the Australian Research Council; the University of Sydney International Development Fund; Douglas and Lola Douglas Scholarship on Child and Adolescent Health; Nadia Verrall Memorial Scholarship; and a James Kentley Memorial Fellowship. This study recruited 26 children aged 4 to 12 years, with mild to moderate CAS of unknown cause, and compared two interventions: the Nuffield Dyspraxia Programme-3 (NDP-3); and the Rapid Syllable Transitions Treatment (ReST). Children were allocated randomly to one of the two treatments. Treatments were delivered intensively in one-hour sessions, four days a week for three weeks, in a university clinic in Australia. Speech pathology students delivered the treatments in the English language. Outcomes were assessed before therapy, immediately after therapy, at one month and four months post-therapy. Our review looked at one-month post-therapy outcomes only.We judged all core outcome domains to be low risk of bias. We downgraded the quality of the evidence by one level to moderate due to imprecision, given that only one RCT was identified. Both the NDP-3 and ReST therapies demonstrated improvement at one month post-treatment. A number of cases in each cohort had recommenced usual treatment by their speech and language pathologist between one month and four months post-treatment (NDP-3: 9/13 participants; ReST: 9/13 participants). Hence, maintenance of treatment effects to four months post-treatment could not be analysed without significant potential bias, and thus this time point was not included for further analysis in this review.There is limited evidence that, when delivered intensively, both the NDP-3 and ReST may effect improvement in word accuracy in 4- to 12-year-old children with CAS, measured by the accuracy of production on treated and non-treated words, speech production consistency and the accuracy of connected speech. The study did not measure functional communication.
AUTHORS' CONCLUSIONS
There is limited evidence that, when delivered intensively, both the NDP-3 and ReST may effect improvement in word accuracy in 4- to 12-year-old children with CAS, measured by the accuracy of production on treated and non-treated words, speech production consistency and the accuracy of connected speech. The study did not measure functional communication. No formal analyses were conducted to compare NDP-3 and ReST by the original study authors, hence one treatment cannot be reliably advocated over the other. We are also unable to say whether either treatment is better than no treatment or treatment as usual. No evidence currently exists to support the effectiveness of other treatments for children aged 4 to 12 years with idiopathic CAS without other comorbid neurodevelopmental disorders. Further RCTs replicating this study would strengthen the evidence base. Similarly, further RCTs are needed of other interventions, in other age ranges and populations with CAS and with co-occurring disorders.
Topics: Apraxias; Child; Child, Preschool; Humans; Speech Disorders; Speech Therapy; Speech-Language Pathology
PubMed: 29845607
DOI: 10.1002/14651858.CD006278.pub3 -
Journal of Thoracic Oncology : Official... Feb 2011Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung... (Review)
Review
International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.
INTRODUCTION
Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies.
METHODS
An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized.
CONCLUSIONS
This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.
Topics: Adenocarcinoma; Humans; Lung Neoplasms; Neoplasm Staging; Societies, Medical
PubMed: 21252716
DOI: 10.1097/JTO.0b013e318206a221 -
Gut Aug 2022Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with...
British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.
BACKGROUND
Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE.
METHODS
The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance.
RESULTS
Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research.
CONCLUSIONS
These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
Topics: Adult; Child; Consensus; Eosinophilic Esophagitis; Gastroenterology; Humans; Quality of Life; Societies, Medical
PubMed: 35606089
DOI: 10.1136/gutjnl-2022-327326 -
European Journal of Cancer (Oxford,... Sep 2021Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based...
BACKGROUND
Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based diagnostic support systems, in particular convolutional neural network (CNN)-based image analysis tools, have shown great potential in medical computer vision. In this systematic review, we summarise recent studies reporting CNN-based approaches for digital biomarkers for characterization and prognostication of gastrointestinal cancer pathology.
METHODS
Pubmed and Medline were screened for peer-reviewed papers dealing with CNN-based gastrointestinal cancer analyses from histological slides, published between 2015 and 2020.Seven hundred and ninety titles and abstracts were screened, and 58 full-text articles were assessed for eligibility.
RESULTS
Sixteen publications fulfilled our inclusion criteria dealing with tumor or precursor lesion characterization or prognostic and predictive biomarkers: 14 studies on colorectal or rectal cancer, three studies on gastric cancer and none on esophageal cancer. These studies were categorised according to their end-points: polyp characterization, tumor characterization and patient outcome. Regarding the translation into clinical practice, we identified several studies demonstrating generalization of the classifier with external tests and comparisons with pathologists, but none presenting clinical implementation.
CONCLUSIONS
Results of recent studies on CNN-based image analysis in gastrointestinal cancer pathology are promising, but studies were conducted in observational and retrospective settings. Large-scale trials are needed to assess performance and predict clinical usefulness. Furthermore, large-scale trials are required for approval of CNN-based prediction models as medical devices.
Topics: Deep Learning; Gastrointestinal Neoplasms; Humans; Treatment Outcome
PubMed: 34391053
DOI: 10.1016/j.ejca.2021.07.012 -
The British Journal of Surgery May 2021Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently...
BACKGROUND
Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged.
METHODS
The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds.
RESULTS
Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided.
CONCLUSION
The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chemoprevention; Colonoscopy; Colorectal Neoplasms, Hereditary Nonpolyposis; Delphi Technique; Digestive System Surgical Procedures; Early Detection of Cancer; Female; Genetic Carrier Screening; Genetic Testing; Genital Neoplasms, Female; Humans; Life Style; Prophylactic Surgical Procedures
PubMed: 34043773
DOI: 10.1002/bjs.11902 -
The Cochrane Database of Systematic... Mar 2015Children with developmental speech sound disorders have difficulties in producing the speech sounds of their native language. These speech difficulties could be due to... (Review)
Review
BACKGROUND
Children with developmental speech sound disorders have difficulties in producing the speech sounds of their native language. These speech difficulties could be due to structural, sensory or neurophysiological causes (e.g. hearing impairment), but more often the cause of the problem is unknown. One treatment approach used by speech-language therapists/pathologists is non-speech oral motor treatment (NSOMT). NSOMTs are non-speech activities that aim to stimulate or improve speech production and treat specific speech errors. For example, using exercises such as smiling, pursing, blowing into horns, blowing bubbles, and lip massage to target lip mobility for the production of speech sounds involving the lips, such as /p/, /b/, and /m/. The efficacy of this treatment approach is controversial, and evidence regarding the efficacy of NSOMTs needs to be examined.
OBJECTIVES
To assess the efficacy of non-speech oral motor treatment (NSOMT) in treating children with developmental speech sound disorders who have speech errors.
SEARCH METHODS
In April 2014 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (R) and Ovid MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Education Resources Information Center (ERIC), PsycINFO and 11 other databases. We also searched five trial and research registers, checked the reference lists of relevant titles identified by the search and contacted researchers to identify other possible published and unpublished studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials that compared (1) NSOMT versus placebo or control; and (2) NSOMT as adjunctive treatment or speech intervention versus speech intervention alone, for children aged three to 16 years with developmental speech sound disorders, as judged by a speech and language therapist. Individuals with an intellectual disability (e.g. Down syndrome) or a physical disability were not excluded.
DATA COLLECTION AND ANALYSIS
The Trials Search Co-ordinator of the Cochrane Developmental, Psychosocial and Learning Problems Group and one review author ran the searches. Two review authors independently screened titles and abstracts to eliminate irrelevant studies, extracted data from the included studies and assessed risk of bias in each of these studies. In cases of ambiguity or information missing from the paper, we contacted trial authors.
MAIN RESULTS
This review identified three studies (from four reports) involving a total of 22 children that investigated the efficacy of NSOMT as adjunctive treatment to conventional speech intervention versus conventional speech intervention for children with speech sound disorders. One study, a randomised controlled trial (RCT), included four boys aged seven years one month to nine years six months - all had speech sound disorders, and two had additional conditions (one was diagnosed as "communication impaired" and the other as "multiply disabled"). Of the two quasi-randomised controlled trials, one included 10 children (six boys and four girls), aged five years eight months to six years nine months, with speech sound disorders as a result of tongue thrust, and the other study included eight children (four boys and four girls), aged three to six years, with moderate to severe articulation disorder only. Two studies did not find NSOMT as adjunctive treatment to be more effective than conventional speech intervention alone, as both intervention and control groups made similar improvements in articulation after receiving treatments. One study reported a change in postintervention articulation test results but used an inappropriate statistical test and did not report the results clearly. None of the included studies examined the effects of NSOMTs on any other primary outcomes, such as speech intelligibility, speech physiology and adverse effects, or on any of the secondary outcomes such as listener acceptability.The RCT was judged at low risk for selection bias. The two quasi-randomised trials used randomisation but did not report the method for generating the random sequence and were judged as having unclear risk of selection bias. The three included studies were deemed to have high risk of performance bias as, given the nature of the intervention, blinding of participants was not possible. Only one study implemented blinding of outcome assessment and was at low risk for detection bias. One study showed high risk of other bias as the baseline characteristics of participants seemed to be unequal. The sample size of each of the included studies was very small, which means it is highly likely that participants in these studies were not representative of its target population. In the light of these serious limitations in methodology, the overall quality of the evidence provided by the included trials is judged to be low. Therefore, further research is very likely to have an important impact on our confidence in the estimate of treatment effect and is likely to change the estimate.
AUTHORS' CONCLUSIONS
The three included studies were small in scale and had a number of serious methodological limitations. In addition, they covered limited types of NSOMTs for treating children with speech sound disorders of unknown origin with the sounds /s/ and /z/. Hence, we judged the overall applicability of the evidence as limited and incomplete. Results of this review are consistent with those of previous reviews: Currently no strong evidence suggests that NSOMTs are an effective treatment or an effective adjunctive treatment for children with developmental speech sound disorders. Lack of strong evidence regarding the treatment efficacy of NSOMTs has implications for clinicians when they make decisions in relation to treatment plans. Well-designed research is needed to carefully investigate NSOMT as a type of treatment for children with speech sound disorders.
Topics: Articulation Disorders; Child; Child, Preschool; Dysphonia; Exercise Therapy; Female; Humans; Language Disorders; Male; Randomized Controlled Trials as Topic; Speech Sound Disorder; Speech Therapy
PubMed: 25805060
DOI: 10.1002/14651858.CD009383.pub2 -
Archives of Pathology & Laboratory... Sep 2023To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2)...
PURPOSE.—
To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
METHODS.—
The Update Panel conducted a systematic literature review to identify signals for updating recommendations.
RESULTS.—
The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations.
RECOMMENDATIONS.—
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
DISCUSSION.—
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.
Topics: Humans; Female; Breast Neoplasms; In Situ Hybridization, Fluorescence; Receptor, ErbB-2; In Situ Hybridization; Biomarkers, Tumor
PubMed: 37303228
DOI: 10.5858/arpa.2023-0950-SA -
The Cochrane Database of Systematic... Aug 2022Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness.
OBJECTIVES
To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence).
AUTHORS' CONCLUSIONS
It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Female; Humans; Male; Memantine; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36006807
DOI: 10.1002/14651858.CD013845.pub2