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PubMed2026

Impaired toilet training and bladder and bowel dysfunction in children with developmental coordination disorder - an underreported issue.

BACKGROUND & OBJECTIVE: Children with Developmental Coordination Disorder (DCD) face significant, yet often overlooked, challenges beyond motor impairments, including difficulties with toilet training and bladder and bowel dysfunctions (BBD). This study aims to explore whether children with DCD exhibit greater difficulties in these areas compared to typically developing children (TDC). METHOD: This cross-sectional case-control study included 84 children aged 5-8 years (42 DCD, 42 TDC), matched by school-grade and sex (33 boys and 9 girls per group). Parents completed the Vancouver Symptom Score for Dysfunctional Elimination Syndrome (VSSDES) to assess BBD symptoms, the Dutch DCD-questionnaire (DCD-Q) to evaluate motor coordination, and additional questions regarding toilet training, elimination diagnosis, and co-occurring conditions. Correlations and exploratory group differences were analysed. RESULTS: Parents of children with DCD reported significantly more toilet training difficulties than parents of controls (p < 0.001), including persistent accidents (47.6% vs. 9.5%), prolonged training (45.2% vs. 4.8%), and difficulties recognizing urination urgency (40.5% vs. 2.4%). The parental report of delayed attainment of bowel and bladder control (p < 0.05) and BBD rates (p < 0.001) was also significantly higher in children with DCD. Exploratory analyses indicated that the prevalence of these outcomes was not significantly different between children with DCD with and without co-occurring ADHD or autism, suggesting a possible primary association with DCD. Additionally, across both children with DCD and TDC, poorer motor skills were associated with more BBD symptoms (r = -0.474, p < 0.001). CONCLUSION: Children with DCD have a higher prevalence of toilet training difficulties and BBD compared to TDC, potentially affecting their psychosocial well-being. Greater awareness is crucial for timely and targeted care. Notably, the study's design, directly comparing children diagnosed with DCD to matched TDC, provides new insights into the prevalence of elimination difficulties in this population.

Humans↗

PubMed2025

Mixed Methods Findings from a Stepped Wedge Hybrid Implementation Trial of ATTAIN NAV: A Mental Health Family Navigation Intervention for Autistic Youth.

ATTAIN NAV (Access to Tailored Autism Integrated Care through Family Navigation) was delivered by family navigators to promote access to and engagement with mental health services for school-age autistic youth. This study used a mixed method, stepped wedge design to test the effects of family navigation on service and clinical outcomes while gathering information on implementation. Primary care providers from six clinics in California and 56 caregiver-child dyads enrolled in and completed the study. Clinics were randomized to either a technology-enhanced or standard family navigation condition. Caregivers completed assessments at baseline and post about child, family and services outcomes, and a subset participated in a post qualitative interview. Quantitative findings demonstrated improvements in child challenging behavior and parent activation across conditions although these improvements were more pronounced for families in the standard FN condition. At post-intervention, families in the standard FN condition reported higher levels of navigation satisfaction, a shorter time to attend their first mental health appointment, and higher engagement with their navigator. Qualitative findings complemented and expanded the quantitative survey findings. The ATTAIN NAV model of family navigation for autistic children with co-occurring mental health needs demonstrates promising implementation, service, and clinical benefits. Clinical Trials Registration. NCT05344378.

Humans↗

PubMed2025

Systematic Review of Symptoms of Catatonia in Autism Spectrum Disorder.

Catatonia is a complex neuropsychiatric syndrome characterized by disturbances in mood, motor function, behavior and speech. It is increasingly recognized in individuals with autism spectrum disorder (ASD), although its identification remains challenging due to the overlapping clinical features of the two conditions. Shared characteristics, such as echophenomena, mannerisms, social indifference and repetitive behaviors can obscure accurate diagnosis. Although reports suggest a significant prevalence of catatonia among individuals with ASD, the condition remains poorly understood and frequently under recognized, leading to substantial diagnostic and treatment challenges. A systematic review was conducted to characterize the symptoms of catatonia in individuals with ASD. The literature search included peer-reviewed journal articles published in English from 1980 onward, focusing on studies examining co-occurring catatonia and ASD. A qualitative framework analysis was implemented to evaluate 45 peer-reviewed studies, with findings interpreted in relation to, and extending beyond, the diagnostic criteria for catatonia outlined in the International Classification of Diseases, 11th revision (ICD-11). The objective was to identify symptom patterns extending beyond current diagnostic frameworks and to support improved clinical recognition and diagnostic precision in ASD populations. The review identified six primary symptom clusters associated with catatonia in individuals with ASD: (1) psychomotor activity, (2) speech disturbances, (3) changes in behavior/skills/functions, (4) mental health symptoms, (5) physiological symptoms, and (6) symptoms related to arousal and awareness. Notably, several symptoms observed within these clusters are not currently included in the ICD-11 diagnostic criteria for catatonia. These additional symptoms include tics, motor compliance, incoherent speech, self-injury, impaired cognition, and appetite changes, suggesting a broader clinical presentation of catatonia in ASD populations than is presently captured in existing diagnostic frameworks. The findings of this review highlight the significance of enhancing clinicians' awareness and understanding of how catatonia manifests in individuals with ASD. Most notably, six symptom clusters, psychomotor changes, speech disturbances, behavioral and functional regression, affective and psychiatric symptoms, physiological symptoms, and arousal/awareness disturbances, were observed. Several symptoms identified in this review are not included in the current diagnostic criteria, and their recognition may facilitate in earlier identification and timely intervention, potentially preventing the severe consequences of untreated catatonia in this population.

Humans↗

PubMed1991

Substance use and symptomatology among adolescent children of alcoholics.

This study assessed the magnitude and specificity of parental alcoholism as a risk factor for internalizing symptomatology, externalizing symptomatology, and alcohol and drug use in adolescence. We evaluated parents' and children's reports of symptomatology and children's reports of alcohol and drug use in a community sample of 454 adolescents. The results showed that parental alcoholism was a moderate to strong risk factor, with stronger risk associated with recent (rather than remitted) parental alcoholism. Multivariate analyses showed that the specificity of risk varied with the outcome measure. In predicting externalizing symptomatology, the risk associated with parental alcoholism was mediated by co-occurring parental psychopathology and environmental stress. However, in predicting alcohol use, the father's alcoholism was a specific risk factor above and beyond the more generalized effects of stress and family disruption.

Adolescent↗

PubMed1986

Empirically derived subclassification of the autistic syndrome.

A method is presented for empirical subclassification of autistic and autisticlike children, based on observations of current behavior. The advantage of the method is that it identifies profiles of co-occurring behaviors and accordingly assigns children to subtypes. The subtypes are more clinically homogeneous than the overall sample of autistic children. Preliminary findings are presented, including an effort to validate the subclasses by suggesting possible relationships between subtype membership and perinatal markers, developmental milestones, and independent measures of concurrent behavior.

Adolescent↗

PubMed1992

Prenatal exposure to heavy metals: effect on childhood cognitive skills and health status.

Prenatal exposure to seven heavy metals (cadmium, chromium, cobalt, lead, mercury, nickel, and silver) was determined for amniotic fluid taken from 92 pregnant women undergoing amniocentesis at approximately 16 to 18 weeks' gestation. Follow-up assessment of their children's cognitive skills and health status was conducted when the children were approximately 3 years of age. The presence of these metals co-occurred in amniotic fluid. A prenatal toxic risk score was derived which was a weighted score reflecting the presence of the various metals in amniotic fluid. The toxic risk score was negatively related to performance on the McCarthy Scales of Children's Abilities and positively related to the number of child illnesses reported. These results suggest the need for further prospective research on the adverse effects of prenatal exposure to various metals in combination.

Adult↗

PubMed1995

An overview of learning disabilities: psychoeducational perspectives.

In general, people with learning disabilities are a heterogeneous population that require a multidisciplinary evaluation and careful, well-planned intervention. Despite this heterogeneity, patterns of problems often co-occur. Therefore, diagnosticians and educators should look beyond single areas of achievement such as reading or arithmetic. In addition, problems in one area of learning typically have secondary impacts on higher levels of learning. That is, comprehension problems typically interfere with expression. Every effort should be made to examine patterns of problems and to avoid fragmentation of services so that each area of underachievement is not treated separately. Although learning disabilities usually interfere with school performance, they are not simply academic handicaps. They interfere with certain social activities as well as occupational pursuits. In many instances, they impact on mental health and self-esteem. Therefore, students need multiple services. And, as emphasized throughout this journal issue, learning disabled individuals may have comorbid conditions such as attention deficit disorder, depression, and neurologic problems. Furthermore, the problems may change over time. Children may first be identified because of language comprehension problems but later have reading or mathematics difficulty. With intervention, oral expressive problems may be alleviated but may be manifested later in written language.

Child↗

PubMed1991

Antisocial alcoholics: are there clinically significant diagnostic subtypes?

Of 360 alcoholic male inpatients assessed with a diagnostic interview, 106 (29%) were found to have a co-occurring diagnosis of antisocial personality. Of these ASP alcoholics, 86 were further subdivided into those with only ASP and alcoholism (n = 38), those with ASP, alcoholism and drug dependence (n = 30) and those with ASP, alcoholism and depression (n = 18; 9 of whom also had drug abuse). Comparisons among the three antisocial groups indicated that they differed in measures of psychopathology and course and severity of alcoholism. When the ASP groups were compared to an alcoholism only group, an earlier onset, more rapid course and increased percentage of many alcoholism symptoms were found in the ASP groups, confirming the findings of other studies.

Adult↗

PubMed1995

Child physical abuse and aggression: preliminary findings on the role of internalizing problems.

OBJECTIVE: To test the prediction that the interaction of physical abuse and internalizing problems will heighten levels of aggressive behavior in a group of disruptive children. METHOD: Fifty-two clinic-referred disruptive children (aged 7 through 15 years) were assessed in terms of history of physical abuse, internalizing behavior problems (rated by parents), and aggressive behavior (rated by parents, teachers, and clinic staff). RESULTS: Physically abused children with co-occurring high levels of internalizing problems (based on a median split) exhibited significantly higher levels of aggression as rated by parents (p < .000) and teachers (p < .020) and a trend toward heightened aggression as rated by staff (p < .08). The patterns were similar across the three independent informants and remained regardless of age, gender, or race. CONCLUSIONS: Physical abuse was related to heightened levels of aggression only in those children who also had emotional difficulties. Results lend some support to a transactional model of the development of aggression, suggesting that problems arise out of interactions between child factors (such as internalizing problems) and adverse family experiences (such as physical abuse).

Adolescent↗

PubMedDate not supplied

HIV infection and rheumatic diseases--autoimmune mechanisms in immunodeficient hosts.

The recognition of a newly acquired immunodeficiency syndrome (AIDS) in 1981 has had dramatic social and economic implications. Eventually, an epidemic of the viral infection developed with a potential to spread globally. The extraordinary breadth of AIDS research lead to the early identification of the causative agent: The human immunodeficiency virus (HIV) is a member of the lentivirus family and is characterized by its ability to remain latent within the genome of the infected host. The primary targets for the HIV are helper T-lymphocytes and monocytes/macrophages, which results in the progressive destruction of immune functions in the infected hosts. Binding to and entry into the cells is facilitated by a high-affinity interaction of a viral glycoprotein and the CD4 molecule. Signs of the immunodeficient state, manifested as a broad spectrum of opportunistic infections initially dominated the clinical presentations of HIV infected patients. Over the last decade, however, the manifestations of HIV infection have steadily grown and, surprisingly, include many rheumatic syndromes and autoimmune phenomena. The finding that HIV-infected individuals present with a highly progressive form of Reiter's syndrome and psoriasis has challenged our understanding of immune functions in HLA-B27 associated disorders. Obviously, CD8+ T-cells can maintain function despite the depletion of CD4+ helper T-cells. Consistent with the current model of the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, patients with these syndromes were described to go into remission when CD4+ T-cells were selectively depleted in active HIV infection. There is growing evidence that complex mechanisms arise from the interaction of the HIV and the human host which extend beyond the initial expectation that the virus only kills CD4+ helper T-cells. Indicating yet another aspect of HIV disease, a new syndrome mimicking Sjögren's syndrome has been encountered in HIV-infected patients and has been named the diffuse infiltrative lymphocytosis syndrome. Dense infiltrates of CD8+, potentially antiviral killer cells, are characteristically found in the salivary glands of patients who express a certain HLA genotype and who are, typically, long-term survivors of the disease. Recent reports have stressed a new mechanism of disease induction in HIV infected patients. Inappropriate induction of potentially destructive cytokines appears to be initiated by the viral infection and the expression of the viral genome seems to be effectively modulated by cytokines. In summary, HIV infection may provide important insights in the pathogenesis of rheumatic diseases co-occurring with HIV infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis, Rheumatoid↗

PubMed2026

A Novel Homozygous Mutation in ARL2BP Causes Multiple Morphological Abnormalities of the Flagella and Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) and multiple morphological abnormalities of the sperm flagella (MMAF) frequently co-occur in male infertility. However, the genetic basis of this syndromic presentation remains unclear. Using whole-exome sequencing, we identified a novel homozygous ARL2BP splice-site mutation (c.294-2A>G) in a 23-year-old infertile male from a consanguineous family who presented with syndromic PCD and MMAF. This variant causes aberrant pre-mRNA splicing and triggers nonsense-mediated mRNA decay, resulting in the complete absence of ARL2BP protein expression. Transmission electron microscopy revealed extensive disorganization of flagellar axonemes with consistent central pair (CP) microtubule depletion and disorganization of peripheral doublets. Immunofluorescence confirmed a severe deficiency of the CP protein SPAG6 in the sperm flagella. Notably, the patient presented without retinal symptoms. Given that ARL2BP-related retinitis pigmentosa generally emerges during the third decade, long-term ophthalmological follow-up is essential to detect delayed-onset retinal degeneration. In conclusion, these findings confirm ARL2BP as a causative gene for both PCD and MMAF, expanding the genotypic and phenotypic spectrum of ciliopathies.

Humans↗

PubMed2025

The effect of TERT promoter mutation on predicting meningioma outcomes: a multi-institutional cohort analysis.

BACKGROUND: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing. METHODS: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of the resection site, and TERTp status evaluated by Nov 1, 2024. Multi-modal profiling was used to assess TERTp mutation, focal gene alterations-including CDKN2A/B loss-and copy number alterations. An adjusted WHO grade was calculated for TERTp-mutant meningiomas, incorporating all WHO criteria except TERTp status. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to quantify the effect of TERTp mutation on the endpoints of overall survival and recurrence-free survival across adjusted WHO grade and co-occurring molecular alterations. FINDINGS: 64 (4·3%) of 1492 meningiomas were TERTp-mutant and 1428 (95·7%) were TERTp-wildtype. Of the TERTp-mutant meningiomas, 33 (51·6%) were from female patients and 31 (48·4%) were from male patients, and the overall median age was 67 years (IQR 60-75). Of the wildtype meningiomas, 965 (67·6%) were from female patients and 463 (32·4%) were from male patients, and the overall median age of the patients was 59 years (IQR 48-70). Data on race was inconsistently reported and thus excluded. The TERTp-mutant patients had a 5-year overall survival (49·4% [95% CI 33·7-72·4]) and 5-year recurrence-free survival (27·6% [95% CI 16·8-45·5]) resembling that of patients with WHO grade 3 TERTp-wildtype tumours (5-year overall survival 32·3% [95% CI 17·2-60·5], p=0·28, 5-year recurrence-free survival 14·3% [5·8-35·2], p=0·28). However, the TERTp-mutant group had heterogenous histological grading and was enriched for aggressive molecular features, with 1p loss present in 44 (77·2%) of 57 profiled tumours and CDKN2A/B loss in 24 (41·4%) of the 58 profiled tumours. Adjusting tumour grade revealed a subset of TERTp-mutant meningiomas that were more molecularly and clinically benign. Among TERTp-mutant tumours, CDKN2A/B loss played a defining role in stratifying tumour behaviour. Multivariable analysis confirmed this, with CDKN2A/B loss being significantly associated with shorter overall survival (HR 3·04 [95% CI 1·67-5·52], p=0·00026) and faster time to recurrence (HR 5·22 [95% CI 3·10-8·79], p<0·0001), while TERTp-mutation did not independently affect overall survival (HR 1·00 [95% CI 0·53-1·87], p=0·99) or recurrence-free survival (1·17 [95% CI 0·75-1·83], p=0·49). Sequencing for TERTp-mutation demonstrated clinical impact only among histologically WHO grade 2 meningiomas. INTERPRETATION: The indolent behaviour of certain TERTp-mutant meningiomas suggests that TERTp mutation is not sufficient to assign the most aggressive meningioma grade. Instead, TERT sequencing might offer prognostic utility in identifying high-risk cases among WHO grade 2 meningiomas. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, Friedberg Charitable Foundation, Courtney Meningioma Research Fund, Fleming Meningioma Research Fund, and the Gray Family Foundation.

Humans↗

PubMed2025

Genomic and Developmental Models to Predict Cognitive and Adaptive Outcomes in Autistic Children.

IMPORTANCE: Although early signs of autism are often observed between 18 and 36 months of age, there is considerable uncertainty regarding future development. Clinicians lack predictive tools to identify those who will later be diagnosed with co-occurring intellectual disability (ID). OBJECTIVE: To predict ID in children diagnosed with autism. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study involved the development and validation of models integrating genetic variants and developmental milestones to predict ID. Models were trained, cross-validated, and tested for generalizability across 3 autism cohorts: Simons Foundation Powering Autism Research (SPARK), Simons Simplex Collection, and MSSNG. Autistic participants were assessed older than 6 years of age for ID. Study data were analyzed from January 2023 to July 2024. EXPOSURES: Ages at attaining early developmental milestones, occurrence of language regression, polygenic scores for cognitive ability and autism, rare copy number variants, de novo loss-of-function and missense variants impacting constrained genes. MAIN OUTCOMES AND MEASURES: The out-of-sample performance of predictive models was assessed using the area under the receiver operating characteristic curve (AUROC), positive predictive values (PPVs), and negative predictive values (NPVs). RESULTS: A total of 5633 autistic participants (4574 male [81.2%]) were included in this analysis. On average, participants were diagnosed with autism at 4 (IQR, 3-7) years of age and assessed for ID at 11 (8-14) years of age, with 1159 participants (20.6%) being diagnosed with ID. The model integrating all predictors yielded an AUROC of 0.653 (95% CI, 0.625-0.681), and this predictive performance was cross-validated and generalized across cohorts. This modest performance reflected that only a subset of individuals carried large-effect variants, high polygenic scores, or presented delayed milestones. However, combinations of genetic variants that are typically not considered clinically relevant by diagnostic laboratories achieved PPVs of 55% and correctly identified 10% of individuals developing ID. The addition of polygenic scores to developmental milestones specifically improved NPVs rather than PPVs. Notably, the ability to stratify ID probabilities using genetic variants was up to 2-fold higher in individuals with delayed milestones compared with those with typical development. CONCLUSIONS AND RELEVANCE: Results of this prognostic study suggest that the growing number of neurodevelopmental condition-associated variants cannot, in most cases, be used alone for predicting ID. However, models combining different classes of variants with developmental milestones provide clinically relevant individual-level predictions that could be useful for targeting early interventions.

Humans↗

PubMed1986

beta-Endorphin/beta-lipotropin immunoreactivity in endogenous depression. Effect of dexamethasone.

This study addresses the question of whether pituitary peptides (ie, beta-endorphin) show regulatory disruption in endogenous depression and, if so, does it co-occur in the same subjects who show cortisol dysregulation. Endogenously depressed patients and psychiatric controls from three centers were evaluated, when not taking medications, and studied for plasma cortisol and beta-endorphin levels. Plasma samples were taken at four time points over one hour, on the basal day, and 16 hours after 1 mg of dexamethasone. From 33% to 69% of the endogenous patients were abnormal in their postdexamethasone cortisol levels, and from 50% to 69% were abnormal on postdexamethasone beta-endorphin values (vs 0% and 8%, respectively, for controls). When endogenous subjects were evaluated for abnormality on both cortisol and beta-endorphin, after dexamethasone, it was found that the two measures of hypothalamic-pituitary-adrenal dysfunction did not necessarily co-vary. In fact when having either abnormal beta-endorphin or cortisol levels (or both) was used as a biological marker a larger number of the endogenous patients were detected than with either measure alone. Our conclusions are as follows: Plasma beta-endorphin shows a circadian rhythm similar to that seen with corticotropin (ACTH) and is suppressable by dexamethasone. In many endogenous patients plasma beta-endorphin levels escape from dexamethasone suppression. Many of these subjects are not cortisol escapers. When abnormality of either the beta-endorphin or cortisol is considered it is clear that both levels of the hypothalamic-pituitary-adrenal axis can be dysregulated in endogenous depression.

Adolescent↗

PubMed2026

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans↗

PubMed1995

Mental health problems and alcohol abuse: co-occurrence and gender differences.

A growing body of research has demonstrated that alcohol abuse co-occurs with a broad range of mental health problems. To date, however, there is a scarcity of data concerning the co-occurrence of alcohol abuse and other problems in people who seek mental health outpatient services and, consequently, about gender differences among them. The present study surveyed 376 clients receiving outpatient services at a mental health center. Results demonstrate that women self-reported significantly more psychophysiological distress and family pathology and men reported more community problems and health concerns. Men drank significantly more than women, were more likely to have had a problem with alcohol over the past year, and were more likely to have been treated for substance abuse. For both men and women, the level of alcohol consumption varied directly with the severity of psychophysiological symptoms and community and health problems.

Adolescent↗

PubMed2026

Exploring cross-category relationships between symptoms in people with hypermobile EDS (hEDS) to identify disability patterns.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with variable symptom presentation across multiple organ systems and significant morbidity. Little is known about hEDS etiology and identifying patterns of symptom co-occurrence can reveal previously unidentified relationships between phenotypes and inform studies of underlying disease pathophysiology for symptoms that may share functional biological pathways. In this exploratory analysis, we specifically assessed the distribution of symptoms in case and controls to identify clusters of co-occurring symptoms. METHODS: We have interrogated clinically relevant symptom areas in 47 females with hEDS, 36 age-matched female controls and 8 hypermobile patients without chronic pain. Studied symptoms include general health, mental health, body pain, vitality and energy, autonomic symptoms, bleeding, and gastrointestinal symptoms. We conducted hierarchal clustering on principle components (HCPC) to identify groups and compared the groups for the previously described symptoms. Radial plots were used to identify relationships between severe symptom categories. RESULTS: Our analysis reveals statistically significantly more severe symptoms in all categories in people with hEDS compared with age- and sex-matched controls and asymptomatic hypermobile patients. HCPC identified clearly separated Low, Moderate, and High symptom groups within participants. The Low dysfunction groups include nearly all controls and hypermobile patients without chronic pain. The High dysfunction group includes ~60% of people with hEDS, while around 40% are in the Moderate dysfunction cluster. Cluster solutions for all participants were stable with moderate fit (silhouette 0.64; Jaccard boot mean 0.91). Group level radial plots showed high bleeding severity across all symptom clusters, while disproportional severity of general health, physical function, limitation of role due to physical symptoms, pain, and social functioning deficits differentiates the High from Moderate and Low Dysfunction clusters. CONCLUSION: Using this analysis at the group level has revealed patterns suggesting a progression of disease symptoms. People with hypermobility do not uniformly have severe symptoms but instead have some symptoms that differentiate from non-hypermobile individuals. While exploratory, using a radar multi-symptom analysis may be used to evaluate disproportionately severe symptoms contributing to the patterns of global symptom severity. These include pain but also ability to perform roles, suggesting strong utility of physical and occupational therapies to emphasize coping. This may also allow better targeting of etiological studies and may have additional utility at an individual level to develop symptom management strategies.

Humans↗

PubMed1987

Maternal toxicity of drugs and metabolic disorders--a possible etiologic factor in the intrauterine death and congenital malformation: a critique on human data.

Human data were searched to determine whether an association of metabolically or drug-induced maternal toxicity with congenital malformations and intrauterine death would be valid for the human species. Intrauterine death was found to occur in association with maternal homeostatic alterations resulting from phenylketonuria and diabetes, and with maternal toxicity from toxemia of pregnancy, leukemia, burns, alcohol, aminopterin, isotretinoin, and possibly trimethadione. A pattern of anomalies found similar (except for minor differences) and thus suggestive of a possible common cause, was observed among anomalies to phenylketonuria, diabetes mellitus, aminopterin, alcohol, warfarin, phenytoin, phenobarbital, trimethadione, valproic acid, and isotretinoin. The pattern usually consisted of deficiencies in pre- and postnatal development, mid-facial hypoplasia, cleft palate, atrial or ventricular septal defects, patent ductus arteriosus, hypospadias, hernias, and other less frequent anomalies. The pattern is tentatively associated with alterations in maternal physiology resulting from phenylketonuria and diabetes; maternal toxicity of aminopterin, alcohol, and diverse factors co-occurring with warfarin use; and therapeutic doses (generally toxic in adults) of phenytoin, phenobarbital, trimethadione, and valproic acid. Whether these fetal malformations and intrauterine deaths would occur at nonmaterno-toxic levels of the above teratogenic agents, and, consequently, the strength of the associations could not be estimated for lack of data. However, human data seem to provide some, though weak, support and not to contradict the previous assumption formulated from animal studies that maternal toxicity may be causally related to fetal malformations and embryo-fetal mortality.

Abnormalities, Drug-Induced↗