Metabolomic profiles in Jamaican children with and without autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls. Objective: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. Methods: We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica (ERAJ-2), which was a 1:1 age (±6 months)-and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and imputation of missing values, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Results: Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three of these metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. Additionally, the amino acid sarcosine exhibited a significant association with ASD. Conclusions: These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

Enhancing long-term survival prediction with two short-term events: Landmarking with a flexible varying coefficient model.

Patients with cardiovascular diseases who experience disease-related short-term events, such as hospitalizations, often exhibit diverse long-term survival outcomes compared to others. In this study, we aim to improve the prediction of long-term survival probability by incorporating two short-term events using a flexible varying coefficient landmark model. Our objective is to predict the long-term survival among patients who survived up to a pre-specified landmark time since the initial admission. Inverse probability weighting estimation equations are formed based on the information of the short-term outcomes before the landmark time. The kernel smoothing method with the use of cross-validation for bandwidth selection is employed to estimate the time-varying coefficients. The predictive performance of the proposed model is evaluated and compared using predictive measures: area under the receiver operating characteristic curve and Brier score. Simulation studies confirm that parameters under the landmark models can be estimated accurately and the predictive performance of the proposed method consistently outperforms existing methods that either do not incorporate or only partially incorporate information from two short-term events. We demonstrate the practical application of our model using a community-based cohort from the Atherosclerosis Risk in Communities (ARIC) study.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Regression analysis of multivariate recurrent event data allowing time-varying dependence with application to stroke registry data.

In multivariate recurrent event data, each patient may repeatedly experience more than one type of event. Analysis of such data gets further complicated by the time-varying dependence structure among different types of recurrent events. The available literature regarding the joint modeling of multivariate recurrent events assumes a constant dependency over time, which is strict and often violated in practice. To close the knowledge gap, we propose a class of flexible shared random effects models for multivariate recurrent event data that allow for time-varying dependence to adequately capture complex correlation structures among different types of recurrent events. We developed an expectation-maximization algorithm for stable and efficient model fitting. Extensive simulation studies demonstrated that the estimators of the proposed approach have satisfactory finite sample performance. We applied the proposed model and the estimating method to data from a cohort of stroke patients identified in the University of Texas Houston Stroke Registry and evaluated the effects of risk factors and the dependence structure of different types of post-stroke readmission events.

Factors associated with blood mercury concentrations and their interactions with three glutathione S-transferase genes (GSTT1, GSTM1, and GSTP1): an exposure assessment study of typically developing Jamaican children.

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms. METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general linear models (GLMs). RESULTS: We identified the child's age, consumption of saltwater fish, canned fish (sardine, mackerel), string beans, grain, and starches (pasta, macaroni, noodles) as the environmental factors significantly associated with BHgCs (all P < 0.05). A significant interaction between consumption of canned fish (sardine, mackerel) and GSTP1 in relation to BHgC using either a co-dominant or recessive genetic model (overall interaction P = 0.01 and P < 0.01, respectively) indicated that consumption of canned fish (sardine, mackerel) was significantly associated with higher mean BHgC only among children with the GSTP1 Ile105Val, Ile/Ile [Ratio of mean Hg (95% CI) = 1.59 (1.09, 2.32), P = 0.02] and Ile/Val [Ratio of mean Hg (95% CI) = 1.46 (1.12, 1.91), P = 0.01] genotypes. CONCLUSIONS: Since this is the first study from Jamaica to report these findings, replication in other populations is recommended.

Multimorbidity phenotypes in ankylosing spondylitis and their association with disease activity and functional impairment: Data from the prospective study of outcomes in ankylosing spondylitis cohort.

OBJECTIVES: To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS). METHODS: Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method was used to examine the associations of multimorbidity counts and multimorbidity clusters with measures of disease activity and functional status over time. RESULTS: Among 1,270 AS patients (9,885 visits) with a median follow-up of 2.9 years (IQ range: 1.0-6.8 years), the prevalence of MM2+ and MM5+ was 49 % and 9 % respectively. We identified five multimorbidity clusters: depression (n = 321, 25 %), hypertension (n = 284, 22 %), uveitis (n = 274, 22 %), no morbidities (n = 238, 19 %), and miscellaneous (n = 153, 12 %). Patients in the depression cluster were more likely to be female and had significantly more morbidities and worse disease activity and functional status compared to those with no morbidities. CONCLUSION: Approximately 49 % of AS patients in the PSOAS cohort had multimorbidity and five distinct multimorbidity phenotypes were identified. In addition to the number of morbidities, the type of morbidity appears to be important to longitudinal outcomes in AS. The depression cluster was associated with worse disease activity and function.

Demonstration of ultrasound-mediated therapeutic delivery of fibrin-targeted pioglitazone-loaded echogenic liposomes into the arterial bed for attenuation of peri-stent restenosis.

Peri-stent restenosis following stent implantation is a major clinical problem. We have previously demonstrated that ultrasound-facilitated liposomal delivery of pioglitazone (PGN) to the arterial wall attenuated in-stent restenosis. To evaluate ultrasound mediated arterial delivery, in Yucatan miniswine, balloon inflations were performed in the carotid and subclavian arteries to simulate stent implantation and induce fibrin formation. The fibrin-binding peptide, GPRPPGGGC, was conjugated to echogenic liposomes (ELIP) containing dinitrophenyl-L-alanine-labelled pioglitazone (DNP-PGN) for targeting purposes. After pre-treating the arteries with nitroglycerine, fibrin-binding peptide-conjugated PGN-loaded ELIP (PAFb-DNP-PGN-ELIP also termed atheroglitatide) were delivered to the injured arteries via an endovascular catheter with an ultrasound core, either with or without ultrasound application (EKOSTM Endovascular System, Boston Scientific). In arteries treated with atheroglitatide, there was substantial delivery of PGN into the superficial layers (5 µm from the lumen) of the arteries with and without ultrasound, [(1951.17 relative fluorescence units (RFU) vs. 1901.17 RFU; P-value = 0.939)]. With ultrasound activation there was increased penetration of PGN into the deeper arterial layers (up to 35 µm from the lumen) [(13195.25 RFU vs. 7681.00 RFU; P-value = 0.005)]. These pre-clinical data demonstrate ultrasound mediated therapeutic vascular delivery to deeper layers of the injured arterial wall. This model has the potential to reduce peri- stent restenosis.

Why Do Some Patients Have Severe Sacroiliac Disease But No Syndesmophytes in Ankylosing Spondylitis? Data From a Nested Case-Control Study.

OBJECTIVE: Sacroiliac (SI) joint and spinal inflammation are characteristic of ankylosing spondylitis (AS), but some patients with AS have been identified who have discordant radiographic disease. We studied an AS subgroup with long-standing disease and fused SI joints. We identified factors associated with discrepant degrees of radiographic damage between the SI joints and spine. METHODS: From the Prospective Study of Outcomes in AS (PSOAS) cohort, patients with a disease duration ≥ 20 years and fused SI joints were included in a nested case-control design. Patients with and without syndesmophytes were used as cases and controls for analysis. We used classification and regression tree (CART) analysis to determine risk factors for syndesmophytes presence and reexamined the validity of the risk factors using univariable logistic regression models. RESULTS: There were 354 patients in the subgroup, 23 of whom lacked syndesmophytes. CART analysis showed females were less likely to have syndesmophytes. The next important predictor was age of symptom onset in males, with age of onset ≤ 16 years being less likely to have syndesmophytes. Univariable analysis confirmed females were less likely to have syndesmophytes (odds ratio [OR] 0.17, 95% CI 0.07-0.41). Syndesmophyte presence was associated with HLA-B27 positivity (P = 0.03) and age of symptom onset > 16 years old (OR 2.72, 95% CI 1.15-6.45). All 23 patients who lacked syndesmophytes were HLA-B27 positive. CONCLUSION: Using CART analysis and univariable modeling, women were less likely to have syndesmophytes despite advanced disease duration and SI joint disease. Patients with younger age of symptom onset were less likely to have syndesmophytes. All patients without syndesmophytes were HLA-B27 positive, indicating HLA-B27 positivity may be more associated with SI disease than spinal disease.

Additive or Interactive Associations of Food Allergies with Glutathione S-Transferase Genes in Relation to ASD and ASD Severity in Jamaican Children.

To investigate additive and interactive associations of food allergies with three glutathione S-transferase (GST) genes in relation to ASD and ASD severity in Jamaican children. Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of food allergies with polymorphisms in GST genes (GSTM1, GSTP1 and GSTT1) in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domains specific comparison scores (CSs) by fitting general linear models. Although food allergies and GST genes were not associated with ASD, ASD cases allergic to non-dairy food had higher mean ADOS-2 Restricted and Repetitive Behaviors (RRB) CS (8.8 vs. 8.0, P = 0.04). In addition, allergy to dairy was associated with higher mean RRB CS only among ASD cases with GSTT1 DD genotype (9.9 vs. 7.8, P < 0.01, interaction P = 0.01), and GSTP1 Val/Val genotype under a recessive genetic model (9.8 vs. 7.8, P = 0.02, interaction P = 0.06). Our findings are consistent with the role for GST genes in ASD and food allergies, though require replication in other populations.

Interactions between Environmental Factors and Glutathione S-Transferase (GST) Genes with Respect to Detectable Blood Aluminum Concentrations in Jamaican Children.

Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2−8 years) who participated as controls in an age- and sex-matched case−control study in Jamaica. We investigated additive and interactive associations among environmental factors and children's genotypes for glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1), in relation to having a detectable blood aluminum concentration (BAlC) of >5.0 µg/L, using multivariable logistic regression models. Findings from interactive models revealed that the odds of having a detectable BAlC was significantly higher among children who ate string beans (p ≤ 0.01), whereas about 40% lower odds of having a detectable BAlC was observed in children with higher parental education level, (p = 0.02). A significant interaction between consumption of saltwater fish and GSTP1 in relation to having a detectable BAlC using either co-dominant or dominant genetic models (overall interaction p = 0.02 for both models) indicated that consumption of saltwater fish was associated with higher odds of having a detectable BAlC only among children with the GSTP1 Ile105Val Ile/Ile genotype using either co-dominant or dominant models [OR (95% CI) = 2.73 (1.07, 6.96), p = 0.04; and OR (95% CI) = 2.74 (1.08, 6.99), p = 0.03]. Since this is the first study from Jamaica that reports such findings, replication in other populations is warranted.

Severity of Child Autistic Symptoms and Parenting Stress in Mothers of Children with Autism Spectrum Disorder in Japan and USA: Cross-Cultural Differences.

The purpose of this study was to compare the relationship between parenting stress and autistic symptom severity in the U.S. and Japan. Fifty-two U.S. and 51 Japanese mothers of children aged 2-12 with autism completed measures of parenting stress and child characteristics, including the parenting stress index (PSI), the social communication questionnaire (SCQ), and social responsiveness scale-2 (SRS-2). There was a nonlinear relationship between the child's autistic symptom severity and parenting stress in both countries. We also found some cultural differences: in the parent domain, the relationships between children's SCQ scores and PSI scores differed significantly between the U.S. and Japan. Our findings suggest that autistic severity symptom scores may reflect cross-cultural differences in parenting beliefs, views toward autism, and response styles for evaluating children's behavior. The findings also suggest that parents need support regardless of the child's autism severity, including those with mild to moderate symptoms. Expanding on this line of research and understanding cultural influences on parenting stress may help service providers and agencies offer more culturally sensitive services, parent-education courses, and intervention programs.

Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder.

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2−8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child's parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

Chronic inflammatory back pain commencing late in life: a neglected concept.

Chronic inflammatory back pain (CIBP) occurs in up to one-third of those with chronic back pain. Criteria for diagnosis of inflammatory back pain include an onset below 50 years. Using the US National Health and Nutrition Examination Survey data for 2009-2010, we showed that 3% of adults aged 50-69 years have features of CIBP with onset on or after 50 years. There is little information in the literature on CIBP of late onset. Patients with late onset CIBP may be falling through the cracks.

Younger age of stroke in low-middle income countries is related to healthcare access and quality.

Stroke is the second leading cause of mortality globally with higher burden and younger age in low-middle income countries (LMICs) than high-income countries (HICs). However, it is unclear to what extent differences in healthcare access and quality (HAQ) and prevalence of risk factors between LMICs and HICs contribute to younger age of stroke in LMICs. In this systematic review, we conducted meta-analysis of 67 articles and compared the mean age of stroke between LMICs and HICs, before and after adjusting for HAQ index. We also compared the prevalence of main stroke risk factors between HICs and LMICs. The unadjusted mean age of stroke in LMICs was significantly lower than HICs (63.1 vs. 68.6), regardless of gender (63.9 vs. 66.6 among men, and 65.6 vs. 70.7 among women) and whether data were collected in population- (64.7 vs. 69.5) or hospital-based (62.6 vs. 65.9) studies (all p < 0.01). However, after adjusting for HAQ index, the difference in the mean age of stroke between LMICs and HICs was not significant (p ≥ 0.10), except among women (p = 0.048). In addition, while the median prevalence of hypertension in LMICs was 23.4% higher than HICs, the prevalence of all other risk factors was lower in LMICs than HICs. Our findings suggest a much larger contribution of HAQ to the younger mean age of stroke in LMICs, as compared with other potential factors. Additional studies on stroke care quality and accessibility are needed in LMICs.

Additive and Interactive Associations of Environmental and Sociodemographic Factors with the Genotypes of Three Glutathione S-Transferase Genes in Relation to the Blood Arsenic Concentrations of Children in Jamaica.

Arsenic (As) is a metalloid that has been classified as a xenobiotic with toxic effects on human beings, especially on children. Since the soil in Jamaica contains As, dietary intake is considered the main source of As exposure in Jamaicans. In addition, glutathione S-transferase (GST) genes, including GSTT1, GSTP1, and GSTM1, play an important role in the metabolism of xenobiotics including As in humans. Using data from 375 typically developing children (2-8 years) in Jamaica, we investigated the environmental and sociodemographic factors, as well as their possible interactions with the children's genotype for GST genes in relation to having a detectable level of blood As concentration (i.e., >1.3 µg/L). Using multivariable logistic regression, we have identified environmental factors significantly associated with blood As concentrations that include a child's age, parental education levels, and the consumption of saltwater fish, cabbage, broad beans, and avocado (all p < 0.01). Based on the multivariable analysis including gene x environment interactions, we found that among children with the Ile/Ile genotype for GSTP1 Ile105Val, children who consumed avocado had higher odds of having a detectable blood As concentration compared to children who did not eat avocado.

Role of faculty characteristics in failing to fail in clinical clerkships.

INTRODUCTION: In the context of competency-based medical education, poor student performance must be accurately documented to allow learners to improve and to protect the public. However, faculty may be reluctant to provide evaluations that could be perceived as negative, and clerkship directors report that some students pass who should have failed. Student perception of faculty may be considered in faculty promotion, teaching awards, and leadership positions. Therefore, faculty of lower academic rank may perceive themselves to be more vulnerable and, therefore, be less likely to document poor student performance. This study investigated faculty characteristics associated with low performance evaluations (LPEs). METHOD: The authors analysed individual faculty evaluations of medical students who completed the third-year clerkships over 15 years using a generalised mixed regression model to assess the association of evaluator academic rank with likelihood of an LPE. Other available factors related to experience or academic vulnerability were incorporated including faculty age, race, ethnicity, and gender. RESULTS: The authors identified 50 120 evaluations by 585 faculty on 3447 students between January 2007 and April 2021. Faculty were more likely to give LPEs at the midpoint (4.9%), compared with the final (1.6%), evaluation (odds ratio [OR] = 4.004, 95% confidence interval [CI] [3.59, 4.53]; p < 0.001). The likelihood of LPE decreased significantly during the 15-year study period (OR = 0.94 [0.90, 0.97]; p < 0.01). Full professors were significantly more likely to give an LPE than assistant professors (OR = 1.62 [1.08, 2.43]; p = 0.02). Women were more likely to give LPEs than men (OR = 1.88 [1.37, 2.58]; p 0.01). Other faculty characteristics including race and experience were not associated with LPE. CONCLUSIONS: The number of LPEs decreased over time, and senior faculty were more likely to document poor medical student performance compared with assistant professors.

Fungi: Friend or Foe? A Mycobiome Evaluation in Children With Autism and Gastrointestinal Symptoms.

ABSTRACT: Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 [ELISA]) were evaluated. We observed no changes in the abundance of total fungal species (alpha diversity) between groups. Samples with identifiable Candida spp. were present in 4 of 19 (21%) ASD + GI, in 5 of 9 (56%) ASD - GI, and in 4 of 16 (25%) TD children (overall P = 0.18). The presence of Candida spp. did not correlate with behavioral or GI symptoms (P = 0.38, P = 0.5, respectively). Fecal calprotectin was normal in all but one child. Finally, there was no significance in serum dectin-1 levels, suggesting no increased fungal immunity in children with ASD. Our data suggest that fungi are present at normal levels in the stool of children with ASD and are not associated with gut inflammation.

Identifying trajectories of radiographic spinal disease in ankylosing spondylitis: a 15-year follow-up study of the PSOAS cohort.

OBJECTIVES: Little is known with certainty about the natural history of spinal disease progression in ankylosing spondylitis (AS). Our objective was to discover if there were distinct patterns of change in vertebral involvement over time and to study associated clinical factors. METHODS: Data were analysed from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) observational cohort. All patients met modified New York Criteria for AS and had ≥2 sets of radiographs scored by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by two independent readers between 2002 and 2017. Group-based trajectory modelling (GBTM) was used to classify patients into distinct groups of longitudinal mSASSS considering sociodemographic and clinical covariables. The optimal trajectory model and number of trajectories was selected using Nagin's Bayesian information criterion (BIC). RESULTS: A total of 561 patients with 1618 radiographs were analysed. The optimum number of trajectory groups identified was four (BIC -4062). These groups were subsequently categorized as: non-progressors (204 patients), late-progressors (147 patients), early-progressors (107 patients) and rapid-progressors (103 patients). Baseline predictors associated with higher spinal disease burden groups included: baseline mSASSS, male gender, longer disease duration, elevated CRP and smoking history. In addition, time-varying anti-TNF use per year was associated with decreased mSASSS progression only in the rapid-progressor group. CONCLUSIONS: GBTM identified four distinct patterns of spinal disease progression in the PSOAS cohort. Male gender, longer disease duration, elevated CRP and smoking were associated with higher spinal disease groups. Independent confirmation in other AS cohorts is needed to confirm these radiographic patterns.

Construct validity for the self-reported competency and sub-construct associated characteristics of Romanian physicians in autism spectrum disorder.

BACKGROUND: Lack of physicians' knowledge regarding mental health, including Autism Spectrum Disorder (ASD) could have adverse effects on affected individuals' health and quality of life. The purpose of this study was to provide construct validity for a modified questionnaire in order to determine the self-reported competency for underlying sub-constructs in ASD, make inferences on perceived competence in ASD based on a sample of Romanian physicians, and identify physicians' characteristics associated with these sub-domains of competency. METHODS: For this survey, we modified a questionnaire that was used in Pakistan and Turkey, and administered it to a sample of 383 practicing physicians in Romania to assess their perceived competency regarding ASD. Exploratory factor analysis on 12 knowledge questions revealed five sub-domains: stigma, potential causes, children's behavior, misconceptions, and educational needs associated with ASD knowledge. Using General Linear Models, we determined physicians' characteristics that predict the total competency score and various competency sub-scores. RESULTS: Seventy-five percent of the responding physicians were female and 30% had over 30 years practicing medicine. The majority (73-94%) of physicians have correctly responded to some basic questions regarding knowledge about ASD. We also found that younger physicians were more knowledgeable about potential causes of ASD than older physicians (Adjusted Mean Score (AMS): 2.90 vs. 2.18, P < 0.01), while older physicians knew more about the behavior of children with ASD (AMS: 0.64 vs. 0.37, P = 0.02). We found a significant interaction (P < 0.01) between television as source of ASD knowledge and city where the clinic is located in relation to knowledge of the physicians regarding stigma related to ASD. However, the total score was not associated with the variables associated with sub-domains. CONCLUSION: Using factor analysis, we demonstrated construct validity of five sub-domains related to Romanian physicians' knowledge about ASD that include stigma, potential causes, behavior in ASD children, special education needs, and misconceptions related to ASD. The lack of significant association of the knowledge of physicians on ASD neither with the Psychiatry nor the Pediatric ward rotations at medical school may support the need for improving the curriculum on ASD in Romanian medical schools.

Correlation between concentrations of four heavy metals in cord blood and childhood blood of Jamaican children.

This study investigated whether the concentrations of four metals [lead (Pb), mercury (Hg), manganese (Mn), and aluminum (Al)] are correlated in cord blood and childhood blood samples from Jamaican children. Cord blood samples were obtained from 21 pregnant women enrolled in the second Jamaican Birth Cohort Study from July 1, 2011 to September 30, 2011, and blood samples were drawn from their children who participated in a follow up study when the children were 4-8 years old. Correlations were assessed by the Pearson or the Spearman's rank correlation coefficient. The mean ages of children at the childhood visit and their mother at the child's birth were 5.5 years and 29.8 years, respectively. About 47.6% of children were male. Statistically significant correlations between cord blood and childhood blood concentrations of Pb (rSpearman =0.45; P = 0.04) and Mn (rPearson=0.48; P = 0.03) were found, and these remained significant when adjusted for the child's sex, age, or both. For Al and Hg, rSpearman=0.29 and 0.08, respectively, but the correlations were not statistically significant (both P ≥ 0.20). A significant correlation between cord blood and childhood blood Pb concentrations for children 4-8 years old has not been previously reported.