Brain age predicted using graph convolutional neural network explains neurodevelopmental trajectory in preterm neonates.

OBJECTIVES: Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome. METHODS: In total, 577 T1 MRI scans of preterm neonates from two different datasets were analyzed; the NEOCIVET pipeline generated cortical surfaces and morphological features, which were then fed to the GCN to predict brain age. The brain age index (BAI; PBA minus chronological age) was used to determine the relationships among preterm birth (i.e., birthweight and birth age), perinatal brain injuries, postnatal events/clinical conditions, BAI at postnatal scan, and neurodevelopmental scores at 30 months. RESULTS: Brain morphology and GCN-based age prediction of preterm neonates without brain lesions (mean absolute error [MAE]: 0.96 weeks) outperformed conventional machine learning methods using no topological information. Structural equation models (SEM) showed that BAI mediated the influence of preterm birth and postnatal clinical factors, but not perinatal brain injuries, on neurodevelopmental outcome at 30 months of age. CONCLUSIONS: Brain morphology may be clinically meaningful in measuring brain age, as it relates to postnatal factors, and predicting neurodevelopmental outcome. CLINICAL RELEVANCE STATEMENT: Understanding the neurodevelopmental trajectory of preterm neonates through the prediction of brain age using a graph convolutional neural network may allow for earlier detection of potential developmental abnormalities and improved interventions, consequently enhancing the prognosis and quality of life in this vulnerable population. KEY POINTS: •Brain age in preterm neonates predicted using a graph convolutional network with brain morphological changes mediates the pre-scan risk factors and post-scan neurodevelopmental outcomes. •Predicted brain age oriented from conventional deep learning approaches, which indicates the neurodevelopmental status in neonates, shows a lack of sensitivity to perinatal risk factors and predicting neurodevelopmental outcomes. •The new brain age index based on brain morphology and graph convolutional network enhances the accuracy and clinical interpretation of predicted brain age for neonates.

Cyto/myeloarchitecture of cortical gray matter and superficial white matter in early neurodevelopment: multimodal MRI study in preterm neonates.

The cerebral cortex undergoes rapid microstructural changes throughout the third trimester. Recently, there has been growing interest on imaging features that represent cyto/myeloarchitecture underlying intracortical myelination, cortical gray matter (GM), and its adjacent superficial whitematter (sWM). Using 92 magnetic resonance imaging scans from 78 preterm neonates, the current study used combined T1-weighted/T2-weighted (T1w/T2w) intensity ratio and diffusion tensor imaging (DTI) measurements, including fractional anisotropy (FA) and mean diffusivity (MD), to characterize the developing cyto/myeloarchitectural architecture. DTI metrics showed a linear trajectory: FA decreased in GM but increased in sWM with time; and MD decreased in both GM and sWM. Conversely, T1w/T2w measurements showed a distinctive parabolic trajectory, revealing additional cyto/myeloarchitectural signature inferred. Furthermore, the spatiotemporal courses were regionally heterogeneous: central, ventral, and temporal regions of GM and sWM exhibited faster T1w/T2w changes; anterior sWM areas exhibited faster FA increases; and central and cingulate areas in GM and sWM exhibited faster MD decreases. These results may explain cyto/myeloarchitectural processes, including dendritic arborization, synaptogenesis, glial proliferation, and radial glial cell organization and apoptosis. Finally, T1w/T2w values were significantly associated with 1-year language and cognitive outcome scores, while MD significantly decreased with intraventricular hemorrhage.

The elephant in the room: cybersecurity in healthcare.

Cybersecurity has seen an increasing frequency and impact of cyberattacks and exposure of Protected Health Information (PHI). The uptake of an Electronic Medical Record (EMR), the exponential adoption of Internet of Things (IoT) devices, and the impact of the COVID-19 pandemic has increased the threat surface presented for cyberattack by the healthcare sector. Within healthcare generally and, more specifically, within anaesthesia and Intensive Care, there has been an explosion in wired and wireless devices used daily in the care of almost every patient-the Internet of Medical Things (IoMT); ventilators, anaesthetic machines, infusion pumps, pacing devices, organ support and a plethora of monitoring modalities. All of these devices, once connected to a hospital network, present another opportunity for a malevolent party to access the hospital systems, either to gain PHI for financial, political or other gain or to attack the systems directly to cause erroneous monitoring, altered settings of any device and even to access the EMR via this IoMT window. This exponential increase in the IoMT and the increasing wireless connectivity of anaesthesia and ICU devices as well as implantable devices presents a real and present danger to patient safety. There has, at the same time, been a chronic underfunding of cybersecurity in healthcare. This lack of cybersecurity investment has left the sector exposed, and with the monetisation of PHI, the introduction of technically unsecure IoT devices for monitoring and direct patient care, the healthcare sector is presenting itself for further devastating cyberattacks or breaches of PHI. Coupled with the immense strain that the COVID-19 pandemic has placed on healthcare and the changes in working patterns of many caregivers, this has further amplified the exposure of the sector to cyberattacks.

Effect of a pediatric fruit and vegetable prescription program on child dietary patterns, food security, and weight status: a study protocol.

BACKGROUND: Although nutrients in fruits and vegetables are necessary for proper development and disease prevention, most US children consume fewer servings than recommended. Prescriptions for fruits and vegetables, written by physicians to exchange for fresh produce, address access and affordability challenges while emphasizing the vital role of diet in health promotion and disease prevention. Michigan's first fruit and vegetable prescription program (FVPP) exclusively for children was introduced in 2016 at one large pediatric clinic in Flint and expanded to a second clinic in 2018. The program provides one $15 prescription for fresh produce to all pediatric patients at every office visit. Prescriptions are redeemable at a year-round farmers' market or a local mobile market. The current study will assess the impact of this FVPP on diet, food security, and weight status of youth. METHODS: Demographically similar pediatric patient groups with varying levels of exposure to the FVPP at baseline will be compared: high exposure (> 24 months), moderate exposure (12-24 months), and no previous exposure. Data collection will focus on youth ages 8-16 years. A total of 700 caregiver-child dyads (one caregiver and one child per household) will be enrolled in the study, with approximately 200 dyads at clinic 1 (high exposure); 200 dyads at clinic 2 (moderate exposure), and 300 dyads at clinic 3 (no previous exposure). Children with no previous exposure will be introduced to the FVPP, and changes in diet, food security, and weight status will be tracked over two years. Specific aims are to (1) compare baseline diet, food security, and weight status between pediatric patients with varying levels of exposure to the FVPP; (2) measure changes in diet, food security, and weight status before and after never-before-exposed children are introduced to the FVPP; and (3) compare mean 12- and 24-month follow-up measures of diet, food security, and weight status in the initial no exposure group to baseline measures in the high exposure group. DISCUSSION: Completion of study aims will provide evidence for the effectiveness of pediatric FVPPs and insights regarding the duration and intensity of exposure necessary to influence change. TRIAL REGISTRATION: The study was registered through clinicaltrials.gov [ID: NCT04767282] on February 23, 2021.

A Culturally Adapted Parenting Intervention for Mexican-Origin Immigrant Families with Adolescents: Integrating Science, Culture, and a Focus on Immigration-Related Adversity.

Low-income Latina/o immigrants are very likely to experience intense contextual challenges in the USA, such as limited exposure to culturally relevant parent training (PT) prevention interventions. This prevention study consisted of an exploratory randomized controlled trial, aimed at empirically testing the implementation feasibility and initial efficacy of a culturally adapted version of the evidence-based PT intervention known as GenerationPMTO©. The parenting intervention was adapted to overtly address immigration-related stressors, discrimination, and challenges associated with biculturalism. Seventy-one Mexican-origin immigrant mothers participated in this study and were allocated to one of two conditions: (a) culturally adapted GenerationPMTO (i.e., CAPAS-Youth) or (b) wait-list control. Measurements were completed at baseline (T1) and intervention completion (T2). When compared to mothers in the control condition at T2, CAPAS-Youth participants reported significant improvements on four of the core parenting practices delivered in the CAPAS-Youth intervention. As hypothesized, no significant differences in limit-setting skills were identified at T2. With regards to adolescents' outcomes, mothers exposed to CAPAS-Youth reported significant improvements in youth internalizing and externalizing behaviors at T2 when compared to a wait-list control condition. Mothers in both conditions also reported significant reductions in levels of immigration-related stress. Current findings indicate the feasibility of implementing CAPAS-Youth within a context of considerable adversity, as well as the beneficial impacts of the parent-based intervention on salient parenting and youth outcomes.

Latent Class Analysis for Repeatedly Measured Multiple Latent Class Variables.

Research on stage-sequential shifts across multiple latent classes can be challenging in part because it may not be possible to observe the particular stage-sequential pattern of a single latent class variable directly. In addition, one latent class variable may affect or be affected by other latent class variables and the associations among multiple latent class variables are not likely to be directly observed either. To address this difficulty, we propose a multivariate latent class analysis for longitudinal data, joint latent class profile analysis (JLCPA), which provides a principle for the systematic identification of not only associations among multiple discrete latent variables but sequential patterns of those associations. We also propose the recursive formula to the EM algorithm to overcome the computational burden in estimating the model parameters, and our simulation study shows that the proposed algorithm is much faster in computing estimates than the standard EM method. In this work, we apply a JLCPA using data from the National Longitudinal Survey of Youth 1997 in order to investigate the multiple drug-taking behavior of early-onset drinkers from their adolescence, via young adulthood, to adulthood.

Prospektive Kohortenstudie von InspECT zur Sicherheit und Wirksamkeit der Elektrochemotherapie bei Hauttumoren und Metastasen in Abhängigkeit von Ulzeration.

HINTERGRUND: Elektrochemotherapie (ECT) ist eine wirksame lokale Behandlung von Hauttumoren. Ziel dieser Studie war es, die Wirksamkeit der ECT bei ulzerierten gegenüber nichtulzerierten Tumoren zu vergleichen und den Effekt auf tumorassoziierte Symptome zu untersuchen. METHODIK: 20 Krebszentren des International Network for Sharing Practices on Electrochemotherapy (InspECT) sammelten prospektiv Daten. Die ECT wurde nach dem ESOPE-Protokoll durchgeführt. Das Therapieansprechen wurde anhand der Entwicklung der Läsionsgröße bewertet. Zusätzlich wurden Schmerzen, Symptome, Leistungsstatus (ECOG-Index) und Gesundheitszustand (EQ-5D-Fragebogen) untersucht. ERGEBNISSE: 716 Patienten mit ulzerierten (n = 302) und nichtulzerierten (n = 414) Hauttumoren und Metastasen wurden eingeschlossen (Mindest-Nachsorge 45 Tage). Nicht-ulzerierte Läsionen sprachen besser auf die ECT an als ulzerierte Läsionen (vollständiges Ansprechen: 65 % gegenüber 51 %, p = 0,0061). Nur 38 % (115/302) der Patienten mit ulzerierten Läsionen vor der ECT wiesen bei der letzten Nachuntersuchung ulzerierte Läsionen auf. Patienten mit ulzerierten Läsionen berichteten über stärkere Schmerzen und schwerere Symptome im Vergleich zu Patienten mit nichtulzerierten Läsionen, die sich nach der ECT signifikant und kontinuierlich besserten. Bei Patienten mit nichtulzerierten Läsionen hingegen nahmen die Schmerzen während der Behandlung vorübergehend zu. Es wurden keine schwerwiegenden Nebenwirkungen beobachtet. SCHLUSSFOLGERUNGEN: Die ECT ist eine sichere und wirksame lokale Behandlung von Hauttumoren. Während die ECT die Symptome insbesondere bei Patienten mit ulzerierten Läsionen verbessert, sollte auf Basis der Daten die Implementation eines perioperativen Schmerzmanagements besonders bei nichtulzerierten Läsionen während der ECT erwogen werden.

Prospective cohort study by InspECT on safety and efficacy of electrochemotherapy for cutaneous tumors and metastases depending on ulceration.

BACKGROUND: Electrochemotherapy (ECT) is an effective local treatment for cutaneous tumors. The aim of this study was to compare the effectiveness of ECT in ulcerated vs. non-ulcerated tumors and investigate the effect on tumor-associated symptoms. METHODS: Twenty cancer centers in the International Network for Sharing Practices on Electrochemotherapy (InspECT) prospectively collected data. ECT was performed following ESOPE protocol. Response was evaluated by lesion size development. Pain, symptoms, performance status (ECOG-Index) and health status (EQ-5D questionnaire) were evaluated. RESULTS: 716 patients with ulcerated (n = 302) and non-ulcerated (n = 414) cutaneous tumors and metastases were included (minimum follow-up of 45 days). Non-ulcerated lesions responded to ECT better than ulcerated lesions (complete response 65 % vs. 51 %, p = 0.0061). Only 38 % (115/302) with ulcerated lesions before ECT presented with ulcerated lesions at final follow-up. Patients with ulcerated lesions reported higher pain and more severe symptoms compared to non-ulcerated lesions, which significantly and continuously improved following ECT. In non-ulcerated lesions however, pain spiked during the treatment. No serious adverse events were reported. CONCLUSIONS: ECT is a safe and effective local treatment for cutaneous tumors. While ECT improves symptoms especially in patients with ulcerated lesions, data suggest the implementation of a perioperative pain management in non-ulcerated lesions during ECT.

Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naive patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals. METHODS: Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year. RESULTS: 19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5-9 mg 1.56 (1.18-2.06) and ≥10 mg 1.91 (1.31-2.79), without increased risk at 0-4 mg 1.04 (0.55-1.59). Cumulative dose over preceding 6 months showed increased aHR at 751-1100 mg 1.43 (1.04-1.98) and >1100 mg 2.05 (1.42-2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08-2.32), without increased risk at shorter durations. One-year analyses were consistent. CONCLUSIONS: Over preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.

COVID-19 and adult congenital heart disease services: impact on support and advice from nurse specialists.

Although the focus on service provision in response to the COVID-19 pandemic has mainly been on acute and particularly intensive care, it is important to consider other services that are still needed. This is especially the case for vulnerable patients with long-term conditions, such as those under the care of an adult congenital heart disease (ACHD) service. The authors conducted a survey of ACHD nurse specialists in centres across the UK to acertain what they were planning in terms of the redeployment of nurse specialists. The results showed a range of plans with an average of half of nurses per centre being moved, but with 65% of the workforce planned to be redeployed to deal with the pandemic. The telephone advice service at the authors' own level 1 centre showed a significant increase in patients seeking advice when compared with the previous year, with large peaks following major Government announcements. Access to specialist advice for patients with complex conditions is of vital interest, for those in a wide range of specialities.

Rationale and design for the study Apixaban versus ClopidoGRel on a background of aspirin in patient undergoing InfraPoPliteal angioplasty for critical limb ischemia: AGRIPPA trial.

BACKGROUND: New antithrombotic strategies that reduce primary thrombosis and restenosis might improve vascular outcomes in patients with peripheral artery disease (PAD) undergoing arterial angioplasty. The study objective is to evaluate the potential benefit of apixaban plus aspirin compared with standard of care dual antiplatelet therapy (DAPT) in reducing thrombotic restenosis and artery re-occlusion in patients undergoing endovascular infrapopliteal revascularization. STUDY DESIGN: This multicenter, parallel-group, prospective, randomized, open-label, blinded-endpoint adjudication, proof-of-concept, exploratory trial aims to randomize 200 patients 72 hours after successful infrapopliteal angioplasty for critical limb ischemia (CLI). Patients will be randomly assigned in a 1:1 ratio to receive oral apixaban (2.5 mg twice daily) plus aspirin (100 mg once daily) for 12 months or clopidogrel (75 mg daily) for at least 3 months on a background of aspirin (100 mg once daily) for 12 months. The primary endpoint is the composite of target lesion revascularization (TLR), major amputation, or restenosis/occlusion (RAS) in addition to major adverse cardiovascular events - MACE (myocardial infarction, stroke or cardiovascular death) at 12 months. The primary safety endpoint is the composite of major bleeding or clinically relevant non-major bleeding at 12 months. SUMMARY: This study will evaluate the efficacy and safety of apixaban 2.5 mg twice daily plus aspirin compared with DAPT (clopidogrel plus aspirin) in patients with CLI undergoing endovascular infrapopliteal revascularization and might prove the concept of an alternative antithrombotic regimen for these patients to be tested in a future large randomized clinical trial.

The Effects of Model Misspecification in Unanchored Matching-Adjusted Indirect Comparison: Results of a Simulation Study.

OBJECTIVES: To assess the performance of unanchored matching-adjusted indirect comparison (MAIC) by matching on first moments or higher moments in a cross-study comparisons under a variety of conditions. A secondary objective was to gauge the performance of the method relative to propensity score weighting (PSW). METHODS: A simulation study was designed based on an oncology example, where MAIC was used to account for differences between a contemporary trial in which patients had more favorable characteristics and a historical control. A variety of scenarios were then tested varying the setup of the simulation study, including violating the implicit or explicit assumptions of MAIC. RESULTS: Under ideal conditions and under a variety of scenarios, MAIC performed well (shown by a low mean absolute error [MAE]) and was unbiased (shown by a mean error [ME] of about zero). The performance of the method deteriorated where the matched characteristics had low explanatory power or there was poor overlap between studies. Only when important characteristics are not included in the matching did the method become biased (nonzero ME). Where the method showed poor performance, this was exaggerated if matching was also performed on the variance (ie, higher moments). Relative to PSW, MAIC provided similar results in most circumstances, although it exhibited slightly higher MAE and a higher chance of exaggerating bias. CONCLUSIONS: MAIC appears well suited to adjust for cross-trial comparisons provided the assumptions underpinning the model are met, with relatively little efficiency loss compared with PSW.

Evaluation of survival extrapolation in immuno-oncology using multiple pre-planned data cuts: learnings to aid in model selection.

BACKGROUND: Due to limited duration of follow up in clinical trials of cancer treatments, estimates of lifetime survival benefits are typically derived using statistical extrapolation methods. To justify the method used, a range of approaches have been proposed including statistical goodness-of-fit tests and comparing estimates against a previous data cut (i.e. interim data collected). In this study, we extend these approaches by presenting a range of extrapolations fitted to four pre-planned data cuts from the JAVELIN Merkel 200 (JM200) trial. By comparing different estimates of survival and goodness-of-fit as JM200 data mature, we undertook an iterative process of fitting and re-fitting survival models to retrospectively identify early indications of likely long-term survival. METHODS: Standard and spline-based parametric models were fitted to overall survival data from each JM200 data cut. Goodness-of-fit was determined using an assessment of the estimated hazard function, information theory-based methods and objective comparisons of estimation accuracy. Best-fitting extrapolations were compared to establish which one provided the most accurate estimation, and how statistical goodness-of-fit differed. RESULTS: Spline-based models provided the closest fit to the final JM200 data cut, though all extrapolation methods based on the earliest data cut underestimated the 'true' long-term survival (difference in restricted mean survival time [RMST] at 36 months: - 1.1 to - 0.5 months). Goodness-of-fit scores illustrated that an increasingly flexible model was favored as data matured. Given an early data cut, a more flexible model better aligned with clinical expectations could be reasonably justified using a range of metrics, including RMST and goodness-of-fit scores (which were typically within a 2-point range of the statistically 'best-fitting' model). CONCLUSIONS: Survival estimates from the spline-based models are more aligned with clinical expectation and provided a better fit to the JM200 data, despite not exhibiting the definitively 'best' statistical goodness-of-fit. Longer-term data are required to further validate extrapolations, though this study illustrates the importance of clinical plausibility when selecting the most appropriate model. In addition, hazard-based plots and goodness-of-fit tests from multiple data cuts present useful approaches to identify when a more flexible model may be advantageous. TRIAL REGISTRATION: JAVELIN Merkel 200 was registered with ClinicalTrials.gov as NCT02155647 on June 4, 2014.

Pilot study of the effectiveness of a xylitol-based drinking water additive to reduce plaque and calculus accumulation in dogs.

Over a period of 208 days a randomized, double-blind clinical trial was conducted to assess plaque and calculus accumulation in dogs provided with a xylitol-based drinking water additive. A crossover design was utilized allowing each dog to participate in each 90-day treatment and control phase. Inclusion of a xylitol drinking water additive resulted in a 5.1% decrease in mean tooth plaque score and a 14.9% decrease in mean calculus score. Daily administration of a palatable, xylitol drinking water additive that required little time and effort reduced plaque and calculus accumulation in dogs.

Étude pilote sur l'efficacité d'un additif à base de xylitol à l'eau de boisson a pour réduire la plaque et l'accumulation de tartre chez les chiens. Pendant une période de 208 jours, un essai clinique randomisé à double-insu a été mené pour évaluer l'accumulation de plaque et de tartre chez des chiens supplémentés avec un additif à base de xylitol à l'eau de boisson. Une étude croisée fut utilisée permettant ainsi à chaque chien de participer dans chaque période de 90 jours au groupe traité et au groupe témoin. L'inclusion d'un additif à base de xylitol à l'eau de boisson a résulté en une diminution de 5,1 % du pointage de plaque dentaire et de 14,9 % du pointage moyen de tartre dentaire. L'administration quotidienne d'un additif palatable à base de xylitol dans l'eau de boisson ne requérant que peu de temps et d'efforts a permis de réduire l'accumulation de plaque et de tartre.(Traduit par Dr Serge Messier).

"Side Effects" Observed Within ~1-90 Days After Cannabis Onset: Epidemiological Estimates for the United States, 2004-2014.

BACKGROUND AND OBJECTIVES: Among newly incident cannabis users, fewer than 4% develop cannabis dependence syndromes within 12 to 24 months, but earlier cannabis side effect (SE) incidence and early syndrome formation remains understudied. We estimate cannabis SE incidence within ~1 to 90 days after first use, and estimate odds ratios (OR) for SE pairs to quantify potential syndromic "running together." METHODS: Each year, 2004 to 2014, the US populations under study consisted of noninstitutionalized civilian residents age 12-years-and-older, sampled for National Surveys on Drug Use and Health. Computerized self-interviews identified 3710 newly incident cannabis users and asked about SEs. Analysis-weighted year-specific SE and SE-SE pair incidence proportions were estimated. Analysis-weighted odds ratio (OR) estimates quantify SE-SE co-occurrences, judged as "greater than chance" when lower bounds (LB) of 95% confidence intervals (CIs) exceed 1.0. Meta-analysis is used to summarize and to check reproducibility. RESULTS: Illustrative of estimates on 17 SEs, roughly 1/2 of cannabis initiates experienced "wanting or trying to cut down or stop using," but 80% of these cut back, such that less than 7% had symptom-like inability to cut back or stop. An estimated 25% had "spent a lot of time getting or using cannabis." The SE-SE paired estimate is 2.8% for those who had spent a lot of time and also had wanted/tried to cut down (95% CI = 2.0, 4.0). OR estimation suggests no syndromic co-occurrence of this SE-SE pair (OR = 0.9; 95% CI = 0.5, 1.6). In contrast, "cannabis causing serious problems at home/work/school" and "continuing to use despite physical problems" were more rare, but had strong SE-SE co-occurrence (OR = 14.8, LB = 2.4). For 78 of 136 possible SE-SE pairs, meta-analysis LB estimates exceeded the 1.0 threshold. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: In these US community samples of cannabis initiates studied soon after first use, the vast majority were free of individual SE experiences counted toward Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition cannabis use disorder diagnoses. For a minority, SE-SE pairs might indicate syndrome formation. These epidemiological meta-analysis estimates might find use in refinement of clinical practice guidelines for fast effective syndrome screens when primary care patients are seen soon after cannabis onset, akin to clinical screening guides designed for newly incident drinkers (Am J Addict 2019;00:1-9).

Quantitative surface analysis of combined MRI and PET enhances detection of focal cortical dysplasias.

OBJECTIVE: Focal cortical dysplasias (FCDs) often cause pharmacoresistant epilepsy, and surgical resection can lead to seizure-freedom. Magnetic resonance imaging (MRI) and positron emission tomography (PET) play complementary roles in FCD identification/localization; nevertheless, many FCDs are small or subtle, and difficult to find on routine radiological inspection. We aimed to automatically detect subtle or visually-unidentifiable FCDs by building a classifier based on an optimized cortical surface sampling of combined MRI and PET features. METHODS: Cortical surfaces of 28 patients with histopathologically-proven FCDs were extracted. Morphology and intensity-based features characterizing FCD lesions were calculated vertex-wise on each cortical surface, and fed to a 2-step (Support Vector Machine and patch-based) classifier. Classifier performance was assessed compared to manual lesion labels. RESULTS: Our classifier using combined feature selections from MRI and PET outperformed both quantitative MRI and multimodal visual analysis in FCD detection (93% vs 82% vs 68%). No false positives were identified in the controls, whereas 3.4% of the vertices outside FCD lesions were also classified to be lesional ("extralesional clusters"). Patients with type I or IIa FCDs displayed a higher prevalence of extralesional clusters at an intermediate distance to the FCD lesions compared to type IIb FCDs (p < 0.05). The former had a correspondingly lower chance of positive surgical outcome (71% vs 91%). CONCLUSIONS: Machine learning with multimodal feature sampling can improve FCD detection. The spread of extralesional clusters characterize different FCD subtypes, and may represent structurally or functionally abnormal tissue on a microscopic scale, with implications for surgical outcomes.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

This corrects the article DOI: 10.1038/pr.2014.47.

Does Starting to Smoke Cigars Trigger Onset of Cannabis Blunt Smoking?

Introduction: Among United States teens during the 1990s, increasing cigar use coincided with increasing use of tobacco cigar shells filled with cannabis, called "blunts." Cigar smokers are more likely to use cannabis, and we hypothesized that starting to smoke cigars might be a probabilistic "trigger" of blunt smoking. We turned to the case-crossover approach to evaluate this hypothesis. Methods: Within US National Surveys on Drug Use and Health, 2009-2013, we identified a nationally representative sample of newly incident blunt smokers aged 12- to 21-years-old (n = 4868) and compared month-of-onsets for smoking of cigars and blunts. Using the subjects-as-their-own-controls case-crossover design, we specified the first month prior to blunt use as a "hazard interval" and the second month prior to blunt use as a "control interval." We used Mantel-Haenszel (MH) estimators to estimate the matched-pairs odds ratio (OR). Results: The MH OR estimate was 1.7 (95% CI = 1.3, 2.3), with excess odds of cigar onsets during the hazard interval relative to the control interval. Two alternative control interval specifications yielded congruent estimates (OR = 2.7 and 2.9, respectively). Conclusions: A short interval right after starting to smoke cigars may be one of increased risk of starting to smoke blunts. We discuss cigar, cigarillo, and "blunt wraps" control approaches that might reduce both tobacco and cannabis-related harms. Implications: If this evidence is correct, increased market-targeting to promote youthful cigar and cigarillo smoking might be followed by increased rates of blunt smoking in a vulnerable population. As noted by others, enhanced risk of smoking-attributable harms might be a consequence of mixed tobacco-cannabis formulations.

A new era for drinking? Epidemiological evidence on adolescent male-female differences in drinking incidence in the United States and Europe.

PURPOSE: We seek answers to three questions about adolescent risk of starting to drink alcoholic beverages: (1) in new United States (US) data, can we reproduce a recently discovered female excess risk? (2) has a female excess risk emerged in European countries? and (3) might the size of country-level female-male differences (FMD) be influenced by macro-level gender equality and development processes? METHODS: Estimates are from US and European surveys of adolescents, 2010-2014. For US estimates, newly incident drinking refers to consuming the first full drink during the 12-month interval just prior to assessment. For all countries, lifetime cumulative incidence of drinking refers to any drinking before assessment of the sampled 15-16 years. RESULTS: Cumulative meta-analysis summary estimates from the US show a highly reproducible female excess in newly incident drinking among 12-17 years (final estimated female-male difference in risk, FMD = 2.1%; 95% confidence interval = 1.5%, 2.7%). Several European countries show female excess risk, estimated as lifetime cumulative incidence of drinking onsets before age 17 years. At the country level, the observed magnitude of FMD in risk is positively associated with the Gender Development Index (especially facets related to education and life expectancy of females relative to males), and with residence in a higher income European country. CONCLUSIONS: New FMD estimates support reproducibility of a female excess risk in the US. In Europe, evidence of a female excess is modest. Educational attainment, life expectancies, and income merit attention in future FMD research on suspected macro-level processes that influence drinking onsets.

Odontogenic Fibromyxoma in a Cat: First Confirmed Case in This Species.

An inflammatory gingival mass surrounding resorbing teeth was diagnosed via biopsy in a 9-year-old domestic shorthair cat. A dorsal rim excision was performed to remove the entire mass with associated teeth and bone. Histopathological diagnosis of the en bloc tissue revealed an odontogenic fibromyxoma. Extensive literature review revealed few case reports of companion animals with this neoplasm, and none in a feline patient. This report documents the clinical presentation, diagnostic differentials, surgical therapy, and long-term follow-up of an odontogenic fibromyxoma in a cat.