Dermatofibromas on the Foot and Ankle: A Clinicopathologic Characterization of 31 Cases.

BACKGROUND: Dermatofibroma (DF) is a common benign soft-tissue tumor. It occurs anywhere on the body but is commonly seen on the upper and lower extremities. It is frequently found in young to middle-aged adults and predominantly in females. METHODS: Thirty-one patients with DF on the foot and ankle diagnosed and treated during a 6-year period were characterized. RESULTS: The patients (16 males, 15 females) were aged 7 to 75 years (average, 55 years). Clinically, 17 patients noted painful symptoms, and 14 were painless. Grossly, DF manifested as a raised red, pink, tan, or skin-colored soft mass. The tumor size ranged from 0.3 to 1.5 cm (average, 0.67 cm in diameter). Twenty-six DFs (84%) were localized on the dorsal surface of the foot and ankle, and five (16%) were found on the plantar aspect. Eighteen patients were treated by surgical excision of the tumor (>0.5 cm), and 13 patients had observational follow-up after punch biopsy due to the small size (≤0.5 cm) and benign nature of these lesions. Further follow-up found that only one patient (3.2%) had a local recurrence, 37 months after surgical excision, which was completely reexcised. Histologically, DF is characterized by proliferation of spindle fibroblasts and histiocytes, in a vague fascicular pattern, and thickened collagen bundles. CONCLUSIONS: Dermatofibroma on the foot and ankle predominantly occurs in patients in their 50s, without a preponderance by sex. It needs to be differentiated from other benign and malignant tumors with histologic analysis and immunostaining with factor XIIIa, CD68, and other biomarkers. Treatment options include either surgical excision or observational follow-up after biopsy, depending on the clinical characteristics and effect on functional activity.

High BMI z-Scores from Different Growth References Are Not Comparable: An Example from a Weight Management Trial with an Anti-Obesity Medication in Pubertal Adolescents with Obesity.

Background: The BMI z-score is a standardized measure of weight status and weight change in children and adolescents. BMI z-scores from various growth references are often considered comparable, and differences among them are underappreciated. Methods: This study reanalyzed data from a weight management clinical study of liraglutide in pubertal adolescents with obesity using growth references from CDC 2000, CDC Extended, World Health Organization (WHO), and International Obesity Task Force. Results: BMI z-score treatment differences varied 2-fold from -0.13 (CDC 2000) to -0.26 (WHO) overall and varied almost 4-fold from -0.05 (CDC 2000) to -0.19 (WHO) among adolescents with high baseline BMI z-score. Conclusions: Depending upon the growth reference used, BMI z-score endpoints can produce highly variable treatment estimates and alter interpretations of clinical meaningfulness. BMI z-scores cited without the associated growth reference cannot be accurately interpreted.

Screening Accuracy of BMI for Adiposity Among 8- to 19-Year-Olds.

BACKGROUND AND OBJECTIVES: Although the limitations of BMI have long been recognized, there are recent concerns that it is not a good screening tool for adiposity. We therefore examined the cross-sectional relation of BMI to adiposity among 6923 8- to 19-year-olds in the National Health and Nutrition Survey from 2011 through 2018. METHODS: Participants were scanned with dual-energy x-ray absorptiometry. Adiposity was expressed as fat mass index (FMI, fat mass kg ÷ m2) and percentage of body fat (%fat). Lean mass was expressed as lean mass index (LMI, lean mass ÷ m2). Regression models and 2 × 2 tables were used to assess the relation of BMI to FMI, %fat, and LMI. RESULTS: Age and BMI accounted (R2) for 90% to 94% of the variability of FMI and LMI in each sex. Associations with %fat were weaker (R2s ∼0.70). We also examined the screening abilities of a BMI ≥ Centers for Disease Control and Prevention 95th percentile for high levels of adiposity and LMI. Cut points were chosen so that prevalences of high values of these variables would be similar to that for high BMI. Of participants with a high BMI, 88% had a high FMI, and 76% had a high %fat. Participants with a high BMI were 29 times more likely to have a high FMI than those with lower BMIs; comparable relative risks were 12 for high %fat and 14 for high LMI. CONCLUSIONS: Despite its limitations, a high BMI is a very good screening tool for identifying children and adolescents with elevated adiposity.

The influence of depression and anxiety on cognition in people with multiple sclerosis: a cross-sectional analysis.

There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2 years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS.

Clinical dimensions of people with co-occurring obsessive-compulsive and related disorders and multiple sclerosis: a scoping review protocol.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated demyelinating disease with a significant burden of neuropsychiatric sequelae. These symptoms, including depression and anxiety, are predictors of morbidity and mortality in people with MS. Despite a high prevalence of obsessive-compulsive disorder in MS, potentially shared pathophysiological mechanisms and overlap in possible treatments, no review has specifically examined the clinical dimensions of people with obsessive-compulsive and related disorders (OCRD) and MS. In this scoping review, we aim to map the available knowledge on the clinical dimensions of people with co-occurring OCRD and MS. Understanding the characteristics of this population in greater detail will inform more patient-centred care and create a framework for future studies. METHODS AND ANALYSIS: We developed a search strategy to identify all articles that include people with co-occurring OCRD and MS. The search strategy (extending to the grey literature) was applied to MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science and ProQuest Dissertations & Theses. Records will undergo title and abstract screening by two independent reviewers. Articles meeting inclusion criteria based on title and abstract screening will go on to full-text review by the two independent reviewers. After reaching a consensus about articles for inclusion in the final review, data will be extracted using a standardised extraction form. The extracted data will include clinical characteristics of patients such as age, gender, medication use and severity of MS, among others. ETHICS AND DISSEMINATION: This scoping review does not require research ethics approval. Results will be shared at national and/or international conferences, in a peer-reviewed journal publication, in a plain language summary and in a webinar for the general public.

From Theory to Practice: Development and Evaluation of a Quality Improvement Curriculum for Psychiatry Residents.

OBJECTIVES: Quality improvement (QI) is a systematic approach used to analyze and address problems in healthcare. Evidence of its success has led some national regulatory bodies to require QI education in residency training programs. However, limited work to date has demonstrated how residency programs can integrate best practices in QI education to design their own curriculum. This study describes the implementation and evaluation of a new QI curriculum, grounded in a theoretical model of how QI education works, for Canadian psychiatry residents. METHODS: PGY-2 and PGY-4 psychiatry residents received a 2.5-h mixed didactic and simulation-based QI workshop as a part of the 2021-2022 academic curriculum. Their knowledge and attitudes toward QI were assessed using the QI Knowledge Application Tool Revised (QIKAT-R) and the Beliefs and Attitudes subscale of the Beliefs, Attitudes, Skills, and Confidence in QI (BASiC-QI). RESULTS: Eleven of 12 residents (92%) who completed the curriculum participated in the study. Average QIKAT-R scores improved from 4.45 to 7.00. Average BASiC-QI Beliefs and Attitudes subscale scores increased by 5.55 points. Residents reported enjoying QI and an increased desire to participate in future QI projects. CONCLUSION: This study demonstrates how a programme theory of QI education can be used to develop an effective, locally-tailored curriculum. This approach can be replicated by other educators to develop or improve QI curricula.

Intimate partner violence and multiple sclerosis.

People with MS may be at heightened risk of intimate partner violence (IPV) compared to the general population; however, little is known about the prevalence of IPV among people with MS or its effects on MS-specific clinical outcomes. Additionally, while MS clinicians often discuss family planning with patients, many clinicians may have received little training in detecting and responding to IPV. Moreover, no studies have investigated how to implement IPV case-finding and resource provision in the MS clinical setting. Overall, there are several scholarly, educational, and implementation-related gaps in IPV-associated care for people with MS. This article aims to summarize the available literature on IPV in people with MS, identify future research questions, and aid MS clinicians in safely addressing IPV while awaiting vital MS-specific knowledge.

Psychological Outcomes of 12-15-Year-Olds with Gender Dysphoria Receiving Pubertal Suppression in the UK: Assessing Reliable and Clinically Significant Change.

The evidence base for psychological benefits of GnRHA for adolescents with gender dysphoria (GD) was deemed "low quality" by the UK National Institute of Health and Care Excellence. Limitations identified include inattention to clinical importance of findings. This secondary analysis of UK clinical study data uses Reliable and Clinically Significant Change approaches to address this gap. The original uncontrolled study collected data within a specialist GD service. Participants were 44 12-15-year-olds with GD. Puberty was suppressed using "triptorelin"; participants were followed-up for 36 months. Secondary analysis used data from parent-report Child Behavior Checklists and Youth Self-Report forms. Reliable change results: 15-34% of participants reliably deteriorated depending on the subscale, time point and parent versus child report. Clinically significant change results: 27-58% were in the borderline (subclinical) or clinical range at baseline (depending on subscale and parent or child report). Rates of clinically significant change ranged from 0 to 35%, decreasing over time toward zero on both self-report and parent-report. The approach offers an established complementary method to analyze individual level change and to examine who might benefit or otherwise from treatment in a field where research designs have been challenged by lack of control groups and low sample sizes.

Trends in Severe Obesity Among Children Aged 2 to 4 Years in WIC: 2010 to 2020.

OBJECTIVES: To examine the prevalence and trends in severe obesity among 16.6 million children aged 2 to 4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) from 2010 to 2020. METHODS: Severe obesity was defined as a sex-specific BMI for age ≥120% of the 95th percentile on the Centers for Disease Control and Prevention growth charts or BMI ≥35 kg/m2. Joinpoint regression was used to identify when changes occurred in the overall trend. Logistic regression was used to compute the adjusted prevalence differences between years controlling for sex, age, and race and ethnicity. RESULTS: The prevalence of severe obesity significantly decreased from 2.1% in 2010 to 1.8% in 2016 and then increased to 2.0% in 2020. From 2010 to 2016, the prevalence decreased significantly among all sociodemographic subgroups except for American Indian/Alaska Native (AI/AN) children. The largest decreases were among 4-year-olds, Asian/Pacific Islander and Hispanic children, and children from higher-income households. However, from 2016 to 2020, the prevalence increased significantly overall and among sociodemographic subgroups, except for AI/AN and non-Hispanic white children. The largest increases occurred in 4-year-olds and Hispanic children. Among 56 WIC agencies, the prevalence significantly declined in 17 agencies, and 1 agency (Mississippi) showed a significant increase from 2010 to 2016. In contrast, 21 agencies had significant increases, and only Alaska had a significant decrease from 2016 to 2020. CONCLUSIONS: Although severe obesity prevalence in toddlers declined from 2010 to 2016, recent trends are upward. Early identification and access to evidence-based family healthy weight programs for at-risk children can support families and child health.

Alterations of neural activity in the prefrontal cortex associated with deficits in working memory performance.

Working memory (WM), a core cognitive function, enables the temporary holding and manipulation of information in mind to support ongoing behavior. Neurophysiological recordings conducted in nonhuman primates have revealed neural correlates of this process in a network of higher-order cortical regions, particularly the prefrontal cortex (PFC). Here, we review the circuit mechanisms and functional importance of WM-related activity in these areas. Recent neurophysiological data indicates that the absence of these neural correlates at different stages of WM is accompanied by distinct behavioral deficits, which are characteristic of various disease states/normal aging and which we review here. Finally, we discuss emerging evidence of electrical stimulation ameliorating these WM deficits in both humans and non-human primates. These results are important for a basic understanding of the neural mechanisms supporting WM, as well as for translational efforts to developing therapies capable of enhancing healthy WM ability or restoring WM from dysfunction.

Redundant representations are required to disambiguate simultaneously presented complex stimuli.

A pedestrian crossing a street during rush hour often looks and listens for potential danger. When they hear several different horns, they localize the cars that are honking and decide whether or not they need to modify their motor plan. How does the pedestrian use this auditory information to pick out the corresponding cars in visual space? The integration of distributed representations like these is called the assignment problem, and it must be solved to integrate distinct representations across but also within sensory modalities. Here, we identify and analyze a solution to the assignment problem: the representation of one or more common stimulus features in pairs of relevant brain regions-for example, estimates of the spatial position of cars are represented in both the visual and auditory systems. We characterize how the reliability of this solution depends on different features of the stimulus set (e.g., the size of the set and the complexity of the stimuli) and the details of the split representations (e.g., the precision of each stimulus representation and the amount of overlapping information). Next, we implement this solution in a biologically plausible receptive field code and show how constraints on the number of neurons and spikes used by the code force the brain to navigate a tradeoff between local and catastrophic errors. We show that, when many spikes and neurons are available, representing stimuli from a single sensory modality can be done more reliably across multiple brain regions, despite the risk of assignment errors. Finally, we show that a feedforward neural network can learn the optimal solution to the assignment problem, even when it receives inputs in two distinct representational formats. We also discuss relevant results on assignment errors from the human working memory literature and show that several key predictions of our theory already have support.

Probability of 5% or Greater Weight Loss or BMI Reduction to Healthy Weight Among Adults With Overweight or Obesity.

Importance: Information on the probability of weight loss among US adults with overweight or obesity is limited. Objective: To assess the probability of 5% or greater weight loss, 10% or greater weight loss, body mass index (BMI) reduction to a lower BMI category, and BMI reduction to the healthy weight category among US adults with initial overweight or obesity overall and by sex and race. Design, Setting, and Participants: This cohort study obtained data from the IQVIA ambulatory electronic medical records database. The sample consists of US ambulatory patients 17 years or older with at least 3 years of BMI information from January 1, 2009, to February 28, 2022. Minimum age was set at 17 years to allow for the change in BMI or weight starting at 18 years. Maximum age was censored at 70 years. Exposures: Initial BMI (calculated as weight in kilograms divided by height in meters squared) category was the independent variable of interest, and the categories were as follows: lower than 18.5 (underweight), 18.5 to 24.9 (healthy weight), 25.0 to 29.9 (overweight), 30.0 to 34.9 (class 1 obesity), 35.0 to 39.9 (class 2 obesity), and 40.0 to 44.9 and 45.0 or higher (class 3 or severe obesity). Main Outcomes and Measures: The 2 main outcomes were 5% or greater weight loss (ie, a ≥5% reduction in initial weight) and BMI reduction to the healthy weight category (ie, BMI of 18.5-24.9). Results: The 18 461 623 individuals in the sample had a median (IQR) age of 54 (40-66) years and included 10 464 598 females (56.7%) as well as 7.7% Black and 72.3% White patients. Overall, 72.5% of patients had overweight or obesity at the initial visit. Among adults with overweight and obesity, the annual probability of 5% or greater weight loss was low (1 in 10) but increased with higher initial BMI (from 1 in 12 individuals with initial overweight to 1 in 6 individuals with initial BMI of 45 or higher). Annual probability of BMI reduction to the healthy weight category ranged from 1 in 19 individuals with initial overweight to 1 in 1667 individuals with initial BMI of 45 or higher. Both outcomes were generally more likely among females than males and were highest among White females. Over the 3 to 14 years of follow-up, 33.4% of persons with overweight and 41.8% of persons with obesity lost 5% or greater of their initial weight. At the same time, 23.2% of persons with overweight and 2.0% of persons with obesity reduced BMI to the healthy weight category. Conclusions and Relevance: Results of this cohort study indicate that the annual probability of 5% or greater weight loss was low (1 in 10) despite the known benefits of clinically meaningful weight loss, but 5% or greater weight loss was more likely than BMI reduction to the healthy weight category, especially for patients with the highest initial BMIs. Clinicians and public health efforts can focus on messaging and referrals to interventions that are aimed at clinically meaningful weight loss (ie, ≥5%) for adults at any level of excess weight.

Lipomas of the Toes: An Eight-Case Series.

BACKGROUND: Lipomas, derived from adipose tissue, most frequently occur in the cephalic regions and proximal extremities, but rarely in the toes. We aimed to highlight the clinical features, diagnosis, and treatment of lipomas of the toes. METHODS: We analyzed 8 patients with lipomas of the toes who were diagnosed and treated during a 5-year period. RESULTS: Lipomas of the toes were equally distributed by sex. Patients ranged in age from 28 to 67 years (mean age, 51.75 years). Six patients (75%) had a single lesion, and all of the patients developed lipomas on the hallux. Most patients (75%) presented with a painless, subcutaneous, slow-growing mass. The duration from symptom onset to surgical excision ranged from 1 month to 20 years (mean, 52.75 months). Lipoma size varied from 0.4 to 3.9 cm in diameter (mean, 1.6 cm). Magnetic resonance imaging showed a well-encapsulated mass with hyperintense signal on T1-weighted images and hypointense signal on T2-weighted images. All of the patients were treated with surgical excision, and no recurrences were found at mean follow-up of 38.5 months. Six patients were diagnosed as having typical lipomas, one a fibrolipoma, and one a spindle cell lipoma, which needs to be differentiated from other benign and malignant lesions. CONCLUSIONS: Lipomas of the toes are rare, slow-growing, painless, subcutaneous tumors. Men and women are equally affected, usually in their 50s. Magnetic resonance imaging is the favored modality for presurgical diagnosis and planning. Complete surgical excision is the optimal treatment, with rare recurrence.

Posterior Parietal Cortex Plays a Causal Role in Abstract Memory-Based Visual Categorical Decisions.

Neural activity in the lateral intraparietal cortex (LIP) correlates with both sensory evaluation and motor planning underlying visuomotor decisions. We previously showed that LIP plays a causal role in visually-based perceptual and categorical decisions, and preferentially contributes to evaluating sensory stimuli over motor planning. In that study, however, monkeys reported their decisions with a saccade to a colored target associated with the correct motion category or direction. Since LIP is known to play a role in saccade planning, it remains unclear whether LIP's causal role in such decisions extend to decision-making tasks which do not involve saccades. Here, we employed reversible pharmacological inactivation of LIP neural activity while two male monkeys performed delayed match to category (DMC) and delayed match to sample (DMS) tasks. In both tasks, monkeys needed to maintain gaze fixation throughout the trial and report whether a test stimulus was a categorical match or nonmatch to the previous sample stimulus by releasing a touch bar. LIP inactivation impaired monkeys' behavioral performance in both tasks, with deficits in both accuracy and reaction time (RT). Furthermore, we recorded LIP neural activity in the DMC task targeting the same cortical locations as in the inactivation experiments. We found significant neural encoding of the sample category, which was correlated with monkeys' categorical decisions in the DMC task. Taken together, our results demonstrate that LIP plays a generalized role in visual categorical decisions independent of the task-structure and motor response modality.SIGNIFICANCE STATEMENT Neural activity in the lateral intraparietal cortex (LIP) correlates with perceptual and categorical decisions, in addition to its role in mediating saccadic eye movements. Past work found that LIP is causally involved in visual decisions that are rapidly reported by saccades in a reaction time based decision making task. Here we use reversible inactivation of LIP to test whether LIP is also causally involved in visual decisions when reported by hand movements during delayed matching tasks. Here we show that LIP inactivation impaired monkeys' task performance during both memory-based discrimination and categorization tasks. These results demonstrate that LIP plays a generalized role in visual categorical decisions independent of the task-structure and motor response modality.

Schema formation in a neural population subspace underlies learning-to-learn in flexible sensorimotor problem-solving.

Learning-to-learn, a progressive speedup of learning while solving a series of similar problems, represents a core process of knowledge acquisition that draws attention in both neuroscience and artificial intelligence. To investigate its underlying brain mechanism, we trained a recurrent neural network model on arbitrary sensorimotor mappings known to depend on the prefrontal cortex. The network displayed an exponential time course of accelerated learning. The neural substrate of a schema emerges within a low-dimensional subspace of population activity; its reuse in new problems facilitates learning by limiting connection weight changes. Our work highlights the weight-driven modifications of the vector field, which determines the population trajectory of a recurrent network and behavior. Such plasticity is especially important for preserving and reusing the learned schema in spite of undesirable changes of the vector field due to the transition to learning a new problem; the accumulated changes across problems account for the learning-to-learn dynamics.

Neuropsychiatric Status of Patients With Multiple Sclerosis Across Disease Duration Intervals.

OBJECTIVES: The neuropsychiatric sequelae of multiple sclerosis (MS) are important predictors of morbidity and mortality. The authors examined how symptoms of depression, anxiety, fatigue, subjective cognitive impairment, and objective cognitive dysfunction varied with disease duration. They also explored changes in the use of disease-modifying therapies, psychotropic medications, and psychotherapies in relation to disease duration. METHODS: A retrospective sample of 464 people with MS was stratified into three groups based on disease duration: <5 years (N=129), 5-10 years (N=101), and >10 years (N=234). Symptoms of depression and anxiety were recorded with the Hospital Anxiety and Depression Scale (HADS); fatigue, with the five-item version of the Modified Fatigue Impact Scale (MFIS-5); subjective cognitive impairment, with the five-item version of the Perceived Deficits Questionnaire (PDQ-5); and cognition, with the Minimal Assessment of Cognitive Function in MS (MACFIMS). RESULTS: There were between-group differences in anxiety symptoms (p<0.01) and degree of cognitive impairment (p=0.03), but there were no differences in depressive symptoms, fatigue, or subjective cognitive difficulties. Anxiety was higher during the first 5 years after diagnosis, and cognitive dysfunction was higher when assessed more than 10 years after diagnosis. With longer disease duration, a greater proportion of participants received psychotropic medications (p<0.01), and lower proportions received disease-modifying therapies (p<0.01) or psychotherapies (p<0.01). CONCLUSIONS: Findings indicated that rates of some neuropsychiatric symptoms, such as anxiety and cognitive dysfunction, may shift with disease duration, whereas other symptoms, such as fatigue and depression, may not. These findings highlight the importance of closely monitoring the mental state of people with MS over time.