Objective
To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome.
Background
There are no consensus criteria ...for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area.
Methods
The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome.
Results
During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on “other” studies) as were diagnostic criteria (96% agreement).
Conclusions
The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.
This manuscript reviews unique aspects of end of life decision-making in pediatrics.
A narrative literature review of pediatric end of life issues was performed in the English language.
While a ...paternalistic approach is typically applied to children with life-limiting medical prognoses, the cognitive, language, and physical variability in this patient population is wide and worthy of review. In end of life discussions in pediatrics, the consideration of a child's input is often not reviewed in depth, although a shared decision-making model is ideal for use, even for children with presumed limitations due to age. This narrative review of end of life decision-making in pediatric care explores nomenclature, the introduction of the concept of death, relevant historical studies, limitations to the shared decision-making model, the current state of end of life autonomy in pediatrics, and future directions and needs. Although progress is being made toward a more uniform and standardized approach to care, few non-institutional protocols exist. Complicating factors in the lack of guidelines include the unique facets of pediatric end of life care, including physical age, paternalism, the cognitive and language capacity of patients, subconscious influencers of parents, and normative values of death in pediatrics.
Although there have been strides in end of life decision-making in pediatrics, further investigation and research is needed in this field.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Autoimmune encephalitis (AIE) comprises a group of rare, immune system-mediated conditions. Clinical manifestations among children are not well-characterized, and there are challenges in ...testing and diagnosis. This can result in treatment delays, which has been found to correlate with poorer long-term outcomes. This challenge is exacerbated by the scarcity of epidemiological reporting of AIE. The objective of this systematic literature review (SLR) was to identify studies reporting epidemiological data on AIE in children. Methods MEDLINE, Embase, the Cochrane Library, and the University of York Centre for Reviews and Dissemination (CRD) were searched in May 2023 for studies reporting on the epidemiology of AIE in children. These were supplemented with additional searches of conference proceedings, gray literature, and the reference lists of identified SLRs. Quality of studies was assessed using a modified version of the Joanna Briggs Institute (JBI) Checklist for Prevalence Studies. Results Forty-three publications reporting on 41 unique studies were included. Nine studies reported incidence estimates of different subtypes of AIE, with only one reporting the incidence of overall AIE in children ≤ 18 years, estimated at 1.54 per million children per year in the Netherlands. Three studies reported the incidence of pediatric N-methyl-D-aspartate receptor (NMDAR)-AIE in United Kingdom (UK), Hong Kong, and Denmark. The other studies reported incidence data for selected populations. Conclusion This SLR highlights a paucity of epidemiology data for AIE in children, which is likely reflective of difficulties in testing and diagnosis. There is a clear need for further research and awareness of these challenges in clinical practice to avoid treatment delays and improve patient outcomes. A deeper understanding of the epidemiology of AIE will help determine the worldwide burden of disease and inform research, health policies and clinical decision-making.
A major component of pediatric acute-onset neuropsychiatric syndrome (PANS) is disruption of sleep. These disturbances have been reported in the acute phase of diagnosis but it is unknown if these ...sleep disruptions persist, especially in patients with chronic static symptoms. This retrospective chart review sought to review polysomnography (PSG) tests of patients in whom PANS has been clinically diagnosed in order to assess sleep architecture, periodic limb movements, and presence of rapid eye movement (REM) sleep without atonia (RSWA) after a chronic static course of symptoms, which were refractory to immunomodulatory interventions.
Patients were retrospectively identified through the PANS clinic at our institution and had to have fully completed a PSG study and be younger than 18 years. PSG with video were reviewed and scored based on established criteria.
We identified 9 patients who met inclusion criteria. The median time from presentation to PSG was 4 years. This study identified PSG-measured periodic limb movement index (PLMI) > 5 events/h in REM sleep in 7 of 9 patients. Two patients with elevated PLMI also demonstrated RSWA, although neither fit a clinical diagnosis of REM sleep behavior disorder. This cohort also demonstrated increased onset of REM sleep (median 134 minutes), insomnia (median total sleep time of 389 minutes), and decreased sleep efficiency (77%).
This study identifies continued sleep disturbances in patients with refractory PANS symptoms several years after diagnosis and treatment. Continued sleep disturbances after presentation and treatment in patients with chronic static PANS may be a contributing factor in prolonged symptomatology of this disease process.
PHANGS–ALMA Data Processing and Pipeline Leroy, Adam K.; Hughes, Annie; Liu, Daizhong ...
The Astrophysical journal. Supplement series,
07/2021, Letnik:
255, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
We describe the processing of the PHANGS–ALMA survey and present the PHANGS–ALMA pipeline, a public software package that processes calibrated interferometric and total power data into ...science-ready data products. PHANGS–ALMA is a large, high-resolution survey of CO(2–1) emission from nearby galaxies. The observations combine ALMA’s main 12 m array, the 7 m array, and total power observations, and use mosaics of dozens to hundreds of individual pointings. We describe the processing of the
u
−
v
data, imaging and deconvolution, linear mosaicking, combining interferometer and total power data, noise estimation, masking, data product creation, and quality assurance. Our pipeline has a general design and can also be applied to Very Large Array and ALMA observations of other spectral lines and continuum emission. We highlight our recipe for deconvolution of complex spectral line observations, which combines multiscale clean, single-scale clean, and automatic mask generation in a way that appears robust and effective. We also emphasize our two-track approach to masking and data product creation. We construct one set of “broadly masked” data products, which have high completeness but significant contamination by noise, and another set of “strictly masked” data products, which have high confidence but exclude faint, low signal-to-noise emission. Our quality assurance tests, supported by simulations, demonstrate that 12 m+7 m deconvolved data recover a total flux that is significantly closer to the total power flux than the 7 m deconvolved data alone. In the appendices, we measure the stability of the ALMA total power calibration in PHANGS–ALMA and test the performance of popular short-spacing correction algorithms.
Abstract Background Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in ...previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD. Methods This study included individuals with DSRD aged 10–30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher’s exact test) were used to describe and compare the characteristics of individuals with and without variants. Results Forty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic ( UNC13D, XIAP, RNASEH2A, and DNASE1L3 ). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger ( p = 0.03, 95% CI 1.21–97.06), rapid clinical decline in less than 1 month ( p = 0.01, 95% CI 1.67–52.06), and MRI abnormalities ( p < 0.001, 95% CI 4.89–527.71). Discussion A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS.
Disease-modifying therapies (DMTs) have revolutionized the management of multiple sclerosis (MS). Many DMTs have a risk of teratogenic outcomes, which is notable as MS disproportionally affects women ...of reproductive age and the rates of unplanned pregnancies among persons with MS (PwMS) are as high as 34%. Prior research suggests that patients' culture may influence their perspectives surrounding family planning. Given our institution's patient population, we compared the spectrum of knowledge in Hispanic and non-Hispanic patients with pediatric-onset MS (POMS) regarding DMTs and their associated risks during pregnancy and possible disparities in their treatment and counseling.
A small cohort of patients with POMS (n = 22) were surveyed on their knowledge and beliefs surrounding family planning and sexual health counseling. Odds ratios and 95% confidence intervals were used to evaluate the association between survey question responses and ethnicity.
No significant differences in beliefs or knowledge regarding sexual health between Hispanic and non-Hispanic participants were identified, but many valuable themes emerged. Internet access and social relationships heavily influence participants’ knowledge surrounding birth control and sexual health. Patients also desired continuous engagement in sexual health counseling.
In this small pilot cohort, cultural views did not significantly influence whether adolescent and young adult patients with POMS seek sexual health resources. Future studies should aim to identify effective interventions for providers to educate PwMS about sexual health and family planning to address the elevated unplanned pregnancy rate in this population and provide the education these patients have vocalized a desire to receive.
This position statement serves to establish the AAN's stance on the methods to address the cost of prescription drugs being considered by state and federal policymakers so that the AAN can continue ...to advocate effectively for its members. Neurologists seek to provide high-value care for patients with neurologic diseases at the lowest cost possible. However, many therapies for neurologic diseases are among the most expensive in the United States. The 3 major cost challenges include (1) unjustified increases in the pricing for drugs used to treat neurologic disorders, (2) the high cost of medications used to treat rare diseases where there are limited or no therapeutic options available, and (3) the high cost of noninnovative (already FDA-approved) therapies that used accelerated FDA approval pathways or Orphan Drug Act designated to expedite approvals in neurologic disorders. In each of these cases, AAN is concerned that the high cost does not deliver sufficient value to patients or society. The AAN's position is that action must be taken to ensure that effective prescription medications are accessible for patients with complex, chronic neurologic conditions. Potential solutions should be affordable, simple, and transparent. Cost-containment efforts must also address the burden on the entire healthcare system because high prescription drug prices may be shifted and absorbed in ways that negatively affect patient and prescriber access to important medications. AAN supports price negotiations, the cost saving potential of generics and biosimilars, development of novel therapeutics, price transparency, and importation.
Background
Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and ...timing of these tests are unknown.
Objective
To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests.
Methods
We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher’s exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race).
Results
We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio AOR = 4.9,
p
= 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (
n
= 70, 79% vs. 52%, AOR = 4.6,
p
= 0.01), but not more recently (
n
= 30, 75% vs. 80%, AOR = 0.2,
p
= 0.1;
p
= 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d,
p
= 0.03).
Conclusions
Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.
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