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The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards. This article provides an overview of the new American Clinical Neurophysiology Society standards for the creation of clinical guidance documents, including clinical guidelines, technical standards, and consensus statements. This process is rooted in the importance of clinical guidance documents and their significance in the context of current behests for updated standards for practicing clinical neurophysiology. The need and rationale for updating the guideline development process from its prior state were described. The updated American Clinical Neurophysiology Society categories for clinical guidance and recommendations were defined and compared. Finally, the new process is summarized, focusing on methodologies, authorship, and conflicts of interest.
Introduction: Previous single-center studies have found a higher prevalence of mental health disorders in parents of children with pediatric stroke compared to general population prevalences of 5% with depression and 6% with anxiety. Social determinants of health may influence mental health outcomes. We aimed to measure associations between social determinants of health and parental report of mental health symptoms following their child’s diagnosis of ischemic stroke.
Methods: We performed a multicenter, international prospective study through the International Pediatric Stroke Study (IPSS). From 2016 to 2021, parents of children within 3.5 years after arterial ischemic stroke enrolled and completed validated and standardized surveys on anxiety (Beck’s Anxiety Inventory II), depression (Beck’s Depression Inventory), post-traumatic stress disorder (PTSD) (Post-Traumatic Stress Disorder Checklist for DSM-5), severity of their child’s stroke deficits (Recovery and Recurrence Questionnaire), and social determinants of health. For our statistical analysis we employed a linear mixed-effects model, both unadjusted and adjusted.
Results: Fifty-two parents (13 fathers, 39 mothers) of 39 children enrolled. Of the 39 children 21 (54%) had perinatal stroke and 18 (46%) had childhood stroke. Median time from stroke diagnosis to parental survey completion was 1.3 years (interquartile range [IQR] 1.0-2.0). On parental surveys, parents scored in the clinical range for: depression in 35% of mothers and 23% of fathers; anxiety in 2% of mothers and 0% of fathers; PTSD in 26% of mothers and 8% of fathers. Lower parental education was significantly associated with higher levels of depression both in our unadjusted (0.02) and adjusted (0.03) models. Interestingly, the child’s functional outcome and parental income were not significantly associated with any parental mental health outcomes.
Conclusion: Among social determinants of health, parental education level may be associated with depression in parents of children with pediatric arterial ischemic stroke and needs further exploration. Parents of children with pediatric arterial ischemic stroke had higher rates of depression and PTSD compared to general population estimates. Further research in this area will help facilitate understanding and development of interventions to prevent these mental health outcomes.
Introduction: Acute treatment for stroke often requires emergent interhospital transfer for access to advanced therapies not available at the initial hospital. Prolonged transfer times have been associated with worse outcomes. Door-in-door-out time (DIDO: the amount of time a patient spends in the transferring emergency department [ED]) is an important quality metric in acute stroke care, with current recommendations for DIDO times ≤ 120 minutes. We sought to characterize trends and predictors of DIDO times for interhospital stroke transfers using the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS).
Methods: We utilized data from the GCNKSS, a population-based epidemiologic stroke study, from the following time points: 1999, 2005, 2010, 2015, and 2020. Patients ≥18 years with acute ischemic stroke (AIS) or hemorrhagic stroke (HS) who presented to an initial ED and were not admitted but were transferred to another hospital were included. The primary outcome was DIDO time. Temporal trends in DIDO time were tested using the Mann-Kendall trend test. Generalized linear mixed effects models with hospital-specific random intercepts were constructed to evaluate the associations between patient- and hospital-level covariates and DIDO time.
Results: Of 13,678 stroke cases over the time periods studied, 1574 patients met inclusion criteria for the overall stroke group (mean age 64.7 [SD: 15.6], 51.6% female), with 851 (54.1%) having AIS and 723 (45.9%) HS. Over the time periods examined, the median DIDO time for the overall stroke group was 213 minutes (IQR 142-305), and DIDO times significantly increased over time (Figure 1; P<.0001). In the overall stroke group, hospital-level factors explained 4.0% of the variation in DIDO time. In the multiple regression model, factors associated with increased DIDO time included: history of prior stroke (+33.6 minutes; P<.0001) and receipt of MRI prior to transfer (+165.7 minutes; P<.0001); whereas EMS transport (-30.0 minutes; P<.001) and increasing NIHSS score (P<.0001) were associated with decreased DIDO time. Results were similar for AIS and HS subgroups (Table 2).
Conclusions: In this population-based epidemiologic study, DIDO times exceeded recommended time targets and increased over time. Hospital-level factors accounted for only a minor proportion of the overall variation in DIDO times, suggesting that future quality improvement efforts should target modifiable clinical and systems factors to improve DIDO times.
Background: Understanding the trends of stroke incidence and how those strokes are distributed across race is a critical step to implement trials and programs to decrease the burden caused by stroke nationally. In 2015, we reported that stroke incidence is decreasing in both Black and White adults. We investigated the continued trends in stroke incidence by race in 2020.
Methods: In this population-based stroke surveillance study, all cases of stroke within a 5-county population surrounding Cincinnati in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2020. Cases were abstracted by study nurses and adjudicated by trained study physicians. Temporal trends were evaluated by age, race (Black or White), and subtype (ischemic stroke (IS), intracranial hemorrhage (ICH), or subarachnoid hemorrhage (SAH)). Stroke incidence rates per 100,000 individuals from 1993 to 2020 were calculated using US Census data and age-, race-, and sex-standardized as appropriate. Trends were evaluated using linear regression. Disparities were evaluated using risk ratios and reported with 95% CIs.
Results: In 2020, we identified 2280 first-ever strokes. Of these, 23% (N=524) were Black adults and 52% (N=1,177) were female. The overall annual incidence of stroke in 2020 was 203/100,000. Table 1 reports the temporal trends of stroke incidence by subtype for both Black and White race from 1993 to 2020. For all races, any stroke increased between 2015 and 2020 (p=0.003, driven largely by an increase in stroke in White adults), while the overall trend since 1993 is no longer declining. Ischemic stroke also increased between 2015 and 2020 (pairwise comparison, p=0.011) in all races. Figure 1 shows the stroke incidence rate of overall stroke (any subtype) over time. The overall risk ratio of any incident stroke between Black and White adults was RR 1.84 (1.66, 2.02; p-value 0.022).
Conclusions: Compared to our analysis after our 2015 study, overall stroke incidence over time is no longer decreasing. Between 2015 and 2020, we observed an increasing rate of stroke in our population. For the first time in a 27-year period we report a significant increase in stroke incidence, mostly driven by an increase in ischemic stroke incidence in whites. ICH/SAH rates are stably higher in blacks compared to whites. More work needs to be done to investigate any possible association to COVID or other traditional risk factors to address racial disparities in stroke burden.
Background: Ongoing surveillance of stroke incidence over time by demographic groups is critical to understand trends in disease burden and effective interventions. Our objective was to examine changes in stroke incidence by sex and age over 27 years.
Methods: In a population-based stroke surveillance study covering a 5-county region of southern Ohio and northern Kentucky, hospital cases of stroke were ascertained and adjudicated by trained study physicians during six 1-year periods (07/1993–06/1994, 1999, 2005, 2010, 2015, 2020). Temporal trends in stroke incidence were evaluated by sex, age, and subtype (ischemic (IS), hemorrhagic (ICH), subarachnoid hemorrhage (SAH)). Stroke incidence rates per 100,000 people were calculated using U.S. Census data and age-, race-, and sex-standardized as appropriate. Trends in incidence over time were evaluated using linear regression, weighted with the inverse of the standard error of the estimated incidence rate. Female:male risk ratios (RRs) were reported in each of the study periods for the overall population stratified by age, and the trend over time was evaluated using linear regression using inverse weighting of the standard error.
Results: 11,813 stroke events occurred in total, 56% in females and 20% in Black patients (Table 1). The trend over time for any stroke (IS, ICH, SAH or unknown) was not significant in females (208 [95%CI 195-221] in 1993/4 to 187 [95%CI 176-198] in 2020, per 100,000, p=0.06) or males (251 [95%CI 233-269] in 1993/4 to 220 [95%CI 207-234] in 2020, per 100,000, p=0.13). The decreasing trend in IS was significant in females (p=0.03) but not males (p=0.07). Trend in ICH was not significant in females (p=0.75) or males (p=0.06), and trend in SAH was not significant in either sex (all trend data in Figure 1). For female: male RRs for any stroke, overall (combined age groups) RRs ranged from 0.83 (95%CI 0.75-0.91) in 1993/4 to 0.97 (95%CI 0.88-1.06) in 2010; trend over time was not significant (p=0.82). RRs varied with age (2020 data in Figure 2) with a U-shaped relationship.
Discussion: Over 27 years in a population-based stroke surveillance study, trends over time in any, IS, ICH, and SAH appear to be stabilizing with the only significant decrease seen in females with IS. Though findings suggest that previously reported decreasing incidence rates in stroke appear to be trending upward in 2020, future work is needed to understand the effect of COVID on 2020 rates and to continue surveillance.
Background: Prior literature has reported patterns of racial differences in percutaneous endoscopic gastrostomy (PEG) placement for patients with post-stroke dysphagia. Reasons for this disproportion are not well understood, but critical for clinical decision making. Long-term implications for PEG placement are considerable, given complication rates and that reducing oral intake can significantly impact recovery of swallow function. In this population-based study, we evaluated the influence of patient-related factors and stroke characteristics on PEG placement.
Methods: All patients, 18 years or older, hospitalized with either ischemic or hemorrhagic stroke in Greater Cincinnati in 2010, 2015, and 2020 were considered for this study. Patients who died within 3 days or transferred to hospice care were not included. Demographics and clinical characteristics of Black and White individuals were compared. Multivariable logistic regression was then used to examine the association between Black race and PEG placement after adjustment for potential confounders. Univariable and multivariable logistic regression analysis (dependent = PEG) was used to determine influential factors for PEG placement. Patient and stroke characteristics between Black and Non-Black patients were compared using Chi-square tests, two-sample t-tests, or Wilcoxon rank-sum tests.
Results: The final sample included 2315 cases, of whom 28.2% were Black (653/2315) and 54.1% were women (1254/2315). Black individuals with stroke were younger (p<0.0001), more likely to have a prior stroke (p=0.0003), had more severe strokes based upon NIHSS (p<.0001), were less likely to be treated at an academic center (p<0.0001), and were more likely to have a PEG placed (p>0.0001).Multivariable analysis revealed that Black race remained associated with PEG placement even after adjustment for potential confounders (aOR 1.47, 95% CI 1.15-1.87).
Discussion: Black stroke patients are more likely to receive PEG, even after adjustment for potential confounders. Additional analyses are underway looking at potential influence of socioeconomic characteristics, patient comorbidities, and lesion location. Given the importance of clinical decision making for alternative access to nutrition and hydration, with the goal of recovery of swallowing function, future studies should examine influence of patient-specific factors including health literacy, familial support, and cultural/patient preferences.
Introduction: ICD-10 codes are often used for stroke research in administrative databases. Few studies have assessed their reliability in large, representative populations of the United States. We validated ICD-10 codes in a large population-based study of stroke in the Greater Cincinnati/Northern Kentucky (GCNK) region.
Methods: We ascertained all acute strokes in the GCNK region during 2020 using validated methodology. All hospitalizations were screened using a comprehensive list of ICD codes in any diagnosis position (G45-46/H34/I60-69). Additional cases were captured through cold pursuit. Each case was adjudicated by a stroke-trained physician. Only acute ischemic stroke (AIS) and hemorrhagic strokes (HS, defined as intracerebral hemorrhage or subarachnoid hemorrhage) were included in this analysis. We examined how many AIS cases were identified using the standard codes used for administrative studies (G46/I63), assessing their sensitivity and positive predictive value (PPV) in the primary or secondary positions. A similar analysis was conducted using standard HS codes (I60/I61). Differences in the demographics of cases identified with standard codes in the primary position, standard codes in the secondary position, or through other methods were then evaluated with Chi-squared and Kruskal-Wallis tests.
Results: We identified 3,522 AIS/HS events in 2020. For AIS (Table 1), we found that standard codes in the primary position had a sensitivity of 72.8% and a PPV of 89.1%. When the standard AIS codes were considered in any diagnosis position, sensitivity improved to 89.3%, but PPV decreased to 82.3%. For HS, standard codes in the primary position had a sensitivity of 80.0% and a PPV of 81.0%. When the standard HS codes were considered in any position, the sensitivity improved to 93.4% but the PPV decreased to 54.4%. When looking at baseline characteristics (Table 2), patients identified through a standard code in the primary position had a lower baseline mRS (overall P<0.01); nursing home residence was also more common in patients identified through a standard code in the secondary position (7.8%, overall P<0.01).
Conclusion: For AIS, standard codes in the primary position showed only moderate sensitivity but reasonable PPV. For HS, standard codes in the primary position had moderate sensitivity and moderate PPV. Restricting analyses to patients with a standard code in the primary position likely selects against patients with more disability at baseline.
Background: Existing data indicate recent increases in the prevalence of stroke and relevant risk factors as well as predicted continued increases in coming years. Our objective was to evaluate population-based data on the prevalence of stroke risk factors and related medication use by sex through 2021.
Methods: Data on the prevalence of stroke risk factors and medication use were taken from our general population random-digit dial survey conducted during 6 time periods: 1995, 2000, 2005, 2011, 2016, and 2021. Due to survey sampling design, survey participants' characteristics (sex, race, age) are representative of the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) ischemic stroke study population. We examined the proportion of females vs. males who reported having hypertension (HTN), hyperlipidemia (HL), diabetes (DM), and current smoking and who reported using antihypertensive medications, lipid-lowering agents, aspirin, and anticoagulants (AC).
Results: Over 6 study periods, a total of 12,336 participants completed the survey; 59% were female, and 25% were Black. Mean age of participants (in years) went up over time in both females (64 [SD 16 . 3] in 1995 to 69 [SD 16.4] in 2021) and males (61 [SD 15.7] in 1995 to 67 [SD 16.8] in 2021), p trend <0.0001 for both). Prevalence of HTN, DM, and HL increased over the 6 study periods in both females and males, and current smoking decreased (Figure 1, all p trend <0.0001). All preventive medications (anti-hypertensives, lipid-lowering, aspirin, and AC) assessed increased over time (Figure 2). In 2021, similar proportions of females vs. males had HTN, DM, DL, and were current smokers (p>0.05). Further, similar proportions of females vs. males were on antihypertensives, lipid-lowering medications, and aspirin, though more men than women were on AC (15% vs. 10%, p<0.05).
Conclusions: In this population-based survey of residents of a 5-county region of southern Ohio and northern Kentucky, the reported prevalence of stroke risk factors increased over a 26-year period in both females and males, as did use of medications used to modify these risk factors. An increasing burden of cardiometabolic risk factors may increase stroke event rates in the future and points to the need for improved primordial prevention.
Background: Black individuals are at a higher risk of stroke, but little is known about racial disparities in functional outcome. Using a representative population-based study, we examined disparities in outcome over multiple timepoints in the first year after acute ischemic stroke (AIS).
Methods: We ascertained all hospitalized AIS events in the Greater Cincinnati Northern Kentucky region from July 2019-December 2020 (Black individuals) and January 2020-December 2020 (White individuals). Potential cases were identified by ICD codes, abstracted, and physician adjudicated. Only patients who survived their initial hospitalization were included. Using a validated approach, modified Rankin Scale (mRS) was determined retrospectively at discharge, 3 months, 6 months, and 1-year post-stroke. Mixed effect ordinal regression was used to investigate the effect of Black race on functional outcome, after adjustment for relevant factors. We collapsed mRS scores of 5 and 6 into one category for the ordinal shift analyses due to the small number of patients with an mRS of 5. A race:time interaction term was considered to assess whether the race-based differences in functional outcome varied by timepoint. Missing data was handled via full information maximum likelihood.
Results: Over the study period, we identified 2541 AIS survivors, of whom 816 (32%) were Black and 1306 (51%) were women (Graphic 1). Unadjusted distributions of mRS scores over 1 year of follow-up are shown in Graphic 2. At 12 months, 25.4% of White individuals (434/1707) and 21.2% of Black individuals (169/799) had an mRS of 0 or 1. When adjusted for age and sex, Black race was associated with a shift towards worse ordinal mRS (Graphic 3, cOR 1.48, 95% CI 1.30-1.68). When other potential confounders were added to the model, the effect of Black race was attenuated but remained significant (cOR 1.16, 95% CI 1.02-1.31). There was no significant interaction between Black race and time after stroke in either model (0.10 and 0.09, respectively).
Conclusions: Using one of the first population-based studies of long-term post-stroke functional outcomes in the U.S., we found that Black individuals experience worse functional outcomes, and this effect was incompletely attenuated when adjusted for comorbidities and initial management. Further research is needed to understand whether these disparities are driven by modifiable social determinants that impact stroke rehabilitation.
The etiology of early-onset scoliosis (EOS) has been shown to significantly influence baseline parent-reported health-related quality of life (HRQoL) measures as assessed by the Early Onset Scoliosis Questionnaire (EOSQ). However, it remains unclear how etiology influences mid-term outcomes following growth friendly instrumentation (GFI) for EOS.
A retrospective review of a multi-center prospective spinal database was performed. Children undergoing primary distraction-based, GFI for EOS with complete baseline, 2-year, and 5-year post-surgical EOSQ were included. The identified children were subdivided by etiology as classified by the C-EOS system. EOSQ scores were compared over time according to etiology cohorts and between instrumentation types. Minimal clinically important difference (MCID) was defined as ≥ 20% change in domain score and compared across etiologies. Dominance analysis was used to assess for drivers of treatment satisfaction.
A total of 178 children (mean 7.3 ± 2.1 years, 51.1% female) were included. The most common etiology was neuromuscular (NM: 36.5%), with the majority of children treated with MCGR (N = 125). Significant differences between etiology groups were present with congenital and idiopathic cohorts demonstrating similar EOSQ domain scores that were significantly higher than neuromuscular and syndromic cohorts. In assessing clinically important changes in EOSQ scores over the 5-year follow-up period, neuromuscular and syndromic patients demonstrated the greatest capacity for improved outcomes. Instrumentation type had no influence on HRQoL scores at 5-year follow-up. Etiology was a driver of satisfaction with syndromic etiology and transfer domain score at 2 years follow-up associated with dissatisfaction.
Curve etiology remains a significant driver of HRQoL domains following growth-friendly instrumentation for EOS. Neuromuscular and syndromic patient have significantly lower domain scores. Despite this, or perhaps because of it, they also demonstrate the greatest capacity for clinically important improvement in HRQoL measures 5 years following intervention.
There are over 100 rheumatic diseases and approximately 300,000 children with a pediatric rheumatic disease (PRD) in the United States. The most common PRDs are juvenile idiopathic arthritis (JIA), childhood‐onset systemic lupus erythematosus (cSLE), and juvenile dermatomyositis (JDM). Effective and safe medications are essential because there are generally no cures for these conditions. Etanercept was the first biologic therapy for the treatment of JIA, approved in 1999. Since then, other biologic disease‐modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease‐modifying antirheumatic drugs (tsDMARDs) blocking relevant immunologic pathways have been approved for the treatment of JIA, resulting in a marked improvement of disease prognosis. Conversely, there is only one bDMARD that has been approved for cSLE, but none are approved for the treatment of JDM. Lack of approved therapeutic options, with established dosing regimens and known efficacy and safety, remains a central challenge in the treatment of all PRDs, including autoinflammatory diseases, and for complications of PRDs. This review provides an overview of bDMARD and tsDMARD treatments studied for the treatment of various subtypes of JIA, summarizes information from bDMARD studies in other PRDs, with a focus on pivotal trials that led to regulatory approvals, and highlights improved outcomes in patients with JIA with the reception of these newer medications. Further, we outline barriers and challenges in the treatment of other PRDs. Last, we summarize the current regulatory landscape for bDMARD studies and medication approvals for patients with PRDs.
Context:
Our study explores the impact of human PTH 1-34 injections (PTH therapy) on growth, areal bone mineral density (BMD), and bone quality (measured by trabecular bone score, TBS) in hypoparathyroidism due to autoimmune polyendocrine syndrome type 1 (APS-1) or an activating variant of the calcium sensing receptor (CaR).
Objective:
To assess associations of 1) age and PTH therapy duration with age-standardized Z-scores for height (HAZ), BMD (BMD-Z), and TBS (TBS-Z) in CaR or APS-1, and 2) APS-1 disease severity with BMD-Z and TBS-Z.
Methods:
This secondary analysis pooled linear growth and lumbar spine (LS) DXA data from studies of hypoparathyroidism with mean baseline age of 13.7±5.5y. Comparing the two diagnostic etiologies (18 APS-1 and 9 CaR), we examined the impact of age and PTH duration on HAZ, LS-BMD-Z, and LS-TBS-Z using longitudinal mixed-effects modeling.
Results:
During PTH therapy, mean HAZ remained below zero in the APS-1 group at all ages, whereas HAZ increased in the CaR group (age by group interaction p<0.0001). Mean LS-BMD-Z were normal (BMD-Z:0±1) for both groups. Mean LS-TBS-Z were near or above zero and differed by group; CaR showed an upward trajectory according to time on PTH whereas the APS-1 group maintained a LS-TBS-Z of approximately 0 (time by group interaction p=0.02). The APS-1 group with greater disease severity (≥7 manifestations) had lower LS-BMD-Z and LS-TBS-Z compared to the less severe APS-1 or CaR groups.
Conclusion:
Our study highlights distinct growth and BMD patterns in APS-1 and CaR and underscores the need for careful monitoring and tailored treatment strategies to optimize growth and bone health.
Gsx2 is a homeodomain transcription factor critical for development of the ventral telencephalon and hindbrain of the mouse. Loss of Gsx2 function results in severe basal ganglia dysgenesis as well as defects in the nucleus tractus solitarius (nTS) of the hindbrain together with respiratory failure at birth. De Mori et al. (2019) reported two patients with severe dystonia and basal ganglia dysgenesis that encode distinct recessive GSX2 variants, including a missense mutation within the homeodomain (GSX2Q251R). Hence, we modelled the homologous Gsx2 mutation (i.e. Gsx2Q252R) in mouse and our biochemical analysis revealed this variant selectively altered DNA binding. Moreover, mice carrying the Gsx2Q252R allele exhibited basal ganglia dysgenesis, albeit to a lesser extent than Gsx2 null mice. A notable difference between Gsx2Q252R and Gsx2 null mice was that Gsx2Q252R mice survive, and hindbrain analysis revealed relative sparing of the glutamatergic nTS neurons and catecholaminergic A1/C1, A2/C2 groups. Thus, the Gsx2Q252R variant is a hypomorph that compromises a subset of Gsx2-dependent neuronal subtypes and highlights a critical role for distinct thresholds of catecholaminergic and/or glutamatergic nTS neurons for viability.
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