Tracheal Narrowing and Its Impact on Anesthesia Care in Patients With Morquio A (Mucopolysaccharidosis Type IVA): An Observational Study.

BACKGROUND: Recently, tracheal narrowing has been recognized as a significant comorbid condition in patients with Morquio A, also known as mucopolysaccharidosis IVA. We studied a large cohort of patients with Morquio A to describe the extent of their tracheal narrowing and its relationship to airway management during anesthesia care. METHODS: This is an observational study, collecting data retrospectively, of a cohort of patients with Morquio A. Ninety-two patients with Morquio A syndrome were enrolled, among whom 44 patients had their airway evaluated by computed tomography angiography and had undergone an anesthetic within a year of the evaluation. Our hypothesis was that the tracheal narrowing as evaluated by computed tomography angiography increases with age in patients with Morquio A. The primary aim of the study was to examine the degree of tracheal narrowing in patients with Morquio A and describe the difficulties encountered during airway management, thus increasing awareness of both the tracheal narrowing and airway management difficulties in this patient population. In addition, the degree of tracheal narrowing was evaluated for its association with age or spirometry parameters using Spearman's rank correlation. Analysis of variance followed by the Bonferroni test was used to further examine the age-based differences in tracheal narrowing for the 3 age groups: 1 to 10 years, 11 to 20 years, and >21 years. RESULTS: Patient age showed a positive correlation with tracheal narrowing ( rs= 0.415; 95% confidence interval [95% CI], 0.138-0.691; P = .005) with older patients having greater narrowing of the trachea. Among spirometry parameters, FEF25%-75% showed an inverse correlation with tracheal narrowing as follows: FEF25%-75% versus tracheal narrowing: ( rs = -0.467; 95% CI, -0.877 to -0.057; P = .007). During anesthetic care, significant airway management difficulties were encountered, including cancelation of surgical procedures, awake intubation using flexible bronchoscope, and failed video laryngoscopy attempts. CONCLUSIONS: Clinically significant tracheal narrowing was present in patients with Morquio A, and the degree of such narrowing likely contributed to the difficulty with airway management during their anesthetic care. Tracheal narrowing worsens with age, but the progression appears to slow down after 20 years of age. In addition to tracheal narrowing, spirometry values of FEF25%-75% may be helpful in the overall evaluation of the airway in patients with Morquio A.

Achondroplasia Natural History Study (CLARITY): 60-year experience with hydrocephalus in achondroplasia from four skeletal dysplasia centers.

OBJECTIVE: The objective of this study was to describe the incidence and management of hydrocephalus in patients with achondroplasia over a 60-year period at four skeletal dysplasia centers. METHODS: The Achondroplasia Natural History Study (CLARITY) is a registry for clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the US from 1957 to 2017. Data were entered and stored in a REDCap database and included surgeries with indications and complications, medical diagnoses, and radiographic information. RESULTS: A total of 1374 patients with achondroplasia were included in this study. Of these, 123 (9%) patients underwent treatment of hydrocephalus at a median age of 14.4 months. There was considerable variation in the percentage of patients treated for hydrocephalus by center and decade of birth, ranging from 0% to 28%, although in the most recent decade, all centers treated less than 6% of their patients, with an average of 2.9% across all centers. Undergoing a cervicomedullary decompression (CMD) was a strong predictor for treatment of hydrocephalus (OR 5.8, 95% CI 3.9-8.4), although that association has disappeared in those born since 2010 (OR 1.1, 95% CI 0.2-5.7). In patients born since 1990, treatment of hydrocephalus with endoscopic third ventriculostomy (ETV) has become more common; it was used as the first line of treatment in 38% of patients in the most recent decade. Kaplan-Meier analysis suggests that a single ETV will treat hydrocephalus in roughly half of these patients. CONCLUSIONS: While many children with achondroplasia have features of hydrocephalus with enlarged intracranial CSF spaces and relative macrocephaly, treatment of hydrocephalus in achondroplasia patients has become relatively uncommon in the last 20 years. Historically, there was a significant association between symptomatic foramen magnum stenosis and treatment of hydrocephalus, although concurrent treatment of both has fallen out of favor with the recognition that CMD alone will treat hydrocephalus in some patients. Despite good experimental data demonstrating that hydrocephalus in achondroplasia is best understood as communicating in nature, ETV appears to be reasonably successful in certain patients and should be considered an option in selected patients.

Achondroplasia natural history study (CLARITY): 60-year experience in orthopedic surgery from four skeletal dysplasia centers.

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database. RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. 12.7% (n = 175) of patients underwent spine surgery at a mean age at first surgery of 22.4 ± 15.3 years old. The median age was 16.7 years old (0.1-67.4). 21.2% (n = 291) of patients underwent lower extremity surgery at a mean age at first surgery of 9.9 ± 8.3 years old with a median age of 8.2 years (0.2-57.8). The most common spinal procedure was decompression (152 patients underwent 271 laminectomy procedures), while the most common lower extremity procedure was osteotomy (200 patients underwent 434 procedures). Fifty-eight (4.2%) patients had both a spine and lower extremity surgery. Specific risk factors increasing the likelihood of orthopedic surgery included: patients with hydrocephalus requiring shunt placement having higher odds of undergoing spine surgery (OR 1.97, 95% CI 1.14-3.26); patients having a cervicomedullary decompression also had higher odds of undergoing spine surgery (OR 1.85, 95% CI 1.30-2.63); and having lower extremity surgery increased the odds of spine surgery (OR 2.05, 95% CI 1.45-2.90). CONCLUSIONS: Orthopedic surgery was a common occurrence in achondroplasia with 29.7% of patients undergoing at least one orthopedic procedure. Spine surgery (12.7%) was less common and occurred at a later age than lower extremity surgery (21.2%). Cervicomedullary decompression and hydrocephalus with shunt placement were associated with an increased risk for spine surgery. The results from CLARITY, the largest natural history study of achondroplasia, should aid clinicians in counseling patients and families about orthopedic surgery.

Route of delivery does not impact postnatal surgical morbidity in pregnancies affected by fetal achondroplasia.

PURPOSE: Pregnancies affected by maternal or fetal achondroplasia present unique challenges. The optimal route of delivery in fetuses with achondroplasia has not been established. Our objective was to determine whether the route of delivery affects postnatal achondroplasia-related surgical burden. METHODS: We conducted a secondary analysis of Achondroplasia Natural History Study (CLARITY), which is a multicenter natural history cohort study of patients with achondroplasia. Achondroplasia-related surgical morbidity, which we defined as the need for one or more postnatal achondroplasia-related surgeries, was assessed in relation to the route of delivery and whether the mother also had achondroplasia. Rate of each individual surgery type (otolaryngology, brain, foramen magnum, spine, and extremity) was also assessed in relation to the route of delivery. RESULTS: Eight hundred fifty-seven patients with achondroplasia with known route of delivery and known maternal stature were included. Three hundred sixty (42%) patients were delivered vaginally, and 497 (58%) patients were delivered by a cesarean delivery. There was no difference in the odds of requiring any postnatal achondroplasia-related surgery in those with achondroplasia who were delivered vaginally compared with those delivered by cesarean birth (odds ratio 0.95, 95% CI = 0.68-1.34, P = .80). No difference was present in the odds of requiring any postnatal achondroplasia-related surgery when route of delivery was compared for fetuses born to 761 average stature mothers (odds ratio 1.05, 95% CI = 0.74-1.51, P = .78). There was also no difference in the odds of requiring each of the individual achondroplasia-related surgeries by route of delivery, including cervicomedullary decompression. CONCLUSION: Our study suggests that it is reasonable for average stature patients carrying a fetus with achondroplasia to undergo a trial of labor in the absence of routine obstetric contraindications.

Agroecological producers shortening food chains during Covid-19: opportunities and challenges in Costa Rica.

The Covid-19 pandemic has compounded the global food insecurity crisis, disproportionately affecting the consumers, farmers, and food workers (UN in Policy brief: impacts of COVID-19 on food security and nutrition, 2020, https://www.un.org/sites/un2.un.org/files/sg_policy_brief_on_covid_impact_on_food_security.pdf). The significant disruptions caused by Covid-19 have called international attention to food security and sparked conversations about how to better support food production and trade. Our paper contributes to a small but growing literature on the impacts and responses of agroecological farmers to Covid-19 in Costa Rica. Specifically, we interviewed 30 agroecological farmers about (1) livelihood disruptions during Covid-19, (2) the areas of food production and sales most affected during this pandemic, and (3) how farmers and consumers are adapting during this crisis. Our findings reveal multiple impacts on agroecological farmers including: economic hardships of lower incomes and inability to pay loans, changes in purchasing and consumption patterns, market disruptions, changes in sales, a decrease in agrotourism, and a shortage of farmworkers. Furthermore, we also report the following farmer adaptation strategies: (1) minimizing distance with consumers to facilitate direct delivery, (2) establishing e-commerce platforms. Based on our findings, we recommend the following: (1) building farmer networks for knowledge sharing, (2) increasing technological support for farmers, and (3) providing government support to ensure that such crises do not increase unemployment among farmers and exacerbate food insecurity.

Otolaryngology Utilization in Patients With Achondroplasia: Results From the CLARITY Study.

OBJECTIVES/HYPOTHESIS: To quantify otolaryngologic surgery utilization in patients with achondroplasia, and to identify any changes in utilization over the past four decades. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study of 1,374 patients with achondroplasia enrolled in the CLARITY retrospective cohort study at four centers of multi-specialty care for patients with achondroplasia. Otolaryngologic surgeries are presented by birth cohort decade. The main outcomes were number of primary and additional otolaryngologic procedures; age at surgery; likelihood of repeated surgery; temporal trends in surgical utilization. RESULTS: In this cohort of 1,374 patients with achondroplasia, 620 (45.1%) had pharyngeal surgery at least once, 150 (10.9%) had pharyngeal surgery on more than one occasion, and patients who had adenoidectomy first were 2.68 times more likely to require a second pharyngeal surgery than those who had adenotonsillectomy. Seven hundred and seventy-nine (56.7%) had tympanostomy tubes placed at least once, and 447 (32.5%) had tympanostomy tubes placed more than one time. Age at first pharyngeal surgery decreased by 1.2 years per birth cohort decade, and age at tympanostomy tube placement decreased by 1.1 years per decade. CONCLUSIONS: Patients with achondroplasia often require otolaryngologic surgery, particularly adenoidectomy and/or tonsillectomy as well as tympanostomy tube placement. Such surgery is performed now more frequently and at younger ages than in earlier decades. While otolaryngologic disease associated with achondroplasia is now recognized earlier and treated more frequently, long-term outcome studies are needed. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1548-1554, 2022.

Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study-a multi-center retrospective cohort study of achondroplasia in the US.

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients. METHODS: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. RESULTS: Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. CONCLUSION: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

Achondroplasia Natural History Study (CLARITY): 60-year experience in cervicomedullary decompression in achondroplasia from four skeletal dysplasia centers.

OBJECTIVE: The authors sought to determine the overall incidence of cervicomedullary decompression (CMD) in patients with achondroplasia and the characteristics associated with those surgeries across multiple institutions with experience caring for individuals with skeletal dysplasias. METHODS: Data from CLARITY (Achondroplasia Natural History Study) for 1374 patients with achondroplasia from four skeletal dysplasia centers (A. I. duPont Hospital for Children, Johns Hopkins University, University of Texas Health, and University of Wisconsin School of Medicine and Public Health) followed from 1957 to 2017 were recorded in a Research Electronic Data Capture (REDCap) database. Data collected and analyzed included surgeries, indications, complications, ages at time of procedures, screening procedures, and medical diagnoses. RESULTS: There were 314 CMD procedures in 281 patients (20.5% of the entire cohort). The median age of first CMD was 1.3 years in males and 1.1 years in females. Over time, there was a decrease in the median age of patients at first CMD. All patients born before 1980 who underwent CMD had the procedure after 5 years of age, whereas 98% of patients born after 2010 underwent CMD before 5 years of age. In addition, a greater proportion of patients born in more recent decades had documented neuroimaging and polysomnography (PSG) prior to CMD. Ventriculoperitoneal shunts (VPSs) were placed more frequently in patients undergoing CMD (23%) than in the entire cohort (8%). Patients who required either CMD or VPS were 7 times more likely to require both surgeries than patients who required neither surgery (OR 7.0, 95% CI 4.66-10.53; p < 0.0001). Overall, 10.3% of patients who underwent CMD required a subsequent CMD. CONCLUSIONS: The prevalence of CMD in this large achondroplasia cohort was 20%, with more recently treated patients undergoing first CMD at younger ages than earlier patients. The use of neuroimaging and PSG screening modalities increased over time, suggesting that increased and better surveillance contributed to earlier identification and intervention in patients with cervicomedullary stenosis and its complications.

Achondroplasia Natural History Study (CLARITY): a multicenter retrospective cohort study of achondroplasia in the United States.

PURPOSE: Achondroplasia is the most common short stature skeletal dysplasia (1:20,000-30,000), but the risk of adverse health outcomes from cardiovascular diseases, pain, poor function, excess weight, and sleep apnea is unclear. A multicenter retrospective natural history study was conducted to understand medical and surgical practices in achondroplasia. METHODS: Data from patients with achondroplasia evaluated by clinical geneticists at Johns Hopkins University, A.I. duPont Hospital for Children, McGovern Medical School UTHealth, and University of Wisconsin were populated into a REDCap database. All available retrospective medical records of anthropometry (length/height, weight, occipitofrontal circumference), surgery, polysomnography (PSG), and imaging (e.g., X-ray, magnetic resonance imaging) were included. RESULTS: Data from 1,374 patients (48.8% female; mean age 15.4 ± 13.9 years) constitute the primary achondroplasia cohort (PAC) with 496 subjects remaining clinically active and eligible for prospective studies. Within the PAC, 76.0% had a de novo FGFR3 pathologic variant and 1,094 (79.6%) had one or more achondroplasia-related surgeries. There are ≥37,000 anthropometry values, 1,631 PSGs and 10,727 imaging studies. CONCLUSION: This is the largest multicenter achondroplasia natural history study, providing a vast array of medical information for use in caring for these patients. This well-phenotyped cohort is a reference population against which future medical and surgical interventions can be compared.

CLARITY: Co-occurrences in achondroplasia-craniosynostosis, seizures, and decreased risk of diabetes mellitus.

Achondroplasia is the most common disproportionate short statured skeletal dysplasia with a prevalence of approximately 1:20,000-30,000. We created the largest database to date of a historical cohort of 1374 patients with achondroplasia (CLARITY-aChondropLasia nAtuRal hIsTory studY). This cohort was queried for the presence of unrecognized or under-recognized features associated with achondroplasia. Craniosynostosis was found to co-occur with achondroplasia in 9 (0.65%) patients in this cohort, which is much higher than the general population prevalence of 3.1-7.2 per 10,000. In addition, 27 patients had seizures (2.0%), an apparent excess as compared to the general population. Only two people had diabetes despite a high rate of adult obesity. This report documents for the first time an increased prevalence of craniosynostosis in persons with achondroplasia, and adds support to previous observations of an apparently higher than expected prevalence of seizures and lower prevalence of diabetes mellitus.

Should We Stop Calling Thanatophoric Dysplasia a Lethal Condition? A Case Report of a Long-Term Survivor.

Thanatophoric dysplasia (TD) is a rare skeletal dysplasia commonly thought to be lethal. In this case report, we discuss a nine-year-old male with TD and review his parents' decision making shortly after their son was born, the technology needed to sustain him, and his parents' perception of his quality of life. We also summarize the clinical course of published long-term survivors with TD. Pediatric Palliative Care teams, especially those conducting perinatal palliative care consultations, are often asked to support families in the face of prognostic uncertainty. Our case report and review of the literature adds to the uncertainty of prognosis in TD and suggests that pediatric palliative care providers should be wary of the label "lethal."

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome.

RNU4ATAC pathogenic variants to date have been associated with microcephalic osteodysplastic primordial dwarfism, type 1 and Roifman syndrome. Both conditions are clinically distinct skeletal dysplasias with microcephalic osteodysplastic primordial dwarfism, type 1 having a more severe phenotype than Roifman syndrome. Some of the overlapping features of the two conditions include developmental delay, microcephaly, and immune deficiency. The features also overlap with Lowry Wood syndrome, another rare but well-defined skeletal dysplasia for which the genetic etiology has not been identified. Characteristic features include multiple epiphyseal dysplasia and microcephaly. Here, we describe three patients with Lowry Wood syndrome with biallelic RNU4ATAC pathogenic variants. This report expands the phenotypic spectrum for biallelic RNU4ATAC disorder causing variants and is the first to establish the genetic cause for Lowry Wood syndrome.

Examining the effects of linking student performance and progression in a tier 2 kindergarten reading intervention.

Despite the emerging evidence base on response to intervention, there is limited research regarding how to effectively use progress-monitoring data to adjust instruction for students in Tier 2 intervention. In this study, we analyzed extant data from a series of randomized experimental studies of a kindergarten supplemental reading intervention to determine whether linking performance on formative assessments to curriculum progression improved kindergarten reading outcomes over standard implementation. We were interested in whether specific progression adjustments would enhance the effects of supplemental reading intervention. Growth-mixture modeling using data from kindergarteners (n = 136) whose intervention progression (e.g. repeat lessons, skip lessons) was adjusted every 4 weeks based on mastery data identified four latent classes characterized by unique profiles of curriculum progression adjustments. Multilevel analyses comparing the performance of students in the four classes with that of propensity matched groups whose intervention was not adjusted (n = 101) indicated positive effects of curriculum progression for (a) students whose formative assessment performance exceeded 90% and received early and sustained lesson acceleration and (b) students who initially performed below 70% on assessments and who repeated early lessons and progressed to conventional implementation. Effects of curriculum adjustments for the two smallest groups were less clear.

Effect of splinting and exercise on intraneural edema of the median nerve in carpal tunnel syndrome--an MRI study to reveal therapeutic mechanisms.

Splinting and nerve and tendon gliding exercises are commonly used to treat carpal tunnel syndrome (CTS). It has been postulated that both modalities reduce intraneural edema. To test this hypothesis, 20 patients with mild to moderate CTS were randomly allocated to either night splinting or a home program of nerve and tendon gliding exercises. Magnetic resonance images of the wrist were taken at baseline, immediately after 10 min of splinting or exercise, and following 1 week of intervention. Primary outcome measures were signal intensity of the median nerve at the wrist as a measure of intraneural edema and palmar bowing of the carpal ligament. Secondary outcome measures were changes in symptom severity and function. Following 1 week of intervention, but not immediately after 10 min, signal intensity of the median nerve was reduced by ≈ 11% at the radioulnar level for both interventions (p = 0.03). This was accompanied by a mild improvement in symptoms and function (p < 0.004). A similar reduction in signal intensity is not observed in patients who only receive advice to remain active. No changes in signal intensity were identified further distally (p > 0.28). Ligament bowing remained unchanged (p > 0.08). Intraneural edema reduction is a likely therapeutic mechanism of splinting and exercise.

Improving pregnancy outcome and reducing avoidable clinical resource utilization through telephonic perinatal care coordination.

The effects of telephonic nursing case management and standard care in a low-income, high-risk pregnancy population, controlling for gestational age at referral and risk factors (medical, demographic, and behavioral) were compared. The hypothesis was that a program of telephonic perinatal nursing care coordination and case management would increase mean gestational ages and mean birth weights and would reduce clinical resource utilization, compared with standard nursing care. The methods focused on a telephonic model developed during the past 16 years that included risk assessment, patient education, coordination of care for home services and clinic appointments, coordination of interventions requested by care providers, and patient advocacy. The patient population, primarily of minority cultural and racial backgrounds, obtained prenatal care from two large obstetric clinics and delivered at a level-3 tertiary care center. They were randomly assigned to treatment (N = 61) and control (N = 50) conditions. Interpreters were used for any contacts with non-English-speaking patients. The results demonstrated increased mean birth weights for the treatment group when intervening variables were controlled. Mean gestational age at delivery was not significantly different between groups. Telephonic case management saved an average of 501.31 dollars per patient in inpatient and outpatient costs combined. In the treatment group, for every dollar spent on case management costs, the savings were 4.08 dollars.

The influence of telephonic nursing care coordination on patient satisfaction in a predominantly low-income, high-risk pregnancy population.

The effect of telephonic nursing case management on patient satisfaction in a predominantly non-Caucasian low-income, high-risk pregnancy population was studied. Patient satisfaction of care was significantly higher for treatment group participants than for controls on 9 of 10 items measuring satisfaction. The satisfaction score of the treatment patients, constructed by summing scores for each item, averaged 8 points higher than the control group's score. Demographics made little difference. Telephonic case management was the strongest predictor of satisfaction in a multiple regression analysis. Satisfaction was unrelated to mode of delivery, infant birth weight, or gestational age. The satisfaction levels of treatment patients were high, whether or not they had outpatient charges. Participants rated the program highly for the nurses' ability to answer questions, overall program experience, the opportunity to ask the nurses questions, health teachings and instructions received, and confidence in the nurse coordinating their care or their child's care.