Longitudinal Assessment of Timed Function Tests in Ambulatory Individuals with SMA Treated with Nusinersen.

BACKGROUND: Ambulatory individuals with spinal muscular atrophy experience weakness and impairments of speed and endurance. This leads to decreased motor skill performance required for daily living including transitioning from floor to stand, climbing stairs, and traversing short and community distances. Motor function improvements have been reported in individuals receiving nusinersen, but changes in timed functional tests (TFTs) which assess shorter distance walking and transitions have not been well documented. OBJECTIVE: To evaluate changes in TFT performance over the course of nusinersen treatment in ambulatory individuals with SMA and identify potential factors [age, SMN2 copy number, BMI, Hammersmith Functional Motor Scale Expanded (HFMSE score), Peroneal Compound Motor Action Potential (CMAP) amplitude] associated with TFT performance. METHODS: Nineteen ambulatory participants receiving nusinersen were followed from 2017 through 2019 (range: 0-900 days, mean 624.7 days, median 780 days); thirteen of 19 (mean age = 11.5 years) completed TFTs. The 10-meter walk/run test, time-to-rise from supine, time-to-rise from sitting, 4-stair climb, 6-minute walk test (6MWT), Hammersmith Expanded and peroneal CMAP were assessed at each visit. Linear mixed-effects models were used to evaluate unadjusted and adjusted changes in these outcomes over time. RESULTS: Apart from time to rise from sitting and from supine, all TFTs were found to improve over the course of treatment after adjusting for baseline age and BMI. CONCLUSIONS: Improvement in TFTs over time in patients with SMA treated with nusinersen suggests that shorter TFTs may have value to assess individuals with SMA who have or later gain ambulatory function during treatment.

Cost Implications of Insurance Associated Disparities in Post-Acute Traumatic Brain and Spinal Cord Injury Rehabilitation.

Abstract Post-acute care after spinal cord injury (SCI) or traumatic brain injury (TBI) influences neurological function regained. Inpatient rehabilitation facilities (IRFs) have more intensive care and result in lower mortality and better functional outcomes compared with skilled nursing facilities (SNFs). This study sought to quantify inpatient rehabilitation access by insurance and estimate the cost implications. We conducted a retrospective observational cohort study utilizing 2015-2017 California Office of Statewide Health Planning and Development database of injured adults with SCI and/or TBI. The primary predictor was insurance status. The outcome was discharge destination (home, IRFs, SNFs, long-term acute care [LTAC]) modeled using multi-variable multinomial mixed-effects logistic regression controlling for age, diagnosis, Weighted Elixhauser Comorbidity Index, and New Injury Severity Score. Cost of care for discharge to IRFs versus SNFs was estimated by adjusted quantile regression. Cost simulation predicted the adjusted cost difference if all publicly insured participants were discharged to an IRF. We identified 83,230 patients with an injury mechanism and a primary acute care hospitalization diagnosis of TBI (90.9%), SCI (8.3%), or both (0.8%) who were discharged to an IRF, SNF, LTAC, or home. Publicly insured patients were more likely than privately insured patients to go to SNFs versus IRFs (odds ratio [OR]: 2.17, 95% confidence interval [CI 2.01-2.34]). Sub-group analysis of 6416 participants showed an adjusted median total cost difference of $18,461 (95% CI [$5,908-$38,064]) and adjusted cost-per-day of the post-acute encounter of $1,045 (95% CI [$752-$2,399]) higher for discharge to IRFs versus SNFs. Cost simulation demonstrated an additional adjusted cost of $364M annually for universal IRF access for the publicly insured. Publicly insured SCI and TBI Californians are less frequently discharged to IRFs compared with their privately insured counterparts resulting in a lower short-term cost of care. However, the consequences of decreased intensive rehabilitation utilization in terms of functional recovery and long-term cost implications require further investigation.

Urinary metal profiles in mother-offspring pairs and their association with early dysglycemia in the International Hyperglycemia and Adverse Pregnancy Outcome Follow Up Study (HAPO-FUS).

BACKGROUND: Variations in dietary intake and environmental exposure patterns of essential and non-essential trace metals influence many aspects of human health throughout the life span. OBJECTIVE: To examine the relationship between urine profiles of essential and non-essential metals in mother-offspring pairs and their association with early dysglycemia. METHODS: Herein, we report findings from an ancillary study to the international Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study (HAPO-FUS) that examined urinary essential and non-essential metal profiles from mothers and offspring ages 10-14 years (1012 mothers, 1013 offspring, 968 matched pairs) from 10 international sites. RESULTS: Our analysis demonstrated a diverse exposure pattern across participating sites. In multiple regression modelling, a positive association between markers of early dysglycemia and urinary zinc was found in both mothers and offspring after adjustment for common risk factors for diabetes. The analysis showed weaker, positive, and negative associations of the 2-h glucose value with urinary selenium and arsenic respectively. A positive association between 2-h glucose values and cadmium was found only in mothers in the fully adjusted model when participants with established diabetes were excluded. There was a high degree of concordance between mother and offspring urinary metal profiles. Mother-to-offspring urinary metal ratios were unique for each metal, providing insights into changes in their homeostasis across the lifespan. SIGNIFICANCE: Urinary levels of essential and non-essential metals are closely correlated between mothers and their offspring in an international cohort. Urinary levels of zinc, selenium, arsenic, and cadmium showed varying degrees of association with early dysglycemia in a comparatively healthy cohort with a low rate of preexisting diabetes. IMPACT STATEMENT: Our data provides novel evidence for a strong correlation between mother and offspring urinary metal patterns with a unique mother-to-offspring ratio for each metal. The study also provides new evidence for a strong positive association between early dysglycemia and urinary zinc, both in mothers and offspring. Weaker positive associations with urinary selenium and cadmium and negative associations with arsenic were also found. The low rate of preexisting diabetes in this population provides the unique advantage of minimizing the confounding effect of preexisting, diabetes related renal changes that would alter the relationship between dysglycemia and renal metal excretion.

Impact of an Electronic Health Record Pain Medication Prescribing Tool on Opioid Prescriptions for Postoperative Pain in Hand, Orthopedic, Plastic, and Spine Surgery Across a Health Care System.

PURPOSE: We hypothesized that a pain management prescribing tool embedded in the electronic health record system of a multihospital health care system would decrease prescription opioids for postoperative pain by hand, orthopedic, plastic, and spine surgeons. METHODS: A prescribing tool for postoperative pain was designed for hand, orthopedic, plastic, and spine surgeons and implemented into electronic discharge order sets in a 10-hospital health care system. Stakeholders were educated on tool use in person and/or by email on 2 occasions. A dashboard was created to monitor opioid pill quantities and morphine milligram equivalents (MMEs) prescribed. Overall compliance with the suggested opioid amounts was assessed for 20 months after tool implementation. A subgroup of 6 hand surgeons, one of whom was instrumental in designing the tool, were evaluated for MMEs prescribed, opioid refills, patient emergency room visits, and patient readmissions within 30 days after discharge. Comparisons in this subgroup were made from 12 months before to 15 months after tool implementation. RESULTS: The mean system-wide compliance with the suggested opioid pill quantities and MMEs prescribed in all 4 specialties improved by less than 5%. In the subgroup of hand surgeons, 5 of whom championed tool use, prescribed MMEs decreased by 10% during each of the 4 quarters before launching the tool and contracted an additional 26% in the first quarter after tool implementation. Opioid refills held steady at 5%, and there were no emergency room visits or readmissions within 30 days after discharge in this patient subgroup. CONCLUSIONS: The prescribing tool had a negligible impact on system-wide compliance with suggested prescription opioid pill quantities and MMEs. In a small group of surgeons who championed the use of the tool, there was a significant and sustained decline in MMEs prescribed without adversely impacting patient refills, emergency room visits, or readmissions. CLINICAL RELEVANCE: An electronic prescribing tool to assist surgeons in lowering opioid prescription pill quantities and MMEs may have a negligible impact on prescribing behavior in a multihospital health care system.

Magnetic Resonance Imaging in Pediatric Myocarditis: Trends and Associations With Cost and Outcome.

BACKGROUND: Cardiac magnetic resonance (CMR) provides tissue characterization and structural and functional data. CMR has high sensitivity and specificity for myocarditis in adults and children. The relationship between pediatric CMR use, cost, and clinical outcome has not been studied. OBJECTIVES: This work aims to describe temporal trends in CMR imaging for pediatric myocarditis and examine associations between CMR use, hospital cost, and outcomes. METHODS: A retrospective cohort study of all inpatients <21 years of age with a diagnosis of myocarditis reported to the Pediatric Health Information System (2004-2019) was performed. Trends in CMR use were examined. A propensity-matched subcohort using center and patient level variables was used to assess whether outcomes differed by CMR use. RESULTS: A total of 4,195 children with myocarditis from 47 hospitals were identified. The median age was 11.5 years (IQR: 1.5-16.0 years) and 2,617 (62%) were male. CMR was used in 23% and mortality occurred in 6%. CMR use during hospitalization increased from 2% in 2004 to 37% in 2019 (odds ratio [OR]: 1.19 [95% CI: 1.17-1.21]). After propensity score matching, CMR use was associated with higher median cost (+$5,340 [95% CI: +$1,739 to +$9,936]) and similar median length of stay (0 days [95% CI: -1 to +1 days]). Using quantile regression, CMR was associated with lower 90th percentile cost (-$77,200 [95% CI: -$127,373 to -$31,339]). More children receiving CMR were discharged alive in the first 30 days after admission (OR: 1.89 days [95% CI: 1.28-2.29]). Within the propensity matched cohort, <10 of 790 CMR recipients died compared to 42 of 790 in the non-CMR group. CONCLUSIONS: CMR use in children with myocarditis has increased over the past 15 years. CMR use is associated with higher cost of hospitalization and similar length of stay for most children but lower cost among the sickest children. CMR use in specific patients may improve clinical outcomes at a lower cost.

A comparison of symptoms of bipolar and unipolar depression in postpartum women.

BACKGROUND: Distinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders. METHODS: We performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4-6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS). RESULTS: The sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse. LIMITATIONS: Only women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data. CONCLUSIONS: Severity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse.

Longitudinal observational study of boxing therapy in Parkinson's disease, including adverse impacts of the COVID-19 lockdown.

BACKGROUND: Parkinson's Disease (PD) is a highly prevalent neurodegenerative disease whose incidence is increasing with an aging population. One of the most serious manifestations of PD is gait instability, leading to falls and subsequent complications that can be debilitating, even fatal. Boxing therapy (BT) uses gait and balance exercises to improve ambulation in people with PD, though its efficacy has not yet been fully proven. METHODS: In the current longitudinal observational study, 98 participants with idiopathic PD underwent twice-weekly BT sessions. Primary outcome was self-reported falls per month; secondary outcomes were quantitative and semi-quantitative gait and balance performance evaluations. Statistical methods included segmented generalized estimating equation with an independent correlation structure, binomial distribution, and log link. RESULTS: The average number of self-reported falls per month per participant decreased by 87%, from 0.86 ± 3.58 prior to BT, to 0.11 ± 0.26 during BT. During the lockdown imposed by COVID-19, this increased to 0.26 ± 0.48 falls per month. Females and those > 65 years old reported the greatest increase in falls during the lockdown period. Post-lockdown resumption of BT resulted in another decline in falls, to 0.14 ± 0.33. Quantitative performance metrics, including standing from a seated position and standing on one leg, largely mirrored the pattern of falls pre-and post-lockdown. CONCLUSIONS: BT may be an effective option for many PD patients.

Longitudinal Study of Boxing Therapy in Parkinson's Disease, Including Adverse Impacts of the COVID-19 Lockdown.

BACKGROUND: Parkinson's Disease (PD) is a highly prevalent neurodegenerative disease whose incidence is increasing with an aging population. One of the most serious manifestations of PD is gait instability, leading to falls and subsequent complications that can be debilitating, even fatal. Boxing therapy (BT) uses gait and balance exercises to improve ambulation in people with PD, though its efficacy has not yet been fully proven. METHODS: In the current longitudinal observational study, 98 participants with idiopathic PD underwent twice-weekly BT sessions. Primary outcome was self-reported falls per month; secondary outcomes were quantitative and semi-quantitative gait and balance performance evaluations. Statistical methods included segmented generalized estimating equation with an independent correlation structure, binomial distribution, and log link. RESULTS: The average number of self-reported falls per month per participant decreased by 87%, from 0.86 ± 3.58 prior to BT, to 0.11 ± 0.26 during BT. During the lockdown imposed by COVID-19, this increased to 0.26 ± 0.48 falls per month. Females and those > 65 years old reported the greatest increase in falls during the lockdown period. Post-lockdown resumption of BT resulted in another decline in falls, to 0.14 ± 0.33. Quantitative performance metrics, including standing from a seated position and standing on one leg, largely mirrored the pattern of falls pre-and post-lockdown. CONCLUSIONS: BT may be an effective option for many PD patients.

National Characteristics of Surgeons Performing Vasectomy: Increasing Specialization and a Persistent Gender Gap.

OBJECTIVE: To describe trends in the characteristics of urologic surgeons performing vasectomy over time. METHODS: We performed a retrospective, cross-sectional study examining surgeon characteristics for case logs from the American Board of Urology between 2004 and 2013. We used generalized estimating equations with a log link and negative binomial distribution to examine demographic differences (gender, rural location, and surgeon volume) in the number of vasectomies surgeons performed over time. RESULTS: Between 2004 and 2013, 5316 urologists had case logs collected within the 7-month certification window. The majority of these surgeons self-identified as general urologists (82.8%), and a small proportion identified as andrology and infertility specialists (1.7%). Across all years, the median number of vasectomies performed per certifying surgeon during the study period was 14 (interquartile range 6-26). The majority of vasectomies were performed by high-volume surgeons (≥ 26 vasectomies) ranging from 49.2% to 66.9% annually, whereas the proportion performed by low-volume (≤ 5 vasectomies) surgeons ranged from 3.3% to 6.6% annually. Male surgeons performed vasectomies 2.20 times more frequently than female surgeons (95% confidence interval 1.93-2.49; P <.0001) across the study period with no evidence to suggest this gap changed over time (gender-year interaction 1.01 [95% confidence interval: 0.97-1.06; p = .576]). CONCLUSION: While the majority of urologists performing vasectomy identify as general urologists, there appears to be a focus on vasectomy practice among a small number of high-volume surgeons. Furthermore, while the number of female surgeons performing vasectomies increased, a gender gap persists in the proportion of vasectomies performed by females.

Interpreting the pharmacoepidemiology literature in obstetrical studies: A guide for clinicians.

Many prescribers are knowledgeable about randomized controlled trials (RCT), but are less familiar with pharmacoepidemiology studies; that is, observational studies in which a pharmacologic agent is the exposure of interest. To date, few clinical trials include pregnant women. With the absence of RCT data, prescribers must largely rely on the pharmacoepidemiology literature to guide prescribing decisions for pregnant patients. We describe different types of pharmacoepidemiology studies and present a flowchart and table checklist to support clinicians to assess the quality of, and thus the validity of conclusions from, pharmacoepidemiology studies. We provide illustrative examples of published observational studies examining antidepressant treatment during pregnancy and fetal and infant outcomes.

Failure to thrive: The socioeconomics of pediatric gastrostomy complications.

PURPOSE: One of the most common procedures in the pediatric population is the placement of a gastrostomy tube. There are significant medical, emotional, and social implications for both patients and caregivers. We hypothesized that socioeconomic status had a significant impact on gastrostomy complications. METHODS: A retrospective chart review was performed. Patient and census data including median household income, unemployment rate, health insurance status, poverty level, and caregiver education level were merged. Statistical tests were conducted against a 2-sided alternative hypothesis with a 0.05 significance level. Outcomes examined were minor and major complications in association with socioeconomic variables. RESULTS: Patients with mechanical complications were younger, weighed less, and had a 72% greater chance of having commercial insurance. Patients with Medicare/self-pay were three times more likely to have a minor complication. The average unemployment rate was 23% greater in families with a major complication. Individuals with a minor complication came from community tracts with a lower percentage of families below the poverty level. CONCLUSION: An association between socioeconomic factors and gastrostomy complications was identified. Insurance status and employment status were more significant predictors than poverty level. Further work with variables for targeted interventions to provide specific family support will allow these children and families to thrive. LEVEL OF EVIDENCE: Level II prognosis study.

Adopting Single-Incision Laparoscopic Appendectomy in Children: Is It Safe During the Learning Curve?

Introduction: Laparoscopic appendectomy is the gold standard for treatment of acute appendicitis. The single-incision laparoscopic surgery (SILS) approach has gained widespread acceptance. This study evaluates the learning curve of contemporarily trained surgeons adopting SILS appendectomy and, more specifically, the safety of the operation during the early phase of this learning curve. Methods: A retrospective review of 974 consecutive pediatric patients younger than 18 years of age, who underwent an appendectomy at a single institution from 2005 to 2018, was performed. Nonperforated and perforated appendicitis cases were included. A subgroup analysis was performed on SILS appendectomy. Outcomes measured included length of operating room and anesthesia time, as well as complication rate. A log-logistics and a Loess smoothing model were used. Results: A total of 438 single-incision laparoscopic appendectomies were reviewed. A trend toward faster operative times was observed for all surgeons as case numbers increased. The odds of still being operated on decreased by 0.997 for each additional case. Based on a 95% confidence band and this experienced time as the standard, we expect adopting surgeons to reach this experienced level after 51 cases. During the early SILS appendectomy learning curve, there was no significant difference in complication rate compared with multiport laparoscopy. Conclusion: As expected, the more single-incision cases were performed, the shorter the operative times. More importantly, there was no increase in complication rate during the learning stage of single-incision appendectomies in either perforated or nonperforated appendicitis.