Comparison of home-based spirometry and oscillometry measurements in school-age children with bronchopulmonary dysplasia.

INTRODUCTION: This study compares home-based oscillometry and spirometry for characterizing respiratory system disease in school-aged children with bronchopulmonary dysplasia (BPD) in clinical research. We hypothesized higher rates of successful completion and abnormal cases identified through oscillometry, with correlations between device measurements. METHODS: Participants 6-12 years old with BPD in the ongoing Air Quality, Environment and Respiratory Outcomes in BPD (AERO-BPD) study performed oscillometry followed by spirometry at two separate home visits. Parameters measured included airway resistance at 5 Hz(R5), resistance from 5 to 19 Hz(R5-19), resonance frequency(Fres), reactance at 5 Hz(X5), area under the curve between Fres and X5(AX), forced expiratory volume in 1 second(FEV1), forced vital capacity(FVC), and FEV1/FVC. Descriptive statistics identified the proportion of successful tests, correlation in measurements, and rate of lung disease for each device. RESULTS: Among 76 subjects with 120 paired observations, 95% and 71% of participants successfully performed oscillometry and spirometry, respectively, at home visit one. 98% and 77% successfully performed oscillometry and spirometry, respectively, at home visit two. Odds ratios favored oscillometry (range 5.31-10.13, p < 0.01). FEV1 correlated with AX (correlation coefficient r = -0.27, p = 0.03); FEV1/FVC with AX (r = -0.32, p = 0.02); and FEV1/FVC with R5 (r = -0.37, p = 0.01). AX exhibited the highest prevalence of abnormality at 25%; other oscillometry parameters ranged from 5%-22%. Forty-five to sixty-four percent of participants had abnormal spirometry. Oscillometry assessments had significantly lower odds of capturing lung disease (odds ratios 0.07-0.24, p < 0.0001). CONCLUSIONS: School-aged children with BPD demonstrated higher success rates in field-based oscillometry than spirometry. Spirometry exhibited higher rates of abnormality than oscillometry. Moderate correlation exists between device measurements.

Relationship between long-acting reversible contraception and acne in a cohort of adolescents and young adults.

BACKGROUND: The use of progestin-only long-acting reversible contraception (LARC) may be a risk factor for acne. Few studies have focused primarily on the effects of hormonal LARC on the development or exacerbation of acne in adolescents and young adults. We sought to understand the incidence and management of acne following hormonal LARC insertion in this adolescent/young adult population. METHODS: A secondary data analysis was conducted of prospectively collected quality improvement (QI) data from the Adolescent Medicine LARC Collaborative. Subjects were evaluated by clinicians in adolescent medicine clinics at participating study sites, and acne severity was documented using a standardized recording instrument and scale. Descriptive statistics were reported as frequencies and percentages for categorical variables or mean and standard deviation (SD) for continuous variables. We compared demographic and clinical characteristics by those who had worsening acne, accounting for site inter-correlation using Cochran-Mantel-Haenszel chi-square tests for categorical variables and linear generalized estimating equation (GEE) regression for continuous variables. RESULTS: Of 1319 subjects who completed LARC insertion, 28.5% (376/1319) experienced worsening acne following use of progestin-only LARC. Acne was a contributing factor to LARC removal in only 3% (40/1319), and the sole reason for removal in 0.4% (5/1319) of all subjects. As this was a secondary analysis of prospectively collected QI data, limitations of this study include incomplete or inaccurate documentation of acne severity. Moreover, LARC insertions without follow-up/removal visits or with only follow-up/removal within 8 weeks of insertion were excluded from our study, which may also bias results. CONCLUSIONS: Adolescents and young adults seeking progestin-only LARC should be counseled about the potential for developing acne or experiencing a worsening of existing acne during LARC use. However, acne was not a common reason for LARC discontinuation.

Characteristics and use of patient-reported outcomes of clinical trials for high-risk neurological medical devices that received FDA premarket approval from 2001 to 2022.

Neurological medical devices have revolutionized the management of neurological disorders, providing diagnostic, therapeutic, and monitoring solutions. High-risk neurological devices, such as deep brain stimulation and neurostimulators, offer groundbreaking treatments, emphasizing patient benefits while considering risks. To gain FDA approval, high-risk Class III devices necessitate premarket approval (PMA) applications with pivotal clinical trials, often assessing patient-reported outcomes (PROs). This article analyzes FDA-approved high-risk neurological devices from 2001 to 2022 via the PMA pathway. It explores device characteristics and pivotal clinical trials, and PRO incorporation. Of the 23 identified devices, pain neurology devices (30.4 %) predominated. All devices were therapeutic, with varying study designs. Pain neurology devices notably emphasized PRO endpoints as expected. This study underscores the significance of PROs in assessing device efficacy and safety, offering insights into regulatory processes and patient-centered care in neurological disorder management.

Delays to care in infantile epileptic spasms syndrome: Racial and ethnic inequities.

OBJECTIVE: Non-Hispanic (NH) Black children are less likely to receive a standard treatment course for infantile epileptic spasms syndrome (IESS) than White/NH children at pediatric tertiary care epilepsy centers in the United States. However, if inequities exist in time to diagnosis is unknown. Diagnostic delays as little as 1 week can be associated with worse developmental outcomes. METHODS: Diagnostic delays were evaluated in a retrospective cohort of 100 children with new onset IESS between January 2019 and May 2022. RESULTS: Children with Black, Indigenous, and People of Color (BIPOC) caregivers were more likely to experience clinically significant delays in referral from first provider to neurologist, when compared to White/NH children, even after controlling for other demographic and clinical variables (odds ratio = 4.98, confidence interval = 1.24-19.94, p = .023). SIGNIFICANCE: Disproportionate diagnostic delays place BIPOC children at risk of adverse developmental and epilepsy outcomes. Further interventional prospective and qualitative studies are needed to address inequities in care.

Continuation rates of hormonal intrauterine devices in adolescents and young adults when placed for contraceptive and non-contraceptive indications.

OBJECTIVE: This study aimed to estimate and compare continuation rates of hormonal intrauterine devices (IUDs) when placed for contraceptive or menstrual management indications in adolescents and young adults. STUDY DESIGN: We conducted a secondary analysis of a prospectively collected database of all hormonal IUD insertions from January 1, 2017 through December 31, 2020, with at least 1-year follow-up, across four Adolescent Medicine practices. IUD insertions without known indication were excluded. RESULTS: A total of 936 IUD insertions were attempted, 45% for contraception only, 18% for menstrual management only, and 37% for both indications. Insertion was successful in 868 (93%) attempts, and success did not differ by indication (p = 0.74). The mean age at insertion was 18.9 years (SD = 2.4 years), with no difference by indication. Of the completed insertions, 650 (75%) had at least one follow-up during the data analysis period. Excluding those without follow-up, the overall continuation rates were 77% at 1 year, 66% at 2 years, and 54% at 3 years. While continuation rates did not differ by indication at 1 year, at 3 years, continuation was highest among those who sought the device for menstrual management only (contraception = 53%, menstrual = 57%, both = 53%, p < 0.01) Malposition was rare (4.0%), as was device expulsion (2.5%), and these did not differ by indication. CONCLUSION: IUD continuation rates were high among adolescents and young adults and did not significantly differ when placed for contraceptive or non-contraceptive indication in the first year of use. IMPLICATIONS: Adolescents and young adults may seek the hormonal IUD for contraception and/or menstrual management. Our study found that IUD continuation rates were high at 1 year regardless of the indication for utilization.

Comparison of Pneumotachometer and Portable Digital Turbine Spirometry for Field-Based Assessment: An Air Quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia Study.

Introduction: Data on the use of remote spirometry are limited in the pediatric population. We sought to assess the feasibility and accuracy of a digital turbine spirometer, Medical International Research (MIR) Spirobank Smart (MIR, New Berlin, WI, USA), compared with a pneumotachography spirometer, Pneumotrac (Vitalograph Inc., Lenexa, KS, USA), in field-based clinical research. Methods: This is a cross-sectional study of a subgroup of school-aged participants enrolled in the Air quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia (BPD) study, who performed same-day paired coached baseline spirometry measurements from the Pneumotrac and MIR devices. Proportion of successful tests was estimated for each device and compared using McNemar's test. Correlation between devices forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was analyzed by Lin's concordance correlation, and Bland-Altman plots were generated. Results: Twenty-one participants with history of BPD completed home spirometry maneuvers on both devices. The mean age of participants was 8.7 years. The mean FEV1 and FVC measurement was 81% predicted and 90.4% predicted, respectively. The proportion of acceptable tests appeared higher using Pneumotrac (81%) than when using MIR (67%), although without evidence of discordance (P = 0.317). Among subjects with successful tests on both devices, Lin's concordance correlation demonstrated moderate agreement (FEV1 r = 0.955, 95% confidence interval [CI]: 0.87-0.98; FVC r = 0.971, CI: 0.91-0.99). The mean difference in FEV1 between Pneumotrac and MIR was 0.079 L (95% limits of agreement were -0.141 to 0.298 L) and FVC was 0.075 L (95% limits of agreement were -0.171 to 0.322 L). These were relatively small and without evidence of systematic or volume-dependent bias. Conclusions: Utilizing turbine spirometers may be a promising and feasible way to perform pulmonary function testing for field research in children.

Influence of extent and age at corpus callosotomy on seizure outcomes. A single center experience.

Corpus callosotomy (CC) is a palliative treatment for drop seizures in patients with drug-resistant nonlocalizable epilepsy. We compared drop seizure outcomes between patients undergoing anterior CC versus complete CC and examined factors impacting outcomes for drop seizures including age at CC and duration of epilepsy. A retrospective review of patients who underwent CC between 2003 and 2022 with a minimum of 6 months postsurgical follow-up was included. Outcome measure for drop seizures included seizure reduction ≥50% from baseline as well as elimination of drop seizures. Thirty-eight patients were included. Overall, ≥50% reduction in drop seizures occurred in nearly 70% (23 out of 33) patients with complete elimination in 58% (19 out of 33). Compared with anterior CC (n = 13), patients undergoing complete CC (n = 25) had increased likelihood of ≥50% reduction (p = 0.006) or elimination (p = 0.024) of drop seizures. Regression analysis showed that complete CC was the primary predictor for improved drop seizure outcomes (elimination, p = 0.014 or ≥50% reduction, p = 0.006), while age at CC and duration of epilepsy did not impact the outcomes. Compared to anterior CC, complete CC was significantly more likely to lead to improvement/freedom from drop seizures. Age at CC or duration of epilepsy did not influence drop seizure outcomes.

Long-acting reversible contraception in gender-diverse adolescents and young adults: Outcomes from a multisite collaborative.

OBJECTIVES: This study aimed to describe the clinical experience of gender-diverse adolescents and young adults receiving long-acting reversible contraception (LARC). STUDY DESIGN: This was a secondary analysis of prospectively collected quality improvement data among gender-diverse adolescents and young adults receiving LARC in four adolescent medicine clinics. RESULTS: Most attempted insertions (59/63) were successful. A majority (54%) chose LARC for both contraception and menstrual management. Pelvic pain/cramping and unsatisfactory bleeding were reported side effects. One known expulsion and six known LARC removals occurred. CONCLUSIONS: Gender-diverse adolescents and young adults had high rates of successful LARC insertion and demonstrated a side effect profile similar to a broader adolescent and young adult population seeking LARC care. IMPLICATIONS: LARC is an important and well-tolerated method of menstrual management and contracention in gender-diverse adolescents and young adults, although more investigation is needed to understand how gender-affirming testosterone therapy may impact the LARC experience in this population.

Comparing COVID-19-related Morbidity and Mortality Between Patients With and Without Substance Use Disorders: A Retrospective Cohort Study.

Objectives: People with substance use disorders (SUD) are suggested to have higher risk of hospitalization, intubation, or death from coronavirus disease 2019 (COVID-19), although data are mixed. Little is known about other COVID-19-related complications in this group. We compared morbidity and mortality among individuals with and without SUD who were admitted to an urban safety net hospital with COVID-19 early in the pandemic, contemporaneous to other published studies on this subject. Methods: We performed a retrospective study of patients ⩾18 years old admitted with COVID-19 from March 16th to April 8th, 2020. SUD included alcohol, opioid, cocaine, amphetamine, and benzodiazepine use disorders and was identified using diagnostic codes, free text clinical documentation, and urine drug screens. The primary outcome was inpatient mortality. Secondary outcomes included clinical complications (eg, secondary infections, venous thromboembolism) and resource utilization (eg, mechanical ventilation, length of stay). We used multivariable regression to assess the relationship between SUD and mortality. Results: Of 409 patients, the mean age was 56 years and 13.7% had SUD. Those with SUD were more likely to be male, have experienced homelessness, have pulmonary disease or hepatitis C, or use tobacco or cannabis. After multivariable analysis, SUD was not associated with mortality (aOR 1.03; 95% CI, 0.31-3.10). Secondary outcomes were also similar between groups. Conclusions: Our findings suggest that persons with and without SUD have similar COVID-19-related outcomes. Previously reported increased COVID-19 complications may be from medical comorbidities.

Mimics of Pediatric Small Vessel Primary Angiitis of the Central Nervous System.

OBJECTIVE: Small vessel primary angiitis of the central nervous system is a rare and often severe disease characterized by central nervous system-restricted inflammatory vasculitis on histopathology. Diagnosis requires brain biopsy for confirmation and is suggested prior to starting immunotherapy when feasible. However, emerging evidence suggests that other neuroinflammatory conditions may have a clinical and radiographic phenotype that mimics small vessel primary angiitis, at times with overlapping pathologic features as well. Such diagnoses, including myelin oligodendrocyte glycoprotein antibody-associated disease and central nervous system-restricted hemophagocytic lymphohistiocytosis, can be non-invasively diagnosed with serum antibody or genetic testing that would prompt different monitoring and treatment paradigms. To determine the ultimate diagnosis of patients who were suspected prior to biopsy to have small vessel primary angiitis, we reviewed the clinical, radiographic, and pathological features of a cohort of patients at a single center undergoing brain biopsy for non-oncologic indications. METHODS: Clinical data were retrospectively extracted from the medical record. Pathology and neuroimaging review was conducted. RESULTS: We identified 21 patients over a 19-year time-period, of whom 14 (66.7%) were ultimately diagnosed with entities other than small vessel primary angiitis that would have obviated the need for brain biopsy. Diagnoses included anti-myelin oligodendrocyte glycoprotein antibody associated disease (n = 9), central nervous system-restricted hemophagocytic lymphohistiocytosis (n = 3), anti-GABAA receptor encephalitis (n = 1), and Aicardi-Goutières syndrome (n = 1). INTERPRETATION: This study highlights the importance of pursuing now readily available non-invasive testing for mimicking diagnoses before performing a brain biopsy for suspected small vessel primary angiitis of the central nervous system. ANN NEUROL 2023;93:109-119.

Real-world feasibility of short-term, unsupervised home spirometry in CF.

OBJECTIVES: The objective of this study was to study the performance of two available home spirometers used by people with Cystic Fibrosis (PwCF) over a short-term period and to assess user experience. STUDY DESIGN: This was a prospective observational study. Participants age 6 years and older were recruited to participate if they could complete acceptable spirometry in the clinic setting. METHODS: Participants used either the NuvoAir Air Next or the ZEPHYRx MIR Spirobank Smart spirometer. They underwent a one-time virtual training session, then completed 2 weeks of daily spirometry followed by 2 months of weekly spirometry. Participants responded to surveys and completed a debrief interview to understand user experience. Statistical analyses examined feasibility, reliability, and accuracy of each spirometer in an unsupervised, real-world setting. RESULTS: We report high adherence (80% [95% CI 61%-92%]) to our study protocol in all session attempts, but lower rates of adherence after discarding sessions performed with inadequate technique (47% [95% CI 28%-66%] to 63% [95% CI 44%-80%]). We found high reliability of each device by analyzing day-to-day variability and good concordance to recent in-clinic testing (NuvoAir r = 0.91 [0.82-0.93]; ZEPHYRx r = 0.70 [0.45-0.84]). Patient experience in this cohort was favorable with most reporting ease of use and reassurance knowing lung function was being tracked over time. CONCLUSIONS: This real-world study showed good performance of two different available home spirometers used by children and adults with CF. While overall adherence was high, suboptimal technique reduced the total interpretable data, possibly limiting feasibility. Future work should focus on developing sustainable training and coaching programs to support the success of home spirometry in a CF chronic care model.

A yeast-based system to study SARS-CoV-2 Mpro structure and to identify nirmatrelvir resistant mutations

The SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as a proxy for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays showed that an E166R substitution conferred strong nirmatrelvir resistance while an E166N mutation compromised activity. On the other hand, N142A and P132H mutations caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used.

Breastfeeding knowledge, attitudes and training amongst Australian community pharmacists.

INTRODUCTION: Pharmacists are one of the most accessible and trusted professionals in the Australian health care system and can have a large impact in supporting and encouraging breastfeeding. AIM: This study aimed to research the knowledge, attitudes and training satisfaction of Australian pharmacists in the area of infant nutrition and breastfeeding. DESIGN, SETTING AND PARTICIPANTS: The mixed method study involved quantitative data collection via an online survey and qualitative data collected via separate semi-structured interviews. All registered pharmacists in the Australian Capital Territory and surrounding regional areas were eligible. Participants were recruited via emailed information sheets and individual onsite recruitment. KEY FINDINGS: Positive attitudes towards and a desire to support and advocate for breastfeeding by pharmacists were hampered by a lack of knowledge, confidence, training and education. CONCLUSIONS AND FUTURE IMPLICATIONS: Government or other non-profit organisations can enhance community-based support for breastfeeding, including developing new education and training programs for pharmacy students and pharmacists.