Long-term persistence to OnabotulinumtoxinA to prevent chronic migraine: Results from 11 years of patient data from a tertiary headache center.

OBJECTIVE: To determine if patients with chronic migraine continue onabotulinumtoxinA (onabotA) long-term. METHODS: We performed a retrospective cohort analysis using aggregated, de-identified patient data from the Stanford Headache Center. We included patients in California who received at least one prescription for onabotA during the years of 2011-2021. The primary outcome was the number of onabotA treatments each patient received. Secondary outcomes included sex, age, race, ethnicity, body mass index (BMI), distance to the treatment facility, and zip code income quartile. RESULTS: A total of 1,551 patients received a mean of 7.60 ± 7.26 treatments and a median of 5 treatments, with 16.2% of patients receiving only one treatment and 10.6% receiving at least 19. Time-to-event survival analysis suggested 26.0% of patients would complete at least 29 treatments if able. Younger age and female sex were associated with statistically significant differences between quartile groups of number of onabotA treatments (p = 0.007, p = 0.015). BMI, distance to treatment facility, and zip code income quartile were not statistically significantly different between quartile groups (p > 0.500 for all). Prescriptions of both triptans and non-onabotA preventive medications showed a statistically significant increase with each higher quartile of number of onabotA treatments (p < 0.001; p < 0.001). DISCUSSION: We show long-term persistence to onabotA is high and that distance to treatment facility and income are not factors in continuation. Our work also demonstrates that as patients continue onabotA over time, there may be an increased need for adjunctive or alternative treatments.

Stereo Camera Setup for 360° Digital Image Correlation to Reveal Smart Structures of Hakea Fruits.

About forty years after its first application, digital image correlation (DIC) has become an established method for measuring surface displacements and deformations of objects under stress. To date, DIC has been used in a variety of in vitro and in vivo studies to biomechanically characterise biological samples in order to reveal biomimetic principles. However, when surfaces of samples strongly deform or twist, they cannot be thoroughly traced. To overcome this challenge, different DIC setups have been developed to provide additional sensor perspectives and, thus, capture larger parts of an object's surface. Herein, we discuss current solutions for this multi-perspective DIC, and we present our own approach to a 360° DIC system based on a single stereo-camera setup. Using this setup, we are able to characterise the desiccation-driven opening mechanism of two woody Hakea fruits over their entire surfaces. Both the breaking mechanism and the actuation of the two valves in predominantly dead plant material are models for smart materials. Based on these results, an evaluation of the setup for 360° DIC regarding its use in deducing biomimetic principles is given. Furthermore, we propose a way to improve and apply the method for future measurements.

Preterm infants experience a nadir in cerebral oxygenation during sleep three months after hospital discharge.

AIM: Preterm infants are at increased risk of Sudden Infant Death Syndrome (SIDS) and frequently experience short central apnoeas which can occur in isolation or a repetitive pattern (periodic breathing). We investigated the relationship between central apnoeas experienced before and over the 6 months after hospital discharge and cerebral oxygenation. METHODS: Preterm infants born between 28 and 32 weeks gestational age (GA) were studied during supine daytime sleep at 32-36 weeks post menstrual age (PMA) (n = 40), 36-40 weeks PMA (n = 27), 3-months corrected age (CA) (n = 20) and 6-months CA (n = 26). Cerebral tissue oxygenation (TOI), peripheral oxygenation (SpO2 ) and heart rate were recorded continuously. The percentage total sleep time (%TST) spent having central apnoeas at each study and cerebral fractional oxygen extraction (SpO2 -TOI/SpO2 ) were calculated. RESULTS: %TST spent with central apnoeas decreased with increasing age in both active sleep (AS) and quiet sleep (QS). TOI tended to be lower and cerebral fractional oxygen extraction higher at 3 months compared to the other studies and this reached statistical significance compared to 32-36 weeks in QS. CONCLUSION: The nadir in cerebral tissue oxygenation at 3 months of age coincides with the peak risk period for SIDS and this may contribute to increased risk in these infants.

Alcohol Use Disorder in Patients with Chronic Migraine: A Retrospective, Observational Study.

OBJECTIVE: The relationship between migraine and alcohol consumption is unclear. We assessed the association between chronic migraine and alcohol use disorder(AUD), relative to chronic disease controls, and in conjunction with common comorbidities. METHODS: We conducted a retrospective, observational study. The primary outcome was the odds ratio for AUD in patients with chronic migraine or with chronic migraine and additional comorbidities relative to controls. RESULTS: A total of 3701 patients with chronic migraine, 4450 patients with low back pain, and 1780 patients with type 2 diabetes mellitus met inclusion criteria. Patients with chronic migraine had a lower risk of AUD relative to both controls of low back pain (OR 0.37; 95% CI: 0.29-0.47, p < 0.001) and type 2 diabetes mellitus (OR 0.39; 95% CI: 0.29-0.52, p < 0.001). Depression was associated with the largest OR for AUD in chronic migraine (OR 8.62; 95% CI: 4.99-14.88, p < 0.001), followed by post-traumatic stress disorder (OR 6.63; 95% CI: 4.13-10.64, p < 0.001) and anxiety (OR 3.58; 95% CI: 2.23-5.75, p < 0.001). CONCLUSION: Patients with chronic migraine had a lower odds ratio of AUD relative to controls. But in patients with chronic migraine, those with comorbid depression, anxiety, or PTSD are at higher risk of AUD. When patients establish care, comorbid factors should be assessed and for those at higher risk, AUD should be screened for at every visit.

Predicting the Risk of Developing Type 1 Diabetes Using a One-Week Continuous Glucose Monitoring Home Test With Classification Enhanced by Machine Learning: An Exploratory Study.

BACKGROUND: Detection of two or more autoantibodies (Ab) in the blood might describe those individuals at increased risk of developing type 1 diabetes (T1D) during the following years. The aim of this exploratory study is to propose a high versus low T1D risk classifier using machine learning technology based on continuous glucose monitoring (CGM) home data. METHODS: Forty-two healthy relatives of people with T1D with mean ± SD age of 23.8 ± 10.5 years, HbA1c (glycated hemoglobin) of 5.3% ± 0.3%, and BMI (body mass index) of 23.2 ± 5.2 kg/m2 with zero (low risk; N = 21), and ≥2 (high risk; N = 21) Ab, were enrolled in an NIH (National Institutes of Health)-funded TrialNet ancillary study. Participants wore a CGM for a week and consumed three standardized liquid mixed meals (SLMM) instead of three breakfasts. Glycemic features were extracted from two-hour post-SLMM CGM traces, compared across groups, and used in four supervised machine learning Ab risk status classifiers. Recursive Feature Elimination (RFE) algorithm was used for feature selection; classifiers were evaluated through 10-fold cross-validation, using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. RESULTS: The percent time of glucose >180 mg/dL (T180), glucose range, and glucose CV (coefficient of variation) were the only significant differences between the glycemic features in the two groups with P values of .040, .035, and .028 respectively. The linear SVM (Support Vector Machine) model with RFE features achieved the best performance of classifying low-risk versus high-risk individuals with AUC-ROC = 0.88. CONCLUSIONS: A machine learning technology, combining a potentially self-administered one-week CGM home test, has the potential to reliably assess the T1D risk.

The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis.

OBJECTIVE: To determine the effect of the introduction of the calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine. BACKGROUND: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market. METHODS: We performed a retrospective cohort analysis using the aggregated de-identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021. RESULTS: We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001). CONCLUSION: The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time.

The utility of ChatGPT in the assessment of literature on the prevention of migraine: an observational, qualitative study.

Background: It is not known how large language models, such as ChatGPT, can be applied toward the assessment of the efficacy of medications, including in the prevention of migraine, and how it might support those claims with existing medical evidence. Methods: We queried ChatGPT-3.5 on the efficacy of 47 medications for the prevention of migraine and then asked it to give citations in support of its assessment. ChatGPT's evaluations were then compared to their FDA approval status for this indication as well as the American Academy of Neurology 2012 evidence-based guidelines for the prevention of migraine. The citations ChatGPT generated for these evaluations were then assessed to see if they were real papers and if they were relevant to the query. Results: ChatGPT affirmed that the 14 medications that have either received FDA approval for prevention of migraine or AAN Grade A/B evidence were effective for migraine. Its assessments of the other 33 medications were unreliable including suggesting possible efficacy for four medications that have never been used for the prevention of migraine. Critically, only 33/115 (29%) of the papers ChatGPT cited were real, while 76/115 (66%) were "hallucinated" not real papers and 6/115 (5%) shared the names of real papers but had not real citations. Conclusion: While ChatGPT produced tailored answers on the efficacy of the queried medications, the results were unreliable and inaccurate because of the overwhelming volume of "hallucinated" articles it generated and cited.

Autonomic cardiovascular control is altered by intermittent hypoxia in preterm infants.

AIM: Preterm infants frequently experience short apnoeas and periodic breathing. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if apnoea and periodic breathing were associated with changes in autonomic control assessed using heart rate variability, thus exacerbating the consequences of respiratory disturbance. METHODS: Forty very preterm infants (15 M/25 F) were studied at 34.3 weeks post-menstrual age with daytime polysomnography. Total power, low frequency (LF, sympathetic+parasympathetic activity) high frequency (HF, parasympathetic activity) and LF/HF (sympathovagal balance) were calculated. RESULTS: Infants were divided into those with above and below the median total sleep time spent with respiratory events: Active sleep (AS) 13%, Quiet sleep (QS) 10%. In AS, including respiratory events, Total power (p < 0.05) and HF power (p < 0.05) were higher in the above median group. During AS excluding respiratory events, Total power (p < 0.05) and HF power (p = 0.061) were higher and LF power (p < 0.01) and LF/HF (p < 0.05) were lower in the above median group. There were no differences in HRV parameters in QS. CONCLUSION: This study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

The Role of Step Therapy in the Treatment of Migraine.

PURPOSE OF REVIEW: This review examines recent evidence and applies bioethical principles to evaluate the benefits and risks of using step therapy in the treatment of migraine. RECENT FINDINGS: With the CGRP mAbs, gepants, and lasmiditan now on the market for up to 5 years, new research, including network meta-analyses and long-term use studies, can evaluate the comparative efficacy, tolerability, and adherence of these medications relative to older acute and preventive medications for the treatment of migraine. Deciding how medications are chosen for patients requires accounting for many factors including sustainability, efficacy, tolerability, and preference. Newer research can help give clarity on the appropriateness of gating certain treatment options behind others.

Developmental consequences of short apneas and periodic breathing in preterm infants.

OBJECTIVE: We investigated the relationship between respiratory events experienced before and after hospital discharge and developmental outcomes at 6 months corrected age (CA). STUDY DESIGN: Preterm infants born between 28-32 weeks gestational age (GA) were studied at 32-36 weeks postmenstrual age (PMA), 36-40 weeks PMA, 3- and 6-months CA. Percentage total sleep time (%TST) with respiratory events (isolated apneas, sequential apneas and periodic breathing (PB)) at each study was calculated. Stepwise multiple linear regressions determined significant predictors of developmental outcomes at 6 months. RESULT: %TST with respiratory events at term were significant predictors of language (R2 = 0.165, ß = -0.416) and motor (R2 = 0.180, ß = -0.485) composite scores of the Bayley Scales of Infant Development at 6 months, independent of GA, birth weight and sex. CONCLUSIONS: In clinically stable very preterm infants at term equivalent age, time spent having respiratory events, was related to a reduction in language and motor outcomes at 6 months.

Predicting Immunological Risk for Stage 1 and Stage 2 Diabetes Using a 1-Week CGM Home Test, Nocturnal Glucose Increments, and Standardized Liquid Mixed Meal Breakfasts, with Classification Enhanced by Machine Learning.

Background: Predicting the risk for type 1 diabetes (T1D) is a significant challenge. We use a 1-week continuous glucose monitoring (CGM) home test to characterize differences in glycemia in at-risk healthy individuals based on autoantibody presence and develop a machine-learning technology for CGM-based islet autoantibody classification. Methods: Sixty healthy relatives of people with T1D with mean ± standard deviation age of 23.7 ± 10.7 years, HbA1c of 5.3% ± 0.3%, and body mass index of 23.8 ± 5.6 kg/m2 with zero (n = 21), one (n = 18), and ≥2 (n = 21) autoantibodies were enrolled in an National Institutes of Health TrialNet ancillary study. Participants wore a CGM for a week and consumed three standardized liquid mixed meals (SLMM) instead of three breakfasts. Glycemic outcomes were computed from weekly, overnight (12:00-06:00), and post-SLMM CGM traces, compared across groups, and used in four supervised machine-learning autoantibody status classifiers. Classifiers were evaluated through 10-fold cross-validation using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. Results: Among all computed glycemia metrics, only three were different across the autoantibodies groups: percent time >180 mg/dL (T180) weekly (P = 0.04), overnight CGM incremental AUC (P = 0.005), and T180 for 75 min post-SLMM CGM traces (P = 0.004). Once overnight and post-SLMM features are incorporated in machine-learning classifiers, a linear support vector machine model achieved the best performance of classifying autoantibody positive versus autoantibody negative participants with AUC-ROC ≥0.81. Conclusion: A new technology combining machine learning with a potentially self-administered 1-week CGM home test can help improve T1D risk detection without the need to visit a hospital or use a medical laboratory. Trial registration: ClinicalTrials.gov registration no. NCT02663661.

The impact of COVID-19 on alcohol sales and consumption in the United States: A retrospective, observational analysis.

Understanding the COVID-19 pandemic's effect on alcohol sales and consumption is critical in mitigating alcohol abuse and morbidity. We sought to determine how the onset of the COVID-19 pandemic and changes in viral incidence affected alcohol sales and consumption in the United States. We conducted a retrospective observational analysis regressing National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcohol sales data and Behavioral Risk Factor Surveillance System (BRFSS) survey data for 14 states for 2017 to 2020 with COVID-19 incidence in 2020 in the United States. The onset of the pandemic was associated with higher monthly alcohol sales per capita of 1.99 standard drinks (95% Confidence Interval: 0.63 to 3.34, p = 0.007). Increases of one COVID-19 case per 100 were associated with lower monthly alcohol sales per capita of 2.98 standard drinks (95% CI: -4.47 to -1.48, p = 0.001) as well as broad decreases in alcohol consumption, notably 0.17 fewer days per month with alcohol use (95% CI: -0.31 to -0.23, p = 0.008) and 0.14 fewer days per month of binge drinking (95% CI: -0.23 to -0.052, p < 0.001). The COVID-19 pandemic is associated with increased monthly average alcohol purchases, but higher viral incidence is linked to lower alcohol purchases and consumption. Continued monitoring is needed to mitigate the effects of higher population alcohol use during the pandemic.

[Shigellosis attended in the emergency department of a regional hospital in southeastern Spain: from their presence to multiresistance]. / Shigelosis atendidas en el servicio de urgencias de un hospital regional del sudeste de España: Desde su presencia a la multirresistencia.

OBJECTIVE: In the bacterial etiology of severe acute infectious diarrhea, except that caused by Clostridioides difficile, most of them have an invasive character and antibiotic treatment will be necessary in specific situations. Shigella is a classic pathogen, in which it is crucial to know the sensitivity to different classic and alternative antimicrobials. The objective of this work was to analyze the presence of shigellosis and the rate of antibiotic resistance. METHODS: A descriptive-retrospective study of the reports of shigellosis of stool cultures issued between January 2016 and April 2022 was conducted. RESULTS: A total of 34 episodes (16 -47.1%- by Shigella sonnei) were observed, as of 2018. There were only 2 pediatric cases. The overall resistance rate to azithromycin, trimethoprim-sulfamethoxazole and ciprofloxacin was 52.9%, 64.7% and 44.1%, respectively. 26.5% were resistant to the 3 groups of antibiotics. There was a higher rate of resistance for S. sonnei. The emergence of resistance to cephalosporins in recent years stands out. Episodes of multidrug-resistant shigellosis were detected between 2020 (1 by S. flexneri) and 2022 (4 by S. sonnei). CONCLUSIONS: The episodes of shigellosis are emerging in our environment with a higher rate of multi-resistance. In this context, current empirical treatments for acute enteroinvasive enteritis are at risk of failure, if necessary.

Content Validation of the Movement Disorder-Childhood Rating Scale (MD-CRS) for Dyskinetic Cerebral Palsy.

BACKGROUND: Dyskinetic cerebral palsy (DCP), a lifelong neurological disorder beginning in early childhood, manifests with hyperkinetic movements and dystonia. The Movement Disorder-Childhood Rating Scale (MD-CRS) is a clinician-reported outcome measure assessing the intensity of movement disorders and their effect on daily life in pediatric patients. Content validity of clinical outcome assessments is key to accurately capturing patient perspective. Evidence demonstrating content validity of the MD-CRS in patients with DCP is needed. This study captures input from patients with DCP and their caregivers regarding the content validity of the MD-CRS. METHODS: This qualitative, noninterventional, cross-sectional study included interviews with children/adolescents (aged six to 18 years) with DCP and caregivers of children with DCP. Participants were asked to describe body regions and daily functions affected by DCP. Caregivers also reviewed MD-CRS Part I to evaluate the relevance of the items and corresponding response options. Descriptions of DCP were coded and mapped to MD-CRS items and response options. Caregiver feedback on MD-CRS Part I was analyzed using inductive content analysis. RESULTS: Eight patients and 12 caregivers were interviewed. Participants confirmed that the body regions and activities listed in the MD-CRS were affected by DCP and that involuntary movements interfered with all motor, oral/verbal, self-care, and video protocol activities. Caregivers endorsed the response options for 12 of 15 items in MD-CRS Part I and suggested clarifications for others. CONCLUSIONS: Participants confirmed that affected body regions and activities listed in the MD-CRS were relevant to their experience with DCP, demonstrating the content validity of this tool in children/adolescents with DCP.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.