Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

Subgroup Analyses by European Country-Specific Reimbursement Requirements Confirm Efficacy for Ixekizumab in Psoriasis.

BACKGROUND: Biologic drugs are generally recommended for treating moderate-to-severe psoriasis. While eligibility criteria are primarily defined by clinical treatment guidelines, access to these therapies varies between European countries and is regulated by country-specific reimbursement criteria. This post-hoc subgroup analysis of integrated data from two phase III trials (UNCOVER-2 and -3) reports the efficacy of ixekizumab relative to that of etanercept in patients with moderate-to-severe plaque psoriasis selected into groups defined by original reimbursement criteria from eight European countries. METHODS: This analysis included baseline and 12-week data from the ixekizumab- and etanercept-treated study populations from UNCOVER-2 and -3. Patients were classified as meeting/not meeting each country-specific biologic eligibility criterion. Efficacy was defined by Psoriasis Area and Severity Index (PASI) 75, 90, and 100 response rates and by Dermatology Life Quality Index (DLQI) (0,1) response rates. Treatment responses across subgroups were analysed using logistic regression models. RESULTS: PASI 75/90/100 response rates were significantly higher for ixekizumab-treated patients than for etanercept-treated patients at week 12 (P<0.05), irrespective of whether predefined reimbursement criteria were met, for all countries, with the exception of PASI 100 response in those meeting reimbursement criteria in Belgium, where sample size was very small. Clinical efficacy outcomes were corroborated by proportions of patients achieving DLQI (0,1) responses. CONCLUSIONS: The overall high efficacy of ixekizumab, and the consistency of the higher treatment effect compared with etanercept, in patients with moderate-to-severe psoriasis across a range of European biologic treatment reimbursement eligibility criteria provides new insights to inform treatment decisions in clinical practice. J Drugs Dermatol. 2022;21(6):659-667. doi:10.36849/JDD.6620.

Ivabradine: pre-clinical and clinical evidence in the setting of ventricular arrhythmias.

BACKGROUND: Ivabradine, an agent lowering the heart rate, acting as a funny current (If) specific inhibitor, is responsible for the sinoatrial node's spontaneous depolarization. According to current guidelines, it is indicated in specific heart failure populations and as a second-line treatment option to improve angina in chronic coronary syndromes. REVIEW OF LITERATURE: The role of ivabradine in the setting of ventricular arrhythmias has been studied in both experimental and clinical studies. Specifically, experimental studies have examined the role of ivabradine in acute myocardial ischemia, reperfusion, digitalis-induced ventricular arrhythmias, and catecholaminergic polymorphic ventricular tachycardia showing promising results. In addition, clinical studies have shown a beneficial role of ivabradine in reducing ventricular arrhythmias. Ivabradine reduced premature ventricular contractions in combination with beta-blockers in dilated cardiomyopathy patients. Similarly, in catecholaminergic polymorphic ventricular tachycardia, ivabradine reduced dobutamine-induced premature ventricular complexes and improved ventricular arrhythmias burden. On the other hand, current data show no beneficial role of ivabradine in reducing ventricular arrhythmias in myocardial ischemia. CONCLUSIONS: Randomized clinical trials are needed to elucidate the role of ivabradine in reducing the burden of ventricular arrhythmias in various clinical settings. HIPPOKRATIA 2022, 26 (2):49-54.

The social and emotional wellbeing of Indigenous LGBTQA+ young people: a global perspective.

There has been scant exploration of the social and emotional wellbeing (SEWB) of young Indigenous populations that identify as LGBTQA+ (Lesbian, Gay, Bisexual, Transgender, Queer/Questioning, Asexual +). Given the vulnerability of this cohort living in Western settler colonial societies, wider investigation is called for to respond to their needs, experiences and aspirations. This paper summarizes existing research on the topic highlighting the lack of scholarship on the intersection of youth, Indigeneity, LGBTQA+ and SEWB. The paper takes a holistic approach to provide a global perspective that draws on an emerging body of literature and research driven by Indigenous scholars in settler colonial societies. The paper points to the importance of understanding converging colonial influences and ongoing contemporary elements, such as racism and marginalization that impact on young Indigenous LGBTQA+ wellbeing.

Federal, state, and institutional barriers to the expansion of medication and telemedicine abortion services in Ohio, Kentucky, and West Virginia during the COVID-19 pandemic.

OBJECTIVES: We aimed to characterize the combined impact of federal, state, and institutional policies on barriers to expanding medication and telemedicine abortion care delivery during the COVID-19 pandemic in the abortion-restrictive states of Ohio, Kentucky, and West Virginia. STUDY DESIGN: We analyzed 4 state policies, 2 COVID-related state executive orders, and clinic-level survey data on medication abortion provision from fourteen abortion facilities in Ohio, Kentucky, and West Virginia from December 2019 to December 2020. We calculated the percent of medication abortions provided at these facilities during the study period by state, to assess changes in medication abortion use during the pandemic. RESULTS: We ascertained that COVID-19-executive orders in Ohio and West Virginia that limited procedural abortion in Spring 2020 coincided with an increase in the overall number and proportion of medication abortions in this region, peaking at 1613 medication abortions (70%) in April 2020. Ohio and West Virginia, which had executive orders limiting procedural abortion, saw relatively greater increases in April compared to Kentucky. Despite temporary lifting of the mifepristone REMS, prepandemic regulations banning telemedicine abortion in Kentucky and West Virginia and requiring in-person clinic visits for medication abortion distribution in Ohio limited clinics' ability to adapt to offer medication abortion by mail. CONCLUSIONS: Our findings illustrate how restrictive medication and telemedicine abortion policies in Ohio, Kentucky, and West Virginia created additional obstacles for patients seeking medication abortion during the pandemic. Permanently lifting federal regulations on in-clinic distribution of mifepristone would only advantage abortion seekers in states without restrictive telehealth and medication abortion policies. State policies that limit access to comprehensive abortion services should be central in larger efforts toward dismantling barriers that impinge upon reproductive autonomy. IMPLICATION STATEMENT: We find that abolishing the REMS on mifepristone would not be enough to expand access to patients in abortion-restrictive states with telemedicine and medication abortion laws. While the REMS is a barrier, it represents one of several hindrances to the expansion of telemedicine abortion distribution across the United States.

Unusual Near-Horizon Cosmic-Ray-like Events Observed by ANITA-IV.

ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.

A Phase 2a Randomized, Double-Blind, Dose-Optimizing Study to Evaluate the Immunogenicity and Safety of a Bivalent DNA Vaccine for Hemorrhagic Fever with Renal Syndrome Delivered by Intramuscular Electroporation.

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic hantaviruses found in Asia and Europe, respectively. DNA vaccines targeting the envelope glycoproteins of these viruses have been constructed and found to elicit neutralizing antibodies when delivered to humans by various technologies including intramuscular electroporation. Here, we report findings from a Phase 2a clinical trial of a combined HTNV/PUUV DNA vaccine delivered at varying doses and administration schedules using the Ichor Medical Systems TriGrid intramuscular electroporation delivery technology. The study was designed to characterize the effects of DNA vaccine dose and number of administrations on the frequency and magnitude of immunological response. Subjects (n = 120) were divided into four cohorts. Cohorts 1 and 2 received a dose of 2 mg of DNA (1 mg per plasmid), and cohorts 3 and 4 received a dose of 1 mg of DNA (0.5 mg per plasmid) each vaccination. Each of the four cohorts received a series of four administrations (days 0, 28, 56 and 168). For cohorts 1 and 3, the DNA vaccine candidate was delivered at each of the four administrations. For cohorts 2 and 4, in order to maintain blinding, subjects received the DNA vaccine on days 0, 56 and 168, but on day 28 received only the phosphate buffered saline vehicle rather the DNA vaccine. Sera were collected on days 0, 28, 56, 84, 140, 168, 196, 252 and 365 and evaluated for the presence of neutralizing antibodies by PUUV and HTNV pseudovirion neutralization assays (PsVNAs). Day 84 was also evaluated by a plaque reduction neutralization test (PRNT). Overall the PsVNA50 geometric mean titers (GMTs) and seropositivity rates among cohorts were similar. Cohort 3 exhibited the highest frequency of subjects that became seropositive to both PUUV and HTNV after vaccination, the highest peak GMT against both viruses, and the highest median titers against both viruses.

Abortion Access in Ohio's Changing Legislative Context, 2010-2018.

Objectives. To examine abortion utilization in Ohio from 2010 to 2018, a period when more than 15 abortion-related laws became effective.Methods. We evaluated changes in abortion rates and ratios examining gestation, geographic distribution, and abortion method in Ohio from 2010 to 2018. We used data from Ohio's Office of Vital Statistics, the Centers for Disease Control and Prevention's Abortion Surveillance Reports, the American Community Survey, and Ohio's Public Health Data Warehouse.Results. During 2010 through 2018, abortion rates declined similarly in Ohio, the Midwest, and the United States. In Ohio, the proportion of early first trimester abortions decreased; the proportion of abortions increased in nearly every later gestation category. Abortion ratios decreased sharply in most rural counties. When clinics closed, abortion ratios dropped in nearby counties.Conclusions. More Ohioans had abortions later in the first trimester, compared with national patterns, suggesting delays to care. Steeper decreases in abortion ratios in rural versus urban counties suggest geographic inequity in abortion access.Public Health Implications. Policies restricting abortion access in Ohio co-occur with delays to care and increasing geographic inequities. Restrictive policies do not improve reproductive health.

The Perirolandic Sign: A Unique Imaging Finding Observed in Association with Polymerase γ-Related Disorders.

Pathogenic variants in the polymerase γ gene (POLG) cause a diverse group of pathologies known as POLG-related disorders. In this report, we describe brain MR imaging findings and electroencephalogram correlates of 13 children with POLG-related disorders at diagnosis and follow-up. At diagnosis, all patients had seizures and 12 had abnormal MR imaging findings. The most common imaging findings were unilateral or bilateral perirolandic (54%) and unilateral or bilateral thalamic signal changes (77%). Association of epilepsia partialis continua with perirolandic and thalamic signal changes was present in 86% and 70% of the patients, respectively. The occipital lobe was affected in 2 patients. On follow-up, 92% of the patients had disease progression or fatal outcome. Rapid volume loss was seen in 77% of the patients. The occipital lobe (61%) and thalamus (61%) were the most affected brain regions. Perirolandic signal changes and seizures may represent a brain imaging biomarker of early-onset pediatric POLG-related disorders.

Neonatal Organ and Tissue Donation for Research: Options Following Death by Natural Causes.

The donation of organs and tissues from neonates (birth to 28 days) for transplantation has been a relatively infrequent occurrence. Less common has been the use of neonatal organs and tissues for research. Specific ethical and legal questions beg for rational and transparent guidelines with which to evaluate referrals of potential donors. Donation of organs and tissues from a neonate can play a key role in the care and support provided to families by health care professionals around the time of a neonate's death. We report on the recovery of neonatal organs and tissues for research. A working group made up of bioethicists, neonatologists, lawyers, obstetric practioners as well as organ procurement and tissue banking professionals evaluated legal, ethical and medical issues. Neonatal donor family members were also consulted. Our primary goals were (a) to ensure that referrals were made in compliance with all applicable federal and state laws, regulations and institutional protocols, and (b) to follow acceptable ethical standards. Algorithms and policies designed to assist in the evaluation of potential neonatal donors were developed. Neonatal donation is proving increasingly valuable for research into areas including diabetes, pulmonary, gastrointestinal, genitourinary and neurological development, rheumatoid arthritis, autism, childhood psychiatric and neurologic disorders, treatment of MRSA infection and pediatric emergency resuscitation. The development of policies and procedures will assist medical professionals who wish to offer the option of donation to family members anticipating the death of a neonate.

A prospective case series of sphenopalatine ganglion pulsed radiofrequency therapy for refractory chronic cluster headache.

BACKGROUND AND PURPOSE: The management options for chronic cluster headache (CCH) are limited and a significant proportion of patients become refractory to pharmacological treatments. Pulsed radiofrequency (PRF) of the sphenopalatine ganglion (SPG) may present an efficacious, minimally invasive treatment modality for patients with refractory CCH. We describe the clinical outcomes of 14 patients with refractory CCH treated with PRF of the SPG. METHODS: Patients with medically refractory CCH who underwent percutaneous SPG-PRF treatment between January 2016 and April 2019 were included in this report. Patients obtaining at least 30% reduction in weekly cluster attacks for at least 3 months were defined as responders. Treatment-related side effects were collected. RESULTS: A total of 14 patients were included in this report (nine males). At a median follow-up of 6.5 (range 6-13) months post-procedure, eight patients (57.1%) were defined as responders to the treatment. Six patients were non-responders and reported either a reduction in frequency and severity of attacks for <3 months (2/6), no improvement (2/6) or temporary worsening of symptoms (1/6). The majority of patients (63.6%, n = 7/11) treated with >45 V were responders compared with responders treated with 45 V (33.3%, n = 1/3). Five patients (35.7%) experienced post-procedural side effects. CONCLUSION: This case series suggests that PRF targeting the SPG might offer a safe, minimally invasive and effective treatment for medically refractory CCH. Given the small number of cases and the short follow-up, larger and more robust studies will be needed to confirm our findings.

Approach to cardiopulmonary resuscitation induced consciousness, an emergency medicine perspective.

BACKGROUND: Cardiopulmonary resuscitation (CPR) remains the key intervention following cardiac arrest because of its ability to continue circulation. Recent focus on high quality compressions during CPR has coincided with more frequent encounters of CPR Induced Consciousness (CPRIC). CPRIC represents a poorly understood patient experience during CPR and defined as signs of consciousness and pain perception during CPR. METHODS: Articles were selected using PubMed, MEDLINE, CINAHL and Scopus search for the keywords "cardiopulmonary resuscitation", "consciousness", "awareness", "resuscitation", "cardio-cerebral resuscitation", "agitation" and "patient experience" yielding 336 articles. Results and their references were assessed for relevance. Articles were filtered by English language and the keyword. Case reports and case series were included. All remaining articles were reviewed and findings were discussed. RESULTS: A total of ten articles were selected, which included data on 123 cases. Sample size varied per study from 1 to 112. Studies included cases of out-of-hospital cardiac arrest and in hospital cardiac arrest. Compressions were manually provided in most cases. Patient total recall was reported in 40% of cases. Use of sedation was reported in 40% of cases. CONCLUSIONS: There is need for continued research to better describe, explain and manage the phenomena of CPRIC. From the articles reviewed here, it is clear that further investigation has the potential to properly elucidate the patient experience including lasting psychological effects of CPRIC. Importantly, there is need for more than recognition of CPRIC from national authorities. Future research efforts should focus on establishing guidelines for the use of sedation and physical restraints, as well as the potential impact of treating CPRIC on survival.

Predicting Pharmacist Dispensing Practices and Comfort Related to Pre-exposure Prophylaxis for HIV Prevention (PrEP).

To identify factors associated with pharmacist dispensing practice and comfort counseling patients about pre-exposure prophylaxis for HIV prevention (PrEP). Cross-sectional 2016 census of Indiana managing pharmacists measured PrEP awareness, comfort dispensing and counseling patients. Modified Poisson models with robust error variance estimated relative risks and confidence intervals. 15.8% of 284 pharmacists had dispensed PrEP and 11.6% had consulted about it. Dispensing and comfort counseling were associated with confidence in knowledge about PrEP medication adherence and adverse effects of PrEP medication; awareness about PrEP before the survey, number of full time pharmacists in their pharmacy, and increases in new HIV cases from 2015 to 2016 in communities served. Comfort counseling about PrEP was associated with the belief that pharmacists can be an important resource for HIV and HCV treatment.

Observation of an Unusual Upward-Going Cosmic-Ray-like Event in the Third Flight of ANITA.

We report on an upward traveling, radio-detected cosmic-ray-like impulsive event with characteristics closely matching an extensive air shower. This event, observed in the third flight of the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload, is consistent with a similar event reported in a previous flight. These events could be produced by the atmospheric decay of an upward-propagating τ lepton produced by a ν_{τ} interaction, although their relatively steep arrival angles create tension with the standard model neutrino cross section. Each of the two events have a posteriori background estimates of ≲10^{-2} events. If these are generated by τ-lepton decay, then either the charged-current ν_{τ} cross section is suppressed at EeV energies, or the events arise at moments when the peak flux of a transient neutrino source was much larger than the typical expected cosmogenic background neutrinos.

Gadolinium DTPA Enhancement Characteristics of the Rat Sciatic Nerve after Crush Injury at 4.7T.

BACKGROUND AND PURPOSE: Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS: In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS: Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS: Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.