Background
The pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We ...investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH).
Methods
A multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated.
Findings
Thirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks (p < 0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in ≥50% of treated attacks, 10 (36%), a ≥50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months.
Interpretation
On-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures.
Objectives
The sphenopalatine ganglion (SPG) plays a pivotal role in cluster headache (CH) pathophysiology as the major efferent parasympathetic relay. We evaluated the long-term effectiveness of SPG ...stimulation in medically refractory, chronic CH patients.
Methods
Thirty-three patients were enrolled in an open-label follow-up study of the original Pathway CH-1 study, and participated through 24 months post-insertion of a microstimulator. Response to therapy was defined as acute effectiveness in ≥ 50% of attacks or a ≥ 50% reduction in attack frequency versus baseline.
Results
In total, 5956 attacks (180.5 ± 344.8, range 2–1581 per patient) were evaluated. At 24 months, 45% (n = 15) of patients were acute responders. Among acute responders, a total of 4340 attacks had been treated, and in 78% of these, effective therapy was achieved using only SPG stimulation (relief from moderate or greater pain or freedom from mild pain or greater). A frequency response was observed in 33% (n = 11) of patients with a mean reduction of attack frequency of 83% versus baseline. In total, 61% (20/33) of all patients were either acute or frequency responders or both. The majority maintained their therapeutic response through the 24-month evaluation.
Conclusions
In the population of disabled, medically refractory chronic CH patients treated in this study, SPG stimulation is an effective acute therapy in 45% of patients, offering sustained effectiveness over 24 months of observation. In addition, a maintained, clinically relevant reduction of attack frequency was observed in a third of patients. These long-term data provide support for the use of SPG stimulation for disabled patients and should be considered after medical treatments fail, are not tolerated or are inconvenient for the patients.
Abstract
Background
Late sequelae of COVID-19 have been reported; however, few studies have investigated the time course or incidence of late new COVID-19–related health conditions (post-COVID ...conditions) after COVID-19 diagnosis. Studies distinguishing post-COVID conditions from late conditions caused by other etiologies are lacking. Using data from a large administrative all-payer database, we assessed type, association, and timing of post-COVID conditions following COVID-19 diagnosis.
Methods
Using the Premier Healthcare Database Special COVID-19 Release (release date, 20 October 2020) data, during March–June 2020, 27 589 inpatients and 46 857 outpatients diagnosed with COVID-19 (case-patients) were 1:1 matched with patients without COVID-19 through the 4-month follow-up period (control-patients) by using propensity score matching. In this matched-cohort study, adjusted ORs were calculated to assess for late conditions that were more common in case-patients than control-patients. Incidence proportion was calculated for conditions that were more common in case-patients than control-patients during 31–120 days following a COVID-19 encounter.
Results
During 31–120 days after an initial COVID-19 inpatient hospitalization, 7.0% of adults experienced ≥1 of 5 post-COVID conditions. Among adult outpatients with COVID-19, 7.7% experienced ≥1 of 10 post-COVID conditions. During 31–60 days after an initial outpatient encounter, adults with COVID-19 were 2.8 times as likely to experience acute pulmonary embolism as outpatient control-patients and also more likely to experience a range of conditions affecting multiple body systems (eg, nonspecific chest pain, fatigue, headache, and respiratory, nervous, circulatory, and gastrointestinal symptoms) than outpatient control-patients.
Conclusions
These findings add to the evidence of late health conditions possibly related to COVID-19 in adults following COVID-19 diagnosis and can inform healthcare practice and resource planning for follow-up COVID-19 care.
Bird nests represent an extended phenotype that is variable among and within species in terms of nest location and construction materials. It has also been suggested that nests indicate niche ...construction, although empirical evidence to support this is lacking. The nest wall is often considered to confer some insulation because this would help minimize the energetic expenditure by the incubating adult. However, it has been previously suggested that nests are constructed primarily for their structural role rather than for insulation, but to date, studies have used a variety of techniques to investigate the insulation of nest walls but only for relatively few species. This study used temperature loggers to determine insulatory values of nests for 16 previously undescribed species and to replicate values for eight previously described species. In addition, data for nest wall insulation that were determined using temperature loggers have been collated for a total of 32 different passerine species. The effects of nest dimensions, mass, and composition on these values were examined. Base thickness, but not wall thickness, and nest mass significantly positively affected insulatory values. This study found that the proportions of feathers and moss in the nest wall significantly positively correlated with insulatory values. This suggests that there is a key role for nest materials in determining insulation, which provides empirical evidence that nest building constitutes niche construction. The data will also help us interpret data from future studies of the thermal properties of nests. Ultimately, we need to develop our understanding of the role of insulatory values in the evolution of nest function.
This cohort study uses data from the Premier Healthcare Database Special COVID-19 Release to assess the association of demographic and clinical characteristics with severe COVID-19 illness among ...hospitalized US pediatric patients with COVID-19.
Introduction Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 ...illness. Methods We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. Results Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio aRR = 1.30; 95% CI, 1.27–1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25–1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24–1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41–1.67) for patients with 1 condition to 3.82 (95% CI, 3.45–4.23) for patients with more than 10 conditions (compared with patients with no conditions). Conclusion Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.
Factor VIII (FVIII) replacement products enable comprehensive care in hemophilia A. Treatment goals in severe hemophilia A are expanding beyond low annualized bleed rates to include long-term ...outcomes associated with high sustained FVIII levels. Endogenous von Willebrand factor (VWF) stabilizes and protects FVIII from degradation and clearance, but it also subjects FVIII to a half-life ceiling of ∼15 to 19 hours. Increasing recombinant FVIII (rFVIII) half-life further is ultimately dependent upon uncoupling rFVIII from endogenous VWF. We have developed a new class of FVIII replacement, rFVIIIFc-VWF-XTEN (BIVV001), that is physically decoupled from endogenous VWF and has enhanced pharmacokinetic properties compared with all previous FVIII products. BIVV001 was bioengineered as a unique fusion protein consisting of a VWF-DʹD3 domain fused to rFVIII via immunoglobulin-G1 Fc domains and 2 XTEN polypeptides (Amunix Pharmaceuticals, Inc, Mountain View, CA). Plasma FVIII half-life after BIVV001 administration in mice and monkeys was 25 to 31 hours and 33 to 34 hours, respectively, representing a three- to fourfold increase in FVIII half-life. Our results showed that multifaceted protein engineering, far beyond a few amino acid substitutions, could significantly improve rFVIII pharmacokinetic properties while maintaining hemostatic function. BIVV001 is the first rFVIII with the potential to significantly change the treatment paradigm for severe hemophilia A by providing optimal protection against all bleed types, with less frequent doses. The protein engineering methods described herein can also be applied to other complex proteins.
•BIVV001 is a novel fusion protein that provides fourfold longer hemostatic control than rFVIII in preclinical hemophilia A models.•BIVV001 has the potential to allow for more optimal, extended protection against all bleeding types in patients with severe hemophilia A.
Display omitted
To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic–ischemic encephalopathy (HIE) and to determine the association between acuity of placental ...abnormalities and clinical characteristics of HIE.
Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system.
Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (−15.9 vs −14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P < .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities.
Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.
ClinicalTrials.gov: NCT02811263
Objectives
To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship.
Methods
Key topics regarding head and neck cancer survivorship were ...identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence.
Results
Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho‐oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and described the role of key clinicians in survivorship including surgical, medical and radiation oncologists; dentists; primary care physicians; psychotherapists; as well as physical, occupational, speech, and respiratory therapists.
Conclusion
Head and neck cancer survivorship is complex and requires a multidisciplinary approach centered around patients and their caregivers. As survival related to head and neck cancer treatment improves, addressing post‐treatment concerns appropriately is critically important to our patient's quality of life. There continues to be a need to define effective and efficient programs that can coordinate this multidisciplinary effort toward survivorship.
PDF
