Rejected

The purpose of this study was to determine the association between asthma and migraine and assess the risk for migraine in patients with asthma. We systematically searched the Cochrane Library, PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), and Excerpta Medica dataBASE (EMBASE) databases from inception to September 26, 2021, for indexed observational studies that examined either the odds or risk of migraine in subjects with asthma. The qualities of the included studies were evaluated using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to calculate the odds ratio for case-control and cross-sectional studies and the risk ratio for cohort studies. Seven observational studies (four cross-sectional and three cohort studies) with a total of 549,534 study subjects were included in this systematic review and meta-analysis and selected for data extraction. Four articles were considered to be of moderate quality; other studies were considered to be of high quality. Asthma was associated with increased odds (OR, 1.85; 95%CI, 1.39-2.45) and risk of migraine (RR, 1.70; 95%CI, 1.52-1.90). The available evidence that supports the existence of an association between asthma and migraine is limited. Clinicians should be aware that patients with asthma show both increased prevalence and incidence of migraine. Further studies are warranted to further clarify the relationship between asthma and migraine. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185881, identifier: CRD42020185881.

Neonatal hypoxia-ischemia encephalopathy (HIE) is the leading cause of neonatal death and poor neurodevelopmental outcomes worldwide. Therapeutic hypothermia (TH), while beneficial, still leaves many HIE treated infants with lifelong disabilities. Furthermore, infants undergoing TH often require treatment for pain and agitation which may lead to further brain injury. For instance, morphine use in animal models has been shown to induce neuronal apoptosis. Dexmedetomidine is a potent α-adrenergic receptor agonist that may be a better alternative to morphine for newborns with HIE treated with TH. Dexmedetomidine provides sedation, analgesia, and prevents shivering but does not suppress ventilation. Importantly, there is increasing evidence that dexmedetomidine has neuroprotective properties. Even though there are limited data on pharmacokinetics (PK), safety and efficacy of dexmedetomidine in infants with HIE, it has been increasingly administered in many centers. To review the current approach to treatment of pain, sedation and shivering in infants with HIE undergoing TH, and to describe a new phase II safety and pharmacokinetics randomized controlled trial that proposes the use of dexmedetomidine vs. morphine in this population. This article presents an overview of the current management of pain and sedation in critically ill infants diagnosed with HIE and undergoing TH for 72 h. The article describes the design and methodology of a randomized, controlled, unmasked multicenter trial of dexmedetomidine vs. morphine administration enrolling 50 (25 per arm) neonates ≥36 weeks of gestation with moderate or severe HIE undergoing TH and that require pain/sedation treatment. Dexmedetomidine may be a better alternative to morphine for the treatment of pain and sedation in newborns with HIE treated with TH. There is increasing evidence that dexmedetomidine has neuroprotective properties in several preclinical studies of injury models including ischemia-reperfusion, inflammation, and traumatic brain injury as well as adult clinical trials of brain trauma. The Dexmedetomidine Use in Infants undergoing Cooling due to Neonatal Encephalopathy (DICE) trial will evaluate whether administration of dexmedetomidine vs. morphine is safe, establish dexmedetomidine optimal dosing by collecting opportunistic PK data, and obtain preliminary neurodevelopmental data to inform a large Phase III efficacy trial with long term neurodevelopment impairment as the primary outcome.

Acute pain in neurosurgical patients is an important issue. Opioids are the most used for pain treatment in the neurosurgical ICU. Potential side effects of opioid use such as oversedation, respiratory depression, hypercapnia, worsening intracranial pressure, nausea, and vomiting may be problems and could interfere with neurologic assessment. Consequently, reducing opioids and use of non-opioid analgesics and adjuvants (N-methyl-D-aspartate antagonists, α2 -adrenergic agonists, anticonvulsants, corticosteroids), as well as non-pharmacological therapies were introduced as a part of a multimodal regimen. Local and regional anesthesia is effective in opioid reduction during the early postoperative period. Among non-opioid agents, acetaminophen and non-steroidal anti-inflammatory drugs are used frequently. Adverse events associated with opioid use in neurosurgical patients are discussed. Larger controlled studies are needed to find optimal pain management tailored to neurologically impaired neurosurgical patients.

Children's complex middle cerebral artery (MCA) aneurysm is a relatively rare occurrence. When the huge aneurysm is located in the MCA bifurcation with an inconspicuous neck and involving numerous arteries, intravascular interventional surgery or aneurysm clipping are often difficult treatment options. At this point, high flow bypass revascularization is necessary as a treatment to preserve cerebral blood flow. In recent years, the internal maxillary artery (IMA) has gradually become the mainstream donor artery of thw high flow bypass. We performed internal maxillary artery -radial artery-middle cerebral artery (IMA-RA-MCA) and superficial temporal artery-middle cerebral artery (STA-MCA) bypass as the treatment of a complex MCA bifurcation aneurysm in consideration of the patient's condition and the advantage of the IMA. According to the author, this case is the youngest reported case of IMA-RA-MCA bypass at present.

Demonstrate that continuous peripheral nerve block (CPNB) may be an alternative with adequate analgesia and a lower incidence of side effects for ischemic pain due peripheral obstructive arterial disease (POAD).

Spinal cord injury is a major cause of lifelong morbidity and functional micturition problems. Some patients are refractory to the available therapeutics, even when used in combination. In this paper we report our results of using gabapentin as an add-on treatment in refractory overactive detrusor cases secondary to spinal cord injury.

An adjuvanted recombinant zoster vaccine (RZV) is licensed for the prevention of herpes zoster. This paper reviews its safety and reactogenicity. A pooled analysis of two pivotal randomized Phase-3 trials (NCT01165177, NCT01165229) in adults ⩾50 years found that more solicited adverse events (AEs) were reported with RZV than placebo. Injection site pain was the most common solicited AE (RZV: 78.0% participants; placebo: 10.9%). Grade-3 pain occurred in 6.4% of RZV and 0.3% of placebo recipients. Myalgia, fatigue, and headache were the most commonly reported general solicited AEs (RZV: 44.7%, 44.5%, and 37.7%, respectively; placebo: 11.7%, 16.5%, and 15.5%, respectively). Most symptoms were mild to moderate in intensity with a median duration of 2-3 days. The intensity of reactogenicity symptoms did not differ substantially after the first and second vaccine doses. The pooled analysis of the pivotal Phase-3 trials did not identify any clinically relevant differences in the overall incidence of serious adverse events (SAEs), fatal AEs or potential immune-mediated diseases (pIMDs) between RZV and placebo. Reactogenicity in five studies of immunocompromised patients ⩾18 years (autologous stem cell transplant, human immunodeficiency virus, solid tumors, hematological malignancies, and renal transplant; NCT01610414, NCT01165203, NCT01798056, NCT01767467, and NCT02058589) was consistent with that observed in the pivotal Phase-3 trials. There were no clinically relevant differences between RZV and placebo in the immunocompromised populations with regard to overall incidence of SAEs, fatal AEs, pIMDs, or AEs related to patients' underlying condition. Post-marketing surveillance found that the most commonly reported AEs were consistent with the reactogenicity profile of the vaccine in clinical trials. Overall, the clinical safety data for RZV are reassuring.

Spinal cord stimulation (SCS) utilizes the delivery of mild electrical pulses via epidural electrodes placed on the dorsal side of the spinal cord, typically to treat chronic pain. The first clinical use of SCS involved the delivery of paresthesia inducing, low-frequency waveforms to the neural targets corresponding to the painful areas. Contemporary SCS therapies now leverage novel therapeutic pathways to limit paresthesia and deliver superior clinical outcomes. Historically, SCS has largely been delivered with fixed stimulation parameters. This approach, referred to as open-loop (OL) SCS, does not account for the fluctuations in spacing-driven by postural changes and activity-between the electrodes and the cord. These fluctuations result in variability in the delivered dose and the volume of tissue activation (VTA) that manifests with each stimulation pulse. Inconsistent dosing may lead to suboptimal therapeutic efficacy and durability. To address this clinical need, closed-loop (CL) SCS systems have been developed to automatically adjust stimulation parameters to compensate for this variability. The evoked compound action potential (ECAP), a biopotential generated by the synchronous activation of dorsal column fibers, is indicative of the VTA resulting from the stimulation pulse. The ECAP may be utilized as a control signal in CL SCS systems to adjust stimulation parameters to reduce variability in the ECAP, and in turn, variability in the VTA. While investigational CL SCS systems with ECAP sensing have so far focused solely on managing paresthesia-based SCS, such systems must also incorporate the stimulation approaches that now define the contemporary clinical practice of SCS. Accordingly, we describe here a flexible, next-generation framework for neural responsive SCS that blends science-based methodologies for pain management with real-time CL control for biophysical variation. We conclude with a clinical example of such a system and the associated performance characteristics.

infection (CDI) is one of the leading causes of hospital-acquired infection attributing to substantial morbidity, mortality, and healthcare cost. Recurrent CDI (rCDI) is common and occurs after effective treatment of first episode. Treatment of rCDI is based on accurate diagnoses, due to difficulty in distinguishing between colonization of spores or CDI; coronavirus disease 2019 (COVID-19) added to the complexity of diagnoses as both entities can co-occur. It is difficult to eradicate rCDI, and there remains a critical gap regarding treatment of rCDI. The treatment goal of rCDI is to reestablish normal microbiota. Fecal microbiota transplantation (FMT) is suggested as a treatment for second episode of rCDI. Based on the collective evidence of all randomized controlled trials, FMT was reported more efficacious compared with vancomycin or fidaxomicin; however, these trials had limited number of patients and all patients were pre-treated with vancomycin prior to FMT. Furthermore, when comparing various routes of instillation and types of preparation of fecal microbiota, no difference was observed in cure rate. Despite the success rate of FMT, there remains a concern for transmission of infectious agents, such as Gram negative bacteremia or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adverse events (diarrhea and abdominal pain), and reports of new diagnoses (inflammatory bowel disease, weight gain and irritable bowel syndrome). To lessen the risk of transmissible infections, donor screening should be performed, which includes screening for medical comorbidities and infectious pathogens in blood and feces. Scheduling complexities and reimbursement places an additional roadblock for using FMT. Microbiome-based therapies are being developed to eliminate the logistical challenges related to FMT. Large prospective and placebo-controlled studies are needed to evaluate the efficacy and long-term safety of FMT, so its use can be justified in clinical practice.

The clinical presentation of pseudotumor cerebri syndrome (PTCS) usually includes headache, nausea, and vomiting with normal physical examination apart from papilledema and diplopia. However, pseudopapilledema, which can be caused by optic nerve drusen, may lead to misdiagnosis. The prevalence of optic nerve drusen in the general population is 0.5-2%. The purpose of our study was to evaluate the prevalence and risk factors of optic nerve drusen among patients with PTCS. Medical records of children evaluated in the pediatric department at Bnai Zion Medical Center due to PTCS between 2008 and 2020 were assessed. Inclusion criteria were children age under 18 years with a PTCS diagnosis and ophthalmic B-mode ultrasonography (US). Exclusion criteria were secondary intracranial hypertension. Thirty-four children were included with a mean age 10.1 years which included 50% boys. A majority of the patients, 24 (72.4%), complained of headaches, while 15 (45.5%) complained of transient visual obscuration, and 9 (26.5%) of vomiting. Visual acuity on presentation was normal (20/20-20/30) in 23 of the children (67%), moderately diminished (20/40-20/80) in 9 (26%), and showing profound loss (20/200) in 2 (7%). Five patients (14.7%) were diagnosed with optic nerve drusen via B-mode ophthalmic ultrasonography (US). However, they still fulfilled the diagnostic criteria for PTCS, and disc swelling improved after treatment. There were no statistically significant differences between the group with optic nerve drusen and the rest of the patients. Optic nerve drusen are common among pediatric patients with PTCS. Diagnosis of optic nerve drusen should not rule out the presence of increased intracranial pressure.