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Frequent Headaches: Evaluation and Management.

Most frequent headaches are typically migraine or tension-type headaches and are often exacerbated by medication overuse. Repeated headaches can induce central sensitization and transformation to chronic headaches that are intractable, are difficult to treat, and cause significant morbidity and costs. A complete history is essential to identify the most likely headache type, indications of serious secondary headaches, and significant comorbidities. A headache diary can document headache frequency, symptoms, initiating and exacerbating conditions, and treatment response over time. Neurologic assessment and physical examination focused on the head and neck are indicated in all patients. Although rare, serious underlying conditions must be excluded by the patient history, screening tools such as SNNOOP10, neurologic and physical examinations, and targeted imaging and other assessments. Medication overuse headache should be suspected in patients with frequent headaches. Medication history should include nonprescription analgesics and substances, including opiates, that may be obtained from others. Patients who overuse opiates, barbiturates, or benzodiazepines require slow tapering and possibly inpatient treatment to prevent acute withdrawal. Patients who overuse other agents can usually withdraw more quickly. Evidence is mixed on the role of medications such as topiramate for patients with medication overuse headache. For the underlying headache, an individualized evidence-based management plan incorporating pharmacologic and nonpharmacologic strategies is necessary. Patients with frequent migraine, tension-type, and cluster headaches should be offered prophylactic therapy. A complete management plan includes addressing risk factors, headache triggers, and common comorbid conditions such as depression, anxiety, substance abuse, and chronic musculoskeletal pain syndromes that can impair treatment effectiveness. Regular scheduled follow-up is important to monitor progress.

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Antisecretory Factor May Reduce ICP in Severe TBI-A Case Series.

Traumatic brain injury (TBI) constitutes a global epidemic. Overall outcome is poor, with mortality ranging from 10 to 70% and significant long-term morbidity. Several experimental reports have claimed effect on traumatic edema, but all clinical trials have failed. Antisecretory factor, an endogenous protein, is commercially available as Salovum®, which is classified as a medical food by the European Union and has been proven effective in experimental trauma models. It has, however, previously not been tested in humans with severe TBI. We hereby report a case series of five adult patients with severe TBI, treated with Salovum. The objective of the intervention was to evaluate safety and, if possible, its effect on intracranial pressure and outcome. Patients received 1 g Salovum per kilo of body weight divided into six doses per 24 h. Each dose was administered through the nasogastric tube. Patients were scheduled for 5 days of treatment with Salovum. Intracranial pressure was controlled in all patients. In three of five patients, intracranial pressure could be controlled with Salovum and deep sedation (no barbiturates), except during periods of gastroparesis. Five of five patients had a favorable short-term outcome, and four of five patients had a favorable long-term outcome. No toxicity was observed. We conclude that at least three of the five treated patients experienced an effect of Salovum with signs of reduction of intracranial pressure and signs of clinical benefit. In order to validate the potential of antisecretory factor in TBI, a prospective, randomized, double-blind, placebo-controlled trial with Salovum has been initiated. Primary outcome for the trial is 30-day mortality; secondary outcomes are treatment intensity level, intracranial pressure, and number of days at the neurointensive care unit.

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Incidence and Lethality of Suicidal Overdoses by Drug Class.

Prior lethality analyses of suicide means have historically treated drug poisoning other than alcohol poisoning as a lumped category. Assessing risk by drug class permits better assessment of prevention opportunities.

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Optimizing the Biodistribution of Radiofluorinated Barbiturate Tracers for Matrix Metalloproteinase Imaging by Introduction of Fluorescent Dyes as Pharmacokinetic Modulators.

Dysregulated expression or activation of matrix metalloproteinases (MMPs) is observed in many kinds of life-threatening diseases. Therefore, MMP imaging-for example, with radiolabeled MMP inhibitors (MMPIs)-potentially represents a valuable tool for clinical diagnostics using noninvasive single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Despite numerous preclinical imaging approaches, translation to a clinical setting has not yet been successful. We introduce and oppose three potential radiofluorinated MMP-targeted imaging probes, modified by the introduction of pentamethine cyanine (Cy5) dyes and therefore containing both radio- as well as fluorescent label with respect to their capability to assess MMP activity by means of scintigraphic (PET) and/or fluorescent (NIRF) imaging. New hybrid MMPI tracer candidates, structurally based on radiofluorinated pyrimidine-2,4,6-triones (barbiturates) from previous approaches, were synthesized by convenient two-step syntheses. In the first step, Cy5 dyes, varying in the number of sulfonate groups ( = 1, 2, or 4) and bearing an additional "clickable" alkyne moiety, were coupled to the barbiturate MMPI by amide formation. In the second step, the [F]fluoride radiolabel was introduced into the resulting Cy5 dye conjugates by "radio-click" chemistry. Biodistribution studies of these hybrid tracer candidates were assessed and compared in C57BL/6 mice by PET as well as fluorescence imaging. MMP activity was imaged in a MMP-positive mouse model of irritant contact dermatitis (ICD) by PET and sequential fluorescence reflectance imaging (FRI), respectively. data were validated by scintillation counting, gelatin zymography, and MMP-histology. Three new potential hybrid MMP imaging probes were prepared, differing essentially in the number of sulfonate groups, introduced by Cy5 dye components. Although the hydrophilicity of these compounds was substantially increased, ( = 1) and ( = 2) were still rapidly eliminated via unfavorable hepatobiliary pathways, as observed in earlier approaches. Only ( = 4) showed delayed clearance and a shift towards higher renal elimination. In the chosen mouse model of ICD, only ( = 4) significantly accumulated in the inflamed mouse ear, which could be precisely visualized by means of PET and FRI.

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Common Toxidromes and the Role of Extracorporeal Detoxification.

Extracorporeal modalities have been used for detoxification for decades, with hemodialysis the preferred and most commonly used modality. Salicylates, lithium, methanol, and ethylene glycol are the most common poisonings treated with dialysis. For each of these common poisonings, a description of the toxidrome including pharmacokinetics, clinical presentation, an overview of treatment, and the role and application of dialysis is outlined. Inhibition of alcohol dehydrogenase to prevent the formation of toxic metabolites in methanol and ethylene glycol is discussed in detail, including the use of fomepizole and ethanol to complement and in some cases prevent the need for hemodialysis. Hemodialysis has been attempted to treat many poisonings, often without success. A description of EXTRIP (Extracorporeal Treatments in Poisoning), a multidisciplinary project examining the evidence for extracorporeal treatments in poisoning, is also described. Recommendations for poisoning with acetaminophen, baclofen, barbiturates, carbamazepine, digoxin, metformin, phenytoin, thallium, theophylline, tricyclic antidepressants, and valproic acid are provided in a comprehensive table.

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Severe hypokalemia and rebound hyperkalemia during barbiturate coma in patients with severe traumatic brain injury.

To evaluate the incidence of severe potassium disturbances during barbiturate coma therapy in patients with severe traumatic brain injury (TBI), and the characteristics of these patients.

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What Are Two Days Worth? Facing Dilemmas Together at the End of Life.


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Common and Alternative Routes of Euthanasia Solution Administration.

There are many acceptable routes of euthanasia solution administration in companion animals. The most common ones are those with consistent use and success, and that align with what is best for the patient, client, and veterinary team. Common injection sites include the venous, hepatic, and renal systems. The barbiturate drugs are in consistent use today, but other drugs may be better given the setting and circumstances at the time. Alternative techniques are available, but only reached for when other more suitable routes of administration are not ideal.

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Sedatives used in children to obtain head CT in the emergency department.

Children in the emergency department who require computerized tomography (CT) of the head often are given sedative medications to facilitate completion of the study with adequate imaging. A prior study found the two most common medications used to obtain head CT in children were pentobarbital and chloral hydrate; however, these medications have become less popular. We hypothesized that there was variability in medication choice amongst providers in the emergency department and there has been a change in the preferred sedatives used in the last decade.

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