Search

Objective: To evaluate the efficacy and safety of a fixed-dose gabapentin taper protocol for alcohol withdrawal in hospitalized patients. Patients and Methods: We retrospectively identified patients admitted to the hospital from January 1, 2016, to April 30, 2018, for alcohol withdrawal syndrome. Based on the treatment that patients received, they were divided into the gabapentin, benzodiazepine, and combination treatment groups. The primary outcome was length of stay, defined as time from admission to either discharge or 36 hours with Clinical Institute Withdrawal Assessment (CIWA) score less than 10. Inverse probability of treatment weight was used to account for differences in baseline characteristics between groups. Results: A total of 443 patients met criteria for inclusion (128, 253, and 62 patients in the gabapentin, benzodiazepine, and combination groups, respectively). Baseline characteristics were similar among all groups. The median gabapentin group length of stay was 4.0 hours shorter than the benzodiazepine group (P=.012). Maximum CIWA score was 2.2 points lower in the gabapentin group (P=.003). No statistical differences were noted among safety outcomes, including incidence of seizure, intensive care unit transfer, or delirium tremens. Results were not statistically altered by inverse probability of treatment weight analysis. Conclusion: A fixed-dose gabapentin taper protocol appears to be an effective and safe alternative to CIWA-driven benzodiazepines in patients hospitalized with alcohol withdrawal syndrome, though further research is necessary to define the potential subpopulations that benefit most.

Gabapentin is frequently used in the treatment of anxiety disorders. However, there are no randomized controlled trials on the effectiveness of this medication in generalized anxiety disorder (GAD), and there are only a few case reports. We present a case of a 59-year-old female with a psychiatric history of GAD. The patient discontinued benzodiazepines after more than 7 years of daily treatment which led to rebound anxiety, benzodiazepine withdrawal symptoms, and suicidal ideation. She was psychiatrically hospitalized and started on gabapentin. Over the next 10 months of outpatient follow-up, she attempted to taper off gabapentin due to personal preference to limit medications. During this time, we observed a clear dose-response pattern of gabapentin on GAD symptoms. In the absence of controlled studies, these findings may offer important information about the effectiveness of gabapentin in GAD.

Epithelial ovarian cancer remains the most lethal gynecologic malignancy despite advances in treatment. The standard management generally involves a combination of surgical tumor debulking and chemotherapy. Over the decades, chemotherapy for ovarian cancer has evolved and currently involves a combination of intravenous platinum and taxane chemotherapy. Over the past decade, three randomized phase III trials have been reported, and all have demonstrated a significant survival advantage for intraperitoneal compared with intravenous chemotherapy. However, there are potential barriers and controversies related to the administration of intraperitoneal chemotherapy in ovarian cancer patients. In this review, we discuss the evolution and current management considerations of chemotherapy for the treatment of epithelial ovarian cancer.

Somatic recordings from CA1 pyramidal cells indicated a persistent upregulation of the h-current (Ih) after experimental febrile seizures. Here, we examined febrile seizure-induced long-term changes in Ih and neuronal excitability in CA1 dendrites. Cell-attached recordings showed that dendritic Ih was significantly upregulated, with a depolarized half-activation potential and increased maximal current. Although enhanced Ih is typically thought to be associated with decreased dendritic excitability, whole-cell dendritic recordings revealed a robust increase in action potential firing after febrile seizures. We turned to computational simulations to understand how the experimentally observed changes in Ih influence dendritic excitability. Unexpectedly, the simulations, performed in three previously published CA1 pyramidal cell models, showed that the experimentally observed increases in Ih resulted in a general enhancement of dendritic excitability, primarily due to the increased Ih-induced depolarization of the resting membrane potential overcoming the excitability-depressing effects of decreased dendritic input resistance. Taken together, these experimental and modeling results reveal that, contrary to the exclusively anti-convulsive role often attributed to increased Ih in epilepsy, the enhanced Ih can co-exist with, and possibly even contribute to, persistent dendritic hyperexcitability following febrile seizures in the developing hippocampus.

The Loyalists have been a relatively unknown group among the early settlers of Cape Breton. This is largely because their numbers were not great, they were swamped by the Scottish [...]

Summary Based on the activity of menadione (M) in the human tumor stem cell assay, we conducted a phase I trial of M in patients with advanced cancer. Forty patients (19 men, 21 women) were treated with 90 courses of M; 82 treatment courses are evaluable for toxicity. The median patient age, Karnofsky performance status, and number of prior chemotherapy regimens were 61 years (range 3274 years), 80% (range 50100%), and two, respectively. M was given by a short (15 h) intravenous infusion every 3 weeks, starting at 40 mg/m2 and escalating by modified Fibonacci scheme to 1360 mg/m2. Toxicity was graded according to the Southwest Oncology Group toxicity scale with defined hypersensitivity reaction (HSR) scales. No grade ?2 hematologic toxicity was observed. Non-hematologic toxicity consisted of a HSR syndrome of paresthesiae of the extremities, facial flushing, burning of the eyes and mucous membranes, chest pain and dyspnea. HSR was defined as Grade I toxicity by the presence of facial numbness, flushing, and/or a tingling sensation or burning of the eyes and mucous membranes. Grade II toxicity was defined as the presence of the same above symptoms plus chest tightness, paresthesiae of extremities and/or dyspnea and chest pain. These toxicities were grade 1 in 3 of 4 patients at a dose of 840 mg/m2. At 1360 mg/m2, 2 of 13 patients suffered grade 1 HSR and 7 of 13 grade 2 HSR No objective partial or complete responses were observed. Plasma menadione concentrations peaked at 1.97.4 M during the infusion in 3 patients receiving 1360 mg/m2. Further phase 1 and 2 combination trials using longer infusion durations have resulted from this trial. [ABSTRACT FROM AUTHOR]

Studies of pathological ion channel regulation as an underlying mechanism of epilepsy have revealed alterations of the h-current in several animal models. While prior reports indicate that downregulation of the h-current is pro-excitatory on the single neuron level, we recently found an upregulation of Ih in hyperexcitable CA1 pyramidal neuron dendrites following experimental febrile seizures. In addition, in several CA1 pyramidal neuron computational models of different complexity, h-current upregulation has been shown to lead to pro-excitable effects. This focused review examines the complex impact of altered h-current on neuronal resting membrane potential (RMP) and input resistance (Rin), as well as reported interactions with other ionic conductances.