scholarly journals Treatment of Severe Alcohol Withdrawal: A Focus on Adjunctive Agents

2017 ◽  
Vol 33 (5) ◽  
pp. 204-212 ◽  
Author(s):  
Erenie Guirguis ◽  
Jonathan Richardson ◽  
Tara Kuhn ◽  
Ashley Fahmy
Keyword(s):  
Clinical Trials ◽  
Alcohol Withdrawal ◽  
English Language ◽  
Case Reports ◽  
Treatment Options ◽  
Delirium Tremens ◽  
Adjunctive Treatment ◽  
Current Evidence ◽  
High Dose ◽  
Keywords Alcohol

Objective:To review adjunctive treatment options for severe alcohol withdrawal. Data Sources: The search strategy included a search of Ovid MEDLINE using keywords alcohol withdrawal, severe alcohol withdrawal, AWS, delirium tremens, delirium, dexmedetomidine, propofol, anticonvulsants, clonidine, and phenobarbital and included articles dated from January 1990 to March 2017. Study Selection and Data Extraction: All English-language clinical trials and case reports assessing the efficacy of adjunctive agents in severe alcohol withdrawal were evaluated. Data Synthesis: Although first-line pharmacotherapy for alcohol withdrawal continues to be benzodiazepines, literature does not clearly define adjunctive treatment options for severe alcohol withdrawal. During severe alcohol withdrawal patients may become unable to tolerate or may become unresponsive to high-dose benzodiazepines. Large doses of benzodiazepines may also result in oversedation, respiratory insufficiency, and worsening delirium. Conclusions: Phenobarbital and dexmedetomidine are both viable adjunctive treatment options for severe alcohol withdrawal. Current evidence has shown these agents decrease the dose requirements of benzodiazepines with limited incidence of adverse reactions. Propofol may also be a viable option in mechanically ventilated patients, but its lack of clear safety and efficacy advantages over current treatment options may limit its use in practice. Clonidine, oral anticonvulsants, and ketamine require further controlled clinical trials to clearly define their role in the treatment of severe alcohol withdrawal.

AR amplification eradication with high-dose testosterone (T) in patients with heavily pretreated mCRPC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 251-251
Author(s):  
Patrick Cotogno ◽  
Elisa M. Ledet ◽  
Joshua Schiff ◽  
Charlotte Manogue ◽  
Brian E. Lewis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Reports ◽  
Therapeutic Option ◽  
Treatment Options ◽  
P53 Mutation ◽  
Cancer Center ◽  
High Dose ◽  
Circulating Free Dna ◽  
Radium 223 ◽  
Heavily Pretreated

251 Background: Patients (Pts) with mCRPC resistant to novel hormones (abi/enza) and taxanes pose a challenge for clinicians. Typically, once these agents are exhausted, clinical trials represent the best therapeutic option; however, many pts are not appropriate for clinical trials due to marrow suppression and/or extensive pre-treatments. Herein we present limited experience with three pts treated with high dose T when therapeutic clinical trial options were not available. Methods: Data was retrospectively collected at Tulane Cancer Center for pt treatment history, laboratory parameters, and circulating free-DNA genomic testing. High dose testosterone was used at a dose of 87.5-100 mg given daily as a 1% testosterone gel applied to the skin. Results: All the mCRPC patients were pre-treated with abi, enza, taxanes, & radium-223. All pts had RBC transfusions due to marrow suppression. All patients were previously treated on clinical trials. After starting high dose T, pt 1 demonstrated a clinical improvement in energy and appetite with a PSA decline from 530 to 45.8 ng/ml (-91.4%) over 30 days. At baseline, cfDNA analyses measured 15.9X AR amplification and 3.7X MYC amplification. The cfDNA also contained 9.8% of P53R273H mutation. Post high-dose T (serum T from castrate to 1462 ng/dL), both of the cfDNA measured amplifications returned to normal and P53 mutation declined to 0.5%. The PSA nadir occurred 30 days after T start; T was stopped 96 days after starting because of PSA rise to 280 ng/ml. The pt then restarted abi, despite prior resistance, and PSA declined from 280 to 65 ng/ml (-76.6%). The 2 other patients had PSA increases and clinical deterioration and high dose T was stopped after 2-3 weeks. Conclusions: Response to high dose T has been reported in occasional case reports going back over 60 years ago (see Brendler H et al. Arch Surg 1950;61:433–40). The frequency of favorable responses is unknown. In one case, a reversal of AR and MYC amplification was observed. The responding patient then was re-sensitized to abi, a drug to which he was previously resistant. Further research, such as the TRANSFORMER trial, is needed to understand the molecular changes and treatment options for this population.

scholarly journals Vitamin C in the Treatment of COVID-19

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1172
Author(s):  
Gregorio Paolo Milani ◽  
Marina Macchi ◽  
Anat Guz-Mark
Keyword(s):  
Clinical Trials ◽  
Vitamin C ◽  
Respiratory Infections ◽  
Medical Condition ◽  
Case Reports ◽  
Case Series ◽  
Theoretical Background ◽  
Current Evidence ◽  
Vitamin C Supplementation ◽  
Essential Nutrient

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.

The Need for Routine Bleomycin Test Dosing in the 21st Century

2005 ◽  
Vol 39 (11) ◽  
pp. 1897-1902 ◽  
Author(s):  
Masha SH Lam
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Case Reports ◽  
Mail Survey ◽  
Signs And Symptoms ◽  
Test Dose ◽  
Host Cells ◽  
High Grade Fever ◽  
Search Terms ◽  
E Mail

OBJECTIVE To review the clinical evidence for routine use of bleomycin test dosing. DATA SOURCES English-language review articles, references from retrieved articles, case reports, and clinical trials were identified from a MEDLINE literature search (1966–July 2005). Key search terms included bleomycin, test dose, anaphylactic reactions, and hypersensitivity. Information from an unpublished E-mail survey, the manufacturer, and the Internet was also used. DATA SYNTHESIS Early clinical trials and isolated case reports suggest that bleomycin-induced acute hypersensitivity reactions occur in 1% of patients with lymphoma and <0.5% of those with solid tumors. The reactions are mainly characterized by high-grade fever, chills, hypotension, and in a few cases, cardiovascular collapse, which can lead to death. The exact mechanism of these reactions is unclear, but is thought to be related to the release of endogenous pyrogens from the host cells. Evidence does not suggest any correlation between doses and the onset or severity of the reactions. Supportive care, including hydration, steroids, antipyretics, and antihistamines, may resolve the symptoms. However, it may not completely prevent recurrences. CONCLUSIONS The incidence of acute hypersensitivity or hyperpyrexic reactions associated with bleomycin is very low, but the reaction is potentially fatal. Clinicians should monitor their patients for any signs and symptoms of acute hyperpyrexic reactions during bleomycin administration. Since the onset of the reactions can occur with any dose of bleomycin and at any time, routine test dosing does not seem to predict when drug reactions may occur.

scholarly journals Suicidality: Once Again, Don’t Blame the Drug Class

2021 ◽  
pp. 153575972110531
Author(s):  
Faught Edward
Keyword(s):  
Clinical Trials ◽  
Suicidal Ideation ◽  
Risk Ratio ◽  
Randomized Clinical Trials ◽  
Rating Scale ◽  
Meta Analysis ◽  
Adjunctive Treatment ◽  
Current Evidence ◽  
Phase 2 ◽  
Increased Risk

Importance Mostantiseizure medications (ASMs) carry a US Food and Drug Administration–mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008. ASMs approved since then carry this warning although they were not similarly studied. Objective To review all placebo-controlled phase 2 and 3 studies of 10 ASMs approved since 2008 to evaluate the risk of suicidality of these drugs compared with placebo. Data Sources Primary publications and secondary safety analyses in PubMed of all phase 2 and 3 randomized placebo-controlled epilepsy trials of ASMs approved since 2008, using keywords epilepsy, antiepileptic drugs, seizures, suicidality, suicidal ideation, and the names of individual drugs. Study Selection All phase 2 and 3 randomized clinical trials of adjunctive treatment of drug-resistant epilepsy and their secondary safety analyses. Data Extraction and Synthesis Articles were reviewed for frequency of suicidality (ideation, attempts, and completed suicides). Mode of suicidality ascertainment included treatment-emergent adverse event reports, Standardized Medical Dictionary for Regulatory Activities queries for events in prespecified categories including suicidal ideation and behavior, prospective collection of suicidality data as a prespecified safety outcome using the Columbia-Suicide Severity Rating Scale, and retrospective evaluation by blinded review using the Columbia-Classification Algorithm of Suicide Assessment. A meta-analysis compared risk for drugs vs placebo of each outcome for all drugs overall and by individual drugs and trials. Main Outcomes and Measures Suicidality (total and by ideation), attempts, and completed suicides. Results Excluding studies that did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (lacosamide, ezogabine, and clobazam), 5 drugs were analyzed: eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Suicidality was evaluated in 17 randomized clinical trials of these drugs, involving 5996 patients, of whom 4000 patients were treated with ASMs and 1996 with placebo. There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, .75; 95% CI, .35–1.60) or attempt (risk ratio, .75; 95% CI, .30–1.87) overall or for any individual drug. Suicidal ideation occurred in 12 of 4000 patients treated with ASMs (.30%) vs 7 of 1996 patients treated with placebo (.35%) ( P  =  .74). Three patients treated with ASMs and no patients treated with placebo attempted suicide ( P  =  .22). There were no completed suicides. Conclusions and Relevance There is no current evidence that the 5 ASMs evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning

scholarly journals Cannabidiol as a Treatment for Mood Disorders: A Systematic Review

2019 ◽  
Vol 65 (4) ◽  
pp. 213-227 ◽  
Author(s):  
Jairo Vinícius Pinto ◽  
Gayatri Saraf ◽  
Christian Frysch ◽  
Daniel Vigo ◽  
Kamyar Keramatian ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mood Disorders ◽  
Observational Studies ◽  
Case Reports ◽  
Health Conditions ◽  
Current Evidence ◽  
Cochrane Central Register ◽  
Level Of Evidence ◽  
Mood Symptoms ◽  
Affective Symptoms

Objective: To review the current evidence for efficacy of cannabidiol in the treatment of mood disorders. Methods: We systematically searched PubMed, Embase, Web of Science, PsychInfo, Scielo, ClinicalTrials.gov , and The Cochrane Central Register of Controlled Trials for studies published up to July 31, 2019. The inclusion criteria were clinical trials, observational studies, or case reports evaluating the effect of pure cannabidiol or cannabidiol mixed with other cannabinoids on mood symptoms related to either mood disorders or other health conditions. The review was reported in accordance with guidelines from Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. Results: Of the 924 records initially yielded by the search, 16 were included in the final sample. Among them, six were clinical studies that used cannabidiol to treat other health conditions but assessed mood symptoms as an additional outcome. Similarly, four tested cannabidiol blended with Δ-9-tetrahydrocannabinol in the treatment of general health conditions and assessed affective symptoms as secondary outcomes. Two were case reports testing cannabidiol. Four studies were observational studies that evaluated the cannabidiol use and its clinical correlates. However, there were no clinical trials investigating the efficacy of cannabidiol, specifically in mood disorders or assessing affective symptoms as the primary outcome. Although some articles point in the direction of benefits of cannabidiol to treat depressive symptoms, the methodology varied in several aspects and the level of evidence is not enough to support its indication as a treatment for mood disorders. Conclusions: There is a lack of evidence to recommend cannabidiol as a treatment for mood disorders. However, considering the preclinical and clinical evidence related to other diseases, cannabidiol might have a role as a treatment for mood disorders. Therefore, there is an urgent need for well-designed clinical trials investigating the efficacy of cannabidiol in mood disorders.

Current Treatment Recommendations for Leishmaniasis

1992 ◽  
Vol 26 (11) ◽  
pp. 1452-1455 ◽  
Author(s):  
Jeffrey T. Moss ◽  
James P. Wilson
Keyword(s):  
English Language ◽  
Clinical Presentation ◽  
Case Reports ◽  
Data Extraction ◽  
Treatment Options ◽  
Medical Personnel ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Management Options ◽  
Governmental Institutions

OBJECTIVE: To review the epidemiology, clinical presentation, risk factors for transmission, and pathogenesis of leishmaniasis, as well as current treatment options for this disease. DATA SOURCES/DATA SELECTION: We reviewed unclassified medical-threat briefing material, subject-matter reviews, and case reports from the world's infectious disease literature. We concentrated on literature pertaining to the pathogenesis and management of leishmaniasis indigenous to Southwest Asia. DATA EXTRACTION: Data from subject reviews published in the English language were evaluated. Case reports and clinical trials provided supplemental data on evolving theories and management options. DATA SYNTHESIS: The clinical presentation of leishmaniasis is highly variable. Management relies heavily upon the use of parenteral antimonial drugs. Although these agents are effective in most cases, toxicity and the emergence of resistance limit the usefulness of standard therapies. Alternative treatment modalities include heat, surgical curettage, ketoconazole, metronidazole, pentamidine, rifampin, amphotericin B, aminoglycosides, allopurinol, and immunotherapy. CONCLUSIONS: Although the number of reported cases of leishmaniasis in the US has generally been low, there is a possibility that more cases may be reported in the future because of the large number of military personnel returning to this country from endemic areas. Medical personnel, particularly those working in governmental institutions, should be familiar with the pathogenesis of this unusual infection as well as potential treatment options.

scholarly journals Treatment of posttraumatic syringomyelia: evidence from a systematic review

2020 ◽  
Vol 162 (10) ◽  
pp. 2541-2556
Author(s):  
Andrea Kleindienst ◽  
Francisco Marin Laut ◽  
Verena Roeckelein ◽  
Michael Buchfelder ◽  
Frank Dodoo-Schittko
Keyword(s):  
Spinal Cord ◽  
English Language ◽  
Spinal Cord Injuries ◽  
Case Reports ◽  
Treatment Options ◽  
Sensory Function ◽  
Time Interval ◽  
Eligibility Criteria ◽  
Cord Injury ◽  
Posttraumatic Syringomyelia

Abstract Background Following spinal cord injury (SCI), the routine use of magnetic resonance imaging (MRI) resulted in an incremental diagnosis of posttraumatic syringomyelia (PTS). However, facing four decades of preferred surgical treatment of PTS, no clear consensus on the recommended treatment exists. We review the literature on PTS regarding therapeutic strategies, outcomes, and complications. Methods We performed a systematic bibliographic search on (“spinal cord injuries” [Mesh] AND “syringomyelia” [Mesh]). English language literature published between 1980 and 2020 was gathered, and case reports and articles examining syrinx due to other causes were excluded. The type of study, interval injury to symptoms, severity and level of injury, therapeutic procedure, duration of follow-up, complications, and outcome were recorded. Results Forty-three observational studies including 1803 individuals met the eligibility criteria. The time interval from SCI to the diagnosis of PTS varied between 42 and 264 months. Eighty-nine percent of patients were treated surgically (n = 1605) with a complication rate of 26%. Symptoms improved in 43% of patients postoperatively and in 2% treated conservatively. Stable disease was documented in 50% of patients postoperatively and in 88% treated conservatively. The percentage of deterioration was similar (surgery 16%, 0.8% dead; conservative 10%). Detailed analysis of surgical outcome with regard to symptoms revealed that pain, motor, and sensory function could be improved in 43 to 55% of patients while motor function deteriorated in around 25%. The preferred methods of surgery were arachnoid lysis (48%) and syrinx drainage (31%). Conclusion Even diagnosing PTS early in its evolution with MRI, to date, no satisfactory standard treatment exists, and the present literature review shows similar outcomes, regardless of the treatment modality. Therefore, PTS remains a neurosurgical challenge. Additional research is required using appropriate study designs for improving treatment options.

scholarly journals Prolonged Use of Oritavancin for Vancomycin-Resistant Enterococcus faecium Prosthetic Valve Endocarditis

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Jennifer A. Johnson ◽  
Eoin R. Feeney ◽  
David W. Kubiak ◽  
G. Ralph Corey
Keyword(s):  
Prosthetic Valve ◽  
Case Reports ◽  
Treatment Options ◽  
Prosthetic Valve Endocarditis ◽  
Additional Treatment ◽  
High Dose ◽  
Vancomycin Resistant Enterococci ◽  
The Us ◽  
Vancomycin Resistant

Abstract Oritavancin is a novel lipoglycopeptide with activity against Gram-positive organisms including streptococci, methicillin-resistant Staphylococcus aureus, vancomycin-resistant S aureus (VRSA), and vancomycin-resistant enterococci (VRE) [1–3]. The US Food and Drug Administration approved oritavancin as a single intravenous dose of 1200 mg for the treatment of acute bacterial skin and skin structure infections on the basis of 2 clinical trials demonstrating noninferiority compared with vancomycin [4, 5]. There are limited options for treatment of serious VRE infections. Monotherapy with daptomycin or tigecycline or linezolid may be sufficient in some cases, but combination therapy is often indicated for severe or complicated infections such as endocarditis. Several antibiotic combinations have been used in isolated case reports with some efficacy, including the following: high-dose ampicillin with an aminoglycoside [6], ampicillin with ceftriaxone or imipenem [7, 8], high-dose daptomycin with ampicillin and gentamicin [9] or with gentamicin and rifampin [10], daptomycin with tigecycline [11, 12], quinupristin-dalfopristin with high-dose ampicillin [13] or doxycycline and rifampin [14], and linezolid with tigecycline [15]. The limited efficacy, limited susceptibility, and extensive toxicities with many of these agents and combinations present barriers to effective treatment. Additional treatment options for VRE endocarditis would be valuable. Although oritavancin has been shown to have in vitro activity against some isolates of VRE, clinical data are lacking. We describe the first use of a prolonged course of oritavancin in the treatment of a serious VRE infection, prosthetic valve endocarditis.

scholarly journals Diagnosis and Treatment of Extended-Spectrum and AmpC β-Lactamase–Producing Organisms

2007 ◽  
Vol 41 (9) ◽  
pp. 1427-1435 ◽  
Author(s):  
Katherine Yang ◽  
B Joseph Guglielmo
Keyword(s):  
Antibiotic Treatment ◽  
English Language ◽  
Randomized Clinical Trials ◽  
Case Reports ◽  
Treatment Options ◽  
False Negative ◽  
In Vitro Susceptibility ◽  
Laboratory Techniques ◽  
Extended Spectrum

Objective: To review the laboratory diagnosis of extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase–producing bacteria and evaluate potential treatment options. Data Sources: A PubMed search, restricted to English-language articles, was conducted (1966–May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles. Study Selection and Data Extraction: All studies that evaluated laboratory methods for the detection of ESBLs and AmpC β-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated. Data Synthesis: Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC β-lactamases are limited, particularly for plasmid-mediated AmpC β-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC β-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms. Conclusions: Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute–recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC β-lactamases. No established guidelines exist for the detection of AmpC β-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC β-lactamase–producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

scholarly journals Update on Systemic Therapy for Advanced Soft-Tissue Sarcoma

2020 ◽  
Vol 27 (11) ◽  
pp. 25-33 ◽  
Author(s):  
A. Smrke ◽  
Y. Wang ◽  
C. Simmons
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
English Language ◽  
Standard Of Care ◽  
Current Evidence ◽  
First Line ◽  
First Line Therapy

Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy. Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria. Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival. Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts.

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