Targeting the Myeloid Lineages and the Immune Microenvironment in Myelodysplastic Syndromes: Novel and Evolving Therapeutic Strategies

2021 ◽  
pp. 106002802110361
Author(s):  
Clement Chung
Keyword(s):  
Myelodysplastic Syndromes ◽  
Targeted Therapies ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Tumor Biology ◽  
Erythroid Differentiation ◽  
Immune Microenvironment ◽  
Signal Transduction Inhibitors ◽  
Apoptosis Inducing Agents

Objective: To discuss the recent and emerging data for novel targeted therapies in myelodysplastic syndromes (MDS). Data Sources: A literature search from January 2015 to June 2021 was performed using the key terms targeted therapies, myelodysplastic syndromes, DNA repair, erythroid differentiation therapy, epigenetic inhibitors, signal transduction inhibitors, and apoptosis-inducing agents. Study Selection and Data Extraction: Relevant clinical trials and articles in the English language were identified and reviewed. Data Synthesis: MDS are a heterogeneous group of malignant blood disorders affecting the bone marrow (BM), ultimately leading to BM failure, acute leukemia, and death. Selection of treatment is influenced by the severity of symptoms, cytopenia, cytogenetics, prognostic category, medical fitness, and patient preferences. Although current therapies such as erythropoiesis stimulating agents (ESAs) and hypomethylating agents (HMAs) help improve anemia and reduce transfusion burden, limited treatment options exist when patients experience treatment failure to ESAs or HMA. Recent regulatory approval of luspatercept, which targets the erythroid differentiation pathway, represents a major therapeutic advance in the management of anemia in MDS patients who are refractory to ESAs. Many investigational targeted therapies that aim at the myeloid lineage signaling pathway and the immune microenvironment are in active development. Relevance to Patient Care and Clinical Practice: This nonexhaustive review summarizes and describes the recent data for targeted therapies for MDS. Conclusion: The development of novel and investigational therapeutic agents continues to contribute to an improved understanding of tumor biology. The precise therapeutic role and timing of these agents remain to be elucidated.

Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab

2000 ◽  
Vol 34 (6) ◽  
pp. 743-760 ◽  
Author(s):  
Brigitte T Luong ◽  
Barbara S Chong ◽  
Dionne M Lowder
Keyword(s):  
Rheumatoid Arthritis ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Pertinent Data

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

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.

Overview of Pharmacologic Treatment of Obesity: Past Experiences, Present Options, and Future Directions

2005 ◽  
Vol 21 (6) ◽  
pp. 319-324
Author(s):  
T Kristopher Harrell ◽  
Leigh Ann Ross ◽  
Deborah S King
Keyword(s):  
Adverse Effects ◽  
Large Scale ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Pharmacologic Treatment ◽  
Related Factors ◽  
Treatment Of Obesity ◽  
Past Experiences ◽  
Pharmacologic Agents

Objective: To review the literature regarding the past, present, and future pharmacologic agents used in the treatment of obesity. Data Sources: Articles were identified by searching MEDLINE (1966–April 2005) and International Pharmaceutical Abstracts (1970–April 2005) using the key words obesity, antiobesity agents, sibutramine, orlistat, phentermine, and leptin. Additional resources were identified by examining the references of the articles cited. Searches were limited by human subject and English language, but were not limited by time of publication. Study Selection and Data Extraction: Large-scale clinical studies of pharmacologic agents used to treat obesity were selected for this review including agents that were previously available, currently available, and those currently undergoing clinical trials. Data Synthesis: Thyroid hormone was the first antiobesity agent used. Several other agents have been withdrawn from the market due to adverse effects. Current therapies indicated for obesity management include orlistat, sibutramine, and noradrenergic agents. Future therapies include both newer agents and existing agents that are principally used for other indications, mainly diabetes, depression, and seizure disorders. Conclusions: Obesity is a major epidemic in the US, affecting over half of the population. Past experiences with the pharmacologic treatment of obesity have been disappointing and, in some cases, harmful to patients. Current options are available that include noradrenergic agents, orlistat, and sibutramine. However, these agents still have only demonstrated limited efficacy for short-term use plus some undesirable adverse effects. Newer treatment options are being evaluated as new pathways are being identified and other related factors are being discovered.

scholarly journals Challenges Experienced by Physiotherapists in Rehabilitation of Individuals With Poststroke Hemineglect: A Review Study

2020 ◽  
Vol 3 (1) ◽  
pp. 10-13
Author(s):  
Mridul Makkar ◽  
Narkeesh Arumugam ◽  
Divya Midha
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Low Frequency ◽  
Functional Independence ◽  
Mirror Therapy ◽  
Treatment Methods ◽  
Study Selection ◽  
Patients Experience ◽  
Theta Burst

Background: Hemineglect is the inability to sense stimuli given on the paretic side. It is most frequently seen in individuals with left hemiplegia resulting from temporoparietal lobe damage. On the basis of duration poststroke, hemineglect can be acute (<3 months) or chronic (>6 months). The patients experience many challenges in rehabilitation of motor function, cognitive function, and in gaining functional independence. Aim: To identify the challenges faced by physiotherapists in rehabilitation of individuals with poststroke hemineglect. Methodology: Data Identification: An English language literature search using Google Scholar, Scopus, PubMed, and Pedro was done. Study Selection: Articles were identified and those which fulfilled the specific requirements were selected. Data Extraction: In accordance with the inclusion criteria, 9 studies done between 1997 and 2017 were reviewed. Results: In this study, we reviewed a number of studies on the treatment of hemineglect which show a variety of treatment options. The various interventions include robotic mirror therapy, repeated parietal theta-burst stimulation, low-frequency transcranial magnetic stimulation, trunk rotation and scanning training, forced use therapy, prism glass adaptation, movement detection bracelets, each of which have different effects. Conclusion: There are a limited number of studies on the different treatment methods that are currently available. Further research is needed on these treatment methods to prove their efficacy and find a suitable method to overcome the challenges that the patients with hemineglect face at present.

Glecaprevir/Pibrentasvir: The First 8-Week, Pangenotypic HCV Treatment Regimen for Patients 12 Years of Age and Older

2019 ◽  
Vol 54 (3) ◽  
pp. 262-276
Author(s):  
Jamie Huff ◽  
Rebecca Andersen
Keyword(s):  
Clinical Trials ◽  
Hepatitis C ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Safety Data ◽  
Hcv Treatment ◽  
Cost Information ◽  
Additional Information ◽  
Compensated Cirrhosis

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, dosing, and cost information of glecaprevir/pibrentasvir in the treatment of hepatitis C virus (HCV). Data Sources: A literature search was conducted between September 2018 and July 2019 using PubMed and Google Scholar with the search terms glecaprevir, pibrentasvir, Mavyret, Maviret, and hepatitis C. Clinicaltrials.gov was searched using the same terms. References of published articles were assessed for additional information. Study Selection and Data Extraction: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir were evaluated. Data Synthesis: Food and Drug Administration–approved glecaprevir/pibrentasvir is considered both safe and efficacious for the treatment of HCV genotypes 1 to 6 and in several patient populations, such as those with treatment-naïve or treatment-experienced HCV; with or without compensated cirrhosis, HIV-1 coinfection, or renal impairment; post–liver or post–kidney transplant; and ≥12 years of age. Sustained virological response rates ranged from 83% to 100% in clinical trials, and safety outcomes appear similar to other guideline-recommended HCV treatment options. Relevance to Patient Care and Clinical Practice: This review discusses the pharmacological, efficacy, and safety data found in glecaprevir/pibrentasvir clinical trials and relates this to guideline recommendations and the practical use of this medication for treatment of HCV. Conclusions: With HCV infection rates remaining elevated, it is important to have safe and efficacious treatment options. Glecaprevir/pibrentasvir is a safe and efficacious guideline-recommended, 8-week treatment for HCV in several patient populations, with these populations likely growing in the near future given ongoing and future studies.

Clinical and pathologic factors associated with survival in BRAFV600E colorectal cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4047-4047
Author(s):  
Van K. Morris ◽  
Bryan K. Kee ◽  
Michael J. Overman ◽  
David R. Fogelman ◽  
Arvind Dasari ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Treatment Options ◽  
Tumor Biology ◽  
Mapk Signaling ◽  
Hepatic Flexure ◽  
Locoregional Therapy ◽  
Cancer Center ◽  
Term Survival ◽  
Primary Tumors ◽  
Pathologic Features

4047 Background: BRAFV600E mutations occur in fewer than 10% of all patients (pts) with metastatic colorectal cancer (mCRC) and arise from sessile serrated adenomas. Despite efficacy with targeted therapies against MAPK signaling and with immunotherapies in this population, survival outcomes for pts with BRAFV600E mCRC in general are poor. Characteristics distinguishing pts with BRAFV600E mCRC with favorable versus unfavorable outcomes have not been well annotated. Methods: Records of 188 pts with BRAFV600E mCRC evaluated at MD Anderson Cancer Center between 3/2010-1/2020 were reviewed. Pts with the shortest and longest metastatic survival (N = 25 for each group) were compared. Associations between prognostic group and clinical/pathologic features were measured by odds ratio and for median survival by log-rank testing. Results: Median metastatic survival differed between the 2 BRAFV600E mCRC populations (8.6 vs 84 months, p < .0001). Pts with poor survival more commonly had primary tumors arising from the hepatic flexure/proximal transverse colon (44% vs 16%, p = .04) and more frequent hepatic involvement (75% vs 28%, p = .001). Pts with favorable survival were more likely to develop metachronous metastases (52% vs 16%, p = .01), have fewer distant organ involvement (median 1 vs 2, p = .02), and undergo definitive locoregional therapy to metastatic disease (44% vs 0%, p = .01). Microsatellite instability (36% vs 4%, p = .008) and a history of tobacco use (44% vs 16%, p = .04) were associated with a favorable prognosis. Durable responses to MAPK-targeted therapies (5/25) and immunotherapy (3/25) were noted in the favorable group. Conclusions: Pts with BRAFV600E mCRC can achieve excellent long-term survival which belies conventional context and is driven by locoregional and systemic treatment options alike. Anatomic localization of the primary tumor and prior exposures may highlight environmental influences on tumor biology which account for the clinical heterogeneity of pts with BRAFV600E mCRC.

Ozenoxacin: A Novel Topical Quinolone for Impetigo

2018 ◽  
Vol 52 (12) ◽  
pp. 1233-1237 ◽  
Author(s):  
Christopher Wren ◽  
Edward Bell ◽  
Lea S. Eiland
Keyword(s):  
Staphylococcus Aureus ◽  
English Language ◽  
Data Extraction ◽  
Phase 1 ◽  
Treatment Options ◽  
Current Treatment ◽  
Systemic Absorption ◽  
Clinical Role ◽  
Study Selection ◽  
Language Data

Objective: To review the data supporting Food and Drug Administration (FDA) labeling of ozenoxacin and evaluate its place in therapy for impetigo. Data Sources: A literature search was conducted using PubMed (1966 to May 2018) and Google Scholar (2000 to May 2018) with the search terms ozenoxacin, T-3912, and GF-001001-00. Other resources included clinicaltrials.gov , the manufacturing product label, and the FDA website. Study Selection and Data Extraction: All relevant English-language data from abstracts, phase 1 to 4 studies, and review articles were included. Data Synthesis: FDA labeling of ozenoxacin was based on 2 phase 3 studies conducted in patients 2 months of age and older. Ozenoxacin demonstrated efficacy and safety for use in bullous or nonbullous impetigo from Staphylococcus aureus or Streptococcus pyogenes as compared with placebo. The lack of systemic absorption results in minimal adverse drug reactions. Studies did not detect possible adverse events commonly associated with other quinolone antibiotics. Relevance to Patient Care and Clinical Practice: This topical quinolone has bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus. Ozenoxacin may have an expanded clinical role for the treatment of localized impetigo if resistance to current therapies increases significantly. However, ozenoxacin is unlikely to play a significant role in the treatment of impetigo in the foreseeable future, because of lack of direct comparative clinical efficacy data with currently recommended therapies and likely high cost. Conclusions: Ozenoxacin, the first nonfluorinated quinolone, is a safe, topical treatment for impetigo in patients 2 months of age and older. Although clinical trials demonstrate efficacy compared with placebo, comparative trials to current treatment options are needed to identify its therapeutic use.

Topical Aminophylline: Is it Safe and Effective in Causing Regional Fat Loss?

1997 ◽  
Vol 13 (2) ◽  
pp. 80-83
Author(s):  
Lisa M Tong ◽  
Kristin R Gericke
Keyword(s):  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Local Concentration ◽  
Drug Induced ◽  
Fat Loss ◽  
Study Selection ◽  
Data Source

Objective: To provide a better understanding of the efficacy and possible adverse effects of topical aminophylline in causing regional fat loss. Data Source: Pertinent English-language literature (1958–1995). Study Selection: Representative articles documenting mechanisms of action and types of drug-induced reactions, as well as treatment options. Data Extraction: Data were extracted only from articles that documented relevant and substantive information backed by clinical studies. Data Synthesis: Topical aminophylline 2% thigh cream has been introduced as a method of treating cellulite, or dimpled thighs and buttocks. The proposed method of action is by increasing local concentration, thereby stimulating lipolysis. Data from two small clinical trials showed that the cream reduced thigh girth and had no known adverse effects. However, adverse dermatologic effects caused by aminophylline have been reported in the past. Conclusions: Topical aminophylline cream appears to be a reasonable option for regional reduction of thigh girth for some people and has not shown any adverse effects. Nevertheless, larger, long-term studies need to be done.

Posaconazole: An Oral Triazole with an Extended Spectrum of Activity

2008 ◽  
Vol 42 (10) ◽  
pp. 1429-1438 ◽  
Author(s):  
Erik J Rachwalski ◽  
Jeffrey T Wieczorkiewicz ◽  
Marc H Scheetz
Keyword(s):  
English Language ◽  
Fungal Infections ◽  
Data Extraction ◽  
Treatment Options ◽  
Drug Application ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug ◽  
Hematopoietic Stem ◽  
Yeasts And Molds

Objective: To summarize the published clinical data on posaconazole, critically review the New Drug Application data submitted to the Food and Drug Administration, and provide information critical for evaluation and formulary positioning. Data Sources: Reported investigations were identified from MEDLINE (1966-June 30, 2008), bibliographies of manuscripts, www.clinicaltrials.gov , and www.fda.gov . Study Selection and Data Extraction: English-language articles were selected. AN available in vitro, animal, clinical, and human studies describing the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, safety, and adverse events of posaconazole were reviewed. Data Synthesis: Posaconazole is an oral broad-spectrum triazole with activity against many yeasts and molds. Resistance to posaconazole has been reported, but has been rare to date. Posaconazole, in doses of 200 mg 3 limes daily, reduced breakthrough invasive fungal infections (OR 0.30; 95% CI 0.12 to 0.71) and aspergillosis incidence (OR 0.31; 95% CI 0.13 to 0.75) in patients receiving hematopoietic stem-cell transplants compared with those receiving fluconazole. Similarly, the same regimen of posaconazole reduced invasive fungal infections (95% CI -9.7 to -2.5) and aspergillosis (CI not reported, p < 0.001) when compared with fluconazole and itraconazole in neutropenic patients. Posaconazole is non-inferior to fluconazole for treatment of oropharyngeal candidiasis (95% CI -6.6 to 5.0), but necessity for this indication remains unclear, as many other treatment options exist. Smaller investigations have analyzed use of posaconazole for patients requiring salvage or alternative treatment for zygomycosis, fusarbsis, cryptococcal meningitis, coccidioidomycosis, and histoplasmosis. Studies are needed to clarify efficacy for such expanded use, and therapeutic drug monitoring may improve outcomes. The most common adverse effects associated with the use of posaconazole include headache, fever, nausea, vomiting, and diarrhea. Conclusions: Posaconazole appears to be a valuable and promising addition to the antifungal armamentarium for prophylaxis and treatment of various fungal processes. At this time, posaconazole should probably be reserved for prophylaxis in patients at high risk for invasive fungal infection, as salvage therapy in refractory or resistant infections, or for patients with intolerance to other therapies.

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder

2021 ◽  
pp. 106002802110084
Author(s):  
Kristin Waters
Keyword(s):  
Adverse Effects ◽  
Pharmacological Treatment ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Language Studies ◽  
Insomnia Disorder ◽  
Study Selection

Objective To provide an overview of the efficacy and safety of lemborexant in the treatment of insomnia disorder by assessing the currently available literature. Data Sources A literature search of PubMed was performed (2010 to March 2021) using the following search terms: lemborexant, sleep, orexin Study Selection and Data Extraction All relevant English-language studies were reviewed and considered, with a focus on phase 3 trials. Data Synthesis The efficacy and safety of lemborexant in the treatment of insomnia disorder in adults was demonstrated in 2 phase 3 trials. Lemborexant significantly reduced latency to persistent sleep compared with placebo. The first study also demonstrated a significant reduction compared with the active control zolpidem ER. Somnolence and headache were relatively common, but the marked adverse effects associated with other medications commonly used to treat insomnia, such as cognitive and psychomotor impairment and complex sleep-related behaviors, were not observed. Relevance to Patient Care and Clinical Practice Although nonpharmacological therapy is considered first-line treatment for insomnia disorder, pharmacological treatment is most commonly utilized. Lemborexant is a viable pharmacological treatment option for patients who are unable to tolerate the adverse effects associated with the most commonly prescribed medications for insomnia, such as benzodiazepines and sedative-hypnotics (Z drugs). This is especially true for geriatric patients, who may be more sensitive to these adverse effects. Conclusion Lemborexant can be recommended to treat insomnia disorder when pharmacological treatment is warranted. It has demonstrated efficacy in clinical trials and is likely better tolerated than most currently available treatment options.

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