scholarly journals What does first-line therapy mean for paediatric multiple sclerosis in the current era?

2020 ◽  
pp. 135245852093764
Author(s):  
Yael Hacohen ◽  
Brenda Banwell ◽  
Olga Ciccarelli
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Cognitive Outcome ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Paediatric Multiple Sclerosis ◽  
The Impact

Paediatric multiple sclerosis (MS) is associated with higher relapse rate, rapid magnetic resonance imaging lesion accrual early in the disease course and worse cognitive outcome and physical disability in the long term compared to adult-onset disease. Current treatment strategies are largely centre-specific and reliant on adult protocols. The aim of this review is to examine which treatment options should be considered first line for paediatric MS and we attempt to answer the question if injectable first-line disease-modifying therapies (DMTs) are still an optimal option. To answer this question, we review the effects of early onset disease on clinical course and outcomes, with specific considerations on risks and benefits of treatments for paediatric MS. Considering the impact of disease activity on brain atrophy, cognitive impairment and development of secondary progressive MS at a younger age, we would recommend treating paediatric MS as a highly active disease, favouring the early use of highly effective DMTs rather than injectable DMTs.

scholarly journals Advanced Gastric Cancer: Current Treatment Landscape and a Future Outlook for Sequential and Personalized Guide: Swiss Expert Statement Article

2021 ◽  
pp. 1-10
Author(s):  
Alexander R. Siebenhüner ◽  
Sara De Dosso ◽  
Daniel Helbling ◽  
Christoforos Astaras ◽  
Petr Szturz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Current Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Her 2 ◽  
The Impact

<b><i>Background:</i></b> Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. <b><i>Summary:</i></b> Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, <i>Epstein-Barr virus</i> expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and &#x3c;70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. <b><i>Key Message:</i></b> In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.

Therapy of highly active pediatric multiple sclerosis

2017 ◽  
Vol 25 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Peter Huppke ◽  
Brenda Huppke ◽  
David Ellenberger ◽  
Kevin Rostasy ◽  
Hannah Hummel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Clinical Course ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Childhood And Adolescence ◽  
Pediatric Multiple Sclerosis ◽  
Highly Active ◽  
The Impact ◽  
Active Disease

Objective: Study aims were to determine the frequency of highly active disease in pediatric multiple sclerosis (MS), the response to natalizumab (NTZ) and fingolimod (FTY) treatment, and the impact of current treatment modalities on the clinical course. Methods: Retrospective single-center study in the German Center for MS in Childhood and Adolescence. Results: Of 144 patients with first MS manifestation between 2011 and 2015, 41.6% fulfilled the criteria for highly active MS. In total, 55 patients treated with NTZ and 23 with FTY demonstrated a significant reduction in relapse rate (NTZ: 95.2%, FTY: 75%), new T2 lesions (NTZ: 97%, FTY: 81%), and contrast-enhancing lesions (NTZ: 97%, FTY: 93%). However, seven patients switched from NTZ to FTY experienced an increase in disease activity. Comparing pediatric MS patients treated in 2005 with those treated in 2015 showed a 46% reduction in relapse rate and a 44% reduction in mean Expanded Disability Status Scale (EDSS). Conclusion: The rate of highly active disease among pediatric MS patients is high; more than 40% in our cohort. Response to NTZ and FTY treatment is similar if not better than observed in adults. Current treatment modalities including earlier treatment initiation and the introduction of NTZ and FTY have significantly improved the clinical course of pediatric MS.

scholarly journals The Optimal First-Line Therapy ofHelicobacter pyloriInfection in Year 2012

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chao-Hung Kuo ◽  
Fu-Chen Kuo ◽  
Huang-Ming Hu ◽  
Chung-Jung Liu ◽  
Sophie S. W. Wang ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Treatment Strategies ◽  
Sequential Therapy ◽  
Antibiotics Resistance ◽  
First Line ◽  
First Line Therapy ◽  
Metronidazole Resistance ◽  
Rescue Treatment ◽  
New Treatment ◽  
H Pylori

This paper reviews the literature about first-line therapies forH. pyloriinfection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.

scholarly journals Pharmacological Interventions for Pulmonary Involvement in Rheumatic Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 251 ◽  
Author(s):  
Eun Ha Kang ◽  
Yeong Wook Song
Keyword(s):  
Rheumatic Diseases ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Pulmonary Involvement ◽  
Current Treatment ◽  
Targeted Agents ◽  
Pharmacological Interventions ◽  
Inflammatory Processes ◽  
Pulmonary Arterial ◽  
Epidemiologic Features

Among the diverse forms of lung involvement, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are two important conditions in patients with rheumatic diseases that are associated with significant morbidity and mortality. The management of ILD and PAH is challenging because the current treatment often provides only limited patient survival benefits. Such challenges derive from their common pathogenic mechanisms, where not only the inflammatory processes of immune cells but also the fibrotic and proliferative processes of nonimmune cells play critical roles in disease progression, making immunosuppressive therapy less effective. Recently, updated treatment strategies adopting targeted agents have been introduced with promising results in clinical trials for ILD ad PAH. This review discusses the epidemiologic features of ILD and PAH among patients with rheumatic diseases (rheumatoid arthritis, myositis, and systemic sclerosis) and the state-of-the-art treatment options, focusing on targeted agents including biologics, antifibrotic agents, and vasodilatory drugs.

Current Treatment Strategies for Multiple Sclerosis - Efficacy Versus Neurological Adverse Effects

2012 ◽  
Vol 18 (2) ◽  
pp. 209-219 ◽  
Author(s):  
Martin S. Weber ◽  
Til Menge ◽  
Klaus Lehmann-Horn ◽  
Helena C. Kronsbein ◽  
Uwe Zettl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Effects ◽  
Treatment Strategies ◽  
Current Treatment

Updates in insomnia diagnosis and treatment

2019 ◽  
Vol 54 (4-5) ◽  
pp. 275-289 ◽  
Author(s):  
Scott Bragg ◽  
JJ Benich ◽  
Natalie Christian ◽  
Josh Visserman ◽  
John Freedy
Keyword(s):  
Drug Therapy ◽  
Behavioral Therapy ◽  
Treatment Plan ◽  
Treatment Options ◽  
First Line ◽  
Safety Concerns ◽  
Diagnostic And Statistical Manual ◽  
First Line Therapy ◽  
Appropriate Treatment ◽  
Central Nervous System Depression

Introduction Insomnia is the most commonly reported sleep disorder and remains undertreated in many patients. New changes to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, have changed the way insomnia is diagnosed. In patients who suffer from insomnia, a number of available treatment options exist including both behavioral therapy and medications. Literature Review: First line therapy for insomnia should always include behavioral modifications such as sleep hygiene and insomnia-oriented cognitive behavioral therapy. In patients deemed to need pharmacotherapy, first line medications include nonbenzodiazepine hypnotics (i.e., z-drugs) and antidepressants depending on the patients’ needs and comorbidities. The risk of next day impairment, parasomnias, and central nervous system depression are some of the most feared side effects with z-drugs. Second line drug therapy includes melatonin and suvorexant. Several concerns exist for suvorexant similar to other insomnia medications, but melatonin remains one of the safest medication alternatives. Other medication options such as benzodiazepines, antihistamines, and antipsychotics should rarely be used because of weak effectiveness data or serious safety concerns. Discussion The most appropriate treatment plan needs to be tailored to meet the needs of individual patients. Many patient factors (e.g., age, other comorbidities, specific problems with sleep) need to be considered before prescribing drug therapy for patients suffering from insomnia. Medications with the best evidence and fewest safety concerns should be prioritized when clinicians work with patients to determine the most appropriate treatment plan. Conclusions Nondrug treatment should be the emphasis for managing insomnia, but several options exist for patients needing multimodal therapy to improve their symptoms and maximize their quality of life. Z-drugs and antidepressants are first line medications options, but other options may be considered when tailored to individual patients. Medications should only be used intermittently and short term until nondrug treatments help to change a patient’s sleep routine.

scholarly journals Cancer missense mutations in the BRC repeats of BRCA2 protein disrupt RAD51 binding and activity leading to chemotherapeutic sensitivity

2021 ◽  
Author(s):  
Judit Jimenez-Sainz ◽  
Joshua Mathew ◽  
Jennifer Garbarino ◽  
Joseph P Eder ◽  
Ryan B Jensen
Keyword(s):  
Genome Stability ◽  
Treatment Options ◽  
Suppressor Gene ◽  
Current Treatment ◽  
Missense Mutations ◽  
Dna Double Strand Breaks ◽  
Clinical Databases ◽  
Brca2 Protein ◽  
Hypomorphic Alleles ◽  
The Impact

BRCA2 is a tumor suppressor gene that maintains genome stability by mediating the high fidelity repair of DNA double-strand breaks (DSBs) through homology-directed repair (HDR). Pathogenic mutations in BRCA2 predispose to breast, ovarian, pancreatic, prostate, and other cancers. Mutations in BRCA2 leading to severe protein truncation predict pathogenicity, however, missense mutations with unknown functional consequences, designated Variants of Uncertain Significance (VUS), comprise 60% of BRCA2 sequence changes deposited in clinical databases. Classifying BRCA2 VUS correctly is critical for relaying clinically actionable information to patients concerning future cancer risk or current treatment options. In this study, we identified and biochemically characterized three BRCA2 VUS located in BRC repeats to determine the impact on canonical HDR functions. Two of the germline variants, S1221P and T1980I, map to conserved residues in BRC2 and BRC7, disrupt RAD51 binding, and are diminished in their ability to stabilize RAD51-ssDNA complexes. We provide supporting cellular evidence that S1221P and T1980I are significantly compromised in their response to chemotherapeutics and ionizing radiation. The third variant, T1346I, lies within the spacer region between BRC2 and BRC3 but remains fully functional. We conclude that T1346I has a neutral impact on BRCA2 function, while S1221P and T1980I are hypomorphic alleles that disrupt the ability of BRCA2 to fully engage and stabilize RAD51 nucleoprotein filaments.

Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

2015 ◽  
Vol 22 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Claire M Modica ◽  
Niels Bergsland ◽  
Michael G Dwyer ◽  
Deepa P Ramasamy ◽  
Ellen Carl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Decline ◽  
Cognitive Processing ◽  
Gray Matter ◽  
Cognitive Reserve ◽  
Cognitive Outcome ◽  
Brain Reserve ◽  
The Impact ◽  
Normal Controls

Background: Cognitive decline is characterized in multiple sclerosis (MS), but the rate and severity vary. The reserve hypothesis proposes that baseline neurological differences impact cognitive outcome in neurodegenerative disease. Objective: To elucidate how brain reserve and cognitive reserve influence subcortical gray matter (SCGM) atrophy and cognitive decline in MS over 3 years. Methods: Seventy-one MS patients and 23 normal controls underwent magnetic resonance imaging and cognitive assessment at baseline and 3-year follow-up. The influence of reserve on cognitive processing speed (CPS) and memory was examined. Results: SCGM volume and cognitive scores were lower in MS than normal controls ( P⩽0.001). Accounting for baseline, comparison of follow-up means yielded a difference between groups in SCGM volume ( P<0.001) but not cognition (NS). Cognitive reserve ( P=0.005), but not brain reserve, contributed to CPS, with only low cognitive reserve MS subjects showing decline in CPS ( P=0.029). SCGM change predicted CPS outcome in MS with low cognitive reserve ( P=0.002) but not high cognitive reserve. There were no effects in the domain of memory. Conclusions: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

Selected natural and synthetic agents effective against Parkinson’s disease with diverse mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Hayrettin Ozan Gulcan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Dopamine Metabolism ◽  
Dopaminergic Agonists ◽  
Alternative Drug ◽  
Synthetic Agents ◽  
Disease Modifying

: Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

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