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Expert Review of Anti-infective Therapy Apr 2017Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of... (Review)
Review
Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.
Topics: Acids, Carbocyclic; Amantadine; Antiviral Agents; Coronavirus Infections; Cyclopentanes; Guanidines; Humans; Immunocompromised Host; Influenza, Human; Oseltamivir; Palivizumab; Paramyxoviridae Infections; Picornaviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Ribavirin; Zanamivir
PubMed: 28067078
DOI: 10.1080/14787210.2017.1279970 -
The Cochrane Database of Systematic... May 2015Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development.
OBJECTIVES
To investigate the efficacy and acceptability of dopamine agonists alone or in combination with any psychosocial intervention for the treatment of of people who misuse cocaine.
SEARCH METHODS
We run the search on 12 January 2015. We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, CINAHL, PsycINFO, ICTRP, clinicaltrials.gov and screened reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing dopamine agonists alone or associated with psychosocial intervention with placebo, no treatment or other pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
Twenty four studies, including 2147 participants, met the inclusion criteria. Comparing any dopamine agonist versus placebo, we found no differences for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). This was also observed when single dopamine agonists were compared against placebo. Comparing amantadine versus antidepressants, we found low quality of evidence that antidepressants performed better for abstinence (RR 0.25, 95% CI 0.12 to 0.53) based on two studies with 44 participants. No differences were found for dropout or adverse events, for both moderate quality of evidence.The major flaws of the included studies concerned selection bias because most studies did not report information about sequence generation (80%) and allocation concealment methods (86%): half of the included studies were judged at unclear risk of performance bias and 62.5% at unclear risk of detection bias for what concerns subjective outcomes.
AUTHORS' CONCLUSIONS
Current evidence from RCTs does not support the use of dopamine agonists for treating cocaine misuse. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment. Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention, which was suggested by the previous Cochrane Review (Soares 2003), is not supported by the results of this Cochrane Review update.
Topics: Amantadine; Antidepressive Agents; Bromocriptine; Cocaine-Related Disorders; Depression; Dopamine Agonists; Humans; Levodopa; Randomized Controlled Trials as Topic; Selection Bias
PubMed: 26014366
DOI: 10.1002/14651858.CD003352.pub4 -
Epilepsia Dec 2023N-methyl-d-aspartate (NMDA) receptors are expressed at synaptic sites, where they mediate fast excitatory neurotransmission. NMDA receptors are critical to brain...
OBJECTIVE
N-methyl-d-aspartate (NMDA) receptors are expressed at synaptic sites, where they mediate fast excitatory neurotransmission. NMDA receptors are critical to brain development and cognitive function. Natural variants to the GRIN1 gene, which encodes the obligatory GluN1 subunit of the NMDA receptor, are associated with severe neurological disorders that include epilepsy, intellectual disability, and developmental delay. Here, we investigated the pathogenicity of three missense variants to the GRIN1 gene, p. Ile148Val (GluN1-3b[I481V]), p.Ala666Ser (GluN1-3b[A666S]), and p.Tyr668His (GluN1-3b[Y668H]).
METHODS
Wild-type and variant-containing NMDA receptors were expressed in HEK293 cells and primary hippocampal neurons. Patch-clamp electrophysiology and pharmacology were used to profile the functional properties of the receptors. Receptor surface expression was evaluated using fluorescently tagged receptors and microscopy.
RESULTS
Our data demonstrate that the GluN1(I481V) variant is inhibited by the open pore blockers ketamine and memantine with reduce potency but otherwise has little effect on receptor function. By contrast, the other two variants exhibit gain-of-function molecular phenotypes. Glycine sensitivity was enhanced in receptors containing the GluN1(A666S) variant and the potency of pore block by memantine and ketamine was reduced, whereas that for MK-801 was increased. The most pronounced functional deficits, however, were found in receptors containing the GluN1(Y668H) variant. GluN1(Y668H)/2A receptors showed impaired surface expression, were more sensitive to glycine and glutamate by an order of magnitude, and exhibited impaired block by extracellular magnesium ions, memantine, ketamine, and MK-801. These variant receptors were also activated by either glutamate or glycine alone. Single-receptor recordings revealed that this receptor variant opened to several conductance levels and activated more frequently than wild-type GluN1/2A receptors.
SIGNIFICANCE
Our study reveals a critical functional locus of the receptor (GluN1[Y668]) that couples receptor gating to ion channel conductance, which when mutated may be associated with neurological disorder.
Topics: Humans; Memantine; Dizocilpine Maleate; Receptors, N-Methyl-D-Aspartate; Ketamine; HEK293 Cells; Glutamates; Neurodevelopmental Disorders; Glycine; Nerve Tissue Proteins
PubMed: 37734923
DOI: 10.1111/epi.17776 -
The Turkish Journal of Pediatrics 2023Catatonia is a complex neuropsychiatric disorder involving stupor, waxy flexibility, and mutism lasting more than 1 hour. It has arisen mostly from mental and neurologic...
BACKGROUND
Catatonia is a complex neuropsychiatric disorder involving stupor, waxy flexibility, and mutism lasting more than 1 hour. It has arisen mostly from mental and neurologic disorders. Organic causes are more prominent in children.
CASE
A 15-year-old female who had refused to eat and drink for 3 days, had not talked, and had stood in a fixed position for long periods was admitted to the inpatient clinic, and she was diagnosed with catatonia. Her maximum score on the Bush-Francis Catatonia Rating Scale (BFCRS) was 15/69 on day 2 of her stay. On neurologic examination, the patient`s cooperation was limited, and she was apathetic to her surroundings and stimuli and inactive. Other neurologic examination findings were normal. To investigate catatonia etiology, her biochemical parameters, thyroid hormone panel, and toxicology screening were conducted but all parameters were normal. Cerebrospinal fluid examination and autoimmune antibodies were negative. Sleep electroencephalography showed diffuse slow background activity, and brain magnetic resonance imaging was normal. As a first-line treatment for catatonia, diazepam was started. With her poor response to diazepam, we continued to evaluate the cause and found the transglutaminase levels were 153 U/mL (normal values, < 10 U/mL). The patient`s duodenal biopsies showed changes consistent with Celiac disease (CD). Catatonic symptoms did not benefit from a gluten-free diet or oral diazepam for 3 weeks. Then, diazepam was replaced with amantadine. With amantadine, the patient recovered within 48 hours, and her BFCRS retreated to 8/69.
CONCLUSIONS
Even without gastrointestinal manifestations, CD may present with neuropsychiatric symptoms. According to this case report, CD should be investigated in patients with unexplained catatonia, and that CD may only present with neuropsychiatric symptoms.
Topics: Child; Female; Humans; Adolescent; Catatonia; Celiac Disease; Amantadine; Biopsy; Diazepam
PubMed: 36866995
DOI: 10.24953/turkjped.2022.411 -
Frontiers in Cellular and Infection... 2020The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. CatL is a lysosomal enzyme that participates in numerous physiological processes, including apoptosis, antigen processing, and extracellular matrix remodeling. CatL is implicated in pathological conditions like invasion and metastasis of tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, and other diseases. CatL expression is up-regulated during chronic inflammation and is involved in degrading extracellular matrix, an important process for SARS-CoV-2 to enter host cells. In addition, CatL is probably involved in processing SARS-CoV-2 spike protein. As its inhibition is detrimental to SARS-CoV-2 infection and possibly exit from cells during late stages of infection, CatL could have been considered a valuable therapeutic target. Therefore, we describe here some drugs already in the market with potential CatL inhibiting capacity that could be used to treat COVID-19 patients. In addition, we discuss the possible role of host genetics in the etiology and spreading of the disease.
Topics: Acute Kidney Injury; Amantadine; Angiotensin-Converting Enzyme 2; COVID-19; Cathepsin L; Chloroquine; Cysteine Proteinase Inhibitors; Genetic Predisposition to Disease; Heparin; Humans; Hydroxychloroquine; Lysosomes; Molecular Targeted Therapy; Pandemics; Receptors, Virus; Respiratory Distress Syndrome; SARS-CoV-2; Serine Endopeptidases; Spike Glycoprotein, Coronavirus; Teicoplanin; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33364201
DOI: 10.3389/fcimb.2020.589505 -
The Cochrane Database of Systematic... Dec 2014Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy.
OBJECTIVES
To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy.
SEARCH METHODS
On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials.
MAIN RESULTS
The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo.
AUTHORS' CONCLUSIONS
One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions.There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials.
Topics: Adult; Amantadine; Ascorbic Acid; Charcot-Marie-Tooth Disease; Child; Fatigue; Guillain-Barre Syndrome; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 25519471
DOI: 10.1002/14651858.CD008146.pub2 -
Contemporary Clinical Trials May 2022COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors...
The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.
BACKGROUND
COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications.
METHODS AND RESULTS
The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine.
CONCLUSIONS
Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome.
CLINICAL TRIAL REGISTRATION
www.
CLINICALTRIALS
gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).
Topics: Amantadine; COVID-19; Humans; Respiratory Insufficiency; SARS-CoV-2; Treatment Outcome; Post-Acute COVID-19 Syndrome; COVID-19 Drug Treatment
PubMed: 35390511
DOI: 10.1016/j.cct.2022.106755 -
Revista de Saude Publica 2023To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020.
OBJECTIVE
To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020.
METHODS
National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels.
RESULTS
Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020.
CONCLUSION
The consumption of medicines indicated to treat Alzheimer's disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.
Topics: Humans; Alzheimer Disease; Donepezil; Memantine; Brazil; Cholinesterase Inhibitors; Piperidines; Phenylcarbamates; Indans
PubMed: 37971177
DOI: 10.11606/s1518-8787.2023057005128 -
Progress in Neuro-psychopharmacology &... Dec 2021The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic... (Review)
Review
The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. In this review, we summarize preclinical evidences and clinical trials that investigated the efficacy of memantine in treating patients with alcohol, opiate, cocaine, and nicotine use disorders and discuss the results from a mechanistic point of view. Memantine has shown efficacy in reducing alcohol and opiate craving, consumption, and withdrawal severity. However, in cocaine and nicotine use disorders, memantine did not have significant effect on cravings or consumption. Additionally, memantine was associated with increased subjective effects of alcohol, cocaine, and nicotine. We discuss possible mechanisms behind this variability. Since memantine transiently blocks NMDA receptors and protects neurons from overstimulation by excessive synaptic glutamate, its efficacy should be observed in drug phases that cause hyperglutamatergic states, while hypoglutamatergic drug use states would not resolve with blocking NMDA receptors. Second, memantine pharmacokinetic studies have been done in rodents and healthy volunteers, but not in patients with substance use disorder. Memantine, opiates, cocaine, and nicotine share the same transporter family at the blood brain barrier. This shared transport mechanism could impact brain concentrations of memantine and its effects. In conclusion, memantine remains an intriguing compound in our pharmacopeia with controversial results in treating certain aspects of drug addiction. Further studies are needed to understand the clinical and biological correlates of its efficacy.
Topics: Animals; Brain; Cocaine; Ethanol; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; Neurons; Opiate Alkaloids; Receptors, N-Methyl-D-Aspartate; Substance-Related Disorders
PubMed: 34324921
DOI: 10.1016/j.pnpbp.2021.110409 -
BMJ Open Jan 2024Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although...
Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial.
INTRODUCTION
Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.
METHODS AND ANALYSIS
The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5-4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12-18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.
ETHICS AND DISSEMINATION
The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.
TRIAL REGISTRATION NUMBER
EudraCT 2021-004868-95; NCT05809414.
Topics: Adult; Humans; Multiple Sclerosis; Transcranial Magnetic Stimulation; Quality of Life; Amantadine; Double-Blind Method; Fatigue; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 38176857
DOI: 10.1136/bmjopen-2023-078661