RESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is the third most common type of muscular dystrophy. This disease presents as a slowly progressive asymmetric muscle weakness that involves the facial, scapular, and upper arm muscles mainly. Currently, there is no established consensus on this disease treatment in terms of medications. We assessed the response to the treatment of the drugs utilized in clinical trials by performing a systematic literature review in English using the preferred reporting items for systematic reviews (PRISMA) and meta-analyses. We only used human clinical trials in patients diagnosed with FSHD that received consistent pharmacological treatment. We included 11 clinical trials that fulfilled our criteria. We concluded that albuterol had statistically significant results in three out of four clinical trials, with improved elbow flexors muscle strength. Vitamin C, vitamin E, zinc gluconate, and selenomethionine showed significant improvement in the maximal voluntary contraction and endurance limit time of quadriceps muscle. At the same time, diltiazem and MYO-029 demonstrate no improvement in function, strength, or muscle mass. Losmapimod, currently in phase I of the ReDUX4 trial, showed promising results. Peradventure, more clinical trials are still needed to address this subject. Nevertheless, this review provides a clear and concise update on the treatment for this disease.
RESUMO
Neurogenic orthostatic hypotension (nOH) is a disabling problem of autonomic dysfunction in patients with Parkinson's disease, which is associated with poor quality of life and higher mortality rates. The purpose of this literature review was to explore and compare the efficacy and safety of droxidopa (an existing treatment) and ampreloxetine (a newer medication) in the treatment of nOH. We used a mixed-method literature review that addresses the epidemiology, pathophysiology, and pharmacological and non-pharmacological management of nOH in Parkinson's disease in a general way, with a more exploratory approach to droxidopa- and ampreloxetine-controlled trial studies. We included a total of 10 studies of randomized controlled trials with eight studies focused on droxidopa and two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH in Parkinson's disease patients with droxidopa or ampreloxetine showed clinically meaningful and statistically significant improvements relative to placebo on the components of the OHSA (Orthostatic Hypotension Symptom Assessment) composite score and OHDAS (Orthostatic Hypotension Daily Activity Scale composite scores) composite score. Droxidopa had an improved effect on daily activities, with an associated increase in standing systolic blood pressure (BP), but the long-term efficacy of droxidopa has not been documented. Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.
RESUMO
Delirium superimposed on dementia (DSD) occurs when patients with pre-existing dementia develop delirium. This complication causes patients to become impaired, posing safety concerns for both hospital staff and patients. Furthermore, there is an increased risk of worsening functional disability and death. Despite medical advances, DSD provides both diagnostic and therapeutic challenges to providers. Identifying at-risk patients and providing personalized medicine and patient care can decrease disease burden in a time-efficient manner. This review delves into bioinformatics-based studies of DSD in order to design and implement a personalized medicine-based approach. Our findings suggest alternative medical treatment methods based on gene-gene interactions, gene-microRNA (miRNA) interactions, gene-drug interactions, and pharmacogenetic variants involved in dementia and psychiatric disorders. We identify 17 genes commonly associated with both dementia and delirium including apolipoprotein E (ApoE), brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), butyrylcholinesterase (BChE), acetylcholinesterase (AChE), DNA methyltransferase 1 (DNMT1), prion protein (PrP), tumor necrosis factor (TNF), serine palmitoyltransferase long chain base subunit 1 (SPTLC1), microtubule-associated protein tau (MAPT), alpha-synuclein (αS), superoxide dismutase 1 (SOD1), amyloid beta precursor protein (APP), neurofilament light (NFL), neurofilament heavy, 5-hydroxytryptamine receptor 2A (HTR2A), and serpin family A member 3 (ERAP3). In addition, we identify six main genes that form an inner concentric model, as well as their associated miRNA. The FDA-approved medications that were found to be effective against the six main genes were identified. Furthermore, the PharmGKB database was used to identify variants of these six genes in order to suggest future treatment options. We also looked at previous research and evidence on biomarkers that could be used to detect DSD. According to research, there are three types of biomarkers that can be used depending on the stage of delirium. The pathological mechanisms underlying delirium are also discussed. This review will identify treatment and diagnostic options for personalized DSD management.
