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Neuroscience and Biobehavioral Reviews Sep 2017The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have... (Review)
Review
The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions.
Topics: Appetite; Brain; Gastrointestinal Tract; Hormones; Humans; Satiation
PubMed: 28669754
DOI: 10.1016/j.neubiorev.2017.06.013 -
Developmental Medicine and Child... Sep 2021To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and... (Meta-Analysis)
Meta-Analysis
AIM
To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia.
METHOD
Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE.
RESULTS
Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis.
INTERPRETATION
Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.
Topics: Baclofen; Botulinum Toxins; Cerebral Palsy; Clonidine; Deep Brain Stimulation; Dystonia; Humans; Injections, Spinal; Levodopa; Neurosurgical Procedures; Trihexyphenidyl
PubMed: 33772789
DOI: 10.1111/dmcn.14874 -
Biology of Blood and Marrow... Mar 2020Relapse after stem cell transplantation for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic... (Review)
Review
Relapse after stem cell transplantation for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first-generation TKI imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph+ ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). We performed database searches (inception to January 2018) using PubMed, Cochrane Library, and Embase. After exclusions, 17 articles were included in this analysis. Imatinib was used post-transplant either prophylactically or preemptively in 12 studies, 7 prospective studies and 5 retrospective studies. Overall survival (OS) for most prospective studies at 1.5 to 3 and 5 years ranged between 62% to 92% and 74.5% to 86.7%. Disease-free survival at 1.5 to 5 years was 60.4% to 92%. Additionally, imatinib failed to show survival benefit in patients who were >CR1 at the time of allo-HSCT. The cumulative OS for most retrospective studies using imatinib at 1 to 2 and 3 to 5 years was 42% to 100% and 33% to 40% respectively. Event-free survival at 1 to 2 and 3 to 5 years was 33.3% to 67% and 20% to 31% respectively. Dasatinib was used as maintenance treatment in 3 retrospective studies (n = 34). The OS for patients with Ph+ ALL using dasatinib as maintenance regimen after allo-HSCT at 1.4 to 3 years was 87% to 100% and disease-free survival at 1.4 to 3 years was 89% to 100%. Ninety-three percent of patients with minimal residual disease (MRD) positive status after allo-HSCT became MRD negative. Three prospective studies used nilotinib. In 2 studies where investigators studied patients with advanced chronic myeloid leukemia and Ph+ ALL, the cumulative OS and event-free survival at 7.5 months to 2 years were 69% to 84% and 56% to 84%, respectively. In the third study (n = 5) in patients with Ph+ ALL, nilotinib use resulted in OS at 5 years of 60%. Our review showed that use of TKIs (all generations) after allo-HSCT for patients in CR1 improved OS when given as a prophylactic or preemptive regimen. Limited data suggest that second-generation TKIs (ie, dasatinib) have a better OS, especially in patients with MRD-positive status. Imatinib did not improve OS in patients who were >CR1 at the time of allo-HSCT; for this population, no data were available with newer generation TKIs. The evaluation of survival benefit with newer generation TKIs and their efficacy in patients in >CR1 needs further study in large randomized clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Protein Kinase Inhibitors; Retrospective Studies; Secondary Prevention; Transplantation, Homologous
PubMed: 31557532
DOI: 10.1016/j.bbmt.2019.09.022 -
Lung Cancer (Amsterdam, Netherlands) Oct 2023Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of... (Meta-Analysis)
Meta-Analysis Review
Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis.
OBJECTIVE
Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of different ALK-TKIs to guide clinical decision making.
MATERIALS AND METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Data were analyzed using random effects and consistency models under the frequency framework.
RESULTS
Of 865 relevant studies, 13 RCTs (encompassing 3,353 patients) were finally included. A network meta-analysis of all-grade AEs, fatal AEs, and treatment discontinuation due to AEs revealed no significant differences among the six ALK-TKIs. The rates of grade 3-4 AEs were: alectinib (16.2%), crizotinib (46.4%), brigatinib (63.7%), ensartinib (75.6%), ceritinib (78.3%), and lorlatinib (91.6%). The toxicity spectra of ALK-TKIs were different. The most frequent AEs associated with crizotinib were gastrointestinal reactions, visual disorders, neutropenia, edema, fatigue, and elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, while those in the alectinib group were anemia and constipation. Diarrhea, hepatotoxicity, and increased serum creatinine were most common with ceritinib. The most frequent AEs in the brigatinib group were gastrointestinal reactions, hypertension, cough, headache, and elevated ALT or AST levels. The most significant toxicities of ensartinib were skin disorders, including pruritus and rash. Changes in lipid levels were the most frequent AEs associated with lorlatinib; weight gain, cognitive effects, and mood effects were lorlatinib-specific AEs.
CONCLUSIONS
The toxicity spectra of ALK-TKIs differed. Alectinib might be the safest ALK-TKI drug according to the combined evidence of grades 3-4 AEs and the combined incidence.
Topics: Humans; Anaplastic Lymphoma Kinase; Protein-Tyrosine Kinases; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Crizotinib; Network Meta-Analysis; Lung Neoplasms; Protein Kinase Inhibitors
PubMed: 37597303
DOI: 10.1016/j.lungcan.2023.107319 -
Clinical Lung Cancer Sep 2023MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was... (Review)
Review
INTRODUCTION
MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was recently approved. Given the heterogeneity in published data of METex14 skipping NSCLC, we conducted a systematic literature review to evaluate its frequency, patient characteristics, and outcomes.
METHODS
On June 13, 2022 we conducted a systematic literature review of publications and conference abstracts reporting frequency, patient characteristics, or outcomes of patients with METex14 skipping NSCLC.
RESULTS
We included 139 studies reporting frequency or patient characteristics (350,997 patients), and 39 studies reporting clinical outcomes (3989 patients). Median METex14 skipping frequency was 2.0% in unselected patients with NSCLC, with minimal geographic variation. Median frequency was 2.4% in adenocarcinoma or nonsquamous subgroups, 12.0% in sarcomatoid, and 1.3% in squamous histology. Patients with METex14 skipping NSCLC were more likely to be elderly, have adenocarcinoma histology; there was no marked sex or smoking status distribution. In first line of treatment, median objective response rate ranged from 50.7% to 68.8% with targeted therapies (both values correspond to MET TKIs), was 33.3% with immunotherapy, and ranged from 23.1% to 27.0% with chemotherapy.
CONCLUSIONS
Patients with METex14 skipping are more likely to have certain characteristics, but no patient subgroup can be ruled out; thus, it is crucial to test all patients with NSCLC to identify suitable candidates for MET inhibitor therapy. MET TKIs appeared to result in higher efficacy outcomes, although no direct comparison with chemotherapy or immunotherapy regimens was found.
Topics: Aged; Humans; Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Exons; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met
PubMed: 37451931
DOI: 10.1016/j.cllc.2023.06.008 -
Advanced Drug Delivery Reviews Jan 2020Skin pigmentation is a result of melanin produced by melanocytes in the epidermis. Melanocyte activity, along with the type and distribution of melanins, is the main...
Skin pigmentation is a result of melanin produced by melanocytes in the epidermis. Melanocyte activity, along with the type and distribution of melanins, is the main driver for diversity of skin pigmentation. Dark melanin acts to protect against the deleterious effects of ultraviolet (UV) radiation, including photo-aging and skin cancer formation. In turn, UV radiation activates skin melanocytes to induce further pigmentation (i.e., "tanning pathway"). The well-characterized MSH/MC1R-cAMP-MITF pathway regulates UV-induced melanization. Pharmacologic activation of this pathway ("sunless tanning") represents a potential strategy for skin cancer prevention, particularly in those with light skin or the "red hair" phenotype who tan poorly after UV exposure due to MC1R inactivating polymorphisms. Skin hyperpigmentation can also occur as a result of inflammatory processes and dermatological disorders such as melasma. While primarily of cosmetic concern, these conditions can dramatically impact quality of life of affected patients. Several topical agents are utilized to treat skin pigmentation disorders. Here, we review melanogenesis induced by UV exposure and the agents that target this pathway.
Topics: Administration, Cutaneous; Cyclic AMP; Dermatologic Agents; Drug Delivery Systems; Humans; Melanins; Pigmentation Disorders; Protein Kinases; Skin Pigmentation; Ultraviolet Rays
PubMed: 32092380
DOI: 10.1016/j.addr.2020.02.002 -
Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
Advances in Nutrition (Bethesda, Md.) Dec 2021Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise...
Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise unpredictable motor fluctuations and other complications. Counteracting these complications with other pharmacological therapies may prompt a vicious circle of side effects, and here, nutritional therapy may have great potential. Knowledge about the role of diet in PD is emerging and multiple studies have investigated nutritional support specifically with respect to levodopa therapy. With this systematic review, we aim to give a comprehensive overview of dietary approaches to optimize levodopa treatment in PD. A systematic search was performed using the databases of PubMed and Scopus between January 1985 and September 2020. Nutritional interventions with the rationale to optimize levodopa therapy in human PD patients were eligible for this study and their quality was assessed with the Cochrane risk-of-bias tool. In total, we included 22 papers that addressed the effects of dietary proteins (n = 10), vitamins (n = 7), fiber (n = 2), soybeans (n = 1), caffeine (n = 1), and ketogenic diets (n = 1) on levodopa therapy. Interventions with protein redistribution diets (PRDs), dietary fiber, vitamin C, and caffeine improved levodopa absorption, thereby enhancing clinical response and reducing motor fluctuations. Furthermore, supplementation of vitamin B-12, vitamin B-6, and folic acid successfully reduced high homocysteine concentrations that emerged from levodopa metabolism and promoted many metabolic and clinical complications, such as neuropathology and osteoporosis. In conclusion, dietary interventions have the potential to optimize levodopa efficacy and control side effects. Nutrition that improves levodopa absorption, including PRDs, fiber, vitamin C, and caffeine, is specifically recommended when fluctuating clinical responses appear. Supplements of vitamin B-12, vitamin B-6, and folic acid are advised along with levodopa initiation to attenuate hyperhomocysteinemia, and importantly, their potential to treat consequent metabolic and clinical complications warrants future research.
Topics: Antiparkinson Agents; Diet; Humans; Levodopa; Parkinson Disease; Vitamin B 12
PubMed: 34113965
DOI: 10.1093/advances/nmab060 -
European Journal of Clinical... Dec 2020To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease.
METHODS
We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson's disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.
RESULTS
Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.
CONCLUSIONS
Dopamine agonists were found to be effective as treatment for Parkinson's disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.
Topics: Dopamine Agonists; Drug Therapy, Combination; Humans; Indans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 32710141
DOI: 10.1007/s00228-020-02961-6 -
BMJ Clinical Evidence Aug 2007Around 1% of adults have Parkinson's disease, with a median time of 9 years between diagnosis and death. (Review)
Review
INTRODUCTION
Around 1% of adults have Parkinson's disease, with a median time of 9 years between diagnosis and death.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with early-stage Parkinson's disease? What are the effects of adding other treatments in people with Parkinson's disease who have motor complications from levodopa? What are the effects of surgery in people with later Parkinson's disease? What are the effects of nursing and rehabilitation treatments in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding a catechol-methyl transferase inhibitor, or dopamine agonist to levodopa; amantadine; dopamine agonists; levodopa (immediate-release, modified-release); monoamine oxidase B inhibitors; occupational therapy; pallidal deep brain stimulation; pallidotomy; Parkinson's disease nurse specialist interventions; physiotherapy; speech and language therapy; subthalamic nucleus deep brain stimulation; subthalamotomy; swallowing therapy; thalamic deep brain stimulation; and thalamotomy.
Topics: Deep Brain Stimulation; Globus Pallidus; Humans; Levodopa; Parkinson Disease; Subthalamic Nucleus
PubMed: 19454106
DOI: No ID Found