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Nutrients Dec 2023Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and... (Review)
Review
BACKGROUND
Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.
METHODS
The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.
RESULTS
Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.
CONCLUSIONS
Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Topics: Humans; Plant Extracts; Withania; Hydrocortisone; Plants, Medicinal; Antioxidants
PubMed: 38140274
DOI: 10.3390/nu15245015 -
Nutrients Sep 2023The benefits of zinc in treating certain gastrointestinal (GI) diseases have been recognized for over two decades. This review aims to explore zinc deficiency (ZD) and... (Review)
Review
The benefits of zinc in treating certain gastrointestinal (GI) diseases have been recognized for over two decades. This review aims to explore zinc deficiency (ZD) and the potential therapeutic value and safety of zinc supplementation in pediatric GI diseases. A systematic review of published articles on ZD and zinc as adjuvant treatments for GI diseases was conducted using various databases. Children with inflammatory bowel disease (IBD), celiac disease, and those receiving long-term proton pump inhibitor treatments are particularly susceptible to ZD. ZD in children with celiac disease and IBD is attributed to insufficient intake, reduced absorption, and increased intestinal loss as a result of the inflammatory process. Zinc plays a crucial role in maintaining the integrity of the gastric mucosa and exerts a gastroprotective action against gastric lesions. Although considerable evidence supports the use of zinc as adjuvant therapy for certain GI diseases in adults, its use is unspecified in children except for infectious diarrhea. Current evidence suggests that zinc supplementation with well-documented dosages helps reduce the duration of diarrhea in children with acute or persistent diarrhea, while there are no specific guidelines for zinc supplementation in children with IBD and celiac disease. Zinc supplementation appears to be beneficial in peptic ulcer disease or gastroesophageal reflux disease. The available evidence highlights the need for intervention programs to enhance zinc status and reduce the morbidity of certain GI diseases in children.
Topics: Adult; Child; Humans; Zinc; Celiac Disease; Diarrhea; Dietary Supplements; Inflammatory Bowel Diseases
PubMed: 37836377
DOI: 10.3390/nu15194093 -
European Archives of... Apr 2023Synkinesis is defined as involuntary movements accompanying by voluntary movements and can occur during the aftermath of peripheral facial palsy, causing functional,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Synkinesis is defined as involuntary movements accompanying by voluntary movements and can occur during the aftermath of peripheral facial palsy, causing functional, aesthetic and psychological problems in the patient. Botulinum toxin A (BTX-A) is frequently used as a safe and effective treatment; however, there is no standardized guideline for the use of BTX-A in synkinesis. The purpose of this article is to review and summarize studies about the BTX-A treatment of synkinesis in patients with a history of peripheral facial palsy; including given dosages, injection sites and time intervals between injections.
MATERIALS AND METHODS
A multi-database systematic literature search was performed in October 2020 using the following databases: Pubmed, Embase, Medline, and The Cochrane Library. Two authors rated the methodological quality of the included studies independently using the 'Newcastle-Ottawa Quality Assessment Scale' for non-randomised studies' (NOS).
RESULTS
Four-thousand-five-hundred-and-nineteen articles were found of which 34 studies met the inclusion criteria, in total comprising 1314 patients. Most studies were assessed to be of 'fair' to 'good' methodological quality. The Cohen's kappa (between author FJ and AS) was 0.78. Thirty-one studies investigated the reported dosage injected, 17 studies reported injection location and 17 studies investigated time intervals. A meta-analysis was performed for three studies comprising 106 patients, on the effects of BTX-A treatment on the Synkinesis Assessment Questionnaire (SAQ) scores. The mean difference was 11.599 (range 9.422-13.766), p < 0.01. However, due to inconsistent reporting of data of the included studies, no relationship with the dosage and location could be assessed.
CONCLUSIONS
Many treatment strategies for synkinesis exist, consisting of varying BTX-A brands, dosages, time intervals and different injection locations. Moreover, the individual complaints are very specific, which complicates creating a standardized chemodenervation treatment protocol. The BTX-A treatment of long-term synkinesis is very individual and further studies should focus on a patient-tailored treatment instead of trying to standardize treatment.
Topics: Humans; Botulinum Toxins, Type A; Facial Paralysis; Synkinesis; Bell Palsy; Treatment Outcome
PubMed: 36544062
DOI: 10.1007/s00405-022-07796-8 -
The Journal of Urology Nov 2023Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms and discomfort. Prior studies have examined the effects of various medication regimens on ureteral stent symptoms. This study utilized Bayesian network meta-analysis to analyze all available evidence on the pharmacological management of ureteral stent-related symptoms.
MATERIALS AND METHODS
In December 2022 a systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines on randomized prospective studies on pharmacological management of ureteral stent-related symptoms reporting outcomes using the Ureteral Stent Symptom Questionnaire score on urinary symptoms and pain. The data were analyzed in Review Manager 5.3 and R Studio where a Bayesian network meta-analysis was performed. Treatments were ranked using surface under the cumulative ranking curve and mean difference vs placebo with 95% credible intervals.
RESULTS
A total of 26 studies were analyzed. These were used to build networks which were modeled to run 100,000 Markov Chain Montecarlo simulations each. Drug-class analysis revealed the most effective class for each domain: for urinary symptoms, sexual performance, general health, and work performance-combined α-blocker and anticholinergic and phosphodiesterase 5 inhibitors; for pain-combined anticholinergic and pregabalin. The following were the most effective drugs and dosages for specific symptoms: for urinary symptoms-combined silodosin 8 mg+solifenacin 10 mg; for pain-combined silodosin 8 mg+solifenacin 10 mg; for sexual performance-tadalafil 5 mg. Combined silodosin 8 mg+solifenacin 10 mg+tadalafil 5 mg has the best general health scores while solifenacin 10 mg had the best work experience scores.
CONCLUSIONS
This network meta-analysis demonstrated that the most effective drug therapy is different for each symptom domain. It is important to consider a patient's chief complaint and domains in order to ascertain the optimal medication regimen for each patient. Further iterations of this analysis can be strengthened by trials that directly compare more of these drugs instead of relying on indirect evidence.
Topics: Humans; Solifenacin Succinate; Tadalafil; Network Meta-Analysis; Prospective Studies; Bayes Theorem; Quality of Life; Ureter; Pain; Cholinergic Antagonists; Stents
PubMed: 37428119
DOI: 10.1097/JU.0000000000003616 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
CNS Drugs Jan 2016Several case reports and epidemiological studies have raised concern about the abuse potential of pregabalin, the use of which has increased substantially over the last... (Review)
Review
BACKGROUND
Several case reports and epidemiological studies have raised concern about the abuse potential of pregabalin, the use of which has increased substantially over the last decade. Pregabalin is, in some cases, used for recreational purposes and it has incurred attention among drug abusers for causing euphoric and dissociative effects when taken in doses exceeding normal therapeutic dosages or used by alternative routes of administration, such as nasal insufflation or venous injection. The magnitude of the abuse potential and the mechanism behind it are not fully known.
OBJECTIVE
The aim of this study was to present a systematic review of the data concerning the abuse potential of pregabalin.
METHODS
We performed a systematic literature search and reviewed the preclinical, clinical and epidemiological data on the abuse potential of pregabalin.
RESULTS
We included preclinical (n = 17), clinical (n = 19) and epidemiological (n = 13) studies addressing the abuse potential of pregabalin. We also reviewed case reports (n = 9) concerning abuse of pregabalin. The preclinical studies indicated that pregabalin possesses modulatory effects on the GABA and glutamate systems, leaving room for an abuse potential. Further, clinical studies reported euphoria as a frequent side effect in patients treated with pregabalin. The majority of case reports concerning abuse of pregabalin involved patients with a history of substance abuse and, similarly, epidemiological studies found evidence of abuse, especially among opiate abusers.
CONCLUSIONS
Overall, the available literature suggests an important clinical abuse potential of pregabalin and prescribers should pay attention to signs of abuse, especially in patients with a history of substance abuse.
Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Euphoria; Humans; Illicit Drugs; Pregabalin; Prescription Drug Misuse; Substance-Related Disorders
PubMed: 26767525
DOI: 10.1007/s40263-015-0303-6 -
International Immunopharmacology Apr 2023This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research. (Review)
Review
OBJECTIVE
This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research.
BACKGROUND
Migraine is a chronic neurovascular disorder that causes disability and a social burden. There are various medications used for migraine prevention regimens, most of which have unwanted side effects and aren't often quite effective. Erenumab is a monoclonal antibody that targets calcitonin gene-related peptide receptors and was recently approved by the Food and Drug Administration for migraine prevention.
METHODS
For this systematic review, we searched through Scopus and PubMed databases using "Erenumab" or "AMG 334" and "migraine" as keywords, and all the studies from 2016 to March 18, 2022, were included. Original English articles assessing any outcomes referring to the efficacy of Erenumab in migraine headache treatment were included in this study.
RESULTS
We found 53 out of 605 papers eligible to be investigated. Erenumab in both dosages of 70 mg and 140 mg could decrease the mean of monthly migraine days and monthly acute migraine-specific medication days. Erenumab also has a higher rate of ≥ 50 %, ≥ 75 %, and 100 % reduction in monthly migraine days from the baseline in different regions. The efficacy of Erenumab was initiated in the first week of administration and sustained throughout and after treatment. Erenumab was also potent in the treatment of migraine with allodynia, aura, prior preventive therapy failure, medication overuse headache, and menstrual migraine. Erenumab also had favorable outcomes in combination therapy with other preventive drugs like Onabotulinumtoxin-A.
CONCLUSION
Erenumab had remarkable efficacy in the short and long-term treatment of episodic and chronic migraine, notably the patients with difficult-to-treat migraine headaches.
Topics: Humans; Calcitonin Gene-Related Peptide Receptor Antagonists; Migraine Disorders; Antibodies, Monoclonal; Chronic Disease; Combined Modality Therapy
PubMed: 37012858
DOI: 10.1016/j.intimp.2022.109366 -
Medicine Nov 2023This systematic review explores the most current evidence regarding the mechanisms of neuropathic pain in patients with different types of diabetes and how this pain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review explores the most current evidence regarding the mechanisms of neuropathic pain in patients with different types of diabetes and how this pain affects different functional and structural components of the neuroanatomical pain pathways. The review also seeks to provide guidelines for the best approach and treatment for patients experiencing this type of pain. The objective is to determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II.
OBJECTIVE
To determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II.
METHODS
We systematically search MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and Web of Science databases.
RESULTS
The findings of this review show that different forms of ALA do not present statistically significant changes for any of the scales included, including total symptom score (standardized mean difference [SMD] = -3.59, confidence interval [CI] = -4.16 to -3.02, and P < .00001), neuropathy impairment score (SMD = -1.42, CI = -3.68 to 0.84, and P = .22), and neuropathy symptom checklist (SMD = -0.09, CI = -0.15 to -0.02, and P = .01).
CONCLUSION
In comparison to the use of a placebo, the findings suggest that ALA does not exhibit significant differences in terms of pain reduction and different functional scales. Moreover, no specific dosages are identified to support the use of ALA for the reduction of neuropathic pain.
Topics: Humans; Thioctic Acid; Diabetes Mellitus, Type 2; Neuralgia; Antioxidants; Diabetes Mellitus, Type 1
PubMed: 37933068
DOI: 10.1097/MD.0000000000035368 -
The Cochrane Database of Systematic... Apr 2015Multiple sclerosis (MS) often leads to severe neurological disability and a serious decline in quality of life. The ideal target of disease-modifying therapy for MS is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) often leads to severe neurological disability and a serious decline in quality of life. The ideal target of disease-modifying therapy for MS is to prevent disability worsening and improve quality of life. Dimethyl fumarate is considered to have an immunomodulatory activity and neuroprotective effect. It has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency as a first-line therapy for adult patients with relapsing-remitting MS (RMSS).
OBJECTIVES
To assess the benefit and safety of dimethyl fumarate as monotherapy or combination therapy versus placebo or other approved disease-modifying drugs (interferon beta, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, alemtuzumab) for patients with MS.
SEARCH METHODS
The Trials Search Co-ordinator searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (4 June 2014). We checked reference lists of published reviews and retrieved articles and searched reports (2004 to June 2014) from the MS societies in Europe and America. We also communicated with investigators participating in trials of dimethyl fumarate and the Biogen Idec Medical Information.
SELECTION CRITERIA
We included randomised, controlled, parallel-group clinical trials (RCTs) with a length of follow-up equal to or greater than one year evaluating dimethyl fumarate, as monotherapy or combination therapy, versus placebo or other approved disease-modifying drugs for patients with MS without restrictions regarding dosage, administration frequency and duration of treatment.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures of The Cochrane Collaboration. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. We contacted the principal investigators of included studies for additional data or confirmation of data.
MAIN RESULTS
Two RCTs were included, involving 2667 adult patients with RRMS to evaluate the efficacy and safety of two dosages of dimethyl fumarate (240 mg orally three times daily or twice daily) by direct comparison with placebo for two years. Among them, a subsample of 1221 (45.8%) patients were selected to participate in MRI evaluations by each study site with MRI capabilities itself. No powered head-to-head study with an active treatment comparator has been found. Meta-analyses showed that dimethyl fumarate both three times daily and twice daily reduced the number of patients with a relapse (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.50 to 0.66, P < 0.00001 and 0.64, 95% CI 0.54 to 0.77, P < 0.00001, respectively) or disability worsening (RR 0.70, 95% CI 0.57 to 0.87, P = 0.0009 and 0.65, 95% CI 0.53 to 0.81, P = 0.0001, respectively) over two years, compared to placebo. The treatment effects were decreased in the likely-case scenario analyses taking the effect of dropouts into consideration. Both dosages also reduced the annualised relapse rate. Data of active lesions on MRI scans were not combined because there was a high risk of selection bias for MRI outcomes and imprecision of MRI data in both studies, as well as an obvious heterogeneity between the studies. In terms of safety profile, both dosages increased the risk for adverse events and the risk for drug discontinuation due to adverse events. The most common adverse events included flushing and gastrointestinal events (upper abdominal pain, nausea and diarrhoea). Uncommon adverse events included lymphopenia and leukopenia, but they were more likely to happen with dimethyl fumarate than with placebo (high dosage: RR 5.25, 95% CI 2.20 to 12.51, P = 0.0002 and 5.23, 95% CI 2.47 to 11.07, P < 0.0001, respectively; low dosage: RR 5.69, 95% CI 2.40 to 13.46, P < 0.0001 and 6.53, 95% CI 3.13 to 13.64, P < 0.00001, respectively). Both studies had a high attrition bias resulting from the unbalanced reasons for dropouts among groups. Quality of evidence for relapse outcome was moderate, but for disability worsening was low.
AUTHORS' CONCLUSIONS
There is moderate-quality evidence to support that dimethyl fumarate at a dose of 240 mg orally three times daily or twice daily reduces both the number of patients with a relapse and the annualised relapse rate over two years of treatment in comparison with placebo. However, the quality of the evidence to support the benefit in reducing the number of patients with disability worsening is low. There is no high-quality data available to evaluate the benefit on MRI outcomes. The common adverse effects such as flushing and gastrointestinal events are mild-to-moderate for most patients. Lymphopenia and leukopenia are uncommon adverse events but significantly associated with dimethyl fumarate. Both dosages of dimethyl fumarate have similar benefit and safety profile, which supports the option of low-dose administration. New studies of high quality and long-term follow-up are needed to evaluate the benefit of dimethyl fumarate on prevention of disability worsening and to observe the long-term adverse effects including progressive multifocal leukoencephalopathy.
Topics: Administration, Oral; Adult; Dimethyl Fumarate; Drug Administration Schedule; Fumarates; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 25900414
DOI: 10.1002/14651858.CD011076.pub2 -
Clinical Therapeutics Nov 2020This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.
METHODS
A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the C and AUC estimates for all INH dosages.
FINDINGS
Ninety studies were included in this systematic review. TB status significantly affected the INH C and AUC estimates. In healthy volunteers, the dose-normalized INH C and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized C and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized C and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH C and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.
IMPLICATIONS
The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.
Topics: Adult; Antitubercular Agents; Arylamine N-Acetyltransferase; Drug Monitoring; Humans; Isoniazid; Tuberculosis
PubMed: 33032843
DOI: 10.1016/j.clinthera.2020.09.009