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Cureus Sep 2023This systematic review and meta-analysis determine how frequently and how seriously gastrointestinal manifestations affect people with type 2 diabetes mellitus on... (Review)
Review
This systematic review and meta-analysis determine how frequently and how seriously gastrointestinal manifestations affect people with type 2 diabetes mellitus on tirzepatide. Tirzepatide is a recently developed drug that attempts to enhance type 2 diabetics' ability to regulate their blood sugar levels and promote weight reduction. Despite its potential benefits, clinical trials have revealed that the medication may lead to gastrointestinal side effects, including nausea, vomiting, decreased appetite, dyspepsia, constipation, and diarrhea. These side effects may negatively affect the drug's efficacy and patient tolerance. A comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library, was conducted to find pertinent studies reporting on the frequency and severity of gastrointestinal symptoms in type 2 diabetes patients receiving tirzepatide. This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Study selection, data extraction, and quality assessment were performed. Six randomized controlled trials with a total of 4,586 patients were included. Most patients received tirzepatide to regulate their blood sugar levels and promote weight reduction, and the comparators were placebo, glucagon-like peptide one receptor agonists drugs, and insulin degludec. The dose of tirzepatide was 5mg, 10mg, and 15mg weekly. The incidence rate of nausea in patients who receive tirzepatide was 20.43%, while the incidence rate in the comparators was 10.47%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.90; 95% CI, 1.89 to 4.44; P ≤ 0.00001). The incidence rate of vomiting in patients who receive tirzepatide was 9.05%, while the rate in the comparators was 4.86%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.69; 95% CI, 1.67 to 4.36; P ≤ 0.0001). The incidence rate of constipation in patients who receive tirzepatide was 2.54%, while the rate in the comparators was 0.856%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 3.08; 95% CI, 1.83 to 5.20; P ≤ 0.0001). The incidence rate of decreased appetite in patients who receive tirzepatide was 9.64%, while the rate in the comparators was 2.88%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 5.04; 95% CI, 3.01 to 8.45; P ≤ 0.00001). The incidence rate of diarrhea in patients who receive tirzepatide was 16.24%, while the rate in the comparators was 8.63%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.07; 95% CI, 1.60 to 2.68; P ≤ 0.00001). The incidence rate of dyspepsia in patients who receive tirzepatide was 7.13%, while the rate in the comparators was 3.31%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.52; 95% CI, 1.58 to 4.01; P ≤ 0.0001). Tirzepatide usage is linked to a significant prevalence of gastrointestinal symptoms, including nausea, constipation, decreased appetite, dyspepsia, diarrhea, and vomiting, in people with type 2 diabetes. These findings may influence clinical decision-making and patient counseling on the use of tirzepatide and have significant implications for the medication's tolerance and efficacy. To find ways to reduce these negative effects and improve therapy for type 2 diabetes patients, more research is required.
PubMed: 37908927
DOI: 10.7759/cureus.46091 -
Autoimmunity Reviews Sep 2013The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors... (Review)
Review
OBJECTIVES
The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy.
SYSTEMATIC REVIEW METHODOLOGY
Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed.
RESULTS AND CONCLUSION
Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50years, and females are affected more frequently, with a female:male ratio of 2:1. The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.
Topics: Autoimmune Diseases; HLA-DRB1 Chains; Humans; Self Tolerance; Uveomeningoencephalitic Syndrome
PubMed: 23567866
DOI: 10.1016/j.autrev.2013.01.004 -
Neuroscience and Biobehavioral Reviews Oct 2018Previous studies have reported conflicting results in terms of acute effects of cannabis in man. Independently of other factors, such discrepancy may be attributable to...
Previous studies have reported conflicting results in terms of acute effects of cannabis in man. Independently of other factors, such discrepancy may be attributable to the different cannabis use history of study volunteers. It is thought that regular cannabis users may develop tolerance to the effects of acute cannabis administration. Here we systematically review all studies examining the effects of single or repeated cannabinoid administration in man as a function of previous cannabis exposure. Research evidence tends to suggest that the acute effects of single cannabinoid administration are less prominent in regular cannabis users compared to non-regular users. Studies of repeated cannabinoid administration more consistently suggest less prominent effects upon repeated exposure. Cognitive function is the domain showing the highest degree of tolerance, with some evidence of complete absence of acute effect (full tolerance). The acute intoxicating, psychotomimetic, and cardiac effects are also blunted upon regular exposure, but to a lesser extent (partial tolerance). Limited research also suggests development of tolerance to other behavioral, physiological, and neural effects of cannabis.
Topics: Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Drug Tolerance; Humans; Marijuana Abuse; Marijuana Use
PubMed: 30056176
DOI: 10.1016/j.neubiorev.2018.07.014 -
The Cochrane Database of Systematic... Mar 2015Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
SEARCH METHODS
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Date of last search: 11 August 2014.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 4 September 2014We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
SELECTION CRITERIA
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data.
MAIN RESULTS
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 μmol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 μmol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS
There is evidence of short-term benefit from using sapropterin in some people with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
Topics: Adult; Biopterins; Child; Child, Preschool; Humans; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 25812600
DOI: 10.1002/14651858.CD008005.pub4 -
Journal of Drug Assessment 2021Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with...
OBJECTIVE
Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI).
METHODS
A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT).
RESULTS
Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, < .005).
CONCLUSIONS
Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.
PubMed: 34676131
DOI: 10.1080/21556660.2021.1989194 -
L'Encephale Dec 2022Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's...
OBJECTIVES
Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation.
METHODS
Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment », « hypersalivation », « induced », « drug », « clozapine »). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study.
RESULTS
Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63).
CONCLUSIONS
In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.
Topics: Female; Humans; Male; Sialorrhea; Clozapine; Quality of Life; Amisulpride; Scopolamine; Cholinergic Antagonists; Antipsychotic Agents
PubMed: 35989107
DOI: 10.1016/j.encep.2022.03.013 -
The Clinical Journal of Pain May 2014A review of the literature was conducted to assess the association between oxytocin (OT) and pain. (Review)
Review
OBJECTIVES
A review of the literature was conducted to assess the association between oxytocin (OT) and pain.
METHODS
PsychInfo, PubMed, and Medline (EBSCO) research databases were searched for peer-reviewed articles written between 1950 and 2012. Of a total of 1166 articles returned, 50 (9 human, 33 animal, and 8 spinal cord samples) met full inclusion criteria and were included in the review.
RESULTS
OT had a reliable effect as defined by increasing pain tolerance in 29 of 33 animal studies reviewed. This effect persisted across central and peripheral modes of administration and type of noxious stimulus used (eg, heat, electric). The results suggest that OT acts as an analgesic for acute pain in animals. Preliminary research with humans offers consistent evidence to suggest that OT decreases pain sensitivity, though the reliability and stability of such effects cannot yet be determined. Although the findings are encouraging, there is a need for methodologically rigorous work in humans where OT is administered centrally.
DISCUSSION
Further research seems to be warranted as the existence of biologically and psychologically plausible mechanisms linking OT and pain have been well supported using animal models with limited but encouraging human research. Implications and recommendations are discussed. Findings from this research may inform therapeutic methods for the management of pain.
Topics: Analgesics; Animals; Databases, Factual; Disease Models, Animal; Humans; Oxytocin; Pain; Spinal Cord
PubMed: 23887343
DOI: 10.1097/AJP.0b013e31829f57df -
Annals of Internal Medicine Nov 2020Strategies to improve patients' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease... (Meta-Analysis)
Meta-Analysis
Interventions to Improve Statin Tolerance and Adherence in Patients at Risk for Cardiovascular Disease : A Systematic Review for the 2020 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Dyslipidemia.
BACKGROUND
Strategies to improve patients' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD).
PURPOSE
To assess the benefits and harms of interventions to improve statin adherence in patients at risk for CVD.
DATA SOURCES
MEDLINE, EMBASE, PubMed, and the Cochrane Library from December 2013 through May 2019 (English language only).
STUDY SELECTION
Systematic reviews (SRs), randomized controlled trials (RCTs), and cohort studies that addressed interventions for improving statin tolerance and adherence.
DATA EXTRACTION
One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy.
DATA SYNTHESIS
One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with statin treatment discontinuation, nondaily statin dosing lowered total cholesterol and LDL-C levels. One large cohort study suggested that more than 90% of patients who discontinued statin treatment could be rechallenged with the same or a different statin and be adherent 1 year after a statin-related adverse event led to discontinuation. Two small cohort studies reported that more than 90% of patients who were previously intolerant to statins and who had low baseline levels of vitamin D were able to adhere to statins 1 year after vitamin D supplementation.
LIMITATION
This is a qualitative synthesis of new evidence with existing meta-analyses, and studies had several methodological shortcomings.
CONCLUSION
Although the strength of evidence for most interventions was low or very low, intensified patient care and rechallenge with the same or a different statin (or a lower dose) seem to be favorable options for improving statin adherence.
PRIMARY FUNDING SOURCE
U.S. Department of Veterans Affairs.
Topics: Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Medication Adherence; Practice Guidelines as Topic
PubMed: 32956601
DOI: 10.7326/M20-4680 -
Microbiology Spectrum Dec 2022Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.
Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.
Topics: Humans; Syphilis; Ceftriaxone; Doxycycline; Minocycline; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Penicillins; Tetracycline; Erythromycin; Hypersensitivity; Observational Studies as Topic
PubMed: 36377935
DOI: 10.1128/spectrum.02977-22 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2010Propofol is a sedative-hypnotic prescription medication that is widely used in anesthesia, long-term sedation, and conscious sedation. It is short acting, effective,... (Review)
Review
CONTEXT
Propofol is a sedative-hypnotic prescription medication that is widely used in anesthesia, long-term sedation, and conscious sedation. It is short acting, effective, and, when used appropriately, safe. It is not a controlled substance by the U.S. Drug Enforcement Administration, suggesting that it has little potential for abuse. The objective of this review was to evaluate the evidence for the abuse potential of propofol.
METHODS
A systematic review of the medical literature was performed using the search terms: propofol, Diprivan, abuse, addiction, tolerance, misuse, and withdrawal. Six online literature citation databases and relevant bibliographies were searched for articles.
RESULTS
Seventy-two articles were identified for review and 45 were relevant to the topic. These articles described propofol's biochemical and pharmacokinetic mechanisms of action that lend themselves to its abuse, propofol's physical and psychological effects that make it alluring as a recreational drug, the current evidence supporting the possibility of tolerance to and withdrawal from propofol, the risk involved in recreational propofol use, and the evidence supporting current abuse of this medication. We found evidence to support propofol's abuse potential from a pharmacological and experiential standpoint with multiple reports describing tolerance, dependence, withdrawal phenomena, abuse, and death from recreational use.
CONCLUSIONS
Propofol has alluring and addictive properties that lend itself to potential recreational abuse and dependence. We recommend that the U.S. Drug Enforcement Administration and other international agencies should consider regulating propofol as a controlled substance.
Topics: Anesthetics, Intravenous; Animals; Drug Tolerance; Drug and Narcotic Control; Humans; Propofol; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; United States
PubMed: 20397799
DOI: 10.3109/15563651003757954