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European Journal of Clinical... Sep 2023Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in... (Review)
Review
PURPOSE
Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in the short-term, emerging evidence shows risks associated with long-term use. Current evidence on global PPI use is scarce. This systematic review aims to evaluate global PPI use in the general population.
METHODS
Ovid MEDLINE, Embase, and International Pharmaceutical Abstracts were systematically searched from inception to 31 March 2023 to identify observational studies on oral PPI use among individuals aged ≥ 18 years. PPI use was classified by demographics and medication factors (dose, duration, and PPI types). The absolute numbers of PPI users for each subcategory were summed and expressed as a percentage.
RESULTS
The search identified data from 28 million PPI users in 23 countries from 65 articles. This review indicated that nearly one-quarter of adults use a PPI. Of those using PPIs, 63% were less than 65 years. 56% of PPI users were female, and "White" ethnicities accounted for 75% of users. Nearly two-thirds of users were on high doses (≥ defined daily dose (DDD)), 25% of users continued PPIs for > 1 year, and 28% of these continued for > 3 years.
CONCLUSION
Given the widespread use PPIs and increasing concern regarding long-term use, this review provides a catalyst to support more rational use, particularly with unnecessary prolonged continuation. Clinicians should review PPI prescriptions regularly and deprescribe when there is no appropriate ongoing indication or evidence of benefit to reduce health harm and treatment cost.
Topics: Adult; Humans; Female; Male; Proton Pump Inhibitors; Upper Gastrointestinal Tract; Health Care Costs; Prescriptions
PubMed: 37420019
DOI: 10.1007/s00228-023-03534-z -
Frontiers in Endocrinology 2023Glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of... (Review)
Review
AIMS/HYPOTHESIS
Glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of type 2 diabetes and obesity. The paucity of data regarding their safety during pregnancy and lactation causes a dilemma for the physician. The aim of the present study was to systematically review all available data on the offspring effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation.
METHODS
We systematically searched PubMed, clinicaltrials.gov, FDA and EMA product information on GLP-1 agonists and SGLT2 inhibitors in pregnancy and lactation from inception up to 19 April 2022 without language restrictions. We approached both the Netherlands Pharmacovigilance Centre Lareb on January 17 2023 and the Teratology Information Service (TIS) of Switzerland on February 6 2023. Eligible studies investigating the safety (including congenital anomalies, fetal growth, perinatal demise) in animals or humans, or reporting the degree of transfer of these drugs to the fetus, breast milk or breastfed neonate. Two reviewers independently assessed and selected studies for inclusion and subsequently resolved discrepancies by discussion.
RESULTS
We included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information). In animal studies, GLP1-agonists were associated with reduced fetal weight and/or growth, delayed ossification and skeletal variants, usually associated with a reduction in maternal weight gain and decreased food consumption. Exendin-4 (GLP1-agonist) was not transported across the maternal-fetal placental interface. In human studies, exenatide (GLP1-agonist) showed a fetal-to-maternal peptide concentration ratio of ≤ 0.017 in ex vivo human placental perfusion in a single placenta. Liraglutide (GLP1-agonist) showed no significant maternal to fetal transfer at least 3.5 hours after maternal exposure in a human study with one subject. In animal studies, GLP-1 agonists were excreted in breast milk; human data on excretion were not available. In animal studies, SGLT2 inhibitors were generally safe during the first trimester but exposure during postnatal day 21 to 90 in juvenile rats, a period coinciding with the late second and third trimester of human renal development, caused dilatation of the renal pelvis and tubules. Human data consisted of a pharmaceutical database of inadvertent pregnancies during SGLT2 inhibitor use, which found an increase in miscarriages and congenital malformations. In animal studies SGLT2 inhibitors were excreted in breast milk and affected neonatal growth, but human data are not available.
CONCLUSION/INTERPRETATION
We found evidence for adverse offspring effects of GLP-1 agonists and SGLT2 inhibitors also in human studies. Our findings broadly support the advice to discontinue GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation, and also support the ongoing registration of pregnancy outcomes in pharmacological databases since the amount of available data is scarce and mostly limited to animal studies.
REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=219877.
Topics: Female; Humans; Pregnancy; Rats; Animals; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Breast Feeding; Placenta; Exenatide; Liraglutide; Lactation
PubMed: 37881498
DOI: 10.3389/fendo.2023.1215356 -
European Respiratory Review : An... Sep 2023The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of... (Review)
Review
BACKGROUND
The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown.
OBJECTIVE
To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma.
METHODS
A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded.
RESULTS
59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10 revision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children.
CONCLUSION
Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.
Topics: Child; Animals; Humans; Aged; Asthma; Acetates; Quinolines; Cyclopropanes; Anti-Asthmatic Agents
PubMed: 37758273
DOI: 10.1183/16000617.0079-2023 -
The British Journal of Dermatology Sep 2023On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked to the occurrence of major adverse cardiovascular events (MACE). However, these inflammatory diseases are proatherogenic; in contrast, patients with atopic dermatitis (AD) do not usually have a high cardiovascular (CV) comorbidity burden.
OBJECTIVES
To perform a systematic review and meta-analysis of MACE in patients with AD treated with JAKi.
METHODS
We systematically searched PubMed, Embase, Cochrane Library and Google Scholar from their inception to 2 September 2022. Cohort studies, randomized controlled trials and pooled safety analyses providing CV safety data on patients taking JAKi for AD were selected. We included patients aged ≥ 12 years. We built a 'controlled-period' cohort (n = 9309; 6000 exposed to JAKi and 3309 exposed to comparators) and an 'all-JAKi' cohort (n = 9118 patients exposed to a JAKi in any of the included studies). The primary outcome was a composite of acute coronary syndrome (ACS), ischaemic stroke and CV death. The broader secondary MACE outcome encompassed ACS, stroke (whether ischaemic or haemorrhagic), transient ischaemic attack and CV death. The frequency of primary and secondary MACE was assessed in both cohorts. A fixed-effects meta-analysis using the Peto method was used to calculate the odds ratio (OR) for MACE in the 'controlled-period' cohort. Evaluation of the risk of bias was done using the Cochrane risk-of-bias tool (version 2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Eight per cent of the records identified initially met the selection criteria, corresponding to 23 records included in the 'all-JAKi' cohort. Patients had been exposed to baricitinib, upadacitinib, abrocitinib, ivarmacitinib, placebo or dupilumab. Four primary events (three with JAKi and one with placebo) and five secondary events (four with JAKi and one with placebo) occurred among 9309 patients in the 'controlled-period' cohort (MACE frequency 0.04% and 0.05%, respectively). Eight primary events and 13 secondary events occurred among 9118 patients in the 'all-JAKi' cohort (MACE frequency 0.08% and 0.14%, respectively). The OR for primary MACE in patients with AD treated with JAKi vs. placebo or dupilumab was 1.35 (95% confidence interval 0.15-12.21; I2 = 12%, very low certainty of evidence).
CONCLUSIONS
Our review highlights rare cases of MACE among JAKi users for AD. JAKi may have little-to-no effect on the occurrence of MACE in patients with AD vs. comparators, but the evidence is uncertain. Real-life long-term population-level safety studies are needed.
Topics: Humans; Janus Kinase Inhibitors; Dermatitis, Atopic; Brain Ischemia; Stroke; Inflammatory Bowel Diseases
PubMed: 37410552
DOI: 10.1093/bjd/ljad229 -
Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.International Journal of Toxicology 2024The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main... (Review)
Review
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.
Topics: Banisteriopsis; Humans; N,N-Dimethyltryptamine; Animals; Plant Extracts; Harmine; Harmaline
PubMed: 38363085
DOI: 10.1177/10915818241230916 -
Research in Veterinary Science Jan 2024This article aims to perform a comparative systematic review of regulations in veterinary medicine between the years 2016 to 2023. It explores the complex web of... (Review)
Review
This article aims to perform a comparative systematic review of regulations in veterinary medicine between the years 2016 to 2023. It explores the complex web of veterinary medicine regulations in various agencies and the nations, including USA (United States of America), EU (European Union), UK (United Kingdom), Japan, Australia, and India. Current article provides the comparative study on the veterinary regulations of different countries, including acts, directives, and drug approval processes. Such as, the specific legislation is needed to address zoonotic diseases. The strategic and regulated stockpiling of the veterinary drugs especially in chronic veterinary disease outbreak. It is essential to develop the dedicated Veterinary Pharmacopoeia for the regulated standardization of the raw materials as well as the formulations. Veterinary medical device is a field which is highly unregulated. There is a need to have regulations for the same. It is important to have dedicated veterinary pharmacovigilance centers which help in improving quality of medications to the livestock farms. After comparing the regulations of different countries. We observed that there is the absence of the zoonotic diseases and pharma stockpiling in every country. There is also an absence of the dedicated veterinary pharmacopoeia in every country. USA and Australia have the veterinary medical device regulation which is not there in other countries. Around the globe only Australia has the dedicated pharmacovigilance center. Including these recommendations into regulatory framework enhances the quality and safety of veterinary medicine. The current article adds a valuable resource for policymakers, veterinarians, and stakeholders in the field of animal health care.
Topics: Animals; Humans; Animal Husbandry; European Union; Japan; United States; Veterinarians; Zoonoses
PubMed: 38016218
DOI: 10.1016/j.rvsc.2023.105101 -
Climacteric : the Journal of the... Dec 2023Studies have shown racial/ethnic differences in the prevalence of vasomotor symptoms (VMS), sleep disturbance and VMS treatment in menopause. To assess the... (Review)
Review
Studies have shown racial/ethnic differences in the prevalence of vasomotor symptoms (VMS), sleep disturbance and VMS treatment in menopause. To assess the reproducibility of these differences, we systematically reviewed observational studies, published in 2000-2021, reporting the prevalence/incidence of VMS, sleep disturbance or treatment use in menopausal women stratified by race/ethnicity. We screened 3799 records from PubMed and Embase and included 27 papers (19 studies). No incidence data were found. Prevalence data varied widely, but some common patterns emerged. In all five studies comparing VMS between Black women and White, Hispanic and/or East Asian women, the prevalence was highest in Black women and lowest in East Asian women. The prevalence of sleep disturbance overall was compared among Black, White and East Asian women in two study populations, and was highest in White women in both papers. Sleep disturbance was more common than VMS in East Asian women. In all four studies comparing hormone therapy use between White women and Black and/or East Asian women, treatment use was more common in White women. These results highlight the need for individualized counseling and treatment, outreach to under-served minorities, and standardized definitions and outcome measures for VMS and sleep disturbance for future studies.
Topics: Female; Humans; Hot Flashes; Reproducibility of Results; Menopause; Ethnicity; Sleep; Vasomotor System
PubMed: 37751852
DOI: 10.1080/13697137.2023.2256658 -
Nutrients Jul 2023Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical... (Review)
Review
Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1-14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.
Topics: Male; Humans; Female; Randomized Controlled Trials as Topic; Vitamins; Dietary Supplements; Vitamin D; Antioxidants; Neoplasms
PubMed: 37513667
DOI: 10.3390/nu15143249 -
Expert Review of Pharmacoeconomics &... 2023The new class of chimeric antigen receptor T-cell has emboldened health-care professionals and patients for a more effective treatment of hematological malignancies,... (Review)
Review
INTRODUCTION
The new class of chimeric antigen receptor T-cell has emboldened health-care professionals and patients for a more effective treatment of hematological malignancies, indicatively lymphoma, acute lymphoblastic leukemia, and myeloma. Nevertheless, their burgeoning procurement costs comprise a litmus stress for health systems across the globe. In this context, this systematic review aims to update the current body of evidence assessing CAR-T economic evaluations and elucidate their financial efficiency.
AREAS COVERED
A systematic review of the economic evaluations of tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel and brexucabtagene autoleucel was performed.
EXPERT OPINION
The updated results corroborated the previously reported favorable cost-effectiveness ratio of CAR-T. They also pointed out differences among CAR-T agents. However, their budget impact emerges as a significant barrier in the reimbursement process. Any proposed Managed Entry Agreement must integrate the ingrained uncertainty of long-term efficacy and precede reimbursement decisions.
Topics: Humans; Cost-Benefit Analysis; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Budgets; Cell- and Tissue-Based Therapy
PubMed: 37288738
DOI: 10.1080/14737167.2023.2214731 -
The Journal of Infectious Diseases Nov 2023Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing.
METHODS
We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance.
RESULTS
We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%.
CONCLUSIONS
RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.
Topics: Adult; Child; Humans; Respiratory Syncytial Virus Infections; Sensitivity and Specificity; Respiratory Syncytial Virus, Human; Viruses; Diagnostic Techniques and Procedures; Nasopharynx; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 37285396
DOI: 10.1093/infdis/jiad185