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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 -
British Journal of Clinical Pharmacology Jul 2016Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not... (Review)
Review
AIM
Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not been standardized internationally. Our aim was to synthesize information about the type and variety of data collected within ADE reporting systems.
METHODS
We developed a systematic search strategy, applied it to four electronic databases, and completed an electronic grey literature search. Two authors reviewed titles and abstracts, and all eligible full-texts. We extracted data using a standardized form, and discussed disagreements until reaching consensus. We synthesized data by collapsing data elements, eliminating duplicate fields and identifying relationships between reporting concepts and data fields using visual analysis software.
RESULTS
We identified 108 ADE reporting systems containing 1782 unique data fields. We mapped them to 33 reporting concepts describing patient information, the ADE, concomitant and suspect drugs, and the reporter. While reporting concepts were fairly consistent, we found variability in data fields and corresponding response options. Few systems clarified the terminology used, and many used multiple drug and disease dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA).
CONCLUSION
We found substantial variability in the data fields used to report ADEs, limiting the comparability of ADE data collected using different reporting systems, and undermining efforts to aggregate data across cohorts. The development of a common standardized data set that can be evaluated with regard to data quality, comparability and reporting rates is likely to optimize ADE data and drug safety surveillance.
Topics: Adverse Drug Reaction Reporting Systems; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance
PubMed: 27016266
DOI: 10.1111/bcp.12944 -
Drug Design, Development and Therapy 2016To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease.
LITERATURE SEARCH
Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles.
METHODS
All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers.
RESULTS
All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died) met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People's Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died).
CONCLUSION
Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published). Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF vaccine is a very safe vaccine that likely confers lifelong immunity.
Topics: Developing Countries; Humans; Multiple Organ Failure; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vaccination; Yellow Fever Vaccine
PubMed: 27784992
DOI: 10.2147/DDDT.S99600 -
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 -
British Journal of Clinical Pharmacology Jul 2016Drug-induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β-adrenoceptor blockers. However,... (Review)
Review
AIM
Drug-induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β-adrenoceptor blockers. However, sources report extremely variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug-induced RP.
METHODS
A systematic review of English and French language articles was performed through Medline (1946-2015) and Embase (1974-2015). Further relevant papers were identified from the reference lists of retrieved articles.
RESULTS
We identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by β-adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism.
CONCLUSION
Drug-induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered.
Topics: Adrenergic beta-Antagonists; Animals; Drug-Related Side Effects and Adverse Reactions; Humans; Prevalence; Raynaud Disease
PubMed: 26949933
DOI: 10.1111/bcp.12912 -
Frontiers in Psychiatry 2023Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its... (Review)
Review
The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression.
INTRODUCTION
Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis.
METHODS
We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated.
RESULTS
A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia.
CONCLUSION
Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.
PubMed: 37502816
DOI: 10.3389/fpsyt.2023.1215807 -
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 -
Medicina (Kaunas, Lithuania) Jan 2021This study explores the legal considerations surrounding medicines management, providing a synthesis of existing knowledge. An integrative systematic review of the... (Review)
Review
This study explores the legal considerations surrounding medicines management, providing a synthesis of existing knowledge. An integrative systematic review of the current international knowledge was performed. The search encompassed the online databases of PubMed (including Medline), Scopus, CINAHL, and Web of Science using MeSH terms and relevant keywords relating to the legal considerations of medicines management in healthcare settings. The search process led to the identification of 6051 studies published between 2010 and 2020, of which six articles were found to be appropriate for data analysis and synthesis based on inclusion criteria. Research methods were varied and included qualitative interviews, mixed-methods designs, retrospective case reports and cross-sectional interrupted time-series analysis. Their foci were on the delegation of medicines management, pharmacovigilance and reporting of adverse drug reactions (ADRs) before and after legislation by nurses, physicians and pharmacists, medico-legal litigation, use of forced medication and the prescription monitoring program. Given the heterogenicity of the studies in terms of aims and research methods, a meta-analysis could not be performed and, therefore, our review findings are presented narratively under the categories of 'healthcare providers' education and monitoring tasks', 'individual and shared responsibility', and 'patients' rights'. This review identifies legal aspects surrounding medicines management, including supervision and monitoring of the effects of medicines; healthcare providers' knowledge and attitudes; support and standardised tools for monitoring and reporting medicines' adverse side effects/ADRs; electronic health record systems; individual and shared perceptions of responsibility; recognition of nurses' roles; detection of sentinel medication errors; covert or non-voluntary administration of medication, and patient participation.
Topics: Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Health Personnel; Humans; Pharmacists; Retrospective Studies
PubMed: 33450903
DOI: 10.3390/medicina57010065 -
Children (Basel, Switzerland) Nov 2022QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However,... (Review)
Review
QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, the interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neonates. Further research in this age category is needed to improve primary screening practices and QTcthresholds, earlier detection of risk factors and precision pharmacovigilance.
PubMed: 36421220
DOI: 10.3390/children9111771 -
The Cochrane Database of Systematic... Feb 2014Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow disease progression. Diacerein is an anthraquinone synthesised in 1980 that interferes with interleukin-1, an inflammatory mediator. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure-modifying drug for OA. This is an update of a Cochrane review first published in 2006.
OBJECTIVES
To assess the benefits and harms of diacerein for the treatment of adults with OA when compared with placebo and other pharmacologically active interventions (nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptom-modifying, slow-acting drugs) for OA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library, Issue 10, 2013, MEDLINE (1966 to 2013), EMBASE (1980 to 2013), LILACS (1982 to 2013), and ACP Journal Club, and we handsearched reference lists of published articles. We also searched the World Health Organization International Clinical Trials Platform ( http://www.who.int/trialsearch/Default.aspx) to identify ongoing trials and screened reference lists of retrieved review articles and trials to identify potentially relevant studies. All searches were up to date as of March 2013. Pharmaceutical companies and authors of published articles were contacted. We searched the websites of the regulatory agencies using the keyword 'diacerein' in November 2013. No language restrictions were applied.
SELECTION CRITERIA
Studies were included if they were randomised or quasi-randomised controlled trials that compared diacerein with placebo or another active pharmacological intervention in participants with OA.
DATA COLLECTION AND ANALYSIS
Data abstraction and quality assessment were performed by two independent investigators, and their results were compared. The Cochrane risk of bias tool was used. The quality of evidence obtained was assessed using the GRADE approach.
MAIN RESULTS
We identified three new trials (141 participants), and this updated review now includes 10 trials, totalling 2,210 participants. The most frequent risk of bias was incomplete outcome data, identified in approximately 80% of the studies. Allocation concealment and random sequence generation were unclear in 90% and 40% of the studies, respectively, because of poor reporting.Low-quality evidence from six trials (1,283 participants) indicates that diacerein has a small beneficial effect on overall pain (measured on a 100 mm visual analogue scale) at three to 36 months (mean difference (MD) -8.65, 95% confidence interval (CI) -15.62 to -1.68), which is equivalent to a 9% pain reduction in the diacerein group (95% CI -16% to -2%) compared with the placebo group. This benefit may not be clinically significant.No statistically significant differences in physical function (4 studies, 1006 participants) were noted between the diacerein and placebo groups (Lequesne impairment index, 0 to 24 points) (MD -0.29, 95% CI -0.87 to 0.28).Low-quality evidence from two trials (616 participants) on slowing of joint space narrowing (a decrease greater than 0.50 mm) in the knee or hip favoured diacerein over placebo (risk ratio (RR) 0.85, 95% CI 0.72 to 0.99), with an absolute risk difference of -6% (95% CI -15% to 2%) and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 8 to 203). Analysis of the knee joint alone (1 study, 170 participants) did not reach statistical significance (RR 0.94, 95% CI 0.51 to 1.74).None of the trials of diacerein versus placebo measured quality of life. According to one trial (161 participants), which compared diacerein versus non-steroidal anti-inflammatory drugs (NSAIDs), the quality of life of participants in the two groups (as assessed by the Short Form (SF)-36 health survey questionnaire (0 to 800 sum score)) did not differ significantly (MD -40.70, 95% CI -85.20 to 3.80).Low-quality evidence from seven trials showed significantly more adverse events in the diacerein group compared with the placebo group after two to 36 months, mainly diarrhoea (RR 3.52, 95% CI 2.42 to 5.11), with an absolute risk increase of 24% (95% CI 12% to 35%), and a number needed to treat for an additional harmful outcome (NNTH) of 4 (95% CI 3 to 7).No statistically significant differences in participant withdrawal due to adverse events were seen at two to 36 months for diacerein compared with placebo (RR 1.29, 95% CI 0.83 to 2.01).A search of regulatory websites found a recommendation from the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) that the marketing authorization of diacerein should be suspended across Europe because of harms (particularly the risk of severe diarrhoea and potentially harmful effects on the liver) outweighing benefits. However, this guidance is not final as the PRAC recommendation will be re-examined.
AUTHORS' CONCLUSIONS
In this update, the strength of evidence for effectiveness outcomes was low to moderate. We confirmed that symptomatic benefit provided by diacerein in terms of pain reduction is minimal. The small benefit derived in terms of joint space narrowing is of questionable clinical relevance and was observed only for OA of the hip. With respect to adverse effects of diacerein, diarrhoea was most frequent. Given the recent guidance issued by the EMA recommending suspension of diacerein in Europe, the EMA website should be consulted for further recommendations regarding the use of diacerein.
Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 24515444
DOI: 10.1002/14651858.CD005117.pub3