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The Cochrane Database of Systematic... Apr 2020Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space, with the aim of reducing the local inflammatory process and, consequently, relieving the symptoms of lumbosacral radicular pain. This Cochrane Review is an update of a review published in Annals of Internal Medicine in 2012. Some placebo-controlled trials have been published recently, which highlights the importance of updating the previous review.
OBJECTIVES
To investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection on pain and disability in patients with lumbosacral radicular pain.
SEARCH METHODS
We searched the following databases without language limitations up to 25 September 2019: Cochrane Back and Neck group trial register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and two trial registers. We also performed citation tracking of included studies and relevant systematic reviews in the field.
SELECTION CRITERIA
We included studies that compared epidural corticosteroid injections of any corticosteroid drug to placebo injections in patients with lumbosacral radicular pain. We accepted all three anatomical approaches (caudal, interlaminar, and transforaminal) to delivering corticosteroids into the epidural space. We considered trials that included a placebo treatment as delivery of an inert substance (i.e. one with no pharmacologic activity), an innocuous substance (e.g. normal saline solution), or a pharmacologically active substance but not one considered to provide sustained benefit (e.g. local anaesthetic), either into the epidural space (i.e. to mimic epidural corticosteroid injection) or adjacent spinal tissue (i.e. subcutaneous, intramuscular, or interspinous tissue). We also included trials in which a local anaesthetic with a short duration of action was used as a placebo and injected together with corticosteroid in the intervention group.
DATA COLLECTION AND ANALYSIS
Two authors independently performed the screening, data extraction, and 'Risk of bias' assessments. In case of insufficient information, we contacted the authors of the original studies or estimated the data. We grouped the outcome data into four time points of assessment: immediate (≤ 2 weeks), short term (> 2 weeks but ≤ 3 months), intermediate term (> 3 months but < 12 months), and long term (≥ 12 months). We assessed the overall quality of evidence for each outcome and time point using the GRADE approach.
MAIN RESULTS
We included 25 clinical trials (from 29 publications) investigating the effects of epidural corticosteroid injections compared to placebo in patients with lumbosacral radicular pain. The included studies provided data for a total of 2470 participants with a mean age ranging from 37.3 to 52.8 years. Seventeen studies included participants with lumbosacral radicular pain with a diagnosis based on clinical assessment and 15 studies included participants with mixed duration of symptoms. The included studies were conducted mainly in North America and Europe. Fifteen studies did not report funding sources, five studies reported not receiving funding, and five reported receiving funding from a non-profit or government source. Eight trials reported data on pain intensity, 12 reported data on disability, and eight studies reported data on adverse events. The duration of the follow-up assessments ranged from 12 hours to 1 year. We considered eight trials to be of high quality because we judged them as having low risk of bias in four out of the five bias domains. We identified one ongoing trial in a trial registry. Epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing leg pain at short-term follow-up (mean difference (MD) -4.93, 95% confidence interval (CI) -8.77 to -1.09 on a 0 to 100 scale; 8 trials, n = 949; moderate-quality evidence (downgraded for risk of bias)). For disability, epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing disability at short-term follow-up (MD -4.18, 95% CI -6.04 to -2.17, on a 0 to 100 scale; 12 trials, n = 1367; moderate-quality evidence (downgraded for risk of bias)). The treatment effects are small, however, and may not be considered clinically important by patients and clinicians (i.e. MD lower than 10%). Most trials provided insufficient information on how or when adverse events were assessed (immediate or short-term follow-up) and only reported adverse drug reactions - that is, adverse events that the trialists attributed to the study treatment. We are very uncertain that epidural corticosteroid injections make no difference compared to placebo injection in the frequency of minor adverse events (risk ratio (RR) 1.14, 95% CI 0.91 to 1.42; 8 trials, n = 877; very low quality evidence (downgraded for risk of bias, inconsistency and imprecision)). Minor adverse events included increased pain during or after the injection, non-specific headache, post-dural puncture headache, irregular periods, accidental dural puncture, thoracic pain, non-local rash, sinusitis, vasovagal response, hypotension, nausea, and tinnitus. One study reported a major drug reaction for one patient on anticoagulant therapy who had a retroperitoneal haematoma as a complication of the corticosteroid injection.
AUTHORS' CONCLUSIONS
This study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain. In addition, no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection. Although the current review identified additional clinical trials, the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small, mainly evident at short-term follow-up and may not be considered clinically important by patients and clinicians (i.e. mean difference lower than 10%). According to GRADE, the quality of the evidence ranged from very low to moderate, suggesting that further studies are likely to play an important role in clarifying the efficacy and tolerability of this treatment. We recommend that further trials should attend to methodological features such as appropriate allocation concealment and blinding of care providers to minimise the potential for biased estimates of treatment and harmful effects.
Topics: Adrenal Cortex Hormones; Adult; Anesthetics, Local; Humans; Injections, Epidural; Lumbosacral Region; Middle Aged; Randomized Controlled Trials as Topic; Sciatica
PubMed: 32271952
DOI: 10.1002/14651858.CD013577 -
Nutrients Apr 2020Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in...
Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in order to identify the current knowledge of the interactions between EDCs in food, the gut microbiota, and metabolic disorders in order to shed light on this complex triad. Exposure to EDCs induces a series of changes including microbial dysbiosis and the induction of xenobiotic pathways and associated genes, enzymes, and metabolites involved in EDC metabolism. The products and by-products released following the microbial metabolism of EDCs can be taken up by the host; therefore, changes in the composition of the microbiota and in the production of microbial metabolites could have a major impact on host metabolism and the development of diseases. The remediation of EDC-induced changes in the gut microbiota might represent an alternative course for the treatment and prevention of metabolic diseases.
Topics: Dysbiosis; Endocrine Disruptors; Food Analysis; Gastrointestinal Microbiome; Humans; Metabolic Diseases
PubMed: 32326280
DOI: 10.3390/nu12041158 -
The Cochrane Database of Systematic... Nov 2021Many infants born preterm develop bronchopulmonary dysplasia (BPD), with lung inflammation playing a role. Corticosteroids have powerful anti-inflammatory effects and... (Review)
Review
BACKGROUND
Many infants born preterm develop bronchopulmonary dysplasia (BPD), with lung inflammation playing a role. Corticosteroids have powerful anti-inflammatory effects and have been used to treat individuals with established BPD. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs.
OBJECTIVES
To examine the relative benefits and adverse effects of late (starting at seven or more days after birth) systemic postnatal corticosteroid treatment for preterm infants with evolving or established BPD.
SEARCH METHODS
We ran an updated search on 25 September 2020 of the following databases: CENTRAL via CRS Web and MEDLINE via OVID. We also searched clinical trials databases and reference lists of retrieved articles for randomised controlled trials (RCTs). We did not include quasi-RCTs.
SELECTION CRITERIA
We selected for inclusion in this review RCTs comparing systemic (intravenous or oral) postnatal corticosteroid treatment versus placebo or no treatment started at seven or more days after birth for preterm infants with evolving or established BPD. We did not include trials of inhaled corticosteroids.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We extracted and analysed data regarding clinical outcomes that included mortality, BPD, and cerebral palsy. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Use of the GRADE approach revealed that the certainty of evidence was high for most of the major outcomes considered, except for BPD at 36 weeks for all studies combined and for the dexamethasone subgroup, which were downgraded one level to moderate because of evidence of publication bias, and for the combined outcome of mortality or BPD at 36 weeks for all studies combined and for the dexamethasone subgroup, which were downgraded one level to moderate because of evidence of substantial heterogeneity. We included 23 RCTs (1817 infants); 21 RCTS (1382 infants) involved dexamethasone (one also included hydrocortisone) and two RCTs (435 infants) involved hydrocortisone only. The overall risk of bias of included studies was low; all were RCTs and most trials used rigorous methods. Late systemic corticosteroids overall reduce mortality to the latest reported age (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.66 to 0.99; 21 studies, 1428 infants; high-certainty evidence). Within the subgroups by drug, neither dexamethasone (RR 0.85, 95% CI 0.66 to 1.11; 19 studies, 993 infants; high-certainty evidence) nor hydrocortisone (RR 0.74, 95% CI 0.54 to 1.02; 2 studies, 435 infants; high-certainty evidence) alone clearly reduce mortality to the latest reported age. We found little evidence for statistical heterogeneity between the dexamethasone and hydrocortisone subgroups (P = 0.51 for subgroup interaction). Late systemic corticosteroids overall probably reduce BPD at 36 weeks' postmenstrual age (PMA) (RR 0.89, 95% CI 0.80 to 0.99; 14 studies, 988 infants; moderate-certainty evidence). Dexamethasone probably reduces BPD at 36 weeks' PMA (RR 0.76, 95% CI 0.66 to 0.87; 12 studies, 553 infants; moderate-certainty evidence), but hydrocortisone does not (RR 1.10, 95% CI 0.92 to 1.31; 2 studies, 435 infants; high-certainty evidence) (P < 0.001 for subgroup interaction). Late systemic corticosteroids overall probably reduce the combined outcome of mortality or BPD at 36 weeks' PMA (RR 0.85, 95% CI 0.79 to 0.92; 14 studies, 988 infants; moderate-certainty evidence). Dexamethasone probably reduces the combined outcome of mortality or BPD at 36 weeks' PMA (RR 0.75, 95% CI 0.67 to 0.84; 12 studies, 553 infants; moderate-certainty evidence), but hydrocortisone does not (RR 0.98, 95% CI 0.88 to 1.09; 2 studies, 435 infants; high-certainty evidence) (P < 0.001 for subgroup interaction). Late systemic corticosteroids overall have little to no effect on cerebral palsy (RR 1.17, 95% CI 0.84 to 1.61; 17 studies, 1290 infants; high-certainty evidence). We found little evidence for statistical heterogeneity between the dexamethasone and hydrocortisone subgroups (P = 0.63 for subgroup interaction). Late systemic corticosteroids overall have little to no effect on the combined outcome of mortality or cerebral palsy (RR 0.90, 95% CI 0.76 to 1.06; 17 studies, 1290 infants; high-certainty evidence). We found little evidence for statistical heterogeneity between the dexamethasone and hydrocortisone subgroups (P = 0.42 for subgroup interaction). Studies had few participants who were not intubated at enrolment; hence, it is not possible to make any meaningful comments on the effectiveness of late corticosteroids in preventing BPD in non-intubated infants, including those who might in the present day be supported by non-invasive techniques such as nasal continuous positive airway pressure or high-flow nasal cannula oxygen/air mixture, but who might still be at high risk of later BPD. Results of two ongoing studies are awaited.
AUTHORS' CONCLUSIONS
Late systemic postnatal corticosteroid treatment (started at seven days or more after birth) reduces the risks of mortality and BPD, and the combined outcome of mortality or BPD, without evidence of increased cerebral palsy. However, the methodological quality of studies determining long-term outcomes is limited, and no studies were powered to detect increased rates of important adverse long-term neurodevelopmental outcomes. This review supports the use of late systemic corticosteroids for infants who cannot be weaned from mechanical ventilation. The role of late systemic corticosteroids for infants who are not intubated is unclear and needs further investigation. Longer-term follow-up into late childhood is vital for assessment of important outcomes that cannot be assessed in early childhood, such as effects of late systemic corticosteroid treatment on higher-order neurological functions, including cognitive function, executive function, academic performance, behaviour, mental health, motor function, and lung function. Further RCTs of late systemic corticosteroids should include longer-term survival free of neurodevelopmental disability as the primary outcome.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Dexamethasone; Drug Administration Schedule; Glucocorticoids; Humans; Infant; Infant, Newborn; Infant, Premature
PubMed: 34758507
DOI: 10.1002/14651858.CD001145.pub5 -
Lipids in Health and Disease Oct 2019Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions...
BACKGROUND
Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations.
METHODS
A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines.
RESULTS
Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes.
CONCLUSIONS
Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.
Topics: Animals; Cardiovascular Diseases; Chronic Disease; DNA Methylation; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Epigenesis, Genetic; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Gene-Environment Interaction; Humans; Insulin Resistance; Lipid Metabolism; Obesity; Trans Fatty Acids
PubMed: 31615571
DOI: 10.1186/s12944-019-1120-6 -
The Cochrane Database of Systematic... Mar 2019Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- and middle-income countries. They are exacerbated in pregnancy due to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- and middle-income countries. They are exacerbated in pregnancy due to the increased demands of the developing fetus, leading to potentially adverse effects on the mother and baby. A consensus is yet to be reached regarding the replacement of iron and folic acid supplementation with MMNs. Since the last update of this Cochrane Review in 2017, evidence from several trials has become available. The findings of this review will be critical to inform policy on micronutrient supplementation in pregnancy.
OBJECTIVES
To evaluate the benefits of oral multiple-micronutrient supplementation during pregnancy on maternal, fetal and infant health outcomes.
SEARCH METHODS
For this 2018 update, on 23 February 2018 we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. We also contacted experts in the field for additional and ongoing trials.
SELECTION CRITERIA
All prospective randomised controlled trials evaluating MMN supplementation with iron and folic acid during pregnancy and its effects on pregnancy outcomes were eligible, irrespective of language or the publication status of the trials. We included cluster-randomised trials, but excluded quasi-randomised trials. Trial reports that were published as abstracts were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We identified 21 trials (involving 142,496 women) as eligible for inclusion in this review, but only 20 trials (involving 141,849 women) contributed data. Of these 20 trials, 19 were conducted in low- and middle-income countries and compared MMN supplements with iron and folic acid to iron, with or without folic acid. One trial conducted in the UK compared MMN supplementation with placebo. In total, eight trials were cluster-randomised.MMN with iron and folic acid versus iron, with or without folic acid (19 trials)MMN supplementation probably led to a slight reduction in preterm births (average risk ratio (RR) 0.95, 95% confidence interval (CI) 0.90 to 1.01; 18 trials, 91,425 participants; moderate-quality evidence), and babies considered small-for-gestational age (SGA) (average RR 0.92, 95% CI 0.88 to 0.97; 17 trials; 57,348 participants; moderate-quality evidence), though the CI for the pooled effect for preterm births just crossed the line of no effect. MMN reduced the number of newborn infants identified as low birthweight (LBW) (average RR 0.88, 95% CI 0.85 to 0.91; 18 trials, 68,801 participants; high-quality evidence). We did not observe any differences between groups for perinatal mortality (average RR 1.00, 95% CI 0.90 to 1.11; 15 trials, 63,922 participants; high-quality evidence). MMN supplementation led to slightly fewer stillbirths (average RR 0.95, 95% CI 0.86 to 1.04; 17 trials, 97,927 participants; high-quality evidence) but, again, the CI for the pooled effect just crossed the line of no effect. MMN supplementation did not have an important effect on neonatal mortality (average RR 1.00, 95% CI 0.89 to 1.12; 14 trials, 80,964 participants; high-quality evidence). We observed little or no difference between groups for the other maternal and pregnancy outcomes: maternal anaemia in the third trimester (average RR 1.04, 95% CI 0.94 to 1.15; 9 trials, 5912 participants), maternal mortality (average RR 1.06, 95% CI 0.72 to 1.54; 6 trials, 106,275 participants), miscarriage (average RR 0.99, 95% CI 0.94 to 1.04; 12 trials, 100,565 participants), delivery via a caesarean section (average RR 1.13, 95% CI 0.99 to 1.29; 5 trials, 12,836 participants), and congenital anomalies (average RR 1.34, 95% CI 0.25 to 7.12; 2 trials, 1958 participants). However, MMN supplementation probably led to a reduction in very preterm births (average RR 0.81, 95% CI 0.71 to 0.93; 4 trials, 37,701 participants). We were unable to assess a number of prespecified, clinically important outcomes due to insufficient or non-available data.When we assessed primary outcomes according to GRADE criteria, the quality of evidence for the review overall was moderate to high. We graded the following outcomes as high quality: LBW, perinatal mortality, stillbirth, and neonatal mortality. The outcomes of preterm birth and SGA we graded as moderate quality; both were downgraded for funnel plot asymmetry, indicating possible publication bias.We carried out sensitivity analyses excluding trials with high levels of sample attrition (> 20%). We found that results were consistent with the main analyses for all outcomes. We explored heterogeneity through subgroup analyses by maternal height, maternal body mass index (BMI), timing of supplementation, dose of iron, and MMN supplement formulation (UNIMMAP versus non-UNIMMAP). There was a greater reduction in preterm births for women with low BMI and among those who took non-UNIMMAP supplements. We also observed subgroup differences for maternal BMI and maternal height for SGA, indicating greater impact among women with greater BMI and height. Though we found that MMN supplementation made little or no difference to perinatal mortality, the analysis demonstrated substantial statistical heterogeneity. We explored this heterogeneity using subgroup analysis and found differences for timing of supplementation, whereby higher impact was observed with later initiation of supplementation. For all other subgroup analyses, the findings were inconclusive.MMN versus placebo (1 trial)A single trial in the UK found little or no important effect of MMN supplementation on preterm births, SGA, or LBW but did find a reduction in maternal anaemia in the third trimester (RR 0.66, 95% CI 0.51 to 0.85), when compared to placebo. This trial did not measure our other outcomes.
AUTHORS' CONCLUSIONS
Our findings suggest a positive impact of MMN supplementation with iron and folic acid on several birth outcomes. MMN supplementation in pregnancy led to a reduction in babies considered LBW, and probably led to a reduction in babies considered SGA. In addition, MMN probably reduced preterm births. No important benefits or harms of MMN supplementation were found for mortality outcomes (stillbirths, perinatal and neonatal mortality). These findings may provide some basis to guide the replacement of iron and folic acid supplements with MMN supplements for pregnant women residing in low- and middle-income countries.
Topics: Dietary Supplements; Drug Interactions; Female; Folic Acid; Humans; Infant, Newborn; Infant, Small for Gestational Age; Iron, Dietary; Micronutrients; Perinatal Mortality; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 30873598
DOI: 10.1002/14651858.CD004905.pub6 -
Medicine Mar 2016Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is... (Meta-Analysis)
Meta-Analysis
Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs. Restriction of dietary vitamin K intake does not seem to be a valid strategy to improve anticoagulation quality with VKAs. It would be, perhaps, more relevant to maintain stable dietary habit, avoiding wide changes in the intake of vitamin K.
Topics: Antifibrinolytic Agents; Blood Coagulation; Dietary Supplements; Humans; International Normalized Ratio; Nutritional Requirements; Thromboembolism; Vitamin K
PubMed: 26962786
DOI: 10.1097/MD.0000000000002895 -
Drugs Jul 2021We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical...
We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.
Topics: Analgesics, Opioid; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Humans; Liver Failure; Pain; Renal Insufficiency; Tapentadol; Tramadol
PubMed: 34196947
DOI: 10.1007/s40265-021-01515-z -
British Journal of Clinical Pharmacology Oct 2017Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review... (Meta-Analysis)
Meta-Analysis Review
AIMS
Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant.
METHODS
We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant. The clinical significance of each reported pharmacokinetic drug interaction was evaluated based on the United States Food and Drug Administration guidance document on conducting drug interaction studies. The probability of an adverse event reported in case reports being due to a drug interaction with aprepitant/fosaprepitant was determined using the Drug Interaction Probability Scale.
RESULTS
A total of 4377 publications were identified. Of these, 64 met inclusion eligibility criteria: 34 described pharmacokinetic drug interactions and 30 described adverse events ascribed to a drug interaction. Clinically significant pharmacokinetic interactions between aprepitant/fosaprepitant and bosutinib PO, cabazitaxel IV, cyclophosphamide IV, dexamethasone PO, methylprednisolone IV, midazolam PO/IV, oxycodone PO and tolbutamide PO were identified, as were adverse events resulting from an interaction between aprepitant/fosaprepitant and alcohol, anthracyclines, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin.
CONCLUSIONS
The potential for a drug interaction with aprepitant and fosaprepitant should be considered when selecting antiemetic therapy.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Ethanol; Humans; Injection Site Reaction; Morpholines; Nausea; Oxycodone; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Vomiting
PubMed: 28470980
DOI: 10.1111/bcp.13322 -
Therapeutics and Clinical Risk... 2023Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the... (Review)
Review
PURPOSE
Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the medications, food and beverages that interact with levothyroxine and to assess their effects, mechanisms and treatments.
METHODS
A systematic review on interfering substances that interact with levothyroxine was performed. Web of Science, Embase, PubMed, the Cochrane library, grey literature from other sources and the lists of references were searched for human studies comparing the levothyroxine efficacy with and without interfering substances. The patient characteristics, drug classes, effects and mechanism were extracted. The NHLBI study quality assessment tools and the JBI critical appraisal checklist were used to assess the quality of included studies.
RESULTS
A total of 107 articles with 128 studies were included. Drugs interactions were revealed in calcium and iron supplements, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, anticonvulsants and other drugs. Some food and beverage could also induce malabsorption. Proposed mechanisms included direct complexing, alkalization, alteration of serum thyroxine-binding globulin levels and acceleration of levothyroxine catabolism via deiodination. Dose adjustment, administration separation and discontinuation of interfering substances can eliminate the interactions. Liquid solutions and soft-gel capsules could eliminate the malabsorption due to chelation and alkalization. The qualities of most included studies were moderate.
CONCLUSION
Lots of medications and food can impair the bioavailability of levothyroxine. Clinicians, patients and pharmaceutical companies should be aware of the possible interactions. Further well-designed studies are needed to provide more solid evidence on treatment and mechanisms.
PubMed: 37384019
DOI: 10.2147/TCRM.S414460 -
Journal of Pharmaceutical Policy and... Apr 2021Drug-related problems (DRPs) can occur at any stages of medication use processes, and a single drug could be associated with multiple DRPs. Once happened, it adversely... (Review)
Review
BACKGROUND
Drug-related problems (DRPs) can occur at any stages of medication use processes, and a single drug could be associated with multiple DRPs. Once happened, it adversely affects health outcomes. In Ethiopia, evaluation of the magnitude and factors associated with DRPs had not been attempted at the national level.
METHOD
The literature search was conducted in the following databases; PubMed, Embase, Medline, and Google Scholar. The quality of the included studies was checked using Joanna Brigg's Institute (JBI's) checklist, and data were analyzed using Stata software (version 14.0). The pooled estimate of DRPs was computed by a Random effect model (DerSimonian-Laird method). Cochran's Q test (I) statistic)), and Begg's correlation and Egger's regression test were assessed for heterogeneity and publication bias, respectively.
RESULT
Overall, 32 studies with a total sample size of 7,129 were included in the review. The estimated pooled prevalence of DRPs was 70% [0.70 (95% CI 0.64-0.76; I = 97.6% p = 0.000)]. Polypharmacy (taking ≥ 5 drugs) [RR = 1.3], medical comorbidity [RR = 1.3], poor medication adherence [RR = 1.7], uncontrolled blood pressure [RR = 1.4], substance use [RR = 1.2], type 2 diabetes [RR = 1.8], significant drug interaction [RR = 1.33], and a negative medication belief [RR = 3.72] significantly influenced the occurrence of DRPs.
CONCLUSION
The estimated national prevalence of DRPs in Ethiopia was high. Presence of medical comorbidity, using multiple drugs, significant drug interaction, poor medication adherence, uncontrolled blood pressure, type 2 diabetes, substance use and a negative belief about medication significantly influenced the occurrence of DRPs. Initiating and/or strengthening pharmaceutical care services at the health care facilities could lower the occurrence of DRPs. PROSPERO registration number CRD42020162329.
PubMed: 33902729
DOI: 10.1186/s40545-021-00312-z