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Arthritis Research & Therapy Dec 2015Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials.
BACKGROUND
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib).
METHODS
A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods.
RESULTS
The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively.
CONCLUSIONS
In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Communicable Diseases; Humans; Janus Kinase 3; Piperidines; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26669566
DOI: 10.1186/s13075-015-0880-2 -
Nutrients Nov 2023Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation,... (Review)
Review
Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation, diagnostic approaches, and risk factors for the condition to inform prevention strategies. An electronic (PubMed database) and manual literature search following the PRISMA approach was conducted (preregistration with the Open Science Framework, accessed on 15 February 2023). Data were described and analyzed using correlation analyses, Chi-square tests, ANOVAs, and regression analyses, and 102 publications (292 cases) were analyzed. The mean age at first symptoms (anemia, various neurological symptoms) was four months; the mean time to diagnosis was 2.6 months. Maternal B12 at diagnosis, exclusive breastfeeding, and a maternal diet low in B12 predicted infant B12, methylmalonic acid, and total homocysteine. Infant B12 deficiency is still not easily diagnosed. Methylmalonic acid and total homocysteine are useful diagnostic parameters in addition to B12 levels. Since maternal B12 status predicts infant B12 status, it would probably be advantageous to target women in early pregnancy or even preconceptionally to prevent infant B12 deficiency, rather than to rely on newborn screening that often does not reliably identify high-risk children.
Topics: Infant; Infant, Newborn; Pregnancy; Child; Humans; Female; Methylmalonic Acid; Vitamin B 12 Deficiency; Vitamin B 12; Breast Feeding; Homocysteine
PubMed: 38068819
DOI: 10.3390/nu15234960 -
The Cochrane Database of Systematic... Sep 2023A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.
OBJECTIVES
Primary objective To assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review. Secondary objectives • To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides. • To assess the effect of pravastatin on withdrawals due to adverse effects.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to September 2021: CENTRAL (2021, Issue 8), Ovid MEDLINE, Ovid Embase, Bireme LILACS, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
Randomized placebo-controlled trials evaluating the dose response of different fixed doses of pravastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered lipid data from placebo-controlled trials into Review Manager 5 as continuous data and withdrawal due to adverse effects (WDAEs) data as dichotomous data. We searched for WDAEs information from all trials. We assessed all trials using Cochrane's risk of bias tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
MAIN RESULTS
Sixty-four RCTs evaluated the dose-related efficacy of pravastatin in 9771 participants. The participants were of any age, with and without evidence of cardiovascular disease, and pravastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over the doses of 5 mg to 160 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol, and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of pravastatin on blood HDL cholesterol. Pravastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 21.7% to 31.9%, total cholesterol by 16.1% to 23.3%,and triglycerides by 5.8% to 20.0%. The certainty of evidence for these effects was judged to be moderate to high. For every two-fold dose increase there was a 3.4% (95% confidence interval (CI) 2.2 to 4.6) decrease in blood LDL cholesterol. This represented a dose-response slope that was less than the other studied statins: atorvastatin, rosuvastatin, fluvastatin, pitavastatin and cerivastatin. From other systematic reviews we conducted on statins for its effect to reduce LDL cholesterol, pravastatin is similar to fluvastatin, but has a decreased effect compared to atorvastatin, rosuvastatin, pitavastatin and cerivastatin. The effect of pravastatin compared to placebo on WADES has a risk ratio (RR) of 0.81 (95% CI 0.63 to 1.03). The certainty of evidence was judged to be very low.
AUTHORS' CONCLUSIONS
Pravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.
Topics: Humans; Infant, Newborn; Infant; Pravastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Fluvastatin; Rosuvastatin Calcium; Drug-Related Side Effects and Adverse Reactions
PubMed: 37721222
DOI: 10.1002/14651858.CD013673.pub2 -
BMJ Clinical Evidence Jun 2007About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2-4 days after birth, and resolves spontaneously after 1-2 weeks. Jaundice is caused... (Review)
Review
INTRODUCTION
About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2-4 days after birth, and resolves spontaneously after 1-2 weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for unconjugated hyperbilirubinaemia in term and preterm infants? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2006 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: albumin infusion, exchange transfusion, home phototherapy, hospital phototherapy, tin-mesoporphyrin.
Topics: Bilirubin; Evidence-Based Medicine; Exchange Transfusion, Whole Blood; Humans; Hyperbilirubinemia; Intensive Care, Neonatal; Jaundice, Neonatal; Phototherapy; Treatment Outcome
PubMed: 19454091
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Jan 2018There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC).
AIM
To assess comparative efficacy and safety of different therapies as first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor(TNF)-α) agents for moderate-severe UC, through a systematic review and network meta-analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach.
METHODS
We identified randomised controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or second-line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
In biologic-naïve patients (12 trials, no head-to-head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials.
CONCLUSIONS
Infliximab and vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked highest as second-line agent, for induction of remission and mucosal healing in patients with moderate-severe UC, based on indirect comparisons. Head-to-head trials are warranted to inform clinical decision-making with greater confidence.
Topics: Adult; Antibodies, Monoclonal, Humanized; Biological Factors; Biological Products; Colitis, Ulcerative; Drug Therapy; Humans; Infliximab; Network Meta-Analysis; Piperidines; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 29205406
DOI: 10.1111/apt.14422 -
European Heart Journal. Cardiovascular... Dec 2022Considering the inconsistencies in the literature on the atorvastatin effect on blood pressure (BP), we performed these meta-analyses. (Meta-Analysis)
Meta-Analysis
AIMS
Considering the inconsistencies in the literature on the atorvastatin effect on blood pressure (BP), we performed these meta-analyses.
METHODS AND RESULTS
Through a search of the Excerpta Medica Database (EMBASE), PubMed, and Web of Science databases, 1412 articles were identified, from which 33 randomized clinical trials (RCT) and 44 pre-clinical were selected. Populations from RCT were stratified according to baseline BP and lipid levels. We performed meta-analyses of the effect of atorvastatin on systolic (SBP), diastolic and mean BP; heart rate (HR); HR variability, and baroreflex. Atorvastatin reduced SBP in the overall population (P = 0.05 vs. placebo; P = 0.03 vs. baseline), in normotensive and hyperlipidaemic (P = 0.04 vs. placebo; P = 0.0001 vs. baseline) and in hypertensive and hyperlipidaemic (P = 0.02 vs. placebo; P = 0.008 vs. baseline) individuals in parallel RCT, but it did not affect SBP in normotensive and normolipidaemic individuals (P = 0.51 vs. placebo; P = 0.4 vs. baseline). Although an effect of atorvastatin was detected in hyperlipidaemic individuals, the meta-regression coefficient for the association of low density lipoprotein (LDL)-cholesterol reduction with SBP reduction in the overall population demonstrated that SBP reduction is not dependent on the changes in LDL-cholesterol. A meta-analysis of preclinical reports demonstrated that SBP was reduced in atorvastatin-treated hypertensive and normolipidaemic rats (spontaneously hypertensive rats: P < 0.00001), but not in normotensive and normolipidaemic rats (control rats: P = 0.97). Atorvastatin also reduced the HR in spontaneously hypertensive rat.
CONCLUSION
Atorvastatin lowers BP independent of LDL-cholesterol levels. Additional studies are needed to estimate the involvement of the autonomic nervous system in the BP-lowering effect of atorvastatin.
Topics: Humans; Rats; Animals; Atorvastatin; Blood Pressure; Heart Rate; Hypertension; Cholesterol
PubMed: 36138492
DOI: 10.1093/ehjcvp/pvac053 -
Journal of Alzheimer's Disease : JAD 2023Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and...
BACKGROUND
Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and cognitive dysfunction have.
OBJECTIVE
The main purpose of this study was to determine micro- and macronutrients and food frequency intake among the LAC population with mild cognitive impairment (MCI) and dementia.
METHODS
A systematic review using PubMed, Cochrane, Lilacs, and Scielo databases. Energy intake as well as micro- and macronutrients intake were analyzed using a random-effect model and presented in a forest plot.
RESULTS
Nine articles were included, an estimated energy intake of 1598.47 kcal (95% CI 1351.07-1845.88) was obtained. A daily consumption of 73.64 g/day (95% CI 64.07-83.2) of protein; 262.17 g/day (95% CI 214.51-309.93) of carbohydrates, and 57.91 g/day (95% CI 49.16-66.66) of fats were reported. A micronutrients daily intake consumption of 201.35μg/day of vitamin B9 (95% CI 125.32-277.38); 5.61μg/day of vitamin B12 (95% CI 2.53-8.70), and 139.67 mg/day of vitamin C (95% CI 59.33-220.02). Mineral intake of 637.32 mg/day of calcium (95% CI 288.54-986.11) and 9 mg/day of iron (95% CI 2.28-15.71) was obtained. A low intake of fruits and vegetables was found.
CONCLUSION
Individuals with MCI and dementia from LAC have a nutritional deficiency characterized by a lower intake of fruits and vegetables, a high consumption of carbohydrates and protein, adequate fats intake and vitamins B12, vitamin C, and iron consumption, but a low intake of vitamin B9 and calcium.
Topics: Humans; Latin America; Calcium; Cognitive Dysfunction; Vitamins; Folic Acid; Energy Intake; Vitamin B 12; Ascorbic Acid; Eating; Dementia; Iron
PubMed: 37302035
DOI: 10.3233/JAD-230231 -
Journal of the American Academy of... Aug 2022
Meta-Analysis
Topics: Dermatitis, Atopic; Humans; Janus Kinase 1; Janus Kinase Inhibitors; Pyrroles; Treatment Outcome
PubMed: 35358602
DOI: 10.1016/j.jaad.2022.03.039 -
Journal of Cardiovascular Pharmacology Aug 2022Postoperative atrial fibrillation (POAF) is a frequently reported postcardiac surgery complication leading to increased in-hospital and long-term mortality rates. Many... (Meta-Analysis)
Meta-Analysis
Postoperative atrial fibrillation (POAF) is a frequently reported postcardiac surgery complication leading to increased in-hospital and long-term mortality rates. Many randomized controlled trials (RCTs) have recently suggested using statins to protect against POAF. Therefore, we performed a systematic literature search and meta-analysis in electronic databases for eligible studies published between January 2006 and January 2022. The principal inclusion criteria were as follows: RCTs' study design, statin-naive patients, total study participants ≥50 units, and statin pretreatment started no more than 21 days before cardiac surgery. In the primary analysis, statin pretreatment reduced the incidence of POAF compared with placebo. Analyzing different molecules, atorvastatin was associated with lower incidence of POAF but rosuvastatin was not. We therefore performed a sensitivity analysis excluding RCTs affected by important risk of biases. Thus, studies whose participants were ≥199 were those eligible for the secondary analysis. No statistically significant difference between statin pretreatment and placebo (OR 0.87; 95% CI: 0.71-1.07, P = 0.18) as well as for atorvastatin (OR 0.88; 95% CI: 0.61-1.28; P = 0.48; I 2 = 84%) and rosuvastatin (OR 0.87; 95% CI: 0.68-1.12, P = 0.29) was observed. To conclude, statin pretreatment before cardiac surgery is not associated with a significant reduction in POAF occurrence.
Topics: Atorvastatin; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Postoperative Complications; Rosuvastatin Calcium
PubMed: 35580320
DOI: 10.1097/FJC.0000000000001294 -
Journal of Cardiac Surgery Oct 2021Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased...
BACKGROUND
Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased cardiac index, and characterized by inadequate response to standard doses of vasopressors, and increased morbidity and mortality. It occurs in 9%-44% of cardiac surgery patients after cardiopulmonary bypass (CPB). The underlying pathophysiology following CPB consists of resistance to vasopressors (inactivation of Ca voltage gated channels) on the one hand and excessive activation of vasodilators (SIRS, iNOS, and low AVP) on the other. Use of angiotensin-converting enzyme inhibitor (ACE-I), calcium channel blockers, amiodarone, heparin, low cardiac reserve (EF < 35%), symptomatic congestive heart failure, and diabetes mellitus are the perioperative risk factors for VPS after cardiac surgery in adults. Till date, there is no consensus about the outcome-oriented therapeutic management of VPS. Vasopressors such as norepinephrine (NE; 0.025-0.2 µg/kg/min) and vasopressin (0.06 U/min or 6 U/h median dose) are the first choice for the treatment. The adjuvant therapy (hydrocortisone, calcium, vitamin C, and thiamine) and rescue therapy (methylene blue [MB] and hydroxocobalamin) are also considered when perfusion goals (meanarterial pressure [MAP] > 60-70 mmHg) are not achieved with nor-epinephrine and/or vasopressin.
AIMS
The aims of this systematic review are to collect all the clinically relevant data to describe the VPS, its potential risk factors, pathophysiology after CPB, and to assess the efficacy, safety, and outcome of the therapeutic management with catecholamine and non-catecholamine vasopressors employed for refractory vasoplegia after cardiac surgery. Also, to elucidate the current and practical approach for management of VPS after cardiac surgery.
MATERIAL AND METHODS
"PubMed," "Google," and "Medline" weresearched, and over 150 recent relevant articles including RCTs, clinical studies, meta-analysis, reviews, case reports, case series and Cochrane data were analyzed for this systematic review. The filter was applied specificallyusing key words like VPS after cardiac surgery, perioperative VPS following CPB, morbidity, and mortality in VPS after cardiac surgery, vasopressors for VPS that improve outcomes, VPS after valve surgery, VPS after CABG surgery, VPS following complex congenital cardiac anomalies corrective surgery, rescue therapy for VPS, adjuvant therapy for VPS, definition of VPS, outcome in VPS after cardiac surgery, etiopathology of VPS following CPB. This review did not require any ethical approval or consent from the patients.
RESULTS
Despite the recent advances in therapy, the mortality remains as high as 30%-50%. NE has been recommended the most frequent used vasopressor for VPS. It restores and maintain the MAP and provides the outcome benefits. Vasopressin rescue therapy is an alternative approach, if catecholamines and fluid infusions fail to improve hemodynamics. It effectively increases vascular tone and lowers CO, and significantly decreases the 30 days mortality. Hence, suggested a first-line vasopressor agent in postcardiac surgery VPS. Terlipressin (1.3μg/kg/h), a longer acting and more specific vasoconstrictor prevents the development of VPS after CPB in patients treated with ACE-I. MB significantly reduces morbidity and mortality of VPS. The Preoperative MB (1%, 2mg/kg/30min, 1h before surgery) administration in high risk (on ACE-I) patients for VPS undergoing CABG surgery, provides 100% protection against VPS, and early of MB significantly reduces operative mortality, and recommended as a rescue therapy for VPS. Hydroxocobalamin (5 g) has been recommended as a rescue agent in VPS refractory to multiple vasopressors. A combination of ascorbic acid (6 g), hydrocortisone (200 mg/day), and thiamine (400 mg/day) as an adjuvant therapy significantly reduces the vasopressors requirement, and provides mortality and morbidity benefits.
CONCLUSION
Currently, the VPS is frequently encountered (9%-40%) in cardiac surgical patients with predisposing patient-specific risk factors and combined with inflammatory response to CPB. Multidrug therapy (NE, MB, AVP, ATII, terlipressin, hydroxocobalamin) targeting multiple receptor systems is recommended in refractory VPS. A combination of high dosage of ascorbic acid, hydrocortisone and thiamine has been used successfully as adjunctive therapyto restore the MAP. We also advocate for the early use of multiagent vasopressors therapy and catecholamine sparing adjunctive agents to restore the systemic perfusion pressure with a goal of preventing the progressive refractory VPS.
Topics: Adult; Cardiopulmonary Bypass; Drug Therapy, Combination; Humans; Hydroxocobalamin; Leprostatic Agents; Vasoplegia
PubMed: 34251716
DOI: 10.1111/jocs.15805