-
The Cochrane Database of Systematic... May 2023Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL).
OBJECTIVES
To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable.
DATA COLLECTION AND ANALYSIS
All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm.
MAIN RESULTS
We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being 'high' or 'some concerns' across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB.
AUTHORS' CONCLUSIONS
Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.
Topics: Male; Female; Adult; Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Network Meta-Analysis; Sunitinib
PubMed: 37146227
DOI: 10.1002/14651858.CD013798.pub2 -
The Cochrane Database of Systematic... Mar 2018Vitamin B deficiency is common, and the incidence increases with age. Most people with vitamin B deficiency are treated in primary care with intramuscular (IM) vitamin... (Review)
Review
BACKGROUND
Vitamin B deficiency is common, and the incidence increases with age. Most people with vitamin B deficiency are treated in primary care with intramuscular (IM) vitamin B. Doctors may not be prescribing oral vitamin B formulations because they may be unaware of this option or have concerns regarding its effectiveness.
OBJECTIVES
To assess the effects of oral vitamin B versus intramuscular vitamin B for vitamin B deficiency.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and LILACS, as well as the WHO ICTRP and ClinicalTrials.gov. The latest search date was 17 July 2017. We applied no language restrictions. We also contacted authors of relevant trials to enquire about other published or unpublished studies and ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing the effect of oral versus IM vitamin B for vitamin B deficiency.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were serum vitamin B levels, clinical signs and symptoms of vitamin B deficiency, and adverse events. Secondary outcomes were health-related quality of life, acceptability to patients, haemoglobin and mean corpuscular volume, total homocysteine and serum methylmalonic acid levels, and socioeconomic effects. We used GRADE to assess the quality of the evidence for important outcomes. We did not perform meta-analyses due to the small number of included trials and substantial clinical heterogeneity.
MAIN RESULTS
Three RCTs met our inclusion criteria. The trials randomised 153 participants (74 participants to oral vitamin B and 79 participants to IM vitamin B). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 38.6 to 72 years. The treatment frequency and daily dose of vitamin B in the oral and IM groups varied among trials. Only one trial had low or unclear risk of bias across all domains and outcome measures. Two trials reported data for serum vitamin B levels. The overall quality of evidence for this outcome was low due to serious imprecision (low number of trials and participants). In two trials employing 1000 μg/day oral vitamin B, there was no clinically relevant difference in vitamin B levels when compared with IM vitamin B. One trial used 2000 μg/day vitamin B and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B. Two trials reported data on adverse events (very low-quality evidence due to risk of performance bias, detection bias, and serious imprecision). One trial stated that no treatment-related adverse events were seen in both the oral and IM vitamin B groups. One trial reported that 2 of 30 participants (6.7%) in the oral vitamin B group left the trial early due to adverse events. Orally taken vitamin B showed lower treatment-associated costs than IM vitamin B in one trial (low-quality evidence due to serious imprecision). No trial reported on clinical signs and symptoms of vitamin B deficiency, health-related quality of life, or acceptability of the treatment scheme.
AUTHORS' CONCLUSIONS
Low quality evidence shows oral and IM vitamin B having similar effects in terms of normalising serum vitamin B levels, but oral treatment costs less. We found very low-quality evidence that oral vitamin B appears as safe as IM vitamin B. Further trials should conduct better randomisation and blinding procedures, recruit more participants, and provide adequate reporting. Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B deficiency, health related-quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting.
Topics: Administration, Oral; Aged; Humans; Injections, Intramuscular; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex
PubMed: 29543316
DOI: 10.1002/14651858.CD004655.pub3 -
Advances in Nutrition (Bethesda, Md.) May 2017Nutrition is considered to be a possible factor in the pathogenesis of the neurological disease multiple sclerosis (MS). Nutrition intervention studies suggest that diet... (Review)
Review
Nutrition is considered to be a possible factor in the pathogenesis of the neurological disease multiple sclerosis (MS). Nutrition intervention studies suggest that diet may be considered as a complementary treatment to control the progression of the disease; a systematic review of the literature on the influence of diet on MS was therefore conducted. The literature search was conducted by using Medlars Online International Literature (MEDLINE) via PubMed and Scopus. Forty-seven articles met the inclusion criteria. The reviewed articles assessed the relations between macro- and micronutrient intakes and MS incidence. The patients involved used alternative therapies (homeopathy), protocolized diets that included particular foods (herbal products such as grape seed extract, ginseng, blueberries, green tea, etc.), or dietary supplements such as vitamin D, carnitine, melatonin, or coenzyme Q10. Current studies suggest that high serum concentrations of vitamin D, a potent immunomodulator, may decrease the risk of MS and the risk of relapse and new lesions, while improving brain lesions and timed tandem walking. Experimental evidence suggests that serum vitamin D concentration is lower during MS relapses than in remission and is associated with a greater degree of disability [Expanded Disability Status Scale (EDSS) score >3]. The findings suggest that circulating vitamin D concentrations can be considered a biomarker of MS and supplemental vitamin D can be used therapeutically. Other studies point to a negative correlation between serum vitamin B-12 concentrations and EDSS score. Vitamin B-12 has fundamental roles in central nervous system function, especially in the methionine synthase-mediated conversion of homocysteine to methionine, which is essential for DNA and RNA synthesis. Therefore, vitamin B-12 deficiency may lead to an increase in the concentration of homocysteine. Further research is clearly necessary to determine whether treatment with vitamin B-12 supplements delays MS progression.
Topics: Diet; Dietary Supplements; Disease Progression; Humans; Multiple Sclerosis; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 28507011
DOI: 10.3945/an.116.014191 -
Experimental Biology and Medicine... Apr 2017A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in... (Review)
Review
A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the extreme levels of meat and meat-derived compounds showed protection against colon cancer, with some essentially negating the impact of meat in the diet. It is essential that better-designed studies be conducted that use relevant concentrations of meat or meat-derived compounds in complex diets representative of the foods consumed by humans.
Topics: Animals; Colonic Neoplasms; Cooking; Diet, Western; Heme; Humans; Iron; Meat; Mutagens; Observational Studies as Topic
PubMed: 28205448
DOI: 10.1177/1535370217693117 -
Lancet (London, England) Mar 2019Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is... (Meta-Analysis)
Meta-Analysis
Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses.
BACKGROUND
Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth.
METHODS
We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134.
FINDINGS
We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001).
INTERPRETATION
The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery.
FUNDING
Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Bile Acids and Salts; Bilirubin; Biomarkers; Case-Control Studies; Cholestasis, Intrahepatic; Cohort Studies; Female; Humans; Infant, Newborn; Perinatal Death; Pregnancy; Pregnancy Complications; Premature Birth; ROC Curve; Randomized Controlled Trials as Topic; Risk Factors; Stillbirth
PubMed: 30773280
DOI: 10.1016/S0140-6736(18)31877-4 -
Diabetes & Metabolic Syndrome Oct 2022Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B deficiency and more severe neuropathy symptoms. There is still no guideline... (Review)
Review
The efficacy of vitamin B supplementation for treating vitamin B deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review.
BACKGROUND AND AIMS
Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B deficiency and more severe neuropathy symptoms. There is still no guideline suggesting vitamin B supplementation for this population. This study aimed to analyze the efficacy of vitamin B supplementation in this population.
METHOD
Studies reporting the efficacy of vitamin B supplementation in metformin-treated T2DM patients were systematically searched in PubMed, Cochrane, EBSCOHost, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Additional relevant studies were searched manually through citations. Study quality and risk of bias were assessed using suitable tools.
RESULTS
Seven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B level, all of which reported a statistically significant increase after supplementation. Significant reductions in homocysteine after supplementation were found in 2 studies. Its effect on neuropathy symptoms was still unclear, with 2 studies reporting a significant improvement and 1 study reporting no significant effect.
CONCLUSIONS
The results of this systematic review support the implementation of vitamin B supplementation for metformin-treated T2DM to prevent or treat vitamin B deficiency and neuropathy. More high-quality clinical studies are required to generate quantitative analysis and to encourage supplementation in available guidelines.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Vitamin B 12; Hypoglycemic Agents; Vitamin B 12 Deficiency; Peripheral Nervous System Diseases; Homocysteine; Dietary Supplements; Vitamins
PubMed: 36240684
DOI: 10.1016/j.dsx.2022.102634 -
BMJ Clinical Evidence Sep 2011About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks. Jaundice is... (Review)
Review
INTRODUCTION
About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 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 question: 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 February 2010 (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 42 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, immunoglobulin, hospital phototherapy, and tin-mesoporphyrin.
Topics: Bilirubin; Humans; Hyperbilirubinemia, Neonatal; Infant, Premature; Jaundice, Neonatal; Phototherapy
PubMed: 21920055
DOI: No ID Found -
Advances in Nutrition (Bethesda, Md.) Dec 2021Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise...
Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise unpredictable motor fluctuations and other complications. Counteracting these complications with other pharmacological therapies may prompt a vicious circle of side effects, and here, nutritional therapy may have great potential. Knowledge about the role of diet in PD is emerging and multiple studies have investigated nutritional support specifically with respect to levodopa therapy. With this systematic review, we aim to give a comprehensive overview of dietary approaches to optimize levodopa treatment in PD. A systematic search was performed using the databases of PubMed and Scopus between January 1985 and September 2020. Nutritional interventions with the rationale to optimize levodopa therapy in human PD patients were eligible for this study and their quality was assessed with the Cochrane risk-of-bias tool. In total, we included 22 papers that addressed the effects of dietary proteins (n = 10), vitamins (n = 7), fiber (n = 2), soybeans (n = 1), caffeine (n = 1), and ketogenic diets (n = 1) on levodopa therapy. Interventions with protein redistribution diets (PRDs), dietary fiber, vitamin C, and caffeine improved levodopa absorption, thereby enhancing clinical response and reducing motor fluctuations. Furthermore, supplementation of vitamin B-12, vitamin B-6, and folic acid successfully reduced high homocysteine concentrations that emerged from levodopa metabolism and promoted many metabolic and clinical complications, such as neuropathology and osteoporosis. In conclusion, dietary interventions have the potential to optimize levodopa efficacy and control side effects. Nutrition that improves levodopa absorption, including PRDs, fiber, vitamin C, and caffeine, is specifically recommended when fluctuating clinical responses appear. Supplements of vitamin B-12, vitamin B-6, and folic acid are advised along with levodopa initiation to attenuate hyperhomocysteinemia, and importantly, their potential to treat consequent metabolic and clinical complications warrants future research.
Topics: Antiparkinson Agents; Diet; Humans; Levodopa; Parkinson Disease; Vitamin B 12
PubMed: 34113965
DOI: 10.1093/advances/nmab060 -
The Cochrane Database of Systematic... Jul 2020Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and...
BACKGROUND
Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and chest tightness, with or without a cough. Statins possess multiple therapeutic effects, including lowering lipid levels in the blood. Statins are reported to have a potential role as an adjunct treatment in asthma. However, comprehensive evidence of the benefits and harms of using statins is required to facilitate decision making.
OBJECTIVES
To assess the benefits and harms of statins as an adjunct therapy for asthma in adults and children.
SEARCH METHODS
We searched for studies in the Cochrane Airways Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP and Embase Ovid SP, from their inception dates We handsearched the proceedings of major respiratory conferences. We also searched clinical trials registries for completed, ongoing and unpublished studies, and scanned the reference lists of included studies and relevant reviews to identify additional studies. The search is current to 7 February 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with a parallel-group design that assessed statins for at least 12 weeks' duration. We considered all participants with a clinical diagnosis of asthma to be eligible, regardless of age, sex, disease severity and previous or current treatment. We planned to include studies reported as full text, those published as abstract only, and unpublished data.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected the studies, extracted outcome data and intervention characteristics from included studies, and assessed risk of bias according to standard Cochrane methodological procedures. We resolved any disagreement through discussion.
MAIN RESULTS
We found only one trial involving a total of 60 people living with asthma. The trial compared the effect of atorvastatin with a placebo (dummy treatment containing lactose) in treating people with chronic asthma. The trial did not report data for the primary outcomes or adverse events. There was uncertainty about the relative effect on forced expiratory volume in one second (FEV) and peak expiratory flow (PEF) in the atorvastatin group compared with the placebo group. The study did not report serious adverse effects for the interventions. The included study had internal discrepancies in its reported data.
AUTHORS' CONCLUSIONS
The evidence was of very low certainty, so we are unable to draw conclusions about the effectiveness and safety of statins to treat asthma. High-quality RCTs are needed to assess the effect of statins on people with asthma. Well-designed multicentre trials with larger samples and longer duration of treatment are required, which assess outcomes such as adverse events, hospital utilisation and costs, to provide better quality evidence. Future studies that include subgroups of obese people with asthma are also required.
Topics: Anti-Asthmatic Agents; Asthma; Atorvastatin; Forced Expiratory Volume; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Peak Expiratory Flow Rate
PubMed: 32668027
DOI: 10.1002/14651858.CD013268.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