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Nutrition Reviews Mar 2022Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of homocysteine levels can benefit cognitive function.
OBJECTIVE
To investigate whether B vitamin supplementation can reduce the risk of cognitive decline and incident dementia.
DATA SOURCES
The PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for articles published from the inception dates to March 1, 2020. Randomized controlled trials (RCT) were included if B vitamins were supplied to investigate their effect on the rate of cognitive decline. Cohort studies investigating dietary intake of B vitamins and the risk of incident dementia were eligible. Cross-sectional studies comparing differences in levels of B vitamins and Hcy were included.
DATA EXTRACTION
Two reviewers independently performed data extraction and assessed the study quality.
DATA ANALYSIS
Random-effect or fixed-effect models, depending on the degree of heterogeneity, were performed to calculate mean differences (MDs), hazard ratios (HRs), and odds ratios (ORs).
RESULTS
A total of 95 studies with 46175 participants (25 RCTs, 20 cohort studies, and 50 cross-sectional studies) were included in this meta-analysis. This meta-analysis supports that B vitamins can benefit cognitive function as measured by Mini-Mental State Examination score changes (6155 participants; MD, 0.14, 95%CI 0.04 to 0.23), and this result was also significant in studies where placebo groups developed cognitive decline (4211 participants; MD, 0.16, 95%CI 0.05 to 0.26), suggesting that B vitamins slow cognitive decline. For the > 12 months interventional period stratum, B vitamin supplementation decreased cognitive decline (3814 participants; MD, 0.15, 95%CI 0.05 to 0.26) compared to placebo; no such outcome was detected for the shorter interventional stratum (806 participants; MD, 0.18, 95%CI -0.25 to 0.61). In the non-dementia population, B vitamin supplementation slowed cognitive decline (3431 participants; MD, 0.15, 95%CI 0.04 to 0.25) compared to placebo; this outcome was not found for the dementia population (642 participants; MD, 0.20, 95%CI -0.35 to 0.75). Lower folate levels (but not B12 or B6 deficiency) and higher Hcy levels were significantly associated with higher risks of dementia (folate: 6654 participants; OR, 1.76, 95%CI 1.24 to 2.50; Hcy: 12665 participants; OR, 2.09, 95%CI 1.60 to 2.74) and cognitive decline (folate: 4336 participants; OR, 1.26, 95%CI 1.02 to 1.55; Hcy: 6149 participants; OR, 1.19, 95%CI 1.05 to 1.34). Among the population without dementia aged 50 years and above, the risk of incident dementia was significantly decreased among individuals with higher intake of folate (13529 participants; HR, 0.61, 95%CI 0.47 to 0.78), whereas higher intake of B12 or B6 was not associated with lower dementia risk.
CONCLUSIONS
This meta-analysis suggests that B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population. Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.
Topics: Aged; Cognition; Cognitive Dysfunction; Dementia; Dietary Supplements; Folic Acid; Humans; Middle Aged; Vitamin B 12; Vitamin B Complex
PubMed: 34432056
DOI: 10.1093/nutrit/nuab057 -
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 -
Nutrition Reviews Jul 2023The popularity of plant-based diets, characterized by a partial or complete exclusion of animal products, has increased significantly over the last 10 years. The... (Meta-Analysis)
Meta-Analysis
CONTEXT
The popularity of plant-based diets, characterized by a partial or complete exclusion of animal products, has increased significantly over the last 10 years. The exclusion of animal products removes the most common sources of vitamin B12, which can lead to vitamin B12 deficiency and result in irreversible damage, such as growth stunting.
OBJECTIVE
This aim of this systematic review and meta-analysis was to qualitatively evaluate all studies on this subject and to quantify the potential difference in vitamin B12 levels in healthy children and adolescents aged 5 to 18 years.
DATA SOURCES
PubMed and Embase databases were searched for relevant studies investigating vitamin B12 levels in healthy children and adolescents aged 5 to 18 years on plant-based diets.
DATA EXTRACTION
Studies were assessed qualitatively with the AXIS tool and quantitatively with Stata 16.0 software.
DATA ANALYSIS
Overall, children and adolescents on plant-based diets had a significantly lower vitamin B12 level than omnivorous children and adolescents (-97 pmol/L; 95%CI, -187 to -7; I2 = 98.5%), a difference that remained statistically significant after adjusting for methodological confounders. After subgroup analyses, this effect was not statistically significant for children and adolescents on vegetarian diets but remained significant in children and adolescents on vegan or macrobiotic diets. Moreover, total vitamin B12 intake nullified the mean difference in vitamin B12 levels.
CONCLUSION
Despite high heterogeneity across studies, these results indicate that children and adolescents on plant-based diets, especially those on vegan and macrobiotic diets, may be at risk of developing vitamin B12 deficiency.
Topics: Child; Humans; Diet; Diet, Vegetarian; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 36413044
DOI: 10.1093/nutrit/nuac096 -
Journal of Alternative and... Dec 2020To assess the efficacy and safety of mecobalamin on peripheral neuropathy. Mecobalamin is an active form of vitamin B12 that has been suggested to be beneficial in... (Meta-Analysis)
Meta-Analysis
To assess the efficacy and safety of mecobalamin on peripheral neuropathy. Mecobalamin is an active form of vitamin B12 that has been suggested to be beneficial in improving nerve conduction and neuropathic pain symptoms. Although it is already widely used in Asia for the treatment of peripheral neuropathies, its efficacy remains unclear. Relevant electronic databases were systematically searched for randomized controlled trials investigating the efficacy and safety of mecobalamin on peripheral neuropathy, from inception through December 2019. Study selection, data extraction, and quality assessment were performed independently by two reviewers. The clinical therapeutic efficacy, pain score, neuropathic symptom score, nerve conduction velocities (NCVs), and adverse events of mecobalamin were assessed and were pooled by using a random-effects model. Heterogeneity was assessed by and chi-squared tests. Fifteen studies with 1707 peripheral neuropathy patients caused by diabetic peripheral neuropathy and herpetic neuropathy were included. Based on Cochrane's risk of bias criteria, most of the included studies (11/15, 73%) were rated high risk of bias, whereas 20% and 7% were rated some concerns and low risk of bias, respectively. In terms of the proportion of patients achieving clinical therapeutic efficacy, mecobalamin alone (risk ratio [RR] = 1.17; 95% confidence interval [CI] 1.03-1.33) and mecobalamin in combination (RR = 1.32; 95% CI 1.21-1.45) are more effective than active control. For NCV outcomes, only mecobalamin combination treatment was effective. Neither mecobalamin alone nor mecobalamin in combination is effective on the pain score and neuropathic symptom outcomes. No serious adverse events associated with mecobalamin were reported during the treatment periods. Our findings indicate that mecobalamin in combination may be effective in improving clinical therapeutic efficacy and NCV outcomes for peripheral neuropathy patients, but the evidence is not clear for mecobalamin alone. More high-quality studies are required to confirm this finding.
Topics: Aged; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Vitamin B 12
PubMed: 32716261
DOI: 10.1089/acm.2020.0068 -
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 -
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 -
The Cochrane Database of Systematic... Mar 2023Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been... (Review)
Review
BACKGROUND
Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.
OBJECTIVES
To assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.
SEARCH METHODS
Searches were conducted on 31 January 2022 in the following databases: CENTRAL via CRS Web, MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.
SELECTION CRITERIA
We included RCTs, cluster-RCTs and quasi-RCTs comparing intermittent phototherapy with continuous phototherapy in jaundiced infants (both term and preterm) up to the age of 30 days. We compared intermittent phototherapy with continuous phototherapy by any method and at any dose and duration as defined by the authors.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Our primary outcomes of interest were rate of decline of serum bilirubin, and kernicterus. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included 12 RCTs (1600 infants) in the review. There is one ongoing study and four awaiting classification. There was little or no difference between intermittent phototherapy and continuous phototherapy with respect to rate of decline of bilirubin in jaundiced newborn infants (MD -0.09 micromol/L/hr, 95% CI -0.21 to 0.03; I² = 61%; 10 studies; 1225 infants; low-certainty evidence). One study involving 60 infants reported no incidence of bilirubin induced brain dysfunction (BIND). It is uncertain whether either intermittent or continuous phototherapy reduces BIND because the certainty of this evidence is very low. There was little or no difference in treatment failure (RD 0.03, 95% CI 0.08 to 0.15; RR 1.63, 95% CI 0.29 to 9.17; 1 study; 75 infants; very low-certainty evidence) or infant mortality (RD -0.01, 95% CI -0.03 to 0.01; RR 0.69, 95% CI 0.37 to 1.31 I² = 0%; 10 studies, 1470 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. Continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. Large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
Topics: Infant; Infant, Newborn; Humans; Jaundice, Neonatal; Phototherapy; Bilirubin; Family
PubMed: 36867730
DOI: 10.1002/14651858.CD008168.pub2 -
The Cochrane Database of Systematic... May 2023Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels.
OBJECTIVES
To determine the diagnostic accuracy of transcutaneous bilirubin measurement for detecting hyperbilirubinaemia in newborns.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies.
SELECTION CRITERIA
We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis.
MAIN RESULTS
We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%.
AUTHORS' CONCLUSIONS
The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement.
Topics: Humans; Infant; Infant, Newborn; Bilirubin; Cross-Sectional Studies; Hyperbilirubinemia; Jaundice, Neonatal; Neonatal Screening; Prospective Studies
PubMed: 37158489
DOI: 10.1002/14651858.CD012660.pub2 -
Gastroenterology May 2020Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis.
METHODS
We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events.
RESULTS
We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37).
CONCLUSIONS
In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.
Topics: Arthritis, Rheumatoid; Azetidines; Herpes Zoster; Heterocyclic Compounds, 3-Ring; Humans; Incidence; Inflammatory Bowel Diseases; Janus Kinase Inhibitors; Janus Kinases; Piperidines; Placebos; Psoriasis; Purines; Pyrazoles; Pyridines; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing; Sulfonamides; Survival Analysis; Treatment Outcome; Triazoles
PubMed: 31926171
DOI: 10.1053/j.gastro.2020.01.001 -
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