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Clinical Gastroenterology and... Sep 2023This study aimed (1) to systematically review controlled trials of solid food diets for the treatment of inflammatory bowel disease (IBD); and (2) to grade the overall... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
This study aimed (1) to systematically review controlled trials of solid food diets for the treatment of inflammatory bowel disease (IBD); and (2) to grade the overall quality of evidence.
METHODS
Systematic review of prospective controlled trials of solid food diets for the induction or maintenance of remission in IBD. Two authors independently performed study selection, data extraction, and assessment of certainty of evidence. Meta-analyses were performed on studies with quantitative data on response, remission, and relapse.
RESULTS
There were 27 studies for meta-analysis. For induction of remission in Crohn's disease (CD), low refined carbohydrate diet and symptoms-guided diet outperformed controls, but studies had serious imprecision and very low certainty of evidence. The Mediterranean diet was similar to the Specific Carbohydrate Diet (low certainty of evidence), and partial enteral nutrition (PEN) was similar to exclusive enteral nutrition (very low certainty of evidence). PEN reduced risk of relapse (very low certainty of evidence), whereas reduction of red meat or refined carbohydrates did not (low certainty of evidence). For ulcerative colitis, diets were similar to controls (very low and low certainty of evidence).
CONCLUSIONS
Among the most robust dietary trials in IBD currently available, certainty of evidence remains very low or low. Nonetheless, emerging data suggest potential benefit with PEN for induction and maintenance of remission in CD. Reduction of red meat and refined carbohydrates might not reduce risk of CD relapse. As more dietary studies become available, the certainty of evidence could improve, thus allowing for more meaningful recommendations for patients.
Topics: Humans; Prospective Studies; Inflammatory Bowel Diseases; Crohn Disease; Remission Induction; Carbohydrates; Recurrence
PubMed: 36470529
DOI: 10.1016/j.cgh.2022.11.026 -
British Journal of Sports Medicine Aug 2023To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population.
DESIGN
Systematic review and cohort-level dose-response meta-analysis.
DATA SOURCES
PubMed, Scopus, Web of Science and reference lists of published studies.
ELIGIBILITY CRITERIA
Prospective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney).
RESULTS
196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted.
CONCLUSIONS
Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. CRD42018095481.
Topics: Male; Adult; Female; Humans; Prospective Studies; Cardiovascular Diseases; Exercise; Neoplasms; Chronic Disease
PubMed: 36854652
DOI: 10.1136/bjsports-2022-105669 -
Journal of Asthma and Allergy 2023Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their... (Review)
Review
BACKGROUND
Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.
RESULTS
Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.
CONCLUSION
Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.
PubMed: 37496824
DOI: 10.2147/JAA.S410592 -
Cancer Communications (London, England) Nov 2023Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the...
OBJECTIVE
Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose-response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers.
METHODS
A systematic review and dose-response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database.
RESULTS
A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose-response curve for lung cancer exhibited a non-linear pattern, with the greatest benefit risk reduction observed at 13,200 MET-minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose-response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET-minutes/week), individuals with high levels of activity (≥ 8,000 MET-minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer.
CONCLUSIONS
This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.
Topics: Humans; Female; Stomach Neoplasms; Prospective Studies; Global Burden of Disease; Nutrition Surveys; Exercise; Breast Neoplasms; Colonic Neoplasms; Risk Assessment; Lung Neoplasms; Liver Neoplasms
PubMed: 37743572
DOI: 10.1002/cac2.12488 -
Digestive Diseases and Sciences Sep 2023Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD).
AIMS
This systematic review and meta-analysis assessed the efficacy and safety of selective IL-23p19 and IL-12/23p40 inhibitors in patients with moderate-to-severe CD.
METHODS
MEDLINE, Embase, and the Cochrane library (CENTRAL) were searched from inception to May 24, 2023, for randomized, placebo- or active comparator-controlled induction and/or maintenance trials of selective IL-23p19 and IL-12/23p40 inhibitors in pediatric and adult patients with CD. The primary outcome was the proportion of patients in clinical remission. Secondary outcomes were clinical response, endoscopic remission, endoscopic response, and safety. Data were pooled using a random-effects model. Risk of bias and certainty of evidence were assessed using the Cochrane risk of bias tool and the GRADE criteria, respectively.
RESULTS
Eighteen trials (n = 5561) were included. Most studies were rated as low risk of bias. Targeting IL-23 was significantly superior to placebo for inducing clinical (risk ratio [RR] = 1.87, 95% confidence interval [CI] 1.58-2.21) and endoscopic (RR = 3.20, 95%CI 2.17-4.70) remission and maintaining clinical remission (RR = 1.39, 95%CI 1.10-1.77) (GRADE high certainty evidence for all outcomes). Subgroup analysis showed that targeting IL-23 was superior to placebo for inducing clinical remission in biologic-naïve (RR = 2.20, 95%CI 1.46-3.32, I = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I = 56.5%, p = 0.01). Targeting IL-23 was associated with a decreased risk of serious adverse events in induction (RR = 0.55, 95%CI 0.44-0.73) and maintenance (RR = 0.72, 95%CI 0.53-0.98) trials compared to placebo (high certainty evidence).
CONCLUSION
Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD.
Topics: Adult; Humans; Child; Crohn Disease; Interleukin-12; Interleukin-23 Subunit p19; Interleukin Inhibitors; Remission Induction; Interleukin-23; Biological Products
PubMed: 37378711
DOI: 10.1007/s10620-023-08014-z -
JAMA Oncology Oct 2023Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with...
IMPORTANCE
Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce.
OBJECTIVE
To conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function.
DATA SOURCES
PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022.
STUDY SELECTION
Randomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 > 50%); otherwise, a fixed-effect model was used.
MAIN OUTCOMES AND MEASURES
The objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome.
RESULTS
A total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; P < .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P < .001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.
PubMed: 37615958
DOI: 10.1001/jamaoncol.2023.3284 -
Clinical and Experimental Rheumatology Oct 2023The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the... (Review)
Review
The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the microbiome and immunity in BD. A systematic search for relevant articles was made on PubMed and the Cochrane Library database using the following terms: "microbiota AND Behçet's disease" or "microbiome AND Behçet's disease". Sixteen articles were included in a qualitative synthesis. This systematic review on the microbiome and Behçet's disease underlines the presence of gut dysbiosis in BD patients. This dysbiosis is marked by (i) a decrease in butyrate-producing bacteria, which could affect T cell differentiation and epigenetic regulation of immune-related genes, (ii) a modification of tryptophan-metabolising bacteria, which could be linked to dysregulated IL-22 secretion, and (iii) a decrease in bacteria known to have anti-inflammatory properties. Regarding oral microbiota, this review underlines the possible role of Streptococcus sanguinis through molecular mimicry and NETosis. Clinical studies of BD have shown that (i) need for dentistry is associated with a more severe course in BD, and (ii) antibiotic-supplemented mouthwash reduces pain and ulcers. Fecal transplantation of BD patients' microbiota into mouse models led to decreased SCFA production, neutrophil activation, and Th1/Th17 responses.Recipient mice showed exacerbated experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). In Herpes Virus Simplex-1 (HSV-1) infected mice mimicking BD, administration of butyrateproducing bacteria improved symptoms and immune variables. The microbiome may thus be involved in BD through immunity regulation and epigenetic modifications.
Topics: Humans; Animals; Mice; Behcet Syndrome; Dysbiosis; Epigenesis, Genetic; Uveitis; Microbiota; Bacteria
PubMed: 37382445
DOI: 10.55563/clinexprheumatol/zbt4gx -
ERJ Open Research Jul 2023Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised... (Review)
Review
BACKGROUND
Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma.
METHODS
We searched four bibliographic databases from inception to 15 March 2021 Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken.
RESULTS
13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated "very low" to "low" for quality of measurement properties and none met all quality standards.
CONCLUSIONS
This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.
PubMed: 37143849
DOI: 10.1183/23120541.00444-2022 -
Communications Medicine Oct 2023Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta...
BACKGROUND
Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.
METHODS
To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument.
RESULTS
We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings.
CONCLUSIONS
While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.
PubMed: 37794169
DOI: 10.1038/s43856-023-00357-y -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in...
BACKGROUND
Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia.
OBJECTIVE
To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments.
METHODS
Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected.
RESULTS
Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression.
CONCLUSIONS
Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.
PubMed: 38405341
DOI: 10.3233/ADR-230045