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The Lancet. Gastroenterology &... Dec 2021Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease.
METHODS
We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values.
FINDINGS
The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias.
INTERPRETATION
Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission.
FUNDING
None.
Topics: Adalimumab; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Benzene Derivatives; Biological Therapy; Carboxylic Acids; Case-Control Studies; Crohn Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Infliximab; Interleukin-12 Subunit p40; Interleukin-23 Subunit p19; Male; Network Meta-Analysis; Placebos; Randomized Controlled Trials as Topic; Remission Induction; Safety; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Ustekinumab
PubMed: 34688373
DOI: 10.1016/S2468-1253(21)00312-5 -
Journal of the American Academy of... May 2022Antibody-based therapies that inhibit proinflammatory cytokine signaling are commonly used in dermatology. Paradoxically, these medications may induce or exacerbate... (Review)
Review
BACKGROUND
Antibody-based therapies that inhibit proinflammatory cytokine signaling are commonly used in dermatology. Paradoxically, these medications may induce or exacerbate inflammatory disorders.
OBJECTIVE
To summarize the spectrum of manifestations, incidence, timing, potential mechanisms of, and general management approaches to paradoxical cutaneous reactions induced by cytokine-targeted antibodies in dermatology.
METHODS
We performed a systematic review and analysis of published cases of cutaneous paradoxical reactions (PRs) reported in association with tumor necrosis factor α, interleukin (IL) 12/23 (p40), IL-17A/17R, IL-23 (p19), and IL-4Rα inhibitors.
RESULTS
We identified 313 articles reporting 2049 cases of PRs. Tumor necrosis factor α inhibitors resulted in 91.2% (1869/2049) of all cases, followed by IL-17/17R (3.5%), IL-4Rα (2.7%), IL-12/23 (2.4%), and IL-23 (0.01%) inhibitors. Psoriasiform and eczematous eruptions were the most commonly reported, but a wide spectrum of patterns were described. Phenotypically overlapping reaction patterns were common. Time to onset typically ranged from weeks to months but could occur more than a year later. Improvement or resolution upon discontinuation of the inciting drug was common.
LIMITATIONS
This was a retrospective analysis.
CONCLUSIONS
Familiarity with the clinical features of PRs from cytokine-blocking antibodies may facilitate efficient recognition and management.
Topics: Antibodies; Cytokines; Dermatology; Humans; Interleukin-23; Psoriasis; Retrospective Studies; Tumor Necrosis Factor-alpha
PubMed: 33307146
DOI: 10.1016/j.jaad.2020.12.010 -
Journal of Clinical Oncology : Official... Oct 2021Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics.
METHODS
A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models.
RESULTS
Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy.
CONCLUSION
These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.
Topics: Breast Neoplasms; Cancer Survivors; Female; Humans; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome
PubMed: 34197218
DOI: 10.1200/JCO.21.00535 -
European Neuropsychopharmacology : the... Jan 2022The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder... (Review)
Review
The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder (BD). The PRISMA method was followed to search the MEDLINE for Randomized Controlled trials, Post-hoc analyses and Meta-analyses and review papers up to August 1st 2020, with the combination of the words 'bipolar', 'manic', 'mania', 'manic depression' and 'manic depressive' and 'randomized'. Trials and meta-analyses concerning the use of lithium either as monotherapy or in combination with other agents in adults were identified concerning acute mania (Ν=64), acute bipolar depression (Ν=78), the maintenance treatment (Ν=73) and the treatment of other issues (N = 93). Treatment guidelines were also identified. Lithium is efficacious for the treatment of acute mania including concomitant psychotic symptoms. In acute bipolar depression it is efficacious only in combination with specific agents. For the maintenance phase, it is efficacious as monotherapy mainly in the prevention of manic while its efficacy for the prevention of depressive episodes is unclear. Its combinations increase its therapeutic value. It is equaly efficacious in rapid and non-rapid cycling patients, in concomitant obsessive-compulsive symptoms, alcohol and substance abuse, the neurocognitive deficit, suicidal ideation and fatigue The current systematic review provided support for the usefulness of lithium against a broad spectrum of clinical issues in Bipolar disorder. Its efficacy is comparable to that of more recently developed agents.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Mania; Randomized Controlled Trials as Topic
PubMed: 34980362
DOI: 10.1016/j.euroneuro.2021.10.003 -
Journal of Gastroenterology Apr 2021The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an...
The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.
Topics: Humans; Anti-Bacterial Agents; Evidence-Based Practice; Japan; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 33620586
DOI: 10.1007/s00535-021-01769-0 -
Journal of Women's Health (2002) Dec 2016Health literacy is thought to impact women's reproductive health, yet no comprehensive systematic reviews have been conducted on the topic. Our objective was to... (Review)
Review
BACKGROUND
Health literacy is thought to impact women's reproductive health, yet no comprehensive systematic reviews have been conducted on the topic. Our objective was to systematically identify, investigate, and summarize research on the relationship between health literacy and women's reproductive health knowledge, behaviors, and outcomes.
METHODS
PRISMA guidelines were used to guide this review. English language, peer-reviewed research articles indexed in MEDLINE as of February 2015 were searched, along with study results posted on Clinicaltrials.gov . Articles were included if they (1) described original data-driven research conducted in developed countries, (2) were published in a peer-reviewed journal, (3) measured health literacy using a validated assessment, (4) reported on the relationship between health literacy and reproductive health outcomes, related knowledge, or behaviors, and (5) consisted of a study population that included reproductive age women.
RESULTS
A total of 34 articles met eligibility criteria and were included in this review. Data were abstracted from articles by two study authors using a standardized form. Abstracted data were then reviewed and summarized in table format. Overall, health literacy was associated with reproductive health knowledge across a spectrum of topics. It was also related to certain health behaviors, such as prenatal vitamin use and breastfeeding. Its relationship with other reproductive behaviors and outcomes remains unclear.
CONCLUSIONS
Health literacy plays an important role in reproductive knowledge and may impact behaviors and outcomes. While further research is necessary, healthcare providers should utilize health literacy best practices now to promote high-quality care for patients.
Topics: Female; Health Behavior; Health Knowledge, Attitudes, Practice; Health Literacy; Humans; Reproductive Health; Sexual Behavior; Women's Health
PubMed: 27564780
DOI: 10.1089/jwh.2016.5810 -
The British Journal of Psychiatry : the... Oct 2016Numerous studies report an association between social support and protection from depression, but no systematic review or meta-analysis exists on this topic. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous studies report an association between social support and protection from depression, but no systematic review or meta-analysis exists on this topic.
AIMS
To review systematically the characteristics of social support (types and source) associated with protection from depression across life periods (childhood and adolescence; adulthood; older age) and by study design (cross-sectional v cohort studies).
METHOD
A systematic literature search conducted in February 2015 yielded 100 eligible studies. Study quality was assessed using a critical appraisal checklist, followed by meta-analyses.
RESULTS
Sources of support varied across life periods, with parental support being most important among children and adolescents, whereas adults and older adults relied more on spouses, followed by family and then friends. Significant heterogeneity in social support measurement was noted. Effects were weaker in both magnitude and significance in cohort studies.
CONCLUSIONS
Knowledge gaps remain due to social support measurement heterogeneity and to evidence of reverse causality bias.
Topics: Adolescent; Adult; Aged; Child; Depression; Depressive Disorder; Humans; Middle Aged; Protective Factors; Social Support; Young Adult
PubMed: 27445355
DOI: 10.1192/bjp.bp.115.169094 -
Medicine Sep 2018Aim of this study was to estimate the prevalence rate of depression in cancer patient caregivers and to identify factors affecting depression and quality of life of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Aim of this study was to estimate the prevalence rate of depression in cancer patient caregivers and to identify factors affecting depression and quality of life of cancer caregivers.
METHODS
Relevant research articles were retrieved after literature search in several electronic databases. Random effects meta-analyses were performed to obtain pooled estimates of the prevalence rates of depression and anxiety; their respective scores, and quality of life scores. Significant relationships between depression and factors related to depression and quality of life reported in individual studies were identified.
RESULTS
Thirty studies were included. Overall, 21,149 caregivers were appraised in these studies (age 52.65 years [95% CI: 49.65, 55.65]; 31.14% [28.40, 33.89] men). The prevalence of depression and anxiety were 42.30% [33.31, 51.29] % and 46.55% [35.59, 57.52], respectively. Quality of life score, as measured with Caregiver Quality of Life-Cancer scale was 64.55 [47.44, 81.66]. Patient's condition, caregiving burden, duration of caregiving, spouse caregiver, caregiver being unemployed, caregiver with chronic disease, caregiver's sleep quality, caregiver's avoidance, financial problems, and female sex were positively associated with depression whereas overall quality of life of caregiver, pre-loss grief, caregiver's education level, caregiver's age, caregiver's sense of coherence, and caregiver's bondage with patient were negatively associated with depression in caregivers.
CONCLUSION
A considerably high prevalence of depression is found in cancer patient caregivers. Several factors may affect depression and their quality of life of cancer patient caregivers.
Topics: Anxiety; Caregivers; Depression; Female; Humans; Male; Neoplasms; Prevalence; Quality of Life; Risk Factors
PubMed: 30278483
DOI: 10.1097/MD.0000000000011863 -
JAMA Network Open Nov 2019Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Marijuana use is common and growing in the United States amid a trend toward legalization. Exposure to tobacco smoke is a well-described preventable cause of many cancers; the association of marijuana use with the development of cancer is not clear.
OBJECTIVE
To assess the association of marijuana use with cancer development.
DATA SOURCES
A search of PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library was conducted on June 11, 2018, and updated on April 30, 2019. A systematic review and meta-analysis of studies published from January 1, 1973, to April 30, 2019, and references of included studies were performed, with data analyzed from January 2 through October 4, 2019.
STUDY SELECTION
English-language studies involving adult marijuana users and reporting cancer development. The search strategy contained the following 2 concepts linked together with the AND operator: marijuana OR marihuana OR tetrahydrocannabinol OR cannabinoid OR cannabis; AND cancer OR malignancy OR carcinoma OR tumor OR neoplasm.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently reviewed titles, abstracts, and full-text articles; 3 reviewers independently assessed study characteristics and graded evidence strength by consensus.
MAIN OUTCOMES AND MEASURES
Rates of cancer in marijuana users, with ever use defined as at least 1 joint-year exposure (equivalent to 1 joint per day for 1 year), compared with nonusers. Meta-analysis was conducted if there were at least 2 studies of the same design addressing the same cancer without high risk of bias when heterogeneity was low to moderate for the following 4 cancers: lung, head and neck squamous cell carcinoma, oral squamous cell carcinoma, and testicular germ cell tumor (TGCT), with comparisons expressed as odds ratios (ORs) with 95% CIs.
RESULTS
Twenty-five English-language studies (19 case-control, 5 cohort, and 1 cross-sectional) were included; few studies (n = 2) were at low risk of bias. In pooled analysis of case-control studies, ever use of marijuana was not associated with head and neck squamous cell carcinoma or oral cancer. In pooled analysis of 3 case-control studies, more than 10 years of marijuana use (joint-years not reported) was associated with TGCT (OR, 1.36; 95% CI, 1.03-1.81; P = .03; I2 = 0%) and nonseminoma TGCT (OR, 1.85; 95% CI, 1.10-3.11; P = .04; I2 = 0%). Evaluations of ever use generally found no association with cancers, but exposure levels were low and poorly defined. Findings for lung cancer were mixed, confounded by few marijuana-only smokers, poor exposure assessment, and inadequate adjustment; meta-analysis was not performed for several outcomes.
CONCLUSIONS AND RELEVANCE
Low-strength evidence suggests that smoking marijuana is associated with developing TGCT; its association with other cancers and the consequences of higher levels of use are unclear. Long-term studies in marijuana-only smokers would improve understanding of marijuana's association with lung, oral, and other cancers.
TRIAL REGISTRATION
PROSPERO identifier: CRD42018102457.
Topics: Humans; Marijuana Use; Neoplasms; Risk Factors
PubMed: 31774524
DOI: 10.1001/jamanetworkopen.2019.16318 -
Clinical Gastroenterology and... Sep 2020We compared the efficacy and safety of different first-line (biologic-naïve) and second-line (prior exposure to tumor necrosis factor [TNF] antagonists) agents for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We compared the efficacy and safety of different first-line (biologic-naïve) and second-line (prior exposure to tumor necrosis factor [TNF] antagonists) agents for treatment of moderate to severely active ulcerative colitis in a systematic review and network meta-analysis.
METHODS
We searched publication databases through September 30, 2019, for randomized trials of adults with moderate to severe ulcerative colitis treated with TNF antagonists, vedolizumab, tofacitinib, or ustekinumab, as first-line or second-line agents, compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of remission and endoscopic improvement; safety outcomes were serious adverse events and infections. We performed a fixed-effects network meta-analysis using the frequentist approach, and calculated odds ratios (ORs) and 95% CI values. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Overall quality of evidence was rated using GRADE (Grading of Recommendations, Assessment, Development and Evaluation).
RESULTS
In biologic-naïve patients, infliximab was ranked highest for induction of clinical remission (OR vs placebo, 4.07; 95% CI, 2.67-6.21; SUCRA, 0.95) and endoscopic improvement (SUCRA, 0.95) (moderate confidence in estimates [CE]). In patients with prior exposure to TNF antagonists, ustekinumab (SUCRA, 0.87) and tofacitinib (SUCRA, 0.87) were ranked highest for induction of clinical remission and were superior to vedolizumab (ustekinumab vs vedolizumab: OR, 5.99; 95% CI, 1.13-31.76 and tofacitinib vs vedolizumab: OR, 6.18; 95% CI, 1.003-8.00; moderate CE) and adalimumab (ustekinumab vs adalimumab: OR, 10.71; 95% CI, 2.01-57.20 and tofacitinib vs adalimumab: OR, 11.05; 95% CI, 1.79-68.41; moderate CE). Vedolizumab had the lowest risk of infections (SUCRA, 0.81), followed by ustekinumab (SUCRA, 0.63) in maintenance trials.
CONCLUSIONS
In a systematic review and network meta-analysis, we found infliximab to be ranked highest in biologic-naïve patients, and ustekinumab and tofacitinib were ranked highest in patients with prior exposure to TNF antagonists, for induction of remission and endoscopic improvement in patients with moderate to severe ulcerative colitis. More trials of direct comparisons are needed to inform clinical decision making with greater confidence.
Topics: Adalimumab; Adult; Colitis, Ulcerative; Humans; Infliximab; Network Meta-Analysis; Ustekinumab
PubMed: 31945470
DOI: 10.1016/j.cgh.2020.01.008