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Computational and Mathematical Methods... 2022Evidences which prove relation between breastfeeding women and risk of breast cancer have been limited. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidences which prove relation between breastfeeding women and risk of breast cancer have been limited.
OBJECTIVE
A meta-analysis was carried out on the basis of published literature from clinical trials and studies among different parts of the world.
METHODS
Studies were analyzed and extracted using PRISMA flowchart. RevMan 5.4.1 was used for analyzing the extracted data. Included studies were fully cited texts with complete information about studies, trails conducted for risk of breast cancer, and breastfeeding correlations.
RESULTS
Menarche age, family history, lactation duration, and menopausal status have a strong effect on the risks of breast cancer. Family history studies concluded that for 95% CI, the risk ratio was 2.66 (2.00, 3.52).
CONCLUSION
Findings have suggested that family history and lactation duration affect the risks of breast cancer.
Topics: Adolescent; Adult; Breast Feeding; Breast Neoplasms; Child; Computational Biology; Female; Humans; Lactation; Menarche; Menopause; Middle Aged; Odds Ratio; Pregnancy; Risk Factors; Young Adult
PubMed: 35126640
DOI: 10.1155/2022/8500910 -
The Cochrane Database of Systematic... May 2022Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.
OBJECTIVES
To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety.
SEARCH METHODS
For this update of the living systematic review, we updated our searches of the following databases monthly to October 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).
DATA COLLECTION AND ANALYSIS
We conducted duplicate study selection, data extraction, risk of bias assessment and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
MAIN RESULTS
This update includes an additional 19 studies, taking the total number of included studies to 167, and randomised participants to 58,912, 67.2% men, mainly recruited from hospitals. Average age was 44.5 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (57%). We assessed a total of 20 treatments. Most (140) trials were multicentric (two to 231 centres). One-third of the studies (57/167) had high risk of bias; 23 unclear risk, and most (87) low risk. Most studies (127/167) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions, except anti-IL23. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 50.19, 95% CI 20.92 to 120.45), bimekizumab (RR 30.27, 95% CI 25.45 to 36.01), ixekizumab (RR 30.19, 95% CI 25.38 to 35.93), risankizumab (RR 28.75, 95% CI 24.03 to 34.39). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab, ixekizumab and risankizumab showed a higher proportion of patients reaching PASI 90 than other anti-IL17 drugs (secukinumab and brodalumab) and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab and brodalumab) and anti-IL23 drugs (risankizumab and guselkumab) except tildrakizumab showed a higher proportion of patients reaching PASI 90 than ustekinumab and three anti-TNF alpha agents (adalimumab, certolizumab and etanercept). Ustekinumab was superior to certolizumab; adalimumab and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with low- to moderate-certainty for all the comparisons (except methotrexate versus placebo, which was high-certainty). The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
AUTHORS' CONCLUSIONS
Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Adalimumab; Adult; Biological Products; Etanercept; Female; Humans; Infliximab; Male; Methotrexate; Network Meta-Analysis; Psoriasis; Systematic Reviews as Topic; Tumor Necrosis Factor-alpha; Ustekinumab
PubMed: 35603936
DOI: 10.1002/14651858.CD011535.pub5 -
JAMA Dermatology Mar 2020The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments.
OBJECTIVE
To estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis.
DATA SOURCES
A systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included.
STUDY SELECTION
Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline.
DATA EXTRACTION AND SYNTHESIS
Data were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis.
MAIN OUTCOMES AND MEASURES
PASI 75, 90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline.
RESULTS
Sixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses.
CONCLUSIONS AND RELEVANCE
This study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.
Topics: Administration, Oral; Adult; Antibodies, Monoclonal; Biological Products; Dermatologic Agents; Humans; Psoriasis; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 32022825
DOI: 10.1001/jamadermatol.2019.4029 -
Diabetes Care May 2016To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 diabetes.
RESEARCH DESIGN AND METHODS
We searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite.
RESULTS
We identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 [1.24-1.48]; I(2) = 9.5%), 36% for leucine (1.36 [1.17-1.58]; I(2) = 37.4%), 35% for valine (1.35 [1.19-1.53]; I(2) = 45.8%), 36% for tyrosine (1.36 [1.19-1.55]; I(2) = 51.6%), and 26% for phenylalanine (1.26 [1.10-1.44]; I(2) = 56%). Glycine and glutamine were inversely associated with type 2 diabetes risk (0.89 [0.81-0.96] and 0.85 [0.82-0.89], respectively; both I(2) = 0.0%).
CONCLUSIONS
In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
Topics: Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Metabolomics; Middle Aged; Prediabetic State; Prospective Studies
PubMed: 27208380
DOI: 10.2337/dc15-2251 -
Clinical Gastroenterology and... Jan 2022Biologics are used routinely in pregnant women with inflammatory bowel disease (IBD), but large-scale data reporting adverse pregnancy outcomes among biologic users are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Biologics are used routinely in pregnant women with inflammatory bowel disease (IBD), but large-scale data reporting adverse pregnancy outcomes among biologic users are lacking. We sought to estimate the prevalence of adverse pregnancy outcomes in women with IBD on biologic therapies.
METHODS
We searched major databases from inception to June 2020 for studies estimating the prevalence of adverse pregnancy outcomes in IBD when using biologics (anti-tumor necrosis factor [TNF], anti-integrins, and anticytokines). Prevalence and relative risk (RR) were pooled using a random-effects model.
RESULTS
Forty-eight studies were included in the meta-analysis comprising 6963 patients. Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% (95% CI, 6%-10%; I = 87.4%) for early pregnancy loss, 9% (95% CI, 7%-11%; I = 89.9%) for preterm birth, 0% (95% CI, 0%-0%; I = 0%) for stillbirth, 8% (95% CI, 5%-10%; I = 87.0%) for low birth weight, and 1% (95% CI, 1%-2%; I = 78.3%) for congenital malformations. These rates are comparable with those published in the general population. In subgroup analyses of a small number of studies, the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab vs anti-TNF users. Meta-regression did not show an association of disease activity or concomitant thiopurine on adverse outcomes. Continued TNF inhibitor use during the third trimester was not associated with risk of preterm birth (RR, 1.41; 95% CI, 0.77-2.60; I = 0%), low birth weight (RR, 1.32; 95% CI, 0.80-2.18; I = 0%), or congenital malformations (RR, 1.28; 95% CI, 0.47-3.49; I = 0%).
CONCLUSIONS
Adverse pregnancy outcomes among pregnant IBD women using biologics are comparable with that of the general population. PROSPERO protocol #CRD42019135721.
Topics: Biological Products; Female; Humans; Infant, Newborn; Inflammatory Bowel Diseases; Pregnancy; Pregnancy Outcome; Premature Birth; Tumor Necrosis Factor Inhibitors
PubMed: 32931960
DOI: 10.1016/j.cgh.2020.09.021 -
The Cochrane Database of Systematic... Nov 2016Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally at birth and should last continually until the end of the first breastfeeding. SSC involves placing the dried, naked baby prone on the mother's bare chest, often covered with a warm blanket. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring fulfillment of basic biological needs. This time frame immediately post birth may represent a 'sensitive period' for programming future physiology and behavior.
OBJECTIVES
To assess the effects of immediate or early SSC for healthy newborn infants compared to standard contact on establishment and maintenance of breastfeeding and infant physiology.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 December 2015), made personal contact with trialists, consulted the bibliography on kangaroo mother care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials that compared immediate or early SSC with usual hospital care.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included 46 trials with 3850 women and their infants; 38 trials with 3472 women and infants contributed data to our analyses. Trials took place in 21 countries, and most recruited small samples (just 12 trials randomized more than 100 women). Eight trials included women who had SSC after cesarean birth. All infants recruited to trials were healthy, and the majority were full term. Six trials studied late preterm infants (greater than 35 weeks' gestation). No included trial met all criteria for good quality with respect to methodology and reporting; no trial was successfully blinded, and all analyses were imprecise due to small sample size. Many analyses had statistical heterogeneity due to considerable differences between SSC and standard care control groups. Results for womenSSC women were more likely than women with standard contact to be breastfeeding at one to four months post birth, though there was some uncertainty in this estimate due to risks of bias in included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07 to 1.43; participants = 887; studies = 14; I² = 41%; GRADE: moderate quality). SSC women also breast fed their infants longer, though data were limited (mean difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies = six; GRADE:low quality); this result was from a sensitivity analysis excluding one trial contributing all of the heterogeneity in the primary analysis. SSC women were probably more likely to exclusively breast feed from hospital discharge to one month post birth and from six weeks to six months post birth, though both analyses had substantial heterogeneity (from discharge average RR 1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I² = 44%; GRADE: moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90; participants = 640; studies = seven; I² = 62%; GRADE: moderate quality).Women in the SCC group had higher mean scores for breastfeeding effectiveness, with moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD 2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I² = 41%). SSC infants were more likely to breast feed successfully during their first feed, with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants = 575; studies = five; I² = 85%). Results for infantsSSC infants had higher SCRIP (stability of the cardio-respiratory system) scores overall, suggesting better stabilization on three physiological parameters. However, there were few infants, and the clinical significance of the test was unclear because trialists reported averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI 0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants = 144; studies = three; GRADE: low quality), but similar temperature to infants in standard care (MD 0.30 degree Celcius (°C) 95% CI 0.13 °C to 0.47 °C; participants = 558; studies = six; I² = 88%; GRADE: low quality). Women and infants after cesarean birthWomen practicing SSC after cesarean birth were probably more likely to breast feed one to four months post birth and to breast feed successfully (IBFAT score), but analyses were based on just two trials and few women. Evidence was insufficient to determine whether SSC could improve breastfeeding at other times after cesarean. Single trials contributed to infant respiratory rate, maternal pain and maternal state anxiety with no power to detect group differences. SubgroupsWe found no differences for any outcome when we compared times of initiation (immediate less than 10 minutes post birth versus early 10 minutes or more post birth) or lengths of contact time (60 minutes or less contact versus more than 60 minutes contact).
AUTHORS' CONCLUSIONS
Evidence supports the use of SSC to promote breastfeeding. Studies with larger sample sizes are necessary to confirm physiological benefit for infants during transition to extra-uterine life and to establish possible dose-response effects and optimal initiation time. Methodological quality of trials remains problematic, and small trials reporting different outcomes with different scales and limited data limit our confidence in the benefits of SSC for infants. Our review included only healthy infants, which limits the range of physiological parameters observed and makes their interpretation difficult.
Topics: Breast Feeding; Female; Humans; Infant; Infant, Newborn; Kangaroo-Mother Care Method; Mother-Child Relations; Mothers; Object Attachment; Randomized Controlled Trials as Topic; Skin Physiological Phenomena; Touch
PubMed: 27885658
DOI: 10.1002/14651858.CD003519.pub4 -
Frontiers in Immunology 2023Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors.... (Review)
Review
Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.
Topics: Humans; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Arthritis, Gouty; Inflammasomes; Polymorphism, Genetic; Genetic Predisposition to Disease; Cytokines
PubMed: 37051231
DOI: 10.3389/fimmu.2023.1137822 -
The American Journal of Medicine Dec 2006Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of... (Meta-Analysis)
Meta-Analysis Review
Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety.
Topics: Humans; Phytotherapy; Plant Extracts; Plant Roots; Sleep Initiation and Maintenance Disorders; Valerian
PubMed: 17145239
DOI: 10.1016/j.amjmed.2006.02.026 -
BMC Pediatrics Feb 2018Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to... (Review)
Review
BACKGROUND
Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity.
METHODS
PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers.
RESULTS
After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion.
CONCLUSION
Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better understand how adversity, its timing and severity, and the presence of individual genetic, epigenetic, and protective factors affects children's health and development.
Topics: Adolescent; Child; Child Abuse; Child, Preschool; Family Relations; Humans; Infant; Infant, Newborn; Life Change Events; Psychological Trauma; Stress, Psychological; Young Adult
PubMed: 29475430
DOI: 10.1186/s12887-018-1037-7 -
BMJ (Clinical Research Ed.) Mar 2022To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.
STUDY SELECTION
Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.
METHODS
A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.
RESULTS
82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I=89%; 0.29, 0.11 to 0.58, I=97%), and solid cancers (0.55, 0.46 to 0.65, I=78%; 0.44, 0.36 to 0.53, I=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I=0%; 0.06, 0.04 to 0.08, I=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I=88%; 0.62, 0.54 to 0.70, I=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I=92%; 0.77, 0.66 to 0.85, I=93%), and solid cancers (0.90, 0.88 to 0.93, I=51%; 0.89, 0.86 to 0.91, I=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I=0%; 0.97, 0.83 to 1.00, I=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.
CONCLUSION
Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021272088.
Topics: COVID-19; COVID-19 Vaccines; Humans; Immunocompetence; SARS-CoV-2; Seroconversion
PubMed: 35236664
DOI: 10.1136/bmj-2021-068632