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The Cochrane Database of Systematic... Mar 2017Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
To estimate and compare the accuracy of first trimester ultrasound markers alone, and in combination with first trimester serum tests for the detection of Down's syndrome.
SEARCH METHODS
We carried out extensive literature searches including MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), and The Database of Abstracts of Reviews of Effects (the Cochrane Library 2011, Issue 7). We checked reference lists and published review articles for additional potentially relevant studies.
SELECTION CRITERIA
Studies evaluating tests of first trimester ultrasound screening, alone or in combination with first trimester serum tests (up to 14 weeks' gestation) for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
DATA COLLECTION AND ANALYSIS
Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
MAIN RESULTS
We included 126 studies (152 publications) involving 1,604,040 fetuses (including 8454 Down's syndrome cases). Studies were generally good quality, although differential verification was common with invasive testing of only high-risk pregnancies. Sixty test combinations were evaluated formed from combinations of 11 different ultrasound markers (nuchal translucency (NT), nasal bone, ductus venosus Doppler, maxillary bone length, fetal heart rate, aberrant right subclavian artery, frontomaxillary facial angle, presence of mitral gap, tricuspid regurgitation, tricuspid blood flow and iliac angle 90 degrees); 12 serum tests (inhibin A, alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (ßhCG), total hCG, pregnancy-associated plasma protein A (PAPP-A), unconjugated oestriol (uE3), disintegrin and metalloprotease 12 (ADAM 12), placental growth factor (PlGF), placental growth hormone (PGH), invasive trophoblast antigen (ITA) (synonymous with hyperglycosylated hCG), growth hormone binding protein (GHBP) and placental protein 13 (PP13)); and maternal age. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free ßhCG.Comparisons of the 10 most frequently evaluated test strategies showed that a combined NT, PAPP-A, free ßhCG and maternal age test strategy significantly outperformed ultrasound markers alone (with or without maternal age) except nasal bone, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). In both direct and indirect comparisons, the combined NT, PAPP-A, free ßhCG and maternal age test strategy showed superior diagnostic accuracy to an NT and maternal age test strategy (P < 0.0001). Based on the indirect comparison of all available studies for the two tests, the sensitivity (95% confidence interval) estimated at a 5% FPR for the combined NT, PAPP-A, free ßhCG and maternal age test strategy (69 studies; 1,173,853 fetuses including 6010 with Down's syndrome) was 87% (86 to 89) and for the NT and maternal age test strategy (50 studies; 530,874 fetuses including 2701 Down's syndrome pregnancies) was 71% (66 to 75). Combinations of NT with other ultrasound markers, PAPP-A and free ßhCG were evaluated in one or two studies and showed sensitivities of more than 90% and specificities of more than 95%.High-risk populations (defined before screening was done, mainly due to advanced maternal age of 35 years or more, or previous pregnancies affected with Down's syndrome) showed lower detection rates compared to routine screening populations at a 5% FPR. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under-ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting test sensitivity. Conversely, for the NT, PAPP-A, free ßhCG and maternal age test strategy, detection rates and false positive rates increased with maternal age in the five studies that provided data separately for the subset of women aged 35 years or more.
AUTHORS' CONCLUSIONS
Test strategies that combine ultrasound markers with serum markers, especially PAPP-A and free ßhCG, and maternal age were significantly better than those involving only ultrasound markers (with or without maternal age) except nasal bone. They detect about nine out of 10 Down's affected pregnancies for a fixed 5% FPR. Although the absence of nasal bone appeared to have a high diagnostic accuracy, only five out of 10 affected Down's pregnancies were detected at a 1% FPR.
Topics: Biomarkers; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; False Positive Reactions; Female; Humans; Maternal Age; Nasal Bone; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28295158
DOI: 10.1002/14651858.CD012600 -
Nutrients Aug 2020Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological...
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.
Topics: Adult; Dietary Supplements; Dysmenorrhea; Endometriosis; Female; Humans; Insulin Resistance; Lipid Metabolism; Male; Menstrual Cycle; Polycystic Ovary Syndrome; Pregnancy; Reproduction; Zinc
PubMed: 32824334
DOI: 10.3390/nu12082464 -
The Cochrane Database of Systematic... Nov 2016Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences.
OBJECTIVES
To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information.
MAIN RESULTS
We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children.
AUTHORS' CONCLUSIONS
This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials.
Topics: Adolescent; Anti-Obesity Agents; Body Mass Index; Child; Cyclobutanes; Fluoxetine; Humans; Lactones; Metformin; Orlistat; Pediatric Obesity; Randomized Controlled Trials as Topic
PubMed: 27899001
DOI: 10.1002/14651858.CD012436 -
The Lancet. Diabetes & Endocrinology Jun 2020Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight.
METHODS
In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496.
FINDINGS
We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p=0·10). Each 1 SD increase in FT concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second.
INTERPRETATION
Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy.
FUNDING
Netherlands Organization for Scientific Research (grant 401.16.020).
Topics: Birth Weight; Female; Gestational Age; Humans; Hypothyroidism; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Complications; Thyroid Function Tests; Thyroid Gland
PubMed: 32445737
DOI: 10.1016/S2213-8587(20)30061-9 -
Sports Medicine (Auckland, N.Z.) Jun 2022Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary...
BACKGROUND
Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary people. The potential benefits of exercise in restoring such altered hormone production and secretion compared to age-matched physically inactive individuals who are ageing remains unclear.
OBJECTIVES
The aim of this systematic review was to summarise the findings of exercise training in modulating levels of ostensibly anabolic and catabolic hormones in adults aged > 40 years.
METHODS
We searched the following electronic databases (to July 2021) without a period limit: Cochrane Library, PubMed, Science Direct, Scopus, SPORTDiscus and Web of Science. Additionally, a manual search for published studies in Google Scholar was conducted for analysis of the 'grey literature' (information produced outside of traditional commercial or academic publishing and distribution channels). The initial search used the terms 'ageing' OR 'advanced age' OR 'old people' OR 'older' OR elderly' AND 'anabolic hormones' OR 'catabolic hormones' OR 'steroid hormones' OR 'sex hormones' OR 'testosterone' OR 'cortisol' OR 'insulin' OR 'insulin-like growth factor-1' OR 'IGF-1' OR 'sex hormone-binding globulin' OR 'SHBG' OR 'growth hormone' OR 'hGH' OR 'dehydroepiandrosterone' OR 'DHEA' OR 'dehydroepiandrosterone sulfate (DHEA-S)' AND 'exercise training' OR 'endurance training' OR 'resistance training' OR ' strength training' OR 'weight-lifting' OR 'high-intensity interval training' OR 'high-intensity interval exercise' OR 'high-intensity intermittent training' OR 'high-intensity intermittent exercise' OR 'interval aerobic training' OR 'interval aerobic exercise' OR 'intermittent aerobic training' OR 'intermittent aerobic exercise' OR 'high-intensity training' OR 'high-intensity exercise' OR 'sprint interval training' OR 'sprint interval exercise' OR 'combined exercise training' OR 'anaerobic training'. Only eligible full texts in English or French were considered for analysis.
RESULTS
Our search identified 484 records, which led to 33 studies for inclusion in the analysis. Different exercise training programs were used with nine studies using endurance training programs, ten studies examining the effects of high-intensity interval training, and 14 studies investigating the effects of resistance training. Most training programs lasted ≥ 2 weeks. Studies, regardless of the design, duration or intensity of exercise training, reported increases in testosterone, sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), human growth hormone (hGH) or dehydroepiandrosterone (DHEA) (effect size: 0.19 < d < 3.37, small to very large) in both older males and females. However, there was no consensus on the effects of exercise on changes in cortisol and insulin in older adults.
CONCLUSION
In conclusion, findings from this systematic review suggest that exercise training increases basal levels of testosterone, IGF-1, SHBG, hGH and DHEA in both male and females over 40 years of age. The increases in blood levels of these hormones were independent of the mode, duration and intensity of the training programs. However, the effects of long-term exercise training on cortisol and insulin levels in elderly people are less clear.
Topics: Adult; Aged; Aging; Dehydroepiandrosterone; Exercise; Female; Hormones; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Insulins; Male; Middle Aged; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34936049
DOI: 10.1007/s40279-021-01612-9 -
Neuro-oncology Jun 2021Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population.
METHODS
Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models.
RESULTS
937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC.
CONCLUSION
There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.
Topics: Brain Neoplasms; Breast Neoplasms; Female; Humans; Incidence; Receptor, ErbB-2; Triple Negative Breast Neoplasms
PubMed: 33367836
DOI: 10.1093/neuonc/noaa285 -
The Cochrane Database of Systematic... Aug 2018Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011.
OBJECTIVES
The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes.
MAIN RESULTS
We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses.
AUTHORS' CONCLUSIONS
In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.
Topics: Adult; Aged; Calcium; Calcium Compounds; Cause of Death; Chelating Agents; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Progression; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Iron Compounds; Lanthanum; Middle Aged; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Renal Dialysis; Sevelamer
PubMed: 30132304
DOI: 10.1002/14651858.CD006023.pub3 -
International Journal of Molecular... Nov 2022Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth... (Review)
Review
Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth factor 21 plays a key role in mediating the metabolic responses to fasting or starvation and acts as an important regulator of energy homeostasis, glucose and lipid metabolism, and insulin sensitivity, in part by its direct action on the central nervous system. Accordingly, pharmacological recombinant fibroblast growth factor 21 therapies have been shown to counteract obesity and its related metabolic disorders in both rodents and nonhuman primates. In this systematic review, we discuss how fibroblast growth factor 21 regulates metabolism and its interactions with the central nervous system. In addition, we also state our vision for possible therapeutic uses of this hepatic-brain axis.
Topics: Animals; Fibroblast Growth Factors; Liver; Insulin Resistance; Brain; Energy Metabolism
PubMed: 36362103
DOI: 10.3390/ijms232113318 -
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
European Review For Medical and... Jan 2017Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general... (Review)
Review
OBJECTIVE
Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general population - approximately 27% and 8%, respectively. This is extremely important in young women, because both disorders are connected with fertility problems. As HT and PCOS occur together, fertility problems may become a serious clinical issue in these patients.
MATERIALS AND METHODS
A systematic literature review in PubMed of PCOS- and HT-related articles in English, published until December 2015 was conducted.
RESULTS
The reasons for joint prevalence still remain unclear. Genetic and autoimmune backgrounds are recognized to be possible common etiological factors. Three genetic polymorphisms have been described to play a role in PCOS as well as in HT. They are polymorphism of the gene for fibrillin 3 (FBN3) regulating the activity of transforming growth factor-b (TGF-b) and regulatory T cell levels, gonadotropin-releasing hormone receptor (GnRHR) polymorphism and CYP1B1 polymorphism standing for estradiol hydroxylation. High estrogen-to-progesterone ratios owing to anovulatory cycles, as well as high estrogen levels during prenatal life, disrupt development of the thymus and its function in maintaining immune tolerance, and are suspected to enhance autoimmune response in PCOS. Vitamin D deficiency could be also involved in the pathogenesis of HT and PCOS.
CONCLUSIONS
The above-mentioned common etiological factors associated with fertility problems in HT and PCOS require further research.
Topics: Cytochrome P-450 CYP1B1; Female; Fibrillins; Hashimoto Disease; Humans; Polycystic Ovary Syndrome; Receptors, LHRH; Transforming Growth Factor beta
PubMed: 28165551
DOI: No ID Found