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Frontiers in Nutrition 2021The modified Dietary Approaches to Stop Hypertension (DASH) diet was a potentially effective treatment for pre-hypertensive and hypertensive patients. The evidence for...
The modified Dietary Approaches to Stop Hypertension (DASH) diet was a potentially effective treatment for pre-hypertensive and hypertensive patients. The evidence for the effect of the modified DASH diet on blood pressure reduction was inconsistent. The study was designed to assess the effects of the modified DASH diet on blood pressure (BP) in hypertensive and pre-hypertensive adults. We searched Medline, Embase, CENTRAL, CNKI, VIP, Wanfang Data, SINOMED, Google Scholar, the World Health Organization's International Clinical Trials Registry Platform, and Clinicaltrials.gov from inception to July 1st, 2021. Randomized controlled trials (RCTs) assessing the effects of the modified DASH diet on systolic and diastolic BP, cardiovascular risk factors (body weight, body mass index, waist circumference, fasting glucose, blood lipids), cardiovascular events, and all-cause mortality were included. Statistical analysis was performed using Stata software. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE. A total of 10 RCTs were included. Compared with control diet, the modified DASH diet could reduce mean systolic (-3.26 mmHg; 95% confidence interval -5.58, -0.94 mmHg; = 0.006) and diastolic (-2.07 mmHg; 95% confidence interval -3.68, -0.46 mmHg; = 0.01) BP. Compared with the controlling diet, the modified DASH diet could reduce systolic BP to a greater extent in trials with a mean baseline BP ≥ 140/90 mmHg compared with <140/90 mmHg. Diastolic BP reduction was greater when the mean body mass index was ≥30 kg/m2 than <30 kg/m. Diastolic BP reduction was more marked in trials with a follow-up time of >8 weeks compared with ≤8 weeks. The modified DASH diet could affect mean waist circumference (difference: 1.57 cm; 95% confidence interval -2.98, -0.15) and triglyceride concentration (difference: 1.04 mol/L; 95% confidence interval -1.47, -0.60). The modified DASH diet can reduce BP, waist circumference, and triglyceride concentration in hypertension patients. A higher baseline BP is associated with more marked systolic and diastolic BP reduction. PROSPERO registration number: CRD42020190860.
PubMed: 34557511
DOI: 10.3389/fnut.2021.725020 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2020Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D supplementation in preventing preeclampsia is controversial. To assess the impact of vitamin D supplementation on the risk of preeclampsia, we performed a systematic review of the literature and a meta-analysis of the available randomized clinical trials (RCTs).
METHODS
The primary outcome was preeclampsia. Subgroup analyses were carried out considering the timing of the supplementation, type of intervention and the study design. Meta-regression analysis, including the amount of vitamin D and maternal age, were planned to explore heterogeneity (PROSPERO database registration number: CRD42019119207).
RESULTS
Data were pooled from 27 RCTs comprising 59 arms, which included overall 4777 participants, of whom 2487 were in the vitamin D-treated arm and 2290 in the control arm. Vitamin D administration in pregnancy was associated with a reduced risk of preeclampsia (odd ratio [OR] 0.37, 95% confidence interval [CI]: 0.26, 0.52; I = 0%). If the vitamin D supplementation was started up to 20 weeks' gestation, the odds was a little lower (OR 0.35, 95% CI: 0.24, 0.50, p < 0.001). The effect was largely independent of the supplementation cessation (until delivery or not), type of intervention (vitamin D alone or in association with calcium), and study design. Increasing dose of vitamin D was associated with reduced incidence of preeclampsia (slope of log OR: -1.1, 95% CI: -1.73, -0.46; p < 0.001).
CONCLUSIONS
Results suggest that vitamin D supplementation may be useful in preventing preeclampsia. These data are especially useful for health-care providers who engage in the management of pregnant women at risk for preeclampsia. Our findings are a call for action to definitively address vitamin D supplementation as a possible intervention strategy in preventing preeclampsia in pregnancy.
Topics: Adolescent; Adult; Avitaminosis; Dietary Supplements; Female; Humans; Incidence; Middle Aged; Pre-Eclampsia; Pregnancy; Protective Factors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin D; Young Adult
PubMed: 31526611
DOI: 10.1016/j.clnu.2019.08.015 -
The Lancet. Infectious Diseases Jul 2021The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase.
METHODS
We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363.
FINDINGS
Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 without; crude OR 4·38 [2·58-7·43]), hypertension (240 [35·0%] of 685 vs 763 [20·6%] of 3695; 2·19 [1·36-3·53]), renal disease (44 [45·8%] of 96 vs 271 [16·0%] of 1690; 4·67 [2·21-9·88]), and cardiovascular disease (nine [23·1%] of 39 vs 155 [8·6%] of 1793; 2·79 [1·04-7·50]). Clinical features during the febrile phase associated with progression to severe disease were vomiting (329 [13·5%] of 2432 with vs 258 [6·8%] of 3797 without; 2·25 [1·87-2·71]), abdominal pain and tenderness (321 [17·7%] of 1814 vs 435 [8·1%] of 5357; 1·92 [1·35-2·74]), spontaneous or mucosal bleeding (147 [17·9%] of 822 vs 676 [10·8%] of 6235; 1·57 [1·13-2·19]), and the presence of clinical fluid accumulation (40 [42·1%] of 95 vs 212 [14·9%] of 1425; 4·61 [2·29-9·26]). During the first 4 days of illness, platelet count was lower (standardised mean difference -0·34 [95% CI -0·54 to -0·15]), serum albumin was lower (-0·5 [-0·86 to -0·15]), and aminotransferase concentrations were higher (aspartate aminotransferase [AST] 1·06 [0·54 to 1·57] and alanine aminotransferase [ALT] 0·73 [0·36 to 1·09]) among individuals who progressed to severe disease. Dengue virus serotype 2 was associated with severe disease in children. Secondary infections (vs primary infections) were also associated with severe disease (1682 [11·8%] of 14 252 with vs 507 [5·2%] of 9660 without; OR 2·26 [95% CI 1·65-3·09]). Although the included studies had a moderate to high risk of bias in terms of study confounding, the risk of bias was low to moderate in other domains. Heterogeneity of the pooled results varied from low to high on different factors.
INTERPRETATION
This analysis supports monitoring of the warning signs described in the 2009 WHO guidelines on dengue. In addition, testing for infecting serotype and monitoring platelet count and serum albumin, AST, and ALT concentrations during the febrile phase of illness could improve the early prediction of severe dengue.
FUNDING
Wellcome Trust, National Institute for Health Research, Collaborative Project to Increase Production of Rural Doctors, and Royal Thai Government.
Topics: Abdominal Pain; Coinfection; Comorbidity; Disease Progression; Fever; Humans; Platelet Count; Risk Factors; Serum Albumin; Severe Dengue; Sex Factors; Vomiting
PubMed: 33640077
DOI: 10.1016/S1473-3099(20)30601-0 -
The Cochrane Database of Systematic... Feb 2023Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. Myo-inositol is one of the intracellular mediators of the insulin signal and correlates with insulin sensitivity in type 2 diabetes. The potential beneficial effect of improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. This is an update of a review first published in 2015.
OBJECTIVES
To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO ICTRP (17 March 2022) and the reference lists of retrieved studies.
SELECTION CRITERIA
We included published and unpublished randomised controlled trials (RCTs) including cluster-RCTs and conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes in pregnant women. We included studies that compared any dose of myo-inositol, alone or in a combination preparation, with no treatment, placebo or another intervention. Quasi-randomised and cross-over trials were not eligible. We excluded women with pre-existing type 1 or type 2 diabetes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted the data. We checked the data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included seven RCTs (one conducted in Ireland, six conducted in Italy) reporting on 1319 women who were 10 weeks to 24 weeks pregnant at the start of the studies. The studies had relatively small sample sizes and the overall risk of bias was low. For the primary maternal outcomes, meta-analysis showed that myo-inositol may reduce the incidence of gestational diabetes (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.31 to 0.90; 6 studies, 1140 women) and hypertensive disorders of pregnancy (RR 0.34, 95% CI 0.19 to 0.61; 5 studies, 1052 women). However, the certainty of the evidence was low to very low. For the primary neonatal outcomes, only one study measured the risk of a large-for-gestational-age infant and found myo-inositol was associated with both appreciable benefit and harm (RR 1.40, 95% CI 0.65 to 3.02; 1 study, 234 infants; low-certainty evidence). None of the included studies reported on the other primary neonatal outcomes (perinatal mortality, mortality or morbidity composite). For the secondary maternal outcomes, we are unclear about the effect of myo-inositol on weight gain during pregnancy (mean difference (MD) -0.25 kilogram (kg), 95% CI -1.26 to 0.75 kg; 4 studies, 831 women) and perineal trauma (RR 4.0, 95% CI 0.45 to 35.25; 1 study, 234 women) because the evidence was assessed as being very low-certainty. Further, myo-inositol may result in little to no difference in caesarean section (RR 0.91, 95% CI 0.77 to 1.07; 4 studies, 829 women; low-certainty evidence). None of the included studies reported on the other secondary maternal outcomes (postnatal depression and the development of subsequent type 2 diabetes mellitus). For the secondary neonatal outcomes, meta-analysis showed no neonatal hypoglycaemia (RR 3.07, 95% CI 0.90 to 10.52; 4 studies; 671 infants; very low-certainty evidence). However, myo-inositol may be associated with a reduction in the incidence of preterm birth (RR 0.35, 95% CI 0.17 to 0.70; 4 studies; 829 infants). There were insufficient data for a number of maternal and neonatal secondary outcomes, and no data were reported for any of the long-term childhood or adulthood outcomes, or for health service utilisation outcomes.
AUTHORS' CONCLUSIONS
Evidence from seven studies shows that antenatal dietary supplementation with myo-inositol during pregnancy may reduce the incidence of gestational diabetes, hypertensive disorders of pregnancy and preterm birth. Limited data suggest that supplementation with myo-inositol may not reduce the risk of a large-for-gestational-age infant. The current evidence is based on small studies that were not powered to detect differences in outcomes such as perinatal mortality and serious infant morbidity. Six of the included studies were conducted in Italy and one in Ireland, which raises concerns about the lack of generalisability to other settings. There is evidence of inconsistency among doses of myo-inositol, the timing of administration and study population. As a result, we downgraded the certainty of the evidence for many outcomes to low or very low certainty. Further studies for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors. Myo-inositol at different doses, frequency and timing of administration, should be compared with placebo, diet and exercise, and pharmacological interventions. Long-term follow-up should be considered and outcomes should include potential harms, including adverse effects.
Topics: Adult; Female; Humans; Pregnancy; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dietary Supplements; Hypertension, Pregnancy-Induced; Inositol; Insulin Resistance; Perinatal Death; Premature Birth
PubMed: 36790138
DOI: 10.1002/14651858.CD011507.pub3 -
BMJ (Clinical Research Ed.) Sep 2020To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists.
STUDY SELECTION
Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.
DATA EXTRACTION
At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.
RESULTS
192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19.
CONCLUSION
Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020178076.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Female; Global Health; Humans; Infant, Newborn; Intensive Care, Neonatal; Pandemics; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Prognosis; Risk Factors; SARS-CoV-2
PubMed: 32873575
DOI: 10.1136/bmj.m3320 -
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.The Cochrane Database of Systematic... Dec 2020Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017.
OBJECTIVES
To assess the effects of administering a course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 September 2020), ClinicalTrials.gov, the databases that contribute to the WHO International Clinical Trials Registry Platform (ICTRP) (3 September 2020), and reference lists of the retrieved studies.
SELECTION CRITERIA
We considered all randomised controlled comparisons of antenatal corticosteroid administration with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following rupture of membranes or spontaneous labour), regardless of other co-morbidity, for inclusion in this review.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness based on predefined criteria developed by Cochrane Pregnancy and Childbirth, extracted data and checked them for accuracy, and assessed the certainty of the evidence using the GRADE approach. Primary outcomes included perinatal death, neonatal death, RDS, intraventricular haemorrhage (IVH), birthweight, developmental delay in childhood and maternal death.
MAIN RESULTS
We included 27 studies (11,272 randomised women and 11,925 neonates) from 20 countries. Ten trials (4422 randomised women) took place in lower- or middle-resource settings. We removed six trials from the analysis that were included in the previous version of the review; this review only includes trials that meet our pre-defined trustworthiness criteria. In 19 trials the women received a single course of steroids. In the remaining eight trials repeated courses may have been prescribed. Fifteen trials were judged to be at low risk of bias, two had a high risk of bias in two or more domains and we ten trials had a high risk of bias due to lack of blinding (placebo was not used in the control arm. Overall, the certainty of evidence was moderate to high, but it was downgraded for IVH due to indirectness; for developmental delay due to risk of bias and for maternal adverse outcomes (death, chorioamnionitis and endometritis) due to imprecision. Neonatal/child outcomes Antenatal corticosteroids reduce the risk of: - perinatal death (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; 9833 infants; 14 studies; high-certainty evidence; 2.3% fewer, 95% CI 1.1% to 3.6% fewer), - neonatal death (RR 0.78, 95% CI 0.70 to 0.87; 10,609 infants; 22 studies; high-certainty evidence; 2.6% fewer, 95% CI 1.5% to 3.6% fewer), - respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78; 11,183 infants; studies = 26; high-certainty evidence; 4.3% fewer, 95% CI 3.2% to 5.2% fewer). Antenatal corticosteroids probably reduce the risk of IVH (RR 0.58, 95% CI 0.45 to 0.75; 8475 infants; 12 studies; moderate-certainty evidence; 1.4% fewer, 95% CI 0.8% to1.8% fewer), and probably have little to no effect on birthweight (mean difference (MD) -14.02 g, 95% CI -33.79 to 5.76; 9551 infants; 19 studies; high-certainty evidence). Antenatal corticosteroids probably lead to a reduction in developmental delay in childhood (RR 0.51, 95% CI 0.27 to 0.97; 600 children; 3 studies; moderate-certainty evidence; 3.8% fewer, 95% CI 0.2% to 5.7% fewer). Maternal outcomes Antenatal corticosteroids probably result in little to no difference in maternal death (RR 1.19, 95% CI 0.36 to 3.89; 6244 women; 6 studies; moderate-certainty evidence; 0.0% fewer, 95% CI 0.1% fewer to 0.5% more), chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08; 8374 women; 15 studies; moderate-certainty evidence; 0.5% fewer, 95% CI 1.1% fewer to 0.3% more), and endometritis (RR 1.14, 95% CI 0.82 to 1.58; 6764 women; 10 studies; moderate-certainty; 0.3% more, 95% CI 0.3% fewer to 1.1% more) The wide 95% CIs in all of these outcomes include possible benefit and possible harm.
AUTHORS' CONCLUSIONS
Evidence from this updated review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and RDS and probably reduces the risk of IVH. This evidence is robust, regardless of resource setting (high, middle or low). Further research should focus on variations in the treatment regimen, effectiveness of the intervention in specific understudied subgroups such as multiple pregnancies and other high-risk obstetric groups, and the risks and benefits in the very early or very late preterm periods. Additionally, outcomes from existing trials with follow-up into childhood and adulthood are needed in order to investigate any longer-term effects of antenatal corticosteroids. We encourage authors of previous studies to provide further information which may answer any remaining questions about the use of antenatal corticosteroids without the need for further randomised controlled trials. Individual patient data meta-analyses from published trials are likely to provide answers for most of the remaining clinical uncertainties.
Topics: Adrenal Cortex Hormones; Betamethasone; Bias; Cerebral Intraventricular Hemorrhage; Developmental Disabilities; Dexamethasone; Female; Fetal Organ Maturity; Humans; Hydrocortisone; Infant, Newborn; Lung; Maternal Death; Perinatal Death; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 33368142
DOI: 10.1002/14651858.CD004454.pub4 -
The Cochrane Database of Systematic... Aug 2022Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium... (Review)
Review
BACKGROUND
Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake. Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion.
OBJECTIVES
To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children.
SEARCH METHODS
We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles, abstracts and full-text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia.
MAIN RESULTS
We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries. The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years. We assessed the overall risk of bias as high in six trials and unclear in 12 trials. LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly. On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt. LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence). LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children.
AUTHORS' CONCLUSIONS
When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.
Topics: Adult; Child; Female; Humans; Hyperkalemia; Hypertension; Hypokalemia; Potassium; Pregnancy; Pregnant Women; Randomized Controlled Trials as Topic; Sodium; Sodium Chloride; Sodium Chloride, Dietary; Stroke
PubMed: 35944931
DOI: 10.1002/14651858.CD015207 -
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 -
Clinical Hypertension Sep 2023In patients with end-stage renal disease (ESRD) undergoing dialysis, hypertension is common but often inadequately controlled. The prevalence of hypertension varies... (Review)
Review
In patients with end-stage renal disease (ESRD) undergoing dialysis, hypertension is common but often inadequately controlled. The prevalence of hypertension varies widely among studies because of differences in the definition of hypertension and the methods of used to measure blood pressure (BP), i.e., peri-dialysis or ambulatory BP monitoring (ABPM). Recently, ABPM has become the gold standard for diagnosing hypertension in dialysis patients. Home BP monitoring can also be a good alternative to ABPM, emphasizing BP measurement outside the hemodialysis (HD) unit. One thing for sure is pre- and post-dialysis BP measurements should not be used alone to diagnose and manage hypertension in dialysis patients. The exact target of BP and the relationship between BP and all-cause mortality or cause-specific mortality are unclear in this population. Many observational studies with HD cohorts have almost universally reported a U-shaped or even an L-shaped association between BP and all-cause mortality, but most of these data are based on the BP measured in HD units. Some data with ABPM have shown a linear association between BP and mortality even in HD patients, similar to the general population. Supporting this, the results of meta-analysis have shown a clear benefit of BP reduction in HD patients. Therefore, further research is needed to determine the optimal target BP in the dialysis population, and for now, an individualized approach is appropriate, with particular emphasis on avoiding excessively low BP. Maintaining euvolemia is of paramount importance for BP control in dialysis patients. Patient heterogeneity and the lack of comparative evidence preclude the recommendation of one class of medication over another for all patients. Recently, however, β-blockers could be considered as a first-line therapy in dialysis patients, as they can reduce sympathetic overactivity and left ventricular hypertrophy, which contribute to the high incidence of arrhythmias and sudden cardiac death. Several studies with mineralocorticoid receptor antagonists have also reported promising results in reducing mortality in dialysis patients. However, safety issues such as hyperkalemia or hypotension should be further evaluated before their use.
PubMed: 37653470
DOI: 10.1186/s40885-023-00240-x -
The Cochrane Database of Systematic... Jan 2021Many people with chronic disease have more than one chronic condition, which is referred to as multimorbidity. The term comorbidity is also used but this is now taken to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many people with chronic disease have more than one chronic condition, which is referred to as multimorbidity. The term comorbidity is also used but this is now taken to mean that there is a defined index condition with other linked conditions, for example diabetes and cardiovascular disease. It is also used when there are combinations of defined conditions that commonly co-exist, for example diabetes and depression. While this is not a new phenomenon, there is greater recognition of its impact and the importance of improving outcomes for individuals affected. Research in the area to date has focused mainly on descriptive epidemiology and impact assessment. There has been limited exploration of the effectiveness of interventions to improve outcomes for people with multimorbidity.
OBJECTIVES
To determine the effectiveness of health-service or patient-oriented interventions designed to improve outcomes in people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual.
SEARCH METHODS
We searched MEDLINE, EMBASE, CINAHL and seven other databases to 28 September 2015. We also searched grey literature and consulted experts in the field for completed or ongoing studies.
SELECTION CRITERIA
Two review authors independently screened and selected studies for inclusion. We considered randomised controlled trials (RCTs), non-randomised clinical trials (NRCTs), controlled before-after studies (CBAs), and interrupted time series analyses (ITS) evaluating interventions to improve outcomes for people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual. This includes studies where participants can have combinations of any condition or have combinations of pre-specified common conditions (comorbidity), for example, hypertension and cardiovascular disease. The comparison was usual care as delivered in that setting.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included studies, evaluated study quality, and judged the certainty of the evidence using the GRADE approach. We conducted a meta-analysis of the results where possible and carried out a narrative synthesis for the remainder of the results. We present the results in a 'Summary of findings' table and tabular format to show effect sizes across all outcome types.
MAIN RESULTS
We identified 17 RCTs examining a range of complex interventions for people with multimorbidity. Nine studies focused on defined comorbid conditions with an emphasis on depression, diabetes and cardiovascular disease. The remaining studies focused on multimorbidity, generally in older people. In 11 studies, the predominant intervention element was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In six studies, the interventions were predominantly patient-oriented, for example, educational or self-management support-type interventions delivered directly to participants. Overall our confidence in the results regarding the effectiveness of interventions ranged from low to high certainty. There was little or no difference in clinical outcomes (based on moderate certainty evidence). Mental health outcomes improved (based on high certainty evidence) and there were modest reductions in mean depression scores for the comorbidity studies that targeted participants with depression (standardized mean difference (SMD) -0.41, 95% confidence interval (CI) -0.63 to -0.2). There was probably a small improvement in patient-reported outcomes (moderate certainty evidence). The intervention may make little or no difference to health service use (low certainty evidence), may slightly improve medication adherence (low certainty evidence), probably slightly improves patient-related health behaviours (moderate certainty evidence), and probably improves provider behaviour in terms of prescribing behaviour and quality of care (moderate certainty evidence). Cost data were limited.
AUTHORS' CONCLUSIONS
This review identifies the emerging evidence to support policy for the management of people with multimorbidity and common comorbidities in primary care and community settings. There are remaining uncertainties about the effectiveness of interventions for people with multimorbidity in general due to the relatively small number of RCTs conducted in this area to date, with mixed findings overall. It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future updates. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression in people with co-morbidity.
Topics: Age Factors; Amblyopia; Chronic Disease; Community Health Services; Disease Management; Growth Disorders; Health Behavior; Health Personnel; Health Services Needs and Demand; Humans; Intellectual Disability; Medication Adherence; Multimorbidity; Patient Reported Outcome Measures; Patient-Centered Care; Primary Health Care; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 33448337
DOI: 10.1002/14651858.CD006560.pub4