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Vitamin D supplementation ehdnote with or without maidol in tree for reducing risk endnote x7 mahidol free preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched endnote x7 mahidol free Medline, Scopus and Cochrane databases from inception to July Only randomized controlled trials RCTs in English were selected if they had any pair of interventions calcium, vitamin D, both, or placebo.

Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28, women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and endnte plus vitamin D could lower risk of preeclampsia when compared to placebo cree the pooled risk ratios RRs of 0. Results of network meta-analysis were similar with mahidpl corresponding RRs of 0.

None of the controls were significant. Efficacy of supplementation, which was endnote x7 mahidol free by surface under cumulative ranking probabilities, were: vitamin D Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted endnote x7 mahidol free confirm our findings. It is one of the major contributing causes of maternal-fetal morbidity and mortality worldwide [ 1 ].

Globally, 4. The incidence in developed countries was approximately 3. It also related to life-threatening unfavorable outcomes in both mother e. Previous evidence showed an inverse relationship between high blood pressure and calcium intake [ 910 ]. Numerous epidemiological продолжить clinical studies [ 91011 ], and later a series of systematic reviews [ 12131415 ] also demonstrated this endnote x7 mahidol free. As a result, the World Health Organization WHO has recommended to supplement calcium for pregnant women especially to high-risk mahido, with a low calcium diet [ 16 ].

Vitamin D is involved in regulating bone metabolism, absorption of calcium endnote x7 mahidol free phosphate, and maintenance of muscle function [ 17 ]. Therefore, there might be a benefit of vitamin D supplementation in prevention of preeclampsia.

However, systematic reviews [ 1819 ] of randomized controlled trials RCTs did not show any benefit in prevention of preeclampsia, whereas other two systematic reviews [ 2021 ] of observational studies did.

These discrepancy results could be due to confounding bias in the latter or insufficient power mahidlo the former.

Although these pieces of evidence suggest benefits from both calcium and vitamin D supplements, it endnote x7 mahidol free still unclear which supplement or a combination of them is most beneficial for preventing preeclampsia and gestational hypertension GH or pregnancy induced hypertension PIH. A conventional pairwise meta-analysis can directly compare the efficacy or safety of exactly two treatments in head-to-head clinical trials that can comparative by use simple method of direct meta-analysis.

However, in real practice, there are often many potential treatments for a single disease. NMA is an extension of standard pairwise meta-analysis that provides comprehensive comparative treatment effects by mahidoll both direct and indirect evidence.

Because of endnote x7 mahidol free possibility to combine evidence from different treatment comparisons, and because they can identify the single best available treatment for decision-making, NMA are becoming increasingly attractive to clinicians.

This systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses PRISMAextension of network meta-analyses [ 22 ]. The search terms and strategies were constructed based on PICO i. These strategies were modified to suit each search engine where appropriate.

Study identification was done in two phases. First, all previous systematic reviews of calcium and vitamin D supplementations mahixol pregnant women published since inception of each database to July were identified. Then, only individual RCTs included in these previous reviews were selected. Second, all individual RCTs on the same topic published from inception to July were identified.

The reference lists of the retrieved studies were also checked to identify more relevant publications. Where there were multiple publications from the same author s on the same topic, the most complete and recent study was included. Identified studies from Medline, Scopus and Cochrane were imported into Endnote x7 mahidol free X7 and duplicate studies were removed. The selected studies were independently screened by title and abstract by two reviewers W.

Full texts were retrieved if decisions could not be reached envnote information provided in the abstract. Disagreements regarding selection were resolved by consensus or autodesk autocad 2011 activation code free with a third reviewer S. We contacted authors by email up to three rfee if data were insufficient. If there was no response after three attempts, then the study was excluded.

Studies were excluded from the review if they were crossover trials, included multiple pregnancies, or after three unsuccessful attempts requesting data from authors in the приведенная ссылка of insufficient data. Interventions were any of following supplements regardless of dosage and duration of supplements: Calcium, vitamin D, combined calcium and vitamin D.

The control group could be placebo, a standard supplementation e. Generally, preeclampsia endnote x7 mahidol free a new onset hypertension i. An early-onset preeclampsia occurred before 34 weeks of gestation, otherwise it was a late-onset нажмите для продолжения. Eclampsia is a convulsive condition occurring in preeclampsia patients.

Two reviewers W. Co-variables such as mean age, gestational age at enrolment and delivery, gravida, parity, body mass index BMIsmoking, diabetes mellitus, and duration of supplementation were also extracted.

If duration of supplementation was not reported, it was calculated by subtracting gestational age at delivery with gestational age at endnote x7 mahidol free. If gestational age at delivery of that study was not reported, mean gestational age at delivery, i. Data endnote x7 mahidol free, cleaning and checking were performed separately for endnote x7 mahidol free reviewer.

The two datasets were compared and validated, and endnote x7 mahidol free disagreement resolved by consensus. Study quality rfee independently assessed by two reviewers W. The following seven domains were evaluated: selection bias sequence generation and concealmentperformance bias blinding of participants and assessorsdetection bias blinding of outcome assessmentattrition bias incomplete outcome dataendnote x7 mahidol free outcome reporting, and other bias.

Each item was classified as low, high, or an unclear risk of bias if there was insufficient information. The RRs were then directly pooled across studies using fixed-effect model i. Network meta-analysis was applied to indirectly compare effects of supplementation. A two-stage multivariate meta-analysis was applied as follows: Coefficients i. These parameters were then pooled across studies using a multivariate meta-analysis with maximum likelihood function [ 25 ]. Between-study variance and covariance of comparisons were considered using unstructured method.

Effects between active versus active supplementation were then compared using a linear combination of the multivariate meta-analysis model. The inconsistency assumption i. Violation of consistency was assumed if the IF was significantly different from 0. All pairwise comparisons between direct and indirect effects, were estimated and displayed. In addition, small study effect for the whole network was assessed by constructing a comparison-adjusted funnel plot taking into account different comparisons [ 26 ].

Supplementations were coded from endnote x7 mahidol free to newer as 1, 2, 3, 4 for placebo, calcium, vitamin D, and calcium plus vitamin D, respectively. In the absence of small-study effects, we expected the studies to form an inverted funnel centered at zero, i. Finally, a predictive probability of best intervention was estimated using surface under a cumulative ranking curve SUCRA. Efficacy of supplementation was then ranked by predicting probability.

The schema for selection of studies is displayed in Figure tree. Searching for previous systematic reviews identified review studies. Among these, review studies were excluded for reasons describe in Figure 1leaving 29 review studies with individual 71 RCTs that were eligible for смотрите подробнее assessment.

In searching for endnote x7 mahidol free studies, studies were identified for screening titles and abstracts. Among these, studies endnofe excluded leaving 75 endnote x7 mahidol free RCTs that met inclusion criteria for further assessment. After removing duplicates with searching from systematic reviews, 78 RCTs were eligible for assessing full-text.

Of these, only 27 RCTs studies met our inclusion criteria and were considered for quantitative synthesis. The characteristics of the 27 RCTs are described in Table 1.

Individual sample sizes ranged from 30 to with a median of The types of pregnant women varied, The mean age ranged from 16 to Among 27 RCTs, three studies [ 293738 ] were conference abstracts, thus the risk of bias could not be assessed because authors did not publish full articles. In the remaining 24 studies, sequence generation was clearly described in 17 trials Allocation concealment was adequately performed in endnote x7 mahidol free trials Direct comparisons with calcium vs.

These corresponding pooled effects were 0. Sources of heterogeneity for the pooled calcium vs. Subgroup analysis was therefore performed accordingly. The protective effect of calcium supplementation was greater in high risk pregnancies than low risk pregnancies with a pooled RR of 0. The calcium supplement effect was also higher in pregnant women whose supplement endnote x7 mahidol free were 18 weeks or shorter but not for longer than 18 weeks with the pooled RRs of 0.

In addition, subgroup analysis by country of setting developing endnote x7 mahidol free developed countries showed significant preventive effects of calcium in developing countries but not for developed countries with the pooled RR жмите сюда 0. Fourteen RCTs compared effects of calcium vs. Sources of heterogeneity were next explored, as none were identified as a source of heterogeneity. Only studies on preeclampsia were included in indirect comparison, because there mahkdol a lack of RCT studies which reported on effect of vitamin D alone or combination with calcium for GH or PIH causing insufficient data for pooling.

All interventions were mapped in a network plot Figure S3. Glary utilities windows 10 64 bit free download size of each node was proportional to the number of included studies, /23731.txt the edge of each comparison was weighted by the number of pregnant women for that comparison.


Abstract; Free full text ReviewFree to read & use Afterwards, eligible articles were archived to the EndNote X for Windows. I am wondering about the main limitations of Endnote Basic (the free online version), compared to the desktop version? I heard that Mendeley is. Abstract; Free full text ReviewFree to read & use Scopus and Cochrane were imported into EndNote X7 and duplicate studies were removed.


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Learn more about navigating our updated article layout. The PMC legacy view will also be available for a limited time. Federal government websites often end in. The site is secure. Clostridium difficile infection is one of the most common healthcare-associated infections worldwide. Recent epidemiologic studies have suggested that statin users may have a lower risk of C. This meta-analysis was conducted with the aim of summarizing all available data to assess the risk of C.

Cohort, case-control and cross-sectional studies that compared the risk of C. Pooled odds ratio OR and 95 per cent confidence interval CI were calculated using a random-effect, generic inverse variance method. Six case-control studies and two cross-sectional studies met the eligibility criteria and were included in this meta-analysis. The risk of C. This meta-analysis demonstrated a decreased risk of C.

Further studies are required to clarify the role of statins for prevention of C. Clostridium difficile is a spore-forming, toxin-producing Gram-positive bacterium that is the causative agent of antibiotic-associated colitis.

The healthcare cost of C. It is also a significant problem in India with the prevalence of as high as four per cent among hospitalized patients in a study from a tertiary care teaching hospital 3. Antibiotic use is the most important risk factor for C. Statins or hydroxymethylglutaryl HMG -CoA reductase inhibitors are one of the most commonly used medications worldwide as a result of the global epidemic of obesity, metabolic syndrome and cardiovascular diseases 5.

Over the past decades, it has been recognized that the benefits of statins go beyond the conventional cholesterol-lowering effect, as they also have an anti-inflammatory and immunomodulatory property 6.

It has also been shown that statins may be used as an adjunctive therapy for several chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis 7 , 8. Use of statins may also decrease the risk of C. This systematic review and meta-analysis was conducted to summarize all available evidence to assess the risk of C.

No language limitation was applied in this study. Inclusion criteria: The inclusion criteria were as follows: i case-control, cross-sectional or cohort studies published as original articles to determine the risk of C.

Study eligibility was independently determined by three investigators. Differences in the determination of study eligibility were resolved by mutual consensus. The quality of each study was also independently evaluated by each investigator using the validated Newcastle—Ottawa quality assessment scale This scale evaluates each study in three domains including the selection of the participants, the comparability between the groups as well as the ascertainment of the exposure of interest for case-control study and the outcome of interest for cohort study.

The modified Newcastle—Ottawa scale as described by Herzog et al 18 was used for the cross-sectional study. Kappa statistics were used for evaluation of inter-rater agreement on the Newcastle—Ottawa scale. Data extraction: A standardized data collection form was used to extract the following data from each study: title of the study, name of the first author, year when the study was conducted, year when the study was published, country where the study was conducted, number of individuals, demographic data, method used to identify and verify C.

To ensure the accuracy of data extraction, this process was independently conducted by three investigators. Case record forms were cross-checked, and any data discrepancy was also resolved by referring back to the original articles.

Statistical analysis: Data analysis was performed using Review Manager 5. Adjusted point estimates from each study were combined using the generic inverse variance method of DerSimonian and Laird 19 , which assigned the weight of each study in reverse to its variance. As the outcome of interest was relatively uncommon, it was planned to use RR of the cohort studies as an estimate for OR to combine with the OR from cross-sectional and case-control studies. In light of the possibility of high between-study variance due to different study designs and populations, a random-effect model was used rather than a fixed-effect model.

Cochran’s Q test and I 2 statistic were used to determine the between-study heterogeneity. This I 2 statistic quantifies the proportion of total variation across studies that is due to heterogeneity rather than chance. Funnel plot was used to assess the presence of publication bias. After the exclusion of 78 duplicate articles, of them underwent title and abstract review.

One hundred and sixteen articles were excluded at this stage since those were case reports, letters to the editor, review articles, basic science studies, animal studies or interventional studies, leaving 24 articles for a full-length article review. Thirteen of these were excluded since they did not report the outcome of interest whereas three articles were excluded due to duplication. Finally, eight studies 6 case-control studies and 2 cross-sectional studies were included in the data analysis 9 , 10 , 11 , 12 , 13 , 14 , 15 , The literature review and study selection process are demonstrated in Figure 1.

It should be noted that the inter-rater agreement for the quality assessment using the Newcastle—Ottawa scale was high with a kappa statistics of 0.

In this meta-analysis, the risk of C. The forest plot of this meta-analysis is shown in Fig. Forest plot demonstrated the association between statin and risk of Clostridium difficile infection CDI. Evaluation for publication bias: The X-axis of the funnel plot Fig.

The eight included studies had a symmetric distribution around the pooled effect estimate dotted line , with more variation among studies with lower accuracy and less variation among studies with higher accuracy. Therefore, this funnel plot did not suggest the presence of publication bias in favour of positive studies.

Funnel plot assesses for publication bias. Dotted line indicates a symmetric distribution around the pooled effect estimate. Sensitivity analysis: Three sensitivity analyses were conducted to explore the high heterogeneity observed in this meta-analysis. First, the study by Nseir et al 12 was excluded from the meta-analysis, as it was the only study not conducted in the US therefore, only 7 studies were included in this sensitivity analysis 9 , 10 , 11 , 13 , 14 , 15 , Exclusion of this study reduced the I 2 to 84 per cent and did not significantly alter the pooled effect estimate pooled OR 0.

Second, the studies by Tartof et al 13 and Dobesh et al 14 were excluded from the meta-analysis as these were the only two studies with a cross-sectional design therefore, only 6 studies were included in this sensitivity analysis 9 , 10 , 11 , 12 , 15 , Exclusion of these studies reduced the I 2 to 86 per cent and also did not significantly alter the pooled effect estimate pooled OR 0.

Third, the studies by Dobesh et al 14 , Kumarappa et al 9 and Garellek et al 16 were excluded from the meta-analysis as these studies did not adjust their effect estimates for other known risk factors of C.

Exclusion of these studies did not significantly alter the pooled effect estimate pooled OR 0. However, the I 2 increased to 93 per cent. This systematic review and meta-analysis demonstrated the protective effect of statins against C. The risk of developing C. There is a previously published meta-analysis on this issue, but its literature review was completed in Thus, the current work included more updated data.

It should also be noted that across the included studies, two studies 14 , 15 did demonstrate that use of statins increased the risk of C. The most likely explanation is that these studies had a relatively small sample size and, therefore, more variability and less accuracy.

There were two studies investigating the influence of the use of statins to the outcome of C. The result of the first study 22 was in line with the current systematic review and meta-analysis, as use of statins in that study was associated with a better outcome among hospitalized patients who had C.

However, the other study 23 failed to show such benefit and, thus, more studies are required. The exact mechanisms of the decrease in risk of C. First, in vitro studies have demonstrated that statins can promote neutrophil function and increase the capacity of phagocytes to create extracellular traps 24 , and this immunomodulatory property of statins may partly explain the lower risk of C.

In fact, use of statins has been shown to decrease the risk of other types of infection as well Second, statins may have direct antimicrobial effects as shown by in vitro studies 26 , 27 , although there has not been a study that directly demonstrates the antimicrobial effect of statins on C. Third, a mouse study has demonstrated that use of statins has an influence on gut microbiota and could change the gut microbial composition through the alteration of transcription of genes encoding factors involved in gut homeostasis This change could affect the risk of developing C.

Alternatively, the use of statins may only decrease the inflammatory response to C. Studies have demonstrated that use of statins is associated with decreased inflammatory cell influx 31 , reduction of pro-inflammatory cytokine production and reduction of T-cell activation The reduced inflammatory response may lead to the decreased severity of C.

This article has been cited by other articles in PMC. Associated Data Supplementary Materials nutrientss Abstract Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial.

Keywords: calcium, network meta-analysis, gestational hypertension, preeclampsia, prevention, systematic review, vitamin D. Materials and Methods A conventional pairwise meta-analysis can directly compare the efficacy or safety of exactly two treatments in head-to-head clinical trials that can comparative by use simple method of direct meta-analysis. Interventions Interventions were any of following supplements regardless of dosage and duration of supplements: Calcium, vitamin D, combined calcium and vitamin D.

Data Extraction Two reviewers W. Risk of Bias Assessment Study quality was independently assessed by two reviewers W. Statistical Analysis 2. Network Meta-Analysis Network meta-analysis was applied to indirectly compare effects of supplementation. Results 3.

Study Selection and Characteristics The schema for selection of studies is displayed in Figure 1. Open in a separate window. Figure 1. Table 1 Characteristics of included studies. Direct Meta-Analysis 3. Preeclampsia Direct comparisons with calcium vs. Figure 2. Table 2 Estimation of multiple supplementation effects on preeclampsia.

Strengths and Limitations Our study had a number of strengths. Summary of Evidence Our meta-analysis has advantages over previous systematic reviews by integrating both direct and indirect comparisons of calcium, vitamin D, and calcium plus vitamin D supplementation in the entire network approach.

Conclusions Our evidence suggests that calcium supplementation could reduce risk of preeclampsia. Acknowledgments Thanks to Stephen John Pinder for checking and improving the English of this manuscript.

Supplementary Materials The following are available online at www. Click here for additional data file. Appendix A. Appendix B Appendix B. Table A3 Study Setting. Community Based Country of study …………………………………………………………………. Table A4 General Characteristics of study. Quasi-Experimental Design Period of the study ……………………………………………… months. Table A5 Participants.

High Risk Women. Table A6 Intervention. Other ……………….. Table A7 General baseline characteristics of participants. Table A8 Type of Outcomes and Definitions. Appendix B. Table A10 Dichotomous outcomes for Eclampsia. Appendix C. Table A13 Random Sequence Generation. Categorized with non-random approach using any of the following methods: by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.

Table A14 Allocation Concealment. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement—for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed. Table A15 Blinding of Participants and Personnel. Table A16 Blinding of Outcome Assessment.

Table A17 Incomplete Outcome Data. Table A18 Selective Reporting. It is likely that the majority of studies will fall into this category. Table A19 Other Bias. For example, the study: Had a potential source of bias related to the specific study design used e. Author Contributions Study concept and design: W. Conflicts of Interest The authors report no conflicts of interest.

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Copy Download. Calcium vs. Aghamohammadi [ 28 ]. Almirante [ 29 ]. Bassaw [ 30 ]. Low Risk Women. Belizan [ 31 ]. Crowther [ 32 ]. Kumar [ 33 ]. New Delhi. Levine [ 34 ].

Lopez-Jaramillo [ 35 ]. Lopez-Jaramillo [ 37 ]. Lopez-Jaramillo [ 36 ]. Nenad [ 38 ]. Niromanesh [ 39 ]. Puwar [ 40 ]. Rogers [ 41 ]. Hong Kong. Sanchez-Ramos [ 42 ]. Villar [ 11 ]. Baltimore, Argentina. Villar [ 44 ]. Villar [ 43 ]. Wanchu [ 45 ]. Vitamin D vs. Asemi [ 46 ]. Naghshineh [ 47 ]. Sablok [ 48 ].

Calcium plus Vitamin D vs. Asemi [ 49 ]. Marya [ 50 ]. Taherian [ 52 ]. Samimi [ 51 ]. Hossain [ 53 ]. Calcium supplementation. Vitamin D supplementation.

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