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Estimation of within-trial interactions in meta-analysis is crucial for reliable assessment of how treatment effects vary across participant subgroups. However, current methods have various limitations. Patients, clinicians and policy-makers need reliable estimates of treatment effects within specific covariate subgroups, on relative and absolute scales, in order to target treatments appropriately--which estimation of an interaction effect does not in itself provide. Also, the focus has been on covariates with only two subgroups, and may exclude relevant data if only a single subgroup is reported. Therefore, in this article we further develop the "within-trial" framework by providing practical methods to (1) estimate within-trial interactions across two or more subgroups; (2) estimate subgroup-specific ("floating") treatment effects that are compatible with the within-trial interactions and make maximum use of available data; and (3) clearly present this data using novel implementation of forest plots. We described the steps involved and apply the methods to two examples taken from previously published meta-analyses, and demonstrate a straightforward implementation in Stata based upon existing code for multivariate meta-analysis. We discuss how the within-trial framework and plots can be utilised with aggregate (or "published") source data, as well as with individual participant data, to effectively demonstrate how treatment effects differ across participant subgroups.

Hospitalized patients with COVID-19 are at high risk for thrombosis and systemic inflammation. Anticoagulation can improve outcomes, but trials have varied in the doses used. This systematic review and prospective meta-analysis includes and analyzes randomized trials registered by September 2024. The analysis compares therapeutic-, prophylactic-, and intermediate-dose anticoagulation with heparins on 28-day mortality, major bleeding, and other clinical outcomes. Background: Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent. Purpose: To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes. Data Sources: Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov with no restriction by trial status or language. Study Selection: Eligible randomized trials assigned patients hospitalized for COVID-19 to higher- versus lower-dose anticoagulation. Data Extraction: 20 eligible trials provided data in a prospectively agreed format. Two further studies were included based on published data. The primary outcome was all-cause mortality 28 days after randomization. Secondary outcomes were progression to invasive mechanical ventilation or death, thromboembolic events, and major bleeding. Data Synthesis: Therapeutic- compared with prophylactic-dose anticoagulation with heparins reduced 28-day mortality (OR, 0.77 [95% CI, 0.64 to 0.93]; I 2  = 29%; 11 trials, 6297 patients, of whom 5456 required low or no oxygen at randomization). The ORs for 28-day mortality were 1.21 (CI, 0.93 to 1.58; I 2  = 0%) for therapeutic-dose compared with intermediate-dose anticoagulation (6 trials, 1803 patients, 843 receiving noninvasive ventilation at randomization) and 0.95 (CI, 0.76 to 1.19; I 2  = 0%; 10 trials, 3897 patients, 2935 receiving no or low oxygen at randomization) for intermediate- versus prophylactic-dose anticoagulation. Treatment effects appeared broadly consistent across predefined patient subgroups, although some analyses were limited in power. Higher- compared with lower-dose anticoagulation was associated with fewer thromboembolic events, but a greater risk for major bleeding. Conclusion: Therapeutic-dose compared with prophylactic-dose anticoagulation reduced 28-day mortality. Mortality was similar for intermediate-dose compared with prophylactic-dose anticoagulation and higher for therapeutic-dose compared with intermediate-dose anticoagulation, although this comparison was not estimated precisely. Primary Funding Source: No direct funding. (PROSPERO: CRD42020213461) [ABSTRACT FROM AUTHOR]

Individual participant data (IPD) meta‐analyses of randomised trials are considered a reliable way to assess participant‐level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers are explored one covariate at a time, which gives rise to the possibility that evidence of treatment‐covariate interaction may be due to confounding from a different, related covariate. We aimed to evaluate current practice when estimating treatment‐covariate interactions in IPD meta‐analysis, specifically focusing on involvement of additional covariates in the models. We reviewed 100 IPD meta‐analyses of randomised trials, published between 2015 and 2020, that assessed at least one treatment‐covariate interaction. We identified four approaches to handling additional covariates: (1) Single interaction model (unadjusted): No additional covariates included (57/100 IPD meta‐analyses); (2) Single interaction model (adjusted): Adjustment for the main effect of at least one additional covariate (35/100); (3) Multiple interactions model: Adjustment for at least one two‐way interaction between treatment and an additional covariate (3/100); and (4) Three‐way interaction model: Three‐way interaction formed between treatment, the additional covariate and the potential effect modifier (5/100). IPD is not being utilised to its fullest extent. In an exemplar dataset, we demonstrate how these approaches lead to different conclusions. Researchers should adjust for additional covariates when estimating interactions in IPD meta‐analysis providing they adjust their main effects, which is already widely recommended. Further, they should consider whether more complex approaches could provide better information on who might benefit most from treatments, improving patient choice and treatment policy and practice. [ABSTRACT FROM AUTHOR]

In network meta‐analysis, studies evaluating multiple treatment comparisons are modeled simultaneously, and estimation is informed by a combination of direct and indirect evidence. Network meta‐analysis relies on an assumption of consistency, meaning that direct and indirect evidence should agree for each treatment comparison. Here we propose new local and global tests for inconsistency and demonstrate their application to three example networks. Because inconsistency is a property of a loop of treatments in the network meta‐analysis, we locate the local test in a loop. We define a model with one inconsistency parameter that can be interpreted as loop inconsistency. The model builds on the existing ideas of node‐splitting and side‐splitting in network meta‐analysis. To provide a global test for inconsistency, we extend the model across multiple independent loops with one degree of freedom per loop. We develop a new algorithm for identifying independent loops within a network meta‐analysis. Our proposed models handle treatments symmetrically, locate inconsistency in loops rather than in nodes or treatment comparisons, and are invariant to choice of reference treatment, making the results less dependent on model parameterization. For testing global inconsistency in network meta‐analysis, our global model uses fewer degrees of freedom than the existing design‐by‐treatment interaction approach and has the potential to increase power. To illustrate our methods, we fit the models to three network meta‐analyses varying in size and complexity. Local and global tests for inconsistency are performed and we demonstrate that the global model is invariant to choice of independent loops. [ABSTRACT FROM AUTHOR]

Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55–85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9–11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (p interaction =0·0019), higher volume of metastases (p interaction =0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (p interaction =0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (–1%, 95% CI –15 to 12, for progression-free survival; 0%, –10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes. UK Medical Research Council and Prostate Cancer UK. [ABSTRACT FROM AUTHOR]

Background: A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence. Methods: Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. Findings: One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71–0·95, p = 0·008]] and sarilumab [0·80 [0·61–1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81–1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28. Conclusions: Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist. [ABSTRACT FROM AUTHOR]

Background: The vast majority of systematic reviews are planned retrospectively, once most eligible trials have completed and reported, and are based on aggregate data that can be extracted from publications. Prior knowledge of trial results can introduce bias into both review and meta-analysis methods, and the omission of unpublished data can lead to reporting biases. We present a collaborative framework for prospective, adaptive meta-analysis (FAME) of aggregate data to provide results that are less prone to bias. Also, with FAME, we monitor how evidence from trials is accumulating, to anticipate the earliest opportunity for a potentially definitive meta-analysis.Methodology: We developed and piloted FAME alongside 4 systematic reviews in prostate cancer, which allowed us to refine the key principles. These are to: (1) start the systematic review process early, while trials are ongoing or yet to report; (2) liaise with trial investigators to develop a detailed picture of all eligible trials; (3) prospectively assess the earliest possible timing for reliable meta-analysis based on the accumulating aggregate data; (4) develop and register (or publish) the systematic review protocol before trials produce results and seek appropriate aggregate data; (5) interpret meta-analysis results taking account of both available and unavailable data; and (6) assess the value of updating the systematic review and meta-analysis. These principles are illustrated via a hypothetical review and their application to 3 published systematic reviews.Conclusions: FAME can reduce the potential for bias, and produce more timely, thorough and reliable systematic reviews of aggregate data. [ABSTRACT FROM AUTHOR]

Background: It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required.Methods and Findings: We used 18 cancer systematic reviews that included IPD meta-analyses: all of those completed and published by the Meta-analysis Group of the MRC Clinical Trials Unit from 1991 to 2010. We extracted or estimated hazard ratios (HRs) and standard errors (SEs) for survival from trial reports and compared these with IPD equivalents at both the trial and meta-analysis level. We also extracted or estimated the number of events. We used paired t tests to assess whether HRs and SEs from published AD differed on average from those from IPD. We assessed agreement, and whether this was associated with trial or meta-analysis characteristics, using the approach of Bland and Altman. The 18 systematic reviews comprised 238 unique trials or trial comparisons, including 37,082 participants. A HR and SE could be generated for 127 trials, representing 53% of the trials and approximately 79% of eligible participants. On average, trial HRs derived from published AD were slightly more in favour of the research interventions than those from IPD (HRAD to HRIPD ratio = 0.95, p = 0.007), but the limits of agreement show that for individual trials, the HRs could deviate substantially. These limits narrowed with an increasing number of participants (p < 0.001) or a greater number (p < 0.001) or proportion (p < 0.001) of events in the AD. On average, meta-analysis HRs from published AD slightly tended to favour the research interventions whether based on fixed-effect (HRAD to HRIPD ratio = 0.97, p = 0.088) or random-effects (HRAD to HRIPD ratio = 0.96, p = 0.044) models, but the limits of agreement show that for individual meta-analyses, agreement was much more variable. These limits tended to narrow with an increasing number (p = 0.077) or proportion of events (p = 0.11) in the AD. However, even when the information size of the AD was large, individual meta-analysis HRs could still differ from their IPD equivalents by a relative 10% in favour of the research intervention to 5% in favour of control. We utilised the results to construct a decision tree for assessing whether an AD meta-analysis includes sufficient information, and when estimates of effects are most likely to be reliable. A lack of power at the meta-analysis level may have prevented us identifying additional factors associated with the reliability of AD meta-analyses, and we cannot be sure that our results are generalisable to all outcomes and effect measures.Conclusions: In this study we found that HRs from published AD were most likely to agree with those from IPD when the information size was large. Based on these findings, we provide guidance for determining systematically when standard AD meta-analysis will likely generate robust clinical conclusions, and when the IPD approach will add considerable value. [ABSTRACT FROM AUTHOR]

This is the first account of the history of our understanding of, and ability to model, solidification microstructures. Its objective is to retrace the scientific steps made, from the earliest observations of the eighteenth century to our present-day understanding of dendrites and eutectics. Because of the abundance of information, especially that added during the present century, sub-division was essential: this being the first of three articles. They cover dendrites and cells from 1700 to 2000, and then from 2001 to 2015 and finally eutectics and peritectics from 1700 to 2015. The authors have striven always to identify the genesis of every advance made, being aware that such a compact history must leave many worthy contributions by the wayside; others will doubtless complete the history. This review shows how cross-fertilisation between theory and experiment, and basic and applied research led to both the posing and answering of challenging fundamental questions, thus rewarding society with beneficial results. [ABSTRACT FROM AUTHOR]

Background: Clinical staging of non-small cell lung cancer (NSCLC) helps determine the prognosis and treatment of patients; few data exist on the accuracy of clinical staging and the impact on treatment and survival of patients. We assessed whether participant or trial characteristics were associated with clinical staging accuracy as well as impact on survival.Methods: We used individual participant data from randomized controlled trials (RCTs), supplied for a meta-analysis of preoperative chemotherapy (± radiotherapy) vs surgery alone (± radiotherapy) in NSCLC. We assessed agreement between clinical TNM (cTNM) stage at randomization and pathologic TNM (pTNM) stage, for participants in the control group.Results: Results are based on 698 patients who received surgery alone (± radiotherapy) with data for cTNM and pTNM stage. Forty-six percent of cases were cTNM stage I, 23% were cTNM stage II, and 31% were cTNM stage IIIa. cTNM stage disagreed with pTNM stage in 48% of cases, with 34% clinically understaged and 14% clinically overstaged. Agreement was not associated with age (P = .12), sex (P = .62), histology (P = .82), staging method (P = .32), or year of randomization (P = .98). Poorer survival in understaged patients was explained by the underlying pTNM stage. Clinical staging failed to detect T4 disease in 10% of cases and misclassified nodal disease in 38%.Conclusions: This study demonstrates suboptimal agreement between clinical and pathologic staging. Discrepancies between clinical and pathologic T and N staging could have led to different treatment decisions in 10% and 38% of cases, respectively. There is therefore a need for further research into improving staging accuracy for patients with stage I-IIIa NSCLC. [ABSTRACT FROM AUTHOR]

Quantitative evidence synthesis through meta-analysis is central to evidence-based medicine. For well-documented reasons, the meta-analysis of individual patient data is held in higher regard than aggregate data. With access to individual patient data, the analysis is not restricted to a "two-stage" approach (combining estimates and standard errors) but can estimate parameters of interest by fitting a single model to all of the data, a so-called "one-stage" analysis. There has been debate about the merits of one- and two-stage analysis. Arguments for one-stage analysis have typically noted that a wider range of models can be fitted and overall estimates may be more precise. The two-stage side has emphasised that the models that can be fitted in two stages are sufficient to answer the relevant questions, with less scope for mistakes because there are fewer modelling choices to be made in the two-stage approach. For Gaussian data, we consider the statistical arguments for flexibility and precision in small-sample settings. Regarding flexibility, several of the models that can be fitted only in one stage may not be of serious interest to most meta-analysis practitioners. Regarding precision, we consider fixed- and random-effects meta-analysis and see that, for a model making certain assumptions, the number of stages used to fit this model is irrelevant; the precision will be approximately equal. Meta-analysts should choose modelling assumptions carefully. Sometimes relevant models can only be fitted in one stage. Otherwise, meta-analysts are free to use whichever procedure is most convenient to fit the identified model. [ABSTRACT FROM AUTHOR]

The synthesis of sterically hindered amines has been a significant challenge in organic chemistry. Herein, we report a modular, three-component coupling that constructs two carbon-nitrogen bonds including a sterically hindered Csp³-N bond using commercially available materials. This process uses an earth-abundant copper catalyst and mild reaction conditions, allowing access to a variety of complex aromatic amines. [ABSTRACT FROM AUTHOR]

The synthesis of sterically hindered anilines has been a significant challenge in organic chemistry. Here we report a Cu-catalyzed radical addition with in situ-generated nitroso compounds to prepare sterically hindered amines directly from readily available materials. The transformation is conducted at room temperature, uses abundant copper salts, and is tolerant of a range of functional groups. [ABSTRACT FROM AUTHOR]

Background and Purpose: Transcranial near-infrared laser therapy (TLT) is a promising and novel method to promote neuroprotection and clinical improvement in both acute and chronic neurodegenerative diseases such as acute ischemic stroke (AIS), traumatic brain injury (TBI), and Alzheimer’s disease (AD) patients based upon efficacy in translational animal models. However, there is limited information in the peer-reviewed literature pertaining to transcranial near-infrared laser transmission (NILT) profiles in various species. Thus, in the present study we systematically evaluated NILT characteristics through the skull of 4 different species: mouse, rat, rabbit and human. Results: Using dehydrated skulls from 3 animal species, using a wavelength of 800nm and a surface power density of 700 mW/cm2, NILT decreased from 40.10% (mouse) to 21.24% (rat) to 11.36% (rabbit) as skull thickness measured at bregma increased from 0.44 mm in mouse to 0.83 mm in rat and then 2.11 mm in rabbit. NILT also significantly increased (p<0.05) when animal skulls were hydrated (i.e. compared to dehydrated); but there was no measurable change in thickness due to hydration. In human calvaria, where mean thickness ranged from 7.19 mm at bregma to 5.91 mm in the parietal skull, only 4.18% and 4.24% of applied near-infrared light was transmitted through the skull. There was a slight (9.2-13.4%), but insignificant effect of hydration state on NILT transmission of human skulls, but there was a significant positive correlation between NILT and thickness at bregma and parietal skull, in both hydrated and dehydrated states. Conclusion: This is the first systematic study to demonstrate differential NILT through the skulls of 4 different species; with an inverse relationship between NILT and skull thickness. With animal skulls, transmission profiles are dependent upon the hydration state of the skull, with significantly greater penetration through hydrated skulls compared to dehydrated skulls. Using human skulls, we demonstrate a significant correlation between thickness and penetration, but there was no correlation with skull density. The results suggest that TLT should be optimized in animals using novel approaches incorporating human skull characteristics, because of significant variance of NILT profiles directly related to skull thickness. [ABSTRACT FROM AUTHOR]

In this article, I describe a command, ipdmetan, that facilitates twostage individual participant data meta-analysis of any measure of effect and its standard error by fitting a specified model to data from each study. The command can estimate random effects and heterogeneity statistics and include additional covariates and interactions. If individual participant data are available for certain studies and aggregate data for others, ipdmetan allows them to be combined in one analysis. This command can produce detailed and flexible forest plots, including ones outside the context of formal meta-analysis. [ABSTRACT FROM AUTHOR]

TheLie algebra version of theKrull-Schmidt theorem is formulated and proved. This leads to amethod for constructing the automorphisms of a direct sum of Lie algebras from the automorphisms of its indecomposable components. For finitedimensional Lie algebras, there is a well-known algorithm for finding such components, so the theorem considerably simplifies the problem of classifying the automorphism groups. We illustrate this by classifying the automorphisms of all indecomposable real Lie algebras of dimension five or less. Our results are presented very concisely, in tabular form. [ABSTRACT FROM AUTHOR]

Background: Multiple micronutrient deficiencies are common among women in low-income countries and may adversely affect pregnancy outcomes. Objective: This meta-analysis reports the effects on newborn size and duration of gestation of multiple micronutrient supplementation mainly compared with iron plus folic acid during pregnancy in recent randomized, controlled trials. Methods: Original data from 12 randomized, controlled trials in Bangladesh, Burkina Faso, China, Guinea-Bissau, Indonesia, Mexico, Nepal, Niger, Pakistan, and Zimbabwe, all providing approximately 1 recommended dietary allowance (RDA) of multiple micronutrients to presumed HIV-negative women, were included. Outcomes included birthweight, other birth measurements, gestation, and incidence of low birthweight (LBW) (< 2500 g), small-for-gestational age birth (SGA, birthweight below the within-each-population 10th percentile), large-for-gestational age birth (LGA, birthweight above the within-each-population 90th percentile), and preterm delivery (< 37 weeks). Results: Compared with control supplementation (mainly with iron-folic acid), multiple micronutrient supplementation was associated with an increase in mean birthweight (pooled estimate: +22.4 g [95% CI, 8.3 to 36.4 g]; p = .002), a reduction in the prevalence of LBW (pooled OR = 0.89 [95% CI, 0.81 to 0.97]; p = .01) and SGA birth (pooled OR = 0.90 [95% CI, 0.82 to 0.99]; p = .03), and an increase in the prevalence of LGA birth (pooled OR = 1.13 [95% CI, 1.00 to 1.28]; p = .04). In most studies, the effects on birthweight were greater in mothers with higher body mass index (BMI). In the pooled analysis, the positive effect of multiple micronutrients on birthweight increased by 7.6 g (95% CI, 1.9 to 13.3 g) per unit increase in maternal BMI (p for interaction = .009). The intervention effect relative to the control group was + 39.0 g (95% CI, +22.0 to +56.1 g) in mothers with BMI of 20 kg/m² or higher compared with -6.0 g (95% CI, -8.8 to +16.8 g) in mothers with BMI under 20 kg/m². There were no significant effects of multiple micronutrient supplementation on birth length or head circumference nor on the duration of gestation (pooled effect: +0.17 day [95% CI, -0.35 to +0.70 day]; p = .51) or the incidence of preterm birth (pooled OR = 1.00 [95% CI, 0.93 to 1.09]; p = .92). Conclusions: Compared with iron-folic acid supplementation alone, maternal supplementation with multiple micronutrients during pregnancy in low-income countries resulted in a small increase in birthweight and a reduction in the prevalence of LBW of about 10%. The effect was greater among women with higher BMI. [ABSTRACT FROM AUTHOR]

Background: Multiple micronutrient deficiencies are common among women in low-income countries and may adversely affect pregnancy outcomes. Objective: To conduct a meta-analysis of the effects on stillbirths and on early and late neonatal mortality of supplementation during pregnancy with multiple micronutrients compared with iron-folic acid in recent randomized, controlled trials. Methods: Twelve randomized, controlled trials were included in the analysis (Bangladesh; Burkina Faso; China; Guinea-Bissau; Indramayu and Lombok, Indonesia; Mexico; Sarlahi and Janakur, Nepal; Niger; Pakistan; and Zimbabwe), all providing approximately 1 recommended dietary allowance (RDA) of multiple micronutrients or iron-folic acid to presumed HIV-negative women. Results: Supplementation providing approximately 1 RDA of multiple micronutrients did not decrease the risk of stillbirth (OR = 1.01; 95% CI, 0.88 to 1.16), early neonatal mortality (OR = 1.23; 95% CI, 0.95 to 1.59), late neonatal mortality (OR = 0.94; 95% CI, 0.73 to 1.23), or perinatal mortality (OR = 1.11; 95% CI, 0.93 to 1.33). Conclusions: Our meta-analysis provides consistent evidence that supplementation providing approximately 1 RDA of multiple micronutrients during pregnancy does not result in any reduction in stillbirths or in early or late neonatal deaths compared with iron-folic acid alone. [ABSTRACT FROM AUTHOR]

This paper reports on the methods and characteristics of 12 studies from developing countries included in a meta-analysis of the impact of antenatal supplements of multiple micronutrients compared with iron-folic acid on micronutrient status, maternal nutritional status, birth outcomes, and neonatal survival. [ABSTRACT FROM AUTHOR]

Investigates the role of thyroid hormone in the physiological perinatal increase in cardiac sarcoplasmic reticulum Ca2+-adenosinetriphosphatase expression in cultured chick embryo. Description of methods used in the study; Immunodetectable SR Ca2+ pump protein; Mechanism of regulation of the SR Ca2+ pump by thyroid hormone.

Abstract. The clinical spectrum of neonatal endocarditis, including bacterial and nonbacterial types, is examined in five case reports that were drawn from nursery experiences over a recent 2-year period. In contrast to previous reports of 100% mortality from neonatal endocarditis, one patient survived. Changing heart murmur and hematuria were most frequently associated with bacterial and nonbacterial endocarditis in four of the five cases. Pulmonary hypertension, thrombocytopenia, and coagulopathy were also associated with nonbacterial endocarditis. Echocardiograms were performed on four of the patients; only one was suggestive of endocarditis. Staphylococcus aureus was isolated from both cases of bacterial endocarditis, including the single survivor. Thus, it is suggested that the initial antibiotic coverage of any neonate with the clinical syndrome of sepsis, hematuria, and a heart murmur include antistaphylococcal coverage for the possibility of bacterial endocarditis. Pediatrics 1983; 71:392-397; bacterial endocarditis, nonbacterial endocarditis, echocardiography, neonatal staphylococcal infection. [ABSTRACT FROM AUTHOR]

The effects of the systemic fungicide tridemorph on fungal and plant protoplasts have been investigated. No evidence of reaction at the plasma-membrane was revealed by microelectrophoresis. The fungicide did not affect oxygen uptake by fungal protoplasts but incorporation of labelled histidine was reduced. Fungi-toxicity tests showed that tridemorph had little effect on spore germination but inhibited mycelial growth. It is suggested that the fungicide may act by interfering with the synthesis of proteins essential for hyphal extension. [ABSTRACT FROM AUTHOR]