A review of the immunomodulating components of maternal breast milk and protection against necrotizing enterocolitis

Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant\u27s gestational and chronological age, lactation stage, and the mother and infant\u27s health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC). Breast milk is a known protective factor in the prevention of NEC when compared with feeding with commercial formula. Breast milk supplements infants with human milk oligosaccharides, leukocytes, cytokines, nitric oxide, and growth factors that attenuate inflammatory responses and provide immunological defenses to reduce the incidence of NEC. This article aims to review the variety of immunomodulating components in breast milk that protect the infant from the development of NEC

Glutamine supplementation to prevent morbidity and mortality in preterm infants

BACKGROUND: Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. OBJECTIVES: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS: We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. AUTHORS' CONCLUSIONS: The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants

The effectiveness of video animations in the education of healthcare practitioners and student practitioners : a systematic review of trials

INTRODUCTION: Video animations are increasingly available in education but without systematic evaluation. This review aimed to collate trials of animations versus other delivery, in student or qualified healthcare practitioners. METHODS: Included studies had the following features: controlled design with random or quasi-random allocation; student or qualified healthcare practitioners; comparing video animation with another format (e.g. textbook, lecture, static images); animation delivered instead of, or in addition to, another format. The primary outcome was knowledge; secondary outcomes were attitudes and cognitions, and behaviours. Multiple databases were searched from 1996-October 2022 using a defined strategy. We also undertook citation searching. Dual, independent decision-making was used for inclusion assessment, data extraction, and quality appraisal. Included studies were appraised using the Cochrane ROB2 tool. Findings were reported using narrative synthesis. RESULTS: We included 13 studies: 11 recruited student practitioners, two recruited qualified practitioners, total n = 1068. Studies evaluated cartoon animations or 2D/3D animations. Knowledge was assessed in ten studies, showing greater knowledge from animations in eight studies. Attitudes and cognitions were assessed in five studies; animations resulted in positive outcomes in three studies, no difference in one study, and worse outcomes in one study. Behaviours were assessed in three studies, animations producing positive outcomes in two studies and there was no difference in one study. Overall risk of bias was 'high' in ten studies and 'some concerns' in three. DISCUSSION: Overall the evidence base is small with mostly 'high' risk of bias. Video animations show promise in practitioner education, particularly for effects on knowledge, but bigger, better research is needed

Naloxone for opioid-exposed newborn infants

BACKGROUND: Naloxone, a specific opioid antagonist, is available for the treatment of newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. It is unclear whether newborn infants may benefit from this therapy and whether naloxone has any harmful effects. OBJECTIVES: To determine the effect of naloxone on the need for and duration of neonatal unit stay in infants of mothers who received opioid analgesia prior to delivery or of mothers who have used a prescribed or non-prescribed opioid during pregnancy. SEARCH METHODS: We searched the following databases in February 2018: the Cochrane Central Register of Controlled Trials (the Cochrane Library 2018, Issue 1), MEDLINE (OvidSP), MEDLINE In process & Other Non-Indexed Citations (OvidSP), Embase (OvidSP), CINAHL (EBSCO), Maternity and Infant Care (OvidSP), and PubMed. We searched for ongoing and completed trials in the WHO International Clinical Trials Registry Platform and the EU Clinical Trials Register. We checked the reference lists of relevant articles to identify further potentially relevant studies. SELECTION CRITERIA: Randomised controlled trials comparing the administration of naloxone versus placebo, or no drug, or another dose of naloxone to newborn infants with suspected or confirmed in utero exposure to opioid. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of Cochrane Neonatal with separate evaluation of trial quality and data extraction by two review authors and synthesis of data using risk ratio, risk difference, and mean difference. MAIN RESULTS: We included nine trials, with 316 participants in total, that compared the effects of naloxone versus placebo or no drug in newborn infants exposed to maternal opioid analgesia prior to delivery. None of the included trials investigated infants born to mothers who had used a prescribed or non-prescribed opioid during pregnancy. None of these trials specifically recruited infants with cardiorespiratory or neurological depression. The main outcomes reported were measures of respiratory function in the first six hours after birth. There is some evidence that naloxone increases alveolar ventilation. The trials did not assess the effect on the primary outcomes of this review (admission to a neonatal unit and failure to establish breastfeeding). AUTHORS' CONCLUSIONS: The existing evidence from randomised controlled trials is insufficient to determine whether naloxone confers any important benefits to newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. Given concerns about the safety of naloxone in this context, it may be appropriate to limit its use to randomised controlled trials that aim to resolve these uncertainties

Determination of stress state in deep subsea formation by combination of hydraulic fracturing in situ test and core analysis: A case study in the IODP Expedition 319

[1] In situ test of hydraulic fracturing (HF) provides the only way to observe in situ stress magnitudes directly. The maximum and minimum horizontal stresses, SHmax and Shmin, are determined from critical borehole pressures, i.e., the reopening pressure Pr and the shut-in pressure Ps, etc, observed during the test. However, there is inevitably a discrepancy between actual and measured values of the critical pressures, and this discrepancy is very significant for Pr. For effective measurement of Pr, it is necessary for the fracturing system to have a sufficiently small compliance. A diagnostic procedure to evaluate whether the compliance of the employed fracturing system is appropriate for SHmax determination from Pr was developed. Furthermore, a new method for stress measurement not restricted by the system compliance and Pr is herein proposed. In this method, the magnitudes and orientations of SHmax and Shmin are determined from (i) the cross-sectional shape of a core sample and (ii) Ps obtained by the HF test performed near the core depth. These ideas were applied for stress measurement in a central region of the Kumano fore-arc basin at a water depth of 2054?m using a 1.6?km riser hole drilled in the Integrated Ocean Drilling Program (IODP) Expedition 319. As a result, the stress decoupling through a boundary at 1285?m below seafloor was detected. The boundary separates new upper layers and old lower ones with an age gap of ~1.8?Ma, which is possibly the accretionary prism. The stress state in the lower layers is consistent with that observed in the outer edge of accretionary prism

A systematic review on the clustering and co-occurrence of multiple risk behaviours.

BACKGROUND: Risk behaviours, such as smoking and physical inactivity account for up to two-thirds of all cardiovascular deaths, and are associated with substantial increased mortality in many conditions including cancer and diabetes. As risk behaviours are thought to co-occur in individuals we conducted a systematic review of studies addressing clustering or co-occurrence of risk behaviours and their predictors. As the main aim of the review was to inform public health policy in England we limited inclusion to studies conducted in the UK. METHODS: Key databases were searched from 1990 to 2016. We included UK based cross-sectional and longitudinal studies that investigated risk behaviours such as smoking, physical inactivity, unhealthy diet. High heterogeneity precluded meta-analyses. RESULTS: Thirty-seven studies were included in the review (32 cross-sectional and five longitudinal). Most studies investigated unhealthy diet, physical inactivity, alcohol misuse, and smoking. In general adult populations, there was relatively strong evidence of clustering between alcohol misuse and smoking; and unhealthy diet and smoking. For young adults, there was evidence of clustering between sexual risk behaviour and smoking, sexual risk behaviour and illicit drug use, and sexual risk behaviour and alcohol misuse. The strongest associations with co-occurrence and clustering of multiple risk behaviours were occupation (up to 4-fold increased odds in lower SES groups) and education (up to 5-fold increased odds in those with no qualifications). CONCLUSIONS: Among general adult populations, alcohol misuse and smoking was the most commonly identified risk behaviour cluster. Among young adults, there was consistent evidence of clustering found between sexual risk behaviour and substance misuse. Socio-economic status was the strongest predictor of engaging in multiple risk behaviours. This suggests the potential for interventions targeting multiple risk behaviours either sequentially or concurrently particularly where there is evidence of clustering. In addition, there is potential for intervening at the social or environmental level due to the strong association with socio-economic status

The effectiveness of video animations as information tools for patients and the general public : A systematic review

Background and objectivesVideo animations are used increasingly as patient information tools; however, we do not know their value compared to other formats of delivery, such as printed materials, verbal consultations or static images.MethodsThis review compares the effectiveness of video animations as information tools vs. other formats of delivery on patient knowledge, attitudes and cognitions, and behaviours. Included studies had the following features: controlled design with random or quasi-random allocation; patients being informed about any health condition or members of the public being informed about a public health topic; comparing video animation with another delivery format. Multiple digital databases were searched from 1996-June 2021. We also undertook citation searching. We used dual, independent decision-making for inclusion assessment, data extraction and quality appraisal. Included studies were appraised using the Cochrane ROB2 tool. Findings were reported using narrative synthesis.ResultsWe included 38 trials, focussed on: explaining medical or surgical procedures (n = 17); management of long-term conditions (n = 11); public health, health-promotion or illness-prevention (n = 10). Studies evaluated cartoon animations (n = 29), 3D animations (n = 6), or 2D animations, “white-board” animations or avatars (n = 1 each). Knowledge was assessed in 30 studies, showing greater knowledge from animations in 19 studies, compared to a range of comparators. Attitudes and cognitions were assessed in 21 studies, and animations resulted in positive outcomes in six studies, null effects in 14 studies, and less positive outcomes than standard care in one study. Patient behaviours were assessed in nine studies, with animations resulting in positive outcomes in four and null effects in the remainder. Overall risk of bias was “high” (n = 18), “some concerns” (n = 16) or “low” (n = 4). Common reasons for increased risk of bias were randomisation processes, small sample size or lack of sample size calculation, missing outcome data, and lack of protocol publication.DiscussionThe overall evidence base is highly variable, with mostly small trials. Video animations show promise as patient information tools, particularly for effects on knowledge, but further evaluation is needed in higher quality studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42021236296

Does digital, multimedia information increase recruitment and retention in a children’s wrist fracture treatment trial, and what do people think of it? A randomised controlled Study Within A Trial (SWAT)

Objectives To evaluate digital, multimedia information (MMI) for its effects on trial recruitment, retention, decisions about participation and acceptability by patients, compared with printed information. Design Study Within A Trial using random cluster allocation within the Forearm Fracture Recovery in Children Evaluation (FORCE) study. Setting Emergency departments in 23 UK hospitals. Participants 1409 children aged 4–16 years attending with a torus (buckle) fracture, and their parents/guardian. Children’s mean age was 9.2 years, 41.0% were female, 77.4% were ethnically White and 90.0% spoke English as a first language. Interventions Participants and their parents/guardian received trial information either via multimedia, including animated videos, talking head videos and text (revised for readability and age appropriateness when needed) on tablet computer (MMI group; n=681), or printed participant information sheet (PIS group; n=728). Outcome measures Primary outcome was recruitment rate to FORCE. Secondary outcomes were Decision Making Questionnaire (nine Likert items, analysed summatively and individually), three ‘free text’ questions (deriving subjective evaluations) and trial retention. Results MMI produced a small, not statistically significant increase in recruitment: 475 (69.8%) participants were recruited from the MMI group; 484 (66.5%) from the PIS group (OR=1.35; 95% CI 0.76 to 2.40, p=0.31). A total of 324 (23.0%) questionnaires were returned and analysed. There was no difference in total Decision-Making Questionnaire scores: adjusted mean difference 0.05 (95% CI −1.23 to 1.32, p=0.94). The MMI group was more likely to report the information ‘very easy’ to understand (89; 57.8% vs 67; 39.4%; Z=2.60, p=0.01) and identify information that was explained well (96; 62.3% vs 71; 41.8%). Almost all FORCE recruits were retained at the 6 weeks’ timepoint and there was no difference in retention rate between the information groups: MMI (473; 99.6%); PIS (481; 99.4%)

Adjunctive colposcopy technologies for assessing suspected cervical abnormalities : systematic reviews and economic evaluation

BACKGROUND: Dynamic Spectral Imaging System (DySIS)map (DySIS Medical Ltd, Edinburgh, UK) and ZedScan (Zilico Limited, Manchester, UK) can be used adjunctively with conventional colposcopy, which may improve the detection of cervical intraepithelial neoplasia (CIN) and cancer. OBJECTIVES: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of DySISmap and ZedScan as adjuncts to standard colposcopy, and to develop a cost-effectiveness model. METHODS: Four parallel systematic reviews were performed on diagnostic accuracy, clinical effectiveness issues, implementation and economic analyses. In January 2017 we searched databases (including MEDLINE and EMBASE) for studies in which DySISmap or ZedScan was used adjunctively with standard colposcopy to detect CIN or cancer in women referred to colposcopy. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Summary estimates of diagnostic accuracy were calculated using bivariate and other regression models when appropriate. Other outcomes were synthesised narratively. A patient-level state-transition model was developed to evaluate the cost-effectiveness of DySISmap and ZedScan under either human papillomavirus (HPV) triage or the HPV primary screening algorithm. The model included two types of clinics ['see and treat' and 'watchful waiting' (i.e. treat later after confirmatory biopsy)], as well as the reason for referral (low-grade or high-grade cytological smear). Sensitivity and scenario analyses were undertaken. RESULTS: Eleven studies were included in the diagnostic review (nine of DySISmap and two of ZedScan), three were included in the clinical effectiveness review (two of DySISmap and one of ZedScan) and five were included in the implementation review (four of DySISmap and one of ZedScan). Adjunctive DySISmap use was found to have a higher sensitivity for detecting CIN grade 2+ (CIN 2+) lesions [81.25%, 95% confidence interval (CI) 72.2% to 87.9%] than standard colposcopy alone (57.91%, 95% CI 47.2% to 67.9%), but with a lower specificity (70.40%, 95% CI 59.4% to 79.5%) than colposcopy (87.41%, 95% CI 81.7% to 91.5%). (Confidential information has been removed.) The base-case cost-effectiveness results showed that adjunctive DySISmap routinely dominated standard colposcopy (it was less costly and more effective). The only exception was for high-grade referrals in a watchful-waiting clinic setting. The incremental cost-effectiveness ratio for ZedScan varied between £272 and £4922 per quality-adjusted life-year. ZedScan also dominated colposcopy alone for high-grade referrals in see-and-treat clinics. These findings appeared to be robust to a wide range of sensitivity and scenario analyses. LIMITATIONS: All but one study was rated as being at a high risk of bias. There was no evidence directly comparing ZedScan with standard colposcopy. No studies directly compared DySIS and ZedScan. CONCLUSIONS: The use of adjunctive DySIS increases the sensitivity for detecting CIN 2+, so it increases the number of high-grade CIN cases that are detected. However, it also reduces specificity, so that more women with no or low-grade CIN will be incorrectly judged as possibly having high-grade CIN. The evidence for ZedScan was limited, but it appears to increase sensitivity and decrease specificity compared with colposcopy alone. The cost-effectiveness of both adjunctive technologies compared with standard colposcopy, under both the HPV triage and primary screening algorithms, appears to be favourable when compared with the conventional thresholds used to determine value in the NHS. FUTURE WORK: More diagnostic accuracy studies of ZedScan are needed, as are studies assessing the diagnostic accuracy for women referred to colposcopy as part of the HPV primary screening programme. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017054515. FUNDING: The National Institute for Health Research Health Technology Assessment programme