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Modern Applied Statistics With S

MEDICAL LITERATURE has been deluged during the past few years with books and papers on penicillin; but a book which has been produced under the general editorship of Sir Alexander Fleming himself represents a complete and authoritative summary of penicillin therapy as it stands today.' The book contains a series of independent contributions by \"experienced and eminent men who have worked with penicillin in Great Britain\". Their opinions and practical methods differ slightly, and there is some overlapping; but these are not disadvantageous, comparison and contrast lending interest to the reading. In the first or general section of the book Fleming contributes two chapters, one on the history and development of penicillin, introducing some interesting sidelights in the romance of discovery, the other on the bacteriological control of penicillin therapy. In both chapters the information is set out in meticulous detail and with a clarity and simplicity which can be enjoyed by all readers. Fleming also gives the right perspective to the place of penicillin amongst the antibiotics and lays down the principles of treatment. Both chapters are well illustrated and are the most outstanding in the book. Included in this first section also are chapters on the chemistry and manufacture of penicillin and its pharmacy, pharmacology and methods of administration. The second section of the book is entirely clinical, giving each author's view on the use of penicillin therapy in a disease or an infection of some particular region of the body. The entire range of peniCillin-sensitive conditions is considered in twenty authoritative and clearly written chapters; these contain many references and illustrations. Dental and veterinary diseases are also given fairly full consideration. The final section is a condensed resume of much of the preceding chapters and is written for. the general practttioner. This chapter is superttuous: it does not contain enough detall to be of much practical value. The book as a Whole, however, will undoubtedly be considered a classical contribution to medical literature and is strongly recommended, not only because of the general interest of its topic, but as a reference book on penicillin therapy of hitherto unequalled excellence. The typography, although conforming to war economy standards, is clear and the paper is good. There is an excellent list of references and the index is satisfactory.

Gray's Anatomy

Background
Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother’s arms, placed in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally at birth and should last continually until the end of the first breastfeeding. SSC involves placing the dried, naked baby prone on the mother's bare chest, often covered with a warm blanket. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring fulfillment of basic biological needs. This time frame immediately post birth may represent a 'sensitive period' for programming future physiology and behavior.

Objectives
To assess the effects of immediate or early SSC for healthy newborn infants compared to standard contact on establishment and maintenance of breastfeeding and infant physiology.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 December 2015), made personal contact with trialists, consulted the bibliography on kangaroo mother care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of retrieved studies.

Selection criteria
Randomized controlled trials that compared immediate or early SSC with usual hospital care.

Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Quality of the evidence was assessed using the GRADE approach.

Main results
We included 46 trials with 3850 women and their infants; 38 trials with 3472 women and infants contributed data to our analyses. Trials took place in 21 countries, and most recruited small samples (just 12 trials randomized more than 100 women). Eight trials included women who had SSC after cesarean birth. All infants recruited to trials were healthy, and the majority were full term. Six trials studied late preterm infants (greater than 35 weeks' gestation). No included trial met all criteria for good quality with respect to methodology and reporting; no trial was successfully blinded, and all analyses were imprecise due to small sample size. Many analyses had statistical heterogeneity due to considerable differences between SSC and standard care control groups.

Results for women

SSC women were more likely than women with standard contact to be breastfeeding at one to four months post birth, though there was some uncertainty in this estimate due to risks of bias in included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07 to 1.43; participants = 887; studies = 14; I² = 41%; GRADE: moderate quality). SSC women also breast fed their infants longer, though data were limited (mean difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies = six; GRADE:low quality); this result was from a sensitivity analysis excluding one trial contributing all of the heterogeneity in the primary analysis. SSC women were probably more likely to exclusively breast feed from hospital discharge to one month post birth and from six weeks to six months post birth, though both analyses had substantial heterogeneity (from discharge average RR 1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I² = 44%; GRADE: moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90; participants = 640; studies = seven; I² = 62%; GRADE: moderate quality).

Women in the SCC group had higher mean scores for breastfeeding effectiveness, with moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD 2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I² = 41%). SSC infants were more likely to breast feed successfully during their first feed, with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants = 575; studies = five; I² = 85%).

Results for infants

SSC infants had higher SCRIP (stability of the cardio-respiratory system) scores overall, suggesting better stabilization on three physiological parameters. However, there were few infants, and the clinical significance of the test was unclear because trialists reported averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI 0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants = 144; studies = three; GRADE: low quality), but similar temperature to infants in standard care (MD 0.30 degree Celcius (°C) 95% CI 0.13 °C to 0.47 °C; participants = 558; studies = six; I² = 88%; GRADE: low quality).

Women and infants after cesarean birth

Women practicing SSC after cesarean birth were probably more likely to breast feed one to four months post birth and to breast feed successfully (IBFAT score), but analyses were based on just two trials and few women. Evidence was insufficient to determine whether SSC could improve breastfeeding at other times after cesarean. Single trials contributed to infant respiratory rate, maternal pain and maternal state anxiety with no power to detect group differences.

Subgroups

We found no differences for any outcome when we compared times of initiation (immediate less than 10 minutes post birth versus early 10 minutes or more post birth) or lengths of contact time (60 minutes or less contact versus more than 60 minutes contact).

Authors' conclusions
Evidence supports the use of SSC to promote breastfeeding. Studies with larger sample sizes are necessary to confirm physiological benefit for infants during transition to extra-uterine life and to establish possible dose-response effects and optimal initiation time. Methodological quality of trials remains problematic, and small trials reporting different outcomes with different scales and limited data limit our confidence in the benefits of SSC for infants. Our review included only healthy infants, which limits the range of physiological parameters observed and makes their interpretation difficult.

/pdf/early-skin-to-skin-contact-for-mothers-and-their-healthy-4t370cqgvm.pdf

Early skin‐to‐skin contact for mothers and their healthy newborn infants

Clinics in Developmental Medicine

G Du Toit, G Roberts, PH Sayre N Engl J Med 2015;372:803–813

To evaluate strategies of early peanut consumption or avoidance for prevention of peanut allergy in patients at risk

The participants were between 4 and 11 months of age at randomization They suffered from severe eczema, egg allergy, or both

A total of 640 patients were evaluated over a 60-month period They were stratified according to their sensitivity to skin testing to peanut extract Those with no measureable wheal were evaluated as not sensitized, those with wheal diameters 1 to 4 mm were considered sensitized, and participants with >4-mm wheal were excluded Participants were randomized to receive an initial supervised feeding …

https://pediatrics.aappublications.org/content/pediatrics/136/Supplement_3/S238.full.pdf

Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

Mammary glands are unique to mammals, with the specific function of synthesizing, secreting, and delivering milk to the newborn. Given this function, it is only during a pregnancy/lactation cycle that the gland reaches a mature developmental state via hormonal influences at the cellular level that effect drastic modifications in the micro- and macro-anatomy of the gland, resulting in remodeling of the gland into a milk-secretory organ. Pubertal and post-pubertal development of the breast in females aids in preparing it to assume a functional state during pregnancy and lactation. Remarkably, this organ has the capacity to regress to a resting state upon cessation of lactation, and then undergo the same cycle of expansion and regression again in subsequent pregnancies during reproductive life. This plasticity suggests tight hormonal regulation, which is paramount for the normal function of the gland. This review presents the current status of knowledge of the normal macro- and micro-anatomy of the human mammary gland and the distinct changes it undergoes during the key developmental stages that characterize it, from embryonic life through to post-menopausal age. In addition, it discusses recent advances in our understanding of the normal function of the breast during lactation, with special reference to breastmilk, its composition, and how it can be utilized as a tool to advance knowledge on normal and aberrant breast development and function. Finally, anatomical and molecular traits associated with aberrant expansion of the breast are discussed to set the basis for future comparisons that may illuminate the origin of breast cancer.

Anatomy of the human mammary gland: Current status of knowledge

Tongue movement and intra-oral vacuum in breastfeeding infants

OBJECTIVE. There is evidence that infants with ankyloglossia can experience breastfeeding difficulties including poor attachment to the breast, suboptimal weight gain, and maternal nipple pain, which may lead to early weaning of the infant. No studies have investigated the cause of these breastfeeding difficulties. The objective of this study was to determine the effectiveness of frenulotomy in infants experiencing persistent breastfeeding difficulties despite professional assistance by measuring changes in milk transfer and tongue movement during breastfeeding before and after frenulotomy. PATIENTS AND METHODS. Twenty-four mother-infant dyads (infant age: 33 ± 28 days) that were experiencing persistent breastfeeding difficulties despite receiving professional advice were recruited. Submental ultrasound scans (Acuson XP10) of the oral cavity were performed both before and ≥7 days after frenulotomy. Milk transfer, pain, and LATCH (latch, audible swallowing, type of nipple, comfort, and hold) scores were recorded before and after frenulotomy. Infant milk intake was measured by using the test-weigh method. RESULTS. For all of the infants, milk intake, milk-transfer rate, LATCH score, and maternal pain scores improved significantly postfrenulotomy. Two groups of infants were identified on ultrasound. One group compressed the tip of the nipple, and the other compressed the base of the nipple with the tongue. These features either resolved or lessened in all except 1 infant after frenulotomy. CONCLUSIONS. Infants with ankyloglossia experiencing persistent breastfeeding difficulties showed less compression of the nipple by the tongue postfrenulotomy, which was associated with improved breastfeeding defined as better attachment, increased milk transfer, and less maternal pain. In the assessment of breastfeeding difficulties, ankyloglossia should be considered as a potential cause.

Frenulotomy for Breastfeeding Infants With Ankyloglossia: Effect on Milk Removal and Sucking Mechanism as Imaged by Ultrasound

Human milk (HM) is the optimal source of nutrition, protection and developmental programming for infants. It is species-specific and consists of various bioactive components, including microRNAs, small non-coding RNAs regulating gene expression at the post-transcriptional level. microRNAs are both intra- and extra-cellular and are present in body fluids of humans and animals. Of these body fluids, HM appears to be one of the richest sources of microRNA, which are highly conserved in its different fractions, with milk cells containing more microRNAs than milk lipids, followed by skim milk. Potential effects of exogenous food-derived microRNAs on gene expression have been demonstrated, together with the stability of milk-derived microRNAs in the gastrointestinal tract. Taken together, these strongly support the notion that milk microRNAs enter the systemic circulation of the HM fed infant and exert tissue-specific immunoprotective and developmental functions. This has initiated intensive research on the origin, fate and functional significance of milk microRNAs. Importantly, recent studies have provided evidence of endogenous synthesis of HM microRNA within the human lactating mammary epithelium. These findings will now form the basis for investigations of the role of microRNA in the epigenetic control of normal and aberrant mammary development, and particularly lactation performance.

/pdf/micrornas-in-breastmilk-and-the-lactating-breast-potential-7ekts698wg.pdf

MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother

Reflecting millions of years of adaptation and optimization, milk is unique to the species that produces it and for the young of which it is intended, with large variations in both lactation strategies and milk composition existing among different mammalian species. Despite this, milk has the consistent function of providing nourishment, protection, and developmental programming to the young, with short- and long-term effects. Among its components that confer these functions, breast milk contains maternal cells, from leukocytes to epithelial cells of various developmental stages that include stem cells, progenitor cells, lactocytes, and myoepithelial cells. Although in the first 150 years since their discovery, breast milk cells were mostly studied for their morphological traits, technological advances in the last decade have allowed characterization of breast milk cell types at the protein and messenger RNA levels. This is now paving the way for investigation of the functions of these cells in the breastfed infant and the use of breast milk as a tool to understand the normal biology of the breast and its pathologies. This review summarizes the current knowledge of breast milk cellular heterogeneity and discusses future prospects and potential applications.

Donna T. Geddes

Papers

Anatomy of the human mammary gland: Current status of knowledge

Tongue movement and intra-oral vacuum in breastfeeding infants

Frenulotomy for Breastfeeding Infants With Ankyloglossia: Effect on Milk Removal and Sucking Mechanism as Imaged by Ultrasound

MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother

Cells in Human Milk State of the Science