A study of elective genome sequencing and pharmacogenetic testing in an unselected population

BACKGROUND: Genome sequencing (GS) of individuals without a medical indication, known as elective GS, is now available at a number of centers around the United States. Here we report the results of elective GS and pharmacogenetic panel testing in 52 individuals at a private genomics clinic in Alabama. METHODS: Individuals seeking elective genomic testing and pharmacogenetic testing were recruited through a private genomics clinic in Huntsville, AL. Individuals underwent clinical genome sequencing with a separate pharmacogenetic testing panel. RESULTS: Six participants (11.5%) had pathogenic or likely pathogenic variants that may explain one or more aspects of their medical history. Ten participants (19%) had variants that altered the risk of disease in the future, including two individuals with clonal hematopoiesis of indeterminate potential. Forty-four participants (85%) were carriers of a recessive or X-linked disorder. All individuals with pharmacogenetic testing had variants that affected current and/or future medications. CONCLUSION: Our study highlights the importance of collecting detailed phenotype information to interpret results in elective GS

Upright Versus Lying Down Position in Second Stage of Labour in Nulliparous Women With Low Dose Epidural: BUMPES Randomised Controlled Trial

INTERVENTIONS Women were allocated to an upright or lying down position, using a secure web based randomisation service, stratified by centre, with no masking of participants or clinicians to the trial interventions. MAIN OUTCOME MEASURES The primary outcome was spontaneous vaginal birth. Women were analysed in the groups into which they were randomly allocated, regardless of position recorded at any time during the second stage of labour (excluding women with no valid consent, who withdrew, or who did not reach second stage before delivery). Secondary outcomes included mode of birth, perineal trauma, infant Apgar, delivery (adjusted risk ratio 1.08, 99% confidence interval 0.99 to 1.18), obstetric anal sphincter injury (1.27, 0.88 to 1.84), infant Apgar score <4 at five minutes (0.66, 0.06 to 6.88), and maternal faecal incontinence at one year (1.18, 0.61 to 2.28). CONCLUSIONS Evidence shows that lying down in the second stage of labour results in more spontaneous vaginal births in nulliparous women with epidural analgesia, with no apparent disadvantages in relation to short or longer term outcomes for mother or baby

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

Narrative review of interventions suitable for well-baby clinics to promote infant attachment security and parents' sensitivity

Aim The aim of this narrative review was to evaluate the evidence for interventions for children's secure attachment relationships and parents’ caregiving sensitivity that could potentially be implemented in the context of a well‐baby clinic. Methods Literature search on programmes for parental caregiving sensitivity and secure attachment for infants aged 0‐24 months. Randomised controlled trials (RCTs) published 1995‐2018 with interventions starting from one week postpartum, and with a maximum of 12 sessions (plus potential booster session) were included. Results We identified 25 studies, of which 22 studied effects of home‐based programmes using video feedback techniques. Positive effects of these interventions in families at risk were found on parental caregiving sensitivity and to a lesser extent also on children's secure or disorganised attachment. The effects of two of these programmes were supported by several RCTs. Three intervention studies based on group and individual psychotherapy showed no significant positive effects. Most of the interventions targeted mothers only. Conclusion The review found some evidence for positive effects of selective interventions with video feedback techniques for children's secure attachment and strong evidence for positive effects on parental caregiving sensitivity. Important knowledge gaps were identified for universal interventions and interventions for fathers and parents with a non‐Western background