A randomised non-inferiority controlled trial of a single versus a four intradermal sterile water injection technique for relief of continuous lower back pain during labour

Background: Almost one third of women suffer continuous lower back pain during labour. Evidence from three systematic reviews demonstrates that sterile water injections (SWI) provide statistically and clinically significant pain relief in women experiencing continuous lower back pain during labour. The most effective technique to administer SWI is yet to be determined. Therefore, the aim of this study is to determine if the single injection SWI technique is no less effective than the routinely used four injection SWI method in reducing continuous lower back pain during labour.Methods/design: The trial protocol was developed in consultation with an interdisciplinary team of clinical researchers. We aim to recruit 319 women presenting at term, seeking analgesia for continuous severe lower back pain during labour. Participants will be recruited from two major maternity hospitals in Australia. Randomised participants are allocated to receive a four or single intradermal needle SWI technique. The primary outcome is the change in self-reported pain measured by visual analogue scale at baseline and thirty minutes post intervention. Secondary outcomes include VAS change scores at 10, 60, 90 and 120 min, analgesia use, mode of birth and maternal satisfaction.Statistical analysis: Sample size was calculated to achieve 90% power at an alpha of 0.025 to detect a non-inferiority margin of ≤ 1 cm on the VAS, using a one-sided, two-sample t-test. Baseline demographic and clinical characteristics will be analysed for comparability between groups. Differences in primary (VAS pain score) and secondary outcomes between groups will be analysed by intention to treat and per protocol analysis using Student's t-test and ANOVA.Conclusion: This study will determine if a single intradermal SWI technique is no less effective than the routinely used four injection technique for lower back pain during labour. The findings will allow midwives to offer women requesting SWI during labour an evidence-based alternative technique more easily administered by staff and accepted by labouring women. Trial Registration: ACTRN12609000964213

Quality of Care Provided in Two Scottish Rural Community Maternity Units: a retrospective case review.

Background: Women in Scotland with uncomplicated pregnancies are encouraged by professional bodies and national guidelines to access community based models of midwife-led care for their labour and birth. The evidence base for these guidelines relates to comparisons of predominantly urban birth settings in England. There appears to be little evidence available about the quality of the care during the antenatal, birth and post birth periods available for women within the Scottish Community Maternity Unit (CMU) model. The research aim was to explore the safety and effectiveness of the maternity services provided at two rural Community Maternity Units in Scotland, both 40 miles by main road access from a tertiary obstetric unit. Methods: Following appropriate NHS and University ethical approval, an anonymous retrospective review of consecutive maternity records for all women who accessed care at the CMUs over a 12 month period (June 2011 to May 2012) was undertaken in 2013 -14. Data was extracted using variables chosen to provide a description of the socio-demographics of the cohort and the process and outcomes of the care provided. Data were analysed using descriptive statistics. Results: Regarding effectiveness, the correct care pathway was allocated to 97.5% of women, early access to antenatal care achieved by 95.7% of women, 94.8% of women at one CMU received continuity of carer and 78.6% of those clinically eligible accessed care in labour. 11.9% were appropriately transferred to obstetrician-led care antenatally and 16.9% were transferred in labour. All women received one-to one care in labour and 67.1% of babies born at the CMUs were breastfed at birth. Regarding safety, severe morbidity for women was rare, perineal trauma of 3rd degree tear occurred for 0.3% of women and 1.0% experienced an episiotomy. Severe post partum haemorrhage occurred for 0.3% of women. Babies admitted to the Neonatal unit were discharged within 48 hours. Conclusion: These findings support the recommendations of professional bodies and national guidelines. Maternity service provision at rural CMUs achieved a consistently high standard of safety and effectiveness when measured against national standards and international evidence

Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk

Human genome-wide association studies have linked single nucleotide polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus with susceptibility to atherosclerotic vascular disease (ASVD). Although this locus encodes three well-characterized tumor suppressors, p16INK4a, p15INK4b, and ARF, the SNPs most strongly associated with ASVD are ∼120 kb from the nearest coding gene within a long non-coding RNA (ncRNA) known as ANRIL (CDKN2BAS). While individuals homozygous for the atherosclerotic risk allele show decreased expression of ANRIL and the coding INK4/ARF transcripts, the mechanism by which such distant genetic variants influence INK4/ARF expression is unknown. Here, using rapid amplification of cDNA ends (RACE) and analysis of next-generation RNA sequencing datasets, we determined the structure and abundance of multiple ANRIL species. Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles. Surprisingly, RACE also identified transcripts containing non-colinear ANRIL exonic sequences, whose expression also correlated with genotype and INK4/ARF expression. These non-polyadenylated RNAs resisted RNAse R digestion and could be PCR amplified using outward-facing primers, suggesting they represent circular RNA structures that could arise from by-products of mRNA splicing. Next-generation DNA sequencing and splice prediction algorithms identified polymorphisms within the ASVD risk interval that may regulate ANRIL splicing and circular ANRIL (cANRIL) production. These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure

Severe male infertility after failed ICSI treatment-a phenomenological study of men's experiences

<p>Abstract</p> <p>Background</p> <p>Male-factor infertility underlies approximately 30% of infertility in couples seeking treatment; of which 10% is due to azoospermia. The development of assisted reproductive technology (ART), enabling the use of epididymal or testicular sperm for fertilization of the partner's oocytes, has made biological fatherhood possible for men with obstructive azoospermia. There is limited knowledge of men's experience of their own infertility. The aim of this study was to describe men's experiences of obstructive azoospermia infertility.</p> <p>Methods</p> <p>Eight men with obstructive azoospermia, who had terminated Swedish public health system ART treatment two years previously without subsequent childbirth, were interviewed using a descriptive phenomenological method.</p> <p>Results</p> <p>The essence of the phenomenon is expressed with a metaphor: climbing a mountain step by step with the aim of reaching the top, i.e. having a child and thus a family with a child. Four constituents are included (1) inadequacy followed by a feeling of redress (2) marginalisation, (3) chivalry (4) extension of life and starting a family as driving forces.</p> <p>Conclusions</p> <p>Knowledge of men's experiences of their own infertility is important as a supporting measure to increase the quality of care of infertile couples. By adopting this facet of gender perspective in fertility treatment guidelines, care can hopefully be optimized.</p

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

Mammalian Mitochondrial DNA Replication Intermediates Are Essentially Duplex but Contain Extensive Tracts of RNA/DNA Hybrid

We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mtDNA replication intermediates (mtRIs) are essentially duplex throughout their length, but contain extensive RNA tracts on one strand. However, the extent of preservation of RNA in such molecules is highly dependent on the preparative method used. These findings strongly support the strand-coupled model of mtDNA replication involving RNA incorporation throughout the lagging strand (RITOLS)

Characteristics, Interventions, and Outcomes of Women Who Used a Birthing Pool: A Prospective Observational Study

Background: Birthing pools are integrated into maternity care in the United Kingdom and are a popular care option for women in midwifery-led units and at home. The objective of this study was to describe and compare maternal characteristics, intrapartum events, interventions, and maternal and neonatal outcomes by planned place of birth for women who used a birthing pool. Methods: A total of 8,924 women at low risk of childbirth complications were recruited from care settings in England, Scotland, and Northern Ireland. Descriptive analysis was performed. Results: Overall, 7,915 (88.9%) women had a spontaneous birth (5,192, 58.3% water births), of whom 4,953 (55.5%) were nulliparas. Fewer nulliparas whose planned place of birth was the community (freestanding midwifery unit or home) had labor augmentation by artificial membrane rupture (149, 11.3% [95% CI: 9.6-13.1]), compared with an alongside midwifery unit (271, 22.7% [95% CI: 20.3-25.2]), or obstetric unit (639, 26.3% [95% CI: 24.5-28.1]). Results were similar for epidural analgesia and episiotomy. More community nulliparas had spontaneous birth (1,172, 88.9% [95% CI: 87.1-90.6]), compared with birth in an alongside midwifery unit (942, 79% [95% CI: 76.6-81.3]) and obstetric unit (1,923, 79.2% [95% CI: 77.5-80.8]); and fewer required hospital transfer (265, 20% [95% CI: 17-22.2]) compared with those in an alongside midwifery unit (370, 31% [95% CI: 28.3-33.7]). Results for multiparas and newborns were similar across care settings. Twenty babies had an umbilical cord snap, 18 (90%) of which occurred during water birth. Conclusions: Birthing pool use was associated with a high frequency of spontaneous birth, particularly among nulliparas. Findings revealed differences in midwifery practice between obstetric units, alongside midwifery units, and the community, which may affect outcomes, particularly for nulliparas. No evidence was found for a difference across care settings in interventions or outcomes in multiparas or in outcomes for newborns. During water birth, it is important to prevent undue traction on the cord as the baby is guided to the surface. © 2012, The Authors Journal compilation © 2012, Wiley Periodicals, Inc