Time to positivity (TTP) of neonatal blood cultures: a trend analysis over a decade from Ireland.

Background and aims: Blood culture (BC) remains gold standard for the evaluation and diagnosis of neonatal sepsis. Time when BC becomes positive and the type of microorganism isolated are crucial in deciding the antimicrobial management. Likely pathogenicity of organisms growing in BC could potentially be predicted based on the "time to positivity" (TTP). We aimed to estimate the predictive value of isolating a likely pathogenic organism depending on TTP; evaluate the aetiological trend and neonatal mortality rate due to culture-proven neonatal sepsis for over a decade and verify whether the application of a "36 hour rule" to discontinue empiric antibiotics in well newborn infants with negative BC would be safe.Methods: Retrospective review of BC results over a 14-year period from a regional neonatal unit in Ireland. Laboratory data were independently extracted in relation to BC results from the laboratory information management system (LIMS-iLAB). Neonatal mortality data were collected from multiple sources. Statistical analysis included logistic regression, chi-square, and Mann-Whitney U-test.Results: Over a 14-year period 11,432 neonatal BC specimens were incubated of which 605 (5.3%) turned positive. Overall, the commonest organism grown was coagulase-negative Staphylococcus (CoNS), 416 (68.8%). Main pathogenic organisms were Staphylococcus aureus 23 (3.8%), Enterococcus spp. 22 (3.6%), E.coli 21 (3.5%), group B Streptococcus (GBS) 18 (3.0%), and Klebsiella species 9 (1.5%). Gram-negative organisms had the shortest TTP, with Klebsiella spp. having a median TTP of 10 h and E. coli 11 h. For Gram-positives, GBS had a median TTP of 12 h, Enterococcus species 14 h, with S. aureus growing at a median time of 15 h. All of the Klebsiella spp. and other Coliforms were detected within 24 h, with, 95.2% of E.coli, 94.4% of GBS, 95.5% of Enterococci, and 95.7% of S. aureus, flagging positive in 24 h. Using logistic regression the omnibus test of the coefficients in the resulting model was significant (p < .001). Our observed coefficient (ß) for TTP was 0.144; shorter the TTP higher was the likelihood of isolating a pathogenic organism, with an odds ratio (OR) of 1.155. We also report a relatively low blood culture proven sepsis-specific neonatal mortality rate of 0.403/1000 live births and in all such instances observed TTP was less than 24 h.Conclusion: Duration of this study exceeds that of most of the neonatal blood culture TTP analysis published to-date. A shorter TTP is an important adjunct to suggest the growth of a pathogenic organism while managing suspected neonatal sepsis. TTP if < 24 h per se would not necessarily confirm the growth of a highly pathogenic organism; however, if a positive growth is likely to happen for a significant neonatal pathogen, in more than 98% the TTP would be within 24 h. This offers the clinician more of negative predictive value than a positive one; when there is no growth in BC. Our observation on TTP reiterate the National Institute of Health and Care Excellence (NICE) guideline of discontinuation of empiric antibiotics after 36 h in and clinically well and BC negative newborn infants.

Neonatal Bacteraemia Among 112,360 Live Births.

Our aims were to determine the incidence of bacteraemia in a cohort of neonatal patients over a 14 year period, to describe the organisms involved, and to establish the rates of sepsis with regard to both early onset sepsis (EOS) and late onset sepsis (LOS). Lastly, we investigated the trends of neonatal sepsis, to determine whether changes in clinical practice influenced the rate of blood culture positivity. With regards to EOS, GBS was the predominant pathogen, followed by E.coli, CoNS, and S. aureus . The overall mean EO rate per 1000 live births (LBs) was 1.19. Looking at LOS, S. aureus , CoNS , Enterococcus spp. were the most common bacteria cultured. The mean LOS rate was 1.88 per 1000 live births. The overall rate of EOS remained fairly steady. GBS remains the major pathogen in EOS; however its incidence has remained largely unchanged over time in relation to both EOS and LOS. Conversely the rate of LOS peaked from 2005-2009, mainly due to an increase in Staphylococcus aureus , CoNS and Enterococcus spp. cases, and then improved dramatically in the following years. This was likely due to a change in hospital policies in relation to hand hygiene and intravenous line placement and maintenance.

Neurodevelopmental outcome of preterm babies of 1999-2009.

The Bayley scale of infant development is employed as the performance indicator at 2 years corrected gestational age for high risk paediatric groups. We compare neurodevelopmental outcomes in two cohorts of VLBW infants born in 1999 to a cohort born a decade later, while also examining the challenges of direct comparison of modified scales: BSID-II (2nd edition of the scales) with Bayley-III, BSID-II was used in the 1999 group and Bayley-III for the 2009 cohort. We demonstrated that over a ten year period there was an improvement in neurodevelopmental scores achieved in VLBW babies. Overall there was almost an 8 point increase in the cognitive scores from the 2009 cohort compared with the 1999 cohort in this time period. The mean motor score increased by 6 points when comparing 1999 and 2009. However we highlight the difficulties in comparing developmental scales, and consider whether Bayley-III overestimates developmental ability?

Recurrent shoulder instability after open reconstruction in athletes involved in collision and contact sports.

The purpose of this study was to evaluate the incidence of recurrent instability in a group of young athletes who underwent open shoulder stabilization with a modified Bankart repair and anterior capsulorrhaphy. Recurrent dislocation was defined as an instability episode resulting in complete dislocation requiring manual reduction. Recurrent subluxation was defined as the subjective history of the shoulder "slipping or popping out" or pain and apprehension that caused cessation of athletics for at least 1 day. Sixty-six patients (64 men and 2 women) were included in the study. A collision sport precipitated instability in 53 patients and a contact sport in 13. The average follow-up was 47 months (range, 24 to 72). The average American Shoulder and Elbow Surgeons score was 95 points (range, 71 to 100). The average Rowe score was 80 points (range, 40 to 100). Two patients had experienced recurrent dislocation after surgery (3%). Eight patients (12%) had rare (fewer than three) episodes of postsurgical subluxation. Five patients (8%) had multiple recurrent subluxations after surgery. Postsurgical recurrent instability was significantly associated with preoperative episodes of subluxation. However, all patients with rare subluxation had an excellent functional result.

Testosterone regulation of gonadotropin production in goldfish.

Gonadotropin (GTH) production in teleosts is primarily regulated by complex interrelationships between the sex steroids, neurotransmitters, and GTH-releasing hormone (GnRH). Both steroids and GnRH individually regulate GTH secretion and subunit (alpha and beta) gene expression. Steroids may exert their actions directly at the level of pituitary, or indirectly by affecting brain GnRH and other neurotransmitters, causing stimulation or inhibition of GTH production. This paper reviews studies concerning the effects of testosterone on basal and GnRH-induced GTH production in the goldfish pituitary. Overall, the findings demonstrate that testosterone and GnRH individually exert stimulatory actions on GTH production, whereas a combination of testosterone and GnRH treatments reduce GTH subunit mRNA levels in the goldfish pituitary. The secretion of GTH hormones, however, is stimulated by GnRH, as well as by combined testosterone and GnRH treatments. The contributing factors that could explain the observed inhibitory effects include decreased transcription, increased posttranscriptional degradation, or increased translation of GtH subunit mRNA in the goldfish pituitary. At the present time, however, we are not able to distinguish between these possibilities.

Effect of testosterone on growth hormone gene expression in the goldfish pituitary.

This study investigated the effects of testosterone and a nonaromatizable androgen, 11 beta-hydroxyandrosterone, on growth hormone gene expression in the goldfish pituitary. In the sexually immature goldfish, treatment with physiological doses of both testosterone and 11 beta-hydroxyandrosterone significantly increased the growth hormone mRNA production above basal levels. However, at supraphysiological doses, treatment with these androgens resulted in a lower level of stimulation or an inhibition of growth hormone mRNA levels. In sexually mature goldfish, testosterone treatment stimulated growth hormone mRNA levels in a dose-related fashion, with a lower level of sensitivity compared with sexually immature fish. To investigate the direct action of testosterone at the level of the pituitary, studies were performed in vitro, using isolated pituitaries obtained from both sexually immature and mature goldfish. A dose-dependent stimulation of the pituitary growth hormone mRNA level was observed in both sexually immature and mature goldfish. Overall, the present results indicate that physiological concentrations of androgens stimulate pituitary growth hormone synthesis in both sexually immature and mature goldfish. The observed stimulatory effect of testosterone occurs directly at the level of the pituitary, although it is possible that testosterone may also exert indirect effects through other neuroendocrine factors.

Single versus two-incision arthroscopic anterior cruciate ligament reconstruction.

The purpose of this study was to compare single (endoscopic) versus two-incision arthroscopic anterior cruciate ligament reconstruction using bone-patellar tendon-bone in a population of young athletes. All patients followed a similar postoperative rehabilitation program. The Lysholm knee score, the International Knee Documentation Committee Score, KT-1000 arthrometric measurements, Lachman tests, pivot shift tests, isokinetic and functional testing, and perioperative complications were used to compare the two techniques. Anteroposterior and lateral radiographs were also evaluated and compared. Group I comprised 51 patients who underwent two-incision arthroscopic ACL reconstruction. The average age was 19.8 years, with a range of 18 to 22. The average follow-up in this group was 31 months (range, 24 to 43 months). Group II, the endoscopic group, consisted of 31 patients with an average age of 19.4 years (range, 18 to 22). The average follow-up was 25 months (range, 24 to 31 months). There were no significant differences between the two groups using subjective, objective, and functional criteria. There did appear to be a trend toward a residual pivot glide in the endoscopic group, but this did not achieve statistical significance. Radiographic analysis demonstrated an increased incidence of screw divergence in the endoscopic group. Intraoperative complications were more common with the endoscopic method.

Effect of testosterone on maturational gonadotropin subunit messenger ribonucleic acid levels in the goldfish pituitary.

In this study, we investigated the effects of testosterone and a nonaromatizable androgen, 11 beta-hydroxyandrosterone, on maturational gonadotropin (GtH-II) subunit gene expression in the goldfish pituitary. While testosterone treatment at physiological doses resulted in stimulation of GtH-II-alpha and -beta subunit mRNA production, time-course and dose-response studies performed on sexually immature goldfish of mixed sex, using a wider dose range exceeding physiological levels, demonstrated a biphasic response to in vivo androgen treatment. Time-related treatment with testosterone and 11 beta-hydroxyandrosterone (20 micrograms/fish) resulted in an initial inhibition of GtH-II subunit mRNA production (12-24 h) followed by stimulation at 72-96 h. In dose-response studies, treatment for 24 h with testosterone resulted in a significant stimulation at the low physiological doses of 0.2 and 2 micrograms/fish. At the supraphysiological level of 20 micrograms/fish, testosterone treatment resulted in no stimulation or in decreased GtH-II subunit mRNA levels compared to the control values. Similarly, treatment with 11 beta-hydroxyandrosterone resulted in a significant stimulation of GtH-II subunit mRNA levels at low physiological concentrations (0.2 microgram/ fish) and an inhibition, or no stimulation, at higher concentrations (2-20 micrograms/fish). In sexually mature goldfish of mixed sex, the biphasic effect of testosterone was not observed in vivo, and treatment with this steroid resulted in stimulation of GtH-II subunit mRNA production in a dose-related manner. To investigate the direct action of testosterone, studies were carried out using isolated goldfish pituitary fragments from goldfish of mixed sex in vitro. Treatment with testosterone at various concentrations was found to stimulate GtH-II subunit mRNA production in pituitary glands obtained from both sexually immature and sexually mature goldfish. Overall, the present study demonstrates a stimulatory effect of testosterone on GtH-II subunit mRNA levels in goldfish. The observed stimulation of basal GtH-II subunit mRNA production by testosterone occurs, in part, through a direct action at the level of the pituitary in both sexually immature and mature goldfish.