Rapid Action of Retinoic Acid on the Hypothalamic Pituitary Adrenal Axis.

Retinoic acid (RA) is the active metabolite of vitamin A but is also used as a medication, primarily for acne in which the treatment regime lasts several months. A number of studies have indicated that treatment with RA over this time period impacts the hypothalamic-pituitary-adrenal (HPA) axis and may contribute to a number of the side-effects of the drug. No studies though have investigated the short-term, early effects RA may have on the HPA axis via the transcriptional pathways activated by the RA receptor. This study investigated the action of RA over 3 days on regulatory components of the HPA axis. Several key genes involved in glucocorticoid feedback pathways in the hippocampus, hypothalamus and pituitary were unchanged after 3-days exposure to RA. Key elements though in the adrenal gland involved in corticosterone and aldosterone synthesis were altered in particular with the Cyp11b2 gene downregulated in vivo and ex vivo. The rapid, 5 h, change in Cyp11b2 expression suggested this activation may be direct. These results highlight the adrenal gland as a target of short-term action of RA and potentially a trigger component in the mechanisms by which the long-term adverse effects of RA treatment occur.

Prescription opioid use in pregnancy.

Prescription medications, including opioid analgesics, are increasingly prescribed in Australia and internationally. More women are presenting in pregnancy with prescription opioid use which can potentially cause harm to the mother and fetus. This article outlines the different types of prescription opioids, defines how prescription opioid use disorder presents clinically and suggests a rational clinical approach to assess and manage patients in the context of pregnancy and their infants.

Oral dosing of rodents using a palatable tablet.

RATIONALE: Delivering orally bioavailable drugs to rodents is an important component to investigating that route of administration in novel treatments for humans. However, the traditional method of oral gavage requires training, is stressful, and can induce oesophageal damage in rodents. OBJECTIVES: To demonstrate a novel administrative technique-palatable gelatine tablets-as a stress-free route of oral delivery. METHODS: Twenty-four male Lister hooded rats were sacrificed for brain tissue analysis at varying time-points after jelly administration of 30 mg/kg of the wake-promoting drug modafinil. A second group of 22 female rats were tested on locomotor activity after 30 mg/kg modafinil, or after vehicle jellies, with the locomotor data compared to the brain tissue concentrations at the corresponding times. RESULTS: Modafinil was present in the brain tissue at all time-points, reducing in concentration over time. The pattern of brain tissue modafinil concentration is comparable to previously reported results following oral gavage. Modafinil-treated rats were more active than control rats, with greater activity during the later time-periods-similar to that previously reported following intraperitoneal injection of 40 mg/kg modafinil. CONCLUSIONS: Palatable jelly tablets are an effective route of administration of thermally stable orally bioavailable compounds, eliminating the stress/discomfort and health risk of oral gavage and presenting as an alternative to previously reported palatable routes of administration where high protein and fat levels may adversely affect appetite for food reward, and uptake rate in the gastrointestinal tract.

Managing opioid overdose in pregnancy with take-home naloxone.

Programs have recently been established in Australia and internationally to allow wider access to naloxone to people at risk of opioid overdose yet there are no guidelines relating to the administration of naloxone to pregnant women, particularly regarding dose requirements and resuscitative measures peculiar to pregnancy. This paper provides practical guidelines to health workers in relation to any complications that may arise during opioid overdose response (including the administration of naloxone) for pregnant women and the follow up required ensuring best possible outcomes for mother and baby.

Two Case Studies Illustrating a Shared Decision-Making Approach to Illicit Methamphetamine Use and Breastfeeding.

Crystal methamphetamine (MA) is a potent psycho-stimulant that is increasingly used worldwide. It is highly addictive, is often made in clandestine laboratories, and can cause serious health issues in adults. Health professionals caring for women in the perinatal period must counsel women about the health risks to infants if they are exposed to MA in breast milk. Most guidelines recommend that women who have current or recent MA use do not breastfeed. This article explores approaches to breastfeeding advice in the context of MA use. Women who have made lifestyle changes, engaged well with services in the antenatal period, and are committed to drug counseling services after discharge from hospital may be supported to breastfeed if they are assessed as safe to do so. The importance of assessing each woman individually when developing infant feeding plans throughout the perinatal period is advocated.

Individuals with severely impaired vision can learn useful orientation and mobility skills in virtual streets and can use them to improve real street safety.

Virtual reality has great potential in training road safety skills to individuals with low vision but the feasibility of such training has not been demonstrated. We tested the hypotheses that low vision individuals could learn useful skills in virtual streets and could apply them to improve real street safety. Twelve participants, whose vision was too poor to use the pedestrian signals were taught by a certified orientation and mobility specialist to determine the safest time to cross the street using the visual and auditory signals made by the start of previously stopped cars at a traffic-light controlled street intersection. Four participants were trained in real streets and eight in virtual streets presented on 3 projection screens. The crossing timing of all participants was evaluated in real streets before and after training. The participants were instructed to say "GO" at the time when they felt the safest to cross the street. A safety score was derived to quantify the GO calls based on its occurrence in the pedestrian phase (when the pedestrian sign did not show DON'T WALK). Before training, > 50% of the GO calls from all participants fell in the DON'T WALK phase of the traffic cycle and thus were totally unsafe. 20% of the GO calls fell in the latter half of the pedestrian phase. These calls were unsafe because one initiated crossing this late might not have sufficient time to walk across the street. After training, 90% of the GO calls fell in the early half of the pedestrian phase. These calls were safer because one initiated crossing in the pedestrian phase and had at least half of the pedestrian phase for walking across. Similar safety changes occurred in both virtual street and real street trained participants. An ANOVA showed a significant increase of the safety scores after training and there was no difference in this safety improvement between the virtual street and real street trained participants. This study demonstrated that virtual reality-based orientation and mobility training could be as efficient as real street training in improving street safety in individuals with severely impaired vision.

How long should infants at risk of drug withdrawal be monitored after birth?

AIM: Neonatal abstinence syndrome (NAS) is an increasingly common disorder diagnosed in infants exposed to various drugs, causing immense financial and social burden. Recommendations from various bodies are for babies to be monitored for 4 to 7 days following birth so that prompt treatment can commence should symptoms develop. We aimed to determine the best post-natal observation period in babies at risk of NAS. METHODS: A retrospective review was undertaken of infants ≥35 weeks' gestation who received treatment for NAS in the period 2001-2010. During this time, the standard post-natal observation period was a minimum of 7 days. Data including drug exposure, day of admission and day of treatment were collected. RESULTS: Two hundred and ten babies were included. Drug exposure was predominantly to opiates (99%); however, most infants (58%) were exposed to additional substances (benzodiazepines, cannabis or amphetamines). Ninety-five per cent of infants were admitted by day 5 of life. Of the babies treated by day 7, 98.5% had been admitted to the nursery by day 5. Infants with polydrug exposure were admitted significantly earlier; however, time to treatment was not significantly different to those exposed to opiate replacement therapy alone. CONCLUSIONS: In our hospital, babies treated for NAS often required admission before day 5. This has implications for hospital resource allocation, suggesting that routine post-natal observation for NAS could be shortened to 5 days. Further research is needed to help identify neonates who require more careful post-natal observation.

Home-based detoxification for neonatal abstinence syndrome reduces length of hospital admission without prolonging treatment.

AIM: Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome, secondary to in utero chemical exposure and characterised by tremor, irritability and feed intolerance. It often requires prolonged hospital treatment and separation of families. Outpatient therapy may reduce this burden, but current literature is sparse. This review aimed to evaluate the safety and efficacy of our home-based detoxification programme and compare it with standard inpatient care. METHODS: Infants requiring treatment for NAS between January 2004 and December 2010 were reviewed. Data on demographics, drug exposure, length of stay and type of therapy were compared between infants selected for home-based therapy and those treated conventionally. RESULTS: Of the 118 infants who were admitted for treatment of NAS, 38 (32%) were managed at home. Infants receiving home-based detoxification had shorter hospital stays (mean 19 days vs. 39 days), with no increase in total duration of treatment (mean 36 days vs. 41 days), and were more likely to be breastfeeding on discharge from hospital care (45% vs. 22%). CONCLUSION: In selected infants, home-based detoxification is associated with reduced hospital stays and increased rates of breastfeeding, without prolonging therapy. Safety of the infants remains paramount, which precludes many from entering such a programme.

Prevalence of attention-deficit/hyperactivity disorder among children with vision impairment.

PURPOSE: To evaluate the prevalence of parent-reported attention-deficit/hyperactivity disorder (ADHD) in two clinics in Alabama serving children with vision impairment. METHODS: The medical records of children 4-17 years of age attending the Alabama School for the Blind (ASB) during the 2010-2011 school year or seen at the University of Alabama at Birmingham (UAB) Center for Low Vision Rehabilitation between 2006 and 2010 were retrospectively reviewed. Sociodemographics, ocular characteristics, and parental report of ADHD diagnosis were obtained. The prevalence of ADHD was compared to national and state figures for age-similar children regardless of comorbidities. The prevalence of ADHD, sociodemographic, and ocular characteristics was also compared between clinical sites. RESULTS: A total of 264 children participated in the study (95 from ASB and 169 from UAB). The prevalence of ADHD among children with visual acuity better than hand motion (n = 245) was 22.9%, which is higher than reported state (14.3%) and national prevalence (9.5%) for children in this age range. The prevalence was similar at ASB (22.4%) and UAB (23.1%). Those with ADHD were similar to those without ADHD with respect to age, sex, and race. Children with ADHD were significantly less likely to have nystagmus and more likely to have better visual acuity (P < 0.05). The prevalence of ADHD among the 19 participants with total or near total vision loss (all from ASB) was 10.5%. CONCLUSIONS: Our analyses suggest that children with vision impairment may be more likely to be diagnosed with ADHD than children in the general population.

Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial.

OBJECTIVE: Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement. METHODS: Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation. RESULTS: In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group. CONCLUSIONS: The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe.

Reappraisal of C-reactive protein as a screening tool for neonatal sepsis.

AIMS: To assess the usefulness of C-reactive protein (CRP) [either alone or in combination with a full blood examination (FBE) and microbiology of gastric aspirate] in predicting the diagnosis of neonatal sepsis compared with routinely available markers of infection. METHODS: A prospective study of quantitative CRP, FBE, gastric aspirate and surface swab microscopy and culture in predicting neonatal sepsis in a level III perinatal referral hospital was performed. RESULTS: Of 301 episodes evaluated over a 5-month period, there was a 5% rate of major (culture proven) sepsis (3% early onset, <72 hours) and 10% rate of modified sepsis. No single test alone was sufficiently reliable as an indicator of infection to be a satisfactory screening tool for early onset sepsis [CRP sensitivity 67%, negative predictive value (NPV) 86%, FBE sensitivity 63%, NPV 80%, gastric aspirate sensitivity 57%, NPV 83%]. CONCLUSION: The three-test combination had a sensitivity of 97%, NPV 98% and likelihood ratio of 49, thus providing a useful diagnostic tool.