START CARE: a protocol for a randomised controlled trial of step-wise budesonide-formoterol reliever-based treatment in children.

Background: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting ß2-agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed. Objective: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma. Methods: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned. Conclusion: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting ß-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.

Eye movement desensitization and reprocessing (EMDR) therapy for posttraumatic stress disorder in adults with serious mental illness within forensic and rehabilitation services: a study protocol for a randomized controlled trial.

BACKGROUND: Eye movement desensitization and reprocessing (EMDR) is an evidenced-based treatment for posttraumatic stress disorder (PTSD). Forensic mental health services provide assessment and treatment of people with mental illness and a history of criminal offending, or those who are at risk of offending. Forensic mental health services include high, medium, and low-security inpatient settings as well as prison in-reach and community outpatient services. There is a high prevalence of PTSD in forensic settings and posttraumatic experiences can arise in people who violently offend in the context of serious mental illness (SMI). Successful treatment of PTSD may reduce the risk of relapse and improve clinical outcomes for this population. This study aims to assess the efficacy, risk of harm, and acceptability of EMDR within forensic and rehabilitation mental health services, as compared to treatment as usual (routine care). METHODS: This is a single-blind, randomized controlled trial comparing EMDR therapy to the waiting list (routine care). Adult forensic mental health service users (n = 46) with SMI and meeting the criteria for PTSD will be included in the study. Participants will be randomized after baseline assessment to either treatment as usual plus waiting list for EMDR or to treatment as usual plus EMDR. The EMDR condition comprises nine sessions, around 60 min in length delivered weekly, the first of which is a case conceptualization session. The primary outcomes are clinician and participant-rated symptoms of PTSD, and adverse events. Secondary outcomes include psychotic symptoms, social functioning, level of disability, self-esteem, depressive symptoms, post-trauma cognitions, and broad domains of complex posttraumatic difficulties. A trained assessor blinded to the treatment condition will assess outcomes at baseline, 10 weeks, and 6 months. Additionally, grounded theory qualitative methods will be used to explore participant experience of EMDR for a subset of participants. DISCUSSION: This study will contribute to the currently limited evidence base for EMDR for PTSD in forensic settings. It is the first randomized clinical trial to assess the efficacy, risk of harm, and acceptability of EMDR for PTSD in people with SMI in either forensic, mental health inpatient, or custodial settings. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Network, ACTRN12618000683235. Registered prospectively on 24 April 2018.

mu-1 opioid receptor stimulation decreases body temperature in conscious, unrestrained neonatal rats.

The influence of mu-selective opioid agonists on neonatal thermoregulatory mechanisms has received little attention. Opioid treatment in adult subjects can cause either hyper- or hypothermia, depending on the experimental conditions, the strain of rat used, and the dose and route of administration of the drug. The present study assessed the effect of two mu opioid agonists on body temperature in neonatal Wistar rats aged 2 to 13 days. Rat pups were administered either saline or one of the two mu-selective opioid agonists, dermorphin (0.4 mg/kg) or fentanyl (0.06 mg/kg), by subcutaneous injection. Continuous rectal temperatures were measured both prior to and following drug or saline injection in freely moving, conscious animals. Ambient temperature in a plethysmograph chamber was maintained within or close to the thermoneutral zone for pups (32 degrees C). To distinguish between mu-1 and mu-2 effects, all animals received either saline or 10 mg/kg of the irreversible mu-1 antagonist naloxonazine (NALZ) 1 day prior to agonist administration. NALZ on its own had no effect on body temperature. Dermorphin and fentanyl both caused a fall in body temperature in pups of all age groups. The temperature decreases ranged from 0.8 degrees -2.2 degrees C. These opioid-induced changes were inhibited by NALZ pretreatment. Although there was no evidence for endogenous mu-1 opioid activity, this study indicated that stimulation of mu-1 opioid receptors causes a decrease in body temperature in conscious, unrestrained neonatal rats under or close to thermoneutral conditions.

Lack of involvement of mu(1) opioid receptors in dermorphin-induced inhibition of hypoxic and hypercapnic ventilation in rat pups.

The effects of dermorphin, a mu-selective opioid agonist, on respiratory responses to altered O(2) and CO(2) during postnatal development were investigated in conscious, unrestrained Wistar rats aged 2-21 days. Respiration was recorded by barometric plethysmography. Dermorphin (4 mg kg(-1)) was administered subcutaneously, and the ventilatory responses to hypoxia (11% O(2), 89% N(2)) in 2-21-day-old pups and hyperoxia (100% O(2)), and hypercapnia (8% CO(2), 92% O(2)) in 2-13-day-old pups were assessed in the presence and absence of the mu(1) receptor antagonist naloxonazine (10 mg kg(-1) s.c.) administered 1 day before testing. Six minutes of hypoxia increased ventilation in all age groups, largely via an increase in frequency. Dermorphin inhibited the ventilatory response to hypoxia, and this inhibition was insensitive to naloxonazine. After 5 min of hyperoxia, ventilation was the same as with air breathing except in the presence of dermorphin, when hyperoxic ventilation was depressed by a naloxonazine-insensitive decrease in frequency. Following this 5 min 100% O(2) exposure, pups were exposed to hypercapnia, and respiratory parameters were measured 5 min later. The ventilatory response to CO(2) was inhibited by dermorphin in a naloxonazine-insensitive manner. There was no evidence for endogenous mu(1) receptor modulation of the ventilatory responses to altered gases in rat pups of any age. Thus, mu opioid-induced inhibition of the hypoxic and hypercapnic responses in young rats does not occur via activation of mu(1) opioid receptors.

Was rurality protective in the 1918 influenza pandemic in New Zealand?

AIMS: This study aimed to examine the impact of rurality on mortality rates from pandemic influenza in New Zealand in 1918. METHODS: Mortality data was obtained from death certificates (in a published source) and denominator population data from the 1916 census (for the European population only). Analyses were conducted on cities (n = 4), towns (n = 111), counties (n = 97). RESULTS: The influenza mortality rate for the towns and cities was more than twice that of the counties that represented rural settings (rate ratio (RR) = 2.13, 95% CI = 2.00-2.27). However, larger towns (population >2000 people) had a significantly lower mortality rate than smaller towns (RR = 0.81, 95%CI = 0.74-0.88). Similarly, cities had a lower mortality rate than larger towns (RR = 0.89, 95%CI = 0.83-0.95). CONCLUSIONS: These results are suggestive that rurality may have provided some protection from mortality during this influenza pandemic. This may have been due to a mix of remoteness and greater social distancing among rural residents. However, the differences in mortality rates between towns and cities may have reflected other factors such as the more organised provision of community care in the larger towns and cities, when compared to smaller towns.

Reliability of ultrasound estimation of fetal weight in term singleton pregnancies.

AIM: To assess the reliability of ultrasound estimation of fetal weight undertaken antenatally at Wellington Hospital (Wellington City, New Zealand) in women with a singleton pregnancy = or >37 weeks gestation. METHOD: Data were collected retrospectively for pregnant women who had undergone ultrasound estimation of fetal weight <7 days prior to a term delivery (= or >37 weeks gestation) over the period of July 1998-June 2005. Stillbirths and multiple pregnancies were excluded. Ultrasound fetal weight estimations, calculated using a locally modified Woo formula, were compared with the infant's actual birth weight. RESULTS: A total of 1177 infants were studied. The mean absolute error and mean signed error (+/-SD) of ultrasound fetal weight estimations were 7.0+/-5.7% and -0.2+/-9.0%, respectively (n=1177). Three-quarters of estimations were within 10% of birth weight. Ultrasonic estimation of fetal weight tended to overestimate the weight of small infants (<2500 g; mean signed error = +3.5%+/-9.1%, n=98) and underestimate the weight of large infants (= or >4000 g; mean signed error = -3.3+/-8.7%, n=170). Both large and normal weight infants of women with diabetes tended to have their weight underestimated (mean signed error = -5.1+/-9.2%, n=48). Sensitivity, specificity, positive predictive value, and negative predictive value for ultrasonic detection of fetal weight = or >4000 g in non-diabetic women were 61%, 96%, 69%, and 94%, respectively. For detection of fetal weight = or >4500, the figures were 50%, 98%, 47%, and 98%, respectively. CONCLUSION: The accuracy of ultrasound estimations of fetal weight performed at Wellington Hospital within 7 days of delivery in term singleton pregnancies was at least similar and sometimes better than that reported in other studies. For one in four women, however, the fetal weight estimation was more than 10% different from the actual birth weight of their infant. Ultrasound measurements had a tendency to overestimate the weight of small infants while underestimating the weight of both large infants and the infants of diabetic mothers. As the reliability of ultrasound estimation of fetal weight to detect larger babies was poor, the use of such an objective measurement in the management of suspected macrosomia in term singleton pregnancies should be avoided.