Has a national recruitment scheme created a positive intervention for Black, Asian or other Minority Ethnic pharmacy trainees?

OBJECTIVES: A National Recruitment Scheme (NRS) for Pharmacy trainees was introduced in England and Wales in 2017, standardising recruitment processes on behalf of employers and with the aim of reducing bias for candidates applying to training posts within the National Health Service (NHS). This research attempted to identify whether the introduction of the NRS had an impact on the recruitment of Black, Asian, or other Minority Ethnic applicants into the most sought-after posts within the Scheme (hospital posts). METHODS: An observational study was undertaken. Anonymised pharmacist trainee recruitment data between the cohort intakes of 2015-16 and 2020-21 was obtained from the pharmacy regulator the General Pharmaceutical Council and a comparison of proportional representations of ethnicities was undertaken, to ascertain whether a greater proportion of applicants from minority backgrounds attained the most sought-after posts in the NHS after the NRS was introduced. A robust generalised linear model was then used to analyse the data using binomial as the variance function and logit as a link function, where the proportion of hospital recruitment was an outcome with a two-way interaction between intervention and ethnicity after adjusting for overall proportion. KEY FINDINGS: The statistical analysis of 18 283 pharmacy trainees in total, of whom 4446 were in hospital, shows a significant overall impact of intervention, with a significant positive change in the proportions of Asian-Pakistani applicants (P-value < 0.001) and Black-African applicants (P-value < 0.001) recruited to hospital posts. CONCLUSIONS: Since the introduction of the NRS there has been a statistically significant impact on the correlation between the overall number of Black, Asian or other Minority Ethnic applicants and their proportion in hospital. That is, not only is the makeup of the hospital cohort increasingly reflecting the diversity of the overall cohort, but also a larger percentage of each ethnic cohort is attaining hospital training places.

Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways in Skeletal Muscle.

AIMS: Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice (Sod1-/-) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1-/- mice. To dissect any underlying cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1-/- mice, we characterized neuromuscular changes in the Sod1-/- model compared with mSod1KO mice and examined degenerative molecular mechanisms and pathways in peripheral nerve and skeletal muscle. RESULTS: In contrast to mSod1KO mice, myofiber atrophy in Sod1-/- mice was associated with increased muscle oxidative damage, neuromuscular junction degeneration, denervation, nerve demyelination, and upregulation of proteins involved in maintenance of myelin sheaths. Proteomic analyses confirmed increased proteasomal activity and adaptive stress responses in muscle of Sod1-/- mice that were absent in mSod1KO mice. Peripheral nerve from neither Sod1-/- nor mSod1KO mice showed increased oxidative damage or molecular responses to increased oxidation compared with wild type mice. Differential cysteine (Cys) labeling revealed a specific redox shift in the catalytic Cys residue of peroxiredoxin 6 (Cys47) in the peripheral nerve from Sod1-/- mice. Innovation and Conclusion: These findings demonstrate that neuromuscular integrity, redox mechanisms, and pathways are differentially altered in nerve and muscle of Sod1-/- and mSod1KO mice. Results support the concept that impaired redox signaling, rather than oxidative damage, in peripheral nerve plays a key role in muscle loss in Sod1-/- mice and potentially sarcopenia during aging. Antioxid. Redox Signal. 28, 275-295.

Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs.

OBJECTIVE: To investigate whether inhaling 50% xenon during hypothermia (HT) offers better neuroprotection than xenon or HT alone. METHODS: Ninety-eight newborn pigs underwent a 45-minute global hypoxic-ischemic insult severe enough to cause permanent brain injury, and 12 pigs underwent sham protocol. Pigs then received intravenous anesthesia and were randomized to 6 treatment groups: (1) normothermia (NT; rectal temperature 38.5 degrees C, n = 18); (2) 18 hours 50% xenon with NT (n = 12); (3) 12 hours HT (rectal temperature 33.5 degrees C, n = 18); (4) 24 hours HT (rectal temperature 33.5 degrees C, n = 17); (5) 18 hours 50% xenon with 12 hours HT (n = 18); and (6) 18 hours 50% xenon with 24 hours HT (n = 17). Fifty percent xenon was administered via a closed circle with 30% oxygen and 20% nitrogen. After 10 hours rewarming, cooled pigs remained normothermic until terminal perfusion fixation at 72 hours. Global and regional brain neuropathology and clinical neurological scores were performed. RESULTS: Xenon (p = 0.011) and 12 or 24 hours HT (p = 0.003) treatments offered significant histological global, and regional neuroprotection. Combining xenon with HT yielded an additive neuroprotective effect, as there was no interaction effect (p = 0.54). Combining Xenon with 24 hours HT offered 75% global histological neuroprotection with similarly improved regional neuroprotection: thalamus (100%), brainstem (100%), white matter (86%), basal ganglia (76%), cortical gray matter (74%), cerebellum (73%), and hippocampus (72%). Neurology scores improved in the 24-hour HT and combined xenon HT groups at 72 hours. INTERPRETATION: Combining xenon with HT is a promising therapy for severely encephalopathic infants, doubling the neuroprotection offered by HT alone.

Liver enzymes cannot be used to predict liver damage after global hypoxia-ischemia in a neonatal pig model.

BACKGROUND: The term newborn pig is an established model for studying both brain and organ pathology after hypoxia-ischemia (HI). Serial liver enzyme activity is often used to predict liver injury but little is known about the relation between consecutive values of different liver enzymes and histologically verified liver injury. OBJECTIVE: To determine whether plasma values of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) differed between newborn pigs with liver injures and pigs with normal livers after a severe global HI insult. METHODS: Nineteen < or =36-hour-old pigs underwent a 45-min global HI insult followed by 72-hour survival. Four histological sections from standardized areas within each liver were examined. Areas under the curve (AUC) for the enzymes were calculated and compared between pigs with pathological changes in the liver (n = 12) and pigs with normal liver histology (n = 7). RESULTS: No differences in AUC for the enzyme values were seen between the groups. However, in pigs with liver injuries a transient significant increase in LDH at the end of the HI insult (928 U/l (567-1,031)) was seen compared to the baseline value (679 U/l (548-866), p = 0.010). Significantly more liver injury was seen in animals with the umbilical vein catheter (UVC) tip inserted into the liver (p = 0.040) compared to animals with the UVC tip located outside the liver. CONCLUSIONS: In newborn pigs subjected to global HI, only LDH increases alongside pathological changes in the liver. Normal values of ALT and AST do not exclude hepatic injury.

Delayed hypothermia as selective head cooling or whole body cooling does not protect brain or body in newborn pig subjected to hypoxia-ischemia.

The neuroprotective efficacy of hypothermia (HT) after hypoxia-ischemia (HI) falls dramatically the longer the delay in initiating HT. Knowledge is scarce regarding protective or adverse effects of HT in organs beyond the brain. In addition, the relative effectiveness of selective head cooling (SHC) and whole body cooling (WBC) has not been studied. We aimed to examine whether 24 h HT, initiated 3 h after global HI is brain- and/or organ-protective using pathology, neurology, and biochemical markers. Fifty,

Analysis of neuronal, glial, endothelial, axonal and apoptotic markers following moderate therapeutic hypothermia and anesthesia in the developing piglet brain.

Hypothermia (HT) by whole body (WBC) or selective head cooling (SHC) reduces hypoxic-ischemic (HI) brain injury; however, whether prolonged hypothermia and/or anesthesia disrupts immature brain development, eg, increases apoptosis, is unknown. Anesthesia increases apoptosis in immature animals. We investigated whether neuroprotective hypothermia and anesthesia disrupts normal brain development. Thirty-eight pigs <24 h old were randomized between five groups and were killed after 72 h: eighteen received a global hypoxic-ischemic insult under anesthesia, eight subsequently cooled by SHC with WBC to T(rectal) 34.5 degrees C for 24 h, followed by 48 h normothermia (NT) at T(rectal) 39.0 degrees C, while 10 remained normothermic. Sixteen underwent anesthetized sham hypoxic-ischemic, six then following normothermia and 10 following hypothermia protocols. There were four normothermic controls. The hypothermia groups demonstrated significant brain hypothermia. In the hypoxic-ischemic groups this conferred approximately 60% neuroprotection reducing histological injury scores in all brain areas. Immunohistochemical/histochemical analyses of neuronal, glial, endothelial, axonal, transcriptional apoptotic markers in areas devoid of histological lesions revealed no hypothermia/normothermia group and differences whether exposed to hypoxic-ischemic or not. Neither 36-h anesthesia nor 24-h hypothermia produced adverse effects at 4-day survival on a panel of brain maturation/neural death markers in newborn pigs. Longer survival studies are necessary to verify the safety of hypothermia in the developing brain.

A neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation.

OBJECT: The combination of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD) remains an important cause of disability in children surviving prematurity. Currently, there is no clear agreement on the management of neonatal IVH, apart from the eventual insertion of a shunt to control PHVD. Cerebrospinal fluid (CSF) shunts are associated with a relatively high complication rate in this population. The development of new treatment options requires greater understanding of the pathophysiological mechanisms of IVH and PHVD, as well as an opportunity to monitor closely their effects on the immature brain. The authors have developed a neonatal large animal model of IVH with long-term survival, allowing the full development of PHVD. METHODS: Fourteen piglets that were 3 to 24 hours old were randomized to receive slow injections of autologous blood, autologous blood with elevated hematocrit, or artificial CSF after induction of general anesthesia. A fourth group served as controls. All animals underwent surgery to form an artificial fontanelle at the bregma. Physiological parameters, including intracranial pressure and electroencephalography, were monitored during injection. RESULTS: Serial cranial ultrasonography studies performed during the 23- to 44-day survival period demonstrated progressive ventricular dilation in the animals injected with blood. Ventricular volumes, measured with image analysis software, confirmed the highest dilation after injection of blood with an elevated hematocrit. Histological evaluation showed fibrosis in the basal subarachnoid space of hydrocephalic piglets. CONCLUSIONS: This piglet model closely replicates human neonatal IVH and PHVD. It allows detailed physiological and ultrasonographic monitoring over a prolonged survival period. It is suitable for evaluation of noninvasive as well as surgical options in the management of IVH and PHVD.

Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia.

BACKGROUND AND PURPOSE: Brain injury after hypoxic-ischemic insults evolves via an apoptotic/necrotic cascade. Glutamate over release and N-methyl-d-aspartate (NMDA) receptor over activation (excitotoxicity) are believed to trigger this process. Xenon is a nontoxic anesthetic gas that reduces neurotransmitter release and functionally antagonizes NMDA receptors. Administering xenon to hypoxic-ischemic newborns might be clinically effective if the neurotoxic processes continue evolving after delivery. We sought to determine whether xenon administration after the initial hypoxic-ischemic insult was neuroprotective. METHODS: Fifty 7-day-old rats received a 90-minute hypoxic insult after unilateral carotid ligation. They were then randomized to breathe 1 of 2 gas mixtures for 3 hours: 50% Xe/30% O2/20% N2 or 30% O2/70% N2. RESULTS: One week after hypoxic-ischemic survival, significant global protection was seen in the xenon group (80% less injury); cortex/white matter (88% versus 25%), hippocampus (62% versus 0%), basal ganglia (81% versus 25%), and thalamus (50% versus 0%; percentage of global damage score in nonxenon versus xenon groups, respectively). CONCLUSIONS: Three hours of xenon administration commenced after hypoxia-ischemia in neonatal rats provides short-term neuroprotection. This finding suggests that treatment with xenon after perinatal asphyxia would also be neuroprotective. Because xenon does not cause other neurotoxic effects and has demonstrated minimal side effects in extensive anesthesia studies, it would make an ideal candidate for the treatment after human perinatal hypoxia-ischemia.

Is zygosity or chorionicity the main determinant of fetal outcome in twin pregnancies?

OBJECTIVE: The purpose of this study was to examine whether fetal outcome in twin pregnancies is dependent on zygosity or chorionicity. STUDY DESIGN: This was a prospective observational study comprised of women with twin pregnancies who attended the fetal medicine unit at St Michael's Hospital, Bristol, Ireland, during the years 1998 to 2000 and who were delivered in hospitals in south west England. After delivery, zygosity was determined with umbilical cord blood with the use of microsatellite markers that were amplified by polymerase chain reaction. Placentae were examined histologically for chorionic type. The perinatal outcomes of 3 groups of monozygotic monochorionic, monozygotic dichorionic, and dizygotic pregnancies were compared with the use of the Mann-Whitney U test and the Fisher's exact test. RESULTS: All 92 dizygotic and 15 monozygotic dichorionic pregnancies resulted in live births. In 7 of the 39 cases in the monozygotic monochorionic group, either both twins were not live born or delivery occurred <24 weeks of gestation. The gestational age at delivery and birth weight were significantly lower, and there were a greater number of cases with birth weight discordancy of >25% in the monochorionic pregnancies compared with the other 2 groups (P < .05). There were no significant differences in any of the study parameters between the monozygotic dichorionic and dizygotic groups. CONCLUSION: Fetal outcome in twin pregnancies is related to chorionicity rather than zygosity.

Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome.

Lactobacilli, principally the strains that are hydrogen peroxide (H(2)O(2)) producing, may have a protective effect against vaginal colonization by pathogenic species such as those that cause bacterial vaginosis. Previous reports have also suggested that H(2)O(2)-producing lactobacilli in the vagina may protect pregnant women against ascending infection of the chorioamniotic membranes and uterine cavity. We report the identification and H(2)O(2) production of lactobacilli isolated from vaginal swabs collected at 20 weeks' gestation from a population of pregnant women at high risk of preterm birth. We also report the correlation between identification and H(2)O(2) production in relation to the outcomes of chorioamnionitis and preterm birth. Lactobacilli were identified by partial 16S rRNA gene sequencing. H(2)O(2) production by isolates was determined by a semiquantitative method. The most commonly isolated species were L. crispatus, L. gasseri, L. vaginalis and L. jensenii. Amounts of H(2)O(2) produced by lactobacilli varied widely. The presence of lactobacilli producing high levels of H(2)O(2) in the vagina of this population of pregnant women was associated with a reduced risk of bacterial vaginosis at 20 weeks' gestation and subsequent chorioamnionitis. L. jensenii and L. vaginalis produced the highest levels of H(2)O(2). We postulate that H(2)O(2)-producing lactobacilli are able to reduce the incidence of ascending infections of the uterus and the subsequent production of proinflammatory molecules which are important in the pathogenesis of chorioamnionitis and preterm birth.

Posthemorrhagic ventricular dilation in the neonate: development and characterization of a rat model.

Intraventricular hemorrhage is a common complication of prematurity. Posthemorrhagic ventricular dilation (PHVD) has a high rate of disability and no safe and effective treatment. Its pathogenesis is poorly understood, largely because of the lack of a satisfactory animal model. We have developed a model of neonatal PHVD in the rat. Seven-day-old (P7) Wistar rat pups were given 80-microl injections of citrated rat blood or artificial cerebrospinal fluid (CSF) into alternate lateral ventricles on P7 and P8. Intracranial pressure was monitored and increased briefly by over 8-fold. Some rats received further 10-microl intraventricular injections of India ink on P21. Animals were weighed daily and simple neurologic tests performed. On P21 (or P22 if India ink had been injected), the rats were perfusion-fixed and blocks processed for paraffin histology. Sixty-five percent of pups injected with blood and 50% injected with artificial CSF developed dilated lateral ventricles, with patchy loss of ependyma, marked astrocytic gliosis, and rarefaction of periventricular white matter. India ink injection revealed slow transit of CSF from the dilated lateral ventricles but eventual passage into the subarachnoid space. Pups that had received intraventricular injections but did not develop ventricular dilation nonetheless had lighter brains than littermate controls (p < 0.001). Body weights were not significantly different from controls. Hydrocephalic animals had reduced motor performance as assessed by a grip traction test (p = 0.0002). This model is well suited to studying the pathogenesis of PHVD.

Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective.

Hypothermia is potentially therapeutic in the management of neonatal hypoxic-ischemic brain injury. However, not all studies have shown a neuroprotective effect. It is suggested that the stress of unsedated hypothermia may interfere with neuroprotection. We propose that selective head cooling (SHC) combined with mild total-body hypothermia during anesthesia enhances local neuroprotection while minimizing the occurrence of systemic side effects and stress associated with unsedated whole-body cooling. Our objective was to determine whether SHC combined with mild total-body hypothermia while anesthetized for a period of 24 hours reduces cerebral damage in our piglet survival model of global hypoxia-ischemia. Eighteen anesthetized piglets received a 45-minute global hypoxic-ischemic insult. The pigs were randomized either to remain normothermic or to receive SHC. We found that the severity of the hypoxic-ischemic insult was similar in the SHC versus the normothermic group, and that the mean neurology scores at 30 and 48 hours and neuropathology scores were significantly better in the SHC group versus the normothermic group. We conclude that selective head cooling combined with mild systemic hypothermia and anesthesia is neuroprotective when started immediately after the insult in our piglet model of hypoxic-ischemic encephalopathy.

Prediction of chorionicity in twin pregnancies at 10-14 weeks of gestation.

OBJECTIVE: To examine the accuracy of sonographic determination of chorionicity in twin pregnancies at 10-14 weeks of gestation. DESIGN: Prospective study on the sonographic prediction of chorionicity at 10-14 weeks of gestation. PARTICIPANTS: During a 30 month period, from October 1997 to May 2000, 165 women attending the departments of fetal medicine or ultrasound. METHODS: Sonographic criteria used in the diagnosis of chorionicity were the number of placental sites, the lambda (lambda) and T signs and the thickness of the inter-twin membrane. The diagnosis of chorionicity was made at the time of the ultrasound examination using all these features and subsequently compared with the postnatal diagnosis, confirmed either by placental histology or discordancy in infant sex. RESULTS: In 150 cases with confirmation of chorionicity following delivery, 116 were postnatally classified as dichorionic and 34 monochorionic. Prenatal ultrasound examination correctly identified chorionicity in 149 (99.3%) cases. The most reliable indicator for dichorionicity was a combination using the lambda sign or two separate placentae with a sensitivity and specificity of 97.4% and 100%, respectively. The most useful test in predicting monochorionicity was the T sign with a sensitivity of 100% and specificity of 98.2%. Measurement of the inter-twin membrane thickness was a less reliable indicator where the sensitivity for dichorionicity and specificity for monochorionicity was only 92.6%. CONCLUSIONS: Ultrasound examination of twin pregnancies at 10-14 weeks of gestation predicts chorionicity with a high degree of accuracy using a combination of the number of placentae, lambda and T signs and inter-twin membrane thickness. All hospitals should encourage departments providing ultrasound services to undertake chorionicity determination when examining women with twin pregnancies at this gestation.