A retrospective analysis comparing set up errors from standard versus customised headrests for head and neck radiotherapy

IntroductionIn response to advice from The National Institute for Health and Care Excellence ⁽¹⁾ to reduce hospital visits during COVID-19, standard headrests were introduced for head and neck radiotherapy within Northern Centre for Cancer Care (NCCC). The standard headrest requires one mould room appointment compared to 3 appointments with customised headrests.MethodsTwo groups of 10 patients treated between December 2019 and June 2020 were retrospectively analysed by 1 observer. Groups were stratified according to age, sex and tumour site. One group had customised headrest and the other had standard headrest. Five hundred and forty seven cone beam computed tomography images were reviewed. A 6 Degree of Freedom match was performed then chin, shoulder and spine position were assessed using dosimetrist drawn structures. Structures out of the tolerance were recorded. A chi-squared test was used for statistical analysis.ResultsThe out of tolerance chin position count recorded was 21 for customised headrest and 36 for standard headrest, p-value 0.046. The shoulder position count was 13 for customised headrest and 77 for standard headrest p-value <0.001. The spine position count was 3 for CHR and 21 for standard headrest, p-value <0.001. This means the headrests compared are not equivalent in terms of set up reproducibility. Overall the standard headrest group had 10 set-up re-scans and no set up re-scans were recorded in the customised headrest group.ConclusionFewer hospital visits with SHR reduce patient exposure to COVID-19. However, CHR provided a more reliable level of immobilisation in this study.Implications for practiceThe radiotherapy service will be reviewed in line with these findings.     

Rapid tolerance and locomotor sensitization in ethanol-naïve adolescent rhesus macaques

Background: Acute and chronic tolerance, as well as locomotor sensitization, have been linked to ethanol intake. This study examined the change in response between 2 acutely administered doses of ethanol in adolescent rhesus macaques, with the objective of investigating rapid tolerance and locomotor sensitization to the behavioral effects of ethanol, and whether these phenomena are related to voluntary ethanol consumption in nonhuman primates. Methods: Rhesus macaques (n = 109, 42 males, 67 females) were administered 2 sequential intravenous doses of ethanol (2.2 g/kg for males, 2.0 g/kg for females) separated by a period of 5 to 30 days. Following each injection, subjects underwent a 30‐minute behavior assessment. Behavioral data were summarized using factor analysis, and compared between the 2 doses using repeated measures ANOVA. The relationship between behavioral response measures and the number of days between doses was analyzed using regression analyses. Following the second ethanol dose, subjects were given free access to an aspartame‐sweetened 8.4% ethanol solution for 1 hour a day for 4 weeks. Percent change in behavioral response measures from dose 1 to dose 2 was analyzed for associations with ethanol consumption using multiple regression analyses. Results: Factor analysis yielded 3 factors: ataxia, stimulation, and jumping. From dose 1 to dose 2 there was a significant decrease in ataxia and a significant increase in stimulation. Peak blood ethanol concentration did not differ between doses. There were no significant associations between the number of days between doses and the magnitude of change in response for any of the behavioral measures. Percent change in stimulation from dose 1 to dose 2 was positively associated with subsequent oral ethanol consumption only in females tested in a social setting. Conclusions: Adolescent rhesus macaques develop rapid tolerance to the motor‐impairing effects of alcohol, while at the same time developing locomotor sensitization. These changes in response are not necessarily short lived, and may persist for some time following the first ethanol dose. Clear and consistent associations between rapid tolerance and locomotor sensitization and ethanol intake levels have yet to be demonstrated, however.     

Development of Tolerance to Inhibitory Effect of Ethanol on Endothelium-dependent Vascular Relaxation in Ethanol-fed Rats

Rats were maintained on liquid diets containing ethanol (35% of total calories) or an equicaloric volume of sucrose instead of ethanol for 10 wk. Vascular strips of isolated rat aortas were mounted in organ chambers to record isometric tension. Ethanol in vitro inhibited the endothelium-dependent relaxation responses to acetylcholine and ATP in both pair-fed control and ethanol-fed rats. The inhibitory effect of ethanol was greater in the pair-fed rats. In addition, the magnitudes of these relaxation responses in the absence of ethanol in vitro in pair-fed rats were similar to those in the presence of ethanol in ethanol-fed rats. In the absence of ethanol in vitro, the relaxations in response to acetylcholine and ATP in the ethanol-fed rats were greater than in the pair-fed rats. These results suggest that chronic ethanol consumption can induce tolerance to ethanol-induced inhibition of endothelium-dependent relaxation responses to acetylcholine and ATP, and that the relaxations can become adapted to the presence of plasma levels of ethanol, which may inhibit the relaxation in vivo. The augmented relaxation in the ethanol-fed rats may result from the mechanism causing tolerance to the inhibitory effect of ethanol.     

Dendritic cell functions: Learning from microbial evasion strategies

Dendritic cells (DCs) are specialized antigen presenting cells (APC) that are fundamental to initiate both immunity and tolerance. DCs play a ‘sentinel’ role to protect our body from potential pathogens and induce tolerogenic responses toward harmless antigens. The flexibility of DCs or macrophages to adapt to the environment and to respond accordingly can be hijacked by pathogens for their own interest to transform a potentially immunogenic APC into a tolerogenic cell with clear consequences in pathogen clearance. While these immune evasion mechanisms can be detrimental for the host, they can highlight important molecular pathways in DCs necessary for their function. In this review we will mention several mechanisms employed by pathogens to evade DC patrolling function.     

Methadone-related death in detention

Oral methadone may be prescribed to detainees with the aim of minimising the risk of fatal opioid poisoning on release. To study the circumstances under which methadone-related deaths can occur in detention, we audited reports of 17 [14 male, 3 female; median (range) age 34 (22–52) years] such deaths, July 2010–December 2011. The median (range) methadone dose was 40 (10–110) mg/d (N = 16). The median (range) post-mortem blood methadone concentration was 0.42 (0.16–1.40) mg/L. Those who died within 7 days of the commencement of methadone treatment were significantly younger (Mann-Whitney U 102.5, p < 0.05), were prescribed a significantly lower dose (U = 80.0, p < 0.05) and had significantly lower blood methadone concentrations at death (U = 106.5, p < 0.02) than in those given methadone long-term. In 8 reports the prisoner had been recorded as either ‘sleepy’ (N = 7), or ‘unwell’ in the hours before death. In 13 deaths, the prisoner was either found dead first thing in the morning, or in one instance could not be roused (‘snoring heavily’). Pneumonia, tracheobronchitis, end-stage cirrhosis, and ischaemic heart disease/coronary artery atherosclerosis were cited as associated factors in four patients, all of whom were on long term stable methadone treatment. Attention to warning signs of likely methadone toxicity (daytime or excessive drowsiness, snoring, nausea/vomiting) and associated risk factors (use of drugs such as benzodiazepines and gabapentinoids, the presence of respiratory infection, liver or renal disease) could help minimise the risk of unexpected death in patients given methadone.     

More Vasopressin mRNA in the Paraventricular Hypothalamic Nucleus of Alcohol-Preferring Rats and High Alcohol-Drinking Rats Selectively Bred for High Alcohol Preference

Both the selectively bred alcohol-preferring (P) and high alcohol-drinking (HAD) rats exhibit alcohol preference, and develop tolerance to alcohol more quickly than their counterparts, the alcohol-nonpreferring (NP) and low alcohol-drinking (LAD) rats, respectively. It has been shown that the P rats retain developed tolerance longer than do NP rats, and alcohol drinking increases concurrently with the development of tolerance. Although alcohol preference and tolerance are fundamental elements of alcoholism, the exact mechanisms underlying these two phenotypes in P and HAD rats are not well understood. Recent studies have suggested that arginine vasopressin (AVP) may be involved in modulation of alcohol tolerance. Accordingly, this study was designed to examine whether the AVP mRNA level in the hypothalamus differs in rats that have been selectively bred for alcohol preference and nonpreference. A ³⁵S-AVP antisense oligodeoxynucleotide probe was used for in situ hybridization to localize AVP mRNA in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), two major sites for AVP synthesis in the hypothalamus. Quantitative autoradiography demonstrated that P rats had higher levels of AVP mRNA in the PVN than NP rats. Similarly, higher levels of AVP mRNA were also found in the PVN of HAD rats, compared with LAD rats. The AVP mRNA levels in the SON were similar in the alcohol-preferring and alcohol-nonpreferring rat lines. Basal plasma AVP levels were higher in NP rats than in P rats as determined by radioimmunoassay, whereas plasma AVP levels were not significantly different between HAD and LAD rats. The results suggest that increased AVP gene expression in the PVN may contribute to alcohol preference and the development of alcohol tolerance.