The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

Female cricket pace bowling: kinematic and anthropometric relationships with ball release speed.

Background: Despite an increase in the professionalism and participation of female cricket, the coaching of female pace bowling is still reliant on male-derived knowledge. Objectives: To investigate the association between key male-derived kinematic and anthropometric parameters and ball release speed (BRS) in female pace bowlers. Methods: Eleven female pace bowlers participated in this study. BRS, and four anthropometric and five kinematic parameters were determined. Stepwise linear regression and Pearson Product Moment correlations were used to identify anthropometric and kinematic parameters linked to BRS. Results: The best predictor of BRS explaining 89% of the observed variance was the bowling shoulder angle at ball release. The best anthropometric predictor of BRS was height explaining 53% of the observed variance. Other parameters correlated with BRS included: run-up speed (r = 0.75, p = 0.013) and arm length (r = 0.61, p = 0.046). When height was controlled for, the front knee angle at front foot contact was also correlated to BRS (r = 0.68, p = 0.044). No relationship was found between trunk flexion and BRS. Conclusion: Faster BRS were characterised by faster run-up speeds, straighter front knees, and delayed arm circumduction similar to male pace bowlers. The lack of relationship between trunk flexion and BRS may highlight female pace bowlers adopting a bowling technique where BRS is contributed to by trunk rotation as well as trunk flexion. This knowledge is likely to be useful in the talent identification and coaching of female pace bowlers.

The Relationship Between Sexual Behavior Stigma and Depression Among Men Who have Sex with Men and Transgender Women in Kigali, Rwanda: a Cross-sectional Study.

To evaluate the role of sexual behavior stigma as a determinant of depressive symptoms among men who have sex with men (MSM) and transgender women (TGW) in Kigali, Rwanda. MSM/TGW aged ≥18 years were recruited using respondent-driven sampling (RDS) between March-August, 2018. Mental health was assessed using the Patient Health Questionnaire (PHQ-9). Sexual behavior stigma from friends and family, healthcare workers, and community members was assessed using a validated instrument. Multinomial logistic regression models were used to determine the association between sexual behavior stigma and depressive symptoms and depression. Secondary analyses further compared depression and depressive symptoms among MSM and TGW. Among the 736 participants included, 14% (106/736) identified as TGW. Depression 8.9% (RDS-adjusted, 7.6%; 95% CI, 4.6-10.6) and mild/moderate symptoms of depression 26.4% (RDS-adjusted, 24.1%; 95% CI, 19.4-28.7) were common and higher among TGW compared to MSM (p < 0.001). Anticipated (41%), perceived (36%), and enacted (45%) stigmas were highly prevalent, and were also significantly higher among TGW (p < 0.001). In multivariable RDS-adjusted analysis, anticipated (relative risk ratio (RRR), 1.88; 95% CI, 1.11-3.19) and perceived (RRR, 2.06; 95% CI, 1.12-3.79) stigmas were associated with a higher prevalence of depressive symptoms. Anticipated (RRR, 4.78; 95% CI, 1.74-13.13) and enacted (RRR, 3.09; 95% CI, 1.61-5.93) stigmas were also associated with a higher prevalence of depression. In secondary analyses, the significant differences between MSM and TGW were lost after adjusting for stigma. These data demonstrate a high burden of depressive symptoms and depression among MSM/TGW in Kigali. Conceptually, stigma is a likely antecedent of mental health stress among MSM and TGW suggesting the potential utility of scaling up stigma mitigation interventions to improve the quality of life and mental health outcomes among sexual and gender minority communities in Rwanda.

Radium-223 in the Treatment of Metastatic Castrate-Resistant Prostate Cancer.

Background Radium 223 (Ra-223) has been successfully utilised for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods All men referred to our institution for Ra-223 from September 2016 to March 2019 were included. Patient demographics, treatments received, toxicities and outcomes were recorded. Overall survival (OS) and progression free survival (PFS) were analysed using the Kaplan-Meier method. Results Complete data was available for 54 men. Median age was 75 years (range 61-86 years). The median number of prior systemic treatments for mCRPC was 2 (range 0-4). Median ECOG performance status was 1 at the start of treatment and 2 at completion. The median number of Ra-223 cycles received was 4 with 37%(n=20) completing all 6 planned cycles. The most common treatment-related toxicity was fatigue seen in 52% of patients ( n=28). Improved pain scores were documented in 76% of men requiring opioid analgesia at the start of treatment. The median OS was 7 months. A good ECOG performance status, fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and chemotherapy naivety were associated with improved OS. Conclusions Ra-223 is a moderately well tolerated palliative treatment amongst Irish men with mCRPC.

Pre-oxygenation with facemask oxygen vs high-flow nasal oxygen vs high-flow nasal oxygen plus mouthpiece: a randomised controlled trial.

High-flow nasal oxygen used before and during apnoea prolongs time to desaturation at induction of anaesthesia. It is unclear how much oxygenation before apnoea prolongs this time. We randomly allocated 84 participants to 3 minutes of pre-oxygenation by one of three methods: 15 l.min-1 by facemask; 50 l.min-1 by high-flow nasal cannulae only; or 50 l.min-1 by high-flow nasal cannulae plus 15 l.min-1 by mouthpiece. We then anaesthetised and intubated the trachea of 79 participants and waited for oxygen saturation to fall to 92%. Median (IQR [range]) times to desaturate to 92% after pre-oxygenation with facemask oxygen, high-flow nasal oxygen only and high-flow nasal oxygen with mouthpiece, were: 309 (208-417 [107-544]) s; 344 (250-393 [194-585]) s; and 386 (328-498 [182-852]) s, respectively, p = 0.014. Time to desaturation after facemask pre-oxygenation was shorter than after combined nasal and mouthpiece pre-oxygenation, p = 0.006. We could not statistically distinguish high-flow nasal oxygen without mouthpiece from the other two groups for this outcome. Median (IQR [range]) arterial oxygen partial pressure after 3 minutes of pre-oxygenation by facemask, nasal cannulae and nasal cannulae plus mouthpiece, was: 49 (36-61 [24-66]) kPa; 57 (48-62 [30-69]) kPa; and 61 (55-64 [36-72]) kPa, respectively, p = 0.003. Oxygen partial pressure after 3 minutes of pre-oxygenation with nasal and mouthpiece combination was greater than after facemask pre-oxygenation, p = 0.002, and after high-flow nasal oxygen alone, p = 0.016. We did not reject the null hypothesis for the pairwise comparison of facemask pre-oxygenation and high-flow nasal pre-oxygenation, p = 0.14.

Apnoeic oxygenation in paediatric anaesthesia: a narrative review.

Apnoeic oxygenation refers to oxygenation in the absence of any patient or ventilator effort to move the lungs. This phenomenon was first described in humans in the mid-20th century but has seen renewed interest in the last decade following the demonstration of apnoeic oxygenation with low-flow, and subsequently high-flow, nasal oxygen. This narrative review summarises our understanding of apnoeic oxygenation in the paediatric population. We examine the evidence supporting oxygenation via tracheal tube, modified laryngoscopes and nasal cannulae. The evidence for prolongation of safe apnoea time at induction of anaesthesia is also appraised. We explore the capacity for carbon dioxide clearance, flow rate selection with high-flow nasal oxygen and complications associated with the technique. It remains uncertain whether apnoeic oxygenation in paediatric patients results in a meaningful clinical benefit compared with standard care for outcomes such as the number of tracheal intubation attempts or the incidence of hypoxaemia. In particular, the role of apnoeic oxygenation in paediatric difficult airway management is unclear as this has not been the targeted focus of any published research to date.

Uses and mechanisms of apnoeic oxygenation: a narrative review.

Apnoeic oxygenation refers to oxygenation in the absence of spontaneous respiration or mechanical ventilation. It has been described in humans for over half a century and has seen a resurgence in interest given its potential to delay oxygen desaturation during airway management, especially with the advent of high-flow nasal cannulae. This narrative review summarises our current understanding of the mechanisms of gas exchange during apnoeic oxygenation and its diverse range of clinical applications, including its use at induction of anaesthesia and for the facilitation of 'tubeless anaesthesia'. Additional discussion covers use in critical care, obese, obstetric and paediatric sub-populations. The article also highlights current research efforts aiming to enhance the evidence base for the use of this technique.

The ophthalmic diagnosis and management of four siblings with Werner syndrome.

INTRODUCTION: Werner syndrome is a rare autosomal recessive disorder caused by mutations in the Werner syndrome WRN gene, on chromosome 8. Those affected manifest early the features of ageing. DISCUSSION: Cataract surgery is prone to post-operative complications in those with Werner syndrome. The development of cystoid macular oedema (CMO) is likely multifactorial. Patients with WS have diabetes mellitus type 2 which can contribute to macular oedema. There is a deposition of abnormal WRN proteins in the macula which also predisposes to macular oedema. The trauma of cataract surgery appears to be the main stimulus for the development of CMO. CMO may, as a result, be difficult to manage in Werner syndrome patients. CONCLUSION: Further study is needed to elucidate the precise role of retinal WRN protein expression in the development of CMO in those with Werner syndrome. A tailored and more successful approach to the treatment of CMO in such patients may result.

Serotonergic regulation of insulin secretion.

The exact physiological role for the monoamine serotonin (5-HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signalling network in islets involving 5-HT is being unravelled. With more than fourteen different 5-HT receptors expressed in human islets and receptor-independent mechanisms in insulin-producing ß-cells, our understanding of 5-HT's regulation of insulin secretion is increasing. It is now widely accepted that failure of the pancreatic ß-cell to release sufficient amounts of insulin is the main cause of type 2 diabetes (T2D), an ongoing global epidemic. In this context, 5-HT signalling may be of importance. In fact, 5-HT may serve an essential role in regulating the release of insulin and glucagon, the two main hormones that control glucose and lipid homoeostasis. In this review, we will discuss past and current understanding of 5-HT's role in the endocrine pancreas.