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IntroductionHypoxia is the main cause of morbidity and mortality in COVID-19. During the COVID-19 pandemic some countries have reduced access to supplemental oxygen (e.g. oxygen rationing), whereas other nations have maintained and even improved access to supplemental oxygen. We examined whether such variation in the access to supplemental oxygen had any bearing on mortality in COVID-19.MethodsThree independent investigators searched for, identified and extracted the nationally recommended target oxygen levels for the commencement of oxygen in COVID-19 pneumonia from the 29 worst affected countries. Mortality estimates were calculated from three independent sources. We then applied linear regression analysis to examine for potential association between national targets for the commencement of oxygen and case fatality rates.ResultsOf the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden and the UK guidelines advised commencing oxygen when oxygen saturations (SpO2) fell to 91% or less. Target SpO2 ranged from 92% to 95% in the other 16 nations. Linear regression analysis demonstrated a strong inverse correlation between the national target for the commencement of oxygen and national case fatality rates (Spearman’s Rho = −0.622, p < 0.001).ConclusionOur study highlights the disparity in oxygen provision for COVID-19 patients between the nations analysed, and indicates such disparity in access to supplemental oxygen may represent a modifiable factor associated with mortality during the pandemic.Key MessagesWhat is already known?There were no prospective clinical trials we could identify relating to COVID-19 and supplemental oxygen, nor any published studies examining access to supplemental oxygen and mortality in COVID-19.There are a number of studies identifying an association with low oxygen saturations at presentation and mortality in COVID-19 pneumonia.There is good quality evidence that a delay in the correction of hypoxia in pneumonia increases mortality.What are the new findings?This study highlights the different thresholds for commencing supplemental oxygen in patients with COVID-19 across 26 nations.Those countries that provide better access to supplemental oxygen have a statistically significant lower mortality rate.Our results support the consensus view that improving access to supplemental oxygen in COVID-19 pneumonia is likely to reduce mortality.

Central pontine myelinolysis is characterised by focal osmotic demyelination within the pons. Its clinical presentation varies, but may include acute paralysis, dysarthria and dysphagia. The cause is traditionally associated with overzealous correction of hyponatraemia in patients who are malnourished, alcoholic or chronically ill. However, it may develop in the context of normal serum sodium, since rapid gradient shifts in brainstem osmolalities can occur in other ways. We present an unusual example of central pontine myelinolysis caused by osmotic shifts secondary to hyperglycaemia in a person with type 1 diabetes mellitus and with consistently normal serum sodium concentrations.

Infection of laboratory mice with Helicobacter spp. is a serious problem for many laboratory animal facilities worldwide. Rederivation and antibiotic treatment are two of the most common methods used to eliminate the bacterial infection from rodent colonies. Forty-seven newly imported mice were suspected to be positive for Helicobacter infection based on PCR analysis of pooled fecal samples from sentinel animals. We treated the mice with a medicated feed containing four antibiotic compounds (amoxicillin, clarithromycin, metronidazole, omeprazole). After eight weeks of continuous administration the animals were negative for H. bilis and H. hepaticus. Frequent retesting of the animals for up to one year proved that the mouse colony remained negative for Helicobacter spp.

Purpose. The in vitro and in situ transport of CGP 65015 ((+)-3-hydroxy-1-(2-hydroxyethyl) -2-hydroxyphenyl-methyl-1 H-pyridin-4-one), a novel oral iron chelator, is described. The predictive power of these data in assessing intestinal absorption in man is described.

□ This study describes the transport of CGP 75254A, a novel oral iron chelator, across Caco-2 cells in an attempt to model intestinal epithelial cell permeability in man. CGP 75254A was dosed to the apical side of Caco-2 cell monolayers, together with [14C]mannitol as an internal permeability standard. The apparent permeability (Papp) was calculated from the cumulative appearance of drug in the basolateral fluid with time. The [14C]mannitol Papp indicated that the Caco-2 monolayers remained intact and that the iron chelator was not toxic to the cells. Permeabilities of CGP 75254A were compared with the Caco-2 permeabilities of compounds of known absorption in man. The results predict that absorption of CGP 75254A is likely to be virtually complete at pH values between 5.5 and 7.0. However, at pH 8.0 permeability is predicted as negligible. Cell permeability data are in full accordance with key physicochemical properties of CGP 75254A and suggest that the drug is passively absorbed. The results, which suggest likely quantitative absorption in vivo, are supported by preliminary pharmacological experiments in marmosets.

Background Kleine-Levin syndrome (KLS) is a rare sleep disorder characterised by recurrent episodes of hypersomnia, cognitive impairment and behavioural changes. The aetiology is unclear, but current opinion focuses on dysfunction within diencephalic pathways. In our experience patients and their relatives often describe severe headache, photophobia and phonophobia during episodes. However headache and other migrainous symptoms are infrequently described in case reports and are not mentioned in the ICSD-2 classification. Aims and objectives: Migraine as a risk marker, a symptomatic feature or an aetiological factor may have been overlooked in the characterisation of KLS. The aim of this study was to investigate the frequency and features of migraine in eleven KLS patients. Methods A proforma was created to identify typical migrainous symptoms and associations. Interviews were conducted by telephone. Collateral histories were obtained to complete clinical pictures, which can be distorted by amnesia. Results Seven patients (64%) experienced migraine between KLS episodes. Atypical and migrainous features of KLS identified during episodes included: headache (73%), photophobia (55%), phonophobia (55%) and nausea (27%). Mean KLS episode duration was 30.4 days in the migraine group vs 12.8 days in the non-migraineurs. Conclusions The association with migraine deserves further investigation, not only as a reliable risk marker but for exploration of the pathophysiology of KLS and novel therapeutic avenues. Initial use of triptans in two of our patients has yielded encouraging results. We encourage others to look for signs of migraine in their patients and consider the use of appropriate therapy.

The effects of light intensity (15-20 lux & 220-290 lux) on the oestrous cycle of albino and normally pigmented mice were examined. The oestrous cycle of both types of mice was shorter at the lower intensity but the difference was significant only with the black mice. The proportion of albino mice from which embryos were recovered was significantly smaller than the proportion of black mice at 15-20 lux but not at 220-290 lux. No significant differences due to strain or light intensity were found in the number of embryos recovered. We conclude that pigmented mice respond in the same way as albino mice to changes in light intensity within the range normally found in laboratory animal accommodation. That is, increased light intensity prolongs the oestrous cycle and the period of vaginal cornification.