The treatment of scarlet fever with specific antitoxic serum

From a study of three hundred and sixty-five cases of Simple Scarlet fever, treated by intramuscular injection of 10 com. of concentrated Scarlet fever streptococcus antitoxic serum, the following are the conclusions:-1 . The administration of antitoxic serum within the first three days of disease produces a very favourable effect upon the specific toxaemia of the disease as manifested by:- (a) A more rapid return to normal of temperature and pulse curves, (b) Marked diminution of nervous symptoms. (c) Definite blanching of the rash which, in 60% of the cases treated, entirely disappeared within 24 hours.2. For cases of simple Scarlet fever of average severity an efficient therapeutic dose should contain enough antitoxin to neutralise 500,000 akin test doses of a standard Scarlet fever toxin, i.e. 5,000 units of antitoxin.3. This should be regarded as the minimum therapeutic dose which ought to be increased according to the severity of the case.4. The methods at present in use of standardising such a serum present considerable difficulties.5. The full therapeutic dose should be given at the earliest possible moment. When thus given the results are, in most cases, strikingly favourable.6. The use of a reliable concentrated serum produces fewer and less severe reactions than an unconcentrated preparation.7 . When given within the first three days of disease it cuts short the course of the disease, lessens the incidence and reduces the severity of complications.8. The administration of serum even on the first day of disease is not an absolute safeguard against the development of complications of the septic type.10. Until more definite data are available it does not seem advisable to further reduce the usual quarantine period of Scarlet fever patients treated with specific antitoxic serum, but the total period of hospitalisation of such patients is reduced owing to the serum therapy reducing the incidence and severity of complications.11. Antitoxin treatment of Scarlet fever does not appear to increase the incidence of relapses beyond normal limits.12. A further period of study is required to determine what influence serum therapy has upon the prevalence of second attacks of the disease.13. The case mortality from Simple Scarlet fever is so low at present that it renders it difficult to determine the effects of serum therapy in further reducing this figure.14. In cases of septic Scarlet fever the specific antitoxic serum only indirectly benefits the initial septic complications by curing the toxaemia.15. There is reason to believe that the treatment of Septic Scarlet fever by a combination of specific antitoxic serum and polyvalent antistreptococcal serum cuts short the course of the disease and lessens the liability to the development of subsequent septic complications.16. Specific antitoxic serum, if given early and in large doses, is an extremely efficacious treatment for cases of Toxic Scarlet fever.17. The intravenous method of administration is more advantageous to toxic cases than the intramuscular route as it ensures a more rapid maximum concentration of antitoxin in the patient’s circulation.9. The therapeutic efficacy of the serum diminishes with each day of delay in its administration and beyond the third day of disease it appears to have little or no effect in influencing the incidence of subsequent complications

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24). Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research