Investigating the effectiveness of commercially available mouthwash on SARS-CoV-2 in vivo using viable virus titre as the primary outcome. A randomised controlled trial.

This multi-arm, parallel group, single-blinded randomised controlled trial aimed to assess three commercially available mouthwashes effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This manuscript has been written in accordance with the CONSORT statement. Methods. Eligible participants were SARS-CoV-2 positive with a positive test in the last 72 h. All participants had mild to moderate symptoms and could provide five saliva samples over a 60 min period. Participants delivered a baseline saliva sample and then used a mouthwash as per manufacturer's instructions. They provided further saliva samples at minute 1, 10, 30 and 60. Participants were randomised to one of four groups; OraWize+, Total Care Listerine, Cool Mint Listerine and water (control). The lab-based research team were blind to the intervention. The research question was: can SARS-CoV-2 be rendered inactive in saliva by using a mouthwash and how long does this effect last? The primary outcome was the amount of viable infectious SARS-CoV-2 virus in the sample, compared to the baseline sample. The secondary outcome measure was the amount of genetic material from the SARS-CoV-2 virus in the sample, measured via PCR testing. Results. In total 100 participants were recruited (25 per group). Eight participants did not receive the allocated intervention and did not have saliva samples collected. There were no adverse events. In total 42 of the 92 participants had viable virus which could be cultured at baseline. Statistical analysis of the primary outcome was not advised due to the reduced level of viable virus at baseline and the positive skewness present in the distribution of log10(titre) data. Observational data of the primary outcome measure is presented. Analysis of the secondary outcome PCR measure showed that there was strong evidence for a decrease in SARS-CoV-2 RNA levels compared to water for all mouthwashes after 1 min, OraWize+ -0.49 (-0.92, -0.05), p-value 0.029, Cool Mint Listerine -0.81 (-1.25, -0.38), p-value<0.001, Total Care Listerine -1.05 (-1.48, -0.62), p-value<0.001. For the remaining timepoints there was generally no evidence of virus level reduction compared to water although there is weak evidence for a decrease at ten minutes using Total Care Listerine -0.44 (-0.88, 0.01), p-value 0.053. Conclusion. The three mouthwashes included in this trial observationally demonstrated a reduction in virus titre level 1 min after use, with virus levels normalising up to 60 min compared to the control. Although an interesting observation, this result could not be statistically analysed. Using the secondary outcome PCR measure all three included mouthwashes reduced virus levels compared to water at 1 min and these results were statistically significant. Clinically this result does not support the use of the included mouthwashes to reduce SARS-CoV-2 levels in saliva.

Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea.

BACKGROUND: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking. AIM: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards. METHODS: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively. FINDINGS: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point-prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset. CONCLUSION: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.

The development of a scoring system for symphysis pubis dysfunction.

Based on a review of the literature, a questionnaire was developed to create a scoring system for pregnancy-related symphysis pubis dysfunction (SPD) and completed by 150 (100 without SPD and 50 with SPD) peri-partum women. The questionnaire was tested for reliability in a sub-set of 21 women. Symptoms that were significantly associated with SPD were identified and used in a scoring system in order to diagnose patients with SPD. SPD was reported by 12% of patients in the first trimester, 34% in the second trimester and 52% in the third trimester. Significant symptoms in patients with SPD were: pubic bone pain on walking, turning over in bed, climbing stairs, standing on one leg, and previous damage to back or pelvis. Using a score of 1 for each of the above symptoms, a score of 2 and above was considered diagnostic of SPD. There was 1 false positive score. As SPD is a clinical condition with no definitive diagnostic test, there is a need for a scoring system that will allow patients to be assessed in terms of their symptoms. This system has the potential to facilitate screening, diagnosis and management of SPD as well as allow monitoring of the patient and assessment of the success of various interventions.

Symphysis pubis dysfunction: a review of the literature.

A review of the literature revealed a multitude of terms used to describe Symphysis Pubis Dysfunction (SPD). No unambiguous definition was found, rather the condition is described in terms of symptoms and signs. These occur due to the physiological pelvic ligament relaxation and increased joint mobility seen in pregnancy. The severity of symptoms varies from mild discomfort to severely debilitating pain. There appears to be no correlation between the degree of relaxation of the symphysis pubis and the level of pain and disability. Treatment is generally conservative and delivery is curative in the majority by 6 months post-partum. There is a need for standardisation of terminology, an agreed definition of SPD and a reliable means of assessment of the condition. Additionally there is a need for scientific evaluation of different forms of treatment.

Counter-proliferative effects of nucleosomal antigens in cultures from lupus patients.

Blood mononuclear cells from 20 lupus patients were cultured in the presence of nucleosomal antigens to determine whether they induce lymphocyte proliferation. The predominant effect seen, however, was one of inhibition of the background proliferation. Such inhibition was rare with cells from female or male controls. Nucleohistone (NH), crude histone and enriched preparations of histones H2A/H4, H2B and H3 showed this effect in approximately one-third of patients, but H1 and single-stranded (ss) DNA had no such activity. Double-stranded (ds) DNA may show this inhibitory action, but further tests are required. ssDNA was the only antigen that showed evidence (two patients) of disease-related stimulation of proliferation. Histones and NH induced proliferation in many subjects but the strongest responders were controls. Patients responded poorly to tuberculin PPD but gave an exceptionally strong proliferative response to pokeweed mitogen. It is suggested that the inhibition of background proliferation in patients is a consequence of the interaction of nucleosomal antigens with sensitised T cells. If T cell sensitisation to histones is an important factor in the development of lupus, the disease may be preventable in those at risk by inducing tolerance to the appropriate peptides.