Immunogenicity and safety of AZD2816, a beta (B.1.351) variant COVID-19 vaccine, and AZD1222 (ChAdOx1 nCoV-19) as third-dose boosters for previously vaccinated adults: a multicentre, randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study in the UK and Poland.

BACKGROUND: This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar to AZD1222 (ChAdOx1 nCoV-19), and AZD1222 as third-dose boosters. METHODS: This phase 2/3, partly double-blinded, randomised, active-controlled study was done at 19 sites in the UK and four in Poland. Adult participants who had received a two-dose AZD1222 or mRNA vaccine primary series were randomly assigned by means of an Interactive Response Technology-Randomisation and Trial Supply Management system (1:1 within each primary-series cohort, stratified by age, sex, and comorbidities) to receive AZD1222 or AZD2816 (intramuscular injection; 5 × 1010 viral particles). Participants, investigators, and all sponsor staff members involved in study conduct were masked to randomisation. AZD1222 and AZD2816 doses were prepared by unmasked study staff members. The primary objectives were to evaluate safety and humoral immunogenicity (non-inferiority of day-29 pseudovirus neutralising antibody geometric mean titre [GMT] against ancestral SARS-CoV-2: AZD1222 booster vs AZD1222 primary series [historical controls]; margin 0·67; SARS-CoV-2-seronegative participants). This study is registered with ClinicalTrials.gov, NCT04973449, and is completed. FINDINGS: Between June 27 and Sept 30, 2021, 1394 participants of the 1741 screened were randomly assigned to AZD1222 or AZD2816 following an AZD1222 (n=373, n=377) or mRNA vaccine (n=322, n=322) primary series. In SARS-CoV-2-seronegative participants receiving AZD1222 or AZD2816, 78% and 80% (AZD1222 primary series) and 90% and 93%, respectively (mRNA vaccine primary series) reported solicited adverse events to the end of day 8; 2%, 2%, 1%, and 1% had serious adverse events and 12%, 12%, 10%, and 11% had adverse events of special interest, respectively, to the end of day 180. The primary immunogenicity non-inferiority endpoint was met: day-29 neutralising antibody GMT ratios (ancestral SARS-CoV-2) were 1·02 (95% CI 0·90-1·14) and 3·47 (3·09-3·89) with AZD1222 booster versus historical controls (AZD1222 and mRNA vaccine primary series, respectively). Responses against beta were greater with AZD2816 versus AZD1222 (GMT ratios, AZD1222, mRNA vaccine primary series 1·84 [1·63-2·08], 2·22 [1·99-2·47]). INTERPRETATION: Both boosters were well tolerated, with immunogenicity against ancestral SARS-CoV-2 similar to AZD1222 primary-series vaccination. AZD2816 gave greater immune responses against beta versus AZD1222. FUNDING: AstraZeneca.

MaxSim: a novel simulation-based education course for OMFS emergencies.

For oral and maxillofacial surgery (OMFS) senior house officers (SHOs) with no formal medical training, the first exposure to emergency scenarios will be the first time they have to manage them, usually alone. Simulation-based education (SBE) has been demonstrated to increase experience and confidence when used in medical education, so an OMFS SBE course was created to facilitate this. The course was centred on scenarios that necessitate a rapid response, including sepsis, retrobulbar haemorrhage, and carotid artery blowout. A questionnaire with a 10-point numerical score was given to assess the change in confidence when managing these scenarios. Learner numbers were limited due to the COVID-19 pandemic, but all 10 completed both questionnaires. There was an even distribution between first and second-year SHOs. Two had received simulation training before, but it was very limited. In all stations every learner felt an increase in confidence, on average by 45% (range 38%-56%, p<0.05) on the 10-point scale. Positive feedback was also given by them all. SBE has been shown to be an invaluable method of training for clinical scenarios and needs to become common in OMFS. The course is to be expanded post COVID-19 to become available nationally.

A Spy took a bite to get the diagnosis right: the benefit of SpyGlass technology in the diagnosis of autoimmune pancreatitis evading traditional diagnostic methods.

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that is often overlooked and is usually characterised clinically by frequent presentations with obstructive jaundice. Serum IgG4 testing as a means to 'rule out' IgG4-related disease may not be as helpful as initially thought and may lead to a missed diagnosis if suspicion is low. We present a patient with a years long history of recurrent pancreatitis ultimately found to have AIP after undergoing evaluation with a relatively new technology, SpyGlass, which allows for direct cholangioscopy and enabled us to make the correct diagnosis.

Concurrent Use of E-cigarettes, Combustible Cigarettes, and Marijuana.

OBJECTIVE: Subgroups of adolescent single and dual e-cigarette and cigarette users have been identified, but usage patterns have changed in recent years, and there has been an increase in marijuana use. Research is needed with current data to identify subgroups of use including marijuana and determine their behavioral correlates. METHODS: We cross classified ever and recent use of e-cigarettes, combustible cigarettes, and marijuana among US high school students in the 2019 Youth Risk Behavior Survey (YRBS), providing 8 different groups. Levels of 14 risk and protective factors were compared across groups in general linear models with demographic covariates using omnibus tests, pairwise comparisons, and planned contrasts. Replicability was tested through identical analyses for 2017 YRBS data. RESULTS: The nonuser group was 43.9% of the sample. The most frequent user groups were triple users (ever-use proportion: 16.9%), dual (e-cigarette and marijuana) users (15.8%), and exclusive e-cigarette users (13.2%). For risk profiles on levels of psychosocial variables, the triple-user group was typically elevated above all other groups. Exclusive e-cigarette users were above nonusers in risk profile but below dual users (both cigarettes and marijuana). Results were similar for ever use and recent use. The patterning of results in 2019 YRBS data were closely replicated in 2017 YRBS data. CONCLUSIONS: Co-occurrence of e-cigarette, cigarette, and marijuana use is currently substantial among adolescents and is associated with an elevated psychosocial risk profile. This has implications for both epidemiology and prevention studies. Further research is needed to study prevalence and identify pathways to triple use.

Aeromedical Transfer of Patients with Viral Hemorrhagic Fever.

For >40 years, the British Royal Air Force has maintained an aeromedical evacuation facility, the Deployable Air Isolator Team (DAIT), to transport patients with possible or confirmed highly infectious diseases to the United Kingdom. Since 2012, the DAIT, a joint Department of Health and Ministry of Defence asset, has successfully transferred 1 case-patient with Crimean-Congo hemorrhagic fever, 5 case-patients with Ebola virus disease, and 5 case-patients with high-risk Ebola virus exposure. Currently, no UK-published guidelines exist on how to transfer such patients. Here we describe the DAIT procedures from collection at point of illness or exposure to delivery into a dedicated specialist center. We provide illustrations of the challenges faced and, where appropriate, the enhancements made to the process over time.

A Presumptive Case of Human Rabies: A Rare Survived Case in Rural Ghana.

Rabies remains endemic in Ghana and continues to pose a major public health threat to humans and animals with a nearly 100% case fatality rate in humans. We report of a presumptive case of human rabies whose survival represents a rare occurrence in rural Ghana and worldwide. Lessons from this case study provide a critically needed focus in helping improve rabies surveillance and case management in Ghana. We report of the survival of a 36-year-old man who developed clinical rabies after he was bitten by his dog, while restraining the dog with a chain. Prior to this, he did not observe any abnormal or rabid behavior in the dog. Following the bite, he did not immediately resort to hospital treatment, but rather to traditional application of herbs to the laceration he sustained after the bite. The reason given for not seeking immediate hospital treatment was that the dog was not rabid and lack of funds to seek hospital care. However, after 10 days he began to show symptoms of confusion, hydrophobia, and photophobia, consistent with rabies virus infection, and was subsequently rushed to the hospital by relatives. At the hospital, he was administered human immune tetanus immunoglobulin, diazepam, ceftriaxone, paracetamol, and intravenous fluids. No rabies vaccine was administered. Six days after commencing treatment, the patient became well, showed neither signs of confusional state, hydrophobia, nor photophobia. He was discharged home after 13 days of commencing treatment. This study provides insight on a presumptive case of human rabies that survived despite non-administration of rabies vaccine after exposure. It also exposes the weaknesses in the health and veterinary systems in rural Ghana regarding rabies surveillance and case management.

Minimally-invasive surgery in the management of symptomatic parotid stones.

Traditionally, large, symptomatic, parotid stones that were refractory to conservative treatment were usually managed by parotidectomy, with the attendant risk to the facial nerve. Microendoscopes have transformed the management of such stones. For large stones that are not amenable to retrieval with a basket the endoscope provides a new dimension to operative surgery. It can guide the surgeon on to the duct and stone without the need to remove the parotid gland. In 2005-2014, 111 consecutive patients underwent endoscopically-assisted operations for the removal of 132 parotid stones at Guy's Hospital. Removal was successful in all but three cases. Long-term follow up (mean (SD) 44 (30) months) was obtained by postal or online survey and telephone, and 92 patients (83%) said that they had no symptoms. Further endoscope-assisted surgery was required in four cases, with preservation of the gland in all patients. Sialocoeles developed postoperatively in 15% (n=17). Transient facial nerve weakness occurred in 4 cases (4%), and there was no case of permanent deficit. Endoscopically-assisted retrieval of parotid stones is a technique to preserve the gland that adds to the current minimally-invasive options for management of parotid calculi.

Factors influencing the uptake of family planning services in the Talensi District, Ghana.

INTRODUCTION: Usage of family planning services in developing countries have been found to avert unintended pregnancies, reduce maternal and child mortality, however, it's usage still remains low. Hence, the objective of this study was to investigate the factors that influence the decision of women in fertility age to go for family planning services. METHODS: This was a descriptive cross-sectional study conducted in Talensi district in the Upper East Region of Ghana. Systematic random sampling was used to recruit 280 residents aged 15-49 years and data was analysed using SPSS version 21.0. RESULTS: The study revealed that 89% (249/280), of respondents were aware of family planning services, 18% (50/280) of respondents had used family planning services in the past. Parity and educational level of respondents were positively associated with usage of family planning services (P<0.05). Major motivating factors to the usage of family planning service were to space children, 94% (47/50) and to prevent pregnancy and sexual transmitted infections 84% (42/50). Major reasons for not accessing family planning services were opposition from husbands, 90% (207/230) and misconceptions about family planning, 83% (191/230). CONCLUSION: Although most women were aware of family planning services in the Talensi district, the uptake of the service was low. Thus, there is the need for the office of the district health directorate to intensify health education on the benefits of family planning with male involvement. The government should also scale up family planning services in the district to make it more accessible.

How to Collect National Institute of Standards and Technology (NIST) Traceable Fluorescence Excitation and Emission Spectra.

Contemporary spectrofluorimeters comprise exciting light sources, excitation and emission monochromators, and detectors that without correction yield data not conforming to an ideal spectral response. The correction of the spectral properties of the exciting and emission light paths first requires calibration of the wavelength and spectral accuracy. The exciting beam path can be corrected up to the sample position using a spectrally corrected reference detection system. The corrected reference response accounts for both the spectral intensity and drift of the exciting light source relative to emission and/or transmission detector responses. The emission detection path must also be corrected for the combined spectral bias of the sample compartment optics, emission monochromator, and detector. There are several crucial issues associated with both excitation and emission correction including the requirement to account for spectral band-pass and resolution, optical band-pass or neutral density filters, and the position and direction of polarizing elements in the light paths. In addition, secondary correction factors are described including (1) subtraction of the solvent's fluorescence background, (2) removal of Rayleigh and Raman scattering lines, as well as (3) correcting for sample concentration-dependent inner-filter effects. The importance of the National Institute of Standards and Technology (NIST) traceable calibration and correction protocols is explained in light of valid intra- and interlaboratory studies and effective spectral qualitative and quantitative analyses including multivariate spectral modeling.