Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.

BACKGROUND: Hospital transmission of SARS-CoV-2 has proved difficult to control, with healthcare-associated infections troublesome throughout. AIM: To understand factors contributing to hospital transmission of infections, which is necessary for containing spread. METHODS: An outbreak of 56 staff and patient cases of COVID-19 over a 31-day period in a tertiary referral unit is presented, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS). FINDINGS: Transmission is documented from staff to staff, staff to patients, and patients to staff, showing disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation, and use of personal protective equipment. There was extensive spread from the index case, despite this patient spending only 10 h bed bound on the ward in strict cubicle isolation and with an initial single target low level (CT = 32) polymerase chain reaction test. CONCLUSION: This investigation highlights how effectively and rapidly SARS-CoV-2 can spread in certain circumstances. It raises questions about infection control measures in place at the time and calls into question the premise that transmissibility can be reliably detected by using lower sensitivity rapid antigen lateral flow tests. We also highlight the value of early intervention in reducing impact as well as the value of WGS in understanding outbreaks.

A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Use of calculations to validate beam quality and relative dose measurements for a kilovoltage X-ray therapy unit.

Relative dosimetry measurements are required to fully commission kilovoltage X-ray units for superficial and orthovoltage X-ray therapy. Validation of these relative dosimetry measurements with Monte Carlo methods is advantageous being independent of the measurement process. In this study use is made of the X-ray spectrum generating program SpekPy along with the EGSnrc Monte Carlo code to calculate depth doses and explore the dosimetry effect of changes in backscatter. These calculations are compared with previously reported measurements for the Pantak SXT 150 X-ray therapy unit. SpekPy can also be used to generate half value layer (HVL) values and these are also compared to previously reported HVL measurements for the same X-ray therapy unit. It was found that agreements of the order of 5% in HVL, 3% in depth dose and 1% in backscatter doses were found between Monte Carlo calculations and the previously published measured data. Exit doses in conditions of lack of full backscatter were explored with Monte Carlo calculations demonstrating reduced exit dose up to 20% in these conditions. It is concluded that SpekPy with Monte Carlo codes such as EGSnrc provides a straightforward approach to validating various relative dosimetry measurements in kilovoltage X-ray dosimetry.

The need to update NCRP 151 data for 10 MV linear accelerator bunker shielding based on new measurements and Monte Carlo simulations.

Linear accelerator bunker shielding protocols such as NCRP 151 have previously been tested against a large sample of measured data from real bunkers and machines but differences in per-energy concrete penetration (TVLs) for 10 MV has not yet been resolved. These differences are likely due to historical beam data and can potentially result in over-exposure of radiation workers and the public. This study examines a cohort of clinical linac bunker survey measurements and compares them to popular shielding protocols. Differences were investigated using contemporary beam data for both Monte Carlo simulation and in analytical equations. For primary barriers, NCRP 151 underestimates the dose rate through concrete by on average a factor of 2 with secondary barriers and maze entrance doses having much better agreement. Use of contemporary beam data in Monte Carlo simulation and an analytical equation yielded TVL values much closer to the measured values compared to NCRP 151. The TVL data in NCRP 151 is outdated and needs to be updated based upon the energy spectra of modern linear accelerators. Until then, physicists should use the TVL values shown in this study instead.

Identification of a predominant cognitive phenotype in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment occurs frequently in multiple sclerosis (MS). However, the prevalence and clinical characteristics of cognitive MS phenotype are not well established. The aim of the study was to characterize the clinical course and neurocognitive impairment of patients with MS meeting an Expanded Disability Status Scale (EDSS)-defined cognitive phenotype. METHODS: A total of 2302 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study were studied. Predominant cognitive MS phenotype was defined as EDSS Cerebral Functional System (FS) subscore ≥3 and remaining EDSS FS subscores ≤2 on at least one clinical visit. Demographic/clinical characteristics, phenotype stability and neurocognitive domain impairment of these subjects were assessed. RESULTS: A total of 60 of 2302 (2.6%) patients (age 52.8 ± 10.8 years, 68% female, 82% relapsing MS) met criteria for phenotype designation. A total of 29 of 60 (48%) were designated within 10 years of their presenting MS symptom. The mean cohort annualized relapse rate was 0.38 and EDSS score at last clinical assessment was 3.2 ± 1.3. Cognitive phenotype status was poorly sustained, with only 27% of subjects maintaining Cerebral FS score ≥2 throughout all follow-up. However, predominant cognitive phenotype subjects with clinical neuropsychiatric testing [n = 39/60 (65%)] frequently had cognitive impairment (1.5 SD below mean) in ≥1 domain [n = 30/39 (77%) of subjects] affecting memory, attention/executive function and processing speed. A total of 11 of 39 (28%) patients had severe-range cognitive impairment (3.0 SD below mean). Cognitive phenotype designation was associated with low rate of employment at last clinical assessment. CONCLUSION: Predominant cognitive MS phenotype is rare, although an EDSS-based definition identifies patients with multidomain cognitive impairment and may serve as a practical screen for identification of patients who might warrant close monitoring of neurocognitive status.

An IAEA survey of radiotherapy practice including quality assurance extent and depth.

Background: The IAEA recommends a quality assurance program in radiotherapy to ensure safe and effective treatments. In this study, radiotherapy departments were surveyed on their current practice including the extent and depth of quality assurance activities.Methods: Radiotherapy departments were voluntarily surveyed in three stages, firstly, in basic facility information, secondly, in quality assurance activities and treatment techniques, and thirdly, in a snapshot of quality assurance, departmental and treatment activities.Results: The IAEA received completed surveys from 381 radiotherapy departments throughout the world with 100 radiotherapy departments completing all three surveys. Dominant patterns were found in linac-based radiotherapy with access to treatment planning systems for 3D-CRT and 3D imaging. Staffing levels for major staff groups were on average in the range recommended by the IAEA. The modal patient workload per EBRT unit was as expected in the range of 21-30 patients per day, however significant instances of high workload (more than 50 patients per day per treatment unit) were reported. Staffing levels were found to correlate with amount of treatment equipment and patient workload. In a self-assessment of quality assurance performance, most radiotherapy departments reported that they would perform at least 60% of the quality assurance activities itemized in the second survey, with particular strength in equipment quality control. In a snapshot survey of quality assurance performance, again equipment quality control practice was well developed, particularly for the treatment equipment.Conclusions: The IAEA surveys provide a snapshot of current radiotherapy practice including quality assurance activities.

Health Care Workers and Patients as Trojan Horses: a COVID19 ward outbreak.

BACKGROUND: Transmission in healthcare settings can result in significant infections in healthcare workers and patients. Understanding infection dynamics has important implications for methods employed in hospitals to prevent nosocomial transmission events. METHODS: In this case series report we describe a cluster of COVID-19 (Coronavirus disease 2019) in a tertiary care university hospital, in the early phases of the epidemic, after hospital visiting had been stopped and when the UK lockdown was in place. FINDINGS: A 48 year old patient developed COVID-19 31 days post-admission and four days after admission to a medical ward from ITU. Infection was likely acquired from an asymptomatic or minimally symptomatic healthcare worker (HCW). Subsequent investigation over a 14 day period revealed symptoms in 23 staff members and five linked cases in patients on the same ward.Nine of the 23 affected staff members provided care for and had direct exposure with the index case. Four staff reported caring for the index case without use of personal protective equipment. One was coughed on directly by the patient 24 hours prior to the onset of symptoms. CONCLUSION: SARS CoV2 infection can be introduced to a ward area by asymptomatic and minimally symptomatic healthcare workers. Staff members and patients can act as Trojan horses carrying infection into and around the hospital, setting up unexpected transmission events.Transmission of infection from pre-symptomatic, asymptomatic and minimally symptomatic individuals means that universal use of measures to prevent transmission is required for successful reduction of transmission events in the hospital setting.

Effect of pregnancy loss on MS disease activity.

OBJECTIVE: To evaluate the effect of pregnancy loss (PL) on MS disease activity. METHODS: Eleven women with first-trimester PLs were identified through a reproductive questionnaire. MS activity (MRI lesions and/or clinical relapses) was compared for the 12 months before conception and after PL. RESULTS: There was MS activity in 7/11 participants after, compared with 3/11 before PL (McNemar's test, p = .29), including MRI activity in 7/11 after, compared with 2/11 before PL (McNemar's test, p = .13). CONCLUSION: Larger studies are needed to confirm this observed trend of increased MS activity following PL.

First nations people's perspectives on barriers and supports for enhancing HPV vaccination: Foundations for sustainable, community-driven strategies.

OBJECTIVE: In Canada, Indigenous people have higher human papillomavirus (HPV) infection rates, lower screening rates for cervical cancer, and higher rates of invasive cancer, leading to worse cervical cancer-related outcomes than observed in non-Indigenous Canadian women. Lingering harms from European colonization drive these health inequities and create public health challenges. Policy guidance is needed to optimize HPV vaccination rates and, thereby, decrease the burden of HPV-related illness, including high-morbidity surgical procedures and chemo-radiotherapy. The Enhancing HPV Vaccination In First Nations Populations in Alberta (EHVINA) project focuses on First Nations, a diverse subset of recognized Indigenous people in Canada, and seeks to increase HPV vaccination among girls and boys living in First Nation communities. METHODS: Developing an effective strategy requires partnership with affected communities to better understand knowledge and perceptions about cancer, healthcare, and the HPV vaccine. A 2017 community gathering was convened to engage First Nations community members, health directors, and health services researchers in dialogue around unique barriers and supports to HPV vaccination in Alberta. Voices of community Elders, parents, health directors, and cancer survivors (n=24) are presented as qualitative evidence to help inform intervention design. RESULTS: Key findings from discussions indicate barriers to HPV vaccination include resource constraints and service infrastructure gaps, historical mistrust in healthcare systems, impacts of changing modes of communication, and community sensitivities regarding sexual health promotion. Supports were identified as strengthened inter-generational relationships in communities. CONCLUSIONS AND FUTURE DIRECTION: Ongoing dialogue and co-development of community-based strategies to increase HPV vaccine uptake are required. The identification of possible barriers to HPV vaccination in a Canadian Indigenous population contributes to limited global literature on this subject and may inform researchers and policy makers who work with Indigenous populations in other regions.

Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count.

BACKGROUND: There is limited data regarding the predictors of hematological abnormalities in multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) or fingolimod (FNG), and the impact of treatment switch on lymphocyte and leukocyte count METHODS: We identified 405 patients on DMF and 300 patients on FNG (treatment duration: at least 12 month) within a large prospective study of MS patients conducted at the Partners MS Center, Brigham and Women's Hospital (CLIMB study) between Jan 2011 to Feb 2016. Patients had complete blood counts with differentials at baseline and every 6 months while on treatment. Most participants had a clinical visit with complete neurologic examinations every 6 months and brain MRI scan every 12 months. T cell subset profile was available for subgroup of patients (n = 116). RESULTS: In the FNG group, the risk of developing lymphopenia grade 4 (< 200) was higher in female patients (p = 0.0117) and those who were previously treated with natalizumab (p = 0.0116), while the risk of lymphopenia grade 3b+4 (< 350) was higher in female patients (p = 0.0009). DMF treated patients with lower baseline lymphocyte count had a higher chance of developing lymphopenia grade 2 (< 800) (p < 0.0001) or 2+3 (< 500) (p < 0.0001). We examined the effect of treatment switch between DMF and FNG. No significant recovery in lymphocyte and leukocyte count was observed after treatment switches. Reduced dosing of FNG in patients with lymphopenia led to increase in lymphocyte count but also increased disease activity in 25% of patients. CONCLUSION: Female sex and prior exposure to natalizumab increased the probability of lymphopenia on FNG, while low absolute lymphocyte count was associated with increased risk of lymphopenia on DMF. Parallel switch did not lead to recovery from hematological abnormalities. Long-term studies with larger number of patients are required to confirm our findings and to establish guidelines for prediction and management of hematological abnormalities.

Moving beyond quality control in diagnostic radiology and the role of the clinically qualified medical physicist.

Quality control (QC), according to ISO definitions, represents the most basic level of quality. It is considered to be the snapshot of the performance or the characteristics of a product or service, in order to verify that it complies with the requirements. Although it is usually believed that "the role of medical physicists in Diagnostic Radiology is QC", this, not only limits the contribution of medical physicists, but is also no longer adequate to meet the needs of Diagnostic Radiology in terms of Quality. In order to assure quality practices more organized activities and efforts are required in the modern era of diagnostic radiology. The complete system of QC is just one element of a comprehensive quality assurance (QA) program that aims at ensuring that the requirements of quality of a product or service will consistently be fulfilled. A comprehensive Quality system, starts even before the procurement of any equipment, as the need analysis and the development of specifications are important components under the QA framework. Further expanding this framework of QA, a comprehensive Quality Management System can provide additional benefits to a Diagnostic Radiology service. Harmonized policies and procedures and elements such as mission statement or job descriptions can provide clarity and consistency in the services provided, enhancing the outcome and representing a solid platform for quality improvement. The International Atomic Energy Agency (IAEA) promotes this comprehensive quality approach in diagnostic imaging and especially supports the field of comprehensive clinical audits as a tool for quality improvement.

Cobalt-60 Machines and Medical Linear Accelerators: Competing Technologies for External Beam Radiotherapy.

Medical linear accelerators (linacs) and cobalt-60 machines are both mature technologies for external beam radiotherapy. A comparison is made between these two technologies in terms of infrastructure and maintenance, dosimetry, shielding requirements, staffing, costs, security, patient throughput and clinical use. Infrastructure and maintenance are more demanding for linacs due to the complex electric componentry. In dosimetry, a higher beam energy, modulated dose rate and smaller focal spot size mean that it is easier to create an optimised treatment with a linac for conformal dose coverage of the tumour while sparing healthy organs at risk. In shielding, the requirements for a concrete bunker are similar for cobalt-60 machines and linacs but extra shielding and protection from neutrons are required for linacs. Staffing levels can be higher for linacs and more staff training is required for linacs. Life cycle costs are higher for linacs, especially multi-energy linacs. Security is more complex for cobalt-60 machines because of the high activity radioactive source. Patient throughput can be affected by source decay for cobalt-60 machines but poor maintenance and breakdowns can severely affect patient throughput for linacs. In clinical use, more complex treatment techniques are easier to achieve with linacs, and the availability of electron beams on high-energy linacs can be useful for certain treatments. In summary, there is no simple answer to the question of the choice of either cobalt-60 machines or linacs for radiotherapy in low- and middle-income countries. In fact a radiotherapy department with a combination of technologies, including orthovoltage X-ray units, may be an option. Local needs, conditions and resources will have to be factored into any decision on technology taking into account the characteristics of both forms of teletherapy, with the primary goal being the sustainability of the radiotherapy service over the useful lifetime of the equipment.

Longitudinal BMI trajectories in multiple sclerosis: Sex differences in association with disease severity.

BACKGROUND: Adolescent obesity is a risk factor for multiple sclerosis (MS), but little is known about changes in body mass index (BMI) after MS onset. OBJECTIVE: To assess the relationship between MS and longitudinal changes in BMI. METHODS: We analyzed prospectively collected BMIs in a cohort of patients with adult-onset MS and matched adult healthy controls (HC) gathered from the same hospital network central clinical data registry. RESULTS: We made three main observations. First, at baseline MS patients had a significantly higher BMI than HC (age- and sex- adjusted mean difference=0.57; 95% CI: 0.15, 0.99; p=0.008). Second, a significant age by MS status interaction was observed (p<0.0001), such that in MS, BMIs did not increase significantly higher in older individuals, whereas BMIs in HCs were higher with increasing age. Third, we observed sex-specific associations with disease severity: higher BMI was associated with higher cross-sectional EDSS in women, but with lower EDSS in men (p=0.003, N=758). There were no longitudinal associations between BMI and EDSS in either sex or in the entire cohort (p=0.65, N=772). CONCLUSION: After MS onset, patients may not experience age-expected increases in BMI. BMI may have sex-specific associations with MS disability scores. More refined measures of body composition are warranted in future studies to distinguish adiposity from muscle mass.

Patients report worse MS symptoms after menopause: findings from an online cohort.

BACKGROUND: Many women with multiple sclerosis (MS) are postmenopausal, yet the impact of menopause on MS symptoms is unknown. OBJECTIVE: To investigate patient-reported impact of menopause in a large online research platform, PatientsLikeMe (PLM). METHODS: A detailed reproductive history survey was deployed to PLM members, and responses were linked to PLM׳s prospectively collected patient-reported severity score (MS Rating Scale, MSRS). The MSRS has previously shown good correlation with physician-derived EDSS scores. RESULTS: Of the 513 respondents, 55% were postmenopausal; 54% of these reported induced menopause. Median age at natural menopause was 51. Surgical menopause occurred at an earlier age (p<0.001) and was associated with more hormone replacement therapy use (p=0.02) than natural menopause. Postmenopausal status, surgical menopause, and earlier age at menopause were all associated with worse MSRS scores (p≤0.01) in regressions adjusting for age, disease type and duration. CONCLUSION: Postmenopausal patients in this study reported worse MS disease severity. Further, this study highlights a utility for online research platforms, which allow for rapid generation of hypotheses that then require validation in clinical settings.

How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis.

OBJECTIVES: We determined the available mechanisms to generate income from outpatient parenteral antimicrobial therapy (OPAT) in the UK and calculated the revenue generated from treatment of an episode of cellulitis. METHODS: Revenue was calculated for patients receiving treatment for cellulitis as an inpatient and for patients receiving OPAT by a series of different payment pathways. Selected established OPAT services in Northern Ireland, Scotland and Wales, where Payment-by-Results (PbR) does not operate, were contacted to determine individual national funding arrangements. RESULTS: In England, a traditional inpatient episode for uncomplicated cellulitis requiring 7 days of treatment generated £1361 of revenue, while OPAT generated revenue ranging from £773 to £2084 for the same length of treatment depending on the payment pathway used. Treatment using OPAT to avoid admission entirely generated £2084, inpatient admission followed by transfer to a virtual OPAT ward at day 2 generated £1361 and inpatient admission followed by discharge from hospital to OPAT at day 2 generated £773. In Northern Ireland, Scotland and Wales block contracts were used and no income was calculable for an individual episode of cellulitis. CONCLUSIONS: No single funding mechanism supports OPAT across the UK. In England, revenue generated by OPAT providers from treatment of cellulitis varied with the OPAT payment pathway used, but equalled or exceeded the income generated from equivalent inpatient care. Cost savings for OPAT and reuse of released inpatient beds will increase revenue further. A single OPAT tariff is proposed.

Need for radiotherapy in low and middle income countries ­ the silent crisis continues.

About 57% of the total number of cancer cases occur in low and middle income countries. Radiotherapy is one of the main components of cancer treatment and requires substantial initial investment in infrastructure and training. Many departments continue to have basic facilities and to use simple techniques, while modern technologies have only been installed in big cities in upper-middle income countries. More than 50% of cancer patients requiring radiotherapy in low and middle income countries lack access to treatment. The situation is dramatic in low income countries, where the proportion is higher than 90%. The overall number of additional teletherapy units needed corresponds to about twice the installed capacity in Europe. The figures for different income level groups clearly show the correlation between gross national income per capita and the availability of services. The range of radiotherapy needs currently covered varies from 0% and 3-4% in low income countries in Latin America and Africa up to 59-79% in upper-middle income countries in Europe and Central Asia. The number of additional radiation oncologists, medical physicist, dosimetrists and radiation therapists (RTTs) required to operate additional radiotherapy departments needed is 43 200 professionals. Training and education programmes are not available in every developing country and in many cases the only option is sending trainees abroad, which is not a cost-effective solution. The implementation of adequate local training should be the following step after establishing the first radiotherapy facility in any country. Joint efforts should be made to establish at least one radiotherapy facility in countries where they do not exist, in order to create radiotherapy communities that could be the base for future expansion.