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 The TVL data in NCRP 151 is outdated and needs to be updated based upon the energy spectra of modern linear accelerators.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.

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.

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.

Low testosterone is associated with disability in men with multiple sclerosis.

BACKGROUND: Gonadal steroids may modulate disease course in multiple sclerosis (MS). OBJECTIVE: To assess the prevalence and clinical associations of hypogonadism in men with MS. METHODS: Male patients, aged 18-65 years, with relapsing-remitting MS (RRMS) or clinically-isolated syndrome (CIS) and their first symptom < 10 years prior were selected from a longitudinal clinical study. We measured their hormones in stored morning blood samples, and collected their Expanded Disability Status Scale (EDSS) scores every 6 months and their Symbol Digit Modalities Test (SDMT) results annually. RESULTS: Our analysis included 96 men with a mean age of 40 years, EDSS of 1.1 and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone < 288 ng/dL); none showed compensatory elevations in luteinizing hormone. Their low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index (BMI) and leptin, and showed no correlation with 25-hydroxy-vitamin D levels. In our primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS (p = 0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT (p = 0.012). CONCLUSIONS: Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation.

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.

AFOMP policy statement no. 4: recommendations for continuing professional development systems for medical physicists in AFOMP countries.

This policy statement, which is the fourth of a series of documents being prepared by the Asia-Oceania Federation of Organizations for Medical Physics Committees Professional Development Committee, gives guidance on how member countries could develop a continuing professional development system for ensuring that its clinical medical physicists are up-to-date in their knowledge and practice. It is not intended to be prescriptive as there are already several CPD systems successfully operated by AFOMP member countries and elsewhere that vary considerably in scope and structure according to local culture, practice and legislation but all of which are capable of ensuring that physicists are up-to-date. It is intended to be advisory and set out options for member countries to develop their individual CPD systems.

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.

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.

HLA (A-B-C and -DRB1) alleles and brain MRI changes in multiple sclerosis: a longitudinal study.

Several major histocompatibility complex (MHC) alleles have been postulated to influence the susceptibility to multiple sclerosis (MS), as well as its clinical/radiological course. In this longitudinal observation, we further explored the impact of human leukocyte antigen (HLA) class I/II alleles on MS outcomes, and we tested the hypothesis that HLA DRB1*1501 might uncover different strata of MS subjects harboring distinct MHC allele associations with magnetic resonance imaging (MRI) measures. Five hundred eighteen MS patients with two-digit HLA typing and at least one brain MRI were recruited for the study. T2-weighted hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) were acquired at each time point. The association between allele count and MRI values was determined using linear regression modeling controlling for age, disease duration and gender. Analyses were also stratified by the presence/absence of HLA DRB1*1501. HLA DRB1*04 was associated with higher T2LV (P=0.006); after stratification, its significance remained only in the presence of HLA DRB1*1501 (P=0.012). The negative effect of HLA DRB1*14 on T2LV was exerted in DRB1*1501-negative group (P=0.012). Longitudinal analysis showed that HLA DRB1*10 was significantly protective on T2LV accrual in the presence of HLA DRB1*1501 (P=0.002). Although the majority of our results did not withstand multiple comparison correction, the differential impact of several HLA alleles in the presence/absence of HLA DRB1*1501 suggests that they may interact in determining the different phenotypic expressions of MS.

Pre-hospital oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: High concentration oxygen is commonly administered during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study was to determine the association between oxygen, severity markers and poor outcomes in AECOPD. METHODS: In an audit of patients with AECOPD arriving by ambulance to the Emergency Department of Wellington Hospital, details of oxygen administration, clinical outcomes and severity markers were documented. The main outcome measure was a composite of death, assisted ventilation, or respiratory failure. Associations between oxygen therapy, severity markers and poor clinical outcomes were assessed by logistic regression. RESULTS: Of 250 patients 77 (31%) died, required assisted ventilation or were in respiratory failure. Increased oxygen flow was associated with increasing risk of death, assisted ventilation or respiratory failure with an odds ratio (OR) of 1.2 (95% CI 1.0-1.4) per 1 L/min oxygen flow. Increasing PaO(2) was associated with a greater risk of a poor outcome with an OR of 1.1 (95% CI 1.0-1.3) per 10 mmHg higher PaO(2). Home oxygen (OR 2.8, 95% CI 1.5-5.1), previous respiratory failure (OR 2.6, 95% CI 1.5-4.6), previous ventilation (OR 3.2, 95% CI 1.7-5.9) and home nebulizer use (OR 2.4, 95% CI 1.4-4.3) were associated with an increased risk of a poor outcome. CONCLUSION: In AECOPD high flow oxygen in the ambulance is associated with poor clinical outcomes. A number of easily identified markers of chronic disease severity indicate an increased risk of a poor clinical outcome.

Development of a dosimetry inter-comparison for IMRT as part of site credentialing for a TROG multi-centre clinical trial for prostate cancer.

A methodology has been developed for a dosimetry inter-comparison of intensity modulated radiation therapy (IMRT) delivery in Australasia. The inter-comparison is part of site credentialing for those sites participating in the prostate fractionated irradiation trial (PROFIT) for intermediate-risk prostate patients developed by the Ontario Clinical Oncology Group and coordinated in Australasia by the Trans Tasman Radiation Oncology Group. Features of the dosimetry inter-comparison design included the use of a dedicated pelvic anthropomorphic phantom, the use of a single CT data set of the phantom including contours and the use of radiochromic film as a dosimeter. Action levels for agreement between measured dose and treatment planning system dose have been proposed based on measurement uncertainty and international experience. A trial run of the dosimetry procedure at the reference centre gave results within the predefined action levels.

AFOMP Policy Statement No. 3: recommendations for the education and training of medical physicists in AFOMP countries.

AFOMP recognizes that clinical medical physicists should demonstrate that they are competent to practice their profession by obtaining appropriate education, training and supervised experience in the specialties of medical physics in which they practice, as well as having a basic knowledge of other specialties. To help its member countries to achieve this, AFOMP has developed this policy to provide guidance when developing medical physicist education and training programs. The policy is compatible with the standards being promoted by the International Organization for Medical Physics and the International Medical Physics Certification Board.

Association between leukotriene receptor antagonist therapy and Churg-Strauss syndrome: an analysis of the FDA AERS database.

BACKGROUND: The possible role of leukotriene receptor antagonist (LTRA) therapy in the pathogenesis of Churg-Strauss syndrome (CSS) is uncertain. The aim was to examine the association between LTRA therapy and CSS in cases registered in the FDA Adverse Event Reporting System (AERS) database. METHODS: All cases of suspected drug-induced CSS reported to the AERS database between November 1997 and April 2003 were reviewed. Subjects in whom LTRAs were the suspected medication and sufficient documentation existed to confirm the diagnosis of CSS were sequentially categorised into one of the following groups: (A) CSS before treatment initiation; (B) oral or inhaled corticosteroids reduced or stopped within 6 months of CSS onset; (C) possible prodromal phase of CSS at treatment initiation; (D) unstable asthma at treatment initiation; (E) stable asthma at treatment initiation. RESULTS: There were 181 case reports of suspected drug-induced CSS with sufficient documentation to confirm a diagnosis of CSS; in 163 (90%) an LTRA was a suspect medication. In 140 of these 163 cases there was sufficient documentation to sequentially categorize the case into groups, with 13 (9%) in A, 27 (19%) in B, 11 (8%) in C, 28 (20%) in D and 61 (44%) in E. CONCLUSION: LTRA therapy was a suspect medication in most confirmed cases of CSS reported in the AERS database. In the majority of cases treated with an LTRA, CSS could not be explained by either corticosteroid withdrawal or pre-existing CSS. These findings are informative in considering the potential associations between LTRA therapy and CSS.

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.

Follow-up of 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families.

The advent of genome-wide association (GWA) studies has revolutionized the detection of disease loci and provided abundant evidence for previously undetected disease loci that can be pooled together in meta-analysis studies or used to design follow-up studies. A total of 1715 SNPs from the Wellcome Trust Case Control Consortium GWA study of type I diabetes (T1D) were selected and a follow-up study was conducted in 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. In addition to the support for previously identified loci (PTPN22/1p13; ERBB3/12q13; SH2B3/12q24; CLEC16A/16p13; UBASH3A/21q22), evidence supporting two new and distinct chromosome locations associated with T1D was observed: FHOD3/18q12 (rs2644261, P=5.9 x 10(-4)) and Xp22 (rs5979785, P=6.8 x 10(-3); http://www.T1DBase.org). There was independent support for both SNPs in a GWA meta-analysis of 7514 cases and 9045 controls (P values=5.0 x 10(-3) and 6.7 x 10(-6), respectively). The chromosome 18q12 region contains four genes, none of which are obvious functional candidate genes. In contrast, the Xp22 SNP is located 30 kb centromeric of the functional candidate genes TLR8 and TLR7 genes. Both TLR8 and TLR7 are functional candidate genes owing to their key roles as pathogen recognition receptors and, in the case of TLR7, overexpression has been associated directly with murine autoimmune disease.

Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3-q14.1.

A candidate gene study was conducted on 10 established type II diabetes genes and 45 genes associated with autoimmune diseases, including type I diabetes (T1D), in a maximum of 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. Associations at P values <10(-3) were found for three known T1D regions at chromosomes 4q27, 12q13.2 and 12q24.13 (http://www.T1DBase.org). Support was obtained for a newly identified T1D candidate locus on chromosome 12q13.3-12q14.1 (rs1678536/KIF5A: P=8.1 x 10(-3); relative risk (RR) for minor allele=0.89, 95% CI=0.82-0.97), which has a separate association from the previously reported T1D candidate locus ERBB3/12q13.2-q13.3. Our new evidence adds to that previously published for the same gene region in a T1D case-control study (rs1678542; P=3.0 x 10(-4); odds ratio (OR)=0.92, 95% CI=0.88-0.96). This region, which contains many genes, has also been associated with rheumatoid arthritis.