Determination of kilovoltage x-ray therapy depth doses with open-ended applicators.

The purpose of this work was to determine percentage depth dose (PDD) curves for kilovoltage x-rays from the WOmed-T105 unit, with open-ended steel applicators and beam qualities ranging from 0.5 to 4.2 mm Al. Measurements were made with parallel plate chambers in a water phantom, with extrapolation based on a fifth order polynomial used to estimate the surface dose. Measurements were also made with parallel plate chambers in a plastic water phantom, with thin plastic sheets used to obtain detailed measurements at shallow depths (less than 1 mm). Monte Carlo simulations were performed using the EGSnrc package, with two different sources as input: a SpekPy simulation of the x-ray beam and a full simulation of the x-ray tube, treatment head and applicators. Results showed that all four methods (two measurements and two simulations) agreed within the measurement uncertainty at depths greater than 2 mm. At shallow depths, significant differences were noted. At depths less than 0.1 mm, the full Monte Carlo simulation and the solid water measurements showed a sharp spike in surface dose which is attributed to electron contamination, which was not seen in the SpekPy Monte Carlo simulation or the extrapolated water measurements. At depths between 0.1 mm and 2 mm, beyond the range of contaminant electrons, the extrapolated water measurements underestimate the dose by up to 13% compared to the full Monte Carlo simulation and the solid water measurements, attributed to fluorescent photons generated in the applicators. This work demonstrates that for open-ended applicators, measurement of depth doses in water with extrapolation of surface dose has the potential to significantly underestimate the dose at shallow depths between the surface and 2 mm, even after eliminating electron contamination from the beam.

A study of polarity effect for various ionization chambers in kilovoltage x-ray beams.

BACKGROUND: Ionization chambers play an essential role in dosimetry measurements for kilovoltage (kV) x-ray beams. Despite their widespread use, there is limited data on the absolute values for the polarity correction factors across a range of commonly employed ionization chambers. PURPOSE: This study aimed to investigate the polarity effects for five different ionization chambers in kV x-ray beams. METHODS: Two plane-parallel chambers being the Advanced Markus and Roos and three cylindrical chambers; 3D PinPoint, Semiflex and Farmer chamber (PTW, Freiburg, Germany), were employed to measure the polarity correction factors. The kV x-ray beams were produced from an Xstrahl 300 unit (Xstrahl Ltd., UK). All measurements were acquired at 2 cm depth in a PTW-MP1 water tank for beams between 60 kVp (HVL 1.29 mm Al) and 300 kVp (HVL 3.08 mm Cu), and field sizes of 2-10 cm diameter for 30 cm focus-source distance (FSD) and 4 × 4 cm2 - 20 × 20 cm2 for 50 cm FSD. The ionization chambers were connected to a PTW-UNIDOS electrometer, and the polarity effect was determined using the AAPM TG-61 code of practice methodology. RESULTS: The study revealed significant polarity effects in ionization chambers, especially in those with smaller volumes. For the plane-parallel chambers, the Advanced Markus chamber exhibited a maximum polarity effect of 2.5%, whereas the Roos chamber showed 0.3% at 150 KVp with the 10 cm circular diameter open-ended applicator. Among the cylindrical chambers at the same beam energy and applicator, the Pinpoint chamber exhibited a 3% polarity effect, followed by Semiflex with 1.7%, and Farmer with 0.4%. However, as the beam energy increased to 300 kVp, the polarity effect significantly increased reaching 8.5% for the Advanced Markus chamber and 13.5% for the PinPoint chamber at a 20 × 20 cm2 field size. Notably, the magnitude of the polarity effect increased with both the field size and beam energy, and was significantly influenced by the size of the chamber's sensitive volume. CONCLUSIONS: The findings demonstrate that ionization chambers can exhibit substantial polarity effects in kV x-ray beams, particularly for those chambers with smaller volumes. Therefore, it is important to account for polarity corrections when conducting relative dose measurements in kV x-ray beams to enhance the dosimetry accuracy and improve patient dose calculations.

Oral antibiotics and mechanical bowel preparation for colorectal surgery: A prospective observational study of surgical site infection and microbial analysis.

PURPOSE: Surgical site infections (SSIs) are common in colorectal surgery. Mechanical bowel preparation (MBP) in conjunction with oral antibiotics (OABs) have been shown to reduce SSI rates. It however is still unclear which OABs to use, and how this can be implemented in practice. METHODS: This is a prospective observational study carried out in Swansea Bay University Health Board during 2019-2021, evaluating the introduction of OABs in a stepwise manner on the incidence of SSI in major colorectal surgery. A control group having MBP only was compared to two OAB groups: one group had MBP plus metronidazole only and the second MBP plus metronidazole and neomycin. A 30-day follow-up after surgery was ascertained via chart review and telephone contact. Logistic regression was performed to estimate the relation between OAB use and SSI, with adjustment for confounding. In a subset of patients, faecal samples were analysed through 16S rRNA amplicon sequencing before and after OAB treatment, depicting the impact of the gut microbiome. RESULTS: In total 160 patients were analysed: 46 patients had MBP only, whilst 76 patients had MBP plus metronidazole only and 38 patients had MBP with metronidazole/neomycin. The SSI rate in the entire cohort was 33.8%, whilst the adjusted ORs for the single- and dual-OAB groups were 0.76 (95% CI: 0.17-1.81) and 0.50 (95% CI: 0.17-1.52). The microbial analysis demonstrated that the relative abundance for many bacterial genera was changed before and after OAB treatment, but no link with SSI development could be shown. CONCLUSIONS: Introduction of OABs in conjunction with MBP in colorectal surgery is feasible, and may potentially lead to lower rates of SSI, as well as altering the community structure of the faecal microbiome. More research is needed, especially considering different OABs and mechanistic studies of the gut microbiome in the context of colorectal surgery.

Prioritizing clinical trial quality assurance for photons and protons: A failure modes and effects analysis (FMEA) comparison.

BACKGROUND AND PURPOSE: The Global Clinical Trials RTQA Harmonization Group (GHG) set out to evaluate and prioritize clinical trial quality assurance. METHODS: The GHG compiled a list of radiotherapy quality assurance (QA) tests performed for proton and photon therapy clinical trials. These tests were compared between modalities to assess whether there was a need for different types of assessments per modality. A failure modes and effects analysis (FMEA) was performed to assess the risk of each QA failure. RESULTS: The risk analysis showed that proton and photon therapy shared four out of five of their highest-risk failures (end-to-end anthropomorphic phantom test, phantom tests using respiratory motion, pre-treatment patient plan review of contouring/outlining, and on-treatment/post-treatment patient plan review of dosimetric coverage). While similar trends were observed, proton therapy had higher risk failures, driven by higher severity scores. A sub-analysis of occurrence × severity scores identified high-risk scores to prioritize for improvements in RTQA detectability. A novel severity scaler was introduced to account for the number of patients affected by each failure. This scaler did not substantially alter the ranking of tests, but it elevated the QA program evaluation to the top 20th percentile. This is the first FMEA performed for clinical trial quality assurance. CONCLUSION: The identification of high-risk errors associated with clinical trials is valuable to prioritize and reduce errors in radiotherapy and improve the quality of trial data and outcomes, and can be applied to optimize clinical radiotherapy QA.

Reaching people receiving opioid agonist therapy at community pharmacies with hepatitis C virus: an international randomised controlled trial.

BACKGROUND: Conventional healthcare models struggle to engage those at risk of hepatitis C virus (HCV) infection. This international study evaluated point-of-care (PoC) HCV RNA diagnostic outreach and direct-acting antiviral (DAA) treatment for individuals receiving opioid agonist therapy (OAT) in community pharmacies. AIMS: We assessed the effectiveness of a roving nurse-led pathway offering PoC HCV RNA testing to OAT clients in community pharmacies relative to conventional care. METHODS: Pharmacies in Scotland, Wales, and Australia were randomised to provide PoC HCV RNA testing or conventional referral. Pharmacists directed OAT clients to on-site nurses (intervention) or local clinics (control). Infected participants were treated with DAAs, alongside OAT. Primary outcome was the number of participants with sustained virologic response at 12 weeks (SVR) and analysed using mixed effects logistic regression in the intention-to-treat (ITT) population. RESULTS: Forty pharmacies were randomised. The ITT population contained 1410 OAT clients. In the conventional arm (n = 648), 62 (10%) agreed to testing, 17 (27%) were tested, 6 (35%) were positive and 5 (83%) initiated treatment. In the intervention arm (n = 762), 148 (19%) agreed to testing, 144 (97%) were tested, 23 (16%) were positive and 22 (96%) initiated treatment. SVR was obtained by 2 (40%; conventional) and 18 (82%; intervention). Intervention arm participants had higher odds of testing, OR 16.95 (7.07-40.64, p < 0.001); treatment, OR 4.29 (1.43-12.92, p = 0.010); and SVR, OR 8.64 (1.82-40.91, p = 0.007). CONCLUSIONS: Nurse-led PoC diagnosis in pharmacies made HCV care more accessible for OAT clients relative to conventional care. However, strategies to improve testing uptake are required. TRIAL REGISTRATION: NCT03935906.

Characterisation of in-room leakage and scattered radiation for the Varian Halcyon linear accelerator.

Unintended sources of secondary radiation resulting from photon beams in linear accelerators are patient scatter, collimator scatter, scatter from surfaces within the bunker, and head leakage. This work characterises the in-room leakage and scattered radiation for the Varian Halcyon linear accelerator. Scattered and leakage radiation for static gantry angles 0°, 45°, and 90° and largest field size 28 × 28 cm2 were measured with an ionisation chamber survey meter at a radial distance of 1.5 m from the isocentre. The scatter within the treatment room was characterised with isocontour maps from measurements of 360° arc deliveries with the largest field size 28 × 28 cm2 at various heights and distances from the isocentre. The transmission through the primary beam stopper was measured with a Farmer ionisation chamber. For static gantry angles, instantaneous dose rate readings were typically around 70 mSv/hr at 1.5 m from the isocentre with lower dose rates at room angles adjacent to the gantry. The head leakage was measured as less than 0.03% of the useful beam. In a full 360° arc, the radiation dose around the Halcyon was coldest in lateral areas, with hotter areas behind and in front of the gantry. The primary beam stopper transmission was measured as 0.019%, reducing the requirement of primary barriers in the shielding design by a factor of 1/500. The results presented in this study can be used to determine the out-of-field dose to patients and to inform bunker shielding designs for Halcyon linear accelerators.

The protective effect of previous COVID-19 infection in a high-prevalence hospital setting.

OBJECTIVE: To assess the protective effect of previous COVID-19 infection for healthcare workers in a high-prevalence setting. METHOD: The COVID-19 antibody and PCR results of 538 healthcare workers on wards with COVID-19 outbreaks from 1 March 2020 to 31 July 2020 were evaluated. Infection rates of the 'previously infected' and 'no evidence of previous infection' groups were compared during second-wave outbreaks between 29 September 2020 and 20 November 2020. RESULTS: One out of 115 individuals previously infected developed infection compared with 104 out of 423 individuals with no evidence of previous infection. Attack rates in staff previously infected was reduced significantly from 24.59% to 0.87% (odds ratio 0.027, 95% CI 0.004-0.195, p<0.001) when compared to the 'no evidence of previous infection' group with the same exposure risk. CONCLUSION: Prior SARS-CoV-2 infection offers significant protection against reinfection and this protection lasts 4 months for the majority of individuals.

Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy.

Sustained viral response (SVR) rates for direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection routinely exceed 95%. However, a small number of patients require retreatment. Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is a potent DAA combination primarily used for the retreatment of patients who failed by DAA therapies. Here we evaluate retreatment outcomes and the effects of resistance-associated substitutions (RAS) in a real-world cohort, including a large number of genotype (GT)3 infected patients. 144 patients from the UK were retreated with SOF/VEL/VOX following virologic failure with first-line DAA treatment regimens. Full-length HCV genome sequencing was performed prior to retreatment with SOF/VEL/VOX. HCV subtypes were assigned and RAS relevant to each genotype were identified. GT1a and GT3a each made up 38% (GT1a n = 55, GT3a n = 54) of the cohort. 40% (n = 58) of patients had liver cirrhosis of whom 7% (n = 4) were decompensated, 10% (n = 14) had hepatocellular carcinoma (HCC) and 8% (n = 12) had received a liver transplant prior to retreatment. The overall retreatment SVR12 rate was 90% (129/144). On univariate analysis, GT3 infection (50/62; SVR = 81%, p = .009), cirrhosis (47/58; SVR = 81%, p = .01) and prior treatment with SOF/VEL (12/17; SVR = 71%, p = .02) or SOF+DCV (14/19; SVR = 74%, p = .012) were significantly associated with retreatment failure, but existence of pre-retreatment RAS was not when viral genotype was taken into account. Retreatment with SOF/VEL/VOX is very successful for non-GT3-infected patients. However, for GT3-infected patients, particularly those with cirrhosis and failed by initial SOF/VEL treatment, SVR rates were significantly lower and alternative retreatment regimens should be considered.

If it ain't broke don't fix it: Lack of review of antimicrobials in 'well' patients - time for a CRP change.

INTRODUCTION: The rising prevalence of multi-resistant organisms threatens the efficacy of current antimicrobial treatments. Antibiotic stewardship is a key factor in slowing the development of resistance and must become part of a clinician's regular practice. National guidance unanimously emphasises the importance of a 48-hour review of antimicrobial prescriptions. We assessed the compliance of antibiotic reviews across two sites in Wales. METHOD: Two cycles of data were retrospectively collected across two teaching hospitals in Wales prior and following introduction of an antimicrobial alert sticker. A univariate odds ratio for 48-hour referral stratified by C-reactive protein (CRP) was calculated in a logistic regression model for the cycle one data. RESULTS: One-hundred and thirty-nine patients were included in the cycle 1 data across both sites. We identified that patients with a CRP ≤100 mg/L (a marker of less severe infection) were less likely to have their antibiotic prescription reviewed by 48 hours. DISCUSSION: Patients with CRP ≤100 mg/L were less likely to receive a 48-hour review of their antimicrobial prescription. Compliance with review improved following introduction of a simple alert measure.

Fluid-repellent surgical mask (FRSM) fit - one size does not fit all.

BACKGROUND: Fluid-repellent surgical masks (FRSMs) are recommended by the UK government for healthcare workers as personal protective equipment (PPE) against SARS-COV-2. UK Infection Prevention and Control (IPC) national guidelines states that 'masks must be well-fitting and fit for purpose, fully covering the mouth and nose'. AIM: To review the fit of the FRSM supplied to the NHS front line workers against the national IPC guidelines and, through re-audit, assess for improvements in fit with FRSM worn with a plastic strap (intervention A) and FFP3 mask (intervention B). METHOD: A three-part closed-loop audit was carried out comprising controlled observation, observation in the clinical area and questionnaire. Re-audit was carried out following interventions A and B. RESULTS: FRSMs slipped below the nose in 43% and below the mouth of 10% of participants during the controlled observation and below the nose (above or below the mouth) in 30% of staff in the clinical area. No masks slipped below the nose or mouth with intervention A or B. 86% of participants reported touching the FRSM to keep it in the correct position and 66% reported touching the FFP3. CONCLUSION: The current supply of FRSMs are poorly fitting for many users and do not meet the UK IPC guideline standard. These issues were not evident when worn with a plastic strap or with FFP3 masks.

A National Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit.

BACKGROUND: Fungal coinfection is a recognized complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in coronavirus disease 2019 (COVID-19) patients with severe respiratory distress are being reported, but comprehensive data are lacking. The aim of this study was to determine the incidence, risk factors, and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress. METHODS: An evaluation of a national, multicenter, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients. RESULTS: One-hundred and thirty-five adults (median age: 57, M/F: 2.2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12.6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P = .0387). The mortality rate was reduced by the use of antifungal therapy (mortality: 38.5% in patients receiving therapy vs 90% in patients not receiving therapy (P = .008). The use of corticosteroids (P = .007) and history of chronic respiratory disease (P = .05) increased the likelihood of aspergillosis. CONCLUSIONS: Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.

The impact of false positive COVID-19 results in an area of low prevalence.

False negative results in COVID-19 testing are well recognised and frequently discussed. False positive results, while less common and less frequently discussed, still have several adverse implications, including potential exposure of a non-infected person to the virus in a cohorted area. Although false positive results are proportionally greater in low prevalence settings, the consequences are significant at all times and potentially of greater significance in high-prevalence settings. We evaluated COVID-19 results in one area during a period of low prevalence. The consequences of these results are discussed and implications for these results in both high and low prevalence settings are considered. We also provide recommendations to minimise the risk and impact of false-positive results.

The clinical sensitivity of a single SARS-CoV-2 upper respiratory tract RT-PCR test for diagnosing COVID-19 using convalescent antibody as a comparator.

The clinical false negative rate of reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on a single upper respiratory tract sample was calculated using convalescent antibody testing as a comparator. The sensitivity in symptomatic individuals was 86.2% (25/29). Of the missed cases, one (3.5%) was detected by repeat RT-PCR, one by CT thorax and two (7.1%) by convalescent antibody. The clinical false negative rate of a single RT-PCR on an upper respiratory tract sample of 14% in symptomatic patients is reassuring when compared to early reports. This report supports a strategy of combining repeat swabbing, use of acute and convalescent antibody testing and CT thorax for COVID-19 diagnosis.

Reaching mEthadone users Attending Community pHarmacies with HCV: an international cluster randomised controlled trial protocol (REACH HCV).

INTRODUCTION: Hepatitis C virus (HCV) is a global public health threat, and novel models of care are required to treat those currently or previously at highest risk of infection, particularly persons who inject drugs (PWID; ever injected), as conventional healthcare models do not have the reach to deliver cure of HCV to disadvantaged, disproportionately affected communities. In Western Europe and Australasia, it is estimated that HCV affects between 0.4% and 1.0% of the regions' populations, accordingly, it affects between 0.4% and 0.7% of the populations of countries in this study (Scotland, Wales and Australia). Reaching mEthadone users Attending Community pHarmacies with HCV (REACH HCV) will evaluate community pharmacy-based diagnostic outreach and HCV treatment against conventional HCV testing and treatment pathways for clients receiving opioid substitution therapy (OST) in community pharmacies. METHODS AND ANALYSIS: REACH HCV is an international multicentre cluster randomised controlled trial with sites in Scotland, Wales and Australia. The sites are community pharmacies which are randomised equally to one of two pathways: the pharmacy intervention pathway or the education-only (control) pathway. Participants are recruited from OST clients in these pharmacies.In the pharmacy intervention pathway, participants receive a rapid point-of-care HCV PCR test in their pharmacy by a study outreach nurse. If positive, direct-acting antivirals (DAAs) are delivered to participants via their pharmacist in line with their OST schedule.In the education-only pathway, pharmacists counsel OST clients on HCV and refer them to the nearest nurse-led clinic or general practitioner offering HCV testing according to standard care protocols. If positive, DAAs are delivered as in the intervention pathway.The primary endpoint for both pathways is sustained viral response at 12 weeks post-treatment . Secondary outcomes are: cost-efficacy by pathway; participants tested by pathway; adherence to therapy by pathway and impact of blood test results on treatment decisions.A statistical analysis plan will be finalised prior to data lock. Analysis will be by intention to treat (ITT) to show superiority. Modified ITT analysis will also be undertaken to explore the steps in the pathways. ETHICS AND DISSEMINATION: The trial received ethical favourable opinion from the East of Scotland Research Ethics Committee 2 (19/ES/0025) for UK sites and approval from the Alfred Hospital Ethics Committee (148/19) for Australian sites and complies with principles of Good Clinical Practice. Final results will be presented in peer-reviewed journals and at relevant conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry NCT03935906. PROTOCOL VERSION: V.4.0-19 March 2020.

Impact of a novel community testing pathway for people with suspected COVID-19 in Wales: a cost-minimisation analysis.

OBJECTIVE: To compare National Health Service (NHS) organisations' testing pathways for patients with suspected COVID-19 in the community versus standard hospital testing practices. PERSPECTIVE: NHS commissioners and services. METHODS: During the containment phase of the COVID-19 pandemic we developed a community model pathway for COVID-19 testing in Wales with testing teams undertaking swabbing for COVID-19 in individuals' usual place of residence. We undertook a cost-minimisation analysis comparing the costs to the NHS in Wales of community testing for COVID-19 versus standard hospital testing practices and ambulance conveyancing. We analysed data from patients with suspected COVID-19 between January and February 2020 and applied assumptions of costs from national contractual and reference costs for ambulances, staffing and transportation with market costs at the time of publication. RESULTS: 177 patients with suspected COVID-19 underwent community testing via local NHS organisations between January and February 2020 with a mean age of 46.1 (IQR 27.5-56.3). This was 92% of total patients who were tested for COVID-19 during this period. We estimate, compared with standard hospital testing practices, cash savings in improved productivity for the NHS of £24,539 during this time period, in addition to further non-monetised benefits for hospital and ambulance flow. CONCLUSIONS: Community testing for COVID-19 in Wales is now an established pathway and continues to bring benefits for patients, local healthcare organisations and the NHS. Further application of this model in other settings and to other infectious diseases may herald promising returns.