Routine Dose Research Articles

Detecting ionizing radiation dose using composite hydrogel-based sensors

Dose verification in radiotherapy is crucial to ensure a safe and efficient outcome of medical treatments. To overcome routine radiation dose detection challenges, a composite hydrogel sensor comprised of fluorescent poly(N-isopropylacrylamide)-based nanogels and clay nanoparticles is reported. The sensing methodology is primarily based on the transition of hydroxyphenyl fluorescein to fluorescence in the presence of OH radicals due to the radiolysis of water molecules under ionizing radiation, whereas the fluorescence intensity of 5(6)-carboxytetramethylrhodamine is stable upon radiation. Harnessing the ratiometric fluorescent strategy, in vitro point- and topographical-dose profiles under X-ray and electron beam irradiation and the in-vivo determination of γ-ray dose are determined without any waiting time after irradiation. The determined dose is comparable to the results of Monto Carlo simulations and clinical treatment planning systems (TPS). Also, the sensing capability of the developed sensor is well maintained, regardless of the types of radiation, dose rate, radiation energy, testing temperature, and storing period. Hence, our sensors show the translational potential for dose verification in radiotherapy.

Clinical and serological association of plasma 25-hydroxyvitamin D (25(OH)D) levels in lupus and the short-term effects of oral vitamin D supplementation

Background and objectivesData on the association of vitamin D levels and clinical phenotype and disease activity in systemic lupus erythematosus (SLE) is controversial. Further, the optimal dose of oral vitamin D supplementation in SLE is not clear. Thus, the present study was designed to determine the association of plasma vitamin D levels with clinical phenotype, disease variables and serology in a large, cohort of SLE from South Asia and to evaluate the short-term effect of two different dosage regimens of oral vitamin D supplementation on disease flares and plasma vitamin D levels.MethodsThis is a two-phase study. Phase I was a cross-sectional analytical study of patients from north (26.85° N) and south India (11.94° N). Plasma 25-hydroxyvitamin-D(25(OH)D) was measured, and its association with demography, serology, disease activity, Galectin-9 and CXCL-10 was analysed. In phase II, patients with SLEDAI-2KG < 10 and on stable immunosuppression were randomised to receive either high dose (weekly 60,000 U*5, followed by 60,000 U monthly) or routine dose (30,000 U monthly) oral vitamin D. Outcomes were assessed at 6 monthsResultsPhase I included 702 patients with a mean age of 29.46 + 10.7 years. The median plasma vitamin D was 22.83 (13.8–31.8) ng/ml. Deficiency (< 20 ng/ml) was seen in 41.5% of patients. Patients from South India had higher vitamin D levels (27.06 ± 20.21 ng/dl) as compared to North India (17.15 ± 16.07 ng/ml) (p < 0.01). Univariate analyses demonstrated weak negative correlation of vitamin D with SLEDAI2K and positive correlation with age. Galactin-9 had modest correlation with SLEDAI2K but not with vitamin D levels. On multiple linear regression, centre of recruitment (β = 4.37) and age (β = 0.18) predicted (p < 0.05) plasma vitamin D levels.In the phase II, 91 randomised to 2 groups completed 6 months. Median change in plasma vitamin D levels was more in high dose (9.5 versus 2.6 ng/ml; p = 0.04). There were 14 SLE flares and six minor adverse events which were equal across both groups.ConclusionVitamin D deficiency is common in SLE. Geographical location of residence is the major determinant rather than the disease activity. The IFN regulated proteins reflect disease activity independent of vitamin D levels. High-dose oral vitamin D supplementation seems safe and more effective in improving vitamin D levels in SLE.Trial registrationThe second phase of this study was a registered randomised controlled trial CTRI/2019/06/019658 [registered on: 14/06/2019].

The Impact of the COVID-19 Pandemic on Uptake of Routine Childhood Immunization: How a Behavioral Science Led Analysis Can Strengthen Vaccination Policy

In addition to the direct health and economic impacts of the COVID-19 pandemic, routine immunization of children for vaccine-preventable diseases has also suffered. Quantitative studies have shown evidence of backsliding in routine immunization, i.e., children failing to receive their vaccinations on schedule. Pandemic restrictions were the cause for some of this behavior, and there are signs that subsequent campaigns and supply-side initiatives have influenced trends toward routine immunization catch-up. However, limited qualitative research indicates that the pandemic may have disrupted parents/caregivers’ decision-making processes around routine immunization, and their attitudes toward vaccination, in ways that could have long-term effects on rates of immunization. Further behavioral research can help elucidate this and provide guidance to policymakers to boost immunization uptake. This policy article explores the decision dynamics leading to missed routine immunization doses during the pandemic, through an analysis of secondary literature, a summary of primary-research studies on COVID-19 vaccine hesitancy conducted during the pandemic across Côte d’Ivoire, Burkina Faso, Kenya and Pakistan, and a summary of a study on the impact of COVID-19 on routine immunization uptake in South Africa. We found that the COVID-19 pandemic severely disrupted prior patterns of engagement with the health system, turning routine immunization from a default decision for parents/caregivers into an “active decision-making” moment. Restrictions on movement, limited routine immunization supplies and other practical impediments combined with fear of contracting COVID-19 at health facilities, misinformation, and fear of vaccine side-effects, creating an emergent behavior of missed immunization doses during the pandemic period. We also found that hesitancy about COVID-19 vaccines may be transferred onto previously accepted vaccines, impacting routine immunization. We identified three decision-making pathways for routine immunization uptake among South African parents/caregivers once the lockdowns were lifted: the “path of procrastination,” the “path of doubt,” and the “path of persistence.” We highlight the policy implications of these, and suggest potential interventions to increase routine immunization uptake for parents/caregivers on each path, as well as for general communications, service delivery, and pandemic readiness.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. Children aged 9months to younger than 5years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Management of Dermatophytosis: Real-World Indian Perspective.

In spite of the availability of multiple consensus statements on dermatophytosis management, different treatment approaches have been experienced in India and require more scrutiny to further update guidelines and improve patient care. To determine the different approaches in dermatophytosis diagnosis and management among dermatologists in India. A web-based questionnaire was created and validated by five panelists with experience of >15 years in dermatophytosis and then circulated to about 2,000 dermatologists in India in September 2021 for a real-world management scenario. Out of 2,000 dermatologists, 459 responded. About half of the dermatologists (51%) routinely conduct potassium hydroxide mount (KOH) at the initiation of therapy. Similarly, about 53% of dermatologists initiate the management of dermatophytosis with combination therapy in all types of dermatophytosis for 4-6 weeks depending upon severity. Different types of combinations are being practiced, such as either two systemic and one topical, two topicals and one systemic, but the combination of one systemic and one topical (69%) is the most commonly practiced. Itraconazole (100 mg twice a day) and luliconazole are the most commonly prescribed antifungal medications. In case of non-response to routine dose of systemic anti-fungals, about 72% of dermatologists up dose them. Most of them continue these drugs for additional 1-2 weeks after clearance of the disease. Additionally, keratolytics and moisturizers are commonly prescribed. Additionally, 62% advise liver function tests (LFTs) at the initiation of therapy, whereas 72% advise monitoring adverse effects due to systemic antifungal drugs during treatment. Combination therapy stood out as the need of the hour in the current menace of dermatophytosis with timely monitoring of laboratory tests for adverse events due to the use of systemic antifungals for a longer duration.

Ferritin screening and Iron treatment for maternal anemia and fetal growth restriction prevention - A multicenter randomized controlled trial (FAIR Study).

Non-anemic iron deficiency precedes iron deficiency anaemia and has an estimated prevalence of 1-2 billion worldwide. Few studies have comprehensively researched the idea of treating non-anemic iron deficiency (NAID) with iron to improve the outcome of the mother and the offspring. FAIR will be a multicenter randomized controlled trial that will be conducted in multiple clinical academic obstetrics units in Lahore (including Services Institute of Medical Sciences, Lahore, Allama Iqbal Medical College, Lahore and Fatima Jinnah Medical University). Pregnant women at gestational age <20 weeks with hemoglobin 11-13 g/L and ferritin below the threshold (<30 ng/ml) will be invited to take part in the study. Randomization will be done by computer based generated random numbers. One group (usual care or oral group) will be offered routine care prophylactic dose of oral iron (30-45 mg/day) and the other group (intervention arm or IV group) will be offered therapeutic dose of IV iron (dose calculated by Ganzoni formula) in addition to usual care. All patients will be followed up till delivery. Primary maternal outcome will be hemoglobin at 36 weeks' gestation. Secondary outcomes are fetal birthweight or small for gestational age, preterm birth, preeclampsia, multidimensional fatigue inventory, breast feeding initiation, blood transfusion, and fetal cord ferritin and hemoglobin. The study will generate evidence as to whether screening serum ferritin in non-anemic pregnant women and replenishing their iron stores will likely reduce the rate of predelivery anemia in pregnant women, improve birthweight and preventing perinatal complications. Tayyiba Wasim is principal Investigator and other members of data management team are Natasha Bushra, Shamsa Humayoun, Khalid Saeed Khan, Fatima Shehbaz, Saba Rasool, Anam Riaz and Sonia Irshad. Principal investigator will assume the full responsibility of Fair trial including training of research assistants, administration of informed consent and protecting participants confidentiality. Data management team will help in the management, development and execution of trial. Khadija Irfan Khawaja is the operational lead for fair trial´s technology team comprising of Aziz Fatima and Zubia Zafar, responsible for gathering requirements from study teams and supporting the operational implementation of technology to drive the collection of high-quality study data. Protocol contributors are Gynae unit I of Services Institute of Medical Sciences/ Services hospital, Lahore, Gynae Unit II of Allama Iqbal Medical College/ Jinnah hospital, Lahore and Gynae unit 1 of Fatima Jinnah Medical College/ Sir Ganga Ram hospital, Lahore. These coordinating centres will recruit patients (sample size=600) and will discuss their progress in trial management meetings quarterly. has an independent chair Prof Samia Malik, one expert member Prof Faiza Bashir and Ms Neelam to represent patients, public and consumers. Trial steering committee with independent chair and member with a patient representative will oversee the study. Chair of steering committee has the authority to stop the trial whenever needed in case of positive or negative results. Steering committee meetings will be held on annual basis. comprises of Dr. Shehnoor Azhar as chair and Prof Ejaz Hussain and Dr. Shehla Javed Akram as members. Data monitoring committee will assess the progress, data safety and if needed critical efficacy points of the clinical study and will show their results quarterly in data interim meetings. The committee will focus on integrity of the whole process and compliance of all sites with all aspects of the protocol. It will perform confidential interim analyses quarterly, which may be used to determine if an effect is observed and if the study should continue to its planned sample size. Data monitoring committee will report to the Chair of the steering committee.

Lessons from Vaccine-Related Poliovirus in Israel, UK and USA.

Genetic variants of vaccine poliovirus type 2, imported from an unknown source, were detected in waste waters in Jerusalem, London and New York in early 2022. Wild poliovirus type 2 was globally eradicated in 1999, but vaccine virus type 2 continued for 16 more years; routine use of the vaccine was discontinued in 2016 and reintroduced occasionally on purpose. As an unintended consequence, type 2 vaccine virus variants (circulating vaccine-derived polioviruses, cVDPVs) that mimic wild viruses' contagiousness and neurovirulence, have been emerging and spreading. To illustrate, in just the past four years (2018-2021), 2296 children developed cVDPV polio in 35 low-income countries. Many assume that virus transmission is via the faecal-oral route. Sustained virus transmission was documented in London and New York, in spite of high standards of sanitation and hygiene. Here, virus transmission cannot be attributed to faecal contamination of food or drinking water (for faecal-oral transmission). Hence, contagious transmission can only be explained by inhalation of droplets/aerosol containing virus shed in pharyngeal fluids (respiratory transmission), as was the classical teaching of polio epidemiology. If transmission efficiency of VDPV is via the respiratory route where hygiene is good, it stands to reason that it is the same case in countries with poor hygiene, since poor hygiene cannot be a barrier against respiratory transmission. By extrapolation, the extreme transmission efficiency of wild polioviruses must also have been due to their ability to exploit respiratory route transmission. These lessons have implications for global polio eradication. It was as a result of assuming faecal-oral transmission that eradication was attempted with live attenuated oral polio vaccine (OPV), ignoring its safety problems and very low efficacy in low-income countries. Inactivated poliovirus vaccine (IPV) is completely safe and highly efficacious in protecting children against polio, with just three routine doses. Protecting all children from polio must be the interim goal of eradication, until poliovirus circulation dies out under sustained immunisation pressure. OPV should be discontinued under cover of immunity induced by IPV to stop the emergence of new lineages of VDPVs, not only type 2, but also types 1 and 3, to expedite the completion of polio eradication.

Initiation and Implementation of Infusional Chemotherapy As a Base Regimen for Increased Risk Lymphoid Malignancy in an Inner-City Academic Institution

Our institution is a 695-bed facility that serves an inner-city population and the surrounding area which together are largely urban and have withstood longstanding obstacles to care including food insecurity, absence of reliable transportation, lack of insurance coverage, and poor health literacy. Such barriers have historically served to limit for many patients, routine outpatient visits, weekly, or even nadir lab work as well as outpatient-based cancer therapy. Institutional barriers include limited nursing resources. Given these challenges, with a change in divisional leadership and the establishment of a new fellowship in hematology/oncology, a simplified and streamlined approach to managing and treating high-risk lymphoid malignancies was planned. Infusional chemotherapy has been shown to have activity in a variety of lymphoid cancers (Wilson, 1993; Dobashi, 1998; Cassaday, 2018). To address inconsistent patient follow-up, a program was instituted, utilizing a dedicated Registered Nurse coordinator making routine proactive phone and electronic check-ins to ascertain patient status; a distinct, direct phone number to call to report symptoms; electronic medical record access for communication; dedicated physician/physician assistant availability; and treatment planning assigned to a single, designated faculty physician with fellow support. Additionally, planned treatment needed inpatient administration, no routine dose alterations, no requirement for patient self-medication, and scheduled single-dose growth factor support. With this in mind, we have utilized an infusional chemotherapy regimen of Hydroxydaunorubicin (Adriamycin) (10 mg/m2), OncovinR (Vincristine) (0.4 mg/m2), and Etoposide (50 mg/m2) by continuous infusion daily for 4 days with Prednisolone 125 mg IV daily for 5 days, and Cyclophosphamide 750 mg/m2 IV on day 5. Peg-filgastrim 6 mg subcutaneously was given following completion of therapy. Cycles were repeated every 21 days. Additions of Rituximab and TKI varied by individual malignancy type. Pt characteristics: 7 males/6 females, median age-45 (range: 19-75), median ECOG status-2, B symptoms-8, LDH elevation-9, no prior therapy-7, disease types: diffuse large B-cell lymphoma-4, large cell unclassifiable, intermediate between DLBCL and classical Hodgkin-2, plasmablastic lymphoma-1, primary effusion lymphoma-1, Burkitt lymphoma-1, lymphoblastic lymphoma-1, acute lymphoblastic leukemia-3.Median number of cycles received = 6 (range: 1-8).Six have had complete responses and four partial responses. One patient with acute lymphoblastic leukemia has undergone transplant and is free of leukemia at 19.9+ months. The median duration of complete response has not been reached at > 6 months. Median survival is ongoing at 11.5+ months. There have been no treatment-related deaths. Three patients required dose modification of Vincristine related to transient paresthesia. There have been no hospitalizations related to toxicity. This systematic approach including an infusional chemotherapy regimen may produce positive downstream effects such as consistency with nursing, a deeper understanding of side effects by nurses and mid-level providers and a predictable patient flow to improve the patient experience and ultimately outcomes. Given the resource constraints experienced at our institution, and potentially other urban teaching institutions, this approach may prove helpful in terms of patient compliance, satisfaction with care, and outcomes.

Measles second dose vaccine utilization and associated factors among children aged 24–35 months in Sub-Saharan Africa, a multi-level analysis from recent DHS surveys

BackgroundAlthough a safe and effective vaccine is available, measles remains an important cause of mortality and morbidity among young children in Sub-Saharan Africa (SSA). The WHO and UNICEF recommended measles-containing vaccine dose 2 (MCV2) in addition to measles-containing vaccine dose 1 (MCV1) through routine services strategies. Many factors could contribute to the routine dose of MCV2 coverage remaining far below targets in many countries of this region. This study aimed to assess the prevalence of MCV2 utilization among children aged 24–35 months and analyze factors associated with it by using recent nationally representative surveys of SSA countries.MethodsSecondary data analysis was done based on recent Demographic and Health Surveys (DHS) data from eight Sub-Saharan African countries. In this region, only eight countries have a record of routine doses of measles-containing vaccine dose 2 in their DHS dataset. The multilevel binary logistic regression model was fitted to identify significantly associated factors. Variables were extracted from each of the eight country’s KR files. Adjusted Odds Ratios (AOR) with a 95% Confidence Interval (CI) and p-value ≤ 0.05 in the multivariable model were used to declare significant factors associated with measles-containing vaccine dose 2 utilization.ResultThe pooled prevalence of MCV2 utilization in SSA was 44.77% (95% CI: 27.10–62.43%). In the multilevel analysis, mothers aged 25–34 years [AOR = 1.15,95% CI (1.05–1.26), mothers aged 35 years and above [AOR = 1.26, 95% CI (1.14–1.41)], maternal secondary education and above [AOR = 1.27, 95% CI (1.13–1.43)], not big problem to access health facilities [AOR = 1.21, 95% CI (1.12–1.31)], four and above ANC visit [AOR = 2.75, 95% CI (2.35–3.24)], PNC visit [AOR = 1.13, 95% CI (1.04–1.23)], health facility delivery [AOR = 2.24, 95% CI (2.04–2.46)], were positively associated with MCV2 utilization. In contrast, multiple twin [AOR = 0.70, 95% CI (0.53–0.95)], rural residence [AOR = 0.69, 95% CI (0.57–0.82)] and high community poverty [AOR = 0.66, 95% CI (0.54–0.80)] were found to be negatively associated with MCV2 utilization.Conclusions and recommendationsMeasles-containing vaccine doses 2 utilization in Sub-Saharan Africa was relatively low. Individual-level factors and community-level factors were significantly associated with low measles-containing vaccine dose 2 utilization. The MCV2 utilization could be improved through public health intervention by targeting rural residents, children of uneducated mothers, economically poor women, and other significant factors this study revealed.

The Determination of Diagnostic Reference Range (DRR) Based on Clinical Indications in Head Computed Tomography (CT) Imaging

Diagnostic reference range (DRR) were introduced to help manage image quality as well as patient dose by providing minimum estimated dose that covers 25–75% range of dose distribution. The International Commission on Radiological Protection (ICRP) (2017) recommended 75th percentile as upper boundary and 25th percentile as lower boundary of DRR [1]. Dose below the lower range should compromised accurate interpretation of the image and dose above the upper range may be in excess and need to be reviewed. Meanwhile, Diagnostic Reference Levels (DRLs) also recommended by ICRP as a guidance to identify any uncommon high dose delivered by computed tomography (CT) scanner. DRLs are established at 75th percentile of dose distribution and should be implemented at international, regional, or local level for dose management.&#x0D; &#x0D; This study aims to establish a local DRR based on five most common clinical indications for adult head CT scanning at Department of Radiology, Hospital Universiti Sains Malaysia (HUSM), Kelantan. This study involved a retrospective survey on adult patient data undergone head CT scan with two CT scanners, Toshiba CT scanner at Trauma Department and Siemens CT scanner at Radiology Department, HUSM. The related data regarding the scanning protocols and dose descriptor (dose length product, DLP) were recorded for the most common clinical indication in head CT scans.&#x0D; &#x0D; Results showed the five most common clinical indication related to head CT scans were abscess, bleeding, stroke, trauma, and tumour. The DLP values were varied based on their clinical indications and CT scanner types. Figure 1 shows boxplots representing the DRRs of dose length product (DLP) based on the five most common clinical indications in head CT scans for Toshiba and Siemens CT scanners. From the figure, the DLP ranges for Toshiba CT scanner were slightly higher than Siemens CT scanners. The lowest DLP value was observed for tumour indication and the highest DLP was bleeding and trauma indications. Clinical indication that requires higher image resolution and details and longer scan length, recorded higher DLP distribution.&#x0D; This study demonstrates that the dose descriptor values, CTDIvol and DLP were varied for similar anatomical region based on different image quality requirement for each clinical indication. Therefore, DRR and DRL should be established based on specific clinical indication and routine dose audit is essential to ensure patients safety.

COVID-19 vaccination uptake for half a million non-EU migrants and refugees in England: a linked retrospective population-based cohort study

BackgroundCOVID-19 has highlighted severe health inequities experienced by certain migrants. Despite evidence suggesting that migrants are at risk of under-immunisation, data are limited for migrants' COVID-19 vaccine uptake in England. MethodsWe did a retrospective population-based cohort study on COVID-19 vaccination uptake in England. We linked the Million Migrant cohort (which includes non-EU migrants and resettled refugees) to the national COVID-19 vaccination dataset, using a stepwise deterministic matching procedure adapted from NHS Digital, and compared migrants with the general population. For migrants who linked to at least one vaccination record, we estimate temporal trends in first dose uptake and differences in second and third dose uptake and consequent delays between Dec 8, 2020, and April 20, 2022, by age, visa type, and ethnicity. FindingsOf the 465 470 migrants who linked to one or more vaccination record, 427 073 (91·8%) received a second dose and 238 721 (51·3%) received a third. Migrants (>30 years) reached 75% first-dose coverage between 1 and 2 weeks after the general population in England, with the gap widening to 6 weeks for younger migrants (16–29 years). Refugees specifically had a higher risk of a delayed second dose (odds ratio 1·75 [95 CI% 1·62–1·88]) and third dose (1·41 [1·31–1·53]). Older migrants (>65 years) were at least four times more likely to have not received their second or third dose compared with those of the same age in England. InterpretationUptake of the first dose was slower across all age groups for migrants compared with the general population. Refugees and older migrants were more likely to have delayed uptake of COVID-19 vaccines and to not have received their second or third dose. Policymakers, researchers, and practitioners should consider how to best drive uptake of COVID-19 and other routine vaccine doses and understand and address personal and structural barriers to vaccination systems for diverse migrant populations. FundingWellcome Trust and UK Research and Innovation.

Biyolojik Ajan Tedavisi Alan Ağır Astımlı Hastalarda COVID-19 Pandemisi Sırasında Tedaviye Uyumdaki Değişiklikler

Aim: This study aimed to evaluate the effects of the COVID-19 pandemic on treatment adherence in patients with severe asthma who were receiving omalizumab and mepolizumab treatment in our clinic. &#x0D; Material and Method: A total of 53 patients with severe asthma, 45 of whom were using omalizumab and 8 of whom were using mepolizumab, were included in the study. The medical records of the patients were recorded anonymously and retrospectively. &#x0D; Results: It was seen that the rate of patients using omalizumab in the study population decreased during the pandemic period compared to the 1-year period before the pandemic. It was observed that approximately 51% of the patients using omalizumab missed routine treatment doses. The major factor in skipping treatment doses was the fear of contracting COVID-19 upon admission to the hospital. In the mepolizumab group, the rate of using biologic agents during the pandemic period increased compared to 1 year before the pandemic. Dose skipping was observed among 37.5% of the patients in this group and it was found that the major risk factor for skipping a dose was the fear of contracting COVID-19 upon admission to the hospital. &#x0D; Conclusion: In this study, it was found that there was a decrease in the duration and rate of use of biologic agent therapies administered in a health institution under the supervision of a healthcare professional among patients with severe asthma during the pandemic.

Personal dosimetry for positron emitters, and occupational exposures from clinical use of gallium-68

The current status and issues regarding positron dosimetry in nuclear medicine are summarized. The suitability of the United Kingdom Health Security Agency extremity and eye beta-gamma personal thermoluminescence dosemeters are then considered. Monte Carlo modelling is performed to determine their responses and derive sets of calibration factors, along with H p(0.07) and H p(3) conversion coefficients, for carbon-11, nitrogen-13, oxygen-15, fluorine-18 and gallium-68 sources, which are commonly used in positron emission tomography (PET) computed tomography; data for these isotopes is assumed extrapolatable to other positron sources. It is found that the dosemeters are adequate for assessing exposures to PET radionuclides, even if their routine calibrations to caesium-137 were maintained. An idealized set of measurements representing gallium-68 exposure scenarios is then described, including reproducible mock-ups of individuals manipulating vials and syringes. Finally, a short case-study is presented that explores occupational doses during routine clinical use of gallium-68. The extremity dosemeter results demonstrated significant variations dependent upon the exposure conditions, with some seen to be comparatively large; whole-body and eye dose rates per activity were found to be lower. The importance of routine dose monitoring of workers is emphasized, with the need for a longer-termed follow-up study demonstrated.

Systemic exposure to hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in New York City.

AimTo investigate the relationship between systemic exposure to hydroxychloroquine (HCQ) and its metabolite desethylhydroxychloroquine (DHCQ) and clinical outcome in severely ill patients treated with a standard oral dose regimen of HCQ during the first wave of COVID‐19 in New York City.MethodsWe correlated retrospective clinical data with drug exposure prospectively assessed from convenience samples using population pharmacokinetics and Bayesian estimation. Systemic exposure was assessed in 215 patients admitted to ICU or COVID‐ward for whom an interleukin‐6 level was requested and who were still alive 24 hours after the last dose of HCQ. Patients received oral HCQ 600 mg twice daily on day 1 followed by 4 days of 400 mg daily.ResultsFifty‐three precent of the patients were intubated at 5.4 ± 6.4 days after admission and 26.5% died at an average of 32.2 ± 19.1 days. QTc at admission was 448 ± 34 ms. Systemic exposure to HCQ and DHCQ demonstrated substantial variability. Cumulative area under the serum concentration–time curve up to infinity for HCQ was 71.4 ± 19.3 h mg/L and for DHCQ 56.5 ± 28.3 h mg/L. Variability in systemic exposure was not clearly explained by renal function, liver function or inflammatory state. In turn, systemic exposure did not correlate with intubation status, survival or QTc prolongation.ConclusionThis study in severely ill patients was not able to find any relationship between systemic exposure to HCQ and DHCQ and clinical outcome at a routine dose regimen and adds to the growing body of evidence that oral HCQ does not alter the course of disease in COVID‐19 patients.

DETERMINATION OF ENTRANCE SURFACE DOSE FOR THREE COMMON PLANAR DIAGNOSTIC X-RAY EXAMINATIONS.

Patient dose during diagnostic radiography procedures primarily depends on the entrance surface dose (ESD) and the exposure area. The purpose of this study was to determine ESD for five common diagnostic X-ray examinations using dose area product and X-ray tube output. The ESDs were estimated in a sample of 340 patients using normalised X-ray output from Philips-PrimaryDiagnost digital X-ray machine equipped with digital flat panel scintillator detector. The resultant mean ESDs for chest postero-anterior/lateral, lumbar spine antero-posterior (AP)/lateral and abdomen AP were 0.49, 2.00, 5.74, 12.79 and 4.62mGy, respectively. The mean and third quartile ESD values of this study were significantly higher than the values found in the literature. This can be attributed to the lower tube potential (kVp) values and the higher tube current-time products (mAs). The methodology used here is a better option for low-resources countries for routine dose monitoring.

Deep learning-based virtual noncalcium imaging in multiple myeloma using dual-energy CT.

Dual-energy CT with virtual noncalcium (VNCa) images allows the evaluation of focal intramedullary bone marrow involvement in patients with multiple myeloma. However, current commercial VNCa techniques suffer from excessive image noise and artifacts due to material decomposition used in synthesizing VNCa images. In this work, we aim to improve VNCa image quality for the assessment of focal multiple myeloma, using an Artificial intelligence based Generalizable Algorithm for mulTi-Energy CT (AGATE) method. AGATE method used a custom dual-task convolutional neural network (CNN) that concurrently carries out material classification and quantification. The material classification task provided an auxiliary regularization to the material quantification task. CNN parameters were optimized using custom loss functions that involved cross-entropy, physics-informed constraints, structural redundancy in spectral and material images, and texture information in spectral images. For training data, CT phantoms (diameters 30 to 45cm)withtissue-mimicking inserts were scanned on a third generation dual-source CT system. Scans were performed at routine dose and half of the routine dose. Small image patches (i.e., 40 × 40 pixels) of tissue-mimicking inserts with known basis material densities were extracted for training samples. Numerically simulated insert materials with various shapes increased diversity of training samples. Generalizability of AGATE was evaluated using CT images from phantoms and patients. In phantoms, material decomposition accuracy was estimated using mean-absolute-percent-error (MAPE), using physical inserts that were not used during the training. Noise power spectrum (NPS) and modulation transfer function (MTF) were compared across phantom sizes and radiation dose levels. Five patients with multiple myeloma underwent dual-energy CT, with VNCa images generated using a commercial method and AGATE. Two fellowship-trained musculoskeletal radiologists reviewed the VNCa images (commercial and AGATE) side-by-side using a dual-monitor display, blinded to VNCa type, rating the image quality for focal multiple myeloma lesion visualization using a 5-level Likert comparison scale (-2=worse visualization and diagnostic confidence, -1=worse visualization but equivalent diagnostic confidence, 0=equivalent visualization and diagnostic confidence, 1=improved visualization but equivalent diagnostic confidence, 2=improved visualization and diagnostic confidence). A post hoc assignment of comparison ratings was performed to rank AGATE images in comparison to commercial ones. AGATE demonstrated consistent material quantification accuracy across phantom sizes and radiation dose levels, with MAPE ranging from 0.7% to 4.4% across all testing materials. Compared to commercial VNCa images, the AGATE-synthesized VNCa images yielded considerably lower image noise (50-77% noise reduction) without compromising noise texture or spatial resolution across different phantom sizes and two radiation doses. AGATE VNCa images had markedly reduced area under NPS curves and maintained NPS peak frequency (0.7 lp/cm to 1.0 lp/cm), with similar MTF curves (50% MTF at 3.0 lp/cm). In patients, AGATE demonstrated reduced image noise and artifacts with improved delineation of focal multiple myeloma lesions (all readers comparison scores indicating improved overall diagnostic image quality [scores 1 or 2]). AGATE demonstrated reduced noise and artifacts in VNCa images and ability to improve visualization of bone marrow lesions for assessing multiple myeloma.

Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability

Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) inhibitor and has a potent antitumor activity against FGFR-aberrant malignancies. Erdafitinib has a narrow therapeutic index, and its pharmacokinetics are influenced by genetic variability and interacting medication. Routine therapeutic drug monitoring and dose adjustment are recommended. This study aims at developing a new UPLC-MS/MS method for determination and quantitation of erdafitinib in human plasma using ibrutinib as an internal standard. The sample ionization was performed by using electrospray ionization in positive mode, and multiple reaction monitoring was used for the quantification of target analytes. The chromatographic separation of erdafitinib and IS was achieved by an UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm). Erdafitinib metabolic stability was studied using intrinsic clearance and in vitro half-life. The greenness of the developed method was evaluated using appropriate, analytical Eco-Scale and AGREE software. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r &gt; 0.99 with a limit of quantitation of 0.5 ng/mL. The accuracy and precision were within acceptable limits and the average recovery and matrix effects were 86.11% and 90.51%, respectively. Erdafitinib metabolic stability was studied and its in vitro half-life was 7.28 min and intrinsic clearance was 95.11 µL/min/mg. The assessment of the greenness profile of the method indicated that the method is eco-friendly. The proposed method can be utilized for therapeutic drug monitoring and pharmacokinetic studies.

Monte Carlo modeling of the Elekta Versa HD and patient dose calculation with EGSnrc/BEAMnrc.

IntroductionNumerous studies have proven the Monte Carlo method to be an accurate means of dose calculation. Although there are several commercial Monte Carlo treatment planning systems (TPSs), some clinics may not have access to these resources. We present a method for routine, independent patient dose calculations from treatment plans generated in a commercial TPS with our own Monte Carlo model using free, open‐source software.Materials and methodsA model of the Elekta Versa HD linear accelerator was developed using the EGSnrc codes. A MATLAB script was created to take clinical patient plans and convert the DICOM RTP files into a format usable by EGSnrc. Ten patients’ treatment plans were exported from the Monaco TPS to be recalculated using EGSnrc. Treatment simulations were done in BEAMnrc, and doses were calculated using Source 21 in DOSXYZnrc. Results were compared to patient plans calculated in the Monaco TPS and evaluated in Verisoft with a gamma criterion of 3%/2 mm.ResultsOur Monte Carlo model was validated within 1%/1‐mm accuracy of measured percent depth doses and profiles. Gamma passing rates ranged from 82.1% to 99.8%, with 7 out of 10 plans having a gamma pass rate over 95%. Lung and prostate patients showed the best agreement with doses calculated in Monaco. All statistical uncertainties in DOSXYZnrc were less than 3.0%.ConclusionA Monte Carlo model for routine patient dose calculation was successfully developed and tested. This model allows users to directly recalculate DICOM RP files containing patients’ plans that have been exported from a commercial TPS.

Progress Toward Measles Elimination - South-East Asia Region, 2003-2020.

In 2013, member states of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goal of measles elimination and rubella and congenital rubella syndrome control† by 2020 (1). In 2014, to provide impetus toward achieving this goal, the Regional Director declared measles elimination and rubella control one of the Regional Flagship Priorities. In 2019, SEAR member states declared a revised goal of eliminating both measles and rubella§ by 2023 (2). The recommended strategies to achieve elimination include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities¶ (SIAs); 2) developing and sustaining a sensitive and timely case-based surveillance system that meets recommended performance indicators**; 3) developing and maintaining an accredited laboratory network; 4) achieving timely identification, investigation, and response to measles outbreaks; and 5) collaborating with other public health initiatives to achieve the preceding four strategies. This report updates a previous report and describes progress toward measles elimination in SEAR during 2003-2020 (3). In 2002, coverage with the first dose of a measles-containing vaccine in routine immunization (MCV1) was 70%, and only three countries in SEAR had added a second routine dose of measles-containing vaccine in routine immunization (MCV2). During 2003-2020, all countries introduced MCV2, and estimated coverage with MCV1 increased 35%, from 65% to 88%, and coverage with MCV2 increased 1,233% from 6% to 80%. Approximately 938 million persons were vaccinated in SIAs. Annual reported measles incidence declined by 92%, from 57.0 to 4.8 cases per 1 million population, and estimated deaths decreased by 97%; an estimated 9.3 million deaths were averted by measles vaccination. By 2020, five countries were verified as having achieved measles elimination. To achieve measles elimination in the region by 2023, additional efforts are urgently needed to strengthen routine immunization services and improve measles-containing vaccine (MCV) coverage, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory capacity.

Right selection of oral anticoagulation for stroke prevention in atrial fibrillation

Atrial fibrillation (AF) is considered as one of the most common cardiac arrhythmias worldwide and is always associated with a significantly increased risk of stroke and thromboembolism. VKAs (Warfarin &amp; Acenocoumarol) are highly effective in reducing the risk of stroke in patients with AF, but bleeding issues &amp; disutility sparked the development of direct oral anticoagulants (DOACs) or NOACs (Novel oral anticoagulants). These drugs, offer the convenience of once or twice daily dosing without the need for laboratory monitoring of coagulation activity (PT/ INR) or routine dose adjustment. Various clinical trials proved their non-inferiority to warfarin (VKA) in reducing the risk of stroke or systemic embolism, and each was associated with markedly lower rates of ICH than well-adjusted warfarin. Yet there are no direct head-to-head comparative trials for the efficacy &amp; safety of NOACs. In this review we try to provide patient centric approach to assist Indian physicians in selecting right OAC therapy for SPAF with respect to best possible evidence and recommendations available worldwide.