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Frontiers in Oncology 2022Dose painting (DP) is a radiation therapy (RT) strategy for patients with heterogeneous tumors delivering higher dose to radiation resistant regions and less to...
PURPOSE
Dose painting (DP) is a radiation therapy (RT) strategy for patients with heterogeneous tumors delivering higher dose to radiation resistant regions and less to sensitive ones, thus aiming to maximize tumor control with limited side effects. The success of DP treatments is influenced by the spatial accuracy in dose delivery. Adaptive RT (ART) workflows can reduce the overall geometric dose delivery uncertainty. The purpose of this study is to dosimetrically compare ART and non-adaptive conventional RT workflows for delivery of DP prescriptions in the treatment of prostate cancer (PCa).
MATERIALS AND METHODS
We performed a planning and treatment simulation study of four study arms. Adaptive and conventional workflows were tested in combination with DP and Homogeneous dose. We used image data from 5 PCa patients that had been treated on the Elekta Unity MR linac; the patients had been imaged in treatment position before each treatment fraction (7 in total). The local radiation sensitivity from apparent diffusion coefficient maps of 15 high-risk PCa patients was modelled in a previous study. these maps were used as input for optimization of DP plans aiming for maximization of tumor control probability (TCP) under rectum dose constraints. A range of prostate doses were planned for the homogeneous arms. Adaptive plans were replanned based on the anatomy-of-the-day, whereas conventional plans were planned using a pre-treatment image and subsequently recalculated on the anatomy-of-the-day. The dose from 7 fractions was accumulated using dose mapping. The endpoints studied were the TCP and dose-volume histogram metrics for organs at risk.
RESULTS
Accumulated DP doses (adaptive and conventional) resulted in high TCP, between 96-99%. The largest difference between adaptive and conventional DP was 2.6 percentage points (in favor of adaptive DP). An analysis of the dose per fraction revealed substantial target misses for one patient in the conventional workflow that-if systematic-could jeopardize the TCP. Compared to homogeneous prescriptions with equal mean prostate dose, DP resulted in slightly higher TCP.
CONCLUSION
Compared to homogeneous dose, DP maintains or marginally increases the TCP. Adaptive DP workflows could avoid target misses compared to conventional workflows.
PubMed: 36237318
DOI: 10.3389/fonc.2022.973067 -
Therapie 2023Nonadherence to the prescribed medication can result in a poor treatment outcome. This study determined the impacts of multiple missed dose or delayed dose scenarios on...
AIM OF THE STUDY
Nonadherence to the prescribed medication can result in a poor treatment outcome. This study determined the impacts of multiple missed dose or delayed dose scenarios on quetiapine (QTP) pharmacokinetics and pharmacodynamics.
METHODS
QTP concentration-time profiles and Brief Psychiatric Rating Scale (BPRS) scores under multiple missed doses and delayed dose scenarios were simulated using Monte Carlo simulations and compared with those of the full adherence scenario using the Mann-Whitney U test. The simulations were performed using the model structure and parameter estimates obtained from Kimko et al's study.
RESULTS
Missing one, two and three consecutive QTP doses significantly decreased trough concentration (C) by 71.4, 103, and 128ng/mL. However, C rapidly increased to values close to those of the full adherence scenario when the regular dose was resumed. Further, all missed dose scenarios did not significantly impact the maximum percent reduction of BPRS score from baseline, but significant impacts on the minimum percent reduction of BPRS score from baseline were observed. However, the change in BPRS score from the full adherence scenario rapidly resumed when the regular dose was taken. Moreover, this study identified that a delayed dose as late as 6 hours did not significantly impact the maximum concentrations when the regular dose was resumed.
CONCLUSION
Based on the simulations, a missed dose can be taken as late as 6 hours before the next scheduled dose, otherwise it should be skipped. For multiple missed doses scenarios, QTP pharmacokinetics and pharmacodynamics rapidly returned to the stage close to the full adherence scenario when a single regular dose was resumed.
PubMed: 36210213
DOI: 10.1016/j.therap.2022.08.001 -
Expert Review of Gastroenterology &... Sep 2022Colonoscopy is a fundamental tool in colorectal cancer (CRC) prevention. Nevertheless, one-fourth of colorectal neoplasms are still missed during colonoscopy,... (Review)
Review
INTRODUCTION
Colonoscopy is a fundamental tool in colorectal cancer (CRC) prevention. Nevertheless, one-fourth of colorectal neoplasms are still missed during colonoscopy, potentially being the main reason for post-colonoscopy colorectal cancer (PCCRC). Adenoma detection rate (ADR) is currently known as the best quality indicator correlating with PCCRC incidence.
AREAS COVERED
We performed a literature review in order to summarize evidences investigating key factors affecting ADR: endoscopists education and training, patient management, endoscopic techniques, improved navigation (exposition defect), and enhanced lesions recognition (vision defect) were considered.
EXPERT OPINION
'Traditional' factors, such as split dose bowel preparation, adequate withdrawal time, and right colon second view, held a significant impact on ADR. Several devices and technologies have been developed to promote high-quality colonoscopy, however artificial intelligence may be considered the most promising tool for ADR improvement, provided that endoscopists education and recording are guaranteed.
Topics: Humans; Artificial Intelligence; Adenoma; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer
PubMed: 36151898
DOI: 10.1080/17474124.2022.2128761 -
MMWR. Morbidity and Mortality Weekly... Oct 2021Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across...
Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).
Topics: Adolescent; Child; Child, Preschool; Diphtheria-Tetanus-Pertussis Vaccine; Global Health; Goals; Humans; Immunization Programs; Immunization Schedule; Infant; Measles Vaccine; Poliovirus Vaccines; Vaccination Coverage; Vaccines; World Health Organization
PubMed: 34710074
DOI: 10.15585/mmwr.mm7043a1 -
Vaccine Sep 2022'Zero-dose' refers to a person who does not receive a single dose of any vaccine in the routine national immunization schedule, while 'missed dose' refers to a person... (Review)
Review
'Zero-dose' refers to a person who does not receive a single dose of any vaccine in the routine national immunization schedule, while 'missed dose' refers to a person who does not complete the schedule. These peopleremain vulnerable to vaccine-preventable diseases, and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. Globally, more 22.7 million children are estimated to be zero- or missed-dose, of which an estimated 3.1 million (∼14 %) reside in Nigeria.We conducted a scoping review tosynthesize recent literature on risk factors and interventions for zero- and missed-dosechildren in Nigeria. Our search identified 127 papers, including research into risk factors only (n = 66); interventions only (n = 34); both risk factors and interventions (n = 18); and publications that made recommendations only (n = 9). The most frequently reported factors influencing childhood vaccine uptake were maternal factors (n = 77), particularly maternal education (n = 22) and access to ante- and perinatal care (n = 19); heterogeneity between different types of communities - including location, region, wealth, religion, population composition, and other challenges (n = 50); access to vaccination, i.e., proximity of facilities with vaccines and vaccinators (n = 37); and awareness about immunization - including safety, efficacy, importance, and schedules (n = 18).Literature assessing implementation of interventions was more scattered, and heavily skewed towards vaccination campaigns and polio eradication efforts. Major evidence gaps exist in how to deliver effective and sustainable routine childhood immunization. Overall, further work is needed to operationalise the learnings from these studies, e.g. through applying findings to Nigeria's next review of vaccination plans, and using this summary as a basis for further investigation and specific recommendations on effective interventions.
Topics: Child; Female; Humans; Immunization; Immunization Programs; Infant; Nigeria; Poliomyelitis; Pregnancy; Vaccination; Vaccines
PubMed: 35973864
DOI: 10.1016/j.vaccine.2022.07.058 -
Bulletin of Mathematical Biology Dec 2021Medication adherence is a well-known problem for pharmaceutical treatment of chronic diseases. Understanding how nonadherence affects treatment efficacy is made...
Medication adherence is a well-known problem for pharmaceutical treatment of chronic diseases. Understanding how nonadherence affects treatment efficacy is made difficult by the ethics of clinical trials that force patients to skip doses of the medication being tested, the unpredictable timing of missed doses by actual patients, and the many competing variables that can either mitigate or magnify the deleterious effects of nonadherence, such as pharmacokinetic absorption and elimination rates, dosing intervals, dose sizes, and adherence rates. In this paper, we formulate and analyze a mathematical model of the drug concentration in an imperfectly adherent patient. Our model takes the form of the standard single compartment pharmacokinetic model with first-order absorption and elimination, except that the patient takes medication only at a given proportion of the prescribed dosing times. Doses are missed randomly, and we use stochastic analysis to study the resulting random drug level in the body. We then use our mathematical results to propose principles for designing drug regimens that are robust to nonadherence. In particular, we quantify the resilience of extended release drugs to nonadherence, which is quite significant in some circumstances, and we show the benefit of taking a double dose following a missed dose if the drug absorption or elimination rate is slow compared to the dosing interval. We further use our results to compare some antiepileptic and antipsychotic drug regimens.
Topics: Anticonvulsants; Humans; Mathematical Concepts; Medication Adherence; Models, Biological; Treatment Outcome
PubMed: 34928435
DOI: 10.1007/s11538-021-00976-3 -
International Journal of Pharmaceutics Jul 2022Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis... (Review)
Review
Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis medications are among those commonly reported. This review provides a summary of the tuberculosis antibiotic cocrystals reported in the literature, providing the main results on current tuberculosis medications utilized in cocrystals. Moreover, anti-tuberculosis cocrystals limitations and advantages are described, including evidence for enhanced solubility, stability and effect. Opportunities to enhance anti-tuberculosis medications and fixed dose combinations using cocrystals are given. Several cocrystal pairs are suggested to enhance the effectiveness of anti-tuberculosis drugs.
Topics: Anti-Bacterial Agents; Biological Availability; Crystallization; Solubility
PubMed: 35738333
DOI: 10.1016/j.ijpharm.2022.121924 -
Eastern Mediterranean Health Journal =... Sep 2023Every year, WHO and UNICEF estimate the immunization coverage for 195 Member States, based on reported data and independent coverage surveys (1,2). These estimates...
Every year, WHO and UNICEF estimate the immunization coverage for 195 Member States, based on reported data and independent coverage surveys (1,2). These estimates indicate progress in reaching children with life-saving vaccines while identifying coverage gaps (3). The 2022 estimates were much awaited, given that the COVID-19 pandemic caused a setback in coverage (1). Overall, there are encouraging signs of recovery in the WHO Eastern Mediterranean Region (EMR). For example, coverage of the third dose diphtheria-pertussis-tetanus containing vaccine (DTPcv3) and the second dose measles containing vaccine (MCV2), both almost restored or exceeded their 85% and 76% pre-pandemic 2019 levels, respectively (1). However, there are disparities across countries. Low-income countries with fragile, weak health systems and those in conflict situation are lagging. The number of children who missed their routine first dose of measles immunization increased from 3 million in 2019 to 3.16 million in 2022 (1). This underperformance, along with the accumulated immunity gap in 2020-2021, exposes us to the risk of preventable deadly outbreaks.
Topics: Child; Humans; Infant; Pandemics; Immunization Programs; COVID-19; Immunization; Vaccination; Measles Vaccine; Diphtheria-Tetanus-Pertussis Vaccine; Mediterranean Region; Measles; Immunization Schedule
PubMed: 37776128
DOI: 10.26719/2023.29.9.681 -
Acta Oncologica (Stockholm, Sweden) Jan 2022Re-irradiation (reRT) is a promising technique for patients with localized recurrence in a previously irradiated area but presents major challenges. These include how to...
BACKGROUND
Re-irradiation (reRT) is a promising technique for patients with localized recurrence in a previously irradiated area but presents major challenges. These include how to deal with anatomical change between two courses of radiotherapy and integration of radiobiology when summating original and re-irradiation doses. The Support Tool for Re-Irradiation Decisions guided by Radiobiology (STRIDeR) project aims to develop a software tool for use in a commercial treatment planning system to facilitate more informed reRT by accounting for anatomical changes and incorporating radiobiology. We evaluated three approaches to dose summation, incorporating anatomical change and radiobiology to differing extents.
METHODS
In a cohort of 21 patients who previously received pelvic re-irradiation the following dose summation strategies were compared: (1) Rigid registration (RIR) and physical dose summation, to reflect the current clinical approach, (2) RIR and radiobiological dose summation in equivalent dose in 2 Gy fractions (EQD2), and (3) Patient-specific deformable image registration (DIR) with EQD2 dose summation.
RESULTS
RIR and physical dose summation (Strategy 1) resulted in high cumulative organ at risk (OAR) doses being 'missed' in 14% of cases, which were highlighted by EQD2 dose summation (Strategy 2). DIR (with EQD2 dose summation; Strategy 3) resulted in improved OAR overlap and distance to agreement metrics compared to RIR (with EQD2 dose summation; Strategy 2) and was consistently preferred in terms of clinical utility. DIR was considered to have a clinically important impact on dose summation in 38% of cases.
CONCLUSION
Re-irradiation cases require individualized assessment when considering dose summation with the previous treatment plan. Fractionation correction is necessary to meaningfully assess cumulative doses and reduce the risk of unintentional OAR overdose. DIR can add clinically relevant information in selected cases, especially for significant anatomical change. Robust solutions for cumulative dose assessment offer the potential for future improved understanding of cumulative OAR tolerances.
Topics: Dose Fractionation, Radiation; Humans; Pelvis; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Re-Irradiation
PubMed: 34586938
DOI: 10.1080/0284186X.2021.1982145 -
British Journal of Nursing (Mark Allen... Aug 2023Elective surgical patients need accurate drug charts to reduce missed medication doses, decreasing the chance of peri-operative complications. The quality improvement...
Elective surgical patients need accurate drug charts to reduce missed medication doses, decreasing the chance of peri-operative complications. The quality improvement project described in this article used four interventions to improve the percentage of missed medication doses. A driver diagram was produced to interrogate the current pathway which highlighted multiple interventions, including changes to elective pro formas, the initial clerking process and nurse-based prescribing. Once implemented, a plan-do-study-act (PDSA) cycle was completed as per NHS Improvement guidelines. Overall, missed medication dose percentage decreased from 9.8% to 0% after the interventions. Two of these changes have been deemed sustainable and have been integrated into elective patient pathways, improving both patient safety and streamlining surgical elective patient services. This project highlights the importance of prescribing practice in a multidisciplinary team. Simple changes to established systems allow for better patient care, and the authors' project provides evidence that empowering nursing staff to take the lead in the medication management of patients can reduce the likelihood of negative outcomes in a patient's admission.
Topics: Humans; Elective Surgical Procedures; Hospitalization; Patient Safety; Patients; Quality Improvement
PubMed: 37596075
DOI: 10.12968/bjon.2023.32.15.730