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JAMA Surgery Mar 2020Initial whole-body computed tomography (WBCT) for screening patients with suspected blunt multiple trauma remains controversial and a source of excess radiation exposure.
IMPORTANCE
Initial whole-body computed tomography (WBCT) for screening patients with suspected blunt multiple trauma remains controversial and a source of excess radiation exposure.
OBJECTIVE
To determine whether low-dose WBCT scanning using an iterative reconstruction algorithm does not increase the rate of missed injury diagnoses at the point of care compared with standard-dose WBCT with the benefit of less radiation exposure.
DESIGN, SETTING, AND PARTICIPANTS
This quasi-experimental, prospective time-series cohort study recruited 1074 consecutive patients admitted for suspected blunt multiple trauma to an academic metropolitan trauma center in Germany from September 3, 2014, through July 26, 2015, for the standard-dose protocol, and from August 7, 2015, through August 20, 2016, for the low-dose protocol. Five hundred sixty-five patients with suspected blunt multiple trauma prospectively received standard-dose WBCT, followed by 509 patients who underwent low-dose WBCT. Confounding was controlled by segmented regression analysis and a secondary multivariate logistic regression model. Data were analyzed from January 16, 2017, through October 14, 2019.
INTERVENTIONS
Standard- or low-dose WBCT.
MAIN OUTCOMES AND MEASURES
The primary outcome was the incidence of missed injury diagnoses at the point of care, using a synopsis of clinical, surgical, and radiological findings as an independent reference test. The secondary outcome was radiation exposure with either imaging strategy.
RESULTS
Of 1074 eligible patients, 971 (mean [SD] age, 52.7 [19.5] years; 649 men [66.8%]) completed the study. A total of 114 patients (11.7%) had multiple trauma, as defined by an Injury Severity Score of 16 or greater. The proportion of patients with any missed injury diagnosis at the point of care was 109 of 468 (23.3%) in the standard-dose and 107 of 503 (21.3%) in the low-dose WBCT groups (risk difference, -2.0% [95% CI, -7.3% to 3.2%]; unadjusted odds ratio, 0.89 [95% CI, 0.66-1.20]; P = .45). Adjustments for autocorrelation and multiple confounding variables did not alter the results. Radiation exposure, measured by the volume computed tomography dose index, was lowered from a median of 11.7 (interquartile range, 11.7-17.6) mGy in the standard-dose WBCT group to 5.9 (interquartile range, 5.9-8.8) mGy in the low-dose WBCT group (P < .001).
CONCLUSIONS AND RELEVANCE
Low-dose WBCT using iterative image reconstruction does not appear to increase the risk of missed injury diagnoses at the point of care compared with standard-dose protocols while almost halving the exposure to diagnostic radiation.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Missed Diagnosis; Multiple Trauma; Prospective Studies; Radiation Dosage; Radiation Exposure; Tomography, X-Ray Computed; Wounds, Nonpenetrating
PubMed: 31940019
DOI: 10.1001/jamasurg.2019.5468 -
Emerging Infectious Diseases Aug 2022To identify demographic factors associated with delaying or not receiving a second dose of the 2-dose primary mRNA COVID-19 vaccine series, we matched 323 million single...
To identify demographic factors associated with delaying or not receiving a second dose of the 2-dose primary mRNA COVID-19 vaccine series, we matched 323 million single Pfizer-BioNTech (https://www.pfizer.com) and Moderna (https://www.modernatx.com) COVID-19 vaccine administration records from 2021 and determined whether second doses were delayed or missed. We used 2 sets of logistic regression models to examine associated factors. Overall, 87.3% of recipients received a timely second dose (≤42 days between first and second dose), 3.4% received a delayed second dose (>42 days between first and second dose), and 9.4% missed the second dose. Persons more likely to have delayed or missed the second dose belonged to several racial/ethnic minority groups, were 18-39 years of age, lived in more socially vulnerable areas, and lived in regions other than the northeastern United States. Logistic regression models identified specific subgroups for providing outreach and encouragement to receive subsequent doses on time.
Topics: COVID-19; COVID-19 Vaccines; Ethnicity; Humans; Minority Groups; RNA, Messenger; United States; Vaccination
PubMed: 35798008
DOI: 10.3201/eid2808.220557 -
Immunotherapy Oct 2023This study aimed to develop a novel dose strategy for subcutaneous immunotherapy to reduce medical waste and financial burdens for patients who are required to restart...
This study aimed to develop a novel dose strategy for subcutaneous immunotherapy to reduce medical waste and financial burdens for patients who are required to restart subcutaneous immunotherapy. A prospective, nonrandomized concurrent controlled trial was performed to assess the safety and advantages of the novel dose-adjustment protocol compared with the conventional one. 76 subjects were grouped to receive novel or conventional dose-adjustment protocols. The injections, visits and time needed to reach the pre-established dose with the novel regimen were decreased. Furthermore, there were no differences in side reactions between the two groups. The novel protocol seemed safe and well tolerated, offering the advantages of time efficiency and reduced healthcare costs.
Topics: Animals; Humans; Allergens; Pyroglyphidae; Prospective Studies; Rhinitis, Allergic; Injections, Subcutaneous; Immunotherapy; Desensitization, Immunologic; Sublingual Immunotherapy
PubMed: 37585664
DOI: 10.2217/imt-2023-0051 -
Medicine and Science in Sports and... Feb 2020While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise...
PURPOSE
While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise science, there is inadequate detail facilitating the standardized reporting of resistance training adherence in the oncology setting. The purpose of this study was to apply a novel method to report resistance training dose, adherence, and tolerance in patients with cancer.
METHODS
A total of 47 prostate cancer patients (70.1 ± 8.9 yr, body mass index, 28.6 ± 4.0) with bone metastatic disease completed an exercise program for 12 wk. We assessed traditional metrics of adherence (attendance and loss to follow-up), in addition to novel proposed metrics (exercise-relative dose intensity, dose modification, and exercise interruption). Total training volume in kilograms (repetitions × sets × training load (weight)) was calculated for each patient.
RESULTS
Attendance assessed from traditional metrics was 79.5% ± 17.0% and four patients (9%) were lost to follow-up. The prescribed and actual cumulative total dose of resistance training was 139,886 ± 69,150 kg and 112,835 ± 83,499 kg, respectively, with a mean exercise-relative dose intensity of 77.4% ± 16.6% (range: 19.4% -99.4%). Resistance training was missed (1-2 consecutive sessions) or interrupted (missed ≥3 consecutive sessions) in 41 (87%) and 24 (51%) participants, respectively. Training dose was modified (reduction in sets, repetitions, or weight) in 40 (85%) of patients. Importantly, using attendance as a traditional metric of adherence, these sessions would have all counted as adherence to the protocol.
CONCLUSIONS
Traditional reporting metrics of resistance training in exercise oncology may overestimate exercise adherence. Our proposed metrics to capture resistance training dose, adherence, and tolerance may have important applications for future studies and clinical practice.
Topics: Aged; Bone Neoplasms; Exercise Therapy; Fatigue; Follow-Up Studies; Humans; Male; Middle Aged; Patient Compliance; Prostatic Neoplasms; Resistance Training; Retrospective Studies; Weight Lifting
PubMed: 31436734
DOI: 10.1249/MSS.0000000000002127 -
European Radiology Jul 2023Validation of [F]FDG PET/CT at ultralow-dose (0.37 MBq/kg) and compared to imaging at half-dose (1.85 MBq/kg).
OBJECTIVES
Validation of [F]FDG PET/CT at ultralow-dose (0.37 MBq/kg) and compared to imaging at half-dose (1.85 MBq/kg).
METHODS
This prospective head-to-head intraindividual study compared dynamic and static parameters of ultralow-dose with half-dose [F]FDG total-body PET/CT. In static imaging, the ultralow-dose groups of PET images were denoted ULD5, 60-65 min; ULD8, 60-68 min; ULD10, 60-70 min; and ULD15, 60-75 min. The half-dose group images were reconstructed to 60-61, 60-62, 60-63, and 60-75 min, defined as LD1, LD2, LD3, and LD15, respectively. A 5-point Likert scale was used to subjectively evaluate the quality of static PET images, with a score greater than 3 considered to meet the requirements for clinical diagnosis.
RESULTS
Thirty participants were included in this study, and in terms of kinetic indicators, no special differences were found between the two groups of normal organs and lesions. In static images, those in groups ULD8 and LD2 achieved scores of [Formula: see text] 3.0, meeting the requirements for clinical diagnosis. In static imaging, four lesions were missed in the LD1 group with a lesion detectability of 89.7% (35/39). In the meantime, lesions were not missed in the whole ultra-low dose group (ULD5, ULD8, ULD10, and ULD15) and half-dose groups (LD2 and LD3).
CONCLUSIONS
Compared with half-dose imaging, ultralow-dose [F]FDG total-body PET/CT imaging is clinically feasible, and there was no meaningful difference between the two groups of quantitative and qualitative analysis either dynamic or static images. Total-body PET/CT with ultralow-dose activity, the corresponding acquisition time of 8 min provides acceptable image quality and lesion detection.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: ChiCTR2000036487 KEY POINTS: • A prospective single-center study showed that the total-body PET scanner allows ultralow-dose [F]FDG imaging with acceptable image quality and lesion detectability. • For the participant, radiation exposure can be reduced with ultralow-dose [F]FDG total-body PET/CT imaging.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Prospective Studies; Feasibility Studies; Tomography, X-Ray Computed; Positron-Emission Tomography
PubMed: 36688971
DOI: 10.1007/s00330-023-09389-3 -
American Journal of Physiology. Heart... May 2021Nicotinic receptors (NRs) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits...
Nicotinic receptors (NRs) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2-subunits and β4-subunits may substitute for each other. In our study, we assessed the hypothetical β-subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4-subunits and α3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology. In the present study, we observed an increase in mRNA levels of the β2 NR subunit in hearts but not vice versa, thus supporting the hypothesis of β NR subunit plasticity that depends on the specific type of missing β-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation.
Topics: Acetylcholine; Animals; Atropine; Cholinesterase Inhibitors; Heart; Hexamethonium; Isoproterenol; Mice; Mice, Knockout; Muscarinic Antagonists; Myocardium; Neostigmine; Receptors, Nicotinic
PubMed: 33769917
DOI: 10.1152/ajpheart.00995.2020 -
Neurology Feb 2023Delayed or missed antiseizure medications (ASMs) doses are common during long-term or lifelong antiepilepsy treatment. This study aims to explore optimal individualized...
BACKGROUND AND OBJECTIVES
Delayed or missed antiseizure medications (ASMs) doses are common during long-term or lifelong antiepilepsy treatment. This study aims to explore optimal individualized remedial dosing regimens for delayed or missed doses of 11 commonly used ASMs.
METHODS
To explore remedial dosing regimens, Monte Carlo simulation was used based on previously identified and published population pharmacokinetic models. Six remedial strategies for delayed or missed doses were investigated. The deviation time outside the individual therapeutic range was used to evaluate each remedial regimen. The influences of patients' demographics, concomitant medication, and scheduled dosing intervals on remedial regimens were assessed. RxODE and Shiny in R were used to perform Monte Carlo simulation and recommend individual remedial regimens.
RESULTS
The recommended remedial regimens were highly correlated with delayed time, scheduled dosing interval, and half-life of the ASM. Moreover, the optimal remedial regimens for pediatric and adult patients were different. The renal function, along with concomitant medication that affects the clearance of the ASM, may also influence the remedial regimens. A web-based dashboard was developed to provide individualized remedial regimens for the delayed or missed dose, and a user-defined module with all parameters that could be defined flexibly by the user was also built.
DISCUSSION
Monte Carlo simulation based on population pharmacokinetic models may provide a rational approach to propose remedial regimens for delayed or missed doses of ASMs in pediatric and adult patients with epilepsy.
Topics: Adult; Humans; Child; Epilepsy; Monte Carlo Method; Computer Simulation; Models, Biological; Drug Administration Schedule
PubMed: 36450606
DOI: 10.1212/WNL.0000000000201604 -
Trends in Plant Science Jan 2023Low doses of contaminants and toxins can stimulate pests feeding on contaminated tissues of host plants and enhance herbivore activity and plant damage. These effects...
Low doses of contaminants and toxins can stimulate pests feeding on contaminated tissues of host plants and enhance herbivore activity and plant damage. These effects are opposite to those of high toxic doses, have largely been missed so far, and could compromise crop production. Thus, they deserve further consideration and study.
Topics: Hormesis; Plants; Environmental Pollutants; Herbivory
PubMed: 36280534
DOI: 10.1016/j.tplants.2022.09.006 -
Tropical Medicine and Infectious Disease Oct 2023The persistent burden of chronic hepatitis B among ≤5-year-old children in Africa suggests missed opportunities for controlling mother-to-child transmission (MTCT) of... (Review)
Review
The persistent burden of chronic hepatitis B among ≤5-year-old children in Africa suggests missed opportunities for controlling mother-to-child transmission (MTCT) of the hepatitis B virus (HBV). This scoping review maps the evidence base on the risk of HBV MTCT, the status of HBV MTCT mitigation strategies including hepatitis B birth-dose vaccination, and the role of systems complexity on the suboptimal adoption and performance of hepatitis B birth-dose vaccination programs in Africa. Overall, 88 peer-reviewed and grey literature sources published between 2000-2022 were included in this review. The growing evidence base consistently argues for a heightened risk of HBV MTCT amidst the HIV co-epidemic in the region. Without universal HBV screening programs integrated within broader antenatal care services, current selective hepatitis B birth-dose vaccination is unlikely to effectively interrupt HBV MTCT. We underscore critical health systems-related barriers to universal adoption and optimal performance of hepatitis B birth-dose vaccination programs in the region. To better conceptualize the role of complexity and system-wide effects on the observed performance of the program, we propose an adapted systems-based logic model. Ultimately, exploring contextualized complex systems approaches to scaling-up universal hepatitis B birth-dose vaccination programs should form an integral part of the regional research agenda.
PubMed: 37888602
DOI: 10.3390/tropicalmed8100474 -
American Journal of Respiratory and... Jan 2023"Forgiveness" charts the ability of a drug or regimen to withstand nonadherence without negative clinical consequences. We aimed to determine the influence of regimen...
"Forgiveness" charts the ability of a drug or regimen to withstand nonadherence without negative clinical consequences. We aimed to determine the influence of regimen length, regimen drugs, and dosing, and when during treatment nonadherence occurs on the forgiveness of antituberculosis regimens. Using data from three randomized controlled trials comparing experimental 4-month regimens for drug-sensitive tuberculosis with the standard 6-month regimen, we used generalized linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. The percentage of doses taken and the absolute number of doses missed were calculated during the intensive and continuation phases of treatment, and overall. A mediation analysis was undertaken to determine how much the association between intensive phase dose-taking and the negative composite outcome was mediated through continuation phase dose-taking. Forgiveness of the 4- and 6-month regimens did not differ for any treatment period. Importantly, 4-month regimens were no less forgiving of small numbers of absolute missed doses than the 6-month regimen (e.g., for 3-7 missed doses vs. no missed doses [baseline], 6-month regimen adjusted risk ratio 1.65 [95% confidence interval, 0.80-3.41] and 4-month regimens 1.80 [1.33-2.45]). No 4-month regimen was conclusively more forgiving than another. We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship. With the current appetite for, and progress toward, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of nonadherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected.
Topics: Humans; Antitubercular Agents; Clinical Protocols; Tuberculosis; Randomized Controlled Trials as Topic
PubMed: 35952354
DOI: 10.1164/rccm.202201-0144OC