scholarly journals High National Rates of High-Dose Dopamine Agonist Prescribing for RLS

SLEEP ◽  
2021 ◽  
Author(s):  
John W Winkelman
Keyword(s):  
Dopamine Agonist ◽  
Daily Maximum ◽  
High Dose ◽  
Patient Age ◽  
Dose Rates ◽  
Patient Âgé ◽  
Related Symptom ◽  
Icd 10 ◽  
High Doses ◽  
Very High

Abstract Study Objectives Long-term dopamine agonist (DA) use in restless legs syndrome (RLS) is associated with augmentation, a dose-related symptom worsening leading to further dose escalation to manage RLS. This study investigated rates and factors of high-dose DA prescribing in US RLS patients. Methods This retrospective analysis examined data from a US longitudinal prescriptions database (October 2017–September 2018). Patients diagnosed with RLS (ICD-10 G255.81) without Parkinson’s disease who were prescribed ropinirole, pramipexole, and/or rotigotine were included. Daily DA dosage was categorized: LOW/MID (FDA-approved/guideline or slightly above FDA-approved [pramipexole]); HIGH (101%–149%); VERY HIGH (>150%). Patient counts were converted to US national estimates. Logistic regression of patient counts evaluated factors associated with HIGH/VERY HIGH DA dosing. Results Of 670,404 RLS patients (131,289,331 therapy days), 58.8% were prescribed DA therapy. Overall, 19.1% of RLS patients were prescribed DAs above maximum FDA-approved/guideline daily doses—over half of these were >150% maximum recommended doses; 67.6% of HIGH/VERY HIGH-dose prescriptions were pramipexole (OR [95% CI] pramipexole vs ropinirole, 5.8 [5.7–6.0]). The highest 1% of DA prescriptions were ≥10× the FDA-recommended maximum daily dose. Rates of HIGH/VERY HIGH DA dosing increased with patient age. Twice as many neurologists (31.1%) prescribed HIGH/VERY HIGH doses vs other specialties (OR [95%CI], 2.1 [1.2–2.0]). Conclusions Approximately 20% of DA-treated RLS patients were prescribed doses above the approved and guideline daily maximum. Pramipexole, Neurology as specialty, and patient age were independently associated with HIGH/VERY HIGH DA dosing. Increased education is warranted regarding risks of high-dose DA exposure in RLS.

scholarly journals Quantifying prescribed high dose opioids in the community and risk of overdose

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joe Schofield ◽  
Deborah Steven ◽  
Rebecca Foster ◽  
Catriona Matheson ◽  
Alexander Baldacchino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Service Improvement ◽  
High Dose ◽  
Opioid Overdose ◽  
Opioid Prescribing ◽  
Patient Level ◽  
Strong Opioid ◽  
High Doses ◽  
Strong Opioids ◽  
Very High

Abstract Background Opioid prescribing for a range of health issues is increasing globally. The risk of fatal and non-fatal overdose is increased among people prescribed strong opioids: in high doses in the context of polypharmacy (the use of multiple medications at the same time), especially with other sedatives; and among people with multiple morbidities including cardiorespiratory, hepatic and renal conditions. This study described and quantified the prescribing of strong opioids, comorbidities and other overdose risk factors among those prescribed strong opioids, and factors associated with high/very high opioid dosage in a regional health authority in Scotland as part of a wider service improvement exercise. Methods Participating practices ran searches to identify patients prescribed strong opioids and their characteristics, polypharmacy, and other overdose risk factors. Data were anonymised before being analysed at practice and patient-level. Morphine Equivalent Doses were calculated for patients based on drug/dose information and classed as Low/Medium/High/Very High. Descriptive statistics were generated on the strong opioid patient population and overdose risk factors. The relationship between the prescribing of strong opioids and practice/patient-level factors was investigated using linear and logistic regression models. Results Eighty-five percent (46/54) of GP practices participated. 12.4% (42,382/341,240) of individuals in participating practices were prescribed opioids and, of these, one third (14,079/42,382) were prescribed strong opioids. The most common comorbidities and overdose risk factors among strong opioid recipients were pain (67.2%), cardiovascular disease (43.2%), and mental health problems (39.3%). There was a positive significant relationship between level of social deprivation among practice caseload and level of strong opioid prescribing (p < 0.001). People prescribed strong opioids tended to be older (mean 59.7 years) and female (8638, 61.4%) and, among a subset of patients, age, gender and opioid drug class were significantly associated with prescribing of High/Very High doses. Conclusions Our findings have identified a large population at potential risk of prescription opioid overdose. There is a need to explore pragmatic models of tailored interventions which may reduce the risk of overdose within this group and clinical practice may need to be tightened to minimise overdose risk for individuals prescribed high dose opioids.

scholarly journals Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4942
Author(s):  
Maria Grazia Ronga ◽  
Marco Cavallone ◽  
Annalisa Patriarca ◽  
Amelia Maia Leite ◽  
Pierre Loap ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Current Knowledge ◽  
High Energy ◽  
High Dose Rate ◽  
Point Of View ◽  
High Dose ◽  
Dose Rates ◽  
High Energy Electrons ◽  
Very High Energy ◽  
Very High

The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.

The radiation chemistry of carbon monoxide at very high dose rates

1970 ◽  
Vol 48 (19) ◽  
pp. 3029-3033 ◽  
Author(s):  
C. Willis ◽  
O. A. Miller
Keyword(s):  
Carbon Dioxide ◽  
Carbon Monoxide ◽  
Excited State ◽  
Oxygen Atom ◽  
Dose Rate ◽  
Electron Accelerator ◽  
Radiation Chemistry ◽  
High Dose ◽  
Dose Rates ◽  
Very High

Carbon monoxide has been irradiated with single intense pulses from an electron accelerator at a dose rate of ~ 2 × 1027 eV g−1 s−1. The yield of carbon dioxide obtained was G(CO2) = 0.7 ± 0.1 with a very small yield of carbon suboxide, G(C3O2) ≤ 0.02.Addition of propene reduces the carbon dioxide yield to almost zero while addition of propane has no effect. This suggests that propene is acting as an oxygen atom scavenger rather than as a quencher of an excited state of carbon monoxide. However, rate constant data do not support this suggestion and it is concluded that the residual yield of carbon dioxide observed at high dose rates arises from reaction 9[Formula: see text]where CO+ is in an A2Π or B2Σ+ state.

Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

2016 ◽  
Vol 61 (14) ◽  
pp. N349-N361 ◽  
Author(s):  
P Fournier ◽  
J C Crosbie ◽  
I Cornelius ◽  
P Berkvens ◽  
M Donzelli ◽  
...  
Keyword(s):  
Absorbed Dose ◽  
High Dose ◽  
X Rays ◽  
Dose Rates ◽  
Absorbed Dose To Water ◽  
Very High

scholarly journals Feasibility Study of a Prostate Cancer FLASH Therapy Treatment With Electrons of High Energy

2021 ◽  
Author(s):  
Alessio Sarti ◽  
Patrizia De Maria ◽  
Battistoni Giuseppe ◽  
Micol De Simoni ◽  
Cinzia Di Felice ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Technological Development ◽  
High Energy ◽  
Planning System ◽  
Treatment Planning System ◽  
High Dose ◽  
Dose Rates ◽  
Very High Energy ◽  
Almost All ◽  
Very High

Abstract Prostate cancer is among the most common cancers in men and one of the leading causes of death worldwide. Different therapies are adopted for its treatment and generally radiotherapy with photons (RT) is the preferred solution in almost all cases. Up to now, in addition to photons, only protons have been implemented as alternative radiotherapy. The use of Very High Energy Electron (VHEE) beams (100-200 MeV) has been suggested in literature but the needed accelerators are more demanding, as far as space and cost are concerned, with respect to standard photon devices, with only limited advantages when compared to protons or other heavy ions. In this contribution we investigate how recent developments in electron beam therapy could reshape the landscape of prostate treatments. The VHEE Treatment Planning System obtained combining an accurate Monte Carlo (MC) simulation with a simple modelling of the FLASH effect (healthy tissues sparing at very high dose rates) is compared with conventional RT. The results demonstrate that FLASH therapy with VHEE beams of 70-130 MeV could represent a valid alternative to standard RT allowing a better sparing of the healthy tissues surrounding the tumour, in the framework of an affordable technological development.

scholarly journals Generation of ultrafast, transient, highly acidic pH spikes in the radiolysis of water at very high dose rates. Relevance for FLASH radiotherapy.

2021 ◽  
Author(s):  
Abida Sultana ◽  
Ahmed Alanazi ◽  
Jintana Meesungnoen ◽  
Jean-Paul Jay-Gerin
Keyword(s):  
High Dose ◽  
Acidic Ph ◽  
Cellular Functions ◽  
Spike Response ◽  
Dose Rates ◽  
Hydronium Ions ◽  
Circular Surface ◽  
Sparing Effect ◽  
Tissue Sparing ◽  
Very High

Monte Carlo multi-track chemistry simulations were carried out to study the effects of high dose rates on the transient yields of hydronium ions (H<sub>3</sub>O<sup>+</sup>) formed during low linear energy transfer (LET) radiolysis of both pure, deaerated and aerated liquid water at 25 °C, in the interval ~1 ps–10 μs. Our simulation model consisted of randomly irradiating water with <i>N</i> interactive tracks of 300-MeV incident protons (LET ~ 0.3 keV/μm), which simultaneously impact perpendicularly on the water within a circular surface. The effect of the dose rate was studied by varying <i>N</i>. Our calculations showed that the radiolytic formation of H<sub>3</sub>O<sup>+</sup> causes the entire irradiated volume to temporarily become very acidic. The magnitude and duration of this abrupt “acid-spike” response depend on the value of <i>N</i>. It is most intense at times less than ~10–100 ns, equal to ~3.4 and 2.8 for <i>N</i> = 500 and 2000 (<i>i.e.</i>, for dose rates of ~1.9 × 10<sup>9</sup> and 8.7 × 10<sup>9</sup> Gy/s, respectively). At longer times, the pH gradually increases for all <i>N</i> values and eventually returns to the neutral value of seven, which corresponds to the non-radiolytic, pre-irradiation concentration of H<sub>3</sub>O<sup>+</sup>. It is worth noting that these early acidic pH responses are very little dependent on the presence or absence of oxygen. Finally, given the importance of pH for many cellular functions, this study suggests that these acidic pH spikes may contribute to the normal tissue-sparing effect of FLASH radiotherapy.

scholarly journals Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

2020 ◽  
Author(s):  
Carlo Cervia ◽  
Jakob Nilsson ◽  
Yves Zurbuchen ◽  
Alan Valaperti ◽  
Jens Schreiner ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Healthcare Workers ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Patient Age ◽  
Mild Disease ◽  
Specific Serum ◽  
Patient Âgé ◽  
Serum Iga ◽  
Very High

AbstractBackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

scholarly journals Unintended Consequence of High-Dose Vitamin C Therapy for an Oncology Patient: Evaluation of Ascorbic Acid Interference With Three Hospital-Use Glucose Meters

2020 ◽  
pp. 193229682093218
Author(s):  
Brooke M. Katzman ◽  
Brandon R. Kelley ◽  
Gayle R. Deobald ◽  
Nikki K. Myhre ◽  
Sean A. Agger ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
High Dose ◽  
Oncology Patient ◽  
Glucose Meter ◽  
High Doses ◽  
The Impact ◽  
Very High ◽  
High Dose Vitamin ◽  
Hospital Use

The use of high-dose vitamin C in cancer care has offered promising results for some patients. However, the intravenous (IV) doses used for these patients can reach concentrations that interfere with some strip-based glucose meters. We characterized the impact of vitamin C interference, from standard to the very high doses used for some cancer protocols, using three different hospital-use glucose meters. For two of the three devices tested, increasing concentrations of ascorbic acid caused false elevations in the glucose measurements. The third glucose meter did not provide inaccurate results, regardless of the vitamin C concentration present. Rather, above a certain threshold, the device generated error messages and no results could be obtained.

scholarly journals Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Josiane F. John ◽  
Diego R. Falci ◽  
Maria Helena Rigatto ◽  
Renata D. Oliveira ◽  
Thaysa G. Kremer ◽  
...  
Keyword(s):  
Renal Failure ◽  
Adverse Event ◽  
Body Weight ◽  
Adverse Events ◽  
Total Dose ◽  
Polymyxin B ◽  
High Dose ◽  
Daily Dose ◽  
High Doses ◽  
Very High

ABSTRACT The use of very high doses of polymyxin B (PMB) against carbapenem-resistant Gram-negative bacilli has been addressed in in vitro experiments as a strategy to improve bacterial killing and suppress resistance emergence. However, the toxicities of very high doses in patients are unknown. We conducted a retrospective cohort study assessing patients receiving PMB at >3 mg/kg of body weight/day or a total dose of ≥250 mg/day. The main outcomes were severe infusion-related adverse events according to the Common Terminology Criteria for Adverse Events and the renal failure category of RIFLE criteria for acute kidney injury (AKI) during treatment. A total of 222 patients were included for analysis of infusion-related events. The mean PMB dose was 3.61 ± 0.97 mg/kg/day (median total dose/day = 268 mg). Severe infusion-related adverse events occurred in two patients, resulting in an incidence of 0.9% (95% confidence interval, 0.2 to 3.2%); one was classified as a life-threatening adverse event, and one was classified as a severe adverse event. Renal failure was analyzed in 115 patients, and 25 (21.7%) patients presented renal failure (54 [47.0%] developed any degree of AKI, categorized as risk [27.8%], injury [25.9%], and failure [46.3%]). Treatment with a vasoactive drug, concomitant treatment with nephrotoxic drugs, and baseline creatinine clearance were independent risk factors for renal failure. Neither the PMB daily dose scaled by body weight nor the total daily dose was associated with renal failure. The in-hospital mortality rate was 60% (134 patients): 26% of deaths (57 patients) occurred during treatment, and none occurred during infusion. Our data suggest that high-dose schemes have an acceptable safety profile and could be further tested in clinical trials assessing strategies to improve patient outcomes and minimize the emergence of PMB resistance.

High Dose Rate Oxygen Implantation for Formation of Silicon-on-Insulator Structures

1990 ◽  
Vol 201 ◽  
Author(s):  
E. Cortesi ◽  
F. Namavar ◽  
R. F. Pinizzotto ◽  
H. Yang
Keyword(s):  
Dose Rate ◽  
Silicon Surface ◽  
High Dose Rate ◽  
Silicon On Insulator ◽  
High Dose ◽  
Surface Oxide Layer ◽  
Dose Rates ◽  
Pit Formation ◽  
Lower Dose Rate ◽  
Very High

AbstractWe have studied Separation by IMplantation of OXygen (SIMOX) processes using very high dose rates (40–60 μA/cm2). For a dose of 4 × 1017 O+/cm2 at 160 keV, the structure formed by implantation at 50 μA/cm2 is very similar to that associated with lower dose rates. The same dose implanted at a dose rate of 60 μA/cm2, however, results in the formation of pits in the silicon surface as well as a somewhat different oxide structure. Implantation through a surface oxide layer appears to result in a structure similar to that associated with lower dose rate implantation. These and higher dose samples suggest that the threshold for pit formation is related to both dose rate and dose.

Sign in / Sign up

Export Citation Format

Share Document