Biological treatment evaluation in thermoradiotherapy: application in cervical cancer patients.

BACKGROUND: Hyperthermia treatment quality is usually evaluated by thermal (dose) parameters, though hyperthermic radiosensitization effects are also influenced by the time interval between the two modalities. This work applies biological modelling for clinical treatment evaluation of cervical cancer patients treated with radiotherapy plus hyperthermia by calculating the equivalent radiation dose (EQDRT, i.e., the dose needed for the same effect with radiation alone). Subsequent analyses evaluate the impact of logistics. METHODS: Biological treatment evaluation was performed for 58 patients treated with 23-28 fractions of 1.8-2 Gy plus 4-5 weekly hyperthermia sessions. Measured temperatures (T50) and recorded time intervals between the radiotherapy and hyperthermia sessions were used to calculate the EQDRT using an extended linear quadratic (LQ) model with hyperthermic LQ parameters based on extensive experimental data. Next, the impact of a 30-min time interval (optimized logistics) as well as a 4­h time interval (suboptimal logistics) was evaluated. RESULTS: Median average measured T50 and recorded time intervals were 41.2 °C (range 39.7-42.5 °C) and 79 min (range 34-125 min), respectively, resulting in a median total dose enhancement (D50) of 5.5 Gy (interquartile range [IQR] 4.0-6.6 Gy). For 30-min time intervals, the enhancement would increase by ~30% to 7.1 Gy (IQR 5.5-8.1 Gy; p < 0.001). In case of 4­h time intervals, an ~ 40% decrease in dose enhancement could be expected: 3.2 Gy (IQR 2.3-3.8 Gy; p < 0.001). Normal tissue enhancement was negligible (< 0.3 Gy), even for short time intervals. CONCLUSION: Biological treatment evaluation is a useful addition to standard thermal (dose) evaluation of hyperthermia treatments. Optimizing logistics to shorten time intervals seems worthwhile to improve treatment efficacy.

Probable effects of polypharmacy and equivalent doses of psychotropic drugs on prevalence of adverse drug events among psychiatric inpatients in a general hospital in Japan.

OBJECTIVE: In psychiatry, polypharmacy or high psychotropic drug doses increase adverse drug event (ADE) prevalence. However, the full relationship between polypharmacy and ADEs is unclear, and few studies have evaluated dose equivalents for psychotropic drugs for ADEs. Thus, we conducted a retrospective analysis to clarify the effects of polypharmacy and chlorpromazine (CP)-, diazepam (DAP)-, and imipramine- equivalent doses on all ADEs in inpatients. METHODS: Psychiatric inpatients in a Japanese hospital from April 1, 2016 to March 31, 2018, were enrolled. ADE severity and causality were assessed. Multiple logistic regression analyses were performed to evaluate ADE risk factors. RESULTS: Among 462 patients analyzed, out of 471 patients enrolled, 145 (31.4%) experienced ADEs. The causality assessment determined that "possible" was 96.5%. The most common ADEs were nervous system disorders (35%). Multiple logistic regression analyses indicated an increase in ADE prevalence with the number of drugs used (≥5; p = 0.026); CP-equivalent dose (p = 0.048); and endocrine, nutritional, and metabolic disorders (p = 0.045). DAP-equivalent dose; infectious and parasitic diseases; and injury, poisoning, and consequences of other external causes decreased ADE prevalence (p = 0.047, 0.022, and 0.021, respectively). CONCLUSIONS: Avoiding polypharmacy in psychiatric inpatients and adjusting drug regimens to safe equivalent doses could reduce ADEs during hospitalization.

Development of the occupational exposure during the production and application of radiopharmaceuticals in Germany.

An increasing number of radiopharmaceuticals and proteins are available for diagnosing and treating various diseases. The demand for existing and newly developed pharmaceutical radionuclides and proteins is steadily increasing. The radiation exposure levels of workers in the radiopharmaceutical industry and nuclear medicine field are closely monitored, specifically their effective dose and equivalent dose, leading to the question, of whether the dawn of radiopharmaceuticals affects the occupational exposure level. This development is analyzed and evaluated with data from the German National Dose Register. Data shows that the effective dose in the work categories production and distribution of radioisotopes as well as nuclear medicine slightly decreased from 1997 to 2021. Over the same period, the hand equivalent dose in nuclear medicine increases steadily, with no discernible trend in production and distribution of radioisotopes. Over the past few decades, intentional efforts and measures have been taken to ensure radiation protection. Instruments for monitoring and dose reduction must be continuously applied. Given the low effective dose, the focus in future shall be on dose reduction following theaslowasreasonablyachievable principle. The development of the hand equivalent dose should be carefully observed in the upcoming years.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cardiologist's exposure to radiation in cath lab measured with InstadoseTMdosimeter.

INTRODUCTION: complex fluoroscopy-guided interventional procedures in cardiology are known to result in higher radiation doses for patients and staff. PURPOSE: to estimate the equivalent dose received in different regions of the cardiologist's body in catheterism (CATH) and percutaneous coronary intervention (PCI) procedures, as well as to evaluate the effectiveness of monitoring the doses in the catheritization laboratory (cath lab) using a direct ion storage dosimeter. MATERIALS AND METHODS: the InstadoseTMand the thermoluminescent dosimeters (TLD-100) were fixed simultaneously in the following regions of the cardiologist's body: near the eyes (left and right), the trunk region (over the lead apron) and the left ankle. Occupational doses were recorded during 86 procedures (60% CATH). RESULTS: catheterization procedures showed third quartile dose values near to the left eye region equal to 0.10 mSv (TLD-100) and 0.12 (InstadoseTM) and for intervention 0.15 mSv (TLD-100 and InstadoseTM). The doses measured in the trunk region, over the lead apron, were about 13% higher for catheterization procedures and 20% higher for intervention procedures compared to left eye region measurements. The Wilcoxon-Mann-Whitney test was applied for unpaired data for all body regions, comparing the data obtained between the TLD-100 and InstadoseTMdosimeters. For CATH and PCI, the responses of the TLD-100 and InstadoseTMdosimeters are considered equal for all analysed regions (p> 0.05) with the exception of the right eye region. CONCLUSION: the InstadoseTMpassive dosimeter can be useful as a complementary assessment in the monitoring of a cardiologist's personal occupational doses in the cath lab.

New operational quantities (RBE ×Dp lens/Φ) for eye lens neutron dosimetry as a function of energy and angle of incidence in the ICRU 95 formalism.

This paper is a continuation of a study published recently by the authors. It presents and discusses computed personal absorbed dose in the lens of the eye (Dp lens/Φ), and a relative biological effectiveness (RBE)-weighted absorbed dose (in terms of an newly proposed operational quantity RBE ×Dp lens/Φ), conversion coefficients for the lens of the eye for neutron exposure at incident energies from thermal to ∼20 MeV and at angles of incidence from 0°to 90°in 15° increments, at 180° and for rotational incidence irradiation geometry (from 0°to 360°in 5°increments). These conversion coefficients were obtained from a simulation model developed for this study that contains the stylised eye model, embedded in the adult UF-ORNL mathematical phantom, whereby the previously stated RBE-weighted absorbed dose was obtained using the proposed RBE versus neutron energy distribution compiled in a previous paper by the authors. The simulations carried out for this study using the Monte Carlo N-Particle transport code version 6.2, were conducted in a realistic human eye model, for the left and right sensitive and whole volume of the lens of the eye, considering the recent proposed redefinition of the operational quantities for external radiation exposure in International Commission on Radiation Units and Measurements (ICRU) report 95. A comprehensive set of tabulated data for neutron fluence-to-dose conversion coefficients (Dp lens/Φin pGy cm2) and RBE-weighted absorbed dose (RBE ×Dp lens/Φin pGy cm2) conversion coefficients is included in this paper as a function of incident neutron energy and angle of incidence. Data forDp lens/Φ(pGy cm2) are compared to similar data from the literature for validation of our model. Data for RBE ×Dp lens/Φ(in pGy cm2), were also compared to the equivalent operational quantityHp(3,α)/Φ(in pSv cm2) conversion coefficients calculated at 3 mm depth in a cylindrical phantom for different incident neutron energies and angles of incidence from 0°to 75°in 15°increments to demonstrate the relevance of this newly proposed operational quantity for doses resulting in tissue reactions (deterministic effects) which should be quoted in Gray (RBE-weighted absorbed dose, RBE ×D(Gy)), rather than Sievert (Sv) which is reserved for stochastic effects. The current neutron weighted absorbed dose (RBE ×Dp lens) is proposed for the tissue reactions in the eye-lens for neutron radiation as per National Council on Radiation Protection and Measurements report 180 and in line with the recent proposal for the review and revision of the System of Radiological Protection to Keeping the International Commission on Radiological Protection (ICRP) recommendations fit for purpose. This method would bring better alignment between the dose limits in ICRP 118 and the new operational quantity consistent with the units of the new eye-lens dose limits without being overly conservative. The utilization of the proposed new operational quantities, as outlined in ICRU 95, has the potential to address the ongoing challenge in enforcing regulatory limits for neutron eye dose, specifically the use of Gy instead of Sv. It should be noted that the applicability of this will vary from country to country as in many countries the legislation is likely to mandate the use ofHp(3) until the regulation is amended. This approach can serve as an interim solution while awaiting the issuance of the new ICRP general recommendations, which is expected to take several years. Implementing the new operational quantities can contribute to enhancing the accuracy and effectiveness of neutron eye dose limit enforcement.

Ambiental Factors in Parkinson's Disease Progression: A Systematic Review.

Background and Objectives: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. Materials and Methods: A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 µm; PM2.5) was positively associated with disease aggravation in two studies. Short-term PM2.5 exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO2, SO2, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Conclusions: There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings.

Biological modeling in thermoradiotherapy: present status and ongoing developments toward routine clinical use.

Biological modeling for anti-cancer treatments using mathematical models can be very supportive in gaining more insight into dynamic processes responsible for cellular response to treatment, and predicting, evaluating and optimizing therapeutic effects of treatment. This review presents an overview of the current status of biological modeling for hyperthermia in combination with radiotherapy (thermoradiotherapy). Various distinct models have been proposed in the literature, with varying complexity; initially aiming to model the effect of hyperthermia alone, and later on to predict the effect of the combined thermoradiotherapy treatment. Most commonly used models are based on an extension of the linear-quadratic (LQ)-model enabling an easy translation to radiotherapy where the LQ model is widely used. Basic predictions of cell survival have further progressed toward 3 D equivalent dose predictions, i.e., the radiation dose that would be needed without hyperthermia to achieve the same biological effect as the combined thermoradiotherapy treatment. This approach, with the use of temperature-dependent model parameters, allows theoretical evaluation of the effectiveness of different treatment strategies in individual patients, as well as in patient cohorts. This review discusses the significant progress that has been made in biological modeling for hyperthermia combined with radiotherapy. In the future, when adequate temperature-dependent LQ-parameters will be available for a large number of tumor sites and normal tissues, biological modeling can be expected to be of great clinical importance to further optimize combined treatments, optimize clinical protocols and guide further clinical studies.

Real-world safety and effectiveness of rotigotine in patients with Parkinson's disease: analysis of a post-marketing surveillance study in Japan.

OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of rotigotine under daily clinical practice in Parkinson's disease patients. METHODS: The study was a prospective, non-interventional, observational study targeting patients who were treated with rotigotine for the first time, with a 1-year follow-up period from September 2013 to August 2016. RESULTS: There were 603 patients in the safety population and 599 patients in the effectiveness population. The mean age was 71.6 years, and the age group of ≥65 and ≥80 years accounted for 80% and 18.6% of all patients, respectively. The frequency of adverse drug reaction (ADR) was 34.3%, and common ADRs were application site reaction (20.2%), typical for transdermal patches. However, the majority of patients recovered or was recovering from these ADRs and were non-serious. Although ADRs related to non-motor symptoms of Parkinson's disease were observed, most of them were non-serious. Total scores of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) (ON-time) significantly decreased from baseline in the effectiveness population. In the analysis of overall improvement in 12 months of post-treatment, ≥70% of patients achieved mild or greater improvement. The safety profiles and improvements in the UPDRS-III score were similar in both the ≥80 years of age group and younger age group. CONCLUSION: There were no new or notable safety concerns observed, and the effectiveness of rotigotine was suggested in daily clinical practice.

New strategy of a lung compensating technique with STR for total body irradiation.

PURPOSE: To determine the thickness of a soft variable shape tungsten rubber (STR) as a lung compensating filter in total body irradiation. METHODS: A tough water (TW) phantom and tough lung (TL) phantom were used as water and lung-equivalent phantoms. The TW with a thickness of 3 cm simulating the thoracic wall was used (upper layer). The TW or TL with a thickness from 1 to 15 cm (1 cm increments) was placed beneath the upper layer (middle layer). The TW with a thickness of 5 cm simulating the mediastinum was placed beneath the middle layer (lower layer), and a farmer ionization chamber was placed beneath this layer. The relative doses of a 10 MV X-rays were then measured. The TL was compensated in 1 mm increments from 1 to 11 mm of the STR, and the thickness of the STR at the same dose of TW (water equivalent) was obtained. RESULTS: The compensating ability of STR increased as the thickness of the TL increased, and an STR with a thickness of 1 mm reduced the dose by 2%-4%, depending on the thickness of lung. The STR thickness as an equivalent dose of TW per cm of TL was approximately linear, and the thickness was 0.62 mm/cm of TL. CONCLUSION: The STR can be used as a lung compensating filter for a water equivalent dose with 0.62 mm of STR per cm of lung.

On the operational quantity for eye lens neutron dosimetry considering ICRU 95 report.

For planned occupational exposure situations, the International Commission on Radiological Protection (ICRP) publication 118 recommends an equivalent dose limit for the lens of the eye of 20 mSv yr-1averaged over 5 yr with no single year exceeding 50 mSv. Regulatory authorities of various jurisdictions worldwide followed some or all, of the ICRP recommendations and implemented reduced occupational lens of eye dose limits in their legislation. As compliance with the eye-lens dose limit will be based on the summation of doses received from all types of radiation, applicable to a variety of workplaces, the contribution of neutrons to eye lens dose will be important where it contributes a significant fraction of the total dose to the eye lens. This work presents and discusses computed personal absorbed dose (Dlens/Φ), and personal dose equivalent (Hp(3)/Φ) as well as a newly proposed relative biological effectiveness (RBE)-weighted absorbed dose (RBE ×Dlens/Φ) conversion coefficients for the lens of the eye for neutron exposure at incident energies from thermal to ∼20 MeV. TheDlens/Φ coefficients were obtained from a simulation model developed for this study that contains the stylised eye model embedded in the adult UF-ORNL mathematical phantom. The modelling techniques used in these simulations were also used to calculateHp(3)/Φ for the International Commission on Radiation Units and Measurements (ICRU) slab and cylinder phantoms. All simulations carried out for this study utilised the Monte Carlo N-Particle (MCNP) series of codes. The results are compared with the related published data. The issue of compliance with the current equivalent dose limit for the lens of the eye is addressed from a neutron perspective considering the recent proposed redefinition of the operational quantities for external radiation exposure in ICRU report 95. The use of a radiation weighted absorbed dose (RBE ×Dlens, in Gy) is proposed for the tissue reactions in the eye-lens for neutron radiation as per the National Council on Radiation Protection and Measurements report 180, and in line with the recent review and revision of the System of Radiological Protection To Keeping the ICRP Recommendations Fit for Purpose, which states that RBE weighted dose should be used for high-Linear energy transfer (LET) radiations such as neutrons. This confirms the earlier statement in ICRP publication 92, paragraph 297 and reiterated in the Executive summary, paragraph (q) of ICRP publication 118. The proposed approach would provide an operational quantity consistent with the units of the new eye-lens dose limits without being overly conservative.

Radiation exposure to the lens of the eye for Japanese nuclear power plant workers.

In Japan, the radiation-dose limit for the lens of the eye was revised in April 2021. Consequently, for workers, the numerical values of the equivalent dose to the lens of the eye are equal to those of the effective dose. Radiation workers, radiation safety officers and licensees must comply with regulations related to radiation protection and optimize protection. The new guidelines on dose monitoring of the lens of the eye developed by the Japan Health Physics Society recommend for the dose to be estimated near the eye for accurate estimation, when the dose to the lens approaches or exceeds the management criteria. However, there is limited information regarding the non-uniform exposure of nuclear power plant workers. In this study, the dose equivalents of high-dose-rate workplaces and the personal doses of 88 workers were estimated at four Japanese commercial nuclear power plant sites (RWR: 3 units and BWR: 3 units) and the dose to the lens of the eye and the exposure situations of the workers were analyzed.

Determination of the internal dose due to the intake of 226Ra and 210Pb in drinking water from deep wells in the Metropolitan Region of Recife-Brazil.

The Metropolitan Region of Recife, the capital of the state of Pernambuco in northeastern Brazil, has a high demographic density and developed under a region of marine phosphorus with high concentrations of phosphate that naturally contains uranium ore, producing ionizing radiation from descendants of the radioisotope 238U where 226Ra and 210Pb are of great importance in verifying the probable harmful effects on human health due to environmental radioactivity. The supply of drinking water is the responsibility of the state-owned company COMPESA which uses wells of great depth to complete the supply of drinking water for the entire population. COMPESA and the RAE Group of the Federal University of Pernambuco developed a joint project to assess the concentrations of 226Ra and 210Pb and estimate the equivalent and effective doses caused by ingesting these radiation sources. According to the above, this research aimed to evaluate concentrations of 226Ra and 210Pb in drinking water samples from 110 deep wells in Recife. The activities of 226Ra and 210Pb ranged from 1.4 ± 0.3 to 119.3 ± 12.9 and from 25.6 ± 3.3 to 563.2 ± 45.6 mBq.L-1, with arithmetic means of 48.1 ± 3.8 and 231.1 ± 20 mBq.L-1, respectively. The equivalent doses average in bone tissue due to 226Ra and 210Pb were 0.45 ± 0.04 and 3.9 ± 0.37 mSv.y-1, and the annual average effective doses were 0.01 ± 0.00 and 0.13 ± 0.01 mSv.y-1, respectively.

The relation between second-generation antipsychotics and laxative use in elderly patients with schizophrenia.

BACKGROUND: We aimed to investigate factors associated with concomitant laxative use among elderly patients with schizophrenia, discharged on second-generation antipsychotics (SGAs), from two large public psychiatric hospitals in Taiwan. METHODS: Elderly patients with schizophrenia who were discharged between 2006 and 2019 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. The Cochrane-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge. RESULTS: A total of 2591 elderly patients with schizophrenia were discharged during the study period, and 1727 of 2591 patients who met the inclusion criteria were included for analysis. Of these 1727 patients, 732 (42.4%) also received concomitant laxatives. Female gender, mood stabiliser use and concomitant diabetes mellitus were found to be associated with increased laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and sulpiride were associated with comparable rates of laxative use. Laxative use rates grew over time from 30.8% in 2006 to 46.6% in 2019 (z = 4.83, P < 0.001). CONCLUSIONS: Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible.

Improved biological dosimetric margin model for different PTV margins with stereotactic body radiation therapy in homogeneous and nonhomogeneous tumor regions.

Background: The purpose of this study was to improve the biological dosimetric margin (BDM) corresponding to different planning target volume (PTV) margins in homogeneous and nonhomogeneous tumor regions using an improved biological conversion factor (BCF) model for stereotactic body radiation therapy (SBRT). Materials and methods: The PTV margin was 5-20 mm from the clinical target volume. The biologically equivalent dose (BED) was calculated using the linear-quadratic model. The biological parameters were α/ß = 10 Gy, and the dose per fraction (DPF) was d = 3-20 Gy/fr. The isocenter was offset at intervals of 1 mm; 95% of the clinical target volume covered more than 90% of the prescribed physical dose, and BED was defined as biological and physical DMs. The BCF formula was defined as a function of the DPF. Results: The difference in the BCF caused by the DPF was within 0.05 for the homogeneous and nonhomogeneous phantoms. In the virtual nonhomogeneous phantom, the data with a PTV margin of 10-20 mm were not significantly different; thus, these were combined to fit the BCF. In the virtual homogeneous phantom, the BCF was fitted to each PTV margin. Conclusions: The current study improved a scheme to estimate the BDM considering the size of the PTV margin and homogeneous and nonhomogeneous regions. This technique is expected to enable BED-based treatment planning using treatment systems based on physical doses for SBRT.

Celecoxib significantly reduces opioid use after shoulder arthroplasty.

BACKGROUND: The opioid crisis has illuminated the risks of opioid use for pain management, with renewed interest in reducing opioid consumption after common orthopedic procedures. Anti-inflammatory medication is an important component of multimodal pain management for patients undergoing orthopedic surgery. The purpose of this study was to evaluate the effect of celecoxib on pain control and opioid use after shoulder surgery. METHODS: Patients scheduled for either total shoulder replacement (group 1) or rotator cuff repair (group 2) were candidates for the study. The exclusion criteria included allergy to celecoxib, coagulopathy, use of anticoagulants, baseline use of long-acting opioids, and a history of medical conditions such as myocardial infarction or stroke. Consenting patients were randomized by type of procedure using block randomization to receive either placebo or celecoxib 1 hour prior to the procedure and for 3 weeks postoperatively. The primary outcome measure assessed was opioid utilization as measured by morphine-equivalent dose (MED). Secondary outcome measures included pain scores at 3 and 6 weeks postoperatively. Data were analyzed using multiple linear regression. RESULTS: Of 1081 patients scheduled for either total shoulder replacement or rotator cuff repair from February 2014 to February 2018, 78 were enrolled for arthroplasty (group 1, with 39 receiving celecoxib and 39 receiving placebo) and 79 were enrolled for rotator cuff repair (group 2, with 40 receiving celecoxib and 39 receiving placebo). Compared with the placebo arm, patients prescribed celecoxib took fewer MEDs by -168 (95% confidence interval [CI], -272 to -64; P < .01) at 3 weeks in the total population and by -197.7 (95% CI, -358 to -38; P = .02) in the arthroplasty group. Similarly, at 6 weeks, total MEDs used was -199 (95% CI, -356 to -42; P < .01) in the total population and -270 (95% CI, -524 to -16; P = .04) in the arthroplasty group. No statistically significant differences in opioid consumption were found between study arms in the cuff repair group, at either 3 or 6 weeks. Of note, preoperative opioid use was statistically associated with higher levels of opioid use in the total population and group 1 at 3 and 6 weeks (P < .01 for all) but not in group 2 (P > .05 for both). CONCLUSIONS: Use of morphine equivalents was statistically significantly less at 3 and 6 weeks in patients who took celecoxib in the total population and in the arthroplasty group. Patients prescribed celecoxib for 3 weeks after shoulder surgery took less opioid medication for pain at 3 and 6 weeks. Multimodal pain control using celecoxib is an effective way to reduce postoperative opioid use in shoulder arthroplasty patients. Preoperative opioid use is associated with higher levels of opioid use after shoulder arthroplasty.

Need for harmonisation of extremity dose monitoring in nuclear medicine: results of a survey amongst national dose registries in Europe.

Staff handling radiopharmaceuticals in nuclear medicine (NM) may receive significant extremity doses. Over the last decade in particular there has been an increase in NM procedures and new radiopharmaceuticals have been introduced. However, literature provides limited recent data on the exposure of the extremities. In addition, proper assessment of the equivalent dose to the skin can be difficult when applied to the fingertips. In order to gain insight in the actual exposure and to find out how European countries are dealing with monitoring of the extremities, a survey was performed amongst European regulatory authorities. The questions covered general aspects of the national dose registries (NDRs), the measured extremity doses and the practice of the monitoring of workers. The survey shows that extremity dosimetry is performed for about 25%-50% of the monitored workers in NM. Also, the recorded extremity doses in the NDRs are low (mean values 5-29 mSv yr-1) compared to the dose limit. Despite the recommendations that have been published in the last 10 years, few countries provide guidance on the wearing position of extremity dosemeters and the correction factor to estimate the maximum equivalent skin dose from the measured dose. This may lead to an underestimation of the maximum skin dose. Thermoluminescence ring dosemeters are widely used, but wrist dosemeters are also very common, even though the correlation of the measurement with the maximum skin dose is worse than for ring dosemeters. Furthermore, not all countries had a central registration of the extremity dose at the time the survey was performed.

Human exposure levels to ionizing radiation in Agbara Industrial Estate: an impact of Industrial activities in Nigeria.

A total of fifty-five soil samples were collected from four locations, namely, residential, industrial, dumpsite, and sewage in Agbara industrial estate, Ogun state, Nigeria. The samples were analyzed using a high purity germanium detector (HPGe) to measure the activity concentration of radionuclides. Background radiation measurements were also taken at each point where soil samples were collected using Geiger Muller (GM) counter. The mean activity concentrations measured in the soil samples were 171.33 for 40K, 9.11 for 232Th, and 5.05 for 226Ra in Bq/kg. The mean absorbed dose rate in the air due to radionuclides (40K, 232Th, and 226Ra) in the soil is calculated to be 14.77 nGy/h, and the mean annual effective dose equivalent (AEDE) is 0.02 mSv/year. The mean equivalent dose rate (EDR) from GM counter for background radiation is 0.22 µSv/h, and the mean annual effective dose rate (AEDR) is 0.39 mSv/year. These values are below the world average values, except EDR and AEDR with mean values higher than the world standard. The comparison of radiation dose rates revealed that radionuclides contributed 6.7% to background radiation. The equivalent dose (EDorgans) for various organs of the body was calculated, and results showed that values do not pose any immediate health hazard. The excess lifetime cancer risk (ELCR) due to exposure to background radiation indicated that the dwellers and industrial workers in the study area may develop cancer over a lifetime due to accumulated dose.

A foundation for reference models for drug combinations with an application to Loewe's reference model.

BACKGROUND: Treating patients with combinations of drugs that have synergistic effects has become widespread practice in the clinic. Drugs work synergistically when the observed effect of a drug combination is larger than the effect predicted by the reference model. The reference model is a theoretical null model that returns the combined effect of given doses of drugs under the assumption that these drugs do not interact. There is ongoing debate on what it means for drugs to not interact. The controversy transcends mathematical punctuality, as different non-interaction principles result in different reference models. A famous reference model that has been in existence for already a long time is Loewe's reference model. Loewe's vision on non-interaction was purely intuitive: two drugs do not interact if all combinations of doses that result in a certain given effect lie on a straight line. RESULTS: We show that Loewe's reference model can be obtained from much more fundamental principles. First, we introduce the new notion of complementary dose. Secondly, we reformulate the existing concept of equivalent dose, whereby our formulation is more general than existing ones. Finally, a very general non-interaction principle is put forward. The proposed non-interaction principle represents a certain interplay between complementary and equivalent doses: drugs are non-interacting if complementarity is preserved under equivalence. It is then shown that Loewe's reference model naturally follows from these principles by an appropriate choice of complementarity. CONCLUSIONS: The presented work increases insight into Loewe's reference model for drug combinations, which is realized by the introduction of a very general non-interaction principle that does not refer to any specific dose-response curve, nor to any property of applicable dose-response curves.

Assessment of biological dosimetric margin for stereotactic body radiation therapy.

PURPOSE: To develop a novel biological dosimetric margin (BDM) and to create a biological conversion factor (BCF) that compensates for the difference between physical dosimetric margin (PDM) and BDM, which provides a novel scheme of a direct estimation of the BDM from the physical dose (PD) distribution. METHODS: The offset to isocenter was applied in 1-mm steps along left-right (LR), anterior-posterior (AP), and cranio-caudal (CC) directions for 10 treatment plans of lung stereotactic body radiation therapy (SBRT) with a prescribed dose of 48 Gy. These plans were recalculated to biological equivalent dose (BED) by the linear-quadratic model for the dose per fraction (DPF) of d = 3-20 Gy/fr and α / ß = 3 - 10 . BDM and PDM were defined so that the region that satisfied that the dose covering 95% (or 98%) of the clinical target volume was greater than or equal to the 90% of the prescribed PD and BED, respectively. An empirical formula of the BCF was created as a function of the DPF. RESULTS: There was no significant difference between LR and AP directions for neither the PDM nor BDM. On the other hand, BDM and PDM in the CC direction were significantly larger than in the other directions. BCFs of D95% and D98% were derived for the transverse (LR and AP) and longitudinal (CC) directions. CONCLUSIONS: A novel scheme to directly estimate the BDM using the BCF was developed. This technique is expected to enable the BED-based SBRT treatment planning using PD-based treatment planning systems.