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Results for “Targeted dosing”

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At least 127 records · Page 7Linked to original sources

PubMed1990

Treatment planning for protocol-based radiation therapy.

Many protocol studies are conducted in which patients are assigned to alternative treatment regimens. Typically the dosimetric specifications will define the maximal and minimal target doses and maximal doses to specified critical normal structures, and the success of the study will depend upon the consistency and reliability with which these dose specifications are applied. We have investigated the use of dose-area histograms to ensure complete adherence to protocol dose specifications. A dose prescription is prepared that defines upper and lower target doses as well as normal tissue dose tolerance levels for all organs of interest. In addition, dose-volume histograms are derived which provide quantitative measures of the extent to which each dose limit has been met. This technique can be used during treatment planning to prevent protocol violations of pre-defined severity, or for retroactive correlation of local tumor recurrence and treatment-related morbidity with dose levels in the target and normal tissues. An example is presented for a protocol study of ca prostate, stages A and B, in which seven treatments were evaluated at the mid-plane for protocol violations.

Clinical Trials as Topic↗

PubMed2003

Irradiation of Maconellicoccus hirsutus (Homoptera: Pseudococcidae) for phytosanitation of agricultural commodities.

Studies on the tolerance of pink hibiscus mealybug, Maconellicoccus hirsutus (Green), to ionizing irradiation were undertaken to determine the dose needed to disinfest commodities of this pest. Overall, radiotolerance of M. hirsutus was found to increase with maturity. Target doses of 50 Gy reduced eclosion of eggs to <50%, but doses as great as 750 Gy did not eliminate hatching during the study. At 100 Gy, M. hirsutus eggs, crawlers, and nymphs were controlled, because progeny were not produced despite crawlers and nymphs living for much longer periods than unexposed individuals. Fecundity of treated crawlers and nymphs was greatly impacted by treatment of 100 Gy; crawlers developing into adults produced no eggs, and 10 adults of 3,983 treated nymphs (0.25%) produced 309 eggs. Few adult females exposed as nymphs deposited eggs because male nymphs died during development, which left the females unfertilized. By comparison, 89% of female nymphs treated at 100 Gy and mated as adults with nonirradiated males produced a total of 1,447 eggs (19 eggs per female). Evidence from this study suggests M. hirsutus reproduces sexually, not parthenogenetically. Adults, the most resistant stage, exposed to target doses of 100 Gy produced eggs that were 1.2% viable, from which a small portion of individuals successfully completed development and produced progeny. A target dose of 250 Gy was sufficient to control adult M. hirsutus because, at that dose, none of the eggs produced by 3,093 irradiated adults eclosed. The minimum dose needed to ensure quarantine security is between 100 and 250 Gy.

Animals↗

PubMed2006

Monte Carlo based IMRT dose verification using MLC log files and R/V outputs.

Conventional IMRT dose verification using film and ion chamber measurements is useful but limited with respect to the actual dose distribution received by the patient. The Monte Carlo simulation has been introduced as an independent dose verification tool for IMRT using the patient CT data and MLC leaf sequence files, which validates the dose calculation accuracy but not the plan delivery accuracy. In this work, we propose a Monte Carlo based IMRT dose verification method that reconstructs the patient dose distribution using the patient CT, actual beam data based on the information from the record and verify system (R/V), and the MLC log files obtained during dose delivery that record the MLC leaf positions and MUs delivered. Comparing the Monte Carlo dose calculation with the original IMRT plan using these data simultaneously validates the accuracy of both the IMRT dose calculation and beam delivery. Such log file based Monte Carlo simulations are expected to be employed as a useful and efficient IMRT QA modality to validate the dose delivered to the patient. We have run Monte Carlo simulations for eight IMRT prostate plans using this method and the results for the target dose were consistent with the original CORVUS treatment plans to within 3.0% and 2.0% with and without heterogeneity corrections in the dose calculation. However, significant dose deviations in nearby critical structures have been observed. The results showed that up to 9.0% of the bladder dose and up to 38.0% of the rectum dose, to which leaf position errors were found to contribute <2%, were underestimated by the CORVUS treatment planning system. The concept of average leaf position error has been defined to analyze MLC leaf position errors for an IMRT plan. A linear correlation between the target dose error and the average position error has been found based on log file based Monte Carlo simulations, showing that an average position error of 0.2 mm can result in a target dose error of about 1.0%.

Computer Simulation↗

PubMed2004

Osteoradionecrosis of the mandibula in patients treated with different fractionations.

PURPOSE: The incidence of osteonecrosis of the mandibula (ON) after irradiation using modern three-dimensional planning as well as hyperfractionation or moderately accelerated irradiation has been evaluated and compared with the incidence of the preceding period. PATIENTS AND METHODS: The records of 268 head and neck cancer patients irradiated between January 1, 1980 and December 31, 1998 with a dose to the mandibula of at least 60 Gy were retrospectively analyzed. All patients had CT-based treatment planning, computerized dose calculation with isodose charts also in several off-axis planes, and regular verification films. RESULTS: The long-term cumulative incidence of ON needing mandibular resection was as follows: after conventional fractionation 6.2% (between 60 and 66.6 Gy target dose) or 20.1% (between > 66.6 and 72 Gy); after hyperfractionated irradiation with a target dose between 72 and 78.8 Gy 6.6%; after concomitant boost irradiation according to the MDA/Houston regime with a dose between 63.9 and 70.5 Gy: no case; after 6 x 2 Gy/week or 7 x 1.8 Gy/week and a total target dose between 66 and 72 Gy approximately 17% or higher (small patient number). CONCLUSION: Comparison of the incidence of ON during the period between 1980 and 1990 with the following period between 1990 and 1998 shows a decrease in risk to a value of approximately 5% using modern three-dimensional techniques as well as hyperfractionation or moderately accelerated fractionation.

Chi-Square Distribution↗

PubMed1995

Improved dose concept for radioiodine therapy of multifocal and disseminated functional thyroid autonomy.

The present study analyzes the improvement of the outcome of radioidine therapy in non-immunogenic hyperthyroidism by adapting the target dose to the 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) prior to radioiodine therapy. The TcTUs is a substitute for the non-suppressible iodine turnover. The 89 patients presented with a basal thyrotropin level of < 0.1 mU/l, normal values for free triiodothyronine and thyroxine and with multifocal or disseminated thyroid autonomy. These terms describe the scintigraphic distribution pattern of autonomous iodine turnover. Thirty-two patients had a TcTUs between 1.6 and 3.2% (group A) and 57 had a TcTUs > 3.2% (group B). Fifty-five patients (three of group A and 52 of group B) were treated previously for overt hyperthyroidism with antithyroid drugs. Target doses of 150 and 200 Gy were used in both groups and 300 Gy in group B only. Six months after radioiodine therapy, a basal TSH level of > or = 0.5 mU/l as criterion of therapy success was observed in 94% of group A and in 54% of group B. Further differentiation of group B shows an increasing success rate with the target dose used: 45% after 150 Gy, 50% after 200 Gy and 90% after 300 Gy. In patients with a basal TSH level of < 0.5 mU/l after radioiodine therapy, the TcTUs was evaluated again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Can low-dose clozapine pharmacokinetics predict steady-state plasma concentration?

Plasma concentrations of clozapine at a given dose vary considerably between patients, but drug levels are not routinely monitored during the normal 4- to 8-week dose escalation period at the beginning of therapy. We hypothesized that the dose required to give a putative threshold therapeutic concentration of 350 micrograms/L could be individualized using pharmacokinetic predictions made at the beginning of normal dose escalation. Low-dose clozapine (25-75 mg every 12 h) was administered to 21 treatment-resistant patients with schizophrenia who had been split into three groups. In group A (six patients), individual target doses were predicted from area under the concentration-time curve data after a single 50-mg dose. In group B (five patients), predictions were made as in group A but at steady state. In group C (10 patients), predictions were based on trough clozapine levels obtained at steady state immediately before dose increase. Dosage was increased, if tolerated, by 25 mg twice daily three times a week for 4-8 weeks according to established clinical practice. Clozapine concentrations were measured weekly, and actual target doses were determined for each patient from dose-concentration plots. In groups A and B, the correlation between actual and predicted target dose was not significant (r = 0.18, p = 0.59). In group C, however, it was significant (r = 0.86, p = 0.0016). These results suggest that individualized doses of clozapine for treatment-resistant patients with schizophrenia can be conveniently predicted from trough drug levels at the start of therapy. Such information would facilitate a more rapid, individualized, and consistent attainment of therapeutic doses than is now the case in clinical practice.

Adult↗

PubMed2002

The effect of set-up uncertainties, contour changes, and tissue inhomogeneities on target dose-volume histograms.

Understanding set-up uncertainty effects on dose distributions is an important clinical problem but difficult to model accurately due to their dependence on tissue inhomogeneities and changes in the surface contour (i.e., variant effects). The aims are: (1) to evaluate and quantify the invariant and variant effects of set-up uncertainties, contour changes and tissue inhomogeneities on target dose-volume histograms (DVHs); (2) to propose a method to interpolate (variant) DVHs. We present a lung cancer patient to estimate the significance of set-up uncertainties, contour changes and tissue inhomogeneities in target DVHs. Differential DVHs are calculated for 15 displacement errors (with respect to the isocenter) using (1) an invariant shift of the dose distribution at the isocenter, (2) a full variant calculation, and (3) a B-spline interpolation applied to sparsely sampled variant DVHs. The collapsed cone algorithm was used for all dose calculations. Dosimetric differences are quantified with the root mean square (RMS) deviation and the equivalent uniform dose (EUD). To determine set-up uncertainty effects, weighted mean EUDs, assuming normally distributed displacement errors, are used. The maximum absolute difference and RMS deviation in the integral DVHs' relative dose between (1) the invariant and calculated curves are 65.2% and 5.8% and (2) the interpolated and calculated curves are 16.9% and 2.5%. Similarly, the maximum absolute difference and RMS deviation in mean EUD as a function of the set-up uncertainty's standard deviation between (1) the invariant and calculated curves are 0.02 and 0.01 Gy; and (2) the interpolated and calculated curves are 0.01 and 0.006 Gy. Since a "worst-case" example is selected, we conclude that, in the majority of clinical cases, the variant effects of contour changes, tissue inhomogeneities and set-up uncertainties on EUD are negligible. Interpolation is a valid, efficient method to approximate DVHs.

Algorithms↗

PubMed2002

Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults.

BACKGROUND: Anticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral gamma-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. OBJECTIVE: To investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. METHODS: Seventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. RESULTS: Cerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). CONCLUSION: This study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature.

Acetates↗

PubMed2000

The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure. Moxonidine Investigators.

OBJECTIVE: To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF). BACKGROUND: Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation. METHODS: Ninety-seven patients with heart failure and New York Heart Association class II-III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn. RESULTS: There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups. CONCLUSIONS: The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.

Administration, Oral↗

PubMed1995

Locally challenging osteo- and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning.

PURPOSE: Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. METHODS AND MATERIALS: Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo-or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). RESULTS: Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12 patients who were controlled for more than 6 months failed locally, yielding a 5-year local control rate of 59% for 15 patients. Overall, 4 patients (27%) developed distant metastasis (two in patients with uncontrolled primary); 4 patients succumbed to their disease, 3 patients died of intercurrent disease, resulting in overall survival of 44% at 5 years. Group 3 (giant cell tumors, osteo- and chondroblastoma): One of 8 patients with giant cell tumor failed locally, 1 patient distantly, and all patients are alive. Three of 4 patients with osteo- or chondroblastoma are alive and well. One patient suffered local recurrence and died of disease. Local control rate and overall survival for this group of 12 patients was 76% and 87% and local control for patients with giant cell tumors 83% at 5 years. In the majority of cases radiotherapy was well tolerated. However, one patient with a large base of skull tumor developed retinopathy, one patient required enucleation of a previously blind eye, and another patient with sacral tumor developed chronic diarrhea. CONCLUSION: Combined proton and photon radiation therapy optimized by 3D treatment planning, allows the delivery of higher radiation doses to tumors of the axial skeleton, while respecting normal tissue constraints. High radiation doses can result in improved long-term local control.

Adolescent↗

PubMed2004

Enalapril in children with Alport syndrome.

Ten pediatric patients with Alport syndrome received enalapril for 5 years. There were nine boys. Eight patients have the X-linked form of the disease and two the autosomal recessive form. The median age at the start of treatment was 10.25 years. Only one patient was hypertensive. The starting dose of enalapril was 0.05 mg/kg; the target dose was 0.5 mg/kg per day. The median dose given effectively was 0.24, 0.37, 0.45, 0.43, and 0.49 mg/kg per day at years of study 1, 2, 3, 4, and 5, respectively. The median urinary protein/creatinine ratio was 1.58 g/g (range 0.49-4.60) before treatment. This decreased to 0.98, 1.09, 1.35, 1.11, and 1.38 g/g after 1, 2, 3, 4, and 5 years, respectively. The median creatinine clearance at baseline was 100 ml/min per 1.73 m2 (range 82-133) and after 5 years 92 ml/min per 1.73 m2 (range 22-115). Three patients did not reach the target dose of enalapril because of orthostatic hypotension. One of them was the only patient to develop chronic renal failure within 5 years. The present study indicates that enalapril reduces urinary protein excretion and preserves glomerular filtration in Alport patients as a group. However, there was individual variation, as in most studies of patients with proteinuric nephropathies given inhibitors of the angiotensin-converting enzyme.

Adolescent↗

PubMed2005

Pallidal index on MRI as a target organ dose of manganese: structural equation model analysis.

We have used a structural equation model (SEM) to analyze the interrelationships among exposure markers, magnetic resonance imaging (MRI) signal index, and neurobehavioral effects. Based on exposure groups, we assessed blood manganese, MRI measurements of pallidal index (PI), and neurobehavioral core test battery (WHO-NCTB) on 111 male workers occupationally exposed to manganese, including welders, smelter workers, and welding rod manufacturing workers. Latent variables were constructed to represent the neurobehavioral effects in an integrated way. The structural equation model revealed that airborne manganese and blood manganese contribute to PI significantly. Manganese exposure in the ambient air may lead to an increase in the internal dose, not only indirectly, by increasing blood manganese level, but also directly, independent of blood concentration. PI significantly contributed to a decrease in neurobehavioral test scores. We found that airborne manganese contributed to PI, and that PI is the most effective predictor of neurobehavioral performance, after adjusting for age and level of education. In conclusion, PI on MRI reflects target organ dose of occupational manganese exposure.

Accidents, Occupational↗

PubMed1988

Prospective detection and assessment of genotoxic hazards: a critical appreciation of the contribution of L. Ehrenberg.

Advances in our understanding of the mechanisms of chemical carcinogenesis are now being applied to improve the quality of prospective risk assessment. The contribution of Ehrenberg and his colleagues (at the University of Stockholm) probably represents the most comprehensive application of mechanistic knowledge to this field during the past 20 years. The strategic approach developed by the Swedish group was based on the identification of differences between man and experimental risk models in factors that determine the relationships between exposure and biological response and the development of methods to compensate for these differences. Many of the critical stages in chemical carcinogenesis and the cellular determinants of these stages have now been identified. As a first step in seeking to improve risk assessment, Ehrenberg introduced the target dose concept, in which the doses of carcinogens penetrating to the cellular target (DNA) are determined. This approach provides an improved basis for determining exposures to carcinogenic agents and also for compensating for species differences in factors such as metabolism that determine the relationships between exposure dose and the dose at the critical target. The target dose concept is now widely accepted and has led to the development of new biomedical monitoring techniques, based, for example, on the measurement of haemoglobin adducts, which are now being applied to detect and identify genotoxic hazards. The introduction of the target dose concept has led to significant improvements in the quality of prospective risk assessment. Further improvements necessitate procedures to compensate for differences between man and prospective risk models in factors that determine subsequent stages of the carcinogenic process. Ehrenberg has proposed that the rad-equivalence approach may be of value in this respect. Its application has accurately predicted the incidence of leukaemias in occupational cohorts which had exposures to ethylene oxide in common. The possible general applicability of this approach is discussed.

Carcinogenicity Tests↗

PubMed2005

[Results of a risk adapted and functional radioiodine therapy in Graves' disease].

UNLABELLED: Aim of this study was to find out, if results of a functional orientated radioiodine therapy in Graves' disease could be optimized using a risk adopted dose concept. PATIENTS, METHOD: 351 patients with Graves' disease were treated for the first time between 11/97 and 8/01. The basic dose was 125 Gy, which was increased up to 250 Gy in a cumulative manner depending on clinical parameters (initial thyroid metabolism, thyroid volume, immunoreactivity). Two different methods of dosimetry were used. Occasional thyreostasis was withdrawn two days before the radioiodine test was started. Follow up was done on average 8 +/- 2.4 (4-17.2) months. TSH > or = 0.27 microIU/mL confirmed as a measure of the success. RESULTS: With improved pretherapeutic dosimetry and a mean target dose of 178 +/- 31 Gy (n=72) therapeutic success occurred in 66.7%, in 51.4% euthyreosis was restalled and in 15.3% of patients hypothyroidism was seen (TSH > 4.20 microIU/mL). With simplified pretherapeutic dosimetry and a mean target dose of 172 +/- 29 Gy (n=279) results were moderately impaired (63.8%, 40.1% and 23.7%). With increasing target dose therapeutic failure increased, as insufficiently adopted risk factors for therapeutic failure turned out the initial thyroid metabolism, the TcTU(s) as the (h)TRAb titer. CONCLUSION: Functional orientated RIT can be optimized by including illness specific characteristics, principal limitations are a high initial thyroid metabolism, a large thyroid volume and a high (h)TRAb-titer.

Graves Disease↗

PubMed1989

Fractionation sensitivity of a functional endpoint: impaired shoulder movement after post-mastectomy radiotherapy.

A clinical radiobiological study of the fractionation sensitivity of impaired shoulder movement after postmastectomy radiotherapy is presented. From 1978 to 1980, 163 breast cancer patients received postmastectomy irradiation delivered in 12 fractions, 2 fractions per week, over a period of 37 to 46 days. The total dose was specified either as a maximum absorbed dose of 51.36 Gy, or as a minimum target dose of 36.6 Gy specified at the level of midaxilla. From 1981 to 1982, 66 patients received a minimum target dose of 40.92 Gy in 22 fractions with 5 fractions per week over a period of 29 to 35 days. The treatment technique remained essentially unchanged during the whole period of 1978 to 1982. Maximal flexion and abduction of the arm were measured with unfixed scapula. A relative score, indicating the grade of impaired shoulder movement on a nominal scale from 0-3, was established by comparison with the mobility of the contralateral arm. In addition, working ability and pain at movement and at rest were evaluated. These performance parameters significantly correlated with the grade of impaired shoulder movement. The occurrence of moderately or severely impaired shoulder movement was analyzed using a mixture model incorporating dose-fractionation, latency, and predisposing clinical factors. The risk of shoulder problems was significantly higher among patients above 60 years of age. The analysis pointed to subcutaneous fibrosis as a disposing factor and indicates that postoperative physical exercise programs are beneficial. Arm edema had no statistically significant influence on shoulder performance. The alpha/beta ratio was estimated at 3.5 Gy with 95% confidence limits (c.l.) [0.7, 6.2] Gy. The length of time to expression of 90% of the ultimate frequency of moderate and severe shoulder impairment was estimated at 3.9 years with 95% confidence limits [3.1, 4.6] years. The nominal standard dose (NSD) formalism failed to produce isoeffective total doses with respect to impaired shoulder movement in the two fractionation schedules. Although the deleterious effects of larger-than-conventional dose fractions have been documented in a number of clinical series, this study represents the first quantitation of the fractionation sensitivity of a functional clinical endpoint.

Adult↗

PubMed1989

Latent-time estimation for late cutaneous and subcutaneous radiation reactions in a single-follow-up clinical study.

In this paper, an analysis of the fractionation sensitivity and latency of subcutaneous fibrosis and telangiectasia in a clinical series is presented. The series comprised 163 breast cancer patients who, from 1978 to 1980, received postmastectomy irradiation delivered in 12 fractions, with 2 fractions per week over a period of 37 to 46 days. The total dose was specified either as a maximum absorbed dose of 51.36 Gy, or as a minimum target dose of 36.6 Gy specified at the level of the mid-axilla. From 1981 to 1982, 66 patients received a minimum target dose of 40.92 Gy in 22 fractions administered as 5 fractions per week over 29 to 35 days. Late complications were evaluated prospectively at a single follow-up after a minimum observation time of 16 months. The clinical endpoints analyzed were subcutaneous fibrosis and telangiectasia. The data were analyzed using a mixture model that incorporates both dose fractionation and latency effects. The length of time to expression of 90% of the ultimate frequency of moderate or severe complications was 3.2 years (95% confidence limits (c.l.) [2.3,3.9] years) and 4.7 years (95% c.l. [4.0,4.8] years) for fibrosis and telangiectasia respectively, while the alpha/beta ratios were 1.9 Gy (95% c.l. [0.8,3.0] Gy) and 3.7 Gy (95% c.l. [0.2,47] Gy), respectively. For subcutaneous fibrosis the time to reach a specific grade of reaction increases with the grade, thus being consistent with the clinical impression that fibrosis progresses in severity over time. If latency and censoring effects are unaccounted for, serious underestimates of the ultimate frequency of radiation complications in groups with incomplete follow-up may result.

Breast Neoplasms↗

PubMed1986

Targeting imipramine dose in children with depression.

The response to imipramine (IMI) in children with depression has been shown to correlate with total levels of IMI plus its active metabolite desmethylimipramine (DMI). The pharmacokinetics of IMI + DMI in children with depression are examined, and the single-point prediction of steady-state IMI + DMI levels at minimum therapeutic concentrations for prepubertal depression is proposed. With a single, 25 mg oral dose of IMI, a plasma concentration of IMI + DMI 24 hours after dosing correlates (r = 0.92) with steady-state IMI + DMI levels in children with depression receiving 3 mg/kg/day IMI. The targeting of IMI dose in the child population with depression to rapidly achieve a minimum therapeutic concentration is shown to be feasible and reliable within theoretic limits.

Absorption↗

PubMed2025

Identification and prognosis of low office and ambulatory blood pressure in patients with heart failure.

BACKGROUND: Low blood pressure (BP) limits the up-titration of guideline-directed medical therapies (GDMTs) and predicts poor outcomes in heart failure (HF). We assessed the value of ambulatory BP monitoring (ABPM) in detecting low BP and its impact on GDMTs optimization and prognosis in HF. METHODS: In 491 HF patients initiating GDMTs from the Risk Evaluation and Management in Heart Failure (REM-HF) study since April 2018 to December 2022, ABPM was measured in addition to office BP. Participants were classified as sustained low systolic BP (SBP) (24-hour and office SBP < 120 mmHg), masked low SBP (24-hour SBP < 120 mmHg, office SBP ≥ 120 mmHg), and no low SBP. The primary outcome was a composite of all-cause mortality and HF rehospitalization. GDMTs target dose achievement was assessed at 3 months. Logistic regression and Cox regression models were used to assess GDMTs optimization and outcomes across SBP groups. RESULTS: Sustained, masked, and no low SBP were observed in 25.3%, 30.8%, and 44.0% of patients, respectively. Both sustained (OR 2.36, 95%CI 1.25-4.47) and masked low SBP (OR 2.32, 95%CI 1.11-4.87) groups were associated with lower likelihood of achieving GDMTs target doses. Over a median 21-month follow-up, all-cause mortality and HF rehospitalization rates were higher in sustained (HR 2.45, 95% CI 1.56-3.86) and masked low SBP (HR 1.68, 95% CI 1.08-2.62) groups. No difference was found in the target dose achievement and outcomes between the two low SBP groups. CONCLUSION: Sustained and masked low SBP were common in HF and both associated with GDMTs intolerance and adverse outcomes.

Humans↗