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PubMed1998

First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy.

PURPOSE: If patients could be ranked according to their projected need for supportive care therapy, then more efficient and less costly treatment algorithms might be developed. This work reports on the construction of a model of neutropenia, dose reduction, or delay that rank-orders patients according to their need for costly supportive care such as granulocyte growth factors. PATIENTS AND METHODS: A case series and consecutive sample of patients treated for breast cancer were studied. Patients had received standard-dose adjuvant chemotherapy for early-stage nonmetastatic breast cancer and were treated by four medical oncologists. Using 95 patients and validated with 80 additional patients, development models were constructed to predict one or more of the following events: neutropenia (absolute neutrophil count [ANC] < or = 250/microL), dose reduction > or = 15% of that scheduled, or treatment delay > or = 7 days. Two approaches to modeling were attempted. The pretreatment approach used only pretreatment predictors such as chemotherapy regimen and radiation history; the conditional approach included, in addition, blood count information obtained in the first cycle of treatment. RESULTS: The pretreatment model was unsuccessful at predicting neutropenia, dose reduction, or delay (c-statistic = 0.63). Conditional models were good predictors of subsequent events after cycle 1 (c-statistic = 0.87 and 0.78 for development and validation samples, respectively). The depth of the first-cycle ANC was an excellent predictor of events in subsequent cycles (P = .0001 to .004). Chemotherapy plus radiation also increased the risk of subsequent events (P = .0011 to .0901). Decline in hemoglobin (HGB) level during the first cycle of therapy was a significant predictor of events in the development study (P = .0074 and .0015), and although the trend was similar in the validation study, HGB decline failed to reach statistical significance. CONCLUSION: It is possible to rank patients according to their need of supportive care based on blood counts observed in the first cycle of therapy. Such rankings may aid in the choice of appropriate supportive care for patients with early-stage breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Comparative means of dose reduction in dental radiography.

This review on dose reduction in dental radiography focuses on criteria for selecting the frequency and type of radiographs to be performed on patients. By making radiographs only when there is a reasonable probability of a finding that will influence patient care, patient exposure and other radiographic costs may be substantially reduced. Patient dose may also be reduced by half by changing from D-speed film to E-speed film for intraoral radiography and by more than half by changing from calcium tungstate intensifying screens to rare-earth intensifying screens for panoramic and cephalometric radiography. Using rectangular collimation for intraoral radiography will also further reduce patient exposure by about fourfold. Finally, the use of time-temperature processing will prevent overexposure of the patient and underprocessing of the radiographs; optimal radiographs will be provided.

Humans↗
PubMed1998

Dose reduction in thorax radiography in simulated neonates with additional filtration and digital luminescence radiography.

PURPOSE: To determine the minimum acceptable radiation dose for an adequate image quality in thorax a.p. radiographs of neonates using mobile X-ray equipment. MATERIAL AND METHODS: The influence of additional filtration (1.0 mm Al + 0.1 mm Cu) on image quality and radiation dose was determined for the speed class 400 screen-film system (SFS) and digital luminescence radiography (DLR) by making radiographs of a test phantom. Conventional and digital thorax a.p. radiographs of a rabbit were produced using various tube current-time products. The quality of the rabbit radiographs was judged by eight radiologists applying image quality criteria according to the German guidelines and the recommendations of the European Community. RESULTS: The added filter resulted in a dose reduction of 39% at 66 kV. DLR gave a further dose reduction of 25% in comparison to the speed class 400 SFS while maintaining adequate image quality, i.e. the radiographs were clinically acceptable with regard to quality criteria. CONCLUSION: The radiation dose resulting from thorax a.p. radiographs of neonates can be reduced by approximately 50% with the use of additional filtration and DLR.

Animals↗
PubMed2005

Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction.

Palmar-plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, fluorouracil, and capecitabine are the most frequently implicated agents. Recently, taxanes, especially docetaxel, have been widely used in combination with capecitabine in patients with metastatic breast cancer (MBC). A high percentage of PPE has been seen in patients undergoing this combination therapy. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. Vitamin E treatment has not been published before, especially without dose reduction of docetaxel-capecitabine therapy. Here we present five MBC patients treated with docetaxel-capecitabine combination therapy in whom PPE was observed during the clinical follow-up period. In all patients grade 2-3 PPE was observed. Vitamin E therapy was started at 300 mg/day p.o. without dose reduction of therapy and after 1 week of treatment PPE began to disappear. We suggest that it could be of interest to consider vitamin E as a preventive drug when drugs with a strong association with PPE are going to be administered.

Aged↗
PubMed2006

Radiation dose reduction to breast and thyroid during MDCT: effectiveness of an in-plane bismuth shield.

PURPOSE: To evaluate dose reduction and image deterioration using in-plane bismuth breast-shielding and thyroid-shielding for MDCT. MATERIAL AND METHODS: Skin and organ doses of thyroid and breast were measured with thermoluminescent dosimeters in a female Alderson-Rando Phantom with and without a 4-ply in-plane bismuth shield. Routine neck (120 kVp, 150 mAs(eff); 16 x 1.5 mm) and chest (120 kVp, 100 mAs(eff); 16 x 1.5 mm) scan protocols were simulated on a 16-row MDCT scanner in three different settings: without shielding, with the shield directly on the surface, and with a 1-cm-thick cotton spacer between surface and shield. Image noise was quantified and compared using the t test. RESULTS: On average, shielding resulted in a 47% organ-dose reduction for the thyroid and 32% for the breast. Placement of the spacer between shield and surface had no significant impact on the measured doses, but significantly decreased the image noise (P < 0.05). CONCLUSION: In-plane bismuth breast and thyroid shielding significantly decreases radiation dose in MDCT without deteriorating image quality.

Artifacts↗
PubMedDate not supplied

Neuropsychological performance in chronic schizophrenia in response to neuroleptic dose reduction.

The effect of 80%-90% neuroleptic dose reductions on neuropsychological function in schizophrenic and schizoaffective patients was examined in a prospective study. A neuropsychological battery was administered in the week prior to neuroleptic reduction followed by retesting at least 6 weeks postreduction. Patients were retested only if they did not relapse after reduction. The design allowed neuropsychological changes due to neuroleptic medications to be assessed independently of general clinical change. Neuropsychological performance was generally stable and unchanging. However, there was a trend toward significant improvement on a dichotic digits task based in improvement in left ear accuracy. Negative symptoms diminished after reduction. Compared with a normal control group, schizophrenics' initial laterality index showed a significantly exaggerated right ear advantage (REA); after reduction, the REA was no longer different from controls. The findings indicate that neuropsychological changes in a small sample of older nonrelapsing chronic schizophrenics are modest. The data suggest that neuroleptics may impair right hemisphere functions in some patients.

Adult↗
PubMed2006

Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*.

In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.

Alanine Transaminase↗
PubMed2005

The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.

BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. AIM: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. METHODS: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. RESULTS: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.

Adult↗
PubMed2000

Randomized study on the conversion of treatment with cyclosporine to azathioprine or mycophenolate mofetil followed by dose reduction.

BACKGROUND: The introduction of cyclosporine (CsA) in kidney transplantation has improved early graft survival. However, its long-term use is associated with impairment of renal function and increased cardiovascular risk factors. To avoid CsA-related long-term adverse effects, patients were converted to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation. METHODS: Between September 1995 and January 1997, 64 stable renal transplant recipients on CsA and prednisone treatment were included in a prospective, randomized study. Patients were randomized for conversion of CsA to 2 mg/kg AZA (n=30) or 1 g of MMF twice daily (n=34). All patients remained on low-dose steroids. To decrease the total immunosuppressive load, a dose reduction in MMF and AZA was performed at 4 and again at 8 months after conversion. Mycophenolic acid trough levels were measured at regular intervals. RESULTS: After conversion, a decrease in serum creatinine was found for both groups: for MMF, 132 to 109 micromol/L (P=0.016); and for AZA, 123 to 112 micromol/L (P<0.0001). After conversion, more acute rejections occurred in the AZA group (11/30) compared to the MMF group (4/34) (P=0.04). Dose reduction of MMF to 500 mg twice daily and of AZA to 1.0 mg/kg elicited three rejections in both groups. The incidence of side effects and infections were similar. CONCLUSION: Discontinuation of CsA spared renal function. In patients converted to MMF significantly less rejections occurred compared to patients converted to AZA. Furthermore, dose reduction of both AZA and MMF is possible in the majority (72%) of the patients.

Adult↗
PubMed1996

Dose reduction in double contrast barium enema by use of low fluoroscopic current.

Under standard conditions double contrast barium enema (DCBE) was carried out on a selected patient cohort using either standard (1.5 mA) or low (0.5 mA) fluoroscopic current. A statistically significant (p < or = 0.01) reduction in total dose was achieved by use of low screening current. This reduction was of the order of 40%. Fluoroscopic image quality was analysed both objectively and subjectively, and was found not to be significantly degraded when the lower current was used. On blinded evaluation all examinations were found to be of diagnostic quality. The use of low fluoroscopic current results in a reduction in patient dose, without compromising fluoroscopic image quality or diagnostic standard of the examination. Low fluoroscopic current technique has been adopted as the standard in our department.

Barium Sulfate↗
PubMed2007

[Dose reduction of conventional antipsychotics: does it reduce tardive dyskinesia?].

The first step in the treatment of tardive dyskinesia is to reduce the dose of antipsychotics. The view sometimes expressed in general practice is that, initially, dose reduction exacerbates tardive dyskinesia, which is an effect that can be explained on theoretical grounds. However, it is apparent from published scientific research that dose reduction of conventional antipsychotics tends to improve tardive dyskinesia rather than exacerbate it.

Antipsychotic Agents↗
PubMed2003

Sequential changes in serum triglyceride levels during adjuvant tamoxifen therapy in breast cancer patients and the effect of dose reduction.

Tamoxifen (TAM) and estrogen increase serum triglyceride (TG) levels, sometimes inducing severe hypertriglyceridemia and possibly contributing to death. Decreasing the dose of estrogen in estrogen replacement therapy may minimize its adverse effects, including the hypertriglyceridemia. The serum TG, total cholesterol, low-density-lipoprotein (LDL) cholesterol and high-density-lipoprotein (HDL) cholesterol were measured periodically in 116 breast cancer patients on adjuvant TAM therapy at a dose of 10 mg twice daily. The serum TG level was significantly increased 15 months after treatment, but the magnitude of increase was clinically insignificant in most patients (n = 102). If TG levels rose above 400 mg/dl, the dose of TAM was reduced to 10 mg once daily (n =14). The TG was lowered to a safer level after the dose reduction of TAM in 10 of 14 patients. The other four patients had early onset hypertriglyceridemia after beginning TAM (within 6 months), and their TG levels did not decrease satisfactorily after dose reduction. Hence, they required antilipemic medication with or without discontinuing TAM. This study suggests that reducing TAM from 10 mg twice daily to 10 mg once daily decreases the marked hypertriglyceridemia that occurs in some patients during TAM treatment.

Antineoplastic Agents, Hormonal↗
PubMed2003

[Dose reduction through gridless technique in digital full-field mammography].

PURPOSE: To determine the role of the scatter grid in digital full-field mammography with respect to image quality and dose and to compare the experimental results with initial clinical experience. MATERIALS AND METHODS: A phantom consisting of 205 fields that enclose gold dots of different thickness and size (CD-Mam phantom, Medical Department, Nijmegen, Netherlands) was used for digital full-field mammography with the conventional grid module and a special gridless module. Four different breast thicknesses were simulated using Plexiglas as scatter material. First, the phantom was exposed at the parameter and dose settings automatically selected in each experimental setup (with and without grid). Subsequently, the phantom was exposed at the different simulated breast thicknesses using the gridless module in combination with the parameters automatically selected for the grid module. This was followed by a series of phantom mammograms obtained with the experimental setup reversed. The 16 mammograms were evaluated by 3 readers and the results compared considering breast thickness, radiation dose, and quality. The gridless module was used for preoperative labeling in 16 patients for comparison of mammograms obtained with and without a grid. RESULTS: For the same entrance dose used in routine mammography, digital mammography without grid is superior to digital mammography with grid when performed on simulated thin breasts (Plexiglas less than 3 cm), with no difference found when performed on simulated large breasts. The advantages of gridless mammography are more pronounced at a markedly reduced entrance dose (identical parenchymal dose without and with grid using the dose automatically selected for the gridless module). This tendency is confirmed by the initial clinical comparison. CONCLUSION: Gridless digital full-field mammography has the potential to reduce the dose further, in addition to already known mechanisms of dose reduction. However, the gridless system must be adjusted (markedly higher "switch-off dose" at the detector) to achieve an overall dose reduction since gridless mammography is inferior to grid mammography for identical doses at the detector plane.

Artifacts↗
PubMed1975

An alternative approach to dose reduction in dental radiography.

A responsible approach to dose reduction in dental radiography requires that relative exposure be related to the specific diagnostic task performed. All but the most demanding tasks can be performed when suitable film is used in conjunction with high-speed screens. Placing the source of radiation inside the mouth permits radiographic information to be recorded on an improved Polaroid cassette that has a relatively high quantum efficiency. As a result, the radiation dose can be significantly reduced in a versatile system which provides for instantaneous processing and interpretation from prints rather than negatives.

Radiation Dosage↗
PubMedDate not supplied

Lipowitz metal shielding thickness for dose reduction of 6-20 MeV electrons.

The relative dose reduction by Lipowitz metal of 6 to 20 MeV electrons from a Varian Associates Clinac-20 linear accelerator has been measured using a parallel plate thin wall ionization chamber. Metal thickness required for a 5% attenuation level for a 10 X 10 cm2 field are as follows: 6 MeV-2.3 mm, 9 MeV-4.4 mm, 12 MeV-8.5 mm, 16 MeV--18.0 mm, 20 MeV-25.0 mm.

Humans↗
PubMed2003

Investigation of dose reduction in neonatal radiography using specially designed phantoms and LiF:Mg,Cu,P TLDs.

Many departments still do not use recommended radiographic parameters to X-ray neonates. Direct, accurate dose measurements of individual examinations may assist a department in justifying technique modifications that provide a substantial dose reduction without a significant loss of image quality. The aim of this study was to investigate dose reduction techniques for neonates in the intensive care unit. Alterations in beam energy (kVp and filtration) and collimation were investigated using specially designed phantoms mimicking a 700 g and 2000 g neonate, and ultrasensitive LiF:Mg,Cu,P thermoluminescence dosimeters (TLDs). Differences in entrance surface dose (ESD) and dose at depth (3 cm or 5 cm) were compared for two, overlapping fields centred individually on the chest and abdomen (Technique 1) and one large chest-abdomen field (Technique 2 or babygram). The large phantom was irradiated at 54 kVp, 60 kVp and 70 kVp without additional filtration and at 66 kVp and 70 kVp with a rare-earth hafnium filter. Focus-film distance (FFD) and mAs were adjusted to maintain optical density (OD) on each radiograph. The baseline dose at 54 kVp and 100 cm FFD was (46+/-2) micro Gy. Increasing the tube potential from 54 kVp to 70 kVp without additional filtration reduced the ESD by 27%. However, the addition of a 0.05 mm hafnium filter at 66 kVp further reduced the radiation dose by 13%, to produce an ESD of (28+/-2) micro Gy. All contrast details were observable at 66 kVp with hafnium filtration. Technique 1 may lead to an increase in effective dose due to field overlap, which diverges at depth, and increased scatter at the periphery of the fields.

Critical Care↗
PubMed2000

Dose reductions and delays: limitations of myelosuppressive chemotherapy.

Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is the major dose-limiting hematologic toxicity, especially in the treatment of potentially curable malignancies such as leukemia, lymphomas, and pediatric cancers. This is becoming increasingly important given the recent trend toward the use of dose-intensive combination chemotherapy regimens facilitated by supportive hematopoietic colony-stimulating factors to prevent chemotherapy-induced febrile neutropenia. The standard preventive measure against chemotherapy-induced depression of platelets in subsequent treatment cycles has been dose reduction and/or dose delay. However, follow-up data from studies in various populations of patients with cancer suggest a correlation between delivery of lower than intended doses and poor outcomes, including reduced disease-free periods and overall survival. Other consequences of thrombocytopenia include the need for platelet transfusions and subsequent exposure to the risk of numerous complications, including bacterial and viral infections; febrile, nonhemolytic transfusion reactions; and transfusion-induced immunosuppression. Furthermore, a large proportion of multitransfused patients become refractory to subsequent infusions. Refractoriness to platelet transfusions is quickly becoming more prominent. The availability of a platelet growth factor--recombinant human interleukin-11(rhIL-11, also known as oprelvekin [Neumega])--provides an effective means of preventing chemotherapy-induced thrombocytopenia and accelerating platelet recovery, thereby facilitating the administration of full doses of chemotherapy during subsequent cycles and avoiding the need for rescue with platelet transfusions.

Antineoplastic Agents↗
PubMed2006

X-ray dose reduction in fluoroscopically guided electrophysiology procedures.

This study assessed the efficacy of a new dose reduction regime in fluoroscopically guided electrophysiology (EP) procedures, which included diagnostic electrophysiological investigations, radiofrequency ablation, and biventricular pacing. A modified dose regime for fluoroscopy was implemented in one of our cardiac electrophysiology laboratories. The x-ray system was programmed with a hierarchy of three fluoroscopy doses, and therefore image quality and settings. The default (lowest) dose mode was not expected to be suitable for all patient sizes or for the entirety of all procedures. Staff raised the dose level in a stepped manner as and when required to optimize the imaging requirements of the procedure. Phantom studies indicated that the low dose mode provided adequate image quality for visualizing EP catheters, while significantly lowering patient skin dose. In 52 clinical cases, questionnaires were used to assess the subjective clinical image quality. The mean image quality score for the low dose setting was rated between "adequate" and "good." The fluoroscopy dose level was raised from the lowest level for 6% of the total fluoroscopy time. Procedural Dose Area Product (DAP) meter readings were analyzed for patients prior to (n = 85) and after (n = 150) the implementation of the low dose regime and showed an overall reduction in DAP rate of 74%. The hierarchical dose regime proved to be acceptable in routine clinical practice for EP procedures, leading to significant reductions in patient doses.

Body Burden↗