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Results for “Targeted dosing”

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At least 145 records · Page 8Linked to original sources

PubMed1999

Phase I and pharmacokinetic study of the oral fluoropyrimidine capecitabine in combination with paclitaxel in patients with advanced solid malignancies.

PURPOSE: To evaluate the feasibility of administering the oral fluoropyrimidine capecitabine in combination with paclitaxel, to characterize the principal toxicities of the combination, to recommend doses for subsequent disease-directed studies, and to determine whether significant pharmacokinetic interactions occur between these agents when combined. PATIENTS AND METHODS: Sixty-six courses of capecitabine and paclitaxel were administered to 17 patients in a two-stage dose-escalation study. Paclitaxel was administered as a 3-hour intravenous (IV) infusion every 3 weeks, and capecitabine was administered continuously as two divided daily doses. During stage I, capecitabine was escalated to a target dose of 1,657 mg/m(2)/d, whereas the paclitaxel dose was fixed at 135 mg/m(2). In stage II, paclitaxel was increased to a target dose of 175 mg/m(2), and the capecitabine dose was the maximum established in stage I. Pharmacokinetics were characterized for each drug when given alone and concurrently. RESULTS: Myelosuppression, predominately neutropenia, was the principal dose-limiting toxicity (DLT). Other toxicities included hand-foot syndrome, diarrhea, hyperbilirubinemia, skin rash, myalgia, and arthralgia. Two patients treated with capecitabine 1,657 mg/m(2)/d and paclitaxel 175 mg/m(2) developed DLTs, whereas none of six patients treated with capecitabine 1,331 mg/m(2)/d and paclitaxel 175 mg/m(2) developed DLTs during course 1. Pharmacokinetic studies indicated that capecitabine and paclitaxel did not affect the pharmacokinetic behavior of each other. No major antitumor responses were noted. CONCLUSION: Recommended combination doses of continuous capecitabine and paclitaxel are capecitabine 1,331 mg/m(2)/d and paclitaxel 175 mg/m(2)/d IV every 3 weeks. Favorable preclinical mechanistic interactions between capecitabine and paclitaxel, as well as an acceptable toxicity profile without clinically relevant pharmacokinetic interactions, support the performance of disease-directed evaluations of this combination.

Administration, Oral↗

PubMed2005

Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III.

BACKGROUND: In patients with chronic heart failure (CHF), a beta-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether beta-blockade as initial therapy may be as useful. METHODS AND RESULTS: We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction < or =35%, who were not receiving ACE inhibitor, beta-blocker, or angiotensin receptor blocker therapy, to open-label monotherapy with either bisoprolol (target dose 10 mg QD; n=505) or enalapril (target dose 10 mg BID; n=505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95% confidence interval (CI) for the absolute between-group difference was <5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment (absolute difference -1.6%, 95% CI -7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment (absolute difference -0.7%, 95% CI -6.6 to 5.1%, HR 0.97; 95% CI 0.78 to 1.21). With bisoprolol-first treatment, 65 patients died, versus 73 with enalapril-first treatment (HR 0.88; 95% CI 0.63 to 1.22), and 151 versus 157 patients were hospitalized (HR 0.95; 95% CI 0.76 to 1.19). CONCLUSIONS: Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril.

Adrenergic beta-Antagonists↗

PubMed1997

Moclobemide for anxiety disorders: a focus on moclobemide for panic disorder.

Moclobemide is a reversible selective inhibitor of monoamine oxidase A. It has proven efficacy in a wide range of depressive disorders, including agitated anxious depression. In an international, multicentre, double-blind parallel-group study, the tolerability and efficacy of moclobemide were compared with that of the selective serotonin reuptake inhibitor fluoxetine. The target dose of moclobemide was 450 mg/day in the dose range of 300-600 mg/day, while the target dose for fluoxetine was 20 mg/day in the dose range of 10-30 mg/day. There were two consecutive studies. The first was an 8-week short-term study of acute adverse events, tolerability and efficacy. The efficacy data showed no significant difference between moclobemide and fluoxetine. Evaluation of the tolerability in a long-term study of up to 1 year is still in progress. A review of the moclobemide safety database for panic disorder with 624 patients showed a marginal increase in events with moclobemide compared with placebo for insomnia (11.2%), dizziness (4.5%) and dry mouth (3.7%), with rates for headaches and nausea lower for moclobemide than placebo. These data suggest moclobemide is a well tolerated and effective treatment for panic disorder.

Adult↗

PubMed2002

Dose finding using the biased coin up-and-down design and isotonic regression.

We are interested in finding a dose that has a prespecified toxicity rate in the target population. In this article, we investigate five estimators of the target dose to be used with the up-and-down biased coin design (BCD) introduced by Durham and Flournoy (1994, Statistical Decision Theory and Related Topics). These estimators are derived using maximum likelihood, weighted least squares, sample averages, and isotonic regression. A linearly interpolated isotonic regression estimate is shown to be simple to derive and to perform as well as or better than the other target dose estimators in terms of mean square error and average number of subjects needed for convergence in most scenarios studied.

Clinical Trials, Phase I as Topic↗

PubMed2003

Dosimetry of high dose skeletal targeted radiotherapy (STR) with 166Ho-DOTMP.

A study was undertaken to determine the maximum tolerated dose of (166)Ho-DOTMP that could be administered safely, without negatively impacting marrow re-engraftment, in patients with multiple myeloma treated with melphalan prior to transplant. Ho-166 DOTMP is a tetraphosphonate that localizes rapidly to bone surface. The Ho-166 physical half-life is 26.8 hr and the maximum beta energy is 1.8 MeV. Standard dosimetry models were adapted for radiation absorbed dose estimates using data obtained from whole body counting of the low abundance photons emitted by (166)Ho. Eighty-three patients received high dose (166)Ho-DOTMP followed by melphalan and transplant of peripheral blood stem cells. Twenty-five patients also received 8 Gy total body radiation (TBI). Dosages administered ranged from 460 to 4476 mCi (166)Ho-DOTMP. Marrow dose was derived using the assumption that all radioactivity not excreted by 20 hours was localized to the bone surfaces, and applying the Eckerman bone and marrow dose model to the calculated bone residence times. The dosimetry of the urinary bladder and kidneys was important because of the rapid excretion of the non-targeted radioactivity via the urinary pathway. The dynamic bladder model was used for bladder wall surface dose, and the ICRP 53 kinetic model was used to model kidney kinetics with an additional blood component included. Marrow doses ranged from 13 to 59 Gy and successful hematapoietic recovery occurred. Bladder doses ranged from 4.7 to 157 Gy. Hemorrhagic cystitis occurred in some patients who received more than 40 Gy to the bladder wall surface. Bladder irrigation was successful in protecting patients from bladder toxicity. Kidney doses ranged from 0.5-7.9 Gy. Kidney toxicity in the form of thrombotic microangiopathy with renal dysfunction was observed, with the severity being related to Ho-166-DOTMP radiation dose and probably the dose rate as well. In a future trial, kidney dosimetry will be assessed using early serial gamma camera imaging and modifications will be implemented to reduce renal toxicity.

Antineoplastic Agents, Alkylating↗

PubMed1996

Transportation dose and doses to extracranial sites during stereotactic radiosurgery with the Leksell Gamma knife.

Two dosimetric aspects of Leksell Gamma knife (LGK) treatment have been investigated in this study: (a) measurement of the small dose (transportation dose) which is absorbed during the patient's transportation into and out of the treatment position within the ionization chamber, and (b) measurements of the doses absorbed by the eyes, thyroid, breast, abdomen, gonads, knee and ankle during the treatment using thermoluminescent dosimetry (TLD). The transportation dose was 0.253 +/- 0.003 Gy, which represented 8.4% of the dose rate (3.005 Gy/min) during measurements. In vivo TLD measurements have been performed on 51 patients. The doses measured in organs and sites of interest were 0.223 +/- 0.168 Gy for the eyes, 0.081 +/- 0.050 Gy for the thyroid, 0.049 +/- 0.033 Gy for the breast, 0.024 +/- 0.18 Gy for the abdomen, 0.012 +/- 0.008 Gy for the gonads, 0.003 +/- 0.002 Gy for the knee and 0.002 +/- 0.002 Gy for the ankle. During LGK radiosurgery, doses to extracranial sites and organs depend mainly on the total target dose and the number of shots used for the treatment. These doses are generally low; the maximum dose was measured for the eyes (approximately 0.7% of the maximum target dose), and the doses to other body organs decrease with increasing distance from the isocenter of the LGK radiation unit.

Abdomen↗

PubMed2005

Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons.

AIM: To characterize gemcitabine aerosol, its in vitro activity against lung cancer cells, its deposition, and tolerance in a non-human primate model. METHODS: In vitro cytotoxicity of nebulized gemcitabine against NCI-H460 and A549 lung cancer cells was tested using a growth inhibition assay and compared with non-nebulized gemcitabine. The (99m)Tc-DTPA-radiolabeled gemcitabine aerosol was characterized by cascade impaction and the gemcitabine mass/(99m)Tc activity relationship was established for further quantitative nuclear imaging. Nine weekly inhalations at a target dose of 1 mg/kg body weight of gemcitabine were performed in three baboons using dynamic scintigraphic acquisitions for continuous monitoring of gemcitabine delivery during inhalation. Gemcitabine plasma concentrations were measured during the first inhalation. RESULTS: Growth inhibition assays for both NCI-H460 and A549 cells did not differ between nebulized and non-nebulized gemcitabine. Aerosol characterization showed a particle mass median aerodynamic diameter of 3.7+/-0.8 microm and a linear relationship between gemcitabine mass (y) and (99m)Tc activity (x) (y=0.82x - 10(-5), R (2)=0.88). No toxicity was observed after nine weekly inhalations of a mean dose of gemcitabine of 11.1 mg (88% of the target dose) as assessed from scintigraphic data. A dose-dependent peak plasma concentration of gemcitabine (20-74 ng/ml) was observed by the tenth minute of inhalation. CONCLUSIONS: We have characterized a gemcitabine aerosol suitable for intrathoracic airway deposition and demonstrated that jet nebulization does not alter the cytotoxic properties of the drug. In a primate model, we have developed a scintigraphic procedure for the monitoring of aerosol deposition, and we have demonstrated the safety of nine weekly aerosol administrations of gemcitabine.

Aerosols↗

PubMedDate not supplied

Accuracy and precision of low-dose insulin administration using syringes, pen injectors, and a pump.

We compared the accuracy and precision of low-dose insulin administration using various devices including, for the first time, an insulin pump. We dispensed 1, 2, and 5 unit(s) of soluble insulin (100 units/mL) 15 times each from a NovoPen (3.0 mL), a BD-Mini Pen (1.5 mL), a Humalog Pen (100 units/mL), 30G Precision Sure-Dose Insulin Syringes, 30G BD Ultra-Fine II Short Needle Syringes, and a H-TRON-plus V100 insulin pump. Each dose was weighed on an analytical scale, and the delivered and target doses were compared. Accuracy was defined by the absolute percent difference from the target dose. Precision was defined as the absolute percent difference from the group sample mean. Overall, we found that the pen and pump devices were more accurate, and the pump more precise, than the syringes at the 1- and 2-unit doses. Syringes were dangerously inaccurate, clinically, at the 1-unit dose. The use of pens and syringes with very fine increment markings (1/2 unit) did not improve accuracy or precision. Earlier researchers used multiple individuals to draw and weigh the samples. In an effort to eliminate the potential introduction of significant error; our study used only 2 investigators: 1 to draw up the doses and another to weigh them. The conclusions in our study were similar to prior studies.

Equipment Design↗

PubMed2003

Intensity modulated radiotherapy treatment planning for dynamic multileaf collimator delivery: influence of different parameters on dose distributions.

BACKGROUND AND PURPOSE: This is an investigation of a dose-based conjugated gradient optimization method (implemented in the CadPlan/Helios system) applied for head and neck tumours. Optimized field fluence distributions are created and transformed into dynamic multileaf collimator (MLC) movements. The aim was to gain knowledge about the influence of different parameters on the dose distribution and how to use the optimization algorithm in an optimum way. MATERIAL AND METHODS: Parameters such as the number of beams, collimator angle and constraints and weight factors have been investigated. Dose escalation to the target volume, the target volume in the build-up region and the way of prescribing the target dose were also investigated. The dose distributions were mainly analysed with physical parameters. RESULTS AND CONCLUSIONS: The optimization algorithm is well suited to create clinical Intensity modulated radiation therapy (IMRT) treatment plans for head and neck tumours even when the target volume is situated in the build-up region. The number of beams is a critical parameter and has a great influence on the dose distribution. The choice of collimator angles is not a critical parameter. The constraints and weight factors have a great influence on the dose distribution and varying these could easily control priorities regarding dose to the target volume or to the surrounding critical organs. Because of dose variations inside the target volume, prescribing to, normalizing to and reporting the mean dose in the target volume for IMRT treatment plans is preferable to the absorbed dose at a point, for example the isocentre point.

Algorithms↗

PubMed1992

Assessment of dose inhomogeneity at target level by in vivo dosimetry: can the recommended 5% accuracy in the dose delivered to the target volume be fulfilled in daily practice?

The inhomogeneity of the dose delivered to the target volume due to irregular body surface and tissue densities remains in many cases unknown, since the dose distribution is calculated for most radiation treatments in only one transverse section and assuming the patient to be water equivalent. In the present study, the transmission and the target absorbed dose homogeneity is assessed for 11 head-and-neck cancer treatments by in vivo measurements with silicon diodes. Besides the dose to the specification point, the dose delivered to 2-4 off-axis points in the midline sagittal plane is estimated from entrance and exit dose measurements. Simultaneously made portal films allow to identify the anatomical structures passed by the beam before reaching the exit diode. The mean deviation from the expected transmission is -6.8% for bone, +6% for air cavities and -2.5% for soft tissue. At the midplane, the mean deviations from the expected target dose are respectively -3.5%, +2.3% and -1.9%. The deviations from the prescribed dose are larger than 5% in 12 out of the 39 target points. The accuracy requirement in target dose delivery of plus or minus 5%, as proposed by ICRU, cannot be fulfilled in 7 out of the 11 patients and is mostly due to irregular body contour and tissue densities. As only a limited number of points are considered, the inhomogeneity in the dose delivered throughout the whole irradiated volume is underestimated as is illustrated from the exit dose profiles obtained from the portal image.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMed2003

Clinical implementation of an automated planning system for gamma knife radiosurgery.

PURPOSE: To evaluate an automated treatment planning system for gamma knife radiosurgery. This planning system was developed in our clinic and is now in routine clinical use. The system simultaneously optimizes the shot sizes, locations, and weights. It also guides the user in selecting the total number of radiation shots. METHODS AND MATERIALS: We assessed the clinical significance of the automated system by comparing an optimized plan with a manual plan for 10 consecutive patients treated at our gamma knife facility. Each treatment plan was analyzed using dose-volume histograms in conjunction with the conformity index, the minimum target dose, and the integral normal tissue dose. RESULTS: On average, the treatment plan produced by the inverse planning tool provided an improved conformity index, a higher minimum target dose, and a reduced volume of the 30% isodose line as compared to the corresponding plan developed by an experienced physician. An optimized treatment plan can typically be produced in 10 min or less. CONCLUSIONS: The automated planning system consistently provides a high-quality treatment plan while reducing the time required for gamma knife treatment planning.

Humans↗

PubMed1998

Dose-dependent CSF acetylcholinesterase inhibition by SDZ ENA 713 in Alzheimer's disease.

INTRODUCTION: This study evaluates the activity of SDZ ENA 713, a centrally-selective acetylcholinesterase (AChE) inhibitor, in the cerebral spinal fluid (CSF) of patients with Alzheimer's disease (AD), and its relationship to central and peripheral pharmacokinetic parameters. METHODS: Eighteen AD patients were enrolled in this open-label, multiple-dose study. Patients were titrated in 1 mg bid/week increments to target doses of 1, 2, 3, 4, 5, or 6 mg bid SDZ ENA 713. After patients had been maintained at their target dose for at least 3 days, continuous CSF samples were obtained via a lumbar catheter for 12.5 h, beginning 0.5 h prior to the final dose of SDZ ENA 713. RESULTS: Dose-dependent inhibition of CSF AChE was significantly correlated (P < 0.05) with plasma drug and metabolite concentrations. The 6 mg bid treatment group showed a maximum mean inhibition of 62% at 5.6 h post-dose. CONCLUSION: Rapid, sustained, dose-dependent inhibition of CSF AChE suggests that SDZ ENA 713 has therapeutic potential in AD patients.

Administration, Oral↗

PubMed2001

Optimized intensity-modulated arc therapy for prostate cancer treatment.

We recently implemented intensity-modulated arc therapy (IMAT) at our institution. In this study, we evaluate the dosimetric merits of the application of this technique to the treatment of prostate cancer. Each IMAT treatment plan incorporated bilateral overlapping arcs. The dose from each beam segment was computed using the three-dimensional dose model of a clinical treatment planning system (Render Plan 3.5, Precision Therapy). The weights assigned to the individual arc segments were optimized using a gradient search method. For 12 patients, comparisons were made between the IMAT treatment plans and corresponding plans using fixed cone-beam intensity-modulated radiotherapy (IMRT) from a commercial inverse planning system (CORVUS, NOMOS Corp.). We found that the optimized IMAT treatments produced similar dose distributions to the IMRT deliveries. Compared with the IMRT treatments, the IMAT treatments produced slightly less target dose homogeneity with consistently greater sparing of the rectum in regions of lower dose. The trade-off between target dose conformity and rectum sparing can be adjusted in both optimization procedures. Because the total beam-on time for IMAT delivery is 1 to 2 minutes with approximately 5-6 minutes of patient setup time, the delivery efficiency of the IMAT treatment was significantly better than the multiple-beam IMRT treatment.

Humans↗

PubMed2002

Optimising parameters for peripheral blood leukapheresis after r-metHuG-CSF (filgrastim) and r-metHuSCF (ancestim) in patients with multiple myeloma: a temporal analysis of CD34(+) absolute counts and subsets.

Patients (n = 69) with multiple myeloma undergoing peripheral blood stem cell collection (PBSC) were treated with cyclophosphamide and a combination of recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) and recombinant methionyl human stem cell factor (r-metHuSCF, ancestim). The objectives of this study were to determine: (1) The proportion of patients reaching a target yield of >or=5 x 10(6) CD34(+) cells/kg in one or two successive large-volume (20 liter) leukapheresis procedures; (2) the optimal collection time for leukapheresis; (3) mobilization kinetics of CD34(+) subsets in response to G-CSF/SCF. All patients were mobilized with cyclophosphamide (2.5 g/m(2)) on day 0 followed by filgrastim (10 microg/kg ) plus ancestim (20 microg/kg) commencing day 1 and continuing to day 11 or 12. Of the 65 evaluable patients, 57 were considered not heavily pretreated and 96.5% obtained a target of >or=5 x 10(6)/kg in one collection. The median CD34(+) cells/kg was 39.5 x 10(6) (range: 5.2-221.2 x 10(6)). Subset analysis demonstrated the number of CD38(-), CD33(-), and CD133(+) peaked at day 11; and CD34(+), CD90(+) cells peaked at day 10. The optimum day for leukapheresis was determined to be day 11. The median absolute peripheral blood CD34(+) cell numbers on day 11 was 665 x 10(6)/l (range: 76-1481 x 10(6)/l). Eight of the 10 heavily pretreated patients were evaluable: three achieved the target dose in one leukapheresis (37.5%) and three (37.5%) achieved the target dose with two leukaphereses. Use of this mobilization strategy allowed the collection of high numbers of CD34(+) cells and early progenitors and the ability to predictably schedule leukapheresis.

Adult↗

PubMed2001

Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study.

OBJECTIVE: This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics. PATIENTS AND METHODS: The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period. RESULTS: The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate withdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volume (-9 +/- 33 vs. +24 +/- 47 ml; p < 0.01). CONCLUSION: The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.

Adult↗

PubMed2006

Thick target neutron dose evaluation for 19F+Al system.

Measured angular distribution of neutron dose from 110 MeV (19)F projectiles bombarding a thick aluminium target is reported. The measurements are carried out with a commercially available rem meter at 0 degrees, 30 degrees, 60 degrees and 90 degrees. The experimental results are compared with calculated dose from different empirical formulations proposed by earlier workers as well as with calculated dose from theoretically estimated energy distributions from the nuclear reaction model code EMPIRE-2.18.

Algorithms↗

PubMed2005

[F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: clinical outcomes and patterns of failure.

PURPOSE: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme. METHODS AND MATERIALS: Forty patients were enrolled. Patients were treated with standard conformal fractionated radiotherapy with volumes defined by MRI imaging. When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to a total dose of 79.4 Gy (n = 30). RESULTS: The estimated 1-year and 2-year overall survival (OS) for the entire group was 70% and 17%, respectively, with a median overall survival of 70 weeks. The estimated 1-year and 2-year progression-free survival (PFS) was 18% and 3%, respectively, with a median of 24 weeks. No significant improvements in OS or PFS were observed for the study group in comparison to institutional historical controls. CONCLUSIONS: Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated no improvement in OS or PFS. This study establishes the feasibility of integrating PET metabolic imaging into radiotherapy treatment planning.

Brain Neoplasms↗

PubMed2001

Underutilisation of ACE inhibitors in patients with congestive heart failure.

Congestive heart failure (CHF) is associated with substantial morbidity and mortality, and is the only major cardiovascular disease increasing in prevalence. Despite abundant evidence to support their efficacy and cost-effectiveness, angiotensin-converting enzyme (ACE) inhibitors are sub-optimally used in patients with CHF. This paper reviews the evidence for the sub-optimal use of ACE inhibitors in patients with CHF, the factors contributing to this, and its implications for health systems. A systematic review of all articles assessing practice patterns (specifically the use of ACE inhibitors in CHF) identified by MEDLINE, search of bibliographies, and contact with content experts was undertaken. 37 studies have documented the use of ACE inhibitors in patients with CHF. Studies assessing use among all patients with CHF document 33% to 67% (median 51%) of all patients discharged from hospital and 10% to 36% (median 26%) of community dwelling patients were prescribed ACE inhibitors. Rates of ACE inhibitor use range from 43% to 90% (median of 71%) amongst those discharged from hospital having known systolic dysfunction, and from 67% to 95% (median of 86%) for those monitored in specialty clinics. Moreover, the dosages used in the 'real world' are substantially lower than those proven efficacious in randomised, controlled trials, with evaluations reporting only a minority of patients achieving target doses and/or an overall mean dose achieved to be less than one-half of the target dose. Factors predicting the use and optimal dose administration of ACE inhibitors are identified, and include variables relating to the setting (previous hospitalisation, specialty clinic follow-up), the physician (cardiology specialty versus family practitioner or general internist, board certification), the patient (increased severity of symptoms, male, younger), and the drug (lower frequency of administration). In light of the substantial evidence for reductions in morbidity and mortality, clearly, the prescription of ACE inhibitors is sub-optimal. Wide variability in ACE inhibitor use is noted, with higher rates consistently reported among patients having systolic dysfunction confirmed by an objective assessment--an apparent minority of the those having CHF. Optimisation of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF by reducing hospitalisations and lengths of hospital stays. It is likely that only multifaceted programs targeted toward the population at large will yield benefits to the healthcare system, given the widespread nature of the sub-optimal prescription of therapies proven effective in the management of patients with CHF.

Angiotensin-Converting Enzyme Inhibitors↗