SEARCH · PubMed Health

Results for “dose reduction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1977

Bromocriptine versus placebo in levodopa treated patients with Parkinson's disease.

Twenty patients with idiopathic parkinsonism who had been on optimal levodopa therapy for at least 3 months prior to the investigation and where effect of the treatment was decreasing or side effects were increasing, were treated with bromocriptine in a double-blind crossover trial during a 12 + 12 weeks period. Reduction in disability scores was found significant. Hyperkinesia was more frequent in the bromocriptine period than in the placebo period, but reduction of dose in six patients for this reason was not followed by deterioration. Both hyperkinesia and other side effects disappeared after dose reduction. Doses were 2.5 mg-40 mg. Bromocriptine seems a valuable supplement to previous therapy in these patients.

Aged↗

PubMed2026

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans↗

PubMed1976

Volume and time factors in interstitial gamma-ray therapy.

The two suppositions which have dictated time-dose and volume relationships in interstitial gamma ray implantation have been examined in the light of recent publications. The first of these assumptions, that total dose reduction is required when the dose rate exceeds 6,000-7,000 rads in seven days, does not appear to be substantiated by clinical experiences. It appears that total dose is the critical treatment parameter and that dose rate may be increased by a factor of two or three without requiring alteration of the total dose. Although the second classical assumption, "volume increase requires dose decrease," has been shown throughout radiation therapy experience to be generally correct, it should not be applied rigidly to interstitial gamma-ray therapy. In fact, recent experiences seem to indicate that compensation with respect to volume is not an absolute necessity. Larger lesions require, if anything, higher doses than small ones. To obtain a high percentage of controlled, lesions there must be no dose reduction, regardless of increased volume treated.

Animals↗

PubMed2026

Shielding performance and clinical applicability of lead-free materials in computed tomography.

Owing to the high radiation exposure associated with computed tomography (CT) examinations and the image quality degradation caused by conventional radiation shielding materials, this study evaluated the dose reduction performance and image quality maintenance potential of a newly developed lead-free composite shielding material. This material was composed of bismuth, tungsten, tungsten carbide, aluminium, and polyurethane. Phantom-based dose measurements demonstrated that the shielding material achieved dose reduction rates ranging from 17.6% to 37.6%, depending on tube voltage. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and changes in tube current-time product (mAs) under a scout-based automatic exposure control (AEC) protocol were analysed according to the presence or absence of the shielding material across regions. For the clinical evaluation, CT scans were performed on four patients. Furthermore, the images were reviewed to evaluate whether this material affected image quality. The shielding material exhibited radiation reduction levels comparable to those reported in previous studies. SNR and CNR analyses showed minor statistical variations in certain regions; however, most differences were not statistically significant, and even significant differences remained within a range that did not compromise diagnostic image quality. Under the scout-based AEC protocol, the use of the shielding material resulted in less than 1% variation in mAs values. No visually perceptible artefacts or clinically significant image quality degradation were observed. The proposed composite shielding material demonstrated the potential to mitigate some limitations of conventional shielding materials and showed preliminary clinical feasibility as an adjunctive strategy for radiation dose reduction in CT examinations.

Radiation Protection↗

PubMedDate not supplied

Dose dependent reduction of glucose utilization by pentobarbital in rat brain.

A new method of determining the rate of glucose utilization in brain regions of individual rats has been used to measure the dose dependency of the reduction of the metabolic activity of the cerebral cortex by pentobarbital. Cerebral cortical glucose utilization is depressed to a basal level of 44% of the control rate when cerebral pentobarbital levels exceed 50 microgram per g of tissue. The major portion of this effect occurs between the cerebral pentobarbital range of 10--20 microgram per g, which can be achieved by 1/5 to 1/10 the normal anesthetic intraperitoneal dosage. If a depression of brain metabolism is responsible for the previously reported protection of the brain from ischemic damage, these data suggest a substantial reduction of brain metabolic rate is achieved in the rat at a barbiturate dosage which may be therapeutically relevant in the human after acute brain ischemia.

Animals↗

PubMed2026

Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia-A 7-year real-world study.

BACKGROUND: Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy, yet real-world data on dose modifications and their differential impact on long-term outcomes remain incompletely defined. This study investigated the incidence, timing, and the effectiveness of drug switching in a real-world CLL cohort. METHODS: In this 7-year retrospective real-world study, 324 CLL/SLL patients treated at a specialized Shanghai outpatient clinic (April 2018-April 2025; median follow-up, 42 months) were analyzed. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Their prognostic impact on progression-free (PFS) and overall survival (OS) was assessed by Kaplan-Meier analysis and multivariate Cox regression. RESULTS: The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced dose reductions or interruptions; infections were the predominant cause (61.9%). The full-dose (FD) group (n = 90) demonstrated superior 4-year PFS (93% vs. 58%, p < .001) and OS (98% vs. 76%, p = .007). Early modifications (0-3 months) were independent predictors of inferior PFS (hazard ratio [HR], 3.93, p = .008) and OS (HR, 3.29, p = .014). Prolonged DI (>14 days) was associated with inferior PFS (HR, 2.64) and OS (HR, 2.15), whereas DR and short DI (≤14 days) had negligible impact. Early (0-3 months) prolonged DI was devastating (3-year PFS, 41.2%; HR, 3.84, p < .001). cBTKi switching (n = 82; 100% nonprogression-driven) shortened DI (median, 6 vs. 14 days) and was independently associated with superior OS (HR, 0.34, p = .018) and PFS (HR, 0.36, p = .022). CONCLUSIONS: Early prolonged DI is the dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival, supporting a timing-aware, DI- versus DR-informed approach to dose management.

Humans↗

PubMed1978

Dose-dependent reductions by naloxone of analgesia induced by cold-water stress.

Animals exposed to cold-water swims, rotation, or inexcapable shocks, display analgesia comparable to that of 10 mg/kg of morphine. The present study investigated whether a narcotic antagonist would eliminate analgesia induced by cold-water swims. In one group of 12 rats, naloxone at 0, 1, 5, 10 and 20 mg/kg was administered at weekly intervals immediately preceding forced cold-water swims (2 degrees C for 3.5 min) and alterations in flinch-jump thresholds were determined 30 min thereafter. In a second group of six rats, the effects of the same dose range of naloxone were determined upon normal flinch-jump thresholds. Naloxone dose-dependently attenuated the cold-water swim-induced analgesia up to a maximal reduction of 50% at 20 mg/kg. In contrast, all doses of naloxone had no effects upon normal flinch-jump thresholds. Since low doses of naloxone completely abolish morphine-induced analgesia, the present data suggest that the analgesia induced by stress is not identical to that of opiates.

Analgesia↗

PubMed1978

Effect of valproic acid on hepatic function.

Altered hepatic function tests occurred in four of 25 patients treated with valproic acid. An average dose reduction in three patients of 10 mg per kilogram per day resulted in reversion of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) to normal. The drug was discontinued in one patient. Careful monitoring of hepatic function is required of patients being treated with valproic acid, but our experience suggests that dose reduction alone may be effective in preventing untoward hepatic side effects.

Adolescent↗

PubMed1979

Reduction of dose in pelvic examinations of infants using modern X-ray techniques.

A simple dose-saving procedure for the diagnosis of congenital hip dysplasia employing a diaphragm in near-focus position is presented. Doses to the skin and the gonads are measured with a phantom, comparing the new and other techniques. With optimal techniques the skin dose is smaller than 2 mR and the gonadal doses lie around 0.1 mR for both male and female patients.

Age Factors↗

PubMed2026

Optimizing Initial Dosing for Tacrolimus and Mycophenolate in Living Donor Liver Transplantation: A Systematic Critical Review.

BACKGROUND: The pharmacokinetics (PK) of immunosuppressive agents in living donor liver transplantation (LDLT) recipients are expected to differ from those in deceased donor liver transplantation (DDLT) recipients because of the smaller initial liver volume transplanted and pathophysiological changes during liver regeneration. Consequently, the hepatic metabolism, CYP enzyme activity, and glucuronidation may be reduced. The PK of tacrolimus (metabolized by CYP3A5) and mycophenolate (metabolized through glucuronidation) are expected to be affected early post-LDLT. However, the initial dosing recommendations for post-LDLT remain unclear. PURPOSE: This study aimed to recommend initial dosing approaches for tacrolimus and mycophenolate in LDLT recipients based on available PK data in humans. METHODS: A PubMed search was conducted in March 2025 to identify studies investigating the PK data of immediate-release tacrolimus and mycophenolate in pediatric or adult LDLT recipients. RESULTS: After screening, 8 and 8 articles on tacrolimus and mycophenolates, respectively, met the review criteria. The current literature suggests that LDLT recipients require lower tacrolimus doses than DDLT recipients, particularly in the early post-transplant period. In addition, CYP3A5 polymorphisms in both donors and recipients contribute to interindividual variability in tacrolimus exposure, further complicating tacrolimus management. Studies on mycophenolate use in LDLT recipients are limited, with insufficient evidence to support dose reduction. CONCLUSIONS: Reducing the initial tacrolimus dose in LDLT recipients by 30%-50% compared with that in DDLT recipients would be reasonable while maintaining the same initial dose of mycophenolate between LDLT and DDLT recipients.

Humans↗

PubMed1977

Effects of methanol extraction residue of Bacillus calmette-Guérin in humans.

Forty patients with histologically confirmed neoplastic diseases were treated with the methanol extraction residue of Bacillus Calmette-Guérin (MER). Thirty-six received concomitant chemotherapy. MER was initially given intradermally twice a month, 1 week apart, at a dose of 200 mug into each of five sites draining different lymph node-bearing areas on the anterior body surface. Thirty-seven patients developed local ulcerations at least 0.5 cm in diameter at MER injection sites. Typical lesion evolution was characterized by erythema and induration followed by vesicle formation and central necrosis. Either granulation tissue or a thick nonulcerated eschar preceded healing, leaving a linear, flat scar. Systemic toxicity consisted of malaise, fever, and myalgias on the day of MER administration. No hematological or biochemical changes directly attributable to MER were observed. Dose titrations in decreasing 10-fold dilutions in a linear array in a single anatomical region were carried out on 35 occasions. All patients but three developed at least a 5-mm induration to the 1-mug dose within 2 weeks of titration. Dose reductions were necessary in 19 instances. The minimal dose that produced a 1-cm inflammatory lesion with central necrosis was 0.01 mug. Serial biopsies were performed. These indicated a time-related series of changes from a nonspecific inflammatory lesion to an acute inflammatory response with microabscesses, followed by noncaseating granulomata and ultimately fibrosis. MER is a quantifiable nonviable immunostimulant that obeys dose-response relationships in its cutaneous lesions.

Antineoplastic Agents↗

PubMed1978

Physical dependence to barbital compared to pentobarbital. IV. Influence of elimination kinetics.

The withdrawal characteristics of barbital and pentobarbital after "chronically equivalent" treatment suggested that the longer acting barbital was less liable to produce physical dependence. Therefore, to distinguish this potential pharmacodynamic difference from the known pharmacokinetic differences between the two drugs, the rate of elimination of each was adjusted to mimic that of the other. The rate of barbiturate elimination after chronically equivalent pentobarbital dosing was reduced by barbital substitution or by first-order pentobarbital dose reduction, with the result that withdrawal signs became mild and appeared later (3 days postdrug). The rate of barbiturate elimination after chronically equivalent barbital dosing was increased by pentobarbital substitution or by peritoneal dialysis of barbital, with the result that withdrawal signs became severe and appeared sooner (within 1 day). These findings conclusively support the key role of the rate of barbiturate elimination to expose underlying physical dependence to barbiturates. Furthermore, "physical dependence" and its expression in "withdrawal" must be regarded separately to evaluate and compare critically the dependence capability of different drugs.

Animals↗

PubMed1979

Small electron beams in radiation therapy.

The use of lead cutouts to produce small beams in electron therapy results in a reduced dose to the patient. The authors investigated this effect for beams with energies less than 8 MeV and diameters of 3 cm or less. Dose measurements were obtained using film and an ionization chamber. Based on these values, corrections were established to account for dose reduction due to cutout spaces and air spaces between the end of the electron cone and the skin surface. Data were also obtained on the dose increase due to backscattering from internal eyeshields.

Electrons↗

PubMed1977

[On the dose-effect relation of allopurinol (author's transl)].

The hypuricemic action(y) of 1H-pyrazolo(3,4-d)pyrimidin-4-ol (allopurinol) is dependent on the serum concentration of uric acid (x). After treatment with allopurinol at doses of 300 mg daily for 8 days there exists a highly significant correlation corresponding the equation y = 0.875x + 3.950. At a level of 8 mg/dl without any therapy serum uric acid concentration is expected to decrease by an average of 3 mg/dl if allopurinol is applied at daily doses of 300 mg in a preparation with or without any retarding effect. Following a dose reduction to 150 mg allopurinol daily over a period of 8 days, too, the mean diminution of the hypuricemic action amounts only to 0.43 +/- 0.26 mg/dl (S.D.). In some cases, however, long-term therapy with allopurinol at daily doses of 150 mg is insufficient to guarantee a normuricemic state.

Adult↗

PubMed1979

National Cooperative Crohn's Disease Study: adverse reactions to study drugs.

Adverse reactions to the drugs employed in the National Cooperative Crohn's Disease Study were sought prospectively at each patient visit and by retrospective review of all patient charts. Prednisone caused evident side effects in over 50% of patients on high-dose suppressive therapy and in approximately one-third of patients on prophylactic dose. Thirty-two percent of patients on high-dose, and 26% on prophylactic-dose prednisone required dose reduction or withdrawal because of side effects. Comparable figures for sulfasalazine were 14% and 12%, and for azathioprine 32% and 20%. The incidence of nausea, vomiting, or anorexia among patients taking sulfasalazine was 46% and 34%, on high and low dose respectively; however, this incidence was no different than that observed among patients taking placebo. These symptoms occasioned withdrawal from the study of only 4% and 3% of patients on high and low doses of sulfasalazine, respectively. Azathioprine produced leukopenia at a dose of 2.5 mg/kg body weight in 15% of patients and the mean white cell count, lymphocyte count, granulocyte count, and hematocrit all fell significantly in patients on this dose. Pancreatitis occurred in 5% of patients taking azathioprine but in no other patients. Sulfasalazine proved to be the safest effective suppressive drug for Crohn's disease. Prednisone toxicity, though substantial, is acceptable in view of its demonstrated suppressive efficacy. Azathioprine was approximately as toxic as prednisone but no more effective than placebo in suppressing active disease. None of the drugs was effective prophylactically, and all showed appreciable long-term toxicity.

Adult↗

PubMed1979

Effect of increased bioavailability of phenytoin tablets on serum phenytoin concentration in epileptic out-patients.

1. The bioavailability of a brand of phenytoin tablets used in Finland was improved in 1976. In the present retrospective study serum concentrations of phenytoin, measured before and after the change of bioavailability, are compared in 50 epileptic out-patients, who for various reasons used exactly the same dose of phenytoin tablets and of other drugs despite the increased bioavailability of phenytoin. 2. The mean increase of serum phenytoin steady-state concentration was about 70% after the change of bioavailability but there were considerable interindividual differences in the response. The mean increase in serum phenytoin was only 28% in patients with serum phenytoin concentrations 5 microgram/ml or less but the mean increase was 100% in patients with serum phenytoin between 5 and 10 microgram/ml. In patients with serum phenytoin concentrations more than 10 microgram/ml the mean increase in concentration was 60-80% after the improvement of bioavailability. However, in these groups of patients some clinically manifested phenytoin intoxications enforced the patients to the control and to dose reduction obviously before the steady-state concentration of phenytoin was reached. 3. On the basis of our experiences and those reported in the literature some proposals are presented to be considered when the bioavailability of phenytoin or of another drug with a narrow therapeutic range and a dose-dependent kinetics has to be changed.

Biological Availability↗

PubMed1979

[General characteristics and comparative evaluation of the radioprotective properties of aryl alkyl amine adrenomimetics in experiments on mice].

The radioprotective effect (RPE) of some arylalkylamines (AAAs) was studied in experiments on mice. Mesaton and its close analogues were injected subcutaneously 15 minutes prior to irradiation at a dose of 800 rad. The protective effect is exerted by AAAs in low doses (25--50 mumole/kg), the compounds show stable and high RPE (80--80% survival, dose reduction factor being 1.3--1.4) and low toxicity (LD50 = 4--8 mumole/kg). AAAs studied are not less effective than aminothiols. Their pharmacological spectrum--K = LD50/ED50 (200--500) is superior to that of known aminothiols and indolylalkylamines.

Animals↗

PubMed1978

Patient exposures and radiation risks in Swedish diagnostic radiology.

Results are reported of measurements around 1974 on a thousand patient at 13 Swedish hospitals, and additionally at several photofluorographic and dental installations. Energy imparted as well as doses to the thyroid, breast, lung, bone marrow, ovary and testis have been calculated for many types of examination. Collective doses have been calculated and risk estimates made. The energy imparted corresponds to an annual mean body dose to the Swedish population of about 1 mGy (100 mrad), and the genetically significant dose was about the same as the 1955 total of 0.4 mGy; in both cases the uncertainty of the estimate is about +/- 50%. The possibility of dose reduction by a factor of 2 or more using available techniques is demonstrated. The risk of future serious injury is estimated to 0.0002 cases per joule of energy imparted to the patient.

Bone Marrow↗