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Results for “Rate control”

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At least 19 recordsLinked to original sources

PubMed1975

Learned heart-rate control by a patient with a ventricular parasystolic rhythm.

A 31-year-old woman with a ventricular parasystolic rhythm is described. The arrhythmia was always absent below a rate of 72 per minute, and always present over a rate of 106 per minute. Voluntary heart-rate control was learned using a biofeedback techinque, as a result of which she could increase her rate by 25 per minute and decrease it by 1-2 per minute. Both voluntary speeding and exercise brought on the arrhythmia, but later in the training she could reach a higher heart-rate before the arrhythmia appeared. Propranolol inhibited the arrhythmia only to the extent that is slowed the heart.

Adult↗

PubMed2026

Family-Wise Error Rate Control in Clinical Trials With Overlapping Populations.

We consider clinical trials with multiple, overlapping patient populations that test multiple treatment policies specifically tailored to these populations. Such designs may lead to multiplicity issues, as false statements will affect several populations. For type I error control, often the family-wise error rate (FWER) is controlled, which is the probability to reject at least one true null hypothesis. If the joint distribution of the test statistics is known, the FWER level can be exhausted by determining critical values or adjusted-levels. The adjustment is typically done under the common ANOVA assumptions. However, the performed tests are then only valid under the rather strong assumption of homogeneous null effects, that is, when the null hypothesis applies to all subpopulations and their intersections. We show that under cancelling null effects, when heterogeneous effects cancel out in some or all subpopulations, this procedure does not provide FWER control. We also suggest different alternatives and compare them in terms of FWER control and their power.

Humans↗

PubMedDate not supplied

Classical conditioning of blood pressure in Macaca mulatta with cardiac rate controlled.

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Animals↗

PubMed1975

Elementary osmotic pump.

The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal.

Animals↗

PubMed1977

Pharmacologic analysis of stretch-induced sinus acceleration of the isolated dog atrium.

Using isolated, blood-perfused atrium preparation of the dogs, the effect of stretch on sinus rate was studied in 11 preparations. Stretching usually produced sinus acceleration in all 11 spontaneously beating atria. Within a range of 0--30 Gm, greater degrees of stretch produced greater degrees of sinus acceleration. During maintained stretch sinus rate slightly reduced but not to the control rate. On release from stretch sinus rate immediately returned to the control rate, and there was occasionally a slowing to rates lower than control in verapamil treated preparations. Atropine, adrenergic beta-receptor blocking agents, propranolol and carteolol, verapamil, and tetrodotoxin did not greatly modify responses to stretching.

Adrenergic beta-Antagonists↗

PubMed1979

Randomized study of control of the primary tumor and survival using preoperative radiation, radiation alone, or surgery alone in head and neck carcinomas.

Fifty-five selected patients with previously untreated squamous cell carcinoma of the head and neck regions were studied in a randomized, prospective manner. The three treatment categories were primary radiation (Gp R), primary surgery (Gp S), and preoperative radiation of 4000 rads in four weeks (Gp R/S). The local control rates for the 44 evaluable patients with a two-year minimum followup were 24%, 39%, and 43% respectively. Further treatment attempts in patients failing initial therapy yielded local control rates of 35%, 39%, and 43% for Gp R, Gp S, and Gp R/S, respectively. None of the local control rates nor the corresponding survival curves were significantly different at P less than 0.10. However, the group sizes were sufficiently small that true differences might not have been detected. Postoperative complications were higher in the primary radiation failures subsequently operated upon compared to the primary surgery group (P = 0.07).

Carcinoma, Squamous Cell↗

PubMed1977

Halothane depresses baroreflex control of heart rate in man.

Baroreflex control of heart rate was determined during three awake control situations and during two depths of halothane anesthesia in man. Baroreflex function was quantiated by calculating the pressor test slope from the R-R interval change on the ECG produced by a pharmacologically induced pressor response. During the three awake control situations the subjects breathed room air or 100 per cent O2 spontaneously or 100 per cent O2 with ventilation controlled. Mean (+/- SD) slopes obtained were 15.1 +/- 4.5, 15.6 +/- 6.8 and 18.4 +/- 9.9, respectively. No significant difference in baroreflex function slope was observed. During light halothane anesthesia (0.7 per cent endtidal) baroreflex function was significantly depressed (mean slope = 2.5 +/- 1.5), and it was abolished at 1.1 per cent end-tidal halothane (mean slope = 0.03 +/- 0.04). It is concluded that halothane anesthesia produces depression of baroreflex control of heart rate in man.

Adult↗

PubMed2026

Comparative efficacy and safety of pharmacokinetically guided and body surface area-based 5-fluorouracil dosing in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Body surface area (BSA)-based 5-fluorouracil (5-FU) dosing remains the standard in colorectal cancer despite substantial interpatient pharmacokinetic variability, which may lead to underexposure, treatment failure, or severe toxicity. This systematic review and meta-analysis evaluated whether pharmacokinetically guided 5-FU dosing improves efficacy and safety compared with conventional BSA-based dosing. METHODS: PubMed/MEDLINE, Embase, and Scopus databases were searched from inception to the final search date. The search identified 1,802 records: PubMed/MEDLINE, 47; Embase, 118; and Scopus, 1,637 records. Comparative randomized and non-randomized studies evaluating pharmacokinetically guided, area under the curve-guided, or therapeutic drug monitoring-based 5-FU dosing versus BSA-based dosing in colorectal cancer were included. Random-effects models were employed. The risk of bias was assessed using RoB 2 and ROBINS-I, and the certainty of evidence was evaluated using GRADE. RESULTS: Five studies comprising 809 unique patients were included. Across the primary severe-toxicity analysis, the pooled denominator was 1,338 reported observations, including 625 in the PK-guided 5-FU dosing arm and 713 in the BSA-based 5-FU dosing arm, because one study reported severe toxicity by treatment cycle rather than by patient. PK-guided dosing was associated with lower severe or grade ≥ 3 toxicity (RR 0.50, 95% CI 0.33-0.76; P = 0.001; I²=79%). PK-guided dosing was also associated with a higher objective response rate (RR 1.50, 95% CI 1.24-1.80; P < 0.0001) and disease control rate (RR 1.18, 95% CI 1.07-1.30; P = 0.001). Severe diarrhea was reduced (RR 0.33, 95% CI 0.18-0.62; P = 0.0006), whereas mucositis, neutropenia/leukopenia, and hand-foot syndrome were not significantly different between dosing strategies. CONCLUSION: PK-guided 5-FU dosing was associated with lower severe toxicity and diarrhea and higher objective response and disease-control rates than conventional BSA-based dosing. However, the evidence was derived from a small and clinically heterogeneous group of studies, and progression-free or overall-survival benefits could not be established. The findings apply predominantly to metastatic colorectal cancer treated with infusional 5-FU within FOLFOX- or FOLFIRI-based regimens. CLINICAL TRIAL REGISTRATION: Not applicable. This study was a systematic review and metaanalysis, and not a clinical trial.

Humans↗

PubMed2026

Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM. A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events. Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16 Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%. SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

Humans↗

PubMed1979

Randomized study of local control and survival following radical surgery or radiation therapy in oral and laryngeal carcinomas.

From 1971 to 1975, 100 patients with glottic, supraglottic, and oral cavity lesions were prospectively randomized between primary radiation treatment and primary surgery. Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx. Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76% and 100% (P=0.32); after secondary salvage attempts, local control rates were 82% and 100%, respectively (P= 0.52). Neither result approached statistical significance. Successful radiation for early glottic larynx lesions resulted in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy. For oral cavity lesions, swallowing was impaired in the same percentage of radiated and operated patients, but fewer primary radiation patients had articulation difficulties. Among the patients with supraglottic larynx lesions, aspiration was not a problem with either radiation or surgery, but successful radiation perhaps maintained a slightly better voice quality.

Carcinoma, Squamous Cell↗

PubMed2026

The clinical value of adding immune checkpoint inhibitors to radiotherapy for cancer: a systematic review and meta-analysis.

BACKGROUND: While several randomized clinical trials (RCTs) have explored the addition of immune checkpoint inhibitor (ICI) treatment for patients undergoing radiotherapy, studies systematically assessing the clinical value of such interventions are lacking. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant RCTs of cancers that received ICIs plus radiotherapy or radiotherapy. Eligible studies were those published in English as of 14 April 2024. Two independent reviewers screened the included studies and extracted relevant data, then selected the random or fixed-effects model based on the I2 statistic. The main outcomes were hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS); Odds ratios (ORs) with 95% CIs for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stratified analysis was performed based on cancer type, ICI type, and the timing of ICI addition. The study was registered on PROSPERO (CRD42024551008). RESULTS: 15 RCTs with 7947 patients were included. Pooled HRs were 0.865 (95% CI, 0.730-1.000; I2 = 72.1%) for OS and 0.799 (0.677-0.922; I2 = 82.0%) for PFS in cancer patients. In cancer types, adding immunotherapy to radiotherapy significantly improved patients with non-small-cell lung cancer (OS: 0.544 [0.371-0.717]; PFS: 0.527 [0.438-0.617]) and cervical cancer (OS: 0.722 [0.578-0.867] and PFS: 0.754 [95%CI, 0.621-0.887]). Regarding the ICIs schedule, adjuvant ICI therapy with pooled HRs was 0.742 (0.649-0.834) for OS and 0.638 (0.579-0.697) for PFS. In addition, the pooled ORs for the incidence of grade 3 or higher treatment-related and immune-related adverse events were 1.227 (1.059-1.421; I2 = 71.9%) and 2.217 (1.743-2.821; I2 = 74.0%), respectively. CONCLUSION: Adding immunotherapy to radiotherapy can provide significant clinical benefits for patients with NSCLC and cervical cancer, and the addition of these ICIs in the adjuvant stage is supported.

Humans↗

PubMed2025

PLSKO: a robust knockoff generator to control false discovery rate in omics variable selection.

MOTIVATION: Integrating the knockoff framework with any variable-selection method delivers stringent false discovery rate (FDR) control without recourse to p-values, offering a powerful alternative for differential expression analysis of high-throughput omics datasets. However, existing knockoff generators rely on restrictive modelling assumptions or coarse approximations that often inflate the FDR when applied to real-world data. RESULTS: We introduce Partial Least Squares Knockoff (PLSKO), an efficient, assumption-free generator that remains robust across diverse omics platforms. Our extensive simulations show that PLSKO is the only method to maintain FDR control with sufficient power in complex non-linear settings. Our semi-simulation studies drawn from RNA-seq, proteomics, metabolomics, and microbiome experiments confirm PLSKO generates valid knockoff variables. In pre-eclampsia multi-omics case studies, we combine PLSKO with Aggregation Knockoff to address the randomness of knockoffs and improve power, and demonstrate the method's ability to recover biologically meaningful features. AVAILABILITY AND IMPLEMENTATION: Our proposed algorithm is available on Github (https://github.com/guannan-yang/PLSKO) and Zenodo (https://doi.org/10.5281/zenodo.16879594).

Algorithms↗

PubMed2025

Relationship Between Cognitive Disorder and First-Line Targeted Therapy for Oncogene Driver-Positive Patients With Non-Small Cell Lung Cancer: Prospective Cohort Study.

BACKGROUND: Previous studies have found and confirmed a correlation between cognitive disorder and chemotherapy. As genetic testing becomes more routine in clinical practice, targeted therapies are increasingly gaining prominence. The relationship between targeted treatment and cognitive function is not yet clear. This study aimed to investigate the correlation between cognitive disorder and targeted treatment by evaluating the changes in cognitive function before and after targeted therapy. OBJECTIVE: This study aims to explore whether targeted therapy affects cognitive function in patients with advanced lung cancer and to explore the association between cognitive function, the inflammatory biomarker C-reactive protein, and psychological stress. METHODS: From the screened cohort of 150 patients with advanced non-small cell lung cancer (NSCLC) with gene mutations, 87 (58%) were rigorously selected for the study. The evaluation instruments used were the Mini-Mental State Examination scale, the Distress Thermometer, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 for assessing quality of life. RESULTS: A significantly lower progression-free survival (PFS) was observed in the group of patients surviving advanced NSCLC with cognitive disorder under targeted therapy in contrast to survivors in the group with no cognitive disorder (hazard ratio=0.347, 95% CI 0.209-0.578; P<.001). Furthermore, the objective response rate and disease control rate for the group with cognitive disorder were noted to be 37.8% and 86.7%, respectively, contrastingly lower than those in the group with no cognitive disorder, recorded at 78.6% and 97.6%, respectively. Significant variances were also noted in the Mini-Mental State Examination scores between patients with and without cognitive disorder both before and after targeted therapy (P<.001 in both cases), with a decreasing trend observed in both groups after targeted therapy. Noteworthy differences were found in quality of life scores both before and after targeted therapy (P<.001 in both cases). In addition, notable disparities were apparent in C-reactive protein levels among the 2 groups before and after treatment (P=.03 and P=.048 for each time point, respectively), with an upward trend observed in both groups after targeted therapy. The multivariate Cox regression analysis demonstrated that cognitive function is an independent risk factor for PFS in patients with NSCLC receiving targeted therapy. CONCLUSIONS: Cognitive disorder may lead to lower quality of life scores and shorter PFS in patients undergoing targeted therapy. Early screening and intervention for such patients could effectively improve clinical outcomes and quality of life.

Humans↗

PubMed1978

An evaluation of fast neutron beam teletherapy of metastatic cervical adenopathy from squamous cell carcinomas of the head and neck region.

One hundred thirteen patients with metastatic cervical adenopathy (MCA) from advanced squamous cell carcinoma of the head and neck completed fast neutron beam irradiation between September 1976 and March 1977. With a maximum follow-up time of 49.9 months (mean 14.5 months), 54% of the total group remain disease-free at the sites of their cervical adenopathy. Control of adenopathy measuring 3 cm or less in maximum dimension was 75% with neutrons only and 87.5% with mixed beams. Nodes measuring 3-6 cm were controlled 38.1% of the time with neutrons only and 59% of the time with mixed beams. Clinical control of adenopathy measuring greater than 6 cm was obtained in 12.5% with neutrons only and 29.4% with mixed beams. For patients with controlled primary tumors, the overall control rate in the neck was 72%; 100% of nodes 3 cm or less were controlled, 82% of nodes measuring from 3-6 cm were controlled, and 42% of nodes greater than 6 cm were controlled. Patients with controlled primary tumors treated with mixed beams had 100% control of nodes measuring 3 cm or less, 96% control of nodes measuring 3-6 cm, and 50% control of nodes measuring greater than 6 cm. Overall, the control rate for mixed beams was significantly better than for treatment with neutrons only. Morbidity was less (both acute and late) in the mixed beam-irradiated group.

Carcinoma, Squamous Cell↗

PubMed1979

Cocaine, d-amphetamine, and pentobarbital effects on responding maintained by food or cocaine in rhesus monkeys.

The effects of IM injections of cocaine, d-amphetamine, and pentobarbital were studied in rhesus monkeys whose lever-press responding was maintained under a second-order fixed-interval, fixed ratio schedule of reinforcement. Within each session, fixed-interval components, ending with the IV injection of 30 microgram/kg cocaine (one group of monkeys) or the delivery of a 300 mg food pellet (second group of monkeys), alternated with fixed-interval components ending without an injection of cocaine or the delivery of food (extinction). Drug pretreatments generally caused comparable dose-related decreases in the overall rates of responding reinforced either by cocaine or by food. Response rates during extinction usually increased and then decreased as the dose of each drug increased. An analysis of the drug effects on response rates in different temporal segments of the fixed intervals showed that in both the reinforcement and extinction components, the normally low control rates of responding which occurred earlier in the intervals were usually increased, while higher control rates which occurred later in the intervals were increased less or decreased. Thus, the effects of these drugs were relatively independent of the reinforcing event (food or cocaine) and tended to depend more on the ongoing rate of responding under these conditions.

Animals↗

PubMed2026

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N = 703) and aggregated data from the RAINBOW-Asia study (N = 440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO + PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size = 564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq + PTX significantly improved PFS compared with RAM + PTX (HR: 0.70; 95% CI: 0.51-0.96; p = 0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18 months at 20 months (95% CI: 0.08-2.27; p = 0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p = 0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p < 0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq + PTX (HR: 0.40, 95% CI: 0.32-0.50; p < 0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq + PTX than with RAM + PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p < 0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p < 0.05). For grade ≥3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq + PTX than with RAM + PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p < 0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq + PTX may be more effective than RAM + PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq + PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult↗

PubMed1979

Statically controlled cooling rate device.

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Blood Platelets↗

PubMed2026

Efficacy and Safety of Durvalumab plus Tremelimumab for Unresectable Hepatocellular Carcinoma: A Real-World Multicenter Observational Study.

Introduction: Durvalumab plus tremelimumab (Durva/Treme) improved survival in the HIMALAYA trial for unresectable hepatocellular carcinoma (HCC), but real-world evidence remains limited. This study aimed to evaluate clinical outcomes of Durva/Treme in routine practice. Methods: This retrospective multicenter study included patients with unresectable or advanced HCC who received Durva/Treme through the Expanded Access Program in Thailand between August 2023 and November 2025. Treatment outcomes and adverse events (AEs) were analyzed and descriptively compared with the HIMALAYA trial. Results: Fifty patients were included; median age was 62 years and 80% were male. Etiologies included hepatitis B (44%), hepatitis C (30%), and nonviral liver disease (26%). Most patients had Child-Pugh A (92%), while 24% had macrovascular invasion, including five with Vp4 portal vein involvement. The objective response rate (ORR) and disease control rate (DCR) were 12% and 60%, respectively. Among 43 patients meeting HIMALAYA eligibility criteria, ORR and DCR were 12% and 56%, respectively. With a median follow-up of 28.9 months, median progression-free survival (mPFS) and overall survival (mOS) were 4.6 and 10.5 months in the overall cohort, and 6.9 and 14.0 months in the HIMALAYA-eligible subgroup. Any-grade AEs occurred in 76% of patients, with grade ≥ 3 AEs in 24%. Hepatitis was the most common toxicity (48% overall; 14% grade ≥ 3). Conclusions: Durva/Treme demonstrated clinically meaningful activity with manageable toxicity in unresectable HCC. Outcomes among HIMALAYA-eligible patients were broadly consistent with the pivotal trial, supporting the feasibility of this regimen in routine clinical practice.

Aged↗