ABSTRACT
The single-pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory ß1 -selective antagonist/ß3 -agonist, and valsartan (80 mg), a renin-angiotensin-aldosterone system inhibitor, is the only Food and Drug Administration-approved ß-blocker/renin-angiotensin-aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration-approved non-ß-blocker/renin-angiotensin-aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine). Additivity is the ratio of placebo-adjusted SPC blood pressure (BP) reduction to the placebo-adjusted monotherapy component BP reduction sums. A weighted average of comparator scores was calculated and compared vs nebivolol/valsartan. Additivity ratio scores for nebivolol/valsartan SPCs (diastolic BP range: 0.735-0.866; systolic BP range: 0.717-0.822) were similar to the comparator weighted average (diastolic BP: 0.837; systolic BP: 0.825). Among the nebivolol/valsartan SPCs, 5/80 mg had the greatest additivity (diastolic BP: 0.866; systolic BP: 0.822). BP reduction contributions with monotherapy were similar for nebivolol/valsartan 5/80 mg SPC. Additivity scores for nebivolol/valsartan and select non-ß-blocker/renin-angiotensin-aldosterone system inhibitor SPCs were comparable.
Subject(s)
Hypertension , Nebivolol , Renin-Angiotensin System/drug effects , Valsartan , Adrenergic beta-1 Receptor Agonists/administration & dosage , Adrenergic beta-1 Receptor Agonists/adverse effects , Adrenergic beta-1 Receptor Agonists/pharmacokinetics , Aged , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin II Type 1 Receptor Blockers/pharmacokinetics , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/classification , Blood Pressure Determination/methods , Dose-Response Relationship, Drug , Drug Combinations , Drug Monitoring/methods , Drug Synergism , Female , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Male , Middle Aged , Nebivolol/administration & dosage , Nebivolol/adverse effects , Nebivolol/pharmacokinetics , Treatment Outcome , Valsartan/administration & dosage , Valsartan/adverse effects , Valsartan/pharmacokineticsABSTRACT
BACKGROUND: Impaired cardiac function in doxorubicin-treated childhood cancer survivors is partly mediated by the disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) and disrupts genes encoding for polypeptides that make adenosine triphosphate. METHODS: This cross-sectional study examined mtDNA copy numbers per cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high-risk acute lymphoblastic leukemia (ALL) who had been treated on Dana-Farber Cancer Institute childhood ALL protocols and had received doxorubicin alone (42%) or doxorubicin with the cardioprotectant dexrazoxane (58%). The number of mtDNA copies per cell and the OXPHOS enzyme activity of nicotinamide adenine dinucleotide dehydrogenase (complex I [CI]) and cytochrome c oxidase (complex IV [CIV]) were measured with quantitative real-time polymerase chain reaction immunoassays and thin-layer chromatography, respectively. RESULTS: At a median follow-up of 7.8 years after treatment, the median number of mtDNA copies per cell for patients treated with doxorubicin alone (1106.3) was significantly higher than the median number for those who had also received dexrazoxane (310.5; P = .001). No significant differences were detected between the groups for CI or CIV activity. CONCLUSIONS: Doxorubicin-treated survivors had an increased number of PBMC mtDNA copies per cell, and concomitant use of dexrazoxane was associated with a lower number of mtDNA copies per cell. Because of a possible compensatory increase in mtDNA copies per cell to maintain mitochondrial function in the setting of mitochondrial dysfunction, overall OXPHOS activity was not different between the groups. The long-term sustainability of this compensatory response in these survivors at risk for cardiac dysfunction over their lifespan is concerning.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cardiotonic Agents/therapeutic use , DNA Copy Number Variations/drug effects , DNA, Mitochondrial/drug effects , Dexrazoxane/therapeutic use , Doxorubicin/adverse effects , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Mitochondria, Heart/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Antibiotics, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Chromatography, Thin Layer , Cross-Sectional Studies , Doxorubicin/administration & dosage , Electron Transport Complex I/drug effects , Electron Transport Complex I/metabolism , Electron Transport Complex IV/drug effects , Electron Transport Complex IV/metabolism , Female , Follow-Up Studies , Humans , Infant , Leukocytes, Mononuclear/enzymology , Male , Mitochondria, Heart/drug effects , Mitochondria, Heart/genetics , Oxidation-Reduction , Phosphorylation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Real-Time Polymerase Chain Reaction , Sex Factors , SurvivorsABSTRACT
Critical-care settings have an opportunity to create healing environments (HEs). For the last decade, achieving this goal has been the task of the American Association of Critical Care Nurses. Today, several models used in these settings embrace synergistic care, healing therapies for patients, and the development of organizational models to improve the HEs for nurses themselves. Creating the HE is not impossible; however, researching the patient's experience within it is complex. This complexity requires researchers to consider biological, behavioral, and social variables on the unit. This article will describe biological and behavioral measures that may be used to examine the critically ill patient's response to an HE. Limitations of these measures are considerable. Future researchers will need to consider a multiplistic approach to the study of this construct.
Subject(s)
Critical Care/organization & administration , Health Facility Environment/organization & administration , Holistic Nursing/organization & administration , Nurse's Role , Nurse-Patient Relations , Humans , Interprofessional Relations , Models, Nursing , Nursing Evaluation Research , Nursing Methodology Research , Organizational Culture , Patient Care Team , United StatesABSTRACT
AIMS: To determine the reliability and validity of the Tobacco Craving Questionnaire (TCQ) and the validity of imagery scripts to elicit self-reported tobacco craving. DESIGN: Active imagery of three auditory scripts that described no-, low- and high-intensity of smoking urge. PARTICIPANTS: Current cigarette smokers (24 men, 24 women) not attempting to quit or reduce smoking. MEASUREMENTS: After each imagery condition, participants completed the 47-item TCQ, a Mood Form and Visual Analog Scale (VAS) questions. FINDINGS: Reliability of measures was demonstrated by internal consistency and unidimensionality of the four TCQ factors across imagery conditions. Criterion-related validity was demonstrated by an orderly increase in scores on the TCQ and VAS craving measures as a function of craving intensity of the imagery scripts. Increases in effect size parameters and parallel decreases in the stability of test-retest reliability for all craving measures indicated the validity of the imagery procedure. Convergent and discriminant validity were established by the craving scripts increasing self-reported craving, the no-craving (positive-affect) script increasing positive mood, the no-craving script not affecting craving and the craving scripts not affecting positive mood. CONCLUSIONS: Findings further demonstrated the reliability and validity of the TCQ as a multi-factorial instrument to assess the construct of tobacco craving and suggested that the lability of craving, rather than inconsistency and instability in its measurement, was responsible for observed effects.
