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Biomedical subjects

G R Morrow

Publications and source records attributed to G R Morrow.

At least 19 recordsLinked to original sources

Progress in reducing anticipatory nausea and vomiting: a study of community practice.

Chemotherapy-related nausea and vomiting (NV) in 300 consecutive patients treated in community practices prior to the availability of 5-HT3 antiemetics (9/87 to 1/91) were compared with NV in a second sample of 300 patients treated after their commercial introduction (9/93 to 2/95). Eighty-six percent of the later patients received 5-HT3 antiemetics, and significantly fewer (43.3%) reported one or more episodes of posttreatment vomiting during their first four cycles of chemotherapy compared with those in the previous sample (55.0%: P < .01). Identical numbers of both groups (79.3%) reported at least one episode of posttreatment nausea. A significant increase in the average duration of both posttreatment nausea (from 28.1 h to 37.2 h; P = 0.001) and posttreatment vomiting (from 10.9 h-16.5 h, P = .02) was found; no significant differences were seen in the reported severity of either symptom. The proportion of patients experiencing at least one episode of anticipatory nausea (31.0% vs 32.0%) or anticipatory vomiting (7.7% vs 6.3%) did not differ significantly (P > 0.5) between groups, nor were there significant differences in the duration or severity of anticipatory symptoms (P > 0.4 for all comparisons). The reduction in the frequency of posttreatment vomiting supports research findings of efficacy. Findings of an increase in duration of posttreatment nausea and emesis and no change in the frequency of posttreatment nausea or in anticipatory symptoms show a continuing need for progress in control of posttreatment emesis and emphasize the need for further research on the control of chemotherapy-induced nausea.

Adolescent

Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics.

Cancer chemotherapy is known to lead to nausea and vomiting in a large proportion of cases. If emesis is severe it can lead in its turn to anticipatory nausea and vomiting (ANV), which cannot be controlled by antiemetic medication. The etiology of ANV and various methods that have been used to counteract the condition are discussed.

Antiemetics

Statistical considerations in the design, conduct and analyses of antiemetic clinical trials. An emerging consensus.

Various aspects of trial design and planning for clinical testing of antiemetic therapies administered to cancer patients are considered. It is generally felt that a randomized double-blind parallel-arm design is the best. Ways of achieving adequate power of such studies are discussed briefly, as is the need for previous identification of primary and secondary end-points. Finally, summary recommendations are given.

Antiemetics

Initial control of chemotherapy-induced nausea and vomiting in patient quality of life.

The side effects commonly experienced by patients receiving chemotherapy for the treatment of cancer can challenge many aspects of daily life. Nausea and vomiting, the most common side effects reported by patients, affect the ability to continue with usual life activities and, thus have a pronounced impact on quality of life. This paper reviews studies of the impact of nausea and emesis on quality of life, and highlights the importance of prevention of these side effects by presenting new data on how persistent uncontrolled nausea and vomiting can be. The Morrow Assessment of Nausea and Emesis (MANE) was used to collect information on symptoms experienced by consecutive patients starting chemotherapy between September 1987 and December 1995 at any of 18 geographically diverse member sites of the University of Rochester Cancer Center Community Clinical Oncology Program. Data from 1,413 patients were collected after each of four successive chemotherapy treatments. Reported incidences of posttreatment nausea and posttreatment vomiting after the first treatment were 59.4% and 28.6%, respectively. Occurrence of nausea/vomiting at the first treatment was a strong predictor of nausea/vomiting at later treatments. Of the 839 patients reporting initial nausea, 763 (90.9%) reported nausea at at least one subsequent treatment, and approximately 59% reported nausea after all three subsequent treatments. Fewer than half (45.6%) of the patients who had no nausea at the first treatment developed it later. The majority (72.0%) of patients reporting vomiting at the first treatment also reported subsequent vomiting, 30.7% of whom experienced emesis at all remaining treatments. Conversely, 76.2% of patients who were emesis-free at the first treatment remained so for all later treatments. These findings show a continuing need for further progress in controlling nausea and vomiting, and demonstrate the importance of aggressive nausea/vomiting control at the first treatment. In addition, more emphasis on controlling chemotherapy-induced nausea after its initial occurrence is necessary.

Antineoplastic Agents

Accumulation of manganese in rat brain following intranasal administration.

Manganese chloride (50-800 micrograms) was injected unilaterally into the right nostril of rats and its accumulation in the central nervous system (CNS) was monitored. Brain manganese levels were elevated in a dose-dependent, time-dependent, and tissue-dependent manner. Elevated levels of manganese were detected in the right olfactory bulb and olfactory tubercle within 12 hr after instillation and remained elevated for at least 3 days. As little as 100 micrograms of manganese chloride was sufficient to increase brain manganese levels. No changes were detected on the left side of the brain. The manganese content of the striatum, the target site for manganese neurotoxicity, was unchanged following acute administration, but was elevated when two injections were made 1 week apart. These results suggest that air-borne manganese can be retrogradely transported along olfactory neurons to the CNS and can reach deeper brain structures under appropriate exposure conditions.

Administration, Intranasal

Cardiac spectral power reflects parasympathetic but not sympathetic nervous system activity in a clinical population.

The purpose of this short communication is to report our clinical findings regarding the use of the low frequency (LF, 0.02-0.15 Hz) and high frequency (HF, > 0.15 Hz) components of the spectral decomposition of heart-rate as indices of sympathetic (SNS) and parasympathetic nervous system (PNS) activity, respectively. Thirty-two females with histologically confirmed ovarian cancer, ranging in age from 46-72 years, participated in an autonomic assessment protocol consisting of a resting heart rate recording and several ANS function tests. The LF, HF and total power measures from the spectral decomposition were highly correlated with one another. In addition, the spectral components were most highly correlated with measures of PNS activity, i.e. standard deviation of heart rate at rest and the ratio of the six longest to the six shortest R-R intervals during deep breathing (E:I ratio). It is concluded, as other researchers have stated, that the use of the HF component of the HR spectrum as a measure of PNS activity is warranted, but caution must be used when interpreting the LF component.

Aged

Frequency and correlates of fatigue in lung cancer patients receiving radiation therapy: implications for management.

The medical records of 50 consecutive patients receiving radiation therapy for histologically diagnosed lung cancer were retrospectively reviewed to determine the frequency of fatigue and its relationship to pain, depression, and other potentially treatable correlates. Fatigue developed in 39 of the 50 patients (78%), and was not strongly related to demographic or disease variables. Pain was experienced by 40 patients (80%), but depression was noted in the records of only six patients (12%). Onset of fatigue closely followed development of pain in only 11 patients. Lower frequency of fatigue in patients with previous surgery or chemotherapy and the likelihood of a response shift suggest these were not significant causes of fatigue. Previous studies highlight a higher frequency of depression in cancer patients and a correlation with treatment-related fatigue. Prospective studies on the relationship between depression and fatigue and the ability of antidepressants to ameliorate treatment-related fatigue are needed.

Adult

Frequency and clinical implications of delayed nausea and delayed emesis.

Studies of the adverse effects of cancer chemotherapy often do not distinguish between delayed and persistent nausea and emesis. Although persistent nausea is simply acute nausea that continues beyond the treatment day, postchemotherapy delayed nausea and delayed vomiting first develop after an initial 24 h free of these symptoms. To access its occurrence in clinical practice, we conducted a structured examination of chemotherapy-induced delayed nausea and emesis in consecutive chemotherapy patients unselected for diagnosis, chemotherapy, or antiemetic usage. Three hundred twenty-seven consecutive with histologically confirmed cancer were followed through three consecutive chemotherapy treatments at three geographically separate institutions. Patient-reported assessments of nausea and emesis were made for each 6-h period over 3 days after chemotherapy. One in three patients developed delayed nausea and one in four incurred delayed emesis. Of >950 chemotherapy treatments assessed, approximately 1 in 6 were characterized by delayed nausea and 1 in 9 by delayed vomiting. We conclude that nausea and emesis that first begin >24 h after chemotherapy are a significant clinical concern. Patients receiving cancer chemotherapy without being admitted to the hospital should be informed of the possible occurrence of delayed nausea and vomiting and be given adequate and appropriate antiemetic medication for use at home for the prevention of these delayed side effects.

Adolescent

Models, mechanisms and management of anticipatory nausea and emesis.

Anticipatory nausea and vomiting (ANV) are learned responses to chemotherapy that develop in up to 25% of patients by the fourth treatment cycle. Post-treatment nausea and emesis must occur before development of ANV can take place. Certain patient characteristics and other responses to chemotherapy can also be used to predict their occurrence. Once they develop, ANV cannot be controlled by pharmacologic means including use of new 5-HT3 receptor antagonists. By contrast, behavioral therapies involving relaxation, most notably systematic desensitization, can be used to effectively treat ANV. Clinic personnel including oncologists and oncology nurses as well as behavioral psychologists can effectively administer systematic desensitization to chemotherapy patients.

Animals

Progress in reducing nausea and emesis. Comparisons of ondansetron (Zofran), granisetron (Kytril), and tropisetron (Navoban).

BACKGROUND: Nausea and vomiting are the most distressing side effects associated with the administration of chemotherapy for neoplastic diseases. Nausea, in particular, often had been ignored in studies of chemotherapy side effects. Recently, progress has been made in the control of chemotherapy-induced nausea and vomiting, due, in part, to a better understanding of the physiologic mechanisms involved. METHODS: This paper reviews recent advances in the control of emesis, focusing on pharmacologic treatments. RESULTS: The efficacy and safety of the serotonin (5-HT3) receptor antagonists granisetron, ondansetron, and tropisetron in the control of acute and delayed emesis and emesis induced by repeat-cycle chemotherapy are summarized. Although differences in study design and definitions of response criteria have made it difficult to compare the studies that have evaluated these three agents, the overall body of literature supports several clinical findings. CONCLUSIONS: (1) The 5HT3 antiemetic agents have been shown to be clinically more effective in the control of nausea and emesis than previously used agents. (2) No one of the three has demonstrated consistently greater efficacy. (3) Efficacy appears to be more pronounced for cisplatin-containing regimens than for moderate or less emetogenic chemotherapy regimens. (4) Effectiveness of the 5HT3 agents appears to be less for delayed nausea and emesis than for acute symptoms. Potential control of anticipatory nausea and emesis has not been investigated. (5) Control over nausea appears to be significantly less than control over emesis. In the studies in which it has been measured, nausea control remains incomplete for approximately half the patients given 5HT3 agents. (6) The efficacy of the agents appears to diminish across repeated days and, perhaps, across repeated chemotherapy cycles. (7) The addition of a steroid such as dexamethasone increases the efficacy of both 5HT3 and other antiemetic agents. This effect also seems to apply to delayed nausea and emesis.

Antiemetics

Autonomic measures associated with chemotherapy-related nausea: techniques and issues.

Advances in antiemetic therapy for cancer patients have been hindered by a lack of understanding of the physiological mechanisms associated with nausea and their corresponding measurement techniques. Here we review conceptual and methodological issues involved in developing an autonomic frame of reference for nausea and outline two strategies for assessing autonomic function. A primarily research-oriented strategy uses heart rate, blood volume pulse, pallor, and skin temperature to assess autonomic activity and reactivity over 24 hr. Peak values of these measures relative to time of emesis, heart rate spectral analyses of autonomic activity, and analyses of the standard deviation of successive differences of beat-to-beat intervals were all associated with subsequent nausea. A primarily clinically oriented strategy assesses normal and abnormal results on eight common bedside clinical tests of autonomic function. The total number of abnormal tests was associated with subsequent nausea. A better understanding of chemotherapy side effect mechanisms is likely to result in less polypharmacy and more effective individualized treatment for cancer patients.

Arrhythmia, Sinus

Behavioral aspects of clinical trials. An integrated framework from behavior theory.

A less-than-optimal proportion of patients with cancer are entered into National Cancer Institute-sponsored clinical trials. This article reviews the literature on accrual in oncology clinical trials to characterize the extent of the problem, identify reasons for low accrual, and suggest ways to promote accrual. Four well known theories of health behavior (the Health Belief Model, Subjective Expected Utility Theory, Protection Motivation Theory, and the Theory of Reasoned Action) point to central concepts involved in understanding patient health-related behavior: (1) the probability that an unwelcomed health event will happen to a patient, (2) the severity of that event if it does occur, (3) the effectiveness of a particular behavior (such as taking part in a clinical trial) to modify the severity, and (4) the cost of adopting that behavior. These concepts form a framework for integrating the available information about accrual to clinical oncology trials. Patient and physician factors previously related to clinical trials suggest specific recommendations for increasing accrual to clinical oncology trials.

Clinical Trials as Topic

Behavioral science in translational research and cancer control.

Behavioral science plays an integral, essential role in cancer control. This review examines that role in two broad areas: (1) in the development and implementation of cancer control technologies, and (2) in the emerging focus on the process of translating cancer research into clinical practice. In developing and implementing cancer control technologies, what we know of human processes as a result of behavioral science is identified as the common link in all stages of the cancer process (prevention, detection, treatment, rehabilitation, terminal care). The value of behavioral science is shown in conservative projections (incorporating likely rates of patient noncooperation) of the health benefits obtainable by the year 2000 if effective behavioral strategies in three key areas were broadly implemented. Smoking prevention and cessation programs could lead to 7.2 million fewer smokers; application of cancer screening programs might result in 45,000 additional 5-year cancer survivors each year; and behavioral programs could lead to improved quality of life in 150,000 patients per year who experience treatment side effects despite the use of antiemetics. Behavioral science also is shown to contribute to translational science by providing a pragmatic conceptual model for clinical practice and facilitating collaborative research between basic scientists and clinical researchers. As an example of behavioral science's contribution to translational research, behavioral issues in genetic screening for cancer risk are outlined based on the experience of several families with the BRCA1 genetic marker and patients with Huntington's disease.

Behavioral Sciences

Behavioral treatment of chemotherapy-induced nausea and vomiting.

Nausea and vomiting associated with chemotherapy most commonly occur after administration of the drug regimen, but a substantial proportion of patients also develop these symptoms in anticipation of treatment, after one or more courses of chemotherapy have been given. Currently available pharmacologic agents are unable to provide complete protection from either anticipatory or post-treatment nausea and emesis associated with cancer chemotherapy. Since anticipatory nausea and vomiting are believed to become conditioned responses through the learning process of classical conditioning, behavioral treatments may be particularly appropriate. Progressive muscle relaxation training is effective in preventing as well as decreasing the frequency of postchemotherapy nausea and vomiting, whereas systematic desensitization has been found to be more effective against anticipatory nausea and emesis. Hypnosis and cognitive distraction have been used mainly in children and adolescents.

Antineoplastic Combined Chemotherapy Protocols

Measurement of quality of life in patients: psychometric analyses of the Functional Living Index-Cancer (FLIC).

Biomedical advances in medical care and treatment have highlighted potential trade-offs between the length and quality of a patient's life. There is increasing need for psychometrically sound measurement of quality of life in medical patients. Psychometric analyses of the Functional Living Index-Cancer (FLIC) were conducted on data from 530 consecutive patients with histologically confirmed cancer. To examine construct validity, a principal components analysis was conducted that revealed a five-factor solution accounting for 70% of the variance in a random half of the original sample and 68% in a cross-replication sample. Content analysis indicated that domains of physical, psychological and social functioning are assessed along with the patient's view of their current well-being and disease symptoms. Convergent-discriminant validity was shown with independent measures of symptoms and anxiety. Most, but not all expected differences in quality of life by demographic and psychological variables were found. Within the limitations imposed by the study and its sample, the FLIC appears to be a conceptually sound, internally consistent instrument worthy of use and further study in other health care samples.

Adolescent

Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists.

Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life. Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists. This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists. Seventy-two consecutive cancer patients with ANV were randomly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was found effective in reducing anticipatory nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care.

Behavior Therapy

Methodology and assessment in clinical anti-emetic research: a meta-analysis of outcome parameters.

There have been major clinical advances in the control of chemotherapy-induced nausea and emesis. These advances were achieved partly by the introduction of new anti-emetic agents but important improvement came from the use of existing agents in ways developed from the results of studies based on new approaches and methods in anti-emetic research. By developing basic research tools, improving methodology and applying psychometrically sound assessments better management or chemotherapy-induced nausea and vomiting has been achieved. The goals of anti-emetic assessment are discussed here along with data and examples of assessment techniques for emesis and nausea. Examination of 153 separate anti-emetic studies between the years of 1975 and 1988 showed that emesis was the most common outcome measure used and that approximately 1 out of five studies measured some other type of outcome usually in the context of nausea and emesis. The frequency of outcome events was most commonly the dimension assessed. Examination of size of the effect of an anti-emetic regimen for these anti-emetic studies showed it to be independent of the type of outcome measured, but to be quite dependent on how the outcome was quantified. For instance, differences in the frequency or incidence of either nausea or emesis were generally larger than measurements made of the duration of either of these.

Antiemetics

Autonomic changes during cancer chemotherapy induced nausea and emesis.

Certain autonomic variables have been shown to be responsive to motion induced nausea and vomiting. Here we report preliminary data on changes in heart rate, blood volume pulse, pallor and skin temperature assessed during a one hour period at baseline, a one hour period of peak nausea, and a one hour period of emesis in five female patients receiving identical cancer chemotherapy and antiemetic drugs according to a common protocol. Examination of coefficients of variation showed that heart rate and face temperature were more stable measures across each of the three time periods than blood volume pulse and pallor. Furthermore, the four measures were found to be more variable during times of emesis than times of nausea. The four measures were shown to be responsive to patient reported nausea and vomiting. Temperature and pallor showed a linear change from baseline to nausea to vomiting. Heart rate and blood volume pulse significantly decreased from baseline time during nausea and then significantly increased from a time of nausea to during emesis. Variations in the time course of each variable change during nausea supported a view that nausea may be more related to a rebound of parasympathetic activity than a slow decrease of sympathetic activity. Replication with larger samples is needed. Examination of the nausea and vomiting of pregnancy, general anaesthesia or different chemotherapeutic agents could help explore whether results reported here are singular or representative of a more generalisable autonomic response associated with patient reported nausea.

Antineoplastic Agents