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PubMedDate not supplied

Rationing decisions and individual responsibility for illness: are all lives equal?

OBJECTIVES: This survey measured individuals' rationing allocation choices for situations in which patients are deemed to hold personal responsibility for their diseases and the influence of different arguments on such choices. METHODS: The association between allocation decisions for liver disease and asthma and the belief that a patient was responsible for his or her illness was modeled using multivariable regression analysis, controlling for the effect of arguments on choices. RESULTS: In data from 310 returned surveys (43% response rate), respondents were 10 to 17 times more likely to allocate liver transplants or asthma treatment to patients they deemed not responsible for their illnesses than to patients they deemed responsible for their conditions (liver transplants: odds ratio [OR] = 10.3, 95% confidence interval ([CI] = 2.5-42.1; asthma: OR = 16.8, 95% CI = 2.1-136.6). CONCLUSIONS: Personal responsibility for illness was an important consideration in respondents' rationing allocation decisions. These choices appeared to be stable although possibly influenced by respondents' interpretations of the survey scenarios and decision tasks.

Adult↗
PubMed2024

eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.

Humans↗
PubMed1994

Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.

BACKGROUND: The efficacy of the step 1 diet in outpatient women with hypercholesterolemia has been debated. METHODS: Forty-one normotriglyceridemic women whose low-density lipoprotein (LDL) cholesterol levels were 3.62 to 5.17 mmol/L (140 to 200 mg/dL) participated in a two-period outpatient diet counseling study that used a 1-month high-fat, high-saturated fatty acid period (Hi-Sat diet) and a 4-month low-fat, low-saturated fatty acid period (step 1 diet). All women were postmenopausal and were not taking hormone replacement therapy. Levels of lipids, lipoproteins, and plasma triglyceride fatty acids were measured five times during the last 2 weeks of each dietary period. Dietary intake was assessed by 7-day food records. RESULTS: The mean reduction in total cholesterol level achieved by the step 1 diet was 0.36 mmol/L (14 mg/dL). The reduction in total cholesterol level was seen in both LDL cholesterol levels (0.28 mmol/L [11 mg/dL]; P < .005) and high-density lipoprotein cholesterol levels (0.08 mmol/L [3 mg/dL]; P = .08). Although individual LDL responsiveness to diet was normally distributed, there was marked variation in response, which could be explained only partially by compliance (change in saturated fat intake, 10%), change in body weight (3%), and an interaction between the palmitic acid content of the plasma and body weight (3%). CONCLUSIONS: A step 1 diet lowers total and LDL cholesterol levels in postmenopausal women. A nonsignificant reduction in high-density lipoprotein cholesterol levels was also observed. Since some women achieved LDL cholesterol levels low enough to obviate the need for drug therapy as primary prevention of coronary heart disease, dietary therapy should remain the first step in the management of hypercholesterolemia in postmenopausal women.

Aged↗
PubMed1998

Dietary treatment of hypercholesterolaemia: lack of relationship between individual response and genetic variation at the lipase loci. The Fluvastatin Genotyping Group.

The individual benefits of dietary therapy for hyperlipidaemia are known to be unpredictable. Variants at the lipoprotein lipase gene have been shown to associate with atherogenic lipoprotein phenotypes and the delayed clearance of triglyceride-rich lipoproteins. Together with variants of the closely homologous hepatic lipase gene, these may influence the extent of amelioration of plasma lipoprotein concentrations seen in dyslipidaemic patients treated with a low saturates/low cholesterol diet. We correlated the lipid changes seen following an 8-week diet in 83 subjects with primary hypercholesterolaemia (fasting plasma cholesterol > 6.5 mmol/L) with alleles of three restriction polymorphisms (LPL-Hind III and Pvu II; HL-Msp I). Although dietary changes produced a significant improvement in fasting lipids [total cholesterol falling by 5.2% (range -27.9% to +24.3%) and low-density lipoprotein cholesterol reduced by 6.0% (-30.5% to +29.3%)], no significant difference in response between different genotypes could be detected.

Adult↗
PubMed1991

Predictive value of the fluorescent cytoprint assay (FCA): a retrospective correlation study of in vitro chemosensitivity and individual responses to chemotherapy.

The potential clinical usefulness of the fluorescent cytoprint assay (FCA) was assessed retrospectively in 73 cancer patients by correlating individual tumor chemosensitivity in vitro with responses to chemotherapy. The data show that the FCA has a sensitivity of 98%, specificity of 81%, and predictive accuracies of 85% and 97% for positive and negative clinical responses, respectively.

Antineoplastic Agents↗
PubMed1996

Flunitrazepam effects on human sleep EEG spectra: Differences in NREM, REM and individual responses.

Flunitrazepam (FNZ) (4mg), an intermediate type benzodiazepine (BDZ) hypnotic, was administered orally to five healthy male subjects (Ss) for seven consecutive nights. Sleep EEG from the baseline night (BLN), the initial drug night (IDN), the fourth and the seventh drug nights (4DN, 7DN) was subjected to fast Fourier transform (FFT) analysis. During NREM sleep of 4DN and 7DN the sigma band (11.0-12.5 Hz) activity was similarly enhanced in every S. In REM of 4DN and 7DN beta band (23.0-29.0 Hz) was enhanced, but with larger variations among Ss. High intra-individual consistency of the relative EEG power patterns on 4DN and 7DN was observed. These results suggest that 1) EEG responses to FNZ are different in sleep states; explorations of these differences may provide better understandings of sleep mechanisms, and 2) individual variations in EEG responses may reflect individual variations of the BDZ receptor system. These methods may be useful for exploring receptor changes in neuropsychiatric disorders.

Adult↗
PubMed2002

Individual response profiles of male Wistar rats in animal models for anxiety and depression.

Previous work has shown that systematic individual differences between male Wistar rats can be detected in tasks like the elevated plus-maze, or the open field. Here, we investigated whether individual profiles of anxiety, as measured with the plus-maze, may predict behavioral response profiles in other tasks where anxiety, aversion, or depressive behaviors are important. Male Wistar rats were initially screened: (A) in an open field; and (B) in an elevated plus-maze. Based on their plus-maze behavior, that is, the time spent in the open arms, the animals were divided into two subgroups with either 'low' or 'high' anxiety (LA or HA) levels. These subgroups were exposed to other experimental anxiety paradigms, namely object burying and two-way active avoidance, and an animal model of depression, the forced swim test. In the plus-maze, the percentage of time spent on, and the number of entries into the open arms were lower in HA than in LA rats. In the object burying task, HA rats showed more burying behavior of Tabasco-coated marbles, and in the active avoidance task, they showed slower acquisition of avoidance learning and higher escape latency as compared to LA rats. Finally, LA and HA rats behaved similarly in the forced swim test; however, the percentage changes of immobility time between test days 1 and 2 were negatively correlated to open field behavior, namely locomotor activity and center entries. On the other hand, the frequencies of rearing in the open field, which can also gauge functional differences between rats (for example responsiveness to novelty, psychomotor activation), were not substantially related to the behavioral profiles in the tests of anxiety and depression. These results show that individual differences of anxiety in the plus-maze can be predictive of behavior in other anxiety models, but not in forced swim test, indicating that they may be determined partly by similar functional and physiological mechanisms.

Adaptation, Psychological↗
PubMed2001

Biochemical markers of individual response to growth hormone replacement in adults.

Options for determining the response to growth hormone (GH) replacement in adults include symptomatic response, changes in body composition and measurement of biochemical markers of GH action. It has become apparent from various studies and during routine clinical practice that abnormal elevation of serum markers of GH action during GH therapy may not be associated with either adverse symptoms or abnormalities in body composition, thereby limiting the value of subjective assessment and physical characteristics as safety markers of over-treatment. Candidate biochemical markers include insulin-like growth factor I (IGF-I), IGF-binding protein 3 (IGFBP-3) and the acid-labile subunit (ALS), and markers of bone remodelling. No single measurement provides an ideal index of adequacy of GH replacement. Serum IGF-I has the greatest utility during GH dose titration as it is more sensitive to changes in GH status than IGFBP-3 and ALS, and is also more sensitive to excessive GH replacement. IGF-I, therefore, provides an important safety marker. Furthermore, changes in IGF-I correlate with improvements in body composition. Changes in circulating insulin and leptin occur during GH therapy, but are significantly influenced by changes in body fat and its distribution and do not provide useful information upon which to gauge responsiveness to GH. Markers of bone remodelling are an important indicator of GH action within individuals, but exhibit wide inter-individual variation which limits their usefulness in defining relative GH responsiveness.

Biomarkers↗
PubMedDate not supplied

Individual responsibility for health. Decision, not discovery.

Health policy sometimes hinges on claims about the responsibility borne by people or corporations for health outcomes. We don't want these claims to be arbitrary, so we construe them as discoveries of plain fact. But we're mistaken. They are interwoven with our values and social institutions. Recognizing that they are allows us to debate them more honestly and thoroughly.

Decision Making↗
PubMed1985

Individual responsiveness to topical pilocarpine and the effects of variations in application technique.

The effects of nasolacrimal obstruction (NLO) and of eyelid closure (EC) were studied in a group of 6 healthy female subject (25-29 years). The aim was to determine the best application technique for patients. NLO or EC for 1 min was assumed to be a maximum time for patient compliance. A standard eye drop bottle was used with a drop volume of about 40 microliter. One drop of a 1% pilocarpine solution was instilled into the lower conjunctival sac of one eye in a randomized manner: a) NLO b) EC c) NLO and EC d) neither NLO nor EC. The effects on the pupil size, static refraction for distance and accommodative power were followed for 2 h. The results showed no significant difference between the 4 techniques. Pronounced interindividual differences but only small intraindividual differences were found in this group of healthy young females. Two subjects always responded strongly, and 2 other subjects always did so weakly. The application of the same amount of pilocarpine ointment (3%) increased and prolonged the effects on pupil size, refraction and accommodation at all points of time without reaching statistical significance compared with eye drops. Pilocarpine ointment caused considerable subjective discomfort. The experiments with pilocarpine suggest that, from a practical point of view, different techniques of application of ocular drugs seem to be a little importance with regard to local effect. The possibility of pronounced individual differences in pharmacological response should be borne in mind. Pilocarpine induced a significant increase in accommodative power.

Accommodation, Ocular↗
PubMed1987

Personality and demographic variables related to individual responsiveness to diving stress.

Thirty U.S. Navy divers were tested for 4 personality and 2 demographic variables. They subsequently were exposed to the stress of being pressurized in a small diving chamber for several hours. Stress responsiveness to this condition was assessed using 3 physiologic and 4 subjective emotionality measures before and after the dive. These physiologic and emotionality measures were factor analyzed and correlated with personality and demographic variables. Difference scores among the physiologic and emotionality measures, indicating responsiveness to stress, correlated significantly with education, diving experience, internality-externality, disinhibition, and socialization. These data indicate that measures of achievement (i.e., diving experience and education), perceived control, sensation seeking, and social adjustment are useful in accounting for individual differences in acute emotional and physiologic responsiveness to stressful diving conditions.

Adult↗
PubMed2003

Monitoring individual response to brain-tumour chemotherapy: proton MR spectroscopy in a patient with recurrent glioma after stereotactic radiotherapy.

Since antineoplastic activity varies, sensitive methods for individual assessment of efficacy are needed. We demonstrate the clinical value of MR spectroscopy in monitoring chemotherapy in a patient with recurrent glioma after stereotactic radiotherapy. Diagnostic imaging before and after chemotherapy included contrast-enhanced MRI, single-voxel proton MR spectroscopy ((1)H MRS), (1)H MR spectroscopic imaging ((1)H SI), and fluorodeoxyglucose (FDG) positron-emission tomography (PET). A significant decrease in choline signal intensity was observed 2 months after chemotherapy indicating tumour chemosensitivity, in line with tumour shrinkage on MRI and decreased uptake of FDG. Assessment of early response by MRS may help to improve treatment protocols in other patients.

Adult↗
PubMed2001

Importance of individual response in symptom score evaluation.

In making treatment decisions for patients with benign prostatic hyperplasia (BPH), physicians have to rely on the efficacy data published in the literature and adapt this to individual patient's needs. Criticism can be made, however, of the randomised clinical trials (RCTs) that are performed, as the patients enrolled are not an adequate reflection of the general patient population. Although internal validity is high in RCTs with regard to inclusion criteria, external validity is reduced. Another failing of RCTs is the way in which patients are assessed. Typically in many studies, symptom improvement is expressed as a percentage of the Symptom Index improvement. This can be misleading if the results of two trials are compared as this value depends on the pre-treatment Symptom Index. Other methods of evaluation should be considered, such as the presentation of direct symptom outcomes (threshold improvement), the cumulative frequency distribution of threshold improvements or linear regression analysis of individual IPSS. All of these means of expressing the results focus clinical evaluation on the patient himself.

Clinical Trials as Topic↗
PubMedDate not supplied

Continuing professional education: individual responsibility, collective consciousness.

Continuing professional education in the United Kingdom is discussed and the influences examined. Within a framework of national, nursing, and local perspectives, the issues and implications for the various individual agencies and personnel are identified. An overview is provided to include agendas for action.

Education, Nursing, Continuing↗
PubMed1989

Cyclobuta-dithymidine induction by solar-simulating UV radiation in human skin: II. Individual responses.

The purpose of this study was to examine cyclobuta-dithymidine (T*T) photoproduct induction and persistence in human skin exposed in situ to simulated solar UV radiation. Small areas of untanned skin in nineteen individuals were exposed using a solar UV apparatus that simulates both the spectrum and intensity of the UV portion of summer midday sunlight at 39 degrees N latitude. The equivalent of approximately 60 min of sunlight exposure (72KJ/m2) was administered, and T*T photoproducts were quantitated by enzyme-linked immunosorbent assay (ELISA) of DNA extracted from skin punch biopsies. Net yields of T*T photoproducts were determined in 10 individuals, with the majority (7 of 10) between 0.02 and 0.12 T*T per kilobase (Kb). The three remaining individuals had higher levels of photoproducts but were not unusually sensitive to solar UV as determined by minimal erythema dose (MED). Percentage loss of T*T photoproducts 4 h after exposure was determined in nine individuals to be 80.2 +/- 14.0%.

Adult↗