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Biomedical subjects

K Hoffman

Publications and source records attributed to K Hoffman.

At least 19 recordsLinked to original sources

Alternative methods of interpreting quality of life data in advanced gastrointestinal cancer patients.

Understanding of how to analyse and interpret quality of life (QoL) data from clinical trials in patients with advanced cancer is limited. In order to increase the knowledge about the possibilities of drawing conclusions from QoL data of these patients, data from 2 trials were reanalysed. A total of 113 patients with pancreatic, biliary or gastric cancer were included in 2 randomised trials comparing chemotherapy and best supportive care (BSC) with BSC alone. Patient benefit was evaluated by the treating physician (subjective response) and by using selected scales and different summary measures of the EORTC QLQ-C30 questionnaire. An increasing number of drop-outs (mainly due to death) with time did not occur in a random fashion. Therefore, the mean scores in the different subscales of the QLQ-C30 obtained during the follow-up of interviewed patients did not reflect the outcome of the randomised population. The scores of the patient-provided summary measure, 'Global health status/QoL', were stable in a rather high proportion of the patients and could not discriminate between the 2 groups. 3 other summary measures revealed greater variability, and they all discriminated between the 2 groups. A high agreement was also seen between the changes in the summary measures and the subjective response. A categorisation of whether an individual patient had benefited or not from the intervention could overcome the problem with the selective attrition.

Adult↗

Glaucoma filtering bleb dysesthesia.

PURPOSE: To determine the prevalence and risk factors for glaucoma filtering bleb dysesthesia (discomfort). METHODS: A prospective cross-sectional observational study of consecutive patients with unilateral glaucoma filtering blebs from trabeculectomy was conducted. A self-report questionnaire was administered, which asked about the frequency and severity of the following symptoms: ocular pain, discomfort, burning, foreign body sensation, and tearing. The following variables were recorded by the investigators: age, race, sex, type and date of glaucoma surgery, antifibrotic agent used, intraocular pressure, location, thickness, and size of bleb, percent coverage of the bleb by the eyelid, angle that the bleb made to the cornea, and the presence of epithelial defects or dellen. Dysesthesia scores between the affected eye and control eye were compared using the paired Student t test. Risk factors for dysesthesia were evaluated using analysis of variance or Pearson correlation coefficient. RESULTS: A total of 97 patients were enrolled in the study. The mean total dysesthesia score (+/-SD, range) in the affected eye was 11.1 (+/-9.4, 0 to 42) and in the unaffected eye 3.4 (+/-4.9, 0 to 25, P =.001). Factors that predisposed to dysesthesia included younger age (P =.005), superonasal location of bleb (P =.036), presence of bubbles (P =.028), and poor lid coverage (P =.013). The steeper the angle of the bleb to the cornea, which was an indirect measure of the height of the bleb, the more likely a patient was to have bubbles (P =.001). CONCLUSION: Eyes with glaucoma filtering blebs experience more dysesthesia than eyes without filtering blebs. Young age, superonasal bleb location, poor lid coverage, and bubble formation are all associated with glaucoma filtering bleb dysesthesia.

Adolescent↗

Presumed topiramate-induced bilateral acute angle-closure glaucoma.

PURPOSE: We describe a case of bilateral angle-closure glaucoma associated with oral topiramate therapy. METHODS: Interventional case report. Case report with echographic illustration. RESULTS: A 51-year-old man developed bilateral acute angle-closure glaucoma 2 weeks after beginning topiramate therapy for bipolar affective disorder. Laser peripheral iridotomy was performed in the right eye without resolution of the acute attack. Echography revealed lens thickening and ciliochoroidal detachments in both eyes. Visual acuity, intraocular pressure, and anterior and posterior segment anatomy normalized 2 weeks after cessation of topiramate therapy. CONCLUSION: Topiramate, a new sulfa-derivative antiepileptic medication, may cause idiosyncratic ciliochoroidal detachments and ciliary body edema leading to anterior displacement of the lens-iris diaphragm, lens thickening, and acute angle-closure glaucoma.

Acute Disease↗

Interpapillary lines--the variable part of the human fingerprint.

The dermatoglyphic pattern of human palms and soles is individually unique and unchanging. Their prints show the course of the papillary ridges as papillary lines. Case reports and a few older studies of repeatedly taken fingerprints could, however, show that so-called interpapillary lines can develop between the papillary lines. The questions of this study were: How often do interpapillary lines occur? Can the differences between papillary and interpapillary ridges be quantified? Five-hundred and two ink prints of the palms and fingers from the archive of the Bochum Police Department were examined retrospectively. In 121 volunteers, the appearance of interpapillary lines was examined prospectively. From the later collective, the fingerprints of 13 people with interpapillary lines and nine people without were examined further by taking two silicon prints and measuring them with laser profilometry In 215 of the 502 ink prints (42.8%) interpapillary lines could be demonstrated. In those subjects younger than 20 years they were less frequently observed (34.1%) than in those above the age of 20 (51.8%). In all cases using laser profilometry the interpapillary lines could be related to a corresponding interpapillary ridge. The interpapillary ridge heights were 24.9 +/- 10.0 microm, significantly lower than the papillary ridges, which measured 59.0 +/- 19.2 microm. Interpapillary ridge widths were with 194.8 +/- 65.1 microm significantly narrower as compared to 435.5 +/- 57.4 microm in the papillary ridge. Those papillary ridges, between which interpapillary ridges were found, were significantly further apart from each other (610.5 +/- 78.9 microm) than those without interpapillary ridges (484.9 +/- 70.6 microm). During the course of a lifetime new ridges between the regular papillary ridges can develop or manifest. The fact that interpapillary lines are more frequently found on the right hands in men and those with increasing age is consistent with the theory that they correspond to degenerative changes and with sensitivity of touch.

Adolescent↗

Structural differences in parent and child reports of children's symptoms of depression and anxiety.

Two cohorts of public elementary school children and their parents (assessed 3 years apart) completed child and parent forms of the Children's Depression Inventory (CDI) and the Revised Children's Manifest Anxiety Scale (RCMAS). Assessments were conducted twice, once during the fall (N = 562) and again during the spring (N = 630) of the 6th grade. Factor analyses revealed 3 factors for each measure. Two of the 3 parent CDI factors manifested some degree of congruence with their counterparts from the child CDI. Similarly, 2 of the 3 RCMAS factors were somewhat congruent across informant types. Differences between parent and child factor structures suggest that parents' and children's reports focus on somewhat different aspects of child psychopathology, and they can make qualitatively different contributions to the multiaxial assessment of children.

Adolescent↗

Treatment of Birt-Hogg-Dubé syndrome with erbium:YAG laser.

We describe a female patient with Birt-Hogg-Dubé syndrome presenting with multiple, disfiguring papules on the cheeks, nose, and ears. In addition, there was evidence of photoaggravation and inflammatory processes in this case. The patient was treated with an erbium:YAG laser. Although the lesions could be successfully ablated up to the papillary dermis without scar formation, a relapse was observed after 6 months. Thus deeper laser ablations may possibly prevent relapses from dermal residual lesions.

Erbium↗

The role of the general practitioner in cancer care and the effect of an extended information routine.

OBJECTIVE: To describe the role of the General Practitioner (GP) in the care of one specified cancer patient per GP, and to explore the GP's knowledge about that patient's disease and treatments, and what information she/he wanted versus received from the specialist clinic. A further aim was to evaluate the effects of an Extended Information Routine (EIR), including increased information from the specialist clinic to the GP. DESIGN: Semi-structured interviews with GPs about a patient randomised between an extended information routine and standard information from the specialist clinics. SETTINGS: Primary Health Care. SUBJECTS: 20 GPs, 10 who received extended information about the specified patient and 10 who did not. MAIN OUTCOME MEASURES: The extent of GPs' contact with the patient, GPs' potential or actual possibilities to support the patient, desired and received information from the specialist clinic. RESULTS AND CONCLUSIONS: GPs are commonly involved in the care of cancer patients, particularly in the diagnostics of the disease but also during the periods of treatment and follow-up. The information from the specialist clinic to the GP is insufficient in standard care. The extended information routine increased the GPs' knowledge of the disease and treatments, and facilitated their possibilities to determine patients' need for support.

Attitude of Health Personnel↗

Are cognitive errors of underestimation predictive or reflective of depressive symptoms in children: a longitudinal study.

Children in Grades 3-8 participated in a longitudinal study of the relation between negative self-evaluation errors and symptoms of depression. Children's self-perceived competence in 5 domains (academic, social, athletic, appearance, and conduct) was compared with teachers' and peers' perceptions. Children's tendency to underestimate their competencies predicted increases in depression scores in only 1 of 6 grade levels. Children's depression scores predicted increases in the underestimation of self-competence over time in all grade levels. Gender differences and developmental differences in the cognitive errors associated with depression scores also emerged. Contrary to A. T. Beck's (1963, 1972) model, negative self-distortions appear to be more reflective than predictive of depression in children.

Adolescent↗

Evaluation of clinical benefit of chemotherapy in patients with upper gastrointestinal cancer.

A new endpoint, the Clinical Benefit Response (CBR), was recently suggested as a means of measuring the effectiveness of palliative chemotherapy in patients with pancreatic cancer. We took advantage of extensive recordings of measurements of treatment effects in two trials in patients with gastrointestinal cancer in order to assess the relevance of CBR criteria. In 151 patients, 53 with pancreatic cancer, 37 with biliary cancer and 61 with gastric cancer, who were randomized between chemotherapy with best supportive care and best supportive care alone, CBR criteria were applied retrospectively to the evaluations of the effects on the patients' well-being made by the treating physician and by the patient in quality-of-life questionnaires, chiefly EORTC QLQ C-30. When compared with subjective response evaluations made by both the physician and the patients' questionnaire data, it was found that CBR overestimated the beneficial effects in certain patients and underestimated them in others. The reason for this overestimation was mainly that the adverse effects of the chemotherapy were not considered appropriately. The underestimation was mainly due to the fact that CBR in practice is dominated by pain assessment, and alterations in other symptoms are also clinically relevant. CBR did, however, show the same differences between the two randomized groups as the subjective response evaluations and the quality-of-life estimations. It is concluded that CBR can be used as a method of measuring the beneficial clinical impact of a treatment strategy in clinical trials, but its limitations in reflecting several important aspects influencing the overall well-being of patients do, however, restrict its use. The criteria designed for use in patients with pancreatic cancer cannot be immediately applied to patients with other cancer types.

Adult↗

Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.

PURPOSE: The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS: One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS: At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION: Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

Adult↗

Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.

BACKGROUND: The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients. PATIENTS AND METHODS: Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03). CONCLUSIONS: The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Adenocarcinoma↗

Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer.

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was tricirbine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed. The maximum dose was 40 mg/m2. Two patients died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks after their last course, one without intervening disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of > or = 35 mg/m2 has unacceptable toxic effects.

Adult↗

Three complementary liquid chromatographic methods for determination of the peptoid cholecystokinin-B antagonist, CI-988, in rat plasma.

Three different liquid chromatographic methods (two quantitative methods which employ fluorescence detection and one qualitative method which employs selected ion-monitoring detection) were developed and validated to provide complementary specificity for determination of CI-988, a cholecystokinin-B antagonist, in rat plasma. The first quantitative method involves isocratic separation of "non-ionized" CI-988 and internal standard on a C-18 column, whereas the alternative quantitative method involves isocratic separation of the "anionic" analytes. These two quantitative HPLC methods rely on the intrinsic fluorescence of CI-988 and internal standard for detection, and both methods are equally sensitive (linear range of 2.0-1000 ng ml-1), accurate (+/- 15% relative error), and precise (< or = 15% relative standard deviation). Plasma CI-988 concentrations for samples (N = 69) assayed with the "non-ionized" separation are linearly correlated with concentrations for the same samples assayed with the "anionic" separation (y = 1.08 chi - 0.57, R = 0.999). In addition, a third qualitative method, HPLC-thermospray mass spectrometry, was developed to provide complementary evaluation of assay specificity through the use of selected CI-988 fragment ion monitoring. When investigating an anomalous chromatographic result that calls into question the specificity of a method, the availability and use of alternative validated chromatographic separations and orthogonal detection schemes are beneficial.

Animals↗

Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer.

BACKGROUND: In certain patients with pancreatic and biliary cancer, chemotherapy may relieve tumour-related symptoms, improve quality of life and possibly prolong survival. The extent of these improvements is not completely known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in patients with pancreatic and biliary cancer. PATIENTS AND METHODS: Between January 1991 and February 1995, 90 eligible patients with pancreatic or biliary cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was either sequential 5-fluorouracil/leucovorin combined with etoposide (FELv) or, in elderly and poor performance patients, the same regimen without etoposide (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: Mean scale scores in the QLQ-C30 improved more often/deteriorated less frequently in the chemotherapy group than in the best supportive care group. More patients in the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (10%, 4/41, P < 0.01). Overall survival was significantly longer in the chemotherapy group (median 6 vs. 2.5 months, P < 0.01). Also, the quality-adjusted survival time was longer for patients randomized to chemotherapy (median 4 vs. 1 months, P < 0.01). The effects were seen both in pancreatic and biliary cancer. CONCLUSIONS: The results show that chemotherapy can add to both quantity and quality of life in advanced pancreatic and biliary cancer. The number of patients who benefit from treatment is, however, still limited; for this reason careful selection before, and close monitoring during, treatment are necessary.

Adult↗