Accurate dosimetry with GafChromic EBT film of a 6 MV photon beam in water: what level is achievable?

This paper focuses on the accuracy, in absolute dose measurements, with GafChromicTM EBT film achievable in water for a 6 MV photon beam up to a dose of 2.3 Gy. Motivation is to get an absolute dose detection system to measure up dose distributions in a (water) phantom, to check dose calculations. An Epson 1680 color (red green blue) transmission flatbed scanner has been used as film scanning system, where the response in the red color channel has been extracted and used for the analyses. The influence of the flatbed film scanner on the film based dose detection process was investigated. The scan procedure has been optimized; i.e. for instance a lateral correction curve was derived to correct the scan value, up to 10%, as a function of optical density and lateral position. Sensitometric curves of different film batches were evaluated in portrait and landscape scan mode. Between various batches important variations in sensitometric curve were observed. Energy dependence of the film is negligible, while a slight variation in dose response is observed for very large angles between film surface and incident photon beam. Improved accuracy in absolute dose detection can be obtained by repetition of a film measurement to tackle at least the inherent presence of film inhomogeneous construction. We state that the overall uncertainty is random in absolute EBT film dose detection and of the order of 1.3% (1 SD) under the condition that the film is scanned in a limited centered area on the scanner and at least two films have been applied. At last we advise to check a new film batch on its characteristics compared to available information, before using that batch for absolute dose measurements.

Reduced 5-FU clearance in a patient with low DPD activity due to heterozygosity for a mutant allele of the DPYD gene.

5-fluorouracil pharmacokinetics, dihydropyrimidine dehydrogenase-activity and DNA sequence analysis were compared between a patient with extreme 5-fluorouracil induced toxicity and six control patients with normal 5-fluorouracil related symptoms. Patients were treated for colorectal cancer and received chemotherapy consisting of leucovorin 20 mg m(-2) plus 5-fluorouracil 425 mg m(-2). Blood sampling was carried out on day 1 of the first cycle. The 5-fluorouracil area under the curve(0-->3h) in the index patient was 24.1 mg h l(-1) compared to 9.8+/-3.6 (range 5.4-15.3) mg h l(-1) in control patients. The 5-fluorouracil clearance was 520 ml min(-1) vs 1293+/-302 (range 980-1780) ml min(-1) in controls. The activity of dihydropyrimidine dehydrogenase in mononuclear cells was lower in the index patient (5.5 nmol mg h(-1)) compared to the six controls (10.3+/-1.6, range 8.0-11.7 nmol mg h(-1)). Sequence analysis of the dihydropyrimidine dehydrogenase gene revealed that the index patient was heterozygous for a IVS14+1G>A point mutation. Our results indicate that the inactivation of one dihydropyrimidine dehydrogenase allele can result in a strong reduction in 5-fluorouracil clearance, causing severe 5-fluorouracil induced toxicity.

Feasibility of a dose-intensive CMF regimen with granulocyte colony-stimulating factor as adjuvant therapy in premenopausal patients with node-positive breast cancer.

Our aim was to study the feasibility of an intensified intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) schedule with the aim to escalate dose intensity (DI). Twenty-three premenopausal breast cancer patients received 6 cycles of adjuvant CMF intravenously on days 1 and 8 every 3 weeks and granulocyte colony-stimulating factor days 9-18. Endpoints were DI and toxicity. Twenty-one out of 23 patients (91%) received the projected total dose and reached > or =85% of the projected DI. Compared to 'classical' CMF, all patients reached > or = 111% DI. Nine patients received the planned schedule without delay. Thirteen patients (57%) were treated for infection and four patients (17%) were hospitalized for febrile neutropenia. Twelve patients received red blood cell transfusions (52%). Radiation therapy (n = 6) had no adverse impact on dose intensity or haematological toxicity. This dose-intensified CMF schedule was accompanied by enhanced haematological toxicity with clinical sequelae, namely fever, intravenous antibiotics and red blood cell transfusions, but allows a high dose intensity in a majority of patients.

MCMI-III as a treatment outcome measure for psychiatric inpatients.

The Million Clinical Multiaxial Inventory-III (MCMI-III) recently was introduced to replace and update the MCMI-II. A sample of 97 psychiatric inpatients were administered the MCMI-III shortly following admission, and again 7-10 days later. Changes in the personality and symptom scales generally paralleled those found in previous work with the MCMI-II, although the mean retest interval was considerably shorter than in the earlier study. However, some differences between the two instruments were observed, confirming the need for ongoing cross-validation work on the MCMI-III as an instrument that is distinct from the MCMI-II.

The relationship of length of stay to MCMI-II and MCMI-III change scores.

Differences between short versus longer lengths of stay on inpatient change scores were evaluated. Test-retest scores of 98 adult psychiatric inpatients tested with the MCMI-II in 1989 were compared with test-retest scores of 97 adult inpatients tested with the MCMI-III in 1995. The two samples of patients were comparable on demographic and diagnostic variables. Findings suggest a smaller degree of change associated with shorter lengths of stay, as measured by effect sizes and the proportions of patients moving from the clinically significant to the clinically nonsignificant range on scales for anxiety and depression.

Comparison of psychiatric day hospital patient and inpatient scores on the MCMI-III.

This study contrasts self-reported symptomatology on the MCMI-III of a sample of 97 psychiatric patients admitted directly to inpatient care with a sample of 75 patients admitted directly to day hospital treatment. The predominant Axis I diagnosis of patients in both samples was an affective disorder. Effect sizes of the degree of change from admission to retesting one week later were calculated and fell generally within the medium effect size range. There were no MCMI-III subscale differences between groups at either test time. A test item dealing with suicidal ideation did differentiate between the groups, with inpatients expressing more suicidal ideation at admission.

The GAF and psychiatric outcome: a descriptive report.

Since the Global Assessment of Functioning Scale (GAF) was introduced in DSM-III-R in 1987, it has been widely used, but minimally researched. This report provides information concerning the use of the GAF in routine clinical practice. Clinicians rated adult inpatients, adult day hospital patients, and adolescent inpatients at admission and discharge from psychiatric treatment. All samples were rated as significantly less dysfunctional at discharge. There were also significant differences in mean levels of dysfunction between the adult and adolescent samples at admission and discharge. These discrepancies were hypothesized to be associated with the GAFs unclear instructional format. Although this study concerned the GAF as described in the DSM-III-R, our findings are likely to be generalizable to DSM-IV, because no substantive changes have been made to the GAF.

Utility of the Inventory of Suicide Orientation-30 (ISO-30) for adolescent psychiatric inpatients: linking clinical decision making with outcome evaluation.

This report describes a study that integrates program evaluation with clinical practice. The subjects were 139 adolescent psychiatric inpatients who were tested with the Inventory of Suicide Orientation-30 (ISO-30) at admission and retested six days after admission. Aggregate analyses showed statistically significant changes in the direction of decreased suicidality on all ISO-30 indices. Further analyses compared the data with normative data from the ISO-30 manual, and also evaluated the relationships between ISO-30 scores and length of stay. Implications of the results and also methods of integrating outcome with clinical practice are discussed.

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study.

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 microg kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 microg kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (> or = grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhIL-3 administration tended to induce a more rapid platelet recovery.

Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer.

The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF and locoregional radiotherapy (on indication). G-CSF was administered if the leukocyte count recovery was insufficient. Fifty-one patients required no G-CSF ("no cytopenia'), and 50 patients received G-CSF ("G-CSF). Twenty-two patients, however, received no G-CSF support despite insufficient leukocyte recovery ("control'). Following G-CSF, leukocyte recovery was adequate in 83% of the chemotherapy cycles. The proportion of the patients who had a dose intensity > or = 85% was 90% in the "no cytopenia' group, 74% in the "G-CSF' group, and 45% in "control' group (p < 0.05). Leukocyte recovery was adequate in 87% of the chemotherapy cycles in the patients who received radiotherapy as compared with 92% of those in the patients without radiotherapy (p < 0.05). In conclusion an adequate leukocyte recovery after G-CSF was found in 83% of all chemotherapy cycles. The dose intensity of the G-CSF group was higher as compared with controls. The impact of radiotherapy on hematological recovery was significant, but not dependent on G-CSF.

Agreement between patient self-report and clinician rating: concurrence between the BSI and the GAF among psychiatric inpatients.

Two rating scales were compared for 200 adult psychiatric inpatients at admission to, and discharge from, the hospital. Patients rated their own psychological symptoms on the Brief Symptom Inventory (BSI), and clinicians rated patients' psychological, social, and occupational functioning on the Global Assessment of Functioning (GAF) Scale. Analyses indicated no significant relationships between symptom distress reported by patients and global functioning rated by clinicians. These findings support previous research that has shown minimal congruence among criterion measures that differ in rating source.

Persistent MAPI scale 6 elevations after inpatient treatment.

Of 81 adolescent inpatients with elevated (> 74) admission scores on scale 6 (forceful/antisocial) of the Millon Adolescent Personality Inventory (MAPI; Millon, Green, & Meagher, 1982), 44 (54.32%) continued to have elevated scale 6 scores on the discharge administration of the test. These 44 subjects (labeled High 6) did not differ significantly from the other 37 subjects (labeled Low 6) on several variables that have been associated with conduct disturbance. The two groups did differ significantly, however, on family size, parental (especially paternal) psychopathology, and prognosis. The High 6 group tended to come from larger families, had a higher frequency of parental pathology, and more often received negative prognoses than did the Low 6 group. A discriminant function analysis conducted on the MAPI expressed concerns scales on the admission administration of the test resulted in a 76.54% correct classification of subjects into the High 6 and Low 6 groups. In general, the High 6 subjects appeared less troubled and more trouble than those subjects in the Low 6 group. The findings of this study demonstrate the potential of the MAPI as a component in the assessment of the treatment amenability of adolescents with disruptive behavior disorders.

Unidimensionality of the Brief Symptom Inventory (BSI) in adult and adolescent inpatients.

This study investigated the factor structure of the Brief Symptom Inventory (BSI; Derogatis, 1992) for adult and adolescent psychiatric inpatients. The BSI was administered to 217 adults and 188 adolescents at admission and discharge from a private psychiatric hospital. Principal components factor analyses revealed that most variance among dimension scores was accounted for by one unrotated factor. Factorial invariance was evident across adult and adolescent samples for admission and discharge scores. Our findings are consistent with previous research on the BSI and Symptom Checklist-90-R (Derogatis, 1977), suggesting that both instruments measure primarily a unidimensional construct of general psychological distress.

The Brief Symptom Inventory (BSI) as an outcome measure for adult psychiatric inpatients.

In this study the Brief Symptom Inventory (BSI; Derogatis & Spencer, 1982) was administered to 89 males and 128 females at admission and discharge from a private psychiatric hospital. For mean scores, statistically significant decreases were observed on all BSI scales and global indices. Effect sizes ranged from high medium to large. Also, when clinical significance indices were calculated with regard to changes made by individual patients, we found that approximately 50% of all inpatients evidenced a decrease on the Global Severity Index (GSI), which meets the dual criteria of significant change and posttreatment functioning in the normal range. Compared with inpatient norms (Derogatis & Spencer, 1982), our sample generally scored higher at admission and lower at discharge.

The MAPI as a treatment outcome measure for adolescent inpatients.

The Millon Adolescent Personality Inventory (MAPI; Millon, Green, & Meagher, 1982) was administered at admission and discharge to 215 hospitalized adolescents. Significant mean score differences were found for both internalizing (affective disorder) and externalizing (disruptive behavior disorder) adolescents. Consistent with theory, internalizing adolescents reported significantly greater distress at both admission and discharge than externalizing adolescents. Finally, test-retest reliability coefficients were somewhat lower than those reported previously (Millon et al., 1982) for hospitalized adolescents.

The MCMI-II depression scales: do they assist in the differential prediction of depressive disorders?

This study examined the diagnostic efficiency of the Millon Clinical Multiaxial Inventory-II (MCMI-II) Major Depression (CC) and Dysthymia (D) scales for the differential prediction of unipolar depressive disorders. The MCMI-II was administered to 109 inpatients at a large private psychiatric hospital in the Midwest. All patients had a primary Axis I diagnosis of a depressive disorder, given at discharge by the attending psychiatrists. When CC scores were compared to clinician diagnoses, results indicated that the sensitivity of the CC scale was improved over what had previously been reported for studies involving the MCMI-I CC scale. However, overall, the D scale functioned slightly better as a predictor of major depression than did the CC scale. One likely factor in explaining this finding is that the CC scale contains very few items assessing vegetative/somatic symptomatology, which are the critical factors in distinguishing major depression from other unipolar depressive disorders.

Individual variability in self-reported improvement for depressed psychiatric inpatients on the MCMI-II.

This study evaluated self-reported symptom improvement on the MCM-II Dysthymia (D) scale for 109 depressed psychiatric inpatients. Rather than presenting the findings in traditional "group mean" format, data were analyzed to highlight the variability of clinical improvement for individual patients. Two criteria for judging clinically significant improvement (Jacobson, Follette, & Revenstorf, 1984) were employed, namely, that the client move from the dysfunctional to functional range during treatment and that the change between pretest and posttest be statistically reliable. Results indicated that 39 (35.8%) of the 109 patients met these criteria.

Interrupting the reenactment cycle: psychotherapy of a sexually traumatized boy.

This case study describes the course in psychotherapy of an eight-year-old boy who had been sexually traumatized at an early age by his biological father. He was seen for 35 individual sessions during a three-month hospitalization. Many of the problems evidenced at admission were conceptualized as ineffective attempts to reenact and master the original trauma. Hospitalization provided an environment in which acting-out behaviors could be controlled in a manner sufficient to allow anxiety to be utilized in psychodynamically oriented therapy. A key element in psychotherapeutic work was the recognition that the boy struggled with positive as well as negative feelings toward his abusing father. Individual therapy provided a context in which these ambivalent feelings could be expressed, which ultimately allowed for developmental progression.

The stability of the MCMI-II for psychiatric inpatients.

The MCMI-II (Millon, 1987) has been introduced recently as a successor to the MCMI-I (Millon, 1983). Because numerous revisions have been made in the MCMI-II, it will need to be cross-validated as an instrument distinct from the MCMI-I. The purposes of this study were to: (1) cross-validate the test-retest stabilities for MCMI-II personality and symptom scales; and (2) compare and contrast the MCMI-II and MCMI-I in regard to scale stability. The MCMI-II was administered to 98 psychiatric inpatients at admission and discharge. Results were generally consistent with the data reported by Millon (1987), in that the basic personality scales evidenced the greatest stability, the pathological personality scales somewhat lower stability, and the symptom scales the least stability. Compared to the MCMI-I, test-retest coefficients were generally higher for the MCMI-II.