A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer.

BACKGROUND: We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. Results In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%). CONCLUSIONS: Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.

Adherence to oral second-generation antipsychotic medications in patients with schizophrenia and bipolar disorder: physicians' perceptions of adherence vs. pharmacy claims.

OBJECTIVE: To compare physician-reported adherence of specific patients to oral second-generation antipsychotics vs. actual adherence rates determined from the patients' pharmacy claims. METHODS: Claims data from the HealthCore Integrated Research Database identified patients with schizophrenia or bipolar disorder with ≥ 1 oral second-generation antipsychotic prescription. The prescribing physicians were identified from the pharmacy claims and asked to complete an Internet survey assessing their perception of medication adherence for 1-2 of their patients and their beliefs regarding adherence to second-generation antipsychotics in general for a 1-year period. Adherence to second-generation antipsychotics was determined for each patient by pharmacy claims for the same period. Physician survey data were merged with patient claims data via unique patient identifiers, and physician-reported adherence rates were compared with claims-based rates as measured by the medication possession ratio. RESULTS: One hundred and fifty-three physicians responded to the survey, representing 214 patients (44 with claims for schizophrenia, 162 with bipolar disorder, 8 with claims for bipolar disorder and schizophrenia). Most physicians (60%) had no formal adherence training. More than two-thirds (68%) reported emphasising the importance of adherence and reported approximately 76% of their patients were adherent (≥ 71% of the time). In the schizophrenia group, 16 of 17 (94%) patients with low-to-moderate (≤ 70%) adherence levels had high (≥ 71%) physician-estimated adherence. In the bipolar disorder group, 62 of 92 (67%) patients with low-to-moderate adherence levels had high physician-estimated adherence. CONCLUSIONS/INTERPRETATION: These analyses suggest that, even when physicians are asked about specific patients in their practice, there is discordance between physician perceptions and adherence as measured through pharmacy claims. This disparity may delay appropriate interventions, potentially contributing to relapses.

A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer.

BACKGROUND: Bcl-2 family genes are frequently amplified in small cell lung cancer (SCLC). A phase I trial was conducted to evaluate the safety of obatoclax, a Bcl-2 family inhibitor, given in combination with standard chemotherapy. METHODS: Eligible patients (3-6 per cohort) had extensive-stage SCLC, measurable disease, ≤ 1 before therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients were treated with escalating doses of obatoclax, either as a 3- or 24-h infusion, on days 1-3 of a 21-day cycle, in combination with carboplatin (area under the curve 5, day 1 only) and etoposide (100 mg m(-2), days 1-3). The primary endpoint was to determine the maximum tolerated dose of obatoclax. RESULTS: Twenty-five patients (56% male; median age 66 years) were enrolled in three dose cohorts for each schedule. Maximum tolerated dose was established with the 3-h infusion at 30 mg per day and was not reached with the 24-h infusion. Compared with the 24-h cohorts, the 3-h cohorts had higher incidence of central nervous system (CNS) adverse events (AEs); dose-limiting toxicities were somnolence, euphoria, and disorientation. These CNS AEs were transient, resolving shortly after the end of infusion, and without sequelae. The response rate was 81% in the 3-h and 44% in the 24-h infusion cohorts. CONCLUSION: Although associated with a higher incidence of transient CNS AEs than the 24-h infusion, 3-h obatoclax infusion combined with carboplatin-etoposide was generally well tolerated at doses of 30 mg per day. Though patient numbers were small, there was a suggestion of improved efficacy in the 3-h infusion group. Obatoclax 30 mg infused intravenously over 3 h on 3 consecutive days will be utilised in future SCLC studies.

Evaluation of a computer-assisted learning programme on the oro-facial signs of child physical abuse (non-accidental injury) by general dental practitioners.

A computer-assisted learning programme with tutorials and self assessment multiple choice questions has been developed. One hundred and two general dental practitioners were asked to evaluate the programme. Over 80% of respondents felt that the programme was easy to use, contained an appropriate level of supporting information, and had improved their knowledge of non-accidental injury. All users of the programme felt that it was a better way of learning than video, audio tapes, and journals or books on the subject. It is concluded that CAL programmes are worthwhile for providing continuing professional education for general dental practitioners.

Evaluation of a computer-assisted learning package on the management of traumatised incisors by general dental practitioners.

UNLABELLED: A computer-assisted learning program with a tutorial, self-assessment exercises and an expert system has been developed. Sixty-seven general dental practitioners were requested to evaluate the program. The results from those practitioners who returned the questionnaire showed that 57% found the program generally easy to use with the appropriate level of difficulty of tasks and content of supporting information, which it was felt improved their knowledge of the management of fractured incisors. CONCLUSION: It is worthwhile to develop such programs for the education of general dental practitioners. All users of this program felt that it was better than video, audio tapes, journals or books on the subject.

Idarubicin-induced pigmentary changes of the nails.

A case of acute myelocytic leukemia of the FAB-M2 subtype in a patient who experienced pigmentary nail changes in conjunction with idarubicin therapy is presented. Although doxorubicin and daunorubicin have been reported to cause nail pigmentation changes, this is the first case report to describe these changes with idarubicin.

Psychiatric impairment in medical students.

This retrospective study of 217 medical students (at one school over an eight-year period) who had sought psychiatric consultation and treatment was designed to verify earlier findings about medical students' psychiatric impairment and to investigate other, more recently highlighted issues. The authors hypothesized that (1) more of the women would be seen for psychiatric consultation; (2) overall, the problems and diagnoses of the students would differ according to gender and academic class; (3) the women would show more evidence of role strain; (4) the women would remain in treatment longer; and (5) for all students, the average length of treatment would be relatively brief. The results of this study indicate that more of the women requested psychiatric consultation; that differences along gender lines regarding chief complaints and psychiatric diagnoses were not significant; and that the women revealed more direct and subtle evidence of role strain but did not remain in treatment longer than the men. The date are discussed in terms of the development and implementation of educational programs that attempt to prevent some of the psychiatric impairments of physicians.

Attitudes of medical school faculty and students toward acquired immunodeficiency syndrome.

Attitudes of faculty and students will influence the success of educational programs to address acquired immunodeficiency syndrome (AIDS). In 1988-89, 170 medical school faculty and 227 students completed needs assessment questionnaires at the University of Louisville, and the results were compared to assess the respondents' attitudes about AIDS. Both the faculty and the students were found to be fearful of infection, had strong negative attitudes toward AIDS patients, and had low levels of confidence in the current knowledge about AIDS. Both cognitive and affective training strategies are recommended to help learners distinguish unwarranted from warranted fears of infection and to increase their empathy for patients with AIDS.

Outcomes of AIDS training for supervisory and nonsupervisory personnel in the workplace.

Dealing with AIDS in the workplace is complicated by a variety of complex issues. One factor influencing how AIDS is dealt with is the difference in knowledge and attitudes between supervisory and nonsupervisory personnel. We surveyed 3834 supervisory and nonsupervisory personnel from a number of businesses and corporations in the Louisville metropolitan area. The differences found in this study suggest strategies for training to address the problem of AIDS in the workplace.

Evaluating the outcomes of AIDS education.

AIDS provides a unique challenge to health educators, requiring continuous evaluation and modification of educational strategies. Pretest and posttest questionnaires were thus used to assess the outcomes of AIDS training sessions. Results show that hour-long sessions result in knowledge acquisition and increased confidence among a demographically representative sample of 3,966 U.S. trainees. Results also reveal the dynamic nature of a training session, with some trainees exhibiting learning and others retaining either correct or incorrect responses or changing from one incorrect to another incorrect answer. Content areas that showed the most learning were sharing a glass or food with and being sneezed on by someone infected with the human immunodeficiency virus (HIV). Areas resistant to learning included the possibility of transmission from receiving blood transfusions, eating in a restaurant where a cook is infected, being bitten by a mosquito, giving mouth-to-mouth resuscitation, and providing first aid to someone infected. Repeat training sessions that take into account affective dimensions as well as the diverse needs of adult learners are recommended.

Risk for depression in families over time: a pilot epidemiologic study.

A random sample of 34 families from the general population were studied over a 15-month period to determine their risk for depression over time. Adults and children in the families were interviewed three times during the 15-month period. Risk for depression was evaluated using four screening instruments, including the Diagnostic Interview Schedule. At the original interview, 40 percent of the families contained one or more members at risk for depression. The 15-month family incidence rate for risk for depression was 26 percent and of continued good mental health 74 percent. The mental health status of 35 percent of the families changed during the 15-month period, suggesting that longitudinal studies can provide a more accurate profile of family mental health than studies of families at a single point in time.

Evaluating the mediating effects of social support upon life events and depressive symptoms.

Previous research has yielded inconsistent results regarding the mediating effects of social support upon psychiatric illness. Using data (N = 2029) gathered as part of a major epidemiologic study in the southeastern United States, the authors examine the relationships among depressive symptoms, social support, stressful life events, and socioeconomic status. As anticipated, direct effects were found for social support, stressful life events, and socioeconomic status upon depressive symptoms. However, when the data were analyzed via three-way analysis of variance and multiple regression (including all possible interaction terms) analysis, no statistically significant interactive effects were found. The authors conclude that these findings clearly demonstrate direct effects of social support and stressful life events upon depressive symptoms. Respondents in the lower social support groups experience the greatest impact of stressful life events; in contrast, persons in high social support groups, although evidencing increased symptom scores with increasing numbers of life events, experience the buffering effect of social support by showing less severe distress.

Talking about sex revisited.

Friends and others are told of 1st intercourse under different conditions. The conditions under which 1st intercourse is reported are related to the scripts which govern the transition from virgin to nonvirgin. This study compares the reporting of 1st intercourse by a group of college students in 1976 with that for a group studied in 1967. The earlier analysis found dramatic gender differences in reporting that interacted with the timing of 1st intercourse and relationship with the 1st partner, suggesting different scripts for men and women. Analysis of the current data suggests a simpler model in which males and females behave in similar ways, and in which only relationship with the partner influences the speed of reporting. The present study suggests that males and females now share a single script and a single standard of behavior for 1st intercourse.

Serial bone scanning: the assessment of treatment response in carcinoma of the prostate.

Serial bone scans and radiographic surveys were performed in 167 patients with histologically proven carcinoma of the prostate: 435 scans and surveys were performed. Nineteen of 99 patients with negative findings on diagnosis have become positive on follow-up. Forty-nine patients had positive findings on presentation; 8 have regressed on follow-up and 26 have progressed; 15 have remained unchanged. This is a sensitive method of follow-up in patients with carcinoma of prostate. Changes occurred in bone scans and skeletal surveys before any alteration in serum acid or alkaline phosphatases, symptoms of metastases or change in prostatic size in the majority of cases. The documentation of progression from MO to M1 disease presents no problems. However, problems in quantitation may arise in patients presenting with M1 disease.