An analysis of reports of depression and suicide in patients treated with isotretinoin.

BACKGROUND: The Food and Drug Administration (FDA) has received reports of depression and suicide in patients treated with isotretinoin. OBJECTIVE: Our purpose was to provide the number and describe the cases of depression and suicide reported to the FDA in US patients treated with isotretinoin and to consider the nature of a possible association between isotretinoin and depression. METHODS: An analysis was made of reports of depression, suicidal ideation, suicide attempt, and suicide in US isotretinoin users voluntarily submitted to the manufacturer and the FDA from 1982 to May 2000 and entered in the FDA's Adverse Event Reporting System database. RESULTS: From marketing of isotretinoin in 1982 to May 2000, the FDA received reports of 37 US patients treated with isotretinoin who committed suicide; 110 who were hospitalized for depression, suicidal ideation, or suicide attempt; and 284 with nonhospitalized depression, for a total of 431 patients. Factors suggesting a possible association between isotretinoin and depression include a temporal association between use of the drug and depression, positive dechallenges (often with psychiatric treatment), positive rechallenges, and possible biologic plausibility. Compared with all drugs in the FDA's Adverse Event Reporting System database to June 2000, isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt. CONCLUSION: The FDA has received reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with isotretinoin. Additional studies are needed to determine whether isotretinoin causes depression and to identify susceptible persons. In the meantime, physicians are advised to inform patients prescribed isotretinoin (and parents, if appropriate) of the possibility of development or worsening of depression. They should advise patients (and parents) to immediately report mood swings and symptoms suggestive of depression such as sadness, crying, loss of appetite, unusual fatigue, withdrawal, and inability to concentrate so that patients can be promptly evaluated for appropriate treatment, including consideration of drug discontinuation and referral for psychiatric care.

Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.

PURPOSE: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). In this study, we review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration. EXPERIMENTAL DESIGN: From the literature and manufacturer's data, we review the activity, tolerability, and pharmacokinetics of gemtuzumab ozogamicin in preclinical and Phase I studies and its activity, efficacy, and side effects in three Phase 2 trials of 142 patients with relapsed AML. RESULTS: In Phase I studies, the major toxicity was myelosuppression, especially neutropenia and thrombocytopenia, resulting from the expression of CD33 on myeloid progenitor cells. The Phase 2 dose was 9 mg/m(2) infused i.v. over 4 h, repeated on day 14. A minority of patients experienced acute infusion-related symptoms, usually transient and occasionally requiring hospitalization. The complete response (CR) rate with full recovery of hematopoiesis was 16%. A subset of patients [CRs with incomplete platelet recovery (CRps)] was identified with blast clearance and neutrophil recovery but incomplete platelet recovery. The duration of responses of CRps appeared to be similar to those of the CRs, although the numbers were small. The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA). After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30%. In the subgroup of patients over 60 years of age, the overall response rate was 26%. Response duration was difficult to establish because of the high prevalence of postremission therapies. Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes. One patient died of liver failure in the Phase 2 trials. CONCLUSIONS: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations. Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. The approved dose was 9 mg/m(2) i.v. over 4 h and repeated in 14 days. Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzumab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations. Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program. Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment. Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin.

Trial endpoints for drug approval in oncology: Chemoprevention.

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

Overcoming barriers to quality wound care: a systems perspective.

The societal burden of chronic wound care is guaranteed to intensify given the increasing elderly population of the United States. Currently 1.5 to 3 million patients with pressure ulcers are being treated at an estimated cost of $5 billion dollars annually. Many more millions suffer from venous, arterial, and neuropathic leg ulcers. When the huge scope of the issue is considered, the enormous challenge of providing quality wound care in the future is evident. Using general systems theory, this article analyzes contemporary salient barriers to quality chronic wound care from individual, group, and societal level systems perspectives. Factors that can help overcome these barriers are targeted, including newly emerging technological facilitators.

Algorithms, critical pathways, and computer software for wound care: contemporary status and future potential.

The contemporary use of algorithms, critical pathways, and computer software significantly affects all aspects of healthcare treatment from primary care to acute trauma management. Guidelines and heuristic devices specific to chronic wound care have been introduced to assist with quality implementation and monitoring of outcomes in a cost-conscious American healthcare system. Some wound care algorithms and critical pathways even have been computerized. This article discusses the differences among the various forms of wound care heuristic methods, describes their advantages and disadvantages, and suggests how they can be successfully implemented in clinical practice settings. Directions for future research also are offered.

Developing critical thinking with active learning strategies.

The development of students' critical thinking abilities is one of the greatest challenges facing contemporary nurse educators, especially those teaching graduate nursing students. Active learning techniques are suggested to promote critical thinking development. The authors describe how active learning strategies nurtured critical thinking processes in a group of adult nurse practitioner students.

Specialty practice, advanced practice, and WOC nursing: current professional issues and future opportunities.

Interest in clarification of the role of the WOC nurse as a specialized or advanced practice practitioner is increasing. Although much has occurred to delineate practice parameters, lack of expectations for specialty versus advanced nursing practice still exists. This article will differentiate advanced, specialty, and WOC nursing practice by examining their legal definitions, educational requirements, licensure, certifications, and practice milieus. Implications for the future of WOC nursing are posed within the context of the evolving American health care system.

Faculty practice in joint appointments: implications for nursing staff development.

Faculty joint appointments can capitalize on the talents and unique knowledge of nurses in varied settings. Altered role expectations, recurring emphases on cost control, and demands for accountability in the transforming health care system urge academic nursing faculty and clinically-based nurses to work together to achieve requisite health care and educational outcomes. This article addresses the types of faculty practice models, discusses three major role types of joint appointments, and presents the benefits and challenges of faculty functioning in joint appointments. Implications for nursing staff development are examined.

Quality-of-life end points in oncology drug trials.

Health-related quality of life (HRQL) is a multidimensional construct that represents the patient's perspective on valued aspects of health and functioning. Over the last several years, the pharmaceutical industry, as well as health care providers and the patient advocacy community, have shown increasing interest in HRQL as an outcome measure. Pharmaceutical companies and other sponsors of cancer clinical trials are seeking novel approaches with which to establish the benefits of treatment and to differentiate their products from other marketed products. Health care providers hope to provide cancer patients with therapies that positively affect their quality of life. To date, however, most oncology drug approvals have been based on traditional end points, such as survival and tumor response rate. This article will focus on some of the lessons learned from recent reviews of HRQL data and will describe some of the many challenges that lie ahead.

The lived experience of having an ileoanal reservoir: a phenomenologic study.

OBJECTIVE: Ileoanal reservoir (IAR) surgery or ileal pouch anal anastomosis is a relatively new surgical technique for people with ulcerative colitis or familial adenomatous polyposis. Little attention has been given to the experiences of people undergoing the procedure. The purpose of this qualitative study was to understand the lived experience of persons who have had construction of an IAR. DESIGN: The study was grounded in the phenomenologic approach of Van Manen to capture the lived experience of having an IAR as perceived by those persons in their everyday world. SETTING AND SUBJECTS: A purposive sample of 10 individuals with direct and personal knowledge of the experience were interviewed in detail. Subjects were recruited by contact with an IAR support group and a local WOCN group. All interviews were conducted in a private setting in a health care facility, school, or the participant's home. METHODS: Data collection involved face-to-face interviews lasting from 1 to 2 hours. Interviews were audiotaped and transcribed. MAIN OUTCOME MEASURES: Demographic data from the interviews were tabulated. Analyses of transcripts revealed 10 essential thematic categories with multiple theme clusters of the IAR experience related to lived body, time, space, and relationships. Analyses were completed by the researcher and a faculty mentor. RESULTS: The particular thematic categories that evolved from the data were (1) restricted life world, (2) living with uncertainty and fear, (3) seeking control, (4) vicious cycles: crisis and normalcy, (5) seeking and giving support, (6) alienation from the body, (7) living with bodily alterations, (8) the gift of time, (9) role and relationship changes, and (10) the end of the tunnel but relative results. All 10 theme categories were correlated with a literature review and other sources. CONCLUSION: The study provides a portrait of courage and survival for individuals experiencing major surgical interventions and bodily invasion associated with IAR after years of living with UC. Implications for nurses and health care personnel and questions for future research are presented.

Keeping them in stitches: humor in perioperative education.

Humor is one of the most effective teaching strategies available to perioperative nurse educators. Humor can be used to teach nursing students, surgical staff, and patients. This article describes the incorporation of humor into perioperative education and presents examples of specific humorous teaching strategies.

Predictive value of preclinical toxicology studies for platinum anticancer drugs.

Rodent and nonrodent toxicology studies are currently expected to support Phase I trials of antineoplastic drugs in the United States. To determine the predictive value of these studies, we initiated a project to compare preclinical and clinical toxicity data within various drug classes. The first class analyzed was the platinum anticancer drugs. Twelve platinum analogues that had both preclinical (mice, rats and/or dogs) and clinical data from matching drug administration schedules were identified. The rodent LD10 (the dose that causes lethality in 10% of treated animals) or dog toxic dose high (a dose that when doubled causes lethality in dogs) correlated well with the human maximally tolerated dose on a mg/m2 basis. For every platinum analogue investigated, one-third the rodent LD10 or one-third the dog toxic dose high in mg/m2 gave a starting dose and a first escalation dose that did not exceed the clinical maximally tolerated dose. The dose-limiting toxicities in patients were previously observed in 7 of 7, 7 of 8, and 9 of 11 mouse, rat, and dog studies, respectively. Our data indicate that mice, rats, and dogs all had value in predicting a safe starting dose and the qualitative toxicities in humans for platinum anticancer compounds. The efficiency of Phase 1 trials could have been improved without sacrificing patient safety by allowing higher starting doses for this drug class than conventionally permitted.

Using wound care algorithms: a content validation study.

PURPOSE: Valid and reliable heuristic devices facilitating optimal wound care are lacking. The objectives of this study were to establish content validation data for a set of wound care algorithms, to identify their associated strengths and weaknesses, and to gain insight into the wound care decision-making process. METHODS: Forty-four registered nurse wound care experts were surveyed and interviewed at national and regional educational meetings. Using a cross-sectional study design and an 83-item, 4-point Likert-type scale, this purposive sample was asked to quantify the degree of validity of the algorithms' decisions and components. Participants' comments were tape-recorded, transcribed, and themes were derived. RESULTS: On a scale of 1 to 4, the mean score of the entire instrument was 3.47 (SD +/- 0.87), the instrument's Content Validity Index was 0.86, and the individual Content Validity Index of 34 of 44 participants was > 0.8. Item scores were lower for those related to packing deep wounds (P < .001). No other significant differences were observed. Qualitative data analysis revealed themes of difficulty associated with wound assessment and care issues, that is, the absence of valid and reliable definitions. CONCLUSION: The wound care algorithms studied proved valid. However, the lack of valid and reliable wound assessment and care definitions hinders optimal use of these instruments. Further research documenting their clinical use is warranted. Research-based practice recommendations should direct the development of future valid and reliable algorithms designed to help nurses provide optimal wound care.

Concept mapping. Navigating the learning process.

Critical thinking, meaningful learning, and concept synthesis are key phrases pervading nursing literature as educators strive to promote optimal learning and improve clinical instruction and problem solving across levels of nursing education. Concept mapping offers a state-of-the-art metacognitive approach to achievement of these important goals. The author explores concept mapping from the perspective of cognitive theory, analyzes its strengths and drawbacks, presents examples of various concept maps and graphic organizers, and suggests pragmatic applications to nursing clinical, classroom, curriculum, and research situations.