Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study.

BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions. OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16). METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16. RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life. CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.

Impact of the COVID-19 pandemic on health-related quality of life and anxiety in pediatric hematology/oncology patients.

Since the World Health Organization declared the COVID-19 pandemic in March 2020, the strain on healthcare services affected patients suffering from various comorbidities and added to the psychological burden. The study aimed to assess the health-related quality of life (HRQoL) and anxiety levels of pediatric Hematology/Oncology patients during the COVID19 pandemic and evaluate the association between anxiety levels and physical, emotional, and social aspects of HRQoL. A cross-sectional study was conducted on 292 children between 2.5 - 13 years with chronic hematological/oncological disorders. Pediatric Quality of Life Generic Core Scale and Spence Children's Anxiety Scale were used for assessment of HRQoL and anxiety, respectively. Linear regression was performed to assess the association between background and COVID-19 related factors with anxiety level. Multivariate Analysis of Variance (MANOVA) was performed to assess the association between the three HRQoL dimensions with child anxiety and different independent variables. Transfusion-dependent patients had lower anxiety levels than patients receiving chemotherapy (B=-14.45, 95% CI=-21.94,-6.95).Children who were aware of the pandemic had lower anxiety scores than those who were not, while those suffering from canceled clinic days had higher anxiety levels (B=-8.66,95% CI=-14.86,-2.45, and B = 7.33,95% CI =1.22,13.45, respectively). Anxiety significantly reduced the three HRQoL domains (B=-0.36, 95% CI=-0.47, -0.24 for physical functioning, B=-0.45, 95% CI =-0.56, -0.33 for social functioning and B=-0.50, 95% CI=-0.63,-0.38 for emotional functioning). This study highlights the effect of the pandemic on the anxiety level and hence the HRQoL of chronic hematological/oncological pediatric patients for guiding policies and interventions to maintain their psychological well-being.

Caregiver-reported clinical characteristics and the burden associated with Kabuki syndrome.

Kabuki syndrome is a genetic disorder that can affect multiple body systems and manifest as congenital abnormalities and both developmental and socio-emotional delays. The condition is largely unknown by most primary care physicians and has no available treatment other than symptomatic management. This research sought to obtain caregiver-reported data about the experience of living with and caring for someone with Kabuki syndrome to fill a gap in the available literature. Fifty-seven caregivers participated in an online survey and reported that Kabuki syndrome affected their children in a wide variety of ways, including a high frequency of visits to various healthcare professionals. Caregivers reported their child experienced problems with hearing, eating, eyes, mouth, immune system, anxiety, depression, autism, teeth, joints, seizures, kidneys, and heart. Caregivers also described the challenges of caring for someone with Kabuki syndrome, including an impact on emotional well-being and the ability to work outside the home. This unique research characterizes the caregiver experience of living with and caring for someone with Kabuki syndrome, both through observed manifestations of Kabuki syndrome in their own children and their experience managing their treatment. Additional research is needed to investigate the patient experience of living with Kabuki syndrome.

Haematopoiesis, or Blood Poetry.

"It was just a few small red dots," I would recount to innumerable sympathetic nurses. They-the dots, not nurses-clustered together on my son's smooth slim neck. I stroked them as I dressed him after the bath. My inner hypochondriac was oddly quiet. Larry, my son, was well, throwing himself through the world with speed, joy, and curiosity. The next day I took him casually to our general practitioner to get these curious freckles checked. Then everything started to tilt. How do I weave it all together? In a string of Facebook posts? In a small impersonal room opposite a stranger while I sip a glass of water? In a series of dark jokes with my husband in the kitchen late at night? In snatches of awkward conversation with friends? In dreams from which I wake gasping? By scouring the sentences of authors and archives? From the discoveries of Paul Ehrlich to the scattered words of Emily Dickinson to the constant mechanical chugging of the IV pump, this interdisciplinary essay delves into the medical and cultural history of blood and bone marrow to tell an acutely personal story.

'You never leave work when you live on a cattle property': Special problems for rural property owners who have to relocate for specialist treatment.

OBJECTIVE: This paper contributes to the literature on relocation for specialist care by providing findings on specific issues impacting on rural farmers and property owners who have to travel to the metropolitan area for specialist care for a haematological malignancy. DESIGN AND SETTING: This paper uses descriptive qualitative research based on 45 interviews with patients with haematology in Queensland. The interviews were audio-recorded, transcribed verbatim, coded and thematically analysed. RESULTS: In addition to issues of distance, farmers and rural property owners who have to relocate for specialist care must deal with problems associated with the lack of opportunity to take absence from the property because of the inescapable pressure of daily farm and property responsibilities and the high cost of, or lack of opportunity to, outsource daily maintenance. Further concerns include the cost of relocation in the context of continuing drought, serious problems sustaining the travel and time away required, and the lack of choice for some but to deal with treatment alone. CONCLUSION: In recent years there has been considerable progress with regard to overcoming the distance barrier for rural and remote patients with cancer through innovative clinical models using technology and telemedicine. However, there has been limited uptake of such models for patients with haematology. The present findings indicate that from the perspective of rural farmers and property owners there are important reasons why the use of innovative strategies should be fostered and expanded.

Participation in clinical research: perspectives of adult patients and parents of pediatric patients undergoing hematopoietic stem cell transplantation.

Despite major improvements over the past several decades, many patients undergoing hematopoietic stem cell transplantations (HSCT) continue to suffer from significant treatment-related morbidity and mortality. Clinical research studies (trials) have been integral to advancing the standard of care in HSCT. However, 1 of the biggest challenges with clinical trials is the low participation rate. Although barriers to participation in cancer clinical trials have been previously explored, studies specific to HSCT are lacking. The current study was undertaken to examine the knowledge, attitudes, and perceptions of HSCT patients regarding clinical trials. As members of focus groups, participants responded to open-ended questions that assessed factors influencing decision-making about HSCT clinical trials. Suggestions for improvements in the recruitment process were also solicited among participants. Seventeen adult HSCT patients and 6 parents of pediatric HSCT patients participated in the study. The median age was 56 years (range, 18 to 70) and 44 years (range, 28 to 54) for adult patients and parents, respectively. Participants universally indicated that too much information was provided within the informed consents and they were intimidated by the medical and legal language. Despite the large amount of information provided to them at the time of study enrollment, the participants had limited knowledge retention and recall of study details. Nevertheless, participants reported overall positive experiences with clinical trial participation and many would readily choose to participate again. A common concern among participants was the uncertainty of study outcome and general lack of feedback about results at the end of the study. Participants suggested that investigators provide more condensed and easier to understand informed consents and follow-up of study findings. These findings could be used to help guide the development of improved consent documents and enhanced participation in research studies, thereby affecting the future design of HSCT research protocols.

Invented fairy tales in groups with onco-haematological children.

BACKGROUND: The impact of an onco-haematological illness for children is a traumatic event that opens to pain, hospitalizations and interrupts the continuity of daily life. It is difficult for the child to make meaning, to share the pain or ask a question related to the illness because, often, the parents or doctors cannot find a way to communicate in a suitable way for the child who remains in a situation of 'unspoken', where, fear, anxiety and pain cannot find a space to express. METHODS: The present research-intervention uses the methodology of invented fairy tales in groups with onco-haematological children, in the hospital, in order to explore the organization of the meanings at the base of the tales co-constructed by the participants underlying weaknesses and strengths of the invented fairy tales in groups intervention. The invented fairy tales in groups is used as a tool, such as a play, to express, share and support the experience of the illness of children. Forty-nine children participated to the invented fairy tales in groups in an onco-haematological hospital. Within a quali-quantitative framework we performed a thematic analysis of elementary context, cluster analysis, on the fairy tales considered as a unique narrative corpus of the thought of the group. RESULTS: The analysis shows four thematic clusters: fantasy as search for a meaning, 29.71%, the group as a space for illusions, 27.90%, the illness as a family problem, 25.72%, anchoring reality, 16.67%. The results highlighted three main carriers of sense: the representation of illness/the relational world/the representation of the institution. CONCLUSIONS: The use of invented-fairy-tales groups allowed the onco-haematological children to tell and share the experience of illness through a different way, which let them express symbolically their pain. The invented fairy tale in groups becomes a mediator of psychic processes which offer new solutions while improving interpersonal relationships/communication between the participants in group.

Influences of Animal-Assisted Intervention With Canine and Feline Pen Pals on Experiences of Living With Cancer and Blood Disorders in Children and Adolescents.

Background: Animal-assisted intervention (AAI) involving live visits with canines shows strong promise to improve quality of life (QOL) in hospitalized youth with cancer or blood disorders. The emerging field of virtual AAI allows access to AAI regardless of setting and extends to children at home. Youth and Pet Survivors™ (YAPS) is a novel form of virtual AAI with dog and cat pen pals who share a diagnosis of cancer or serious illness. Little is known about how exchanging letters with animals with a shared diagnosis influences perceived QOL, and how the human-animal bond (HAB) is expressed in letter narratives. Method: A thematic narrative analysis approach was used to analyze a secondary dataset consisting of letters and interviews from children in YAPS. The research team designed a conceptual framework to guide the analysis, integrating concepts of perceived QOL, the HAB, and emotional social support. Results: Collectively, the letter and interview texts illustrated cocreated stories of the HAB. Themes included the virtual HAB as a mirror, constructing identity in the context of the HAB, expressions of the mutuality of the HAB, happiness with having a pen pal, illness story, and connection to normalcy. Answers to research questions operationalize the influence of virtual AAI. Discussion: Having an animal pen pal improved perceived QOL and was a potent source of emotional social support across the illness trajectory, supporting YAPS as a nurse-led intervention for facilitating adjustment to illness. This study adds a conceptual framework and scientific evidence to the emerging field of virtual AAI.

How I conduct the family meeting to discuss the limitation of life-sustaining interventions: a recipe for success.

The meeting with the family of a hospitalized patient dying with advanced cancer or hematologic disease in which the limitation of life-sustaining interventions is discussed can be a challenge, particularly for junior physicians. A successful conclusion to this discussion involves an outcome in which the family, without coercion or manipulation, comes to accept that the appropriate care has been provided to their loved one, while the caregivers are enabled to provide care that is goal-directed and patient-centered. This type of result can be achieved through an approach in which patient-focused recommendations are offered in the context of diligent efforts to establish and sustain trust, thoughtful preparation, and respectful discussions with the family.

Long-term recovery after hematopoietic cell transplantation: predictors of quality-of-life concerns.

This prospective longitudinal study examined the quality of life (QOL) after hematopoietic cell transplantation (HCT) and identified risk factors of poor QOL in 312 adult autologous and allogeneic HCT patients. Physical, psychological, social, and spiritual well-being was assessed before HCT, 6 months, and 1, 2, and 3 years after HCT. For all HCT patients, physical QOL was stable from before to after HCT (P > .05); psychologic (P < .001), social (P < .001), and spiritual (P = .03) QOL improved at 6 months. Study noncompleters (because of illness or death) had worse QOL. Allogeneic patients reported worse physical and psychologic well-being (P < .05). Older patients reported worse physical but better social well-being regardless of HCT type (P < .05). Two or more domains were affected by race/ethnicity, household income, and education in autologous patients, and by body mass index (BMI), decline in BMI, primary diagnosis, and chronic graft-versus-host disease (GVHD) in allogeneic patients (P < .05). At 3 years, 74% of HCT patients were employed full or part time. Older autologous patients with lower pre-HCT income were less likely to work (P < .05); allogeneic patients with chronic GVHD were less likely to work (P = .002). Multidisciplinary efforts to identify and support vulnerable subgroups after HCT need to be developed.

Patients' quality of life after allogeneic haematopoietic stem cell transplantation: mixed-methods study.

Allogeneic haematopoietic stem cell transplantation (HSCT) is an increasingly widespread therapy method. It is associated with many socio-psychological and physical risks. Forty-four subjects, who were clinically monitored at the Bolzano BMT Centre including a follow-up period of at least 3 months, completed the questionnaire Functional Assessment of Chronic Illness Therapy-Bone Marrow Transplantation (version 4). Semi-structured, problem-oriented interviews were conducted with seven randomly selected subjects, the results of which were subjected to a summarising content analysis according to Mayring. The results from the quantitative and qualitative parts were compared based on triangulation. In the random sample, 22.7% stated that they were highly satisfied with their current quality of life (QOL). Throughout all dimensions of the questionnaire, women showed lower scores than men. The results revealed a positive correlation between the post-HSCT period and QOL (r(s)=0.338, P=0.025), especially regarding the social/family (r(s)=0.411, P=0.006) and emotional well-being (r(s)=0.306, P=0.043). The interviews primarily revealed dependence and inability to work. The support received from family, friends and hospital staff and the shift in priorities because of the transplantation were perceived as positive. The comparison mainly leads to corresponding results of the quantitative and qualitative parts of the study. Patient self-rating using questionnaires and interviews plays a direct and relevant role in the assessment of the QOL after allogeneic HSCT.

Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies.

BACKGROUND: Substantial uncertainty exists about prevalence of mood disorders in patients with cancer, including those in oncological, haematological, and palliative-care settings. We aimed to quantitatively summarise the prevalence of depression, anxiety, and adjustments disorders in these settings. METHODS: We searched Medline, PsycINFO, Embase, and Web of Knowledge for studies that examined well-defined depression, anxiety, and adjustment disorder in adults with cancer in oncological, haematological, and palliative-care settings. We restricted studies to those using psychiatric interviews. Studies were reviewed in accordance with PRISMA guidelines and a proportion meta-analysis was done. FINDINGS: We identified 24 studies with 4007 individuals across seven countries in palliative-care settings. Meta-analytical pooled prevalence of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria was 16·5% (95% CI 13·1-20·3), 14·3% (11·1-17·9) for DSM-defined major depression, and 9·6% (3·6-18·1) for DSM-defined minor depression. Prevalence of adjustment disorder alone was 15·4% (10·1-21·6) and of anxiety disorders 9·8% (6·8-13·2). Prevalence of all types of depression combined was of 24·6% (17·5-32·4), depression or adjustment disorder 24·7% (20·8-28·8), and all types of mood disorder 29·0% (10·1-52·9). We identified 70 studies with 10,071 individuals across 14 countries in oncological and haematological settings. Prevalence of depression by DSM or ICD criteria was 16·3% (13·4-19·5); for DSM-defined major depression it was 14·9% (12·2-17·7) and for DSM-defined minor depression 19·2% (9·1-31·9). Prevalence of adjustment disorder was 19·4% (14·5-24·8), anxiety 10·3% (5·1-17·0), and dysthymia 2·7% (1·7-4·0). Combination diagnoses were common; all types of depression occurred in 20·7% (12·9-29·8) of patients, depression or adjustment disorder in 31·6% (25·0-38·7), and any mood disorder in 38·2% (28·4-48·6). There were few consistent correlates of depression: there was no effect of age, sex, or clinical setting and inadequate data to examine cancer type and illness duration. INTERPRETATION: Interview-defined depression and anxiety is less common in patients with cancer than previously thought, although some combination of mood disorders occurs in 30-40% of patients in hospital settings without a significant difference between palliative-care and non-palliative-care settings. Clinicians should remain vigilant for mood complications, not just depression. FUNDING: None.

Increased self-transcendence in patients with intractable diseases.

AIMS: Patients with intractable disease require long-term treatment and experience repeated bouts of progressive symptoms and resolutions, which cause them severe suffering. The aim of this study was to elucidate the concepts of self-transcendence and subjective well-being in patients with intractable disease. METHODS: Forty-four patients with intractable disease (men/women: 22/22) participated. The diseases of the participants were classified into five systems: (i) neural/muscle system; (ii) digestive system; (iii) immunity/blood system; (iv) visual system; and (v) bone/joint system. The controls were 1854 healthy individuals (men/women: 935/869). Participants completed the Self-Transcendence Scale (STS) and the Japanese version of the World Health Organization-Subjective Inventory. The Japanese version of the Mini-International Neuropsychiatric Interview was also used for the intractable disease group. RESULTS: Analysis of covariance found a significant increase in STS score among the intractable disease group (P < 0.001). Multiple regression analysis showed that the positive affect measured by the World Health Organization-Subjective Inventory showed the greatest effect on the STS score for the intractable disease group (ß = 0.539, P < 0.001). CONCLUSION: As a life-changing experience, an intractable disease may influence an increase in self-transcendence. The results also showed that there was a strong correlation between self-transcendence and respondents' subjective well-being. Our results suggest that patients with life-changing intractable disease can have a high level of self-transcendence, which may lead them to regain mental well-being, and increase their psychological health even in situations that cause physical and mental suffering.

Oral factitious injury in a child diagnosed with Kabuki syndrome.

Factitious injury or self-injurious behavior is a common manifestation in children affected by neurologic, developmental, or psychiatric disease. The nature and presentation of this behavior in the oral cavity varies among diagnoses, and such behavior can be easily missed. This report describes the presence of self-injurious behavior in a child diagnosed with Kabuki syndrome who presented to a pediatric dentistry referral practice for evaluation of gingival bleeding, and provides a brief overview of the known etiology and management of this challenging condition. Clinicians should be aware of the possibility of self-injurious behavior when treating children diagnosed with Kabuki syndrome.

Ethical issues on preventions and management of blood genetics disorders--Islamic views.

Ethical issues are of concern to all members of the health team and the community at large, particularly in relation to chronic and genetic diseases. The fear from the negative social impact, including stigmatization of the carriers of a genetic disease and the affected individual is of a particular concern to the individual and his family. Members of the health team should protect the individual autonomy, observe the ethical principles including beneficence, nonmaleficent, justice, and confidentiality, and maintain high level of professional competence. In addition, Islamic/Arab costumes and traditional issues need to be respected in these communities. This article will outline the prevention and management of common blood genetic disorders in the high of Islamic ethical teachings, where the individuals benefit is paramount.

Lavender Aromatherapy: Examining the Effects of Lavender Oil Patches on Patients in the Hematology-Oncology Setting.

BACKGROUND: Lavender aromatherapy treatment has been used for the general inpatient population to promote relaxation during hospitalization; however, limited research has been conducted on its efficacy with an inpatient hematology-oncology population. OBJECTIVES: The purpose of this mixed-methods study was to determine the feasibility of wearable overnight lavender aromatherapy skin patches as a patient-directed nursing intervention for 40 patients on an inpatient hematology-oncology unit. METHODS: Data were collected during a two-month period using the Lavender Satisfaction Assessment and the Generalized Anxiety Disorder-7 (GAD-7) scale. Patient demographics and open-ended responses were also collected. FINDINGS: After implementing the overnight aromatherapy patches, about half of the participants reported an absence of anxiety or measurable anxiety symptoms, and participants perceived better sleep quality and duration. The results indicate that a nurse- and patient-driven aromatherapy intervention can improve the quality of care on an inpatient hematology-oncology unit.

The Korean-Advance Directive Model and Factors Associated With Its Completion Among Patients With Hematologic Disorders.

The objective of this pilot study was to examine factors associated with the completion of advance directives (ADs) among patients with hematologic disorders in Korea. Using a descriptive design, patients with largely hematologic malignancies completed the questionnaires, including the Korean-Advance Directive (K-AD) model, which pertains to values, treatment wishes, and proxy appointment. Of 45 patients (aged 48.7 ± 10.7 years, 51.1% men), two-thirds had leukemia (40.0%) and lymphoma (26.7%). "Dying comfortably" was the most frequently selected value (n = 20). Regarding treatment wishes, hospice care was the most desired type (n = 22), whereas aggressive treatments, such as cardiopulmonary resuscitation, were less preferred (n = 3). The patient's spouse was most frequently appointed as a proxy (n = 27). Patients who completed all the 3 components of the K-AD model (51.1%) were less depressed (t = -2.31; P = .028) and more likely to perceive the benefits of the K-AD model (t = 2.07; P = .045), compared with the noncompleters (48.9%). Further, being male (odds ratio [OR], 6.42; P = .031), having higher scores on depressive symptoms (OR, 1.28; P = .016), and perceived barriers (OR, 1.08; P = .040) were associated with lower tendency to complete the K-AD model. These findings support the need for earlier introduction of ADs in hematologic disorders, with consideration of modifiable factors such as depression or barriers to end-of-life care decisions.

CNS complications in children receiving chemotherapy or hematopoietic stem cell transplantation: retrospective analysis and clinical study of survivors.

BACKGROUND: Clinical studies analyzing CNS complications in pediatric oncology systematically are rare. PROCEDURE: In a single center retrospective analysis, CNS complications in 950 subsequent pediatric patients treated between 1992 and 2004 by chemotherapy or hematopoietic stem cell transplantation (HSCT) were studied. Forty-six patients had pre-existing CNS diseases and were excluded. Out of the 904 remaining, 76 (8.4%) had 82 CNS complications. RESULTS: The most common manifestations were seizures (in 50.6% of the CNS episodes), altered states of consciousness, and motor deficits (in 47.5% of the episodes each). CNS complications were caused by infections (26.8%), toxicity (25.6%), neoplasma (13.4%), vascular (10.9%), and metabolic disturbances (8.5%). In 14.6%, the mechanism remained unclear. Patients (23.7%) died from the CNS event. Neoplastic disorders had the worst (50%) while metabolic the best (0% mortality) prognosis. Imaging techniques were the most effective diagnostic measures, followed by laboratory analysis, clinical examination, and CSF analysis. A neuro-psychological (CBCL, CFT-1/-20-testing) examination could be done in 21 of 32 long-term survivors. Seven had a major, 3 minor neurological impairment, 11 were normal in all tests. CONCLUSIONS: These data show that there is not one typical CNS complication, but a wide variety. There is no close connection between either underlying disease or symptoms and cause of the complication. Prognosis is variable. About two thirds of the long-term survivors could lead a normal life.

Haematological toxicity of drugs used in psychiatry.

Almost all classes of psychotropic agents have been reported to cause blood dyscrasias. Mechanisms include direct toxic effects upon the bone marrow, the formation of antibodies against haematopoietic precursors or involve peripheral destruction of cells. Agranulocytosis is probably the most important drug-related blood dyscrasia. The mortality from drug-induced agranulocytosis is 5-10% in Western countries. The manifestations of agranulocytosis are secondary to infection. Aggressive treatment with intravenous broad-spectrum antimicrobials and bone marrow stimulants may be required. Of drugs encountered in psychiatry, antipsychotics including clozapine (risk of agranulocytosis approximately 0.8%, predominantly in the first year of treatment) and phenothiazines (chlorpromazine agranulocytosis risk approximately 0.13%), and antiepileptics (notably carbamazepine, neutropenia risk approximately 0.5%) are the most common causes of drug-related neutropenia/agranulocytosis. Drugs known to cause neutropenia should not be used concomitantly with other drugs known to cause this problem. High temperature and other indicators of possible infection should be looked for routinely during treatment. Clozapine is well known as a drug that can cause blood dyscrasias, but olanzapine and other atypicals may also cause similar problems. In addition to genetic factors, there are likely to be dose-related and immunological components to these phenomena. Important lessons have been learnt from the haematological monitoring that is necessary with clozapine and the monitoring has been very successful in preventing deaths related to clozapine-induced agranulocytosis. Continuing research into the mechanisms of drug-induced neutropenia and agranulocytosis may serve to further enhance the safe use not only of clozapine, but also of other agents.