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Pager-based activity sampling (PAS) is described as a cost-effective and unobtrusive method for sampling residents' activities in clinical settings. A sample program evaluation is presented using residents in an urban children's hospital resident-training program. The purposes of the program evaluation were: (a) to establish a behavioral baseline that would help clinical faculty understand how residents were using their time, and (b) to determine whether alterations in the way residents were assigned within the hospital resulted in desired changes to time spent. The primary rationale for changing resident-assignment policies were: (a) to decrease the time residents were spending in transit between various locations within the hospital, and (b) to increase the time spent by residents in educational activities and in direct contact with patients and their families. This PAS application demonstrates that the technique can produce statistically supportable conclusions, at minimal cost, without unduly disrupting either the residents or their patients. PAS is compared with other time-sampling methods, its limitations are discussed, and suggestions for future applications are provided. [ABSTRACT FROM AUTHOR]

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term ® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness., (© 2023. Society for Prevention Research.)

Background: Adolescents in the United States account for one-fifth of new HIV cases, and have the highest rate of undiagnosed HIV, with more than half (51%) not knowing their status. It is a crucial public health concern to help equip youth with the information and autonomy to minimize their risk and know their status. Serious videogames are emerging as valuable tools for health and behavior change in adolescents, and have potential to engage this population and increase their use of HIV testing and counseling (HTC). The purpose of this study was to: (I) modify an original serious game targeting risk reduction and HIV prevention developed by the play2PREVENT Lab and create a new serious game that focuses on HTC; (II) evaluate its feasibility and acceptability; (III) pilot-test the assessment measures that are subsequently being used in a large randomized controlled trial., Methods: Three focus groups with adolescents, aged 14-17 (n=13, mean age =15), informed artwork and storylines for PlayTest! After the game was completed, a pilot test was conducted using a one-group pretest-posttest design to collect data on: (I) participants' gameplay satisfaction and experience; (II) the validity of the project's assessments. Twenty-six participants, aged 15-16 were enrolled from a local after-school program. Participants played PlayTest! twice weekly for three weeks. Data were collected on behavior, intentions, knowledge, perceived susceptibility, and attitudes related to HTC at baseline, post-gameplay (three weeks), and follow-up (six weeks)., Results: For the focus groups used in the game development, four major themes emerged: (I) adolescents have strong misperceptions about HTC, including who should get tested and what the test entails; (II) adolescents have incorrect knowledge about how HIV is contracted, spread, and treated; (III) adolescents are supportive of their peers getting tested for HIV, but are not likely to get tested themselves; (IV) while the majority of adolescents know where to get tested for HIV, social stigma, misperceptions around HTC, and fear of having a positive diagnosis keep them from seeking it. For the pilot study, overall, participant experience with the game was highly favorable. The assessments were sensitive enough to capture changes in our target variables: intentions (P=0.037) and knowledge (P=0.025) related to HTC at follow-up., Conclusions: The PlayTest! game provides promising results regarding using an engaging and evidence-informed videogame intervention to promote HTC in adolescents., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/mhealth.2020.01.05). The authors have no conflicts of interest to declare., (2020 mHealth. All rights reserved.)

Objective: Develop and test feasibility of a mobile videogame intervention to decrease high-risk sexual behavior in black and Hispanic adolescents. Materials and Methods: Iterative design to develop intervention in partnership with target audience. Feasibility and preliminary impact data collected at baseline, following 2-3 hours of gameplay and at 8-week follow-up. Results: Twenty-six 15-17-year-olds completed pilot testing: 16 (62%) were male, 20 (77%) black or Hispanic. Pilot testing demonstrated feasibility, including producing a usable videogame prototype, incorporating videogame testing within a high school, and participants' acceptability of the videogame. Participants' gameplay experience reflected that most would play the videogame again (77%), stated that they felt responsible for the choices they made in the videogame (73%), and would tell their friends to play the videogame (58%). Most suggested adding more videogame content to further engage participants. From baseline to follow-up, participants demonstrated improvements in condom and contraception self-efficacy ( P  = 0.003), risk perceptions ( P  = 0.009), and high-risk sexual behavior knowledge ( P  < 0.0001). Among black or Hispanic adolescents, we found improvements in summary measures of intentions ( P  = 0.04), self-efficacy ( P  = 0.003), risk perceptions ( P  = 0.002), and sexual knowledge ( P  = 0.0002). Adolescents with previous sexual experience showed similar improvements. Conclusion: Pilot testing of an innovative videogame, developed in partnership with the target audience, demonstrated feasibility and preliminary impact with this cohort of black or Hispanic adolescents. We developed a usable videogame prototype and gained important data about how to enhance the next videogame iteration. Future plans include targeting an older age group to maximize our ability to measure potential impact among sexually experienced adolescents.

Objectives: The purpose of this anatomic investigation is to (1) establish accuracy of dry needle placement into the medial third of the piriformis muscle as it exits the pelvis from the greater sciatic notch in unembalmed cadaveric specimens, while avoiding puncture of the sciatic nerve, and (2) establish guidelines for dry needle length selection., Methods: Dry needles were placed in nineteen unembalmed cadaveric posterior hips. Dissection of the posterior hip musculature was performed to confirm location of the needle. A binary decision (yes/no) was made to determine whether the needle reached the piriformis muscle, went through the piriformis muscle, and/or pierced the sciatic nerve. Additionally, mean adipose tissue thickness, gluteus maximus muscle thickness, and perpendicular distance from the needle to the exiting sciatic nerve were recorded., Results: The needle reached the medial third of the piriformis in 16 out of 19 hips (84.2% accuracy) and never punctured the sciatic nerve. There was a fair ( r  = 0.493) and good ( r  = 0.759) correlation between the needle length and the mean fat thickness for the left and right hips, respectively., Discussion: A physical therapist was able to use bony landmark palpation to locate the piriformis muscle and use estimated adipose tissue thickness to choose a sufficient needle length to reach the medial third of the piriformis muscle. While the needle placement technique was safe and no sciatic nerve puncture occurred, the proximity of the piriformis muscle to the sciatic nerve warrants caution during needle placement., Level of Evidence: 2c.

Study Design: A cross-sectional cadaveric examination of displacement and strain measured at the level of the cervical nerve roots during upper limb neural tension testing (ULNTT) with median nerve bias., Objective: To determine the displacement and strain of cervical nerve roots C5-C8 during ULNTT with minimal disruption of surrounding tissues., Summary of Background Data: Clinical examination of neural pathology involving cervical nerve roots is difficult because of the transient nature of pathologies, such as cervical radiculopathy, entrapment neuropathies, and thoracic outlet syndrome. Cadaveric studies have demonstrated significant displacement and strain in lumbosacral nerve roots during neurodynamic testing of the lower extremity. Examination into the biomechanical behaviors of cervical nerve roots during ULNTT has not been performed., Methods: Eleven unembalmed cadavers were positioned supine as though undergoing ULNTT. Radiolucent markers were implanted into cervical nerve roots C5-C8. Posteroanterior fluoroscopic images were captured at resting and ULNTT positioning. Images were digitized and displacement and strain were calculated., Results: ULNTT resulted in significant inferolateral displacement (average, 2.16 mm-4.32 mm, P < 0.001) of cervical nerve roots C5-C8. There was a significant difference in inferolateral displacement between the C5 and C6 nerve roots (3.15 mm vs. 4.32 mm, P = 0.009). ULNTT resulted in significant strain (average, 6.80%-11.87%, P < 0.001) of cervical nerve roots C5-C8. There was a significant difference in strain between the C5 and C6 nerve roots (6.60% vs. 11.87%, P = 0.03)., Conclusion: ULNTT caused significant inferolateral displacement and strain in cervical nerve roots C5-C8. These results provide the mechanical foundation for the use of ULNTT in clinical evaluation of pathology in the cervical region, such as in cervical radiculopathy, entrapment neuropathies, and thoracic outlet syndrome., Level of Evidence: 2.

Study Design: A cross-sectional cadaveric examination of the mechanical effect of foraminal ligaments on cervical nerve root displacement and strain., Objective: To determine the role of foraminal ligaments by examining differences in cervical nerve root displacement and strain during upper limb neural tension testing (ULNTT) before and after selective cutting of foraminal ligaments., Summary of Background Data: Although investigators have determined that lumbar spine foraminal ligaments limit displacement and strain of lumbosacral nerve roots, similar studies have not been conducted to prove that it is true for the cervical region. Because the size, shape, and orientation of cervical spine foraminal ligaments are similar to those in the lumbar spine, it is hypothesized that foraminal ligaments in the cervical spine will function in a similar fashion., Methods: Radiolucent markers were implanted into cervical nerve roots C5-C8 of 9 unembalmed cadavers. Posteroanterior fluoroscopic images were captured at resting and upper limb neural tension testing positioning before and after selective cutting of foraminal ligaments., Results: Selective cutting of foraminal ligaments resulted in significant increases in inferolateral displacement (average, 2.94 mm [ligaments intact]-3.87 mm [ligaments cut], P < 0.05) and strain (average, 9.33% [ligaments intact]-16.31% [ligaments cut], P < 0.03) of cervical nerve roots C5-C8 during upper limb neural tension testing., Conclusion: Foraminal ligaments in the cervical spine limited cervical nerve root displacement and strain during upper limb neural tension testing. Foraminal ligaments seem to have a protective role, reducing displacement and strain to cervical nerve roots during tension events., Level of Evidence: 2.

Previous studies have not reported activities associated with injuries in initial entry training (IET) because these data were seldom available in medical records and not contained in electronic databases. This investigation obtained activities associated with outpatient encounters in IET recorded by primary medical care providers at Fort Leonard Wood, Missouri. Data were entered into a standard database that included fields for diagnosis and activity associated with the injury. Fifty percent of the new injury encounters (i.e., exclusive of follow-ups) were not associated with a specific event but were reported as having a gradual onset. Other activities included physical training (16%), road marching (15%), confidence/obstacle courses (5%), and barracks activities (3%). Risks per unit of training time were estimated at 13, 62, and 97 injuries per hour for physical training, road marching, and the confidence/obstacle courses, respectively. The most frequently recorded diagnoses were joint pain (27%), strains (15%), blisters (14%), sprains (13%), and tendonitis (12%). The types of injuries and their anatomical locations were similar to those reported in other IET investigations, although blister-related encounters were higher. This investigation identifies activities with the highest risk of injury in IET and those that should be targeted for injury prevention efforts., (Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.)

Objective: To compare localized retinal function with corresponding histopathologic findings in advanced retinoblastoma., Methods: The medical records and specimens of 7 children with Reese-Ellsworth stage V retinoblastoma (8 eyes) were retrospectively reviewed from January 1, 2005, through March 1, 2008. The patients underwent multifocal electroretinogram (mfERG) testing while imaging of the fundus was being performed. After enucleation of these eyes, retinal layers in a 10-mm-long section centered on the optic nerve were scored for histopathology., Results: Visual acuity at presentation was 20/3000 to light perception in 6 of 6 eyes. Histopathologic analysis of the central retina revealed atrophy of all retinal layers in 4 eyes, moderate atrophy in 2 eyes, and mild atrophy with intact photoreceptors in 2 eyes. The mfERG amplitude was extinguished, moderately reduced, or mildly reduced when there was severe, moderate, or minimal atrophy of the outer retinal layers, respectively., Conclusions: In advanced retinoblastoma, the mfERG amplitude provides a functional index of histopathologic retinal damage. When the retina is attached at presentation, the presence of a recordable mfERG indicates the potential for vision. When the retina is detached at presentation and reattaches after chemotherapy, the presence of a recordable mfERG also indicates the potential for limited vision. When the retina is detached or reattached, extinction of the mfERG is associated with severe retinal damage that may preclude visual recovery.

Background: This report summarizes a phase 1 study conducted by the Children's Cancer Group (CCG) to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-leukemia activity of paclitaxel in children with advanced stage leukemias., Procedure: This study examined two dose escalation schedules of intravenous paclitaxel. Doses ranged from 250 to 500 mg/m(2) every 21 days in schedule A and 105 to 200 mg/m(2) weekly x 3 every 28 days in schedule B. Serial plasma samples for pharmacokinetic studies were obtained after the first paclitaxel dose., Results: Sixty-three patients (median 10 years) with refractory or relapsed leukemia (ALL) (n = 39), acute myeloid leukemia (AML) (n = 19), biphenotypic (n = 4), and JCML (n = 1)) were enrolled. The DLTs in schedule A were grade 4 hypertension and hyperbilirubinemia with an MTD of 430 mg/m(2) every 21 days. The DLTs in schedule B were coagulopathy, hyperkalemia, hyperbilirubinemia, elevated SGOT (n = 1, 125 mg/m(2)), peripheral neuropathy (n = 1, 200 mg/m(2)), and typhlitis (n = 1, 200 mg/m(2)) with an MTD of 182 mg/m(2) weekly x 3 every 28 days. Among 54 evaluable patients, there was one complete response (CR), three partial responses (PR), and five patients with stable disease (SD). The mean terminal elimination half-life was 9.5 +/- 3.4 hr and the mean plasma clearance was 23 +/- 11 L/hr/m(2)., Conclusions: Paclitaxel was tolerated at 430 mg/m(2) every 21 days and at 182 mg/m(2)/dose weekly x 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%., ((c) 2008 Wiley-Liss, Inc.)

Background: The empiric administration of anti-microbial therapy significantly reduces the morbidity and mortality associated with febrile neutropenic episodes in oncology patients. Outpatient empiric antibiotic therapy can be safely administered to a subset of febrile neutropenic patients at low risk for clinical complications., Procedure: Pediatric cancer patients presenting with febrile neutropenia after non-myeloablative chemotherapy and who met institutional criteria for early hospital discharge following a minimum of 48-hr inpatient empiric intravenous ceftazidime were eligible for the study. The feasibility and efficacy of an outpatient continuation therapy of oral ciprofloxacin (CPR) 25-30 mg/kg/day divided BID and amoxicillin (AMX) 30-50 mg/kg/day divided TID was assessed., Results: Thirty febrile neutropenic episodes in 26 patients were treated with outpatient oral CPR/AMX therapy. Oral CPR/AMX therapy was feasible in 28 (93%) and efficacious in 26 (87%) of treatment episodes. CPR/AMX was discontinued due to abdominal pain and diarrhea (n = 2), recurrent fever (n = 3), or gastrointestinal bleeding (n = 1). No patient developed new bacteremia or cardiopulmonary decompensation. Bone/joint pain or gastrointestinal symptoms occurred in 27% of treatment episodes. Duration of neutropenia, lower absolute neutrophil count (ANC) (< 100/mm(3)) at start of oral antibiotic therapy and active malignant disease were associated with failure of oral antibiotic therapy., Conclusions: It is feasible to administer oral CPR/AMX as continuation antibiotic therapy for a selected subgroup of febrile neutropenic episodes defined after initial hospitalization and empiric antibiotic therapy. Prospectively randomized trials will be required to analyze adequately the efficacy of an oral CPR/AMX outpatient antibiotic regimen for treatment of febrile neutropenia in pediatric oncology patients., (Copyright 2003 Wiley-Liss, Inc.)

Background: To improve the prognosis for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), and undifferentiated sarcoma (UDS), we tested the feasibility of a brief, intensive regimen of chemotherapy that maximizes dose intensity., Procedure: Twenty-four children and adolescents with metastatic sarcomas received VACIME chemotherapy, consisting of eight courses of vincristine 2 mg/m(2) on day 0; doxorubicin 20 mg/m(2)/day on days 0-3; cyclophosphamide 360 mg/m(2)/day on days 0-4; ifosfamide 1,800 mg/m(2)/day on days 0-4; mesna 2,400 mg/m(2)/day; and etoposide 100 mg/m(2)/day on days 0-4. Doxorubicin was omitted in courses 7 and 8. Granulocyte colony-stimulating factor (G-CSF) was used routinely following each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery and resolution of nonhematopoietic toxicities permitted. Surgical resection followed course 6, and radiotherapy followed the completion of all therapy., Results: Thirteen patients achieved a complete response (CR) with chemotherapy alone, and seven more achieved a CR following surgical resection after course 6 (overall CR rate 83%). There was one toxic death. Thirteen patients developed progressive disease, with 2- and 4-year event-free survivals (95% confidence interval) of 50% (30-70%) and 45% (25-65%), respectively. Myelosuppression was severe and cumulative, leading to dose reductions and chemotherapy interval delays. Mucositis was the most common nonhematopoietic toxicity., Conclusions: VACIME chemotherapy was a feasible dose-intensive regimen for pediatric patients with metastatic sarcomas. Cumulative hematopoietic toxicity and severe mucositis limited the delivery of chemotherapy as prescribed. The CR and 2-year event-free survival rates were superior to those of most previously reported regimens., (Copyright 2000 Wiley-Liss, Inc.)

Purpose: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols., Patients and Methods: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies., Results: Most patients (>95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11)., Conclusion: Outcome for infants on CCG-107 and CCG- 1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.

Nearly 80 percent of infant leukemias present with an abnormality involving the MLL gene at 11q23. Moreover, secondary acute myeloid leukemias (AML) that occur as the result of chemotherapy agents, which are known to inhibit DNA topoisomerase II, often manifest the same MLL abnormalities. It has been hypothesized that de novo infant leukemias may occur as a result of maternal exposure to agents in diet and medications that inhibit DNA topoisomerase II. Three epidemiologic studies of childhood leukemia with similar methodologies were conducted in the United States and Canada over the past 10 years by the Children's Cancer Group (CCG). Of the total 771 mothers of infants diagnosed at one year of age or less (< 12.5 months) who originally were interviewed (303 infant cases and 468 matched controls) across the three studies, follow-up questionnaire data on maternal exposure to potential DNA topoisomerase II inhibitors during pregnancy were available on 84 cases and 97 matched controls in the US. For maternal diet, a composite variable was created that consisted of 10 foods identified alpha priori as containing DNA topoisomerase II inhibitors. There were no significant trends with increasing maternal consumption for either the overall group, or the acute lymphoblastic leukemia (ALL) stratum. However, within the AML stratum, there was a statistically significant positive association (P trend = 0.04) with increasing consumption of DNA topoisomerase II-inhibitor containing foods (odds ratio [OR] = 9.8, 95 percent confidence interval [CI] = 1.1-84.8; OR = 10.2, CI = 1.1-96.4; for medium and high consumption, respectively). Other potential topoisomerase II inhibitors were explored; no significant findings were found. Results of this preliminary study, in combination with molecular data, should be used in future investigations of childhood leukemia (particularly, infant) to justify the incorporation of a detailed dietary history.

Purpose: Patients with metastatic retinoblastoma have a poor outcome. Hope that early detection of extraocular spread will improve survival has led to routine monitoring with bone marrow and cerebrospinal fluid (CSF) examinations. In light of cost and patient morbidity, the clinical utility of this practice is questioned., Patients and Methods: We have performed 254 serial bone marrow aspirations and 164 lumbar punctures in 60 children with retinoblastoma., Results: Two patients with extensive intraocular disease at diagnosis developed positive bone marrow aspirations, although no patient died of distant metastasis. Three patients developed positive CSF examinations. All had neurologic symptoms at the time of CSF positivity., Conclusions: We recommend performing staging bone marrow and CSF evaluations only in patients with clinical, histologic, or radiologic evidence of local or systemic extension (Pratt stage III-IV), or in patients presenting with one Reese-Ellsworth group V eye and retrolaminar or extrascleral extension of their tumor. We recommend limiting follow-up bone marrow and CSF evaluations to patients who develop objective signs and symptoms of metastatic or regionally recurrent disease.

Whether low level radiation exposure before conception increases the risk of leukemia in offspring has been much debated. No study has specifically evaluated the effect of parental preconception diagnostic X-ray exposure in the development of leukemia among infants. Mothers of 302 infant leukemia cases (diagnosed at < or = 18 months of age) and 558 individually matched regional controls, and fathers of 250 cases and 361 controls, were independently interviewed to obtain information on X-ray exposures. Paternal preconception X-ray exposure was associated with an increased risk of infant leukemia, higher risks being linked to exposures closer to conception. X-ray related leukemia risk varied with exposure site and histopathological type, the highest risk being for acute lymphocytic leukemia related to two or more X-rays of the lower gastrointestinal (GI) tract and lower abdomen (odds ratio, 3.78; 95% confidence interval, 1.49-9.64). A positive association was observed between acute lymphocytic leukemia and number of paternal X-rays of the lower GI and lower abdomen (trend test, P < 0.01), upper GI (P = 0.04), and chest (P = 0.08). Exposures of head and neck and limbs were unrelated to risk. The risk of acute myelogenous leukemia was unrelated to paternal X-ray exposure, except for a marginally significant association (trend test, P = 0.07) for upper GI X-rays. No consistent association between maternal X-ray exposure and infant leukemia was observed. The results of this study suggest that paternal low level radiation exposure before conception is associated with an increased risk of infant leukemia, although the nature of this association needs to be further evaluated.

Purpose: To determine the risk factors that influence the visual outcomes of patients with macular retinoblastoma who are treated with radiation therapy., Methods: The medical records of all patients with macular retinoblastoma treated with radiation therapy between 1980 and 1990 were reviewed. Ten patients were entered into the study. Features analyzed included patient age, laterality of eye involvement, location and size of macular tumor(s) at the time of diagnosis, treatment course, and most recent visual acuity., Findings: Ten of 11 eyes (10 patients) were successfully treated with external beam radiation. Eight patients obtained visual acuities ranging from 20/25 to 20/100; two patients had visual acuities of 20/200 or less. The best visual acuities were noted in patients whose tumor(s) did not involve the fovea and were relatively small. The worse visual acuities were noted in patients with binocular vision whose tumors invaded the fovea and were larger in size. In two of three patients in whom both eyes were retained, superimposed amblyopia developed in the eye with macular retinoblastoma., Conclusion: The authors' findings indicate that most patients with macular retinoblastoma who are treated with external beam radiation have favorable visual outcomes, but final visual acuity depends on the size of the tumor and involvement of the fovea. Patients in whom both eyes are retained are predisposed to further visual loss from amblyopia.

Within the context of a coping model, the present study attempted to determine variables associated with good and poor adjustment for siblings (N = 129) of pediatric cancer patients. Family cohesion and adaptability were found to mediate the impact of pediatric cancer on the healthy sibling. Specifically, high levels of family cohesion and adaptability were associated with better adaptation for siblings. Some support also was found for Folkman, Schaefer, and Lazarus' (1979) coping model, as the following variables, proposed by the model, predicted sibling adjustment to pediatric cancer: health/energy/morale, social support, and utilitarian resources. Results from this study stress the need to examine the child in a variety of ecological contexts (e.g., parental and familial functioning; neighborhood/community support).

An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.

Idarubicin (4-demethoxydaunomycin) is an anthracycline analogue with striking in vitro and in vivo activity against murine leukemias. Based on activity in adults with acute lymphoblastic leukemia, the Childrens Cancer Study Group initiated studies to evaluate idarubicin in children with leukemia in second or subsequent relapses. As part of those studies, we have characterized the plasma pharmacokinetics of idarubicin and the major circulating metabolite idarubicinol in 21 patients. Idarubicin plasma elimination was described by a three-compartment open model following i.v. infusion (10-15 mg/m2) on a schedule of weekly for 3 weeks and on a schedule of daily for 3 days every 3 weeks (total dose, 30-45 mg/m2). There was substantial variability in idarubicin elimination among patients, but no indication of dose-dependent or of schedule-dependent changes in pharmacokinetic parameters. The mean terminal half-life, total body clearance, and steady state volume of distribution were 17.6 h, 679 ml/min/m2, and 562 l/m2, respectively. Idarubicinol elimination was prolonged compared to that of the parent drug with a terminal half-life of 56.8 h. This metabolite clearly accumulated in plasma during the 3 days of treatment on the schedule of daily for 3 days. Urinary recoveries (48 h) of idarubicin and idarubicinol after a single dose of idarubicin were 2.4 and 10.1%, respectively. Idarubicin was detected in 2 of 21 cerebrospinal fluid samples obtained 18-30 h after administration. In marked contrast, idarubicinol was detected in 20 of those 21 samples. Concentrations in the 20 samples varied from 0.22-1.05 ng/ml with a mean value of 0.51 ng/ml.