Fatal Apophysomyces elegans infection transmitted by deceased donor renal allografts.

Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near-drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant-related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near-drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near-drowning events. Attention to aseptic technique during organ recovery and processing is re-emphasized.

Control of an outbreak due to an adamantane-resistant strain of influenza A (H3N2) in a chronic care facility.

BACKGROUND: Chronic care facility residents are at risk of severe influenza infection and death. Adamantanes have been used by chronic care facilities for influenza A prophylaxis; however, genotypic resistance has altered prophylaxis recommendations. An outbreak of influenza A (H3N2) in a chronic care facility housing neurologically impaired children and young adults and subsequent control measures are described. PATIENTS AND METHODS: Resident charts were retrospectively reviewed. Isolates were characterized by strain identification and pyrosequencing. RESULTS: Although 95 (97%) of 98 residents had been immunized against influenza at the start of the influenza season, 16 (84%) of 19 case patients were identified on the first floor. However, following implementation of enhanced infection control practices and adamantane prophylaxis, only 10 (13%) of 79 case patients were identified on the second floor. Subsequent pyrosequencing studies revealed a serine to asparagine mutation at position 31 of the M2 protein. CONCLUSIONS: Enhanced infection control precautions and adamantane prophylaxis were used to control spread of influenza in a chronic care facility. This outbreak demonstrates the importance of timely and consistent implementation of infection control measures in controlling influenza outbreaks in long term care facilities and raises questions about a possible role for adamantanes in preventing transmission of adamantane-resistant influenza A viruses.

Lack of caregivers limits use of outpatient hematopoietic stem cell transplant program.

Our goal was to compare direct and indirect medical costs and quality of life associated with inpatient vs outpatient autologous hematopoietic stem cell transplantation (AuHSCT). Twenty-one sequential outpatients and 26 inpatients were enrolled on this prospective trial. All candidates for AuHSCT were screened for eligibility for outpatient transplantation. Patients with either breast cancer or hematologic malignancy, insurance coverage for the outpatient procedure, one to three caregivers available to provide 24 h coverage, and no significant comorbidities were eligible to participate. Patients without caregivers or insurance coverage for outpatient transplant were accrued to the study in a consecutive manner as inpatient controls, based on willingness to participate in the quality of life portion of the study and to permit review of their hospital and billing records. Approximately half of all 139 prospective outpatient candidates were ineligible because they lacked a caregiver. Most commonly, the patient without a caregiver was single or widowed or their family and friends were needed to provide childcare. Most caregivers were college educated from families with incomes greater than US dollars 80000. Indirect costs to the caregivers totaled a median of US dollars 2520 (range US dollars 684-US dollars 4508), with the majority attributed to lost 'opportunity costs'. Overall, there were significant differences in the total costs of treatment for inpatient vs outpatient AuHSCT (US dollars 40985 vs US dollars 29210, P < 0.01)). In general, no significant differences were detected between inpatient and outpatient scores on quality of life measures. Although significant cost savings were associated with outpatient transplantation, this approach was applicable to only half of our otherwise eligible candidates because of a lack of caregivers. The financial burden associated with the caretaking role may underlie this finding.

Psychosocial adjustment of patients and caregivers prior to allogeneic bone marrow transplantation.

There are many studies that examine the psychosocial adjustment of survivors of bone marrow transplantation (BMT). On the other hand, there are relatively few studies that examine the psychosocial adjustment of patients prior to BMT, and even fewer that focus on the psychosocial adjustment of the patient's caregiver. The purpose of the present study was to assess performance status and psychosocial adjustment to illness, mood and stress response of patients and caregivers prior to admission for allogeneic BMT. Forty patients and their 39 caregivers were assessed using standardized measures. One-fourth of the patients reported clinical levels of psychosocial maladjustment on the Psychosocial Adjustment to Illness Scale and had greater adjustment problems than BMT survivors. Approximately one-third (35%) and one-quarter (23%) of the patients reported significant symptoms of intrusive and avoidance stress responses, respectively on the Impact of Events Scale. Caregivers reported more impairments in family relationships than patients, but overall reported similar distress to that of patients. Information about the pre-BMT process appears to be critical to understanding the psychosocial impact that BMT can have on patients and their caregivers.

Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination.

PURPOSE: To prospectively evaluate performance and quality of life (QOL) in advanced-stage head and neck cancer (HNC) patients on a curative-intent, concomitant-chemoradiotherapy (CT/XRT) (twice-daily radiation, fluorouracil, hydroxyurea, and cisplatin) regimen aimed at improving locoregional control, survival, and QOL. PATIENTS AND METHODS: Sixty-four patients were assessed before, during, and at 3-month intervals after treatment. Standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck), performance (Performance Status Scale for Head and Neck Cancer Patients and Karnofsky Performance Status Rating Scale), and patient-reported symptoms (McMaster University Head and Neck Radiotherapy Questionnaire) were administered. RESULTS: Acute treatment toxicities were severe, with declines in virtually all QOL and functional domains. Marked improvement was seen by 12 months; general functional and physical measures returned to baseline levels of good to excellent. Although up to a third of the patients continued to report problems with swallowing, hoarseness, and mouth pain, these difficulties were present in similar magnitudes before treatment. The following symptoms were more frequent at 12 months: dry mouth (58% v 17%), difficulties tasting (32% v 8%), and soft food diet (82% v 42%). Twelve-month diet was not related to pretreatment functioning, disease, treatment, or patient characteristics. Twelve-month QOL was best predicted by pretreatment QOL, with very little relationship to residual side effects or functional impairments. Small numbers of patients in four of the five disease sites precluded examination of outcome by site. CONCLUSION: These data support the feasibility of intense CT/XRT as primary treatment for advanced HNC. Results confirm acute toxicity but indicate that many of the treatment-related performance and QOL declines resolve by 12 months. The persistent inability to eat a full range of foods warrants further attention and monitoring.

Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer.

This study evaluated post-treatment performance and quality of life (QOL) outcome in head and neck cancer (HNC) patients treated with organ preservation, intensive chemoradiotherapy (FHX). Participants were 47 Stage II-IV HNC patients with no evidence of disease at least one year post-completion of organ preservation, concomitant FHX treatment. Patients were assessed via a semi-structured in-person interview, standardized measures of QOL (FACT-H&N, CES-D), performance (PSS-HN) and patients' perception of residual side effects. Disease, treatment and toxicity data were retrieved from medical charts and protocol records. The most salient performance impairment was inability to eat a normal solid food diet, with 50% of patients able to eat soft foods or take liquids only. This specific functional deficit was not related to global QOL, nor to specific quality of life dimensions. Dry mouth, the most frequent and severe residual effect, was not associated with outcome diet, depression or QOL. Residual pain, seen in only 15% of patients, appeared to influence both functional and QOL parameters as well as being a marker for other troublesome symptoms. Twenty-three per cent of patients were depressed; depression was associated with past problems related to alcohol abuse. Decreased QOL and increased depressive symptomatology were related to total number and severity of residual effects. The data highlight the importance of systematic study of QOL dimensions and caution against making assumptions about patients' experience of particular disease and treatment sequelae.

Sulfated carbohydrate compounds prevent microbial adherence by sexually transmitted disease pathogens.

Heparan sulfate (HS) serves as a receptor for adherence of herpes simplex viruses, Chlamydia trachomatis, Neisseria gonorrhoeae, and, indirectly, human immunodeficiency virus. Using primary human culture systems, we identified sulfated carbohydrate compounds that resemble HS and competitively inhibit infection by these pathogens. These compounds are candidates for intravaginal formulations for the prevention of sexually transmitted diseases.

The Performance Status Scale for Head and Neck Cancer Patients and the Functional Assessment of Cancer Therapy-Head and Neck Scale. A study of utility and validity.

BACKGROUND: The goal of this investigation was to examine the relationship between, and application of, two disease specific quality of life (QL) measures currently being employed for head and neck cancer patients: the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-H&N) and the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN). METHODS: The FACT-H&N and PSS-HN were administered to 151 head and neck cancer patients with a range of disease sites, treatment status (on vs. off treatment), and treatment modalities (surgery, radiation, and chemotherapy). RESULTS: FACT-H&N subscale and total scores and PSS-HN subscale scores proved sensitive to patients groups (showed significant and clinically meaningful differences) on the basis of treatment status (on vs. off treatment) and global performance status (Karnofsky scores). The pattern of correlations between FACT-H&N and PSS-HN subscales supported the scales' construct (convergent vs. divergent) validity. The strongest and most significant associations were observed between PSS-HN Normalcy of Diet and Eating in Public, and the head and neck subscale (HNS) of FACT-H&N, both of which were designed to measure the unique problems of head and neck cancer patients. More modest associations were observed between subscales measuring physical and functional areas of performance, social functioning, and emotional well-being. CONCLUSIONS: The FACT-HNS was found to be reliable and valid when applied to head and neck cancer patients. It clearly adds information to that collected by the parent (core) instrument. The PSS-HN also provides unique information, independent of that provided by the Karnofsky or the FACT-H&N. This study supported the multidimensional nature of QL for head and neck cancer patients, and thus the importance of assessing disease specific concerns in addition to general health status when assessing functional and QL outcome.

Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry.

Although heparan sulfate (HS) serves as an initial receptor for the binding of both herpes simplex virus type 1 (HSV-1) and HSV-2 to cell surfaces, the two serotypes differ in epidemiology, cell tropism, and ability to compete for viral receptors in vitro. These observations are not necessarily contradictory and can be explained if the two serotypes recognize different structural features of HS. To compare the specific features of HS important for the binding and infection of HSV-1 and HSV-2, we took advantage of structural similarities between heparin and cell surface HS and compared the abilities of chemically modified heparin compounds to inhibit plaque formation. We found that the antiviral activity of heparin for both serotypes was independent of anticoagulant activity. Moreover, specific negatively charged regions of the polysaccharide, including N sulfations and the carboxyl groups, are key structural features for interactions of both HSV-1 and HSV-2 with cell surfaces since N desulfation or carboxyl reduction abolished heparin's antiviral activity. In contrast, 6-O sulfations and 2-,3-O sulfations are important determinants primarily for HSV- 1 infection. The O-desulfated heparins had little or no inhibitory effect on HSV-1 infection but inhibited HSV-2 infection. Using a series of intertypic recombinant mutant viruses, we found that susceptibility to O-desulfated heparins can be transferred to HSV-1 by the gene for glycoprotein C of HSV-2 (gC-2). This supports the notion that the envelope glycoproteins of HSV-1 and HSV-2 interact with different affinities for different structural features of heparin. To determine if the modified heparin compounds inhibited plaque formation by competing with cell surface HS for viral attachment, binding studies were also performed. As anticipated, most compounds inhibited binding and plaque formation in parallel. However, several compounds inhibited the binding of HSV-1 to cells during the initial attachment period at 4 degrees C; this inhibitory effect was reversed when the cells and inoculum were shifted to 37 degrees C. This temperature-dependent differential response to modified heparin compounds was evident primarily when glycoprotein C of HSV-1 (gC-1) was present in the virion envelope. Minimal temperature-dependent differences were seen for HSV-1 with gC-1 deleted and for HSV-2. These results suggest differences in the interactions of HSV-1 and HSV-2 with cell surface HS that may influence cell tropism.

Coping strategies and psychological distress in cancer patients before autologous bone marrow transplant.

The increased use of bone marrow transplantation (BMT) to treat a variety of cancers has led researchers to study psychological functioning of BMT patients. The majority of studies conducted, however, has focused on adjustment after transplantation. Cancer patients' use of coping strategies before undergoing this procedure may also relate to levels of psychological distress. Our aims were (1) to provide normative coping data, controlling for situation-specific variables with a homogeneous sample, targeted stressor, and fixed time point, using the Ways of Coping Questionnaire; and (2) to identify coping strategies associated with distress before high-dose chemotherapy. Subjects were 49 patients scheduled to receive high-dose chemotherapy and an autologous bone marrow transplant. Consistent with previous coping research, we found that escape-avoidance was related to psychological distress on several measures. Item endorsement analyses of the escape-avoidance subscale suggest that patients may have used more passive than active avoidance strategies. Subsequent participation in a longitudinal study was not affected by initial levels of avoidant coping.