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Biomedical subjects

S J Knight

Publications and source records attributed to S J Knight.

At least 19 recordsLinked to original sources

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.

Adult↗

Submicroscopic 8pter deletion, mild mental retardation, and behavioral problems caused by a familial t(8;20)(p23;p13).

Microscopically visible distal 8p deletions have been associated with growth and mental impairment, minor facial anomalies, congenital heart defects, and behavioral problems. We report two cousins with mild retardation and behavioral problems, including inappropriate sexual behavior and pyromania. Familial learning difficulties on the grandfather's side incompatible with Mendelian inheritance prompted telomere screening, which detected a submicroscopic terminal 8p deletion of < 5.1 Mb. The cousins' mothers both carried a t(8;20)(p23;p13) balanced translocation. The frequently observed microcephaly in patients with microscopically visible deletions of 8pter is lacking in both cousins, suggesting that the gene(s) causing the microcephaly is centromeric to the deleted region. The absence of cardiac defects in the cousins confirms the more proximal location of gene(s) causing these abnormalities in other reported cases with microscopically visible 8pter deletions and supports involvement of the GATA4 gene. Moreover, the current cases predict the presence of a putative gene(s) involved in behavior in the most telomeric 5.1 Mb of the p-arm of chromosome 8. This first clinical report of a submicroscopic subtelomeric 8p deletion gives more insight into the so-called 8p- syndrome and demonstrates the difficulty in making a clinical diagnosis for a submicroscopic 8pter deletion in an individual patient with mental retardation.

Behavioral Symptoms↗

Spouse ratings of quality of life in patients with metastatic prostate cancer of lower socioeconomic status: an assessment of feasibility, reliability, and validity.

OBJECTIVES: To examine the reliability and validity of spousal assessments by evaluating the collateral quality-of-life (QOL) ratings of patients of lower socioeconomic status with metastatic prostate cancer because collateral ratings provide supplemental information when advanced cancer limits patient self-report. METHODS: Patients with Stage D2 prostate cancer (n = 36) of lower socioeconomic status completed validated QOL instruments (Functional Assessment of Cancer Therapy-General [FACT-G], European Organization for Research and Treatment of Cancer-Quality of Life-30, and Quality of Life Index). Spouses completed a modified FACT-G, and physicians rated performance status using Karnofsky's scale. RESULTS: The internal consistency reliability was moderate to high for patient ratings on all FACT-G subscales and for spousal ratings on the modified FACT-G physical, functional, and emotional subscales. The spouses' ratings of the patients on the social and doctor relationship subscales were below the accepted criterion for a measure's use in group comparisons. The comparisons of the mean values of the FACT-G revealed agreement between patients and spouses, except that the spouses rated the patients as having poorer emotional function than did the patients. The intraclass correlations were moderate to high for the functional and emotional subscales and were low, but significant, for the physical and social subscales. The patient and spouse FACT-G ratings correlated with the patient ratings and physician ratings across the instruments for the functional and physical domains (r = 0.48 to 0.77, for patients; r = 0.31 to 0.70, for spouses), with less consistent relationships for the social and emotional domains. CONCLUSIONS: The collateral QOL assessments from spouses are potentially useful in assessing the functional status in patients of lower socioeconomic status with metastatic prostate cancer. For subjective domains, such as the social domain, direct patient assessments are needed.

Cross-Sectional Studies↗

Health literacy and shared decision making for prostate cancer patients with low socioeconomic status.

Quality of life (QOL) considerations are important in the treatment decision making process for prostate cancer patients. Although patient involvement in the treatment decision process has been encouraged, low health literacy can limit patient understanding of the complex information about treatments and their probable QOL outcomes and is a barrier to patient participation in the decision-making process. The objectives of the study were to evaluate (i) knowledge, level of satisfaction, and treatment preferences and intentions of men newly diagnosed with prostate cancer after participation in a CD-ROM shared decision making program; and (ii) the relationship between prostate cancer knowledge and health literacy. Thirty newly diagnosed prostate cancer patients from two Veteran's Administration (VA) hospitals in Chicago completed a demographic questionnaire and participated in an interactive CD-ROM shared decision making program. Subsequently, knowledge of prostate cancer, satisfaction with the information in the computer CD-ROM program, treatment preferences, and likelihood of following treatment preferences were assessed using interviewer-administered questionnaires. Health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM). The Pearson correlation test was used to assess the relationship between health literacy and prostate cancer knowledge. The chi2 test and the Fischer exact test were used to evaluate relationships between patient demographics and other variables. More than three-quarters of the patients rated the information in the CD-ROM as "very satisfactory" (highest possible rating). Two-thirds of the patients (21 of 30) selected a treatment after participation in the CD-ROM program and 90.5% of these patients stated that they were very or somewhat likely to adhere to their selection. However, prostate cancer knowledge was variable, with one-third of the patients scoring 69.9% or lower. Participants' health literacy was equivalent to a 7th-8th grade reading level (mean = 57.1+/-10.9), and more than one-third of participants (36.7%) had lower than 9th grade literacy levels. Participants' prostate cancer knowledge was correlated with health literacy (Pearson correlation rhor = 0.65, rhop = 0.0001). Patients were satisfied with the interactive shared decision making CD-ROM program, and two-thirds of patients were able to select a preferred treatment based on the information presented in the program that they intended to follow. However, prostate cancer knowledge scores varied among participants after participation in the CD-ROM program, raising doubts that patients were adequately informed to make appropriate choices regarding their treatment. Lower prostate cancer knowledge scores corresponded to lower literacy scores, indicating that low literacy may have hindered patient understanding of the shared decision making program. The development of shared decision making tools should include collaborative efforts with the target population to improve the success of shared decision making programs among patients with low health literacy.

Aged↗

Clinical studies on submicroscopic subtelomeric rearrangements: a checklist.

BACKGROUND: Submicroscopic subtelomeric chromosome defects have been found in 7.4% of children with moderate to severe mental retardation and in 0.5% of children with mild retardation. Effective clinical preselection is essential because of the technical complexities and cost of screening for subtelomere deletions. METHODS: We studied 29 patients with a known subtelomeric defect and assessed clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history. Controls were 110 children with mental retardation of unknown aetiology with normal G banded karyotype and no detectable submicroscopic subtelomeric abnormalities. RESULTS: Prenatal onset of growth retardation was found in 37% compared to 9% of the controls (p<0.0005). A higher percentage of positive family history for mental retardation was reported in the study group than the controls (50% v 21%, p=0.002). Miscarriage(s) were observed in only 8% of the mothers of subtelomeric cases compared to 30% of controls (p=0.028) which was, however, not significant after a Bonferroni correction. Common features (>30%) among subtelomeric deletion cases were microcephaly, short stature, hypertelorism, nasal and ear anomalies, hand anomalies, and cryptorchidism. Two or more facial dysmorphic features were observed in 83% of the subtelomere patients. None of these features was significantly different from the controls. Using the results, a five item checklist was developed which allowed exclusion from further testing in 20% of the mentally retarded children (95% CI 13-28%) in our study without missing any subtelomere cases. As our control group was selected for the "chromosomal phenotype", the specificity of the checklist is likely to be higher in an unselected group of mentally retarded subjects. CONCLUSIONS: Our results suggest that good indicators for subtelomeric defects are prenatal onset of growth retardation and a positive family history for mental retardation. These clinical criteria, in addition to features suggestive of a chromosomal phenotype, resulted in the development of a five item checklist which will improve the diagnostic pick up rate of subtelomeric defects among mentally retarded subjects.

Abnormalities, Multiple↗

An optimized set of human telomere clones for studying telomere integrity and architecture.

Telomere-specific clones are a valuable resource for the characterization of chromosomal rearrangements. We previously reported a first-generation set of human telomere probes consisting of 34 genomic clones, which were a known distance from the end of the chromosome ( approximately 300 kb), and 7 clones corresponding to the most distal markers on the integrated genetic/physical map (1p, 5p, 6p, 9p, 12p, 15q, and 20q). Subsequently, this resource has been optimized and completed: the size of the genomic clones has been expanded to a target size of 100-200 kb, which is optimal for use in genome-scanning methodologies, and additional probes for the remaining seven telomeres have been identified. For each clone we give an associated mapped sequence-tagged site and provide distances from the telomere estimated using a combination of fiberFISH, interphase FISH, sequence analysis, and radiation-hybrid mapping. This updated set of telomeric clones is an invaluable resource for clinical diagnosis and represents an important contribution to genetic and physical mapping efforts aimed at telomeric regions.

Chromosomes, Artificial, Yeast↗

A boy with a submicroscopic 22qter deletion, general overgrowth and features suggestive of FG syndrome.

Over recent years, submicroscopic subtelomeric rearrangements have been shown to be a significant cause of mental retardation and, therefore, such abnormalities should be considered in every child with moderate to severe retardation with additional features suggestive of a chromosomal abnormality. The FG syndrome is an X-linked recessive mental retardation syndrome with congenital hypotonia, relative macrocephaly, a characteristic facies and constipation. We describe a severely mentally retarded boy with a history of severe constipation, truncal hypotonia, facial dysmorphism, fetal pads, and joint laxity, leading to an initial diagnosis of FG syndrome at the age of 3 years. Clinical re-evaluation at the age of 6 years, when he showed signs of general overgrowth, initiated a telomere screen, and a submicroscopic 22q13.3 telomere deletion was detected. The features suggestive of FG syndrome in this boy with a 22q13.3--> qter deletion may indicate testing for submicroscopic 22qter deletions in patients with atypical features of FG syndrome without a definite X-linked family history.

Abnormalities, Multiple↗

Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis.

Chromosomal rearrangements involving the ends of chromosomes (telomeres) are emerging as an important cause of human genetic diseases. This review describes the development of first and second generation sets of telomere specific clones, together with advances in fluorescence in situ hybridisation (FISH) technology, which have made the prospect of screening for telomeric rearrangements a realistic goal. Initial FISH studies using the telomere specific clones indicate that they will be a valuable diagnostic tool for the investigation of mental retardation, the characterisation of known abnormalities detected by conventional cytogenetic analysis, spontaneous recurrent miscarriages, infertility, haematological malignancies, and preimplantation diagnosis, as well as other fields of clinical interest. In addition, they may help investigate telomere structure and function and can be used in the identification of dosage sensitive genes involved in human genetic disease.

Chromosome Aberrations↗

NCCN Practice Guidelines for Cancer-Related Fatigue.

These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue.

Exercise↗

Subtle chromosomal rearrangements in children with unexplained mental retardation.

BACKGROUND: No explanation for moderate to severe mental retardation is apparent in about 40% of cases. Although small chromosomal rearrangements may account for some undiagnosed cases, a lack of genome-wide screening methods has made it impossible to ascertain the frequency of such abnormalities. METHODS: A fluorescence in-situ hybridisation (FISH) test was used to examine the integrity of chromosome ends in 284 children with unexplained moderate to severe retardation, and in 182 children with unexplained mild retardation. 75 normal men were also tested. When a chromosomal rearrangement was found, its size was estimated, and members of the child's family were investigated. FINDINGS: Subtle chromosomal abnormalities occurred with a frequency of 7.4% in the children with moderate to severe mental retardation, and of 0.5% in the children with mild retardation. The abnormalities had an estimated population prevalence of 2.1 per 10,000, and were familial in almost half of cases. INTERPRETATION: Once recognisable syndromes have been excluded, abnormalities that include the ends of chromosomes are the commonest cause of mental retardation in children with undiagnosed moderate to severe mental retardation. Owing to the high prevalence of familial cases, screening for subtle chromosomal rearrangements is warranted in children with unexplained moderate to severe mental retardation.

Adolescent↗

Quality of life in low-income patients with metastatic prostate cancer: divergent and convergent validity of three instruments.

Few studies have evaluated Quality Of Life (QOL) among low-income patients with cancer. Information is needed about the feasibility and psychometric characteristics of QOL instruments in these populations. The purpose of this study was to examine the convergent and discriminant relationships between scales of three QOL instruments: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC), Functional Assessment of Cancer Therapy--General (FACT), and Quality of Life Index (QLI). Participants included 110 men with metastatic prostate cancer of whom 94% were low income and 62% were African-American. Interviewers administered the questionnaires. Cronbach alpha internal consistency reliabilities were 0.57 to 0.90 for the EORTC, 0.65 to 0.86 for the FACT, and 0.63 for the QLI. Convergent validity was supported for the EORTC and FACT scales measuring emotional, physical, and role/functional dimensions (r = 0.54 to 0.72), but not on scales measuring social function (r = 0.12). Divergent validity was supported between dissimilar scales (r = 0.14 to 0.38). Analysis with receiver operating characteristics curves provided empirical support for the EORTC and FACT as multidimensional measures. These findings suggest that, even in busy clinical settings with low literacy patients, interviewer-administered EORTC and FACT QOL instruments can provide valid and reliable information.

Aged↗

QOL and outcomes research in prostate cancer patients with low socioeconomic status.

The VA Cancer of the Prostate Outcomes Study (VA CaPOS) is collecting quality-of-life (QOL) information from prostate cancer patients, spouses, and physicians at six VA medical centers. Currently, 601 men with prostate cancer are included in the study, most of whom are of low socioeconomic status and over half of whom are African-American. Quality-of-life responses were most favorable for newly diagnosed patients, intermediate for those with stable metastatic disease, and poorest for those with progressive metastatic disease. Patients could not provide reliable estimates of their own preferences for future QOL states but responded reliably to questions phrased as a comparison of the preferences of two hypothetical patients. High out-of-pocket costs for hormonal therapies, lack of health insurance, and a belief that the non-VA system offered poorer services were the most common reasons for patient transferral to the VA system. Satisfaction with medical care was generally high. While African-American patients were more likely to have advanced prostate cancer at diagnosis, after adjustment for differences in health literacy, race was no longer a significant predictor of advanced disease. The VA CaPOS provides useful information on health status and patient satisfaction of VA prostate cancer patients. Long-term evaluations are needed to detect clinically meaningful QOL information as the disease progresses.

Adult↗

A case of recurrent congenital fetal anomalies associated with a familial subtelomeric translocation.

The potential of a new fluorescent in situ hybridization technique is discussed, which uses a complete set of telomeric probes to reveal cryptic chromosome rearrangements that remain undetected by standard cytogenetic analysis. We report the obstetric history of a patient who had a termination of pregnancy at 20 weeks for a fetus with multiple congenital anomalies but a normal male karyotype using conventional G-banding analysis on a mid-trimester placental biopsy. In a subsequent pregnancy, a diaphragmatic hernia and intra-uterine growth restriction were detected at 34 weeks' gestation and a fetal blood sample showed a normal female karotype. However, her child was born with dysmorphic features and additional severe abnormalities including microcephaly, anophthalmos and left fixed talipes. The child has shown marked developmental delay. In view of a strong family history of congenital abnormalities and recurrent miscarriage suggestive of a familial translocation, a fluorescent in situ hybridization technique using specific telomeric probes was performed on blood from the affected child and her parents. An unbalanced subtelomeric translocation was detected involving the long arms of chromosomes 2 and 7 in the child and a balanced translocation was detected in her father. Accurate genetic counselling and the opportunity for early prenatal diagnosis can now be offered to this family.

Abnormalities, Multiple↗

Desktop telemedicine in vascular surgery: some preliminary findings.

OBJECTIVE: Surgical specialists have generally underutilized telemedicine technologies. This report describes the use of real-time interactive-video telemedicine to augment the care of vascular surgical patients in underserved rural areas within our region. MATERIALS AND METHODS: The telemedicine system at Fletcher-Allen Health Care (FAHC) and the University of Vermont in Burlington utilizes desktop video conferencing technology with terrestrial transmission at 384 kbps. The current system was initiated in January 1996, and there are at present 18 external sites and multiple locations at FAHC, including the vascular laboratory, angiography suites, operating rooms, and the home of one vascular surgeon. During the first 12 months of operation, the vascular surgeons were asked to complete a questionnaire to evaluate the technology and its usefulness in clinical care. The use of the telemedicine system by the vascular surgeons was monitored by the questionnaires, phone bills, and a special "no charge" billing code. Telemedicine events were classified as clinical or educational. RESULTS: In the 26 months since implementation, 107 events have taken place, including both clinical and educational uses. There were 103 clinical uses by three vascular surgeons, including five emergency uses. A joint Vermont-Maine vascular educational conference has taken place four times. Overall, use by vascular surgery represented 14.2% of all telemedicine events in the first year or 30.9% of all clinical events during that time period. Use of telemedicine was reported to have improved patient care in 96% of the cases. Eighty percent of the telemedicine uses in the first year saved patient travel. There were no diagnostic errors, as determined by in-person clinical follow-up, attributable to the telemedicine system use. CONCLUSIONS: Use of a real-time video telemedicine has great potential for vascular surgeons, but cost-effectiveness studies may be needed prior to its widespread adoption.

Angiography↗

Del(18p) shown to be a cryptic translocation using a multiprobe FISH assay for subtelomeric chromosome rearrangements.

We have previously described a fluorescence in situ hybridisation (FISH) assay for the simultaneous analysis of all human subtelomeric regions using a single microscope slide. Here we report the use of this multiprobe FISH assay in the study of a patient whose karyotype was reported by G banding analysis as 46,XX,del(18)(p11.2). Although the proband had some features suggestive of a chromosomal abnormality, relatively few of the specific features of del(18p) were present. She was a 37 year old female with mild distal spinal muscular atrophy (SMA), arthritis of the hands, an abnormal chest shape (pectus excavatum), and an unusual skin condition (keratosis pilaris). Reverse chromosome painting with degenerate oligonucleotide primer-polymerase chain reaction (DOP-PCR) amplified del(18p) chromosomes as a probe confirmed the abnormality as del(18p), with no evidence of any other chromosome involvement. Subsequently, the multiprobe FISH assay confirmed deletion of 18p subtelomeric sequence. However, the assay also showed that sequences corresponding to the 2p subtelomeric probe were present on the tip of the shortened 18p. The patient is therefore monosomic for 18p11.2-pter and trisomic for 2p25-pter, and the revised karyotype is 46,XX,der(18)t(2;18)(p25; p11.2). We believe that a proportion of all cases reported as telomeric deletions may be cryptic translocations involving other chromosome subtelomeric regions. Further studies such as this are necessary to define accurately the clinical characteristics associated with pure monosomy in chromosomal deletion syndromes.

Adult↗

Quality of life in metastatic prostate cancer among men of lower socioeconomic status: feasibility and criterion related validity of 3 measures.

PURPOSE: Identification of metastatic disease progression is often difficult but important. Previous studies of quality of life in metastatic disease have been limited by the small number of respondents who were not white or of lower socioeconomic status. Quality of life assessment is generally done using self-administration techniques but this method is of limited usefulness for patients of low socioeconomic status, many of whom have limited reading abilities. We evaluated the feasibility and validity of interviewer administration of 3 quality of life instruments for patients of low socioeconomic status with metastatic prostate cancer. MATERIALS AND METHODS: We used instruments previously validated with self-administration methodology, including the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-30, Functional Assessment of Cancer Therapy-General Scale and Quality of Life Index. Subjects were men with metastatic prostate cancer with stable (78) or progressive (32) disease at 4 Veterans Affairs medical centers and 1 other site. Of the patients 94% were Veterans Affairs patients and more than 60% were black. RESULTS: Each quality of life instrument required less than 10 minutes of interviewer administration and was able to discriminate between patients with stable versus progressive disease on several health status domains. CONCLUSIONS: These data support the feasibility and validity of quality of life measurement in patients of low socioeconomic status with metastatic prostate cancer. Consideration should be given to adding quality of life instruments to patient encounter even among low socioeconomic status, low literacy populations.

Aged↗