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Pharmacotherapeutic treatment of nightmares and insomnia in posttraumatic stress disorder: an overview of the literature.

Sleep disturbances are hallmark symptoms of posttraumatic stress disorder (PTSD). Where the subjective experience of nightmares and insomnia in PTSD patients is very real indeed and demands treatment, objective research findings on disordered sleep architecture in PTSD are inconclusive and inconsistent. After reviewing the literature an insufficient number of controlled studies are published to formulate evidence-based guidelines. Several studies have methodological limitations, such as small group sizes and heterogenic samples. Large randomized controlled trials (RCTs) need to be conducted in order to further develop adequate therapeutic interventions. Objective parameters for insomnia and nightmares need to be identified for understanding underlying mechanisms of disturbed sleep in PTSD, and for evaluating therapy.

Anti-Anxiety Agents↗

Technical aspects and clinical impact of hematopoietic progenitor subset quantification.

As high-dose therapy for malignancies is now being applied to newly diagnosed patients as adjuvant therapy, it has become a requirement that quality and safety assessment of hematopoietic stem cell grafts be evidence-based. This process has developed a new institution in medicine, the stem cell laboratory. In most cases this speciality has evolved from or within hematological research laboratories. However, the increased routine technologies applied in quality evaluation, ex vivo manipulation and safety assessment in stem cell handling naturally places this activity in transfusion medicine. Multiparametric flow cytometry can identify progenitor subsets in normal human bone marrow and peripheral blood, and such subset quantification has been used retrospectively to predict three-lineage engraftment following high-dose therapy for malignancies. Published single center data have suggested an impact on clinical outcome, and a standardized technique for subset enumeration needs to be established before prospective multicenter trials can be initiated to document the prognostic value of such quality assessment in autografting. Based on experiences of CD34 enumeration, which we consider to be the first step in quality assessment of hematopoietic stem cell grafts, this review discusses flow cytometry subset identification by lineage-specific differentiation markers, stromal-dependent adherence molecules, and regulatory growth factor receptors from a technical point of view. The aim of this review is:To recommend a simple method based on the experiences of the Nordic workshop III on subset identification; To present new molecular genetic-based methods for future use in quality assessment; and To propose new endpoints necessary for validation of the likely clinical impact of subsets in prospective trials. As sample differences between blood and marrow result in technical difficulties, this review only focuses on the methodology of identifying subsets in blood and leukapheresis products. Methods for subset analysis in diagnostic bone marrow samples will be covered in a forthcoming review.

Antigens, CD34↗

Methodological hurdles in conducting pharmacoeconomic analyses.

As total healthcare spending increases throughout the world, greater emphasis is being placed on research which demonstrates value for medical interventions, including new and existing pharmaceuticals. Pharmacoeconomic evaluations can assist manufacturers, insurers, clinicians, governmental agencies, policy-makers and consumers to make informed, appropriate decisions about adoption and application of new medications. Because of the far-reaching implications of this research, it is important that researchers adequately address methodological challenges. In this article, we describe the uses of results of pharmacoeconomic trials, identify and discuss various study designs and methods for gathering nonclinical outcome data which may differ significantly from clinical outcome data, and consider the importance and difficulty of incorporating the patients' experience into such trials. Researchers in this area must give specific consideration to sample size estimation for economic outcomes, and carefully handle time issues including duration of observation for complications and discounting of future health and financial consequences. Costs from different perspectives associated with resource use should be assembled in a standard fashion. Use of charges which may not be standardised across geographical or organisational boundaries are discouraged. Inclusion of appropriate health-related quality-of-life (HR-QOL) and utility instruments is increasingly important, but controversy over the best methods still exists. While there is little question of the importance of pharmacoeconomic evaluations, they are expensive. Well designed and executed pharmacoeconomic trials can justify this expense by helping decision-makers understand which treatments have value.

Economics, Pharmaceutical↗

Recent advances in epidemiological field techniques in filariasis.

There have been very few advances in epidemiological field techniques for filariasis in recent years. Advances in other areas of study of filariasis have been published and a summary of some of those which have some application to field technology will be given. Studies on vectors involving host influences on the development of filariae and the use of DNA probes for vector speciation were reported as well as the development of techniques that yielded species-specific identification of larvae in mosquito vectors. Experiments on animal transmission potentials also have been described. Mathematical models are becoming popular for various biological systems. It is postulated that models will enable workers to make predictions on prevalence of diseases and effect of control measures. A model has been proposed for bancroftian filariasis transmission dynamics and frequency distribution of microfilariae in blood samples. Other statistical methodologies have been published relating to age and sex distribution and frequency distribution and one suggested that females have increased resistance to filariasis, especially in the reproductive years. Advances in diagnostic technologies are highly relevant to the epidemiology of filariasis. The development of antibody and especially antigen detection systems using monoclonal antibodies, DNA probes, and polymerase chain reactions, etc, will make a significant impact on the identification of infected persons. Findings along other lines may also have application to field epidemiology. The quantitative blood count (QBC) acridine orange hematocrit tube has also been found to be of value in diagnosis. Elevated levels of ecdysteroids found in other filarial infections should be tested in cases of lymphatic filariasis.

Animals↗

Perceptions of effectiveness of nurse-managed clinics: A cross-cultural study.

OBJECTIVE: To study perceptions of the effectiveness of two nurse-managed clinics (NMCs), one in the United States and the other in New Zealand. DESIGN: Cross-cultural evaluation study utilizing qualitative methodology; two rounds of in-depth interviews were tape recorded, transcribed verbatim, and analyzed for themes. SAMPLE: Data were initially collected from 21 participants. Sixteen of the original participants participated in a second interview. INTERVENTION: The first round of interviews and provisional data analysis were conducted in the respective NMCs; joint data analysis to identify themes and develop a preliminary joint report of findings followed. Sixteen participants responded to the provisional report; additional data analysis resulted in the final report of findings. RESULTS: Analysis of the data yielded three categories: the NMC milieu affects perceived effectiveness; perceptions are shaped by contrasting with past experiences; and the level of care affects personal health care decisions. CONCLUSIONS: The milieu created in the NMC enhances perceptions of effectiveness and responsibility for personal health care. Further research related to effectiveness of NMC models of care and client outcomes is needed. Qualitative methodology is recommended for cross-cultural research.

Attitude of Health Personnel↗

Social processes used by African American women in making decisions about mammography screening.

PURPOSE: To describe the social processes used by African American (AA) women ages > or = 50 years in making decisions about mammography screening. DESIGN: Grounded theory methodology. METHODS: Tape-recorded interviews with a researcher-designed, semi-structured interview guide with an initial and theoretical sample of 30 AA women ages 52 to 71 of diverse socioeconomic status. Interviews occurred in various settings such as the church rectory, women's homes, and work settings. Extensive written field notes and tapes were transcribed verbatim immediately after the interviews by an experienced transcriptionist. FINDINGS: The women's decisions about mammography screening were associated with five social processes: (a) acknowledging prior experiences with healthcare providers and systems; (b) reporting fears and fatalistic beliefs of breast cancer and related treatment; (c) valuing the opinions of significant others; (d) relying on religious beliefs and supports; and (e) caregiving responsibilities of significant others. The processes were further differentiated by three distinct decision-making styles: taking charge, enduring, and protesting. CONCLUSIONS: Each of the social processes was reported equally and emphasized by the diverse sample of AA women in decisions related to mammography screening. Mammography screening decisions were heavily influenced by caregiving responsibilities. Further research is needed to explain and understand this social process on the health and well-being of AA women over time.

Adaptation, Psychological↗

Light scattering in lens research: an essay on accomplishments and promises.

This paper briefly reviews light scattering methodologies in lens research. In the phenomenological sense cataract formation (lens opacities or turbidities) in its early stages can be described by enhanced scattering of light. In the analytical sense information is obtained on the molecular entities involved in light scattering. In Section 2, different methodologies (mainly static and dynamic) of light scattering experiments are described, which had been used successfully in lens research. In Section 3 the problem of interpretation of light scattering data in condensed phase is considered. It is pointed out that due to interparticle interactions the concentration dependence of the data must be considered. If dilution or thin sectioning of samples is not an option, it is better to report molecular parameters in terms of diffusion coefficients or decay times. In Section 4, a case is made to encourage light scattering experiments in the polarized/depolarized modes both in static and dynamic light scatterings. Preliminary data obtained with polarized/depolarized dynamic light scattering measurements on alpha-crystallin and interpreted in view of model systems and literature data imply that the molecule is a compact sphere with somewhat restricted segment mobility. The preliminary nature of this information is due to the unavailability of high power lasers and efficient polarizers in my lab at the time of these experiments.

Biomedical Research↗

Patients' experiences of readiness for discharge following a total hip replacement.

In recent years there has been a reduction in the length of stay of patients undergoing total hip replacement, as hospitals have attempted to reduce costs. A reduced length of stay requires patients undergoing total hip replacement to achieve independence over increasingly shorter periods. Clinical experience indicates that many of these patients feel unready or reluctant to be discharged to home, even though they are physically capable. Information is required about psychosocial factors that may affect or delay discharge. This naturalistic study used grounded theory methodology to explore the perceptions of discharge readiness of people who had undergone a total hip replacement. Using purposive sampling, five participants were interviewed prior to discharge from an acute hospital. The analysis resulted in the emergence of three categories: 'Confidence', 'Family and friends', and 'Feeling safe'. Participants wanted to feel safe both in the hospital and at home. Their own confidence levels and the presence of family and friends at home had a strong influence on feelings of safety. The core category and main concern of participants appeared to be about feeling safe. Participants who felt safe perceived they were ready to be discharged. Healthcare professionals can recognise and question patients about some of these factors that influence feelings of safety and readiness for discharge. Recognising concerns of patients prior to discharge will promote good patient care and discharge planning that is more acceptable to patients and carers.

Adult↗

Independent component analysis of microarray data in the study of endometrial cancer.

Gene microarray technology is highly effective in screening for differential gene expression and has hence become a popular tool in the molecular investigation of cancer. When applied to tumours, molecular characteristics may be correlated with clinical features such as response to chemotherapy. Exploitation of the huge amount of data generated by microarrays is difficult, however, and constitutes a major challenge in the advancement of this methodology. Independent component analysis (ICA), a modern statistical method, allows us to better understand data in such complex and noisy measurement environments. The technique has the potential to significantly increase the quality of the resulting data and improve the biological validity of subsequent analysis. We performed microarray experiments on 31 postmenopausal endometrial biopsies, comprising 11 benign and 20 malignant samples. We compared ICA to the established methods of principal component analysis (PCA), Cyber-T, and SAM. We show that ICA generated patterns that clearly characterized the malignant samples studied, in contrast to PCA. Moreover, ICA improved the biological validity of the genes identified as differentially expressed in endometrial carcinoma, compared to those found by Cyber-T and SAM. In particular, several genes involved in lipid metabolism that are differentially expressed in endometrial carcinoma were only found using this method. This report highlights the potential of ICA in the analysis of microarray data.

Endometrial Neoplasms↗

Patients' decision-making for migraine and chronic daily headache management. A qualitative study.

The objective of this study was to gain insight into the patients' decision-making for migraine and chronic daily headache management. Patients were recruited by theoretical sampling in Surrey (UK). Semi-structured and tape-recorded interviews (n = 13) were conducted, transcribed verbatim, coded and analysed according to the grounded theory methodology. Thirteen patients (8 migraine and 5 chronic daily headache) described their management. All patients employed multiple behaviours to manage their headaches. From the patients' descriptions emerged their decision-making. Based on experience, perceptions and new information, the decision-making process involved four stages: headache severity, evaluation, decision making and behaviours. Although the participants were passive with regards to certain management strategies, overall they were actively involved in treating and preventing their headaches. Furthermore, they were active decision-makers in choosing appropriate management. Migraine and chronic daily headache patients are actively involved in managing their headaches. They are key decision-makers and should not be overlooked as a resource for effective management.

Adult↗

Subjective well-being and initial dysphoric reaction under antipsychotic drugs - concepts, measurement and clinical relevance.

Since the introduction of neuroleptics in 1952, many studies have examined objective aspects of efficacy and tolerability. Despite the fact that neuroleptic treatment should also improve the patient's subjective experiences, this outcome criterion has been neglected in the past. This is unfortunate, as subjective well-being with treatment appears to be strongly related to patients' readiness to take their medication. The few existing studies differ in methodology and are difficult to compare due to a number of weaknesses, including varying underlying concepts, used assessment scales, or small sample sizes. Negative subjective well-being may manifest itself throughout the entire neuroleptic treatment, even as early as in the first 48 hours after neuroleptic treatment starts (initial dysphoric reaction, IDR). The aetiology of reduced subjective well-being or IDR is not fully explained; neuroleptic side effects, especially affective, cognitive and motor adverse events, differential effects of varying psychopathology or biopsychosocial are factors in discussion. The clinical impression is characterised by symptoms as dysphoria/anhedonia, reduced vitality, and emotional indifference, which could have a negative impact on relevant clinical factors such as response or medication adherence, and therefore on outcome. With regard to pharmacological treatment, evidence suggests that atypical antipsychotics induce less negative subjective effects than conventional neuroleptics, and that various new-generation antipsychotics could be evaluated differently by patients. This article reviews existing literature in order to approach relevant questions for pharmacotherapy.

Antipsychotic Agents↗

Bayesian hierarchical model for identifying changes in gene expression from microarray experiments.

Recent developments in microarrays technology enable researchers to study simultaneously the expression of thousands of genes from one cell line or tissue sample. This new technology is often used to assess changes in mRNA expression upon a specified transfection for a cell line in order to identify target genes. For such experiments, the range of differential expression is moderate, and teasing out the modified genes is challenging and calls for detailed modeling. The aim of this paper is to propose a methodological framework for studies that investigate differential gene expression through microarrays technology that is based on a fully Bayesian mixture approach (Richardson and Green, 1997). A case study that investigated those genes that were differentially expressed in two cell lines (normal and modified by a gene transfection) is provided to illustrate the performance and usefulness of this approach.

Bayes Theorem↗

Managing in the New Zealand health service. The interpretation of experience.

This paper investigates the managerial life and experiences of a group of service leaders in one region of the New Zealand health service. Through a complexity map methodology, creative interviewing, participant storytelling and presentation of their experiential narratives, the paper seeks to investigate how service leaders make sense of their complexity. First, the paper outlines the New Zealand health service context. Second, the paper introduces the sample of managers involved in the study. Third, the methodological framework of the study is outlined. Fourth, the data collected are described in the context of Gabriel's "tropes of story work". Fifth, the concept of "narrative thought" is introduced to interpret the use of attributions by health service managers as a means of fulfilling their needs and desires. The paper concludes by suggesting that through narrative sense-making managers are able to maintain a strong sense of self and identity even in stressful, pressurised, difficult and complex circumstances.

Administrative Personnel↗

Molecular hematology. Qualitative to quantitative techniques.

Over the last decade molecular diagnostics technology has developed dramatically from the most laborious, time- consuming southern blot methodology through the revolution of polymerase chain reaction PCR technology to the most reliable, fast, and contamination free molecular analyzer, the real-time quantitative-PCR. The Section of Hematology, Department of Pathology and Laboratory Medicine at King Faisal Specialist Hospital and Research Center has shared this experience during the last 10 years with more than 6,546 samples submitted for the analysis of different gene rearrangements, fusion gene transcripts and gene mutations including Ig heavy chain gene rearrangement for B-cell malignancies, T-cell receptor gamma chain gene rearrangement for T-cell malignancies, BCR/ABL-P210 and P190 fusion gene transcripts, for chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia, PML/RARalpha fusion gene for promyelocytic leukemia, AML1/ETO for acute myeloid leukemia AML-M2 with t8;21, CBFB/MYH11 for AML M4E0 with inv 16, BCL-2 for follicular lymphoma, and BCL-1 for mantle cell lymphoma. Hence, most molecular assays are qualitative in nature, quantitative assays are deemed necessary in the monitoring and follow-up of minimal residual disease in leukemia and lymphoma, and proved in our experience to serve as an essential tool to confirm complete remission CR post-chemotherapy and bone marrow transplantation, and to detect signs of early relapse for proper clinical intervention. In this manuscript, we retrospectively review our experience in molecular hematology and propose our recommended guidelines at King Faisal Specialist Hospital and Research Center.

Bone Marrow↗

Mothers' perceptions of the care-by-parent program prior to hospital discharge of their preterm infants.

PURPOSE: This research was conducted to gain an understanding of the care-by-parent experience for mothers of preterm infants. DESIGN: Phenomenologic methodology was used to explore the experiences of six mothers. Each participant slept overnight with her infant in a private hospital room. The mother assumed responsibility for her infant's care, knowing that nursing staff assistance was available if needed. Interviews were conducted on the following day and again after the infant had been home at least four days. SAMPLE: The participants were six mothers of preterm infants. MAIN OUTCOME VARIABLE: Mothers' experiences as they assumed responsibility in caring for their preterm infants away from the intensive care nursery. RESULTS: Findings revealed that the care-by-parent experience gives the mother an opportunity to assume full responsibility for her preterm infant's care, tests the reality of caregiving, helps her learn about caregiving activities and her infant's patterns of behavior, and confirms her readiness for independent parenting and the infant's readiness for discharge home. These findings confirm the benefits of rooming-in prior to discharge of preterm infants and provide guidelines for discharge planning.

Attitude to Health↗

Genotoxicity of aerosol extracts. Some methodological aspects and the contribution of urban and industrial locations.

The genotoxicity of aerosol extracts was investigated with the Ames test and an SCE test in vitro. In addition to experiments to evaluate current techniques, a so-called gradient study was carried out in an industrialized part of The Netherlands to obtain insight into the contribution of urban and industrial locations to the genotoxicity of aerosol extracts. The influence of variations in the sampling was investigated. The results indicate that moderate variations in the volume of air sampled per unit of time and of the duration of the sampling period do not have a great influence on the effect measured. Experiments with filters impregnated with 14C-labelled benzo[a]pyrene showed that this compound is converted during sampling into directly active mutagens; no evaporation occurred. The results of experiments to evaluate the extraction procedure indicated that an 8-h Soxhlet extraction with methanol is better than, or as good as, Soxhlet extraction with other solvents. The gradient study showed that the aerosol downwind from industrial/urban areas exerted a reproducibly stronger effect in the Ames test and the SCE test when compared with aerosol from sea air.

Aerosols↗

Discrimination and scoring using small sets of genes for two-sample microarray data.

Comparison of gene expression for two groups of individuals form an important subclass of microarray experiments. We study multivariate procedures, in particular use of Hotelling's T2 for discrimination between the groups with a special emphasis on methods based on few genes only. We apply the methods to data from an experiment with a group of atopic dermatitis patients compared with a control group. We also compare our methodology to other recently proposed methods on publicly available datasets. It is found that (i) use of several genes gives a much improved discrimination of the groups as compared to one gene only, (ii) the genes that play the most important role in the multivariate analysis are not necessarily those that rank first in univariate comparisons of the groups, (iii) Linear Discriminant Analysis carried out with sets of 2-5 genes selected according to their Hotelling T2 give results comparable to state-of-the-art methods using many more genes, a feature of our method which might be crucial in clinical applications. Finding groups of genes that together give optimal multivariate discrimination (given the size of the group) can identify crucial pathways and networks of genes responsible for a disease. The computer code that we developed to make computations is available as an R package.

Algorithms↗

Researching the symptoms of menopause: an exercise in methodology.

This paper deals with the methodological problems involved in the measurement of physical and psychological morbidity among menopausal women. A sample of 477 women were interviewed six times over a 3-yr period. In addition to questions about their menstrual status, the women were asked at each interview to complete a checklist of physical, menopausal, and psychological symptoms. Factor analysis was performed on the symptom experience to determine if symptoms could be grouped together in ways which would demonstrate clinically useful constructs and be stable over time. One-way analysis of variance showed a significant relationship only between the vasomotor symptoms and menopausal status.

Adult↗