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PubMed1997

Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units.

OBJECTIVES: To compare the frequency and preventability of adverse drug events and potential adverse drug events in intensive care units (ICUs) and non-ICUs. To evaluate systems factors involving the individual caregivers, care unit teams, and patients involved in each adverse drug event by comparing ICUs with non-ICUs and medical ICUs with surgical ICUs. DESIGN: Prospective cohort study. Participants included all 4,031 adult admissions to a stratified, random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical ICUs and four medical and two surgical general care units. SETTING: Two tertiary care hospitals: Eleven medical and surgical units, including two medical and three surgical ICUs. PATIENTS: Adult admissions (n = 4,031). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rate of preventable adverse drug events and potential adverse drug events, length of stay, charges, costs, and measures of the unit's environment. Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented adverse drug events or potential adverse drug events and as to severity and preventability. Those individuals involved in the preventable adverse drug event and potential adverse drug event underwent detailed interviews by peer case-investigators. The rate of preventable adverse drug events and potential adverse drug events in ICUs was 19 events per 1000 patient days, nearly twice that rate of non-ICUs (p <.01). The medical ICU rate (25 events per 1000 patient days) was significantly (p <.05) higher than the surgical ICU rate (14 events per 1000 patient days). When adjusted for the number of drugs used in the previous 24 hrs or ordered since admission, there were no differences in rates between ICUs and non-ICUs. ICU acuity, length of stay, and severity of the adverse drug event were greater in ICUs than non-ICUs, but there were no differences between medical ICU and surgical ICU patients. Structured interviews indicated almost no differences between ICUs and non-ICUs for many characteristics of the patient, patient care team, systems, and individual caregivers. CONCLUSIONS: The rate of preventable and potential adverse drug events was twice as high in ICUs compared with non-ICUs. However, when adjusted for the number of drugs ordered, there was no greater likelihood for preventable adverse drug events and potential adverse drug events to occur in ICUs than in non-ICUs. Preventable adverse drug events and potential adverse drug events occurred in units that functioned normally and involved caregivers who were working under reasonably normal circumstances, not at the extremes of workload, stress, or a difficult environment.

Adult↗

PubMed2000

Stability of the Iceberg Profile as a function of perceived difficulty in defeating an opponent.

9 starters and 8 nonstarters of a university women's softball team completed the Profile of Mood States prior to playing the team perceived to be the most and least difficult to defeat in their conference. A significant interaction indicated that nonstarters displayed higher fatigue prior to playing the opponent perceived as most difficult to defeat. In addition, significant mean differences were found between starters and nonstarters on constructs of Anger, Confusion, Tension, and Depression, suggesting that nonstarters may not share same psychological profile as their peers who start.

Adult↗

PubMed2002

Intraoperative neurophysiological monitoring in pediatric neurosurgery: why, when, how?

INTRODUCTION: This review is primarily based on peer-reviewed scientific publications and on the authors' experience in the field of intraoperative neurophysiology. The purpose is a critical analysis of the role of intraoperative neurophysiological monitoring (INM) during various neurosurgical procedures, emphasizing the aspects that mainly concern the pediatric population. Original papers related to the field of intraoperative neurophysiology were collected using medline. INM consists in monitoring (continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (functional identification and preservation of anatomically ambiguous nervous tissue) techniques. We attempted to delineate indications for intraoperative neurophysiological techniques according to their feasibility and reliability (specificity and sensitivity). DISCUSSION AND CONCLUSIONS: In compiling this review, controversies about indications, methodologies and the usefulness of some INM techniques have surfaced. These discrepancies are often due to lack of familiarity with new techniques in groups from around the globe. Accordingly, internationally accepted guidelines for INM are still far from being established. Nevertheless, the studies reviewed provide sufficient evidence to enable us to make the following recommendations. (1) INM is mandatory whenever neurological complications are expected on the basis of a known pathophysiological mechanism. INM becomes optional when its role is limited to predicting postoperative outcome or it is used for purely research purposes. (2) INM should always be performed when any of the following are involved: supratentorial lesions in the central region and language-related cortex; brain stem tumors; intramedullary spinal cord tumors; conus-cauda equina tumors; rhizotomy for relief of spasticity; spina bifida with tethered cord. (3) Monitoring of motor evoked potentials (MEPs) is now a feasible and reliable technique that can be used under general anesthesia. MEP monitoring is the most appropriate technique to assess the functional integrity of descending motor pathways in the brain, the brain stem and, especially, the spinal cord. (4) Somatosensory evoked potential (SEP) monitoring is of value in assessment of the functional integrity of sensory pathways leading from the peripheral nerve, through the dorsal column and to the sensory cortex. SEPs cannot provide reliable information on the functional integrity of the motor system (for which MEPs should be used). (5) Monitoring of brain stem auditory evoked potentials remains a standard technique during surgery in the brain stem, the cerebellopontine angle, and the posterior fossa. (6) Mapping techniques (such as the phase reversal and the direct cortical/subcortical stimulation techniques) are invaluable and strongly recommended for brain surgery in eloquent cortex or along subcortical motor pathways. (7) Mapping of the motor nuclei of the VIIth, IXth-Xth and XIIth cranial nerves on the floor of the fourth ventricle is of great value in identification of "safe entry zones" into the brain stem. Techniques for mapping cranial nerves in the cerebellopontine angle and cauda equina have also been standardized. Other techniques, although safe and feasible, still lack a strong validation in terms of prognostic value and correlation with the postoperative neurological outcome. These techniques include monitoring of the bulbocavernosus reflex, monitoring of the corticobulbar tracts, and mapping of the dorsal columns. These techniques, however, are expected to open up new perspectives in the near future.

Brain Mapping↗

PubMed2024

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.

Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes to their regulatory foundations are limited. Here, we introduce Multiome Perturb-seq, extending single-cell CRISPR screens to simultaneously measure perturbation-induced changes in gene expression and chromatin accessibility. We apply Multiome Perturb-seq in a CRISPRi screen of 13 chromatin remodelers in human RPE-1 cells, achieving efficient assignment of sgRNA identities to single nuclei via an improved method for capturing barcode transcripts from nuclear RNA. We organize expression and accessibility measurements into coherent programs describing the integrated effects of perturbations on cell state, finding that ARID1A and SUZ12 knockdowns induce programs enriched for developmental features. Modeling of perturbation-induced heterogeneity connects accessibility changes to changes in gene expression, highlighting the value of multimodal profiling. Overall, our method provides a scalable and simply implemented system to dissect the regulatory logic underpinning cell state. A record of this paper's transparent peer review process is included in the supplemental information.

Humans↗

PubMed2005

Amyloid beta peptide as a physiological modulator of neuronal 'A'-type K+ current.

Control of neuronal spiking patterns resides, in part, in the type and degree of expression of voltage-gated K(+) channel subunits. Previous studies have revealed that soluble forms of the Alzheimer's disease associated amyloid beta protein (Abeta) can increase the 'A'-type current in neurones. In this study, we define the molecular basis for this increase and show that endogenous production of Abeta is important in the modulation of Kv4.2 and Kv4.3 subunit expression in central neurones. A-type K(+) currents, and Kv4.2 and Kv4.3 subunit expression, were transiently increased in cerebellar granule neurones by the 1-40 and 1-42 forms of Abeta (100nM, 2-24h). Currents through recombinant Kv4.2 channels expressed in HEK293 cells were increased in a similar fashion to those through the native channels. Increases in 'A'-type current could be prevented by the use of cycloheximide and brefeldin A, indicating that protein expression and trafficking processes were altered by Abeta, rather than protein degredation. Endogenous Abeta production in cerebellar granule neurones was blocked using inhibitors of either gamma- or beta-secretase and resulted in decreased K(+) current. Crucially this could be prevented by co-application of exogenous Abeta (1nM), however, no change in Kv4.2 or Kv4.3 subunit expression occurred. These data show that Abeta is a modulator of Kv4 subunit expression in neurones at both the functional and the molecular level. Thus Abeta is not only involved in Alzheimer pathology, but is also an important physiological regulator of ion channel expression and hence neuronal excitability.

Amyloid Precursor Protein Secretases↗

PubMed2004

Taking hold of some kind of life: how developmental tasks relate to trajectories of well-being during the transition to adulthood.

The purpose of this study was to examine how successes and difficulties with various developmental tasks of early adulthood relate to the course of well-being. Three waves of national panel data spanning ages 18-26 were drawn from the Monitoring the Future study (N = 3518). Based on self-reports, respondents were assigned scores (succeeding, maintaining, or stalling) to reflect progress in seven domains of developmental tasks: education, work, financial autonomy, romantic involvement, peer involvement, substance abuse avoidance, and citizenship. We identified trajectory groups of well-being (based on self-esteem, self-efficacy, and social support) that reflect diverging trajectories during the transition: steady-high versus high-decreasing, and low-increasing versus steady-low. Logistic regression analyses were conducted to predict membership in the diverging well-being trajectory groups as a function of developmental task domain scores. Maintaining or gaining a salutary trajectory of well-being across the transition was found to be a function of more success and less stalling across the developmental tasks, specifically in the work, romantic involvement, and citizenship domains. Compensatory effects (e.g., succeeding in education compensated for not succeeding in work) and threshold effects (e.g., succeeding in both achievement and affiliation domains was necessary for a salutary trajectory) were also found.

Adolescent↗

PubMed2003

Biology and functions of human leukocyte antigen-G in health and sickness.

In 1998, the first International Conference on human leukocyte antigen-G (HLA-G) was held in Paris. At that time, HLA-G was still a new HLA class I molecule, few aspects of its immunological functions were known, and its expression by tumors was just being described. In 1998, tools to properly study HLA-G were lacking, especially monoclonal antibodies, and three conclusions were drawn after the congress: (i) animal models were needed, (ii) the biology of HLA-G isoforms had to be confirmed, and (iii) HLA-G expression by tumors required clarification. Five years later, these three issues have been addressed. HLA-G is now gaining pace and is investigated for its immuno-inhibitory functions in the context of multiple pathologies. Eighty five oral presentations were given this year for more than 200 investigators working on HLA-G by speakers from over 20 countries. The success of the 3rd International Conference on HLA-G reflects the interest and tremendous work of the many research teams which, over the years, contributed to the publication of more than 500 peer-review articles. We summarize the key points that were presented and discussed during this meeting.

Autoimmune Diseases↗

PubMed2003

Genome evolution reveals biochemical networks and functional modules.

The analysis of completely sequenced genomes uncovers an astonishing variability between species in terms of gene content and order. During genome history, the genes are frequently rear-ranged, duplicated, lost, or transferred horizontally between genomes. These events appear to be stochastic, yet they are under selective constraints resulting from the functional interactions between genes. These genomic constraints form the basis for a variety of techniques that employ systematic genome comparisons to predict functional associations among genes. The most powerful techniques to date are based on conserved gene neighborhood, gene fusion events, and common phylogenetic distributions of gene families. Here we show that these techniques, if integrated quantitatively and applied to a sufficiently large number of genomes, have reached a resolution which allows the characterization of function at a higher level than that of the individual gene: global modularity becomes detectable in a functional protein network. In Escherichia coli, the predicted modules can be bench-marked by comparison to known metabolic pathways. We found as many as 74% of the known metabolic enzymes clustering together in modules, with an average pathway specificity of at least 84%. The modules extend beyond metabolism, and have led to hundreds of reliable functional predictions both at the protein and pathway level. The results indicate that modularity in protein networks is intrinsically encoded in present-day genomes.

Amino Acids↗

PubMed1999

Neuropsychological outcome following unilateral pallidotomy.

Despite the findings of significantly improved motor functioning following pallidotomy for the treatment of Parkinson's disease, the cognitive sequelae following surgery have yet to be clearly defined. With increasing knowledge of the surgery's effect on frontostriatal circuits, the cognitive processes potentially affected by the procedure require further exploration to evaluate fully the efficacy of the treatment. We reviewed 10 studies on the neuropsychological outcome after pallidotomy that were published in peer-reviewed journals. A general agreement exists that pallidotomy is a relatively safe and effective treatment for ameliorating the motor symptoms of Parkinson's disease, with relatively few cognitive changes reported following surgery. However, a number of conceptual and methodological concerns, including diverse selection criteria, small sample sizes and short follow-up periods, limit the interpretation and generalizability of these findings. These concerns are discussed in detail, along with a summary of the current neuropsychological literature, suggested guidelines for the conduct of research and future research directions. The neuropsychological findings are critically reviewed and tabulated by study, cognitive domain and follow-up period, with particular emphasis on hemisphere-specific cognitive changes.

Affect↗

PubMed1999

Construction of a variability map for eukaryotic large subunit ribosomal RNA.

In this paper, we present a variability map of the eukaryotic large subunit ribosomal RNA, showing the distribution of variable and conserved sites in this molecule. The variability of each site in this map is indicated by means of a colored dot. Construction of the variability map was based on the substitution rate calibration (SRC) method, in which the substitution rate of each nucleotide site is computed by looking at the frequency with which sequence pairs differ at that site as a function of their evolutionary distance. Variability maps constructed by this method provide a much more accurate and objective description of site-to-site variability than visual inspection of sequence alignments.

Animals↗

PubMed1993

Bereavement or depression? The impact of the loss of a friend to suicide.

OBJECTIVE: To determine whether the depressive reactions experienced by youth exposed to suicide were uncomplicated bereavement or bona fide major depression. METHOD: In a sample of 146 friends and acquaintances of 26 adolescent suicide victims, 43 (29%) developed a depressive episode subsequent to exposure to suicide, 18 were depressed before exposure, and 85 were never depressed. The three groups were compared. RESULTS: Those who became depressed after exposure were similar to those who were depressed before exposure. Both depressed groups differed from the nondepressed exposed group with respect to functional impairment, depressive symptom pattern and severity, convergent validity with other measures of depression, personal and family history of depression, and stressful life events. Previous depressives showed greater comorbidity with nonaffective disorders than those who became depressed after exposure. Those who became depressed after exposure compared with both the previous and nondepressive had a closer relationship with the suicide victims, showed more severe grief, and showed more intense exposure to the suicide. CONCLUSIONS: Depressive reactions occurring after exposure to suicide appear to be bona fide major depression, occurring as a complication of bereavement. Youth exposed to suicide should be carefully screened and followed up. Should a symptomatic picture of depression and functional impairment ensue, such exposed youth should be treated accordingly for a major depressive episode.

Adolescent↗

PubMed2004

Psychosocial functioning in youths at high risk to develop major depressive disorder.

OBJECTIVE: To compare the psychosocial functioning of children and adolescents at high risk of major depressive disorder with youths with acute major depressive disorder and healthy controls. METHOD: High-risk (n = 57), major depressive disorder (n = 71), and healthy control (n = 48) youths and their families were recruited from 1987 to 1996 and assessed for psychopathology using standardized instruments. Except for 16 children who had disruptive disorders, the high-risk children were free of psychopathology. A parent completed the Psychosocial Schedule to evaluate the mother-child, father-child, marital relationships, and child-friend relationships and the child's school performance. RESULTS: Overall, high-risk and healthy controls had similar psychosocial functioning. Marital relationships were worse in the high-risk children with psychopathology. Youths with major depressive disorder had significantly more psychosocial problems and school difficulties than those at high risk and healthy controls in most domains measured. Controlling for age, pubertal stage, race, sex, family composition, current and lifetime parental depression, and current and lifetime parental nonmood psychopathology yielded similar results. CONCLUSIONS: The family and peer interactions of high-risk youths were similar to the interactions of healthy controls. Although family dysfunctional patterns seem to mainly depend on the child's depressive symptoms, longitudinal studies are needed to establish causality.

Acute Disease↗

PubMed1981

Group dynamic practices applied to health education.

The application of group dynamic techniques as pedagogical tools transforms the classroom into a laboratory for living. In such an environment, concepts relative to man's behavior are not only explained but learned experimentally through the interactive process. Through utilization of this model, the health educator can provide an opportunity for different groups at school to learn about each other's values as well as appreciate their differences. Coping with peer pressure, shyness, others' feelings and defense mechanisms become a part of the learning process. The difficulties of responsible decision making can be periodically examined. Personal expression by a wide range of students is at best difficult to accomplish, and the use of materials and media as motivational devices can not be viewed as ends in themselves. They need to be utilized with regard to a functional analysis of the group dynamic process. Such an analysis should include the teacher's own biases, communication patterns, student roles, reasons for resistance and awareness of sub groups. After making a diagnosis of the system, the teacher is then in a position to orchestrate class behavior through a variety of strategic moves. Such moves include recreating communication channels, controlling stress levels, manipulating seating and modeling desirable behaviors. By incorporating aspects of therapeutic techniques into his/her teaching style, the teacher must not only be knowledgeable but astute and inventive as well.

Adolescent↗

PubMedDate not supplied

Differences that make a difference: comparisons of metacomponential functioning and knowledge base among groups of high and low IQ learning disabled, mildly mentally retarded, and normally achieving adults.

To determine if cognition among persons with learning disabilities (LD) and mild mental retardation (MMR) is similar, we compared metacomponential functioning and knowledge acquisition across groups of incarcerated adults with LD and high IQ (HIQLD), with LD and low IQ (LIQLD), with normal achievement (NA), and with MMR. The Slosson Intelligence Test Computer Report (Nicholson, 1984) formula established criteria for group inclusion. Metacomponential functioning among 77 males and 26 females was measured by a confidence test (Echternacht, Boldt, & Sellman, 1971) designed for the general knowledge subtest of the SRA Achievement Battery (Naslund, Thorpe, & Lefever, 1982). Knowledge base and group membership were significantly related to metacomponential ability (R2 = .84). Persons with HIQLD and LIQLD performed better than those with MMR on both measures. The HIQLD, however, did not outperform their peers with NA. Results show that (a) knowledge base is the best predictor of metacomponential skill, (b) metacomponential orchestration differentiates persons with HIQLD from those with LIQLD and both groups from persons with MMR, and (c) IQ mediates metacognition, but does not explain it. Education should emphasize knowledge acquisition for people with HIQLD; people with LIQLD and MMR require more attention to metacognition.

Achievement↗

PubMedDate not supplied

Open versus closed kinetic chain exercises for patellofemoral pain. A prospective, randomized study.

The goal of this prospective study was to evaluate the efficacy of open versus closed kinetic chain exercises in the nonoperative management of patellofemoral pain. Sixty patients were randomized into a 5-week program that consisted of only closed kinetic chain exercises or only open kinetic chain exercises. Muscle characteristics, subjective symptoms, and functional performance were evaluated in this study at the time of the initial physical examination, at the end of the treatment period, and 3 months later. Both groups experienced a statistically significant decrease in pain and an increase in functional performance. This study shows that both open and closed kinetic chain exercise programs lead to an improved subjective and clinical outcome in patients with anterior knee pain. The few significantly better functional results for some of the tested parameters in the closed kinetic chain group suggest that this type of treatment is a little more effective than the open kinetic chain program in the treatment of these patients.

Adolescent↗

PubMedDate not supplied

Allogeneic hematopoietic stem cells from sources other than bone marrow: biological and technical aspects.

BACKGROUND AND OBJECTIVE: Identification and characterization of hematopoietic stem cells in peripheral blood (PB) and cord blood (CB) have suggested feasible alternatives to conventional allogeneic bone marrow (BM) transplantation. The growing interest in this use of allogeneic stem cells has prompted the Working Group on CD34-positive Hematopoietic Cells to review this subject by analyzing its biological and technical aspects. EVIDENCE AND INFORMATION SOURCES: The method used for preparing this review was informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the individual points in order to reach an agreement on the various concepts, and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of hematopoietic stem cell biology and processing, and have contributed original papers published in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF ART: Several studies have now shown that hematopoietic stem cells collected from peripheral blood after the administration of G-CSF, or from cord blood upon delivery, are capable of supporting rapid and complete reconstitution of BM function in allogeneic recipients. Perhaps more importantly, reinfusion of large numbers of HLA-matched T-cells from PB collections or T-cells with various degrees of HLA disparity from CB did not result in a higher incidence or greater severity of acute graft-versus-host disease than expected with BM. Based on the data reviewed, operative guidelines for mobilization, collection and graft processing are provided. PERSPECTIVES: It should be remembered that despite the growing interest, these procedures must be still considered as advanced clinical research and should be included in formal clinical trials aimed at demonstrating their definitive role in stem cell transplantation. In this regard, a large European randomized study is currently comparing PB and BM allografts. However, the possibility of collecting large quantities of hematopoietic progenitor-stem cells, perhaps with reduced allo-reactivity, offers an exciting perspective for widening the number of potential stem cell donors and greater leeway for graft manipulation than is possible with BM.

Animals↗

PubMed1996

Utility of a verbal reasoning test in indicating vocational readiness following traumatic brain injury.

Present tests are often inadequate to assess subtle aspects of cognitive-communicative functioning following traumatic brain injury (TBI), making it difficult to predict vocational readiness, particularly for those in professional occupations. This study examined the viability of the Ross Test of Higher Cognitive Processes (RTHCP) as a measure of verbal reasoning deficits following TBI. The verbal reasoning performance of a 43-year-old lawyer with TBI was compared, at two stages in his rehabilitation, to that of a peer group of lawyers (n = 43). The RTHCP detected noticeable differences in speed and accuracy of performance at different stages of recovery. The RTHCP also revealed individual differences among the peer group, who presumably were competent in verbal reasoning. Thus, the RTHCP may be an effective tool to measure subtle deficits in verbal reasoning post-TBI. Some cautions in using this test for the TBI population are presented, as well as suggestions for further test development and validation.

Adult↗

PubMed1999

Home-based multisystemic therapy as an alternative to the hospitalization of youths in psychiatric crisis: clinical outcomes.

OBJECTIVE: The primary purpose of this study was to determine whether multisystemic therapy (MST), modified for use with youths presenting psychiatric emergencies, can serve as a clinically viable alternative to inpatient psychiatric hospitalization. METHOD: One hundred sixteen children and adolescents approved for emergency psychiatric hospitalization were randomly assigned to home-based MST or inpatient hospitalization. Assessments examining symptomatology, antisocial behavior, self-esteem, family relations, peer relations, school attendance, and consumer satisfaction were conducted at 3 times: within 24 hours of recruitment into the project, shortly after the hospitalized youth was released from the hospital (1-2 weeks after recruitment), and at the completion of MST home-based services (average of 4 months postrecruitment). RESULTS: MST was more effective than emergency hospitalization at decreasing youths' externalizing symptoms and improving their family functioning and school attendance. Hospitalization was more effective than MST at improving youths' self-esteem. Consumer satisfaction scores were higher in the MST condition. CONCLUSIONS: The findings support the view that an intensive, well-specified, and empirically supported treatment model, with judicious access to placement, can effectively serve as a family- and community-based alternative to the emergency psychiatric hospitalization of children and adolescents.

Activities of Daily Living↗