Biomedical subjects
J Clough
Publications and source records attributed to J Clough.
Improving medication safety across a multihospital system.
BACKGROUND: The Massachusetts Coalition for the Prevention of Medical Errors and the Institute for Healthcare Improvement have identified 16 best practices to reduce adverse drug events. CareGroup, a network of six hospitals in eastern Massachusetts, multiplied its routine use of these best practices tenfold in the first 18 months of its medication reliability project. DEVELOPING THE COLLABORATIVE STRATEGY: Although CareGroup's long-term plans included technological advances such as clinical order entry, computer systems in the pharmacy, dispensing stations on patient floors, and bedside bar-coding, efforts first focused on manual improvements feasible within a year's time. A 4-year strategy involves helping the medication reliability team leaders at each hospital to create impressive local results, publicize the results to their colleagues, invite their clinical colleagues to learn to use plan-do-study-act (PDSA) cycles, and have colleagues lead PDSA cycles themselves. At monthly or bimonthly task force meetings, team results are presented and team leaders are given specific assignments for their teams. CASE STUDIES: One project reduced the time to blood anticoagulation for heparinized patients. The second dramatically reduced lookalike/soundalike errors. The third improved the safety of patient-controlled analgesia. The fourth reduced coumadin incidents. The fifth improved the education of patients about their medications. The sixth greatly reduced the morning dispensing backlog in the pharmacy. SUCCESS FACTORS: Key success factors, in addition to leadership, are the use of data, forcing functions, appropriate pacing, inexpensive practices, and a consultant. The pace needed to implement the best practices overall made it imperative to make many changes rapidly. Often, the team initiated several changes at one time, rather than sequencing changes in successive PDSA cycles. LIMITATIONS, BARRIERS, AND NEXT DIRECTIONS: CareGroup faces key challenges in measurement and in spreading and deepening the involvement of clinicians, particularly physicians. It lacks an overall, objective measure of medication safety. Spread of the changes made has been incomplete although the adoption of the best practices increased tenfold (from 6 to 60) in 21 months. Two of the case study interventions--in coumadin order sequencing and dedicating a pharmacy technician to order entry--have been implemented at only one site to date, even though the adoption of the change ideas across hospitals is encouraged. The eventual impact of the changes planned for the future, through automated systems such as computerized order entry, is much larger. Considerable progress is anticipated in adoption of best practices; improvement in top-priority areas of each hospital; improved automation and technology in ordering, dispensing, and administering medication; and better reporting.
Personal exposure to nitrogen dioxide and risk of airflow obstruction in asthmatic children with upper respiratory infection.
BACKGROUND: Several studies have linked air pollution by nitrogen dioxide (NO(2)) with increased hospital admissions for asthma in children. Exacerbations of asthma in children are often precipitated by upper respiratory infections. It is therefore possible that NO(2) increases the risk of airways obstruction when asthmatic children develop upper respiratory infections. METHODS: To test this hypothesis a sample of 114 asthmatic children aged 7-12 years were followed for a total of up to 13 months. Probable upper respiratory infections were identified by consensus review of daily symptom diaries, and episodes of airways obstruction from serial records of peak expiratory flow (PEF). Personal exposures to NO(2) were measured with Palmes tubes that were changed weekly. Generalised estimating equations were used to assess the relative risk (RR) of an asthmatic exacerbation starting within seven days of an upper respiratory infection according to estimated NO(2) exposure during the one week period from two days before to four days after the onset of the infection. RESULTS: The children were followed for an average of 34 weeks during which 318 upper respiratory infections and 224 episodes of reduced PEF were diagnosed. PEF episodes were much more likely to occur in the seven days following the onset of an upper respiratory infection than at other times. Estimated exposures to NO(2) at the time of infections were generally low (geometric mean 10.6 microg/m(3)). Compared with exposures of < or = 8 microg/m(3), exposures of >28 microg/m(3) were associated with a RR of 1.9 (95% confidence interval 1.1 to 3.4) for the development of an asthmatic episode within seven days of an infection. CONCLUSIONS: The findings give some support to the hypothesis that NO(2) increases the risk of asthmatic exacerbations following respiratory infections, even at relatively low levels of exposure. Further studies in populations with higher exposures would be useful.
Pigmented schwannoma of the ventral spinal cord.
Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man. Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors.
Selection of a hospital for a transfer: the roles of patients, families, physicians and payers.
OBJECTIVE: This study investigates the reasons for hospital transfers and the role patients, their families, physicians, and payers play in the choice of a referral center. DATA SOURCES: A thirty-three item questionnaire and clinical data from the hospital's discharge database. STUDY DESIGN: A study of all 307 hospital transfer patients admitted between November 9 and December 3, 1993 was conducted to understand the factors contributing to the increase in transfers and the reasons patients were sent to CCH. Data on the transfer decision were collected by interviewing patients 48 hours after admittance to the hospital or by telephone if they were discharged before an interview could be completed. Two hundred and sixty-two (85%) patients were interviewed. PRINCIPLE FINDINGS: (1) Almost 58% of transfers were patient-initiated or -influenced; the remainder were physician- (38%) or payer-directed (4%); (2) More than 78% of the patients identified lack of clinical expertise/technology at originating hospital as the main reason for transferring. Other reasons included: established CCH patient status (43%), CCH marketing (31%), and concerns regarding quality of care at originating hospital (10%). Financial and quality dumping were not identified as reasons for the transfer. New patients to CCH were more likely to indicate that marketing and lack of clinical resources at originating hospital were reasons for selecting CCH than previous patients. CONCLUSIONS: Patients significantly influenced the transfer decision and the transfer decision-making process can be influenced by marketing. The opinions of the consumer should not be underestimated, especially by those seeking non-marketing solutions to health care reform.
The Disability Discrimination Act 1995--an OHP challenge.
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Rat eosinophils: isolation and characterization of superoxide production.
Studies with isolated cells are important to the understanding of mechanisms by which eosinophils participate in allergic inflammation. Due to species variability, isolation techniques and cell biology need to be defined for each source. We developed methods to obtain rat eosinophils with purity and viability exceeding 90%, characterized the superoxide anion production of these cells in response to standard activators, and compared these results with those previously obtained in our laboratories with the use of human eosinophils. Rat eosinophils responded vigorously to phorbol myristate acetate and poorly to platelet-activating factor and to N-formyl-methionyl-leucyl-phenylalanine, parallel to the responses of human eosinophils. In contrast, rat eosinophils responded unlike human eosinophils to other activators, having a larger response to calcium ionophore A23187, a smaller response to serum-treated or serum-opsonized zymosan, and a negative rather than positive modulatory effect of cytochalasin B. We conclude that rat eosinophils can be obtained in high purity and with intact responsiveness to a number of different activators.
Calcium bioavailability from a calcium- and sulfate-rich mineral water, compared with milk, in young adult women.
Some mineral waters have a high calcium content and may contribute a significant part of the human daily requirements. Calcium bioavailability from a calcium- and sulfate-rich mineral water (CS-W) containing 11.2 mmol Ca/L (467 mg/L) was compared with that from milk in nine healthy young women. Calcium absorption was measured in the fasting state with a dual-label stable-isotope technique. Fractional absorption rates from milk and CS-W were 25.0 +/- 6.7% and 23.8 +/- 4.8% (means +/- SD), respectively, and did not differ significantly (P = 0.05). Urine was collected for 36 h after the administration of the oral stable isotope while the subjects consumed a controlled diet and a quantity of milk or CS-W providing 25 mmol (1000 mg) Ca. No significant difference was found in the excretion of calcium, nor in the excretion of the two stable isotopes. Mean urinary sulfate excretion was significantly increased by 35% when the CS-W was consumed. No significant correlation was found between 36-h urinary excretion of the intravenous calcium tracer and sulfate, sodium, or urine volume. Therefore, calcium from the CS-W was as well absorbed and retained as that from milk, and no calciuric effect of sulfate was found, showing that such mineral waters can be valuable dietary sources of calcium.
Effects of airway parasympathetic tone on responses to intravenous bronchoconstrictor agonists in rats.
To test the hypothesis that parasympathetic airway tone may affect airway responsiveness, we measured bronchoconstrictor responses to intravenous bethanechol (BCh) in anesthetized vagotomized rats with and without background vagal nerve stimulation and developed a predictive model based on pharmacological additivity between endogenous and intravenous agonists. A high degree of agreement (r2 = 0.93) between the measured and predicted responses indicated that intravenous BCh and parasympathetic tone had bronchoconstrictor effects that were pharmacologically additive. An expansion of the additive model was used to determine that the percentage of decrease in respiratory system conductance (Grs) would be a measure of airway response independent of background parasympathetic tone. As predicted, the percentage of decrease in Grs after intravenous BCh was minimally affected by background vagal stimulation. However, the percentage of decrease in Grs was augmented by vagal stimulation for intravenous 5-hydroxytryptamine hydrochloride, a known parasympathetic neuromodulator, and for methacholine, an agonist with nicotinic as well as muscarinic activity (P < 0.02 for each agonist). We conclude that airway parasympathetic tone can be a source of variability for airway responsiveness when substances having neuromodulatory activity are involved in the provocative challenge.
Association of mononuclear cells and eosinophils with airway resistance and responsiveness in rat pulmonary inflammatory responses.
To evaluate the association of various leukocytes with pulmonary resistance and methacholine responsiveness, we induced pulmonary eosinophil-rich inflammation in IgE-sensitized (ovalbumin) Sprague Dawley rats. Sensitized rats were challenged with either relevant (OA) or irrelevant antigen by tracheal insufflation a) with no other treatment, b) in conjunction with intravenous Sephadex beads pretreatment, or c) with antigen coupled covalently to Sepharose beads. About 24 h after antigen challenge, respiratory system resistance (Rrs), response to aerosolized methacholine, and pulmonary histopathology were evaluated. Challenge with OA, insufflation with Sepharose, and treatment with i.v. Sephadex all independently increased inflammatory cell infiltrates, but the combination of OA with the other agents did not significantly enhance the inflammatory response over OA alone. Interactive stepwise regression techniques were utilized to identify correlates for Rrs and methacholine responsiveness. Mononuclear cell score was a significant predictor (p < .01) for Rrs, and insufflation of Sepharose had a significant independent effect on Rrs (p = .01) above that predicted by mononuclear cell infiltrates. Conversely, eosinophil score and neutrophil score were not significant predictors for Rrs, and challenges with antigen or Sephadex had no significant independent effect on Rrs beyond that predicted from mononuclear cell infiltrates. Eosinophil score was the only significant histological predictor for methacholine responsiveness (p < .0001). Challenges with Sephadex, antigen and Sepharose did not significantly change methacholine responsiveness independently of the changes associated with eosinophil infiltrates. These findings suggest that mononuclear cells and eosinophils contribute to increases in airway resistance and responsiveness, respectively, following the induction of pulmonary inflammation by both allergic and non-allergic stimuli.
Resource management education: an imaginative approach.
"Outcomes," a resource management game, promotes case management philosophies and strategies. This unique approach to teaching offsets the nurses' fear of change by learning in a relaxed environment.
Anesthetic effects on pulmonary allergic responses in rats: changes in sensitivity to serotonin.
Subsequent to observations that pulmonary responses to antigen challenge are of different magnitudes in sensitized rats that are anesthetized with different drugs, we conducted studies to test whether the alterations in responses were due to changes in airway responsiveness to cholinergic or serotonergic challenge, opioid-receptor mediated events, or changes in mast cell mediator release. Immunoglobulin E-sensitized rats anesthetized with ketamine/urethan had larger changes in lung resistance and plasma histamine after pulmonary antigen challenge compared with rats anesthetized with fentanyl-droperidol. Blockade of opioid receptors with naloxone did not affect the responses. In unsensitized rats, airway responses to aerosolized methacholine were similar for the two anesthetics, indicating unchanged smooth muscle responsiveness; however, airway responses to intravenous serotonin were enhanced by ketamine and ablated by droperidol. We conclude that ketamine- and droperidol-induced alterations of pulmonary allergic responses are due to changes in sensitivity to serotonin and in mast cell mediator release. We speculate that mast cell mediator release may be modulated by a serotonin receptor-linked mechanism.
Nitrogen mustard as induction therapy for rheumatoid arthritis: clinical and immunologic effects.
We treated 5 patients diagnosed with rheumatoid arthritis (RA) with nitrogen mustard (HN2) and monitored clinical and immunologic variables. HN2, 0.3 mg/kg ideal body weight was given over 7 days. Disease activity and immune function were monitored during and after treatment. Duration of morning stiffness (p = 0.0044), joint count (p = 0.0140), and assessment of pain (p = 0.0264) and function (p = 0.0057) improved by Day 6. T lymphocytes (p = 0.0060), especially T memory cells (CD4CD29; p = 0.0017) fell dramatically. HN2 is effective for rapidly gaining control of active RA. This effect is T cell specific.
Pseudohypoproteinemia and multiple myeloma.
Paraproteinemia is an important diagnostic feature of multiple myeloma. The M-protein level reflects tumor burden and helps to determine the response to chemotherapy. A case is described that illustrates the phenomenon of reversible in vitro gelification of an M-protein. Paraprotein IgG1-kappa formed a concentration- and temperature-dependent gel, which was reversed by agitation. Measurement of paraprotein without previous vortexing of the specimen can erroneously lower the apparent M-protein level as well as reduce serum viscosity levels. This phenomenon can downstage the disease at diagnosis, produce inappropriate assessment of treatment response, or lead to premature withdrawal of chemotherapy. In addition, misdiagnosis of hyperviscosity syndrome can occur with serious clinical consequences.
The inhibitory actions of azelastine hydrochloride on the early and late bronchoconstrictor responses to inhaled allergen in atopic asthma.
We have examined the effect of azelastine hydrochloride, 8.8 mg, on the early and late responses to inhaled allergen in a group of 12 atopic subjects with asthma. On two separate days, 3 weeks apart, patients were administered either oral azelastine, 8.8 mg, or matched placebo. Four hours later they inhaled via nebulizer, a dose of allergen (grass pollen or Dermatophagoides pteronyssinus) that had previously been demonstrated to produce a 25% fall in FEV1. Plasma-histamine concentrations and FEV1 levels were measured at intervals during the subsequent 8 hours. After placebo, allergen inhalation produced rapid bronchoconstriction in all subjects with a maximum mean fall in FEV1 at 30 minutes of 22.8 +/- 3.4% from the postsaline baseline value. Five subjects also developed a late bronchoconstriction response with a fall in FEV1 of greater than 15% from postsaline baseline value between 2 and 8 hours after challenge. Azelastine reduced the bronchoconstrictor response during the first 10 minutes and produced a maximum mean fall at 30 minutes of 21.2 +/- 4.4% from the postsaline baseline value. Azelastine had a marked inhibitory effect, reducing the maximum mean fall from 23.9 +/- 6.3% to 9.6 +/- 3.9% from the postsaline baseline value. Analysis of the area under the FEV1 response time-course curves revealed that azelastine reduced the early response (first 2 hours) by 32.5% (p less than 0.05) (all subjects) and reduced the late response (2 to 8 hours) by 70.2% (p less than 0.05) (n = 5). Azelastine had no significant inhibitory effect on the early increase in plasma histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Uncontrolled trial of cryofiltration in rheumatoid arthritis.
In an open trial of cryofiltration in rheumatoid arthritis at our institution, 19 patients received 464 treatments; the intensive schedule of ten treatments in 5 weeks was completed in 14 of the 19, and excellent to good clinical response was achieved in ten of these. The combined results demonstrated significant reductions in Ritchie index, morning stiffness, and 50-foot-walk time in the intensive treatment period, as well as significant increases in hand grip strengths. In the maintenance treatment period treatment frequency was individually selected and at less frequent intervals. Changes in clinical parameters were notably less. Although significant correlations were observed between the percent change in clinical parameters and the percent change in biochemical and hematological parameters, no consistent pattern was found. The favorable results of this trial and other uncontrolled trials has led to a two-center double-blind controlled trial of cryofiltration in rheumatoid arthritis that is now in progress.