Radical change in healthcare organization: mapping transition between templates, enabling factors, and implementation processes.

PURPOSE: The purpose of this paper is to examine: the content of radical change by mapping differences between two templates for organizing delivery of healthcare; the enabling and constraining mechanisms underlying major change from one template to another; and the processes implicated in change implementation. DESIGN/METHODOLOGY/APPROACH: Longitudinal, qualitative case study design allowed the tracking, over a four-year period, of the transformation of healthcare service in a community from provider-centered, fragmented delivery to patient-centered, integrated delivery. The authors conducted 90 interviews at three intervals, observed meetings, and analyzed internal and external documents. Concepts on content, process and mechanisms were used to analyze the data. FINDINGS: Transition from one template to another involves radical change in structures/systems and underlying values. Mechanisms precipitating and enabling change include: powerful stakeholders' dissatisfaction with current template and commitment to a new one, willingness to resource the change, provision of credible leadership, and manipulation of incentive programs. Radical change is underlain by a series of micro change processes that involve emergent, non-linear dynamics, and that follow their own track with enabling and constraining mechanisms. ORIGINALITY/VALUE: The paper describes a case of positive, successful change. Implications include importance of: attention to power dynamics, persistent leadership, elimination of boundaries between collaborating groups, and aligning incentives with desired practice changes; and attending to both variance and process in understanding healthcare change.

Change agency in a primary health care context: the case of distributed leadership.

BACKGROUND: Integration of services across disciplines and organizations has been pursued increasingly in the primary care sector. Successful integration requires adept leadership of change. There have been questions about the extent to which studies on change agency that focus on a stand-alone leader are applicable in the complex setting of health care. It has been suggested that a model of collective leadership is more appropriate to this setting. PURPOSE: The objective is to understand the dynamics of collective or distributed leadership by attending to change agency roles in a context involving collaboration across health organizations. The study examines how change agency roles develop, evolve, interact, and complement each other. It also examines the bases of the change agents' ability to exercise influence. METHODOLOGY: A qualitative, longitudinal case study allowed us to map the evolution of a successful model of leadership. We tracked changes and agents' roles by engaging in extensive observations and conducting 74 interviews over a period of 4 years. FINDINGS: The findings point to the importance of the distributed change leadership model in contexts where legitimacy, authority, resources, and ability to influence complex change are dispersed across loci. Distributed leadership has both planned and emergent components, and its success in bringing about change is associated with the social capital prevalent in the site. PRACTICE IMPLICATIONS: Change leaders need to build a winning coalition of agents with complementary skills and resources that support the change. Successful change leadership involves investing time in finding common ground across stakeholders and in building credibility and trust. Having an agent whose main responsibility is to manage the change process is likely to bring more success than asking busy health care practitioners to take on this charge because in the latter case, there is likelihood of dilution of change focus and momentum.

Sequential histomorphometric analysis of regenerate osteogenesis following mandibular distraction in the rat.

Few studies of distraction osteogenesis in the craniofacial region have examined the dynamic nature of the bone healing process. This study investigated bone formation in distraction sites at various times following slow, moderate, and rapid rates of mandibular distraction in adult rats. After a 3-day latency period, 16 groups of 8-9 rats underwent unilateral mandibular distraction for 5 days at four different rates (0, 0.2, 0.4, and 0.6 mm/day) and were sacrificed at four different time points (6, 10, 24, and 38 days). Vital bone labels were injected prior to sacrifice and histological sections were examined under epifluorescence to measure mineral apposition rate (MAR) and the number of red and green pixels that corresponded to the wavelengths of the two bone labels. These pixel counts were designed to quantify the amount of fluorescent bone formation. For MAR and the pixel counts, no significant differences were found between the distraction rate groups. Over time, MAR was significantly higher (p < 0.001) at 24 days (4.50 microm/day) compared to 38 days (3.78 microm/day). Thus, MAR appears to be elevated at mid-consolidation compared to late consolidation. The pixel counts showed that the 6-day (mid-distraction) and 10-day (early consolidation) time points had significantly lower total fluorescent activity compared to the 24-day (mid-consolidation) and 38-day (late consolidation) time points (p < 0.001). The red, green, and red + green pixel counts were found to correlate significantly but weakly with microdensity (r = 0.318, 0.307, and 0.334, respectively). The pixel counts and microdensity both showed similar patterns over time.

Mutations in SID2, a novel gene in Saccharomyces cerevisiae, cause synthetic lethality with sic1 deletion and may cause a defect during S phase.

SIC1 encodes a nonessential B-type cyclin/CDK inhibitor that functions at the G1/S transition and the exit from mitosis. To understand more completely the regulation of these transitions, mutations causing synthetic lethality with sic1 Delta were isolated. In this screen, we identified a novel gene, SID2, which encodes an essential protein that appears to be required for DNA replication or repair. sid2-1 sic1 Delta strains and sid2-21 temperature-sensitive strains arrest preanaphase as large-budded cells with a single nucleus, a short spindle, and an approximately 2C DNA content. RAD9, which is necessary for the DNA damage checkpoint, is required for the preanaphase arrest of sid2-1 sic1 Delta cells. Analysis of chromosomes in mutant sid2-21 cells by field inversion gel electrophoresis suggests the presence of replication forks and bubbles at the arrest. Deleting the two S phase cyclins, CLB5 and CLB6, substantially suppresses the sid2-1 sic1 Delta inviability, while stabilizing Clb5 protein exacerbates the defects of sid2-1 sic1 Delta cells. In synchronized sid2-1 mutant strains, the onset of replication appears normal, but completion of DNA synthesis is delayed. sid2-1 mutants are sensitive to hydroxyurea indicating that sid2-1 cells may suffer DNA damage that, when combined with additional insult, leads to a decrease in viability. Consistent with this hypothesis, sid2-1 rad9 cells are dead or very slow growing even when SIC1 is expressed.

The effects of hyperoxia on performance during simulated firefighting work.

This study evaluated the effects of hyperoxia (inspired oxygen fraction = 40%) on performance during a simulated firefighting work circuit (SFWC) consisting of five events. On separate days, 17 subjects completed at least three orientation trials followed by two experimental trials while breathing either normoxic (NOX) and hyperoxic (HOX) gas mixtures that were randomly assigned in double-blind, cross-over design. Previously, ventilatory threshold (Tvent) and VO2max had been determined during graded exercise (GXT) on a cycle ergometer. Lactate concentration in venous blood was assessed at exactly 5 min after both the experimental trials and after the GXT. Total time to complete the SFWC was decreased by 4% (p < 0.05) with HOX. No differences were observed in individual event times early in the circuit, however HOX resulted in a 12% improvement (p < 0.05) on the final event. A significantly decreased rating of perceived exertion (RPE) was also recorded immediately prior to the final event. No differences were observed in mean heart rate or post-exercise blood lactate when comparing NOX to HOX. Heart rates during the SFWC (both conditions) were higher than HR at Tvent, but lower than HR at VO2max (p<0.05). Post-SFWC lactate values were higher (p<0.05) than post-VO2max. These results demonstrate that hyperoxia provided a small but significant increase in performance during short duration, high intensity simulated firefighting work.

Cerebrospinal fluid and plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management.

UNLABELLED: Twenty-three patients treated with intracerebroventricular (ICV) morphine in this study not only obtained excellent pain relief without rapid increases in dose, but also experienced a reduction in morphine-related side effects. By 24 h after initiation of ICV morphine, the mean trough cerebrospinal fluid (CSF) morphine concentration (approximately 20 microM) was 50-fold higher than the baseline concentration (approximately 0.4 microM), and the CSF concentration of morphine-6-glucuronide (M6G) was undetectable (<0.01 microM). The mean CSF concentration of morphine-3-glucuronide (M3G) decreased 90%, from a baseline concentration of 1 microM to 0.1 microM by Day 7 postventriculostomy. Thereafter, the mean trough CSF M3G concentration remained relatively constant while ICV morphine was continued, although the concomitant M3G plasma concentrations were undetectable (<0.01 microM). The large increase in the CSF morphine concentration in patients receiving ICV morphine strongly suggests that increased CSF morphine levels are unlikely to be the primary cause of analgesic tolerance or undesirable excitatory side effects (hyperalgesia, myoclonus, seizures) experienced by some patients receiving chronic large-dose systemic morphine. IMPLICATIONS: After initiation of intracerebroventricular morphine, cancer patients experienced excellent pain relief. Although the mean morphine concentration in cerebrospinal fluid increased 50-fold relative to preventriculostomy levels, rapid dose increases did not occur, which suggests that increased cerebrospinal fluid morphine levels are unlikely to be the main cause of analgesic tolerance.

Comparison of 18% ethanol and mechanical debridement for epithelial removal before photorefractive keratectomy.

PURPOSE: To assess the safety of alcohol compared to mechanical debridement for epithelial removal prior to photorefractive keratectomy (PRK). METHODS: Forty-one second eyes of 41 patients underwent epithelial removal using alcohol prior to PRK with a Nidek EC-5000 excimer laser. The results were compared with the results of the 41 first eyes of the same patients that had mechanical debridement. RESULTS: Initial results showed that the alcohol treated group tended to stay slightly hyperopic but had less haze compared to the mechanical debridement group. The treating surgeons favored alcohol as the preferred method of epithelium removal. CONCLUSION: Alcohol debridement is an effective procedure although algorithms may have to be altered to take into account the slightly different healing process postoperatively.

Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration.

The pharmacokinetics of oxycodone have been determined after single-dose administration by the intravenous (4.6-7.3 mg), oral (tablets, 9.1 mg and syrup, 9.1 mg), and rectal (30 mg) routes, in 48 patients undergoing minor surgery. There were no significant differences in the mean elimination half-lives between the intravenous (5.45 +/- 1.43 h), oral tablets (5.65 +/- 1.13 h), oral syrup (4.80 +/- 1.13 h), and rectal suppository (5.40 +/- 1.19 h) formulations of oxycodone. After intravenous administration, the mean plasma clearance of oxycodone was 25.5 +/- 10.1 L/h and the mean volume of distribution at steady state was 2.5 +/- 0.8 L/kg. The mean normalized area under the curve (AUC/D) obtained after intravenous dosing (48.2 +/- 30.2 micrograms.h/L/mg) was more than twice the AUC/D values obtained after the administration of oxycodone tablets (19.8 +/- 3.5 micrograms.h/L/mg), oxycodone syrup (17.5 +/- 5.3 micrograms.h/L/mg), and rectal suppository (20.3 +/- 5.1 micrograms.h/L/mg), indicating that the amount of oxycodone reaching the systemic circulation after the extravascular routes of administration was < 50% of that obtained after intravenous dosing. The mean absorption lag times after oxycodone tablets (0.52 +/- 0.33 h), oxycodone syrup (0.48 +/- 0.40 h), and rectal suppository (0.76 +/- 0.47 h) were consistent with the onset of pharmacological effects reported by the patients.

Personal and parental alcohol abuse, and victimization in obese binge eaters and nonbingeing obese.

Current obesity research has begun to emphasize the importance of pretreatment assessment and more individually tailored treatment protocols. Obese binge eaters have been identified as a subgroup of the obese who do not respond well to standard behavioral treatment programs. We were interested in identifying variables that are important to consider when assessing and treating obese binge eaters. The present study assessed the prevalence of personal alcohol abuse, parental alcohol abuse, and victimization in 62 males and 274 females seeking treatment for obesity. Obese binge eaters (OBE) had significantly greater rates of personal alcohol abuse, parental alcohol abuse, and victimization than the nonbingeing obese (NBO) in our sample. Further studies of the OBE population are recommended.

Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index.

Oral complications can be serious and disabling problems for patients undergoing cancer therapy. Therefore, the authors wanted to develop a sensitive and specific instrument to measure oral mucosal changes during therapy. The Oral Mucosa Rating Scale (OMRS) has an examination rating scale to quantify the type and severity of clinically evident oral mucosal changes (atrophy, erythema, ulceration, and pseudomembranous, hyperkeratotic, lichenoid, and edematous changes), with a scale ranging from 0 to 3 (normal to severe). Separate visual analogue scales are obtained for oral pain and dryness. One hundred eighty-eight bone marrow transplant recipients were studied from before transplant through day 42 after transplant. The OMRS then was used to develop a specific index for assessing acute oral mucositis after bone marrow transplant--the Oral Mucositis Index (OMI). The OMI internal consistency measures (Chronbach alpha and Guttman split-half coefficients) were strong (range, 0.84 to 0.93). Support for the validity of the OMI is presented. These scales should help improve the study of oral complications of cancer therapy.

Angiotensin-converting enzyme inhibitors: new orally active 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.

The preparation of a series of 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) in vitro and in vivo were examined. These compounds are assumed to act as prodrugs since they undergo rapid ring-opening reactions to give the corresponding biologically active free SH compounds when incubated with rat plasma or when treated with aqueous 0.1 N HCl or phosphate buffer (pH 7.4). The thiazepines 23-25 and 30 are potent inhibitors of ACE when administered po to rats and are comparable in potency to captopril (1). The most active thiazines in rats, po, were 42 and 45. Of the benzothiazepines studied, 22a was the most active in inhibiting ACE in the conscious normotensive rat, ID50 = 0.15 mg/kg, po. The acute antihypertensive effects of oral administration of a number of these compounds on mean arterial pressure and heart rate were studied in spontaneously hypertensive rats (SHR) maintained on a sodium-deficient diet.

Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives.

A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.

Inhibition of nuclear-protein phosphorylation in vitro by beryllium.

Endogenous cyclic-nucleotide-independent protein phosphorylation by ATP at pH 6.5 in adult rat liver nuclei in vitro is inhibited by beryllium (Be2+), but under the same conditions nuclear-protein dephosphorylation appears to be insensitive to Be2+. Prior incubation of nuclei with Be2+ is necessary to demonstrate the inhibition of phosphorylation, which increases as the pH is decreased from pH 8.0 to 6.5. The extent of inhibition can be related to the level of nuclear Be2+ binding and, evidence suggests, may be caused by direct or indirect interference by Be2+ with Mg2+ binding sites normally required to facilitate protein phosphorylation.