Challenges to effective incident review management: administrative and clinical factors.

Incident review (IR) is a process for achieving a better understanding of problems related to the health and safety of clients and the integrity of healthcare facilities. The IR process ensures that the quality and the performance of care in a facility continue to be maintained and improved over time. Because of the practical realities of administrative and clinical care issues, the process of implementing IR and related interventions is often challenging. This paper examines the IR process and the barriers that affect and impede it.

Incident review management: a systemic approach to performance improvements.

Incident reporting has emerged as a cornerstone of sound quality improvement programs. Sentinel events, "a serious and undesirable occurrence involving the loss of life, limb, or function of an individual served" (Joint Commission on Accreditation of Healthcare Organizations, 1996), is a mandated indicator for Joint Commission standards of accreditation for audited healthcare facilities. Properly investigated and documented individual incidents can lead to systemic improvements, which may enhance the quality of client care and the integrity of the healthcare facility. This article proposes a systemic approach to the incident review (IR) process in long-term healthcare facilities. This comprehensive approach incorporates identification, investigation, and management of the IR process from the inception of a problem to the continued follow-up to ensure that improvement plans are effectively implemented.

Clinical utility of a new contrast option from magnetization transfer contrast.

Two magnetization transfer (MT) contrast effects, a T2-like effect and the improved contrast observed when gadolinium is used with MT, are combined in a single sequence. Forty patients (22 males:18 females; mean age, 45 years (23-87)) with suspected intracranial pathology underwent MRI on a 1.5 Tesla system. Of 46 lesions; seven were ischemic, five infective, seven neoplastic, four hemorrhagic, four multiple sclerosis, seven human immunodeficiency virus (HIV) leukoencephalopathy, nine normal/miscellaneous, and three gliosis. A conventional spin-echo sequence (TR 900 TE 15) was used with on-resonance binomial MT pulses. The sequence was performed postgadolinium +/- MT. The signal intensity ratios +/- MT were: white matter, 0.62 +/- 0.03; gray matter, 0.75 +/- 0.04; ischemia, edema, and demyelination, 0.75 (0.57-0.86); and gadolinium/methemoglobin, 0.85 (0.81-0.98). Areas which exhibited MT had T2-like contrast and those that did not maintained expected contrast for the given parameters. The result was a combination of T2-like contrast, gadolinium enhancement, and dark cerebrospinal fluid (CSF) providing both increased sensitivity to lesions which exhibited both contrast features and improved delineation of periventricular lesions. Furthermore, the differential signal between T2-like contrast of edema and gadolinium enhancement in neoplastic or infective lesions was maintained.

MR angiography of normal pelvic arteries: comparison of signal intensity and contrast-to-noise ratio for three different inflow techniques.

OBJECTIVE: Two-dimensional (2D) time-of-flight (TOF) MR angiography has been the standard technique for evaluating arteries of the lower extremity. However, this technique is limited by artifacts resulting from vessel pulsation, as well as by relatively poor vessel-to-background contrast. The purpose of this study was to evaluate two cardiac-gated inflow techniques to determine whether they exhibited better contrast and signal performance than the standard technique of 2D TOF MR angiography of the iliac arteries. SUBJECTS AND METHODS: Fourteen subjects who had no clinical evidence of vascular disease had standard 2D TOF, gated 2D TOF, and gated 2D turbo field-echo MR angiography. Images were evaluated for signal-intensity ratio, signal-to-noise ratio, and contrast-to-noise ratio, in addition to qualitative evaluation. RESULTS: Turbo field-echo MR angiography exhibited significantly higher signal-intensity, signal-to-noise, and contrast-to-noise ratios than did either gated or standard MR angiography for all vessel segments. We found no significant difference between gated and standard 2D TOF techniques for any vessel segment. Qualitative features of turbo field-echo MR angiography included improved visualization of horizontal vessel segments compared with the standard 2D TOF technique, less effective venous saturation compared with either the gated or standard 2D TOF technique, and increased ghosting artifacts compared with the gated 2D TOF technique. CONCLUSION: Two-dimensional turbo field-echo MR angiography exhibits improved signal and contrast for evaluation of normal iliac segments compared with standard or gated 2D TOF MR angiography. This technique should replace standard 2D TOF MR angiography for evaluation of the iliac arteries.

Chemistry in a microenvironment of low pH, generated with the aid of an immobilized proteinase.

alpha-Chymotrypsin, when immobilized in a collodion membrane, exhibits high activity and remarkable stability. When the immobilized proteinase is exposed to 15 mM ethyl N-acetyl-L-tyrosinate in dilute pH 8.5 buffer it generates a microenvironment which, indicator studies suggest, has an effective pH of approximately 4. The presence of this locally highly acidic region produces a marked increase in the rate of hydrolysis of BzPheal = Ala dissolved in the buffer solution (BzPheal = Ala is the acylhydrazide obtained from the reaction between N-benzoyl-L-phenylalaninal and N-acetyl-L-alanine hydrazide). The observed rate is 10-times greater than in comparable control experiments incorporating a concentrated buffer solution, in which a pH-gradient does not form. The enhanced hydrolysis rate is quantitatively explained if it is attributed to the approximately 20 microliters of pH 4 solution within the membrane. Other experimental data are also consistent with this hypothesis.

Acid-sensitive latent inhibitors for proteolytic enzymes: synthesis and characterization.

The reaction between peptide aldehydes and acylhydrazones affords derivatives that represent potential prodrugs for selective inhibition of lysosomal enzymes. BzPheal = Ala, obtained from the reaction between N-benzoyl-L-phenylalaninal and N-acetyl-L-alanine hydrazide, has been most carefully studied. When BzPheal = Ala is introduced into ongoing reactions catalyzed by alpha-chymotrypsin or papain, the rate of these reactions diminishes more rapidly with time than do those of controls lacking BzPheal = Ala. Furthermore, the disparity between run and control is much greater at pH 5 than at pH 7. The extent of inhibition (defined as explained in the text) at pH 5 can exceed that at pH 7 by 25-40-fold. The data are quantitatively explained by a reaction scheme that recognizes three important properties of BzPheal = Ala: (1) It undergoes hydrolysis at pH 5-7 to regenerate N-benzoyl-L-phenylalaninal; (2) the aldehyde thus liberated is a far more potent inhibitor for serine or cysteine proteases than is BzPheal = Ala; and (3) the rate constant for hydrolysis of BzPheal = Ala at pH 5 greatly exceeds that at pH 7.

Quantification of blood flow with dynamic MR imaging and presaturation bolus tracking.

A technique is described for rapid imaging of blood flow and dynamic measurement of its velocity. The method is a combination of bolus tracking and low-flip-angle gradient-echo cine angiography. This method provides precise determination of velocity with high temporal resolution in a single measurement. Unlike what occurs in phase imaging techniques, flow is displayed directly, eliminating potential errors that result from non-flow-related sources of phase shifts. Manipulation of raw data sets is avoided. Results obtained from a flow phantom, healthy volunteers, and a patient with an aortic aneurysm demonstrate the capability of the technique to track flow at low and high velocities and to differentiate flowing blood from thrombus. Because of its conceptual simplicity, rapidity, and lack of susceptibility to extraneous phase shifts, this technique may prove ideal for in vivo flow measurement and evaluation of flow patterns.

Pulse sequence optimization for T2-weighted MR imaging of the brain.

The authors implemented bipolar velocity compensated pulse techniques for T2-weighted MR imaging of the brain. Signal-to-noise (S/N) and image quality was compared for pulse sequences with standard and optimized RF pulses, low and regular bandwidth versions and cardiac triggering. Images from bipolar velocity compensated sequences allowed better visualization of vessels and basilar cisterns and improved image quality relative to standard sequences without velocity compensation. The implementation of optimized RF pulses with bipolar sequences resulted in further improvement in image quality. Single echo sequences consistently had improved image quality and signal-to-noise relative to the second echo of a double echo sequence. Low bandwidth bipolar sequences with extended sampling period had 30% higher S/N, but at the cost of slight loss in edge definition. The highest image quality was obtained with the bipolar, optimized RF, single echo sequence. Using this technique contiguous high quality image slices could be obtained with velocity compensation. The addition of cardiac triggering to bipolar sequences resulted in slight improvement in image quality, but this difference was marginal and probably rarely necessary for MR imaging of the brain.

MR imaging section profile optimization: improved contrast and detection of lesions.

A computer-optimized radio-frequency (RF) pulse for sharper section definition was implemented for T2-weighted magnetic resonance (MR) imaging of the head. Twenty-four patients underwent MR imaging with this technique and also with a conventional spin-echo technique with a sinc pulse filtered with a Hamming window. The contrast between gray and white matter improved 20%-40%, depending on the echo time. In ten patients with multiple sclerosis, use of the computer-optimized RF pulse resulted in detection of 37% more lesions, and power deposition was reduced by 36%. The computer-optimized RF pulse improved image contrast and lesion detection.

FRODO pulse sequences: a new means of eliminating motion, flow, and wraparound artifacts.

Magnetic resonance images of the spine, chest, abdomen, and pelvis are commonly degraded by ghost artifacts. The authors have developed a new technique named FRODO (Flow and Respiratory artifact Obliteration with Directed Orthogonal pulses) to suppress these artifacts. Signal from tissues responsible for the artifacts is eliminated by use of radio frequency pulses specifically optimized for high selectivity to saturate proton magnetization over one or more independently defined slabs (large rectangular volumes) of tissue. Ghost artifacts from pulsatile flow in the heart and blood vessels, as well as from respiratory motion and swallowing, are suppressed. Additional applications of this technique include elimination of intraluminal signal in blood vessels and suppression of wraparound artifact along the phase-encoding axis. Preliminary clinical experience suggests that the FRODO technique, in conjunction with other flow compensation methods, may provide a definitive solution to the problem of motion in spine imaging. FRODO pulse sequences may also prove useful for imaging of blood vessels, heart, abdomen, and other areas where motion, flow, or wraparound artifacts limit image quality.

Fluorine-19 NMR spectroscopic studies of the metabolism of 5-fluorouracil in the liver of patients undergoing chemotherapy.

Fluorine-19 nuclear magnetic resonance allows direct observation of fluorinated drugs and their metabolites in the human body without background signal from the tissue. A well-known fluorinated chemotherapeutic drug, 5-fluorouracil, and its metabolites were observed noninvasively in the liver of three patients undergoing cancer chemotherapy. Spectra were obtained at 1.5 T with a surface coil centered over the right lobe of the patient's liver. Administration of 1.5 gm of 5-fluorouracil was done after positioning in the magnet. Serial spectra, collected over a 2-h period, revealed both the nature of the metabolites present in the liver, and the time course of each patient's metabolism. These observations represent the first noninvasive NMR study of drugs in human patients and show the feasibility of using in vivo F-19 NMR spectroscopy for human studies of fluorinated compounds.

Selective population inversion in NMR.

Population inversion of a selected region of a spectrum is a concept which has wide application in both NMR spectroscopy and imaging. While inversion of population at any one frequency is a trivial matter, ensuring an accurate inversion over a specified bandwidth, with negligible perturbation of the magnetization outside that bandwidth, is a major problem. However, by using as a driving function a complex radiofrequency (r.f.) pulse with an envelope of the form (sech beta t)1+5i where 1/beta is the temporal width and t is time, we have found that above a critical r.f. power threshold, magnetization is accurately inverted over a very sharply defined bandwidth, while outside that region, magnetization is returned to its initial position, and population is unaffected. Within the broad limits imposed by our equipment, we have also discovered that the phenomenon is independent of the incident r.f. power.

Investigation of binding between recA protein and single-stranded polynucleotides with the aid of a fluorescent deoxyribonucleic acid derivative.

The availability of epsilon DNA, a fluorescent ssDNA derivative, has made it possible to examine quantitatively the interactions between recA protein and single-stranded polynucleotides. Fluorescence titrations of epsilon DNA with recA protein and vice versa establish that each recA protein monomer covers 5.5 epsilon DNA nucleotides and that the dissociation constant of the recA-epsilon DNA complex is 10 nM. Fluorescence titrations of recA protein-epsilon DNA mixtures with poly(dT) establish that each recA protein monomer covers 5.1 poly(dT) nucleotides and that the dissociation constant of the recA-poly(dT) complex is 0.03 nM. Observations on how the addition of ssDNA affects the fluorescence of recA protein-epsilon DNA mixtures establish that the dissociation constant of the recA-ssDNA complex exceeds 20 microM. Stopped-flow kinetics in which excess recA protein binds to epsilon DNA indicate that k2 = 6 X 10(6) M-1 s-1 for the process. A more approximate kinetic technique indicates that recA protein binds to epsilon DNA at least one-tenth as fast as to poly(dT); the rate constant for dissociation of recA-epsilon DNA exceeds that for recA-poly(dT) by at least 30-fold. epsilon DNA is proven to be a versatile reagent for studying single-stranded polynucleotide-protein interactions. Not only can its own complexes with protein be investigated but also, under suitable circumstances, it can be used as a fluorescent probe to explore complexes incorporating nonfluorescent polynucleotides.

Surprising consequences of the tendency of pepsin to catalyze condensation reactions between small peptides.

Pepsin catalyzes numerous acyl-transfer reactions. Are peptic acyl-enzyme intermediates involved in such reactions? To start, we examine the cleavage of Leu-Trp-Met-Arg at pH 3.4-4.5 in the presence of 25 mM tryptophanamide. Substantial amounts of Leu-TrpNH2 are generated. However, the appearance of this acyl-transfer product cannot be attributed to the intervention of Leu-pepsin and its trapping by tryptophanamide. Experiment proves that Leu-Trp-Met-Arg affords Leu3, which, in turn, reacts with tryptophanamide to produce Leu-TrpNH2. Both the formation of Leu3 from Leu-Trp-Met-Arg and the conversion of Leu3 + tryptophanamide into Leu-TrpNH2 can potentially implicate the generation and trapping of a Leu-pepsin intermediate. Does experiment support either possibility? The answer is no. Our data show that most of the Leu3 derived from Leu-Trp-Met-Arg stems from an autocatalytic condensation process whereby Leu3 already present speeds the conversion of the leucine residues of unreacted Leu-Trp-Met-Arg into more Leu3. Technical problems have prevented us from determining whether the first Leu3 formed results from the trapping of an acyl-enzyme intermediate. The generation of Leu-TrpNH2 from Leu3 was studied primarily via a more tractable analogous reaction: Leu-Trp-Leu + tryptophanamide leads to Leu-TrpNH2. The mechanism governing these transformations is highly complex. Its major feature is an initial condensation between two molecules of substrate. All the examples investigated further illustrate the marked tendency of pepsin to catalyze condensation reactions between suitably constructed small peptides. The prevalence of these reactions complicates the interpretation of much data bearing on pepsin's mechanism of action.

Direct observation of complexes formed between recA protein and a fluorescent single-stranded deoxyribonucleic acid derivative.

The reaction of chloroacetaldehyde with single-stranded DNA (ssDNA) yields epsilon DNA, a highly fluorescent substance. The binding of recA protein to epsilon DNA nearly doubles its fluorescence yield. The enhanced fluorescence signals the formation of a recA-epsilon DNA complex. This complex exhibits an ATPase activity as great as that of the corresponding recA-ssDNA complex. Addition of a saturating concentration of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) to a solution of the recA-epsilon DNA complex yields a further rise in fluorescence. Saturation with ATP produces the same rise. The nucleotide triphosphates have converted the recA-epsilon DNA complex into the respective ATP gamma S-recA-epsilon DNA and ATP-recA-epsilon DNA complexes. The fluorescence changes that accompany the formation of the three complexes have enabled us to (1) establish by titration that recA protein binds to 6.0 +/- 0.3 nucleotides of epsilon DNA, (2) show that the binding of ATP to the recA-epsilon DNA complex is highly cooperative under various conditions, with a Hill coefficient of 2.4-4.9 and Kapp = 25 +/- 2 micro M, (3) show that the binding of ATP gamma S is also highly cooperative, with a Hill coefficient of 3.3-4.2 and Kapp congruent to 0.5 micro M, and (4) perform initial measurements on the rate at which recA protein transfers between polynucleotides. The experiments provide the first direct observation of an ATP-recA-ssDNA-like complex, and they illuminate some of the properties of such complexes.

Enzyme-catalyzed condensation reactions which initiate rapid peptic cleavage of substrates. 1. How the structure of an activating peptide determines its efficiency.

The addition of a small peptide can significantly increase the rate at which pepsin cleaves a substrate at pH 4.5. Why? In order to find out, we have determined spectrophotometrically the relative ability of over a dozen peptides to speed the initial rate of disappearance of Phe-Trp-NH2 and Leu-Trp-Met-Arg. Here are some of the criteria which establish the reliability of the acquired kinetic data: (1) rates depend linearly on [E] and , to a good approximation, on [activator], (2) measurements with both substrates yield the same ranking for the activators tested; (3) high-pressure liquid chromatographic investigations independently confirm conclusions derived from the spectrophotometric studies. The best activators found were Z-Ala-Phe and Ala-Leu. At 3.2 mM they are respectively 60 and 30 times more effective than an equal concentration of A-(Ala)2. The two-step mechanism given below (for Phe-Trp-NH2) best explains the structural specificity found, as well as other observations on the nature of these activated cleavages. It assumes that reaction commences when pepsin catalyzes synthesis of a peptide bond between activator and substrate. The polypeptide so formed subsequently undergoes scission at a different bond. The modified activator liberated, here designated Z-AA2-AA1-Phe, can eventually provide a variety of reaction products, as the succeeding paper demonstrates.

Mechanistic features of pepsin-catalyzed amino transfer reactions.

Peptic cleavage of N-trifluoroacetyl-L-tryptophan (CF3CO-Trp) at pH 2.45 to 5.4 in the presence of L-beta-phenyllactic acid (Pla) yields much PlaTrp. Formation of PlaTrp represents a typical peptic amino transfer reaction. In this instance PlaTrp undoubtedly derives from a reaction between the acceptor, Pla, and the carboxylate anion, CF3CO-TrpCOOO- (or a species obtained from it). This observation suggests that in general the anionic form of a substrate, such as AcPheTrpCOOO- in the case of AcPheTrp, may be the primary source of the amino acid residue transferred in amino transpeptidations. Other evidence supports the validity of the proposal. Furthermore it has the virtue of rationally explaining why AcPheTrpNH2-like substrates fail to participate in amino transpeptidations and why these reactions tend to increase in importance at high pH.

Comparison of in vitro antibacterial activity of three oral cephalosporins: cefaclor, cephalexin, and cephradine.

Cefaclor, a new oral cephalosporin, was compared in vitro with cephalexin and cephradine against 233 organisms. Evaluations were performed in Mueller-Hinton and nutrient broth and agar using two inoculum sizes. In agar, cefaclor had greater antibacterial activity than either cephalexin or cephradine against isolates of Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella typhi. All three drugs were relatively inactive against isolates of enterococci, Enterobacter species, and indole-positive Proteus. Cefaclor, however, did exhibit the greatest activity of the three antibiotics against these organisms. Although there was wide variability with respect to test parameters, the broth results generally paralleled the agar results. In nutrient broth a clear separation of the results with these three cephalosporins was seen with K. pneumoniae, E. coli, and S. typhi. Cefaclor was the most active, cephalexin had intermediate activity, and cephradine was the least active. From the data obtained in this in vitro study, it can be concluded that cefaclor, which has a substituted chloro group attached to the molecule, had increased antibacterial activity over cephalexin and cephradine. Comparative clinical trials with cefaclor will determine whether the differences outlined above are of clinical significance.