Characteristics of patients with pneumonia who are discharged from hospitals against medical advice.
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Adult↗
Biomedical subjects
M A Moskowitz
Publications and source records attributed to M A Moskowitz.
Variation in hospital rates of intraaortic balloon pump use in coronary artery bypass operations.
BACKGROUND: Little is known about regional patterns of intraaortic balloon pump (IABP) use in coronary artery bypass graft (CABG) operations. Our objectives were (1) to identify clinical variables associated with IABP use, and (2) to examine risk-adjusted rates of IABP use for 12 Massachusetts hospitals performing CABG operations. METHODS: We used hospital discharge data to identify 6944 CABG surgical cases. Logistic regression was used to identify clinical variables associated with IABP use, and the resulting multivariate model was then used to risk adjust hospital rates of IABP use. RESULTS: The IABP was used in 13.4% of the CABG surgical cases. The clinical variables independently associated with IABP use were cardiogenic shock, same admission angioplasty, prior CABG operation, cardiac arrest, congestive heart failure, recent myocardial infarction, and urgent admission status. Risk-adjusted rates of IABP use varied widely across hospitals from 7.8% to 20.8% (p < 0.0001). CONCLUSIONS: Hospital rates of IABP use vary considerably in Massachusetts. This practice variation may be related to the persistent uncertainty regarding the precise clinical indications for the IABP in this patient population.
Aged↗
Effects of PNU-109,291, a selective 5-HT1D receptor agonist, on electrically induced dural plasma extravasation and capsaicin-evoked c-fos immunoreactivity within trigeminal nucleus caudalis.
We studied the effects of PNU-109291 [(S)-(-)-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-isoc hroman-6-carboxamide], a receptor agonist showing 5000-fold selectivity for primate 5-HT1D versus 5-HT1B receptors (Ennis et al., J. Med. Chem. 41, 2180-2183), on dural neurogenic inflammation and on c-fos like immunoreactivity within trigeminal nucleus caudalis evoked by electrical and chemical activation of trigeminal afferents, respectively. Subcutaneous injection of PNU-109291 in male guinea pigs dose-dependently reduced dural extravasation of [125I]-labeled bovine serum albumin evoked by trigeminal ganglion stimulation with an IC50 of 4.2 nmol kg(-1). A dose of 73.3 nmol kg(-1) blocked the response completely. The selective 5-HT1B/1D receptor antagonist GR-127935 (> or = 2 micromol kg(-1) i.v.) prevented this effect. In addition, the number of c-fos immunoreactive cells within guinea pig trigeminal nucleus caudalis induced by chemical meningeal stimulation (intracisternally administered capsaicin) was reduced by more than 50% with PNU-109291 (> or = 122.2 nmol kg(-1) administered s.c. 45 min before and 15 min after capsaicin). These data indicate that the 5-HT1D receptor subtype plays a significant role in suppressing meningeal neurogenic inflammation and attenuating trigeminal nociception in these guinea pig models. Since 5-HT1D receptor mRNA and protein are expressed in trigeminal ganglia but not vascular smooth muscle, the 5-HT1D receptor subtype may become a useful therapeutic target for migraine and related headaches.
Animals↗
Pathobiology of ischaemic stroke: an integrated view.
Brain injury following transient or permanent focal cerebral ischaemia (stroke) develops from a complex series of pathophysiological events that evolve in time and space. In this article, the relevance of excitotoxicity, peri-infarct depolarizations, inflammation and apoptosis to delayed mechanisms of damage within the peri-infarct zone or ischaemic penumbra are discussed. While focusing on potentially new avenues of treatment, the issue of why many clinical stroke trials have so far proved disappointing is addressed. This article provides a framework that can be used to generate testable hypotheses and treatment strategies that are linked to the appearance of specific pathophysiological events within the ischaemic brain.
Acute-Phase Reaction↗
Patient assertiveness and physician decision-making among older breast cancer patients.
The objective of this study was to determine whether assertive patient behavior influences physician decision-making in the treatment of older breast cancer patients. One hundred and twenty-eight physicians saw videotapes depicting women seeking care for breast cancer and then recommended evaluation and treatment plans. Identical scripts were used, but the age, race, socioeconomic status, mobility, general health, and assertive behavior of the patients were experimentally varied along with the physician's specialty and length of practice. No direct effects of assertive patient behavior were seen. However, black, comorbid, and lower SES women were more likely to have full staging of their tumors ordered when they made an assertive request. Treatment recommendations also showed an interaction of assertiveness with patient's age and social class as well as physicians' specialty. The results indicate that a moderately assertive patient request may change provider behavior, although the effects of assertiveness vary most by what type of patient demonstrates this behavior. In particular, assertiveness led to more careful diagnostic testing for patients who came from groups that are "disadvantaged."
Aged↗
Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade.
Necrotic and apoptotic cell death both play a role mediating tissue injury following brain trauma. Caspase-1 (interleukin-1beta converting enzyme) is activated and oligonucleosomal DNA fragmentation is detected in traumatized brain tissue. Reduction of tissue injury and free radical production following brain trauma was achieved in a transgenic mouse expressing a dominant negative inhibitor of caspase-1 in the brain. Neuroprotection was also conferred by pharmacological inhibition of caspase-1 by intracerebroventricular administration of the selective inhibitor of caspase-1, acetyl-Tyr-Val-Ala-Asp-chloromethyl-ketone or the non-selective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. These results indicate that inhibition of caspase-1-like caspases reduces trauma-mediated brain tissue injury. In addition, we demonstrate an in vivo functional interaction between interleukin-1beta converting enyzme-like caspases and free radical production pathways, implicating free radical production as a downstream mediator of the caspase cell death cascade.
Amino Acid Chloromethyl Ketones↗
Non-NMDA glutamate receptors modulate capsaicin induced c-fos expression within trigeminal nucleus caudalis.
1. We examined the effects of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulpho namide (NBQX), the kainate receptor antagonists gamma-(R-)-glutamylaminomethanesulphonic acid (GAMS) and 6,7,8,9-tetrahydro-5-nitro-1H-benz[g]indole-2,3-dione-3-oxime (NS-102), and the group III metabotropic glutamate receptor (mGluR) agonist 2-amino-4-phosphono-S-butanoic acid (L-AP4) on c-fos-like immunoreactivity (c-fos LI) in trigeminal caudalis (Sp5C), lateral reticular (LRt), medullary reticular (Md) and solitary tract (Sol) nuclei, after intracisternal injection of capsaicin in urethane anaesthetized Sprague-Dawley rats. 2. Few c-fos labelled cells were observed within Sp5C in capsaicin-vehicle treated animals. The number of positive c-fos cells increased by 17 fold after intracisternal capsaicin (5 nmol) administration. 3. Pretreatment with CNQX (0.02, 0.1, 0.6, 3 and 15 mg kg-1) or NBQX (0.01, 0.1 and 1 mg kg-1), administered intraperitoneally 15 min before capsaicin, significantly reduced labelled cells within Sp5C by a maximum of 45 and 34%, respectively. The number of c-fox LI cells within LRt, Md and Sol was not affected. Pretreatment with L-AP4 (1, 3 and 10 mg kg-1) decreased the number of Sp5C c-fos LI cells by a maximum of 30%, whereas GAMS (1 and 10 mg kg-1) and NS-102 (1 and 5 mg kg-1) did not show any significant effect. 4. These results suggest that blockade of AMPA receptors, but not kainate receptors, or the activation of group III mGluRs, decrease the response of Sp5C neurons to trigeminovascular activation. Thus, in addition to NMDA receptors, mGluRs and AMPA receptors may modulate cephalic pain and may provide a potential therapeutic target for antimigraine drugs.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Perfusion weighted imaging during migraine: spontaneous visual aura and headache.
Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n = 6), 7 during the headache phase following visual aura (n = 3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly decreased (27% +/- 0.07) in occipital cortex contralateral to the affected hemifield. rCBV was decreased (15% +/- 0.12) and mean transit time increased (32% +/- 0.3), persisting up to 2.5 h into the headache phase. Other brain regions did not show significant perfusion changes. During migraine without aura, no significant hemodynamic changes were observed. In one patient who experienced both migraine with and without aura, perfusion deficits were observed only during migraine with aura. These findings suggest that decremental blood flow changes in occipital lobe are most characteristic of migraine with aura.
Adult↗
Care during menopause: comparison of a women's health practice and traditional care.
Despite the growth in primary care-based women's health centers, little is known about the characteristics of women's health patients and the quality of care provided in women's health centers versus traditional practices. Our objective was to compare a women's health practice and a general internal medicine practice on issues of care during menopause. A cross-sectional survey was administered simultaneously to patients aged 50-70 and their primary care physicians in a women's health practice and an affiliated general internal medicine practice. The survey asked patients about health behaviors, past and current hormone use, menopausal symptoms, and attitudes about menopause. Physicians were asked to estimate their patients' attitudes. Patients in women's health practices were younger, more likely to be smokers, and more likely to have had a prior hysterectomy. Women's health patients were somewhat more likely to report concerns related to menopausal symptoms. Women's health patients and patients attending the general internal medicine practice reported similar rates of past or current use of hormone therapy, after adjusting for prior hysterectomy and age. Physicians in women's health and general medicine were similar in their ability to estimate their patients' attitudes. In the general internal medicine practice, female physicians tended to better estimate their patients' attitudes than their male colleagues. Patients seeking care in a women's health practice differed in symptoms and concerns about the menopause compared with patients in a traditional primary care setting. Physicians' understanding of patients' menopausal concerns did not differ between the two practices. However, there may be gender differences in physicians' understanding of patients' concerns.
Attitude to Health↗
Functional status outcomes for assessment of quality in long-term care.
OBJECTIVE: Although decline in functional status has been recommended as a quality indicator in long-term care, studies examining its use provide no consensus on which definition of functional status outcome is the most appropriate to use for quality assessment. We examined whether different definitions of decline in functional status affect judgments of quality of care provided in Department of Veterans Affairs (VA) long-term care facilities. METHODS: Six measures of functional status outcome that are prominent in the literature were considered. The sample consisted of 15 409 individuals who resided in VA long-term care facilities at any time from 4/1/95 to 10/1/95. Activities of daily living variables were used to generate measures of functional status. Differences between residents' baseline and semi-annual assessments were considered and facility performance using the various definitions of functional status were described. RESULTS: The percentage of residents seen as declining in functional status ranged from 7.7% to 31.5%, depending upon the definition applied. The definition of functional status also affected rankings, z-scores, and 'outlier' status for facilities. CONCLUSION: Judgments of facility performance are sensitive to how outcome measures are defined. Careful selection of an appropriate definition of functional status outcome is needed when assessing quality in long-term care.
Activities of Daily Living↗
The cerebral metabolic consequences of nitric oxide synthase deficiency: glucose utilization in endothelial and neuronal nitric oxide synthase null mice.
Nitric oxide has multiple physiologic roles in the CNS. Inhibiting nitric oxide synthesis might therefore alter functional activity within the brain. We used [14C]-2-deoxyglucose in vivo autoradiography to measure local CMRglc in "knockout" mice lacking the genes for either the endothelial (eNOS) or neuronal (nNOS) isoforms of nitric oxide synthase, and in the progenitor strains (SV129, C57B1/6). Glucose utilization levels did not significantly differ between nNOS and eNOS knockout mice and C57B1/6 mice in any of the 48 brain regions examined, but were relatively lower in some subcortical regions in SV129 mice.
Animals↗
Evidence of a cerebrovascular postarteriole windkessel with delayed compliance.
A pronounced temporal mismatch was observed between the responses of relative cerebral blood volume (rCBV) measured by magnetic resonance imaging and relative cerebral blood flow measured by laser-Doppler flowmetry in rat somatosensory cortex after electrical forepaw stimulation. The increase of relative cerebral blood flow after stimulus onset and decrease after stimulus cessation were accurately described with a single exponential time constant of 2.4 +/- 0.8 seconds. In contrast, rCBV exhibited two distinct and nearly sequential processes after both onset and cessation of stimulation. A rapid change of rCBV (1.5 +/- 0.8 seconds) occurring immediately after onset and cessation was not statistically different from the time constant for relative cerebral blood flow. However, a slow phase of increase (onset) and decrease (cessation) with an exponential time constant of 14 +/- 13 seconds began approximately 8 seconds after the rapid phase of CBV change. A modified windkessel model was developed to describe the temporal evolution of rCBV as a rapid elastic response of capillaries and veins followed by slow venous relaxation of stress. Venous delayed compliance was suggested as the mechanism for the poststimulus undershoot in blood oxygen-sensitive magnetic resonance imaging signal that has been observed in this animal model and in human data.
Algorithms↗
Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice.
In a process called ischemic preconditioning, a brief, sublethal ischemic insult protects tissue from subsequent, more severe injury. There have been no reports of rapidly induced ischemic preconditioning. The authors sought to develop a model of cerebral ischemic preconditioning in the mouse that can be applied to transgenic and knockout animals. They found that brief middle cerebral artery (MCA) occlusion only minutes before a severe ischemic insult can induce protection from that insult. Here the investigators describe a mouse model of preconditioning using intraluminal MCA occlusion as both the conditioning and the test stimulus. One or three 5-minute episodes of ischemia given 30 minutes before MCA occlusion for 1 or 24 hours (permanent occlusion) confer significant protection as assessed by infarct volume measurements 24 hours later.
Animals↗
Do hip replacements improve outcomes for hip fracture patients?
BACKGROUND: Hip fracture is a common problem among older Americans. Two types of procedures are available for repairing hip fractures: hip replacement and open or closed reduction with or without internal fixation. The assumption has been that hip replacement produces better functional outcomes. Although that is the common wisdom, outcome studies evaluating hip replacement for treatment of hip fracture are few and have not clearly documented its superiority. OBJECTIVES: To compare outcomes of hip fracture patients who receive hip replacement versus another stabilizing procedure (open or closed reduction with or without internal fixation). DESIGN: Prospective cohort study. PARTICIPANTS: We studied 332 patients (age, > 65) who were hospitalized for a femoral neck fracture and discharged alive. MEASUREMENTS: We examined 2 treatment groups, hip replacement versus another procedure, on 6 outcomes [Activities of Daily Living (ADLs), walking, living situation (institutionalized or not), perceived health (excellent/good vs. fair/poor), rehospitalization, and mortality] at 3 postdischarge times (6 weeks, 6 months and 1 year). RESULTS: Mean age was 80, 80% were female, 96% White, 28% married, and 71% had a hip replacement. The treatment groups were similar at baseline (3 months before admission as reported at discharge) on ADLs, walking, living situation, and perceived health (all P > 0.24). After adjusting for demographics, clinical characteristics, fracture characteristics, and prior ADLs, walking ability, living situation, and perceived health, patients with a hip replacement did not do better at 6 weeks, 6 months, or 1 year post-discharge on any of the 6 outcome measures (all 18 P > 0.10). A global test of all 6 outcomes finds hip replacement patients doing less well at one year (P = 0.02). CONCLUSIONS: Despite the commonly held belief that hip replacement is a superior treatment for hip fracture, we found no suggestion of better outcomes for hip replacement on any of 6 key outcomes.
Activities of Daily Living↗
Patterns of use of common major procedures in medical care of older adults.
OBJECTIVES: We analyzed Medicare data to determine the influence of age, mortality during the study year, and high individual Medicare costs on the frequency of hospitalization for the most common major procedures and for general medical diagnoses. METHODS: We used 1992 Medicare data to classify the most frequent diagnosis related groups (DRGs), representing one-half of all admissions, as procedural or general medical. We studied the frequency of hospitalization for the most common procedures (bowel surgery, cardiovascular procedures, hip and femur surgery) and for general medical care in the entire Medicare population, in persons aged 65 to 74, 75 to 84, and 85 or older, in those who died, and in the 5% of persons whose annual Medicare costs were the highest. RESULTS: In the entire population, common procedures accounted for 21% of the most frequent DRGs. Among those who died, the procedures were performed in only 8% of admissions. In the 5% of persons with the highest Medicare costs, 28% of admissions involved procedures. Admissions for cardiovascular procedures and for cancer chemotherapy decreased with age and were infrequent in persons 85 years and older. Hip and femur procedures increased with age and accounted for 70% of the common procedures in persons 85 years and older. CONCLUSIONS: The most common major procedures account for a minority of hospitalizations of persons more than age 65, of persons 85 and older, of those who died, and of persons with the highest Medicare expenditures. Most hospitalizations are for general medical care. Major procedures appear to be used with restraint in the very old and in persons in their last year of life.
Aged↗
Neuroprotective effects of gelsolin during murine stroke.
Increased Ca2+ influx through activated N-methyl-D-aspartate (NMDA) receptors and voltage-dependent Ca2+ channels (VDCC) is a major determinant of cell injury following brain ischemia. The activity of these channels is modulated by dynamic changes in the actin cytoskeleton, which may occur, in part, through the actions of the actin filament-severing protein gelsolin. We show that gelsolin-null neurons have enhanced cell death and rapid, sustained elevation of Ca2+ levels following glucose/oxygen deprivation, as well as augmented cytosolic Ca2+ levels in nerve terminals following depolarization in vitro. Moreover, major increases in infarct size are seen in gelsolin-null mice after reversible middle cerebral artery occlusion, compared with controls. In addition, treatment with cytochalasin D, a fungal toxin that depolymerizes actin filaments, reduced the infarct size of both gelsolin-null and control mice to the same final volume. Hence, enhancement or mimicry of gelsolin activity may be neuroprotective during stroke.
Animals↗
How much better can we predict dialysis patient survival using clinical data?
OBJECTIVE: To use three approaches to compare dialysis survival prediction based on variables included in the Standardized Mortality Ratio (SMR) with prediction based on a clinically enriched set of variables. DATA SOURCE: The United States Renal Data System Case Mix Severity data set containing demographic, clinical, functional, nutritional, and treatment details about a random sample of 4,797 adult dialysis patients from 291 treatment units, incident to dialysis in 1986 and 1987. STUDY DESIGN: This observational study uses baseline patient characteristics in two proportional hazards survival models: the BASE model incorporates age, race, sex, and cause of end-stage renal disease (ESRD); the FULL model includes these and additional clinical information. We compare each model's performance using (1) the c-index, (2) observed median survival in strata of predicted risk, and (3) predicted survival for patients with different characteristics. PRINCIPAL FINDINGS: The FULL model's c-index (0.709, 0.708-0.711) is significantly higher than that of the BASE model (0.675, 0.675-0.676), indicating better discrimination. Second, the sickest patients identified by the FULL model were in fact sicker than those identified as sickest by the BASE model, with observed median survival of 451 days versus 524. Third, survival predictions for sickest patients using the FULL model are one-third shorter than those based on the BASE model. CONCLUSIONS: The model with more detailed clinical information predicted survival better than the BASE model. Clinical characteristics enable more accurate predictions, particularly for the sickest patients. Thus, clinical characteristics should be considered when making quality assessments for dialysis patients.
Adult↗
High altitude headache. Lessons from headaches at sea level.
There is little known about high altitude headache, except that it is an important and serious problem that often heralds the onset of acute mountain sickness. We do know that the brain itself is an insensate organ except for its meninges which contain sensory axons projecting from the trigeminal nerve. These nerve fibers travel in proximity to meningeal blood vessels and constitute an important component of the trigeminovascular system. Signals generated at high altitude which may activate the trigeminovascular system can arise from brain, blood or the blood vessel wall, include protons, neurotransmitters and other potential noxious agents which can discharge or sensitize small unmyelinated fibers. Brain edema and raised intracranial pressure may cause headache by compressing brain structures leading to displacement and stretching of the pain-sensitive intracranial structures. Small hemorrhage may irritate and discharge these fibers chemically. Furthermore, high altitude seems capable of decreasing the threshold of response to sensory stimulation. Therefore, headache can be attributed to activation of a common pathway, the trigeminovascular system by both chemical or mechanical stimulation.
Altitude↗