The natural history of functional morbidity in hospitalized older patients

This study provides data on changes in the functional status of older patients that are associated with acute hospitalization. Seventy-one patients over the age of 74 admitted to the medical service of Stanford University Hospital between February and May 1987 received functional assessments covering seven domains: mobility, transfer, toileting, incontinence, feeding, grooming, and mental status. Assessments were obtained by report from the patient's caregiver (or the patient when he or she lived alone) for 2 weeks before admission; from the patient's nurse on day 2 of hospitalization and on the day before discharge; and again from the caregiver (or patient) 1 week after discharge. The sample had a mean age of 84, covered 37 Diagnostic Related Groups, and had a median length of stay of 8 days. Between baseline and day 2, statistically significant deteriorations occurred for the overall functional score and for the individual scores for mobility, transfer, toileting, feeding, and grooming. None of these scores improved significantly by discharge. In the case of mobility, 65% of the patients experienced a decline in score between baseline and day 2. Between day 2 and discharge, 67% showed no improvement, and another 10% deteriorated further. These data suggest that older patients may experience a burden of new and worsened functional impairment during hospitalization that improves at a much slower rate than the acute illness. An awareness of delayed functional recovery should influence discharge planning for older patients. Greater efforts to prevent functional decline in the hospitalized older patient may be warranted.     

Immediate response of 5-methoxytryptophol in the circulation to hypoglycaemic stress induced by insulin.

Pineal indoles have been shown to affect the release of anterior pituitary hormones but details of the interrelationships are lacking. Using a new gas chromatography-mass spectrometry (g.c.-m.s.) assay the concentration of 5-methoxytryptophol (ML) was measured in plasma samples obtained from 16 children undergoing investigation of pituitary function for delayed growth. All the children received an insulin tolerance test (ITT) to study their endocrine response to stress. Some children received luteinizing hormone releasing hormone (LH-RH) and/or thyrotrophin releasing hormone (TRH). The change in concentration of ML during an ITT was similar to the change in concentration of blood sugar; a drop at 20 min followed by a rise at 30 min. This was not significantly altered by the administration of LH-RH or TRH, nor was there a different pattern of response in children who were deficient in growth hormone as opposed to those with idiopathic delayed growth. The fall in concentration of ML with stress may mediate the increased secretion of pituitary hormones. Alternatively, the pineal gland may respond directly to insulin.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Human platelet signaling defect characterized by impaired production of inositol-1,4,5-triphosphate and phosphatidic acid and diminished Pleckstrin phosphorylation: evidence for defective phospholipase C activation

Signal transduction on platelet activation involves phosphoinositide- specific phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositides and formation of inositol-1,4,5-triphosphate [I(1,4,5)P3], which mediates Ca2+ mobilization, and diacylglycerol (DG), which activates protein kinase C (PKC) to phosphorylate a 47-kD protein (Pleckstrin). We studied these events in two related patients previously reported (Blood 74:664, 1989) to have abnormal aggregation and 14C-serotonin secretion, and impaired intracellular Ca2+ mobilization in response to several agonists. Thrombin-induced I(1,4,5)P3 and phosphatidic acid formation were diminished. Pleckstrin phosphorylation was impaired on activation with thrombin, platelet- activating factor, and ionophore A23187, but was normal with PKC activator 1,2-dioctonyl-sn-glycerol (DiC8). Ca2+ mobilization induced by guanosine triphosphate (GTP) analog guanosine 5'-0-(3 thiotriphosphate) (GTP gamma S) was diminished. Pretreatment with either A23187 or DiC8 did not correct the impaired adenine diphosphate- induced secretion; however, upon stimulation with A23187 plus DiC8, pleckstrin phosphorylation and secretion were normal, indicating that both PKC activation and Ca2+ mobilization are essential for normal secretion. We conclude that these patients have a unique inherited platelet defect in formation of two key intracellular mediators [I(1,4,5)P3 and DG] and in the responses mediated by them due to a defect in postreceptor mechanisms of PLC activation.     

Examining Pharmacy Workforce Issues in the United States and the United Kingdom

Objective. To examine available data and actions surrounding current pharmacy workforce issues in the United States and United Kingdom.Methods. Published pharmacy workforce data from the United States and United Kingdom were gathered from various sources, including PUBMED, Internet search engines, and pharmacy organization websites. Data was collated from additional sources including scientific literature, internal documents, news releases, and policy positions.Results. The number of colleges and schools of pharmacy has expanded by approximately 50% in both the United States and United Kingdom over the previous decade. In the United States, continued demand for the pharmacy workforce has been forecasted, but this need is based on outdated supply figures and assumptions for economic recovery. In the United Kingdom, workforce modeling has predicted a significant future oversupply of pharmacists, and action within the profession has attempted to address the situation through educational planning and regulation.Conclusion. Workforce planning is an essential task for sustaining a healthy profession. Recent workforce planning mechanisms in the United Kingdom may provide guidance for renewed efforts within the profession in the United States.     

A clinic-based mammography intervention targeting inner-city women

OBJECTIVE: The objective was to evaluate the effect of a clinic-based intervention program on mammography use by inner-city women. DESIGN: A randomized controlled trial employing firm system methodology was conducted. SETTING: The study setting was a general internal medicine clinic in the university-affiliated county hospital serving metropolitan Seattle. PARTICIPANTS: Women aged 50 to 74 years with at least one routine clinic appointment (when they were due for mammography) during the study period were enrolled in the trial (n = 314). INTERVENTIONS: The intervention program emphasized nursing involvement and included physician education, provider prompts, use of audiovisual and printed patient education materials, transportation assistance in the form of bus passes, preappointment telephone or postcard reminders, and rescheduling assistance. Control firm women received usual care. MEASUREMENTS AND MAIN RESULTS: Mammography completion within 8 weeks of clinic visits was significantly higher among intervention (49%) than control (22%) firm women (p < .001). These effects persisted after adjustment for potential confounding by age, race, medical insurance coverage, and previous mammography experience at the hospital (odds ratio 3.5; 95% confidence interval 1.9, 6.5). The intervention effect was modified by type of insurance coverage as well as prior mammography history. Process evaluation indicated that bus passes and rescheduling efforts did not contribute to the observed increases in screening participation. CONCLUSIONS: A clinic-based program incorporating physician education, provider prompts, patient education materials, and appointment reminders and emphasizing nursing involvement can facilitate adherence to breast cancer screening guidelines among inner-city women.     

Acquired granular pool defect in stored platelets

Platelets stored as concentrates (PC) for 72 h at 22 degrees C develop a functional defect. Alterations in adenine nucleotides of platelets have been shown to affect platelet function. Adenine nucleotide content of platelets was measured before and after storage and a decrease of 27.1 /+- 1.7% (mean /+- SE) in ATP and 39.1 /+- 2.6% in ADP were found in 34 PC stored with final volume of 50 ml. In 11 PC with 30 ml volume. ATP and ADP decreased by 39.4 /+- 3.2% and 49.4 /+- 2.1%, respectively. The mean ATP to ADP ratio of stored platelets was significantly higher than of fresh platelets in both groups, suggesting a relatively greater decrease in granular than metabolic pool nucleotides. Levels of low affinity platelet factor 4 measured by radioimmunoassay in plasma from 0.86 /+- 0.08 microgram/ml in the fresh PC to 8.59 /+- 0.39 microgram/ml in stored PC, indicating a concomitant alpha-granular secretion. Labeling of metabolic pool with 14C-adenine revealed a mean decrease in the adenylate energy charge of 2.0 /+- 0.4% in 12 of 16 stored PC, with a lower ATP and higher hypoxanthine labeling in stored as compared to fresh platelets. These observations suggest that stored platelets develop an acquired defect in both dense and alpha granules and in their ability to maintain ATP homeostasis.     

Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's syndrome

Clinical features such as weight gain, depression, hypertension, and menstrual irregularities, although common in the general population, may raise the possibility of Cushing's syndrome. Up to 30% of urine cortisol and dexamethasone suppression screening tests may return an incorrect result, suggesting that better tests are needed. This study evaluated the utility of nighttime salivary cortisol measurement as a screening test for Cushing's syndrome. We evaluated 139 inpatients and 4 outpatients with possible Cushing's syndrome, 16 inpatients and 7 outpatients with other nonadrenal disorders, and 34 healthy outpatients. Using cut points that excluded all subjects without Cushing's syndrome, we compared the sensitivity for the detection of Cushing's syndrome of nighttime salivary cortisol levels (2330 and 2400 h for inpatients and bedtime for outpatients), simultaneous inpatient serum cortisol levels, and urine glucocorticoid excretion. An assay- specific inpatient 2400-h salivary cortisol or an outpatient bedtime salivary cortisol greater than 550 ng/dl (15.2 nmol/liter) identified 93% of patients with Cushing's syndrome (confidence interval, 89-98%) and excluded all individuals without the disorder. Salivary cortisol measurements worked as well as plasma measurements and better than urine glucocorticoid excretion. We concluded that bedtime salivary cortisol measurement is a practical and accurate screening test for the diagnosis of Cushing's syndrome.