A review of the reliability and validity of the Edmonton Symptom Assessment System.

BACKGROUND: Systematic symptom reporting by patients and the use of questionnaires such as the Edmonton Symptom Assessment System (ESAS) have potential to improve clinical encounters and patient satisfaction. We review findings from published studies of the ESAS to guide use of the system and to focus research. METHODS: A systematic search for articles from 1991 through 2007 found thirty-nine peer-reviewed papers from 25 different institutions, thirty-three of which focused on patients with cancer. Observations, data, and statistics were collated according to relevance, reliability, validity, and responsiveness. RESULTS: Findings apply predominantly to symptomatic palliative patients with advanced cancer who were no longer receiving active oncologic therapies. Uncertainty about summarizing findings arises from frequent modification of the ESAS (altered items, scales, and time periods). Overall, reliability is established for daily administration. Scores are skewed, with a floor effect, but the relative order of symptoms by mean scores is similar across studies. Emotional symptoms are poorly captured by the depression and anxiety items. An equally weighted summation of scores may estimate a construct of "physical symptom distress," which in turn is related to performance status, palliative goals, quality of life, and well-being. CONCLUSIONS: The ESAS is reliable, but it has restricted validity, and its use requires a sound clinical process to help interpret scores and to give them an appropriate level of attention. Research priorities are to further develop the ESAS for assessing a greater number of important physical symptoms (and to target "physical symptom distress"), and to develop a similar instrument for emotional symptoms.

Seeking and obtaining mental health services: what do parents expect?

This study examined parents' expectations about seeking and obtaining mental health care. Using the Expectations of Mental Health Care survey, structured interviews were conducted with 235 parents with children between the ages of 5 and 19; most were African American. Expectations were assessed in four areas: treatment effectiveness, provider/client relationship, accessibility of mental health services, and social and cultural factors, e.g., stigma. Parents reported a number of negative expectations, and black parents had significantly more negative expectations than white parents. The findings suggest that attitudes and expectations may influence parents' decision to seek mental health care for their child.

Salt form selection and characterization of LY333531 mesylate monohydrate.

LY333531 is a potent protein kinase C(beta) (PKC(beta)) inhibitor currently under development for the treatment of diabetic complications. Seven salts of LY333531 (hydrochloride, sulfate, mesylate, succinate, tartrate, acetate and phosphate) were evaluated during the early phase of development. Physical property screening techniques including microscopy, DSC, TGA, XRPD, hygroscopicity and solubility were utilized to narrow the selection to two salts: the mesylate and hydrochloride. Identification of the optimal salt form was based upon solubility, bioavailability, physical stability and purity. During the evaluation process three hydrated forms (anhydrate, monohydrate, and tetrahydrate) of the hydrochloride salt were identified. The mesylate salt was found to give only one, a monohydrate. Processing parameters (e.g. filtration rate, crystal form stability) demonstrated that the anhydrate was the preferred form of the hydrochloride salt. Bioavailability studies in dogs indicated that the C(max) and area under the plasma concentration vs. time curve (AUC) for LY333531 and its active metabolite, LY338522, following administration of the mesylate salt were approximately 2.6 times those obtained after the LY333531 HCl dose. This difference was presumed to be due primarily to the fact that the mesylate was five times more soluble than the hydrochloride salt in water. These factors led to selection and development of LY333531 mesylate monohydrate as the active pharmaceutical ingredient for clinical evaluation.

Contemporary cardiac rehabilitation: patient characteristics and temporal trends over the past decade.

BACKGROUND: Recent and dramatic therapeutic advances, aggressive care of the elderly, and a heightened awareness of secondary prevention have had a significant, albeit incompletely described, impact on cardiac rehabilitation (CR) programs. The authors did a retrospective analysis on 1,848 patients from their phase II CR program that were treated over the past decade. The authors sought to identify and analyze how advances in cardiovascular care might be related to temporal changes in demographics, medical comorbidities, coronary artery disease risk factors, and cardiovascular history among individuals with cardiac disease who have completed the phase II CR program over a 10-year period. METHODS: Cardiac rehabilitation records were reviewed from 1986 to 1996 at Akron City Hospital. The data were compiled prospectively by nurses and exercise physiologists and were subsequently analyzed. The charts reviewed were from 1,848 patients who completed outpatient phase II CR. RESULTS: The program began in 1986 with 53 patients completing CR and evolved to 309 in 1996. There has been an increase in the number of elderly patients referred to and completing the program. The number of participants older than 65 years of age increased from 28.3% in 1986 to 52.1% in 1996. Cardiac rehabilitation participants reflect the known demographics of patients with clinical coronary artery disease. Men outnumber women and, on average, the female participants are older than the male participants. There has been a statistically significant increase in medical comorbidities over the course of the study. Although the absolute number of patients entering CR after coronary artery bypass graft survey has remained fairly constant, there has been a dramatic increase in the absolute number of patients entering CR after percutaneous tansluminal coronary angioplasty (with the latter recently comprising a majority of CR participants). CONCLUSION: There is a significant trend in the attendance and completion of CR programs by older individuals, which suggests a greater awareness of patients and their physicians. The growth of the program is fueled by high-risk patients with more comorbidities who potentially are the group of patients able to obtain the greatest absolute benefit from CR.

Expression of multiple Na+/H+ exchanger isoforms in rat parotid acinar and ductal cells.

Several members of the Na+/H+ exchanger gene family (NHE1, NHE2, NHE3, and NHE4) with unique functional properties have been cloned from rat epithelial tissues. The present study examined the molecular and pharmacological properties of Na+/H+ exchange in rat parotid salivary gland cells. In acinar cells superfused with a physiological salt solution (145 mM Na+), Na+/H+ exchanger activity was inhibited by low concentrations of the amiloride derivative ethylisopropyl amiloride (EIPA; IC50 = 0.014 +/- 0.005 microM), suggesting the expression of amiloride-sensitive isoforms NHE1 and/or NHE2. Semiquantitative RT-PCR confirmed that NHE1 transcripts are most abundant in this cell type. In contrast, the intermediate sensitivity of ductal cells to EIPA indicated that inhibitor-sensitive and -resistant Na+/H+ exchanger isoforms are coexpressed. Ductal cells were about one order of magnitude more resistant to EIPA (IC50 = 0.754 +/- 0.104 microM) than cell lines expressing NHE1 or NHE2 (IC50 = 0.076 +/- 0.013 or 0.055 +/- 0.015 microM, respectively). Conversely, ductal cells were nearly one order of magnitude more sensitive to EIPA than a cell line expressing the NHE3 isoform (IC50 = 6.25 +/- 1.89 microM). Semiquantitative RT-PCR demonstrated that both NHE1 and NHE3 transcripts are expressed in ducts. NHE1 was immunolocalized to the basolateral membranes of acinar and ductal cells, whereas NHE3 was exclusively seen in the apical membrane of ductal cells. Immunoblotting, immunolocalization, and semiquantitative RT-PCR experiments failed to detect NHE2 expression in either cell type. Taken together, our results demonstrate that NHE1 is the dominant functional Na+/H+ exchanger in the plasma membrane of rat parotid acinar cells, whereas NHE1 and NHE3 act in concert to regulate the intracellular pH of ductal cells.

Detection of interstitial lung abnormalities on picture archive and communication system video monitors.

The purpose of this study was to compare the detection of interstitial lung abnormalities on video display workstation monitors between radiologists experienced with video image interpretation and radiologists who lack this experience. Twenty-four patients with interstitial lung abnormalities documented by high-resolution computed tomography (HRCT) and lung biopsy, and 26 control patients with no history of pulmonary disease or a normal HRCT and normal chest radiographs were studied. Images were acquired using storage phosphor digital radiography and displayed on 1,640 x 2,048 pixel resolution video monitors. Five board-certified radiologists evaluated the images in a blinded and randomized manner by using a six-point presence of abnormality grading scale. Three radiologists were from 1 to 4 years out of residency and considered to be experienced workstation monitor readers with between 1 to 3 years of video monitor image interpretation. For the inexperienced readers, one radiologist had no prior experience with reading images from a video monitor and was direct out of residency, and the other radiologist had less than 4 months of intermittent exposure and was 1 year out of residency. Sensitivity and specificity were determined for individual readers. Positive predictive values, negative predictive values, accuracy, and receiver-operating curves were also generated. A comparison was made between experienced and inexperienced readers. For readers experienced with video monitor image interpretation, the sensitivity ranged from 87.5% to 92%, specificity from 69% to 92%, positive predictive value (PPV) from 73% to 87.5%, negative predictive value (NPV) from 87% to 90%, and accuracy from 80% to 88%. For inexperienced readers, these values were sensitivity 58%, specificity 50% to 65%, PPV 52% to 61%, NPV 56.5% to 63%, and accuracy 54% to 62%. Comparing image interpretation between experienced and inexperienced readers, there were statistically significant differences for sensitivity (P < .01), specificity (P < .01), PPV (P < .05), NPV (P < .05), accuracy (P < .05), and area under the receiver operator curve (Az) (P < .01). Within the respective experienced and inexperienced groups, no statistical significant differences were present. Our results show that digitally acquired chest radiographs displayed on high-resolution workstation monitors are adequate for the detection of interstitial lung abnormalities when the images are interpreted by radiologists experienced with video image interpretation. Radiologists inexperienced with video monitor image interpretation, however, cannot reliably interpret images for the detection of interstitial lung abnormalities.

Both M1 and M3 receptors regulate exocrine secretion by mucous acini.

We investigated the role of M1 and M3 receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments, we derived affinity values (KB) from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The KB for 4-DAMP is similar to its affinity value [equilibrium dissociation constant from competition studies (Ki); 1.81 nM] determined from radioligand competition experiments. In contrast, the KB for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion experiments, we found that the M1 receptor antagonist, M1-toxin, induces a rightward shift in the concentration-response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of M1-toxin appears specific for M1 receptor blockade, since the toxin abolishes acinar high-affinity pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both M1 and M3 receptors directly regulating mucous acinar exocrine secretion and indicate M3 receptors alone are insufficient to induce a maximal muscarinic response.

Identification and treatment of children's mental health problems by primary care providers: a critical review of research.

This article critically reviews research studies on the identification and treatment of children's mental health problems by primary care providers. Using a valid and reliable instrument to guide the review, the investigators examined the methods and findings of all 13 studies published on the topic from 1979 to 1994. Overall, primary care providers appeared to underidentify mental health problems among children and adolescents, especially those whose emotional impairments were not overtly severe. Large proportions of youngsters identified as having mental health problems did not receive needed treatment.

Regulation of mucous acinar exocrine secretion with age.

Denny and co-workers (Navazesh et al., 1992) recently reported decreased concentrations of MG1 and MG2 mucins in resting and stimulated whole human saliva with age. The current study was therefore conducted to examine whether there is a corresponding attenuation with age in stimulus secretion coupling regulating mucous cell exocrine secretion. We utilized an in vitro model system, isolated rat sublingual acini, to evaluate the regulation of mucous cell exocrine secretion. Rat sublingual glands are similar to human sublingual and minor mucous glands, both histologically and in terms of their pattern of innervation, which is predominantly parasympathetic. Mucin secretion is thus activated primarily by muscarinic cholinergic agonist and to a lesser extent by vasoactive intestinal peptide (VIP), which is co-localized with acetylcholine in parasympathetic nerve terminals. We isolated sublingual mucous acini from five-month-old and 24-month-old rats and compared the concentration responses for mucin secretion induced by VIP and the muscarinic agonist, arecaidine propargyl ester (APE). Concentration-response curves for VIP were nearly identical for mucous acini from the five-month-old and 24-month-old animals. Values for basal secretion, maximal secretion, and EC50 (approximately equal to 200 nmol/L VIP) were statistically equivalent between both age groups. Concentration-response curves for APE were also very similar between age groups, with no statistically significant difference in basal secretion or EC50 values (approximately equal to 50 nmol/L APE). Maximal secretion was slightly less but statistically different for 24-month-old vs. five-month-old animals, 158% vs. 169% above basal secretion, respectively. Collectively, we found no substantial age-related changes in the secretory responsiveness of salivary mucous cells.

Barriers to the use of preventive health care services for children.

This article describes findings from interviews of parents targeted for outreach efforts that encouraged them to use Medicaid's Early and Periodic Screening, Diagnosis and Treatment(EPSDT) Program. Begun in the 1970s, the EPSDT program held out the promise of ensuring that needy children would receive comprehensive preventive care. With only one-third of eligible children in the United States receiving EPSDT checkups, the program has yet to fulfill its promise. This study sought to understand parents' perceptions of barriers to using EPSDT by interviewing (a) 110 parents who did not schedule EPSDT checkups for their children after being exposed to outreach efforts and (b) 30 parents who did. Although the EPSDT Program is designed to provide health care at no charge and to provide assistance with appointment scheduling and transportation, these low-income parents identified significant barriers to care. Reasons for not using EPSDT services included (a) competing family or personal issues and priorities; (b) perceived or actual barriers in the health care system; and (c) issues related directly to problems with the outreach efforts. Parents who successfully negotiated these barriers and received EPSDT services encountered additional barriers, for example, scheduling and transportation difficulties, long waiting room times, or care that they perceived to be either unresponsive to their medical needs or interpersonally disrespectful. The implications for future outreach efforts and improving access to preventive health care services are discussed.

Health outcomes of children receiving EPSDT checkups: a pilot study.

This pilot study used medical records to examine the health outcomes of children receiving care in Medicaid's Early and Periodic Screening, Diagnosis and Treatment (EPSDT) program. Medical records from 76 children seen for EPSDT visits during a 6-month period were reviewed to assess whether health problems were identified and whether treatment, follow-up, or referral care was provided. Health problems were identified for 43% of the children; 22% received treatment, and 18% were referred for specialty care. Checkups uncovered fewer problems than would be expected in a poor, largely minority population. Almost one third of the children referred for specialty care apparently did not receive such care. The study verified the need for further research and provides direction for future study.

Glibenclamide does not reverse attenuated vasoreactivity to acute or chronic hypoxia.

Recent studies from our laboratory have shown that acute and chronic hypoxic exposures are associated with attenuated systemic vasoreactivity in conscious rats. The present studies examined the role of adenosine triphosphate-sensitive potassium channels (KATP channels) in modulating the pressor and vasoconstrictor responses to phenylephrine (PE) in conscious instrumented rats 1) during acute hypoxia or 2) after chronic hypoxic exposure. Mean arterial pressure, mean cardiac output, and total peripheral resistance were assessed before and after graded infusions of PE in both groups of rats under normoxic or hypoxic conditions. Additionally, the role of KATP channels in attenuating vasoreactivity was determined by administration of glibenclamide (KATP channel blocker) before PE infusions. Acute hypoxia (12% O2) was associated with reduced pressor and constrictor responses to PE in control animals. Furthermore, acute return to room air did not restore the pressor and constrictor responses in the chronically hypoxic rats. Glibenclamide infusion did not influence the pressor or vasoconstrictor responses to PE in either group of animals during normoxia or acute hypoxia. Therefore, our data suggest that opening of KATP channels is not involved in the attenuated vasoreactivity associated with acute and chronic hypoxia in the conscious rat.

Comprehensiveness of well child checkups for children receiving Medicaid: a pilot study.

Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) is a Medicaid program designed to provide comprehensive well child care for children from low-income families. Each EPSDT checkup should include a physical examination; medical history; assessment of development, nutrition, and immunizations; assessment of hearing, vision, and dental status; and anticipatory guidance. This pilot study of the medical records of 76 children receiving EPSDT checkups in six rural counties in North Carolina provided a preliminary assessment of whether EPSDT checkups included the required components. The study showed that health care providers frequently did not provide adequate documentation of the care provided at the checkup, and it raised questions as to whether children received the required components of the EPSDT checkup.

The wartime need for aeromedical evacuation physicians: the U.S. Air Force experience during Operation Desert Storm.

Air transportation has been the primary method of moving patients by the armed services of the United States since 1949. It is fast, reliable, and allows for centralized medical care. Aeromedical Evacuation (AE), performed by the U.S. Air Force under Department of Defense directive, was intended as a method to transport medically stable patients. Modern warfare has evolved into a process capable of generating large numbers of casualties in a short period of time that can overwhelm local medical facilities. Such casualties would then require immediate transportation in order to obtain appropriate treatment. The terrorist bombing of the U.S. Marine barracks in Beirut and the 1989 military action in Panama (Operation Just Cause) are recent experiences where unstable casualties were transported by an AE system not designed to care for acute injuries while en route to definitive care. During Operation Desert Storm, Aeromedical Evacuation Flight Surgeons (AE/FS's) augmented AE crews and provided flexibility to transport critically ill patients. Future planning should augment designated AE crews with appropriately trained physicians and include equipment on aircraft to resuscitate patients that decompensate inflight.

Guidance for using a pilot study: an example of research on minority children.

Sound research requires careful definition of the research problem, identification of critical variables and the sources of data for variables, design of procedures and instruments to ensure valid and reliable data, and appropriate and comprehensive data analyses. Additionally, adequate personnel, time, and budgetary resources are required. To help ensure that research addressing minority health issues meets these requirements, this article provides investigators with practical guidance for using pilot projects, not simply as small nongeneralizable studies but also as techniques to address each of these issues. The authors provide examples from real-life research, addressing the health outcomes of minority children who receive care through the Early and Periodic Screening Diagnosis.

Accuracy of exercise 201Tl myocardial scintigraphy in asymptomatic young men.

BACKGROUND: Little is known about the diagnostic usefulness of 201Tl scintigraphy for detecting asymptomatic coronary artery disease in apparently healthy men. We thus evaluated planar 201Tl exercise myocardial scintigraphy in 845 asymptomatic male military aircrew undergoing coronary arteriography because of abnormal noninvasive tests suggesting possible myocardial ischemia. METHODS AND RESULTS: Patients were stratified by prior disease risk into six subgroups using age (< 45 and > or = 45 years) and ratio of total to high density lipoprotein cholesterol (< 4.5, 4.5-6.0, and > 6.0). Significant coronary artery disease (> or = 50% diameter stenosis in any major coronary artery) was present in 143 (16.9% prevalence). Overall sensitivity and specificity of 201Tl scintigraphy adjusted for verification bias were estimated to be 45 +/- 4% and 78 +/- 1%, respectively. These values are lower than corresponding values accepted for clinical populations. Positive and negative predictive values varied across subgroups. A normal thallium scan indicated low risk of disease, but an abnormal test was likely to be a false-positive result. A logistic equation was retrospectively fit to the data for estimating the probability of disease given age, cholesterol ratio, and thallium results. Within each quintile of estimated risk, the average risk did not differ significantly from the observed disease prevalence. CONCLUSIONS: Exercise 201Tl scintigraphy is limited by the frequent occurrence of false-positive tests in detecting asymptomatic, anatomic coronary artery disease in young men in accordance with Bayesian probability theory.

8;14 chromosome translocation in a negative bone marrow aspirate from a patient with Burkitt's lymphoma.

A patient with Burkitt's lymphoma is described who, on presentation, had a bone marrow aspirate which did not show abnormal cells. Cells from the bone marrow were cultured and an 8;14 chromosome translocation was identified. This finding allowed us to upgrade the stage of disease from III to IV with therapeutic as well as prognostic implications.

The invasion of HeLa cells by Salmonella typhimurium: reversible and irreversible bacterial attachment and the role of bacterial motility.

The interactions which brought about the invasion of HeLa cells by Salmonella typhimurium consisted of a sequence of three phases. Initially, the motility of the bacteria facilitated their contact with the HeLa cells whereupon the bacteria became attached in a reversible manner (i.e. the bacteria could be removed readily by washing the HeLa cell monolayers with Hanks' Balanced Salt solution). The binding forces responsible for reversible attachment were probably the weak long-range forces of the secondary minimum level of attractive interactions between the bacterium and the HeLa cell. Reversible attachment was a necessary interlude before the bacteria became irreversibly attached to the surfaces of the HeLa cells (i.e. the bacteria were no longer removed by the washing procedure that removed the reversibly attached salmonellae). Irreversible attachment was prevented in solutions of low ionic strength; the forces responsible were probably those of the primary minimum generated between the HeLa cell and a bacterial adhesion which was capable of acting over only short distances between the reversibly attached bacterium and the HeLa cell (i.e. probably less than 15 nm). Only irreversibly attached bacteria proceeded to the third phase and were internalized by the HeLa cells.

The attachment to, and invasion of HeLa cells by Salmonella typhimurium: the contribution of mannose-sensitive and mannose-resistant haemagglutinating activities.

The association of the haemagglutinating activities of Salmonella typhimurium cultures with bacterial adhesion to HeLa cells, and the internalization of the bacteria by HeLa cells, was studied. Adhesion was not inhibited by alpha-methyl-D-mannoside (i.e. adhesion was mannose-resistant), and only four of the six strains tested produced type 1 fimbriae and the associated mannose-sensitive haemagglutinin (MSHA). The other two strains belonged to the non-fimbriate FIRN biogroup. Cultures of all six strains contained a mannose-resistant haemagglutinating (MRHA) activity when grown at 37 degrees C, but cultures of only one fimbriate and one non-fimbriate strain did so when grown at 18 degrees C. From the comparison of cultures grown at 18 degrees C and 37 degrees C, and of mutant strains with the phenotypes MRHA-negative/MSHA-positive, or MRHA-positive/MSHA-negative, it was concluded that the MRHA activity was responsible for the attachment of salmonellae to HeLa cells. Only bacterial adhesion that was resistant to mannose resulted in the internalization of the bacteria by the HeLa cells.