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Measuring health changes among severely ill patients. The floor phenomenon.

The interest in measuring health status with survey instruments has not been matched with an analysis of their performance characteristics in the field. We used the Medical Outcome Study Short Form (MOS-20) to assess health outcomes among patients who were hospitalized in one of two public hospitals. We mailed the MOS-20 and a series of transition questions, which asked about changes in health, to patients admitted in the previous year. We received 414 completed surveys from 480 patients at baseline and follow-up data on 90% of these patients six months later. Baseline MOS-20 scores for study patients were significantly lower, corresponding to worse health, than previously reported outpatient and general population cohorts. While the direction of change on serial applications of the MOS-20 paralleled the patients' perception of change reported on transition questions, many patients who reported their health had become worse also recorded the lowest possible score on the MOS-20 at baseline. These low baseline MOS-20 scores prohibited the recognition of larger declines in function during the follow-up period. This floor in the response range creates an instrument bias against documenting a decline in health among severely ill patients, the group in which it may be most important to detect such a change.

Acute Disease↗

Non-operative management of stab wounds to the abdomen with omental evisceration.

A consecutive series of 14 patients with anterior abdominal stab wounds and omental evisceration treated at the Kingston Public Hospital Jamaica over a 3-year period is presented. During this period 223 patients with abdominal stab wounds were seen of which 66 had omental evisceration. Conservative surgical management was the approach followed in 14 patients who presented without signs of peritonitis. There were no late complications or missed visceral injuries necessitating laparotomy. Serial physical examination was the method used to select patients for conservative surgical management with the exclusion of patients with deteriorating clinical signs or peritonitis. Omental evisceration through an abdominal stab wound in a patient with stable clinical signs and without evidence of peritonitis is not an absolute indication for exploratory laparotomy.

Abdominal Injuries↗

[Report of the "Health and Environment" commission of the National Academy of pharmacy. Carbon monoxide and environmental health: are carbon monoxide levels in urban areas a health hazard?].

In an urban environment, carbon monoxide is produced by incomplete combustion, particularly in motor vehicles. Air pollution caused by CO produced by motor vehicles is controlled by legislation. Legal regulations have considerably lowered emission levels authorized for new vehicles and total CO emission levels. CO levels in the environment (urban environment in general and zones close to motorways) have thus declined. CO remains a public health concern both as a pollutant and as an indicator of air quality. We recall here the more recent approaches used to assess CO-related hazards developed by the Environmental Protection Agency in the United States and pertinent conclusions backing up previously defined reference levels. We then report recent French data concerning CO emission, environmental levels and evaluation procedures for different situations of human exposure: geographical situations, mode of transportation, police force, air sentinels. The third part of this article is devoted to biological data (interaction between CO and hemo-proteins, CO neurotransmitter?) and epidemiological data (serial surveys). The discussion centers on the limitations of epidemiological data and on the difficulty in evaluating hazards solely on the basis of a carboxyhemoglobin threshold. This latter point is particularly important because carboxyhemoglobin is only one of many indicators of air quality. Finally recommendations are proposed concerning weather-related aspects, evaluation of human exposure, and ways of improving biological and epidemiological data.

Air Pollutants↗

Binge drug use independently predicts HIV seroconversion among injection drug users: implications for public health strategies.

Several studies have highlighted risk factors that cause HIV vulnerability among injection drug users (IDUs); these studies in turn have prompted public health officials to take action to minimize these risks. We sought to evaluate the potential association between binge drug use and HIV seroconversion and, subsequently, risk factors associated with binge drug use among a cohort of IDUs. To do this, we performed analyses of (1) associations with HIV seroconversion and (2) associations with binge drug use among participants enrolled in the Vancouver Injection Drug Users Study (VIDUS), a prospective cohort of IDU. Because serial measures for each individual were available, we undertook a time-updated Cox regression analysis to detect associations with HIV incidence and variables potentially associated with binge drug use were evaluated by using generalized estimating equations (GEE). Overall, 1548 IDU were enrolled into the VIDUS cohort between May 1996 and May 2003. There were 1013 individuals who were HIV seronegative at enrollment and had at least one follow-up visit; 125 (12%) became HIV positive during the study period for a cumulative incidence rate of 14% at 64 months after enrollment. In the final multivariate model, binge drug use [Adjusted Hazards Ratio: 1.61 (CI: 1.12, 2.31)] was independently associated with HIV seroconversion. In subanalyses, when we evaluated associations with binge drug use in GEE analyses, borrowing [Odds Ratio (OR): 153 (CI: 1.33-1.76)] and lending [OR: 1.73 (CI: 1.50-1.98)] syringes, sex trade work [OR: 1.14 (CI: 1.01-1.29)], frequent cocaine [OR: 2.34 (CI: 2.11-2.60)] and heroin [OR: 1.29 (CI: 1.17-1.43)] injection were independently associated with binge drug use and methadone [OR: 0.80 (CI: 0.71-0.89)] was protective against binge drug use. Our study identified an independent association between binge drug use and HIV incidence and demonstrated several high-risk drug practices associated with bingeing. Given the unaddressed public health risks associated with bingeing, a public health response protocol must be developed to minimize the personal and public health risks associated with the binge use of drugs.

British Columbia↗

National Cancer Institute initiative: Lung image database resource for imaging research.

Preliminary clinical studies suggest that spiral computed tomography (CT) of the lungs can improve early detection of lung cancer in high-risk individuals. More clinical studies are needed, however, before public health recommendations can be proposed for population-based screening. Spiral CT generates large-volume data sets and thus poses problems in terms of implementation of efficient and cost-effective screening methods. Image processing algorithms such as computer assisted diagnostic (CAD) methods have the potential to assist in lesion (eg, nodule) detection on spiral CT studies. CAD methods may also be used to characterize nodules by either assessing the stability or change in size of lesions based on evaluation of serial CT studies, or quantitatively measuring the temporal parameters related to contrast dynamics when using contrast material-enhanced CT studies. CAD methods therefore have the potential to enhance the sensitivity and specificity of spiral CT lung screening studies. Lung cancer screening studies now under investigation create an opportunity to develop an image database that will allow comparison and optimization of CAD algorithms. This database could serve as an important national resource for the academic and industrial research community that is currently involved in the development of CAD methods. The National Cancer Institute request for applications (RFA) (CA-01-001) has already been announced (April 2000) to establish and support a consortium of academic centers to develop this database, the consortium to be referred to as the Lung Image Database Consortium (LIDC). This RFA is now closed. Five academic sites have been selected to be members of the LIDC, the first meeting of this consortium is planned for spring of 2001, and a public meeting is to be held in 2002. This report is abstracted from the previously published RFA to serve as an example of how an initiative is developed by the National Cancer Institute to support a research resource. For specific details of the RFA, please access the following Internet site: http://www. nci.nih.gov/bip/NCI-DIPinisumm.htm#a11.

Algorithms↗

Gene expression profiling in islet biology and diabetes research.

Following the sequencing of most of the human and mouse genomes, the next task for physicians and scientists will be to assess the relative levels of expression of these genes during development, following exposure to various nutritional and pharmacological conditions, and in disease states such as diabetes and related metabolic disorders. This review provides an overview of the various methodologies available for monitoring global gene expression. Use of cDNA libraries, Expressed Sequence Tag (EST) sequencing projects and databases, differential display (DD), serial analysis of gene expression (SAGE), subtractive cloning, and both cDNA and oligo microarrays are discussed, along with their merits and limitations. The Endocrine Pancreas Consortium http://www.cbil.upenn.edu/EPConDB/ has constructed mouse and human cDNA libraries from adult and various stages of embryonic development of endocrine pancreas. Over 100,000 ESTs have been deposited in public databases, and each clone is available through the IMAGE Consortium. A guide to Internet access is provided for future investigation.

Animals↗

Phenotypic expression of HA-NA combinations in human-avian influenza A virus reassortants.

Human-avian and human-mammalian influenza A virus reassortant clones with the neuraminidase (NA) gene of the A/USSR/90/77 (H1N1) strain and hemagglutinin (HA) genes of H3, H4 and H13 subtypes had been shown in an earlier publication to produce low HA yields in the embryonated chicken eggs. The low HA titers had been shown to be due, at least in part, to the formation of virion clusters at 4 degrees C; the clustering was removed by the treatment with bacterial neuraminidase [Rudneva et al., Arch. Virol (1993) 133: 437-450]. By serial passages of the reassortants in chick embryos non-aggregating variants were selected: the variants produced HA titers of the same order as A/USSR/90/77 parent virus. The assessment of the virus yields by the analysis of the partially purified virus preparations from fixed volumes of the allantoic fluid revealed that actual virion yields of the initial reassortants were lower than the yields of their passaged variants or of the parent viruses. The passaged variant of a reassortant possessing the HA gene of A/Duck/Ukraine/1/63 (H3N2) virus differed from the original (non-passaged) reassortant and from the parent A/Duck/Ukraine/1/63 virus in the reaction with a panel of monoclonal antibodies against H3 hemagglutinin. The data suggest that some HA-NA combinations may lead to an incomplete functional match between HA and NA and to the formation of low-yield reassortants, thus representing a possible limiting factor in the emergence of new HA-NA combinations in natural conditions.

Animals↗

Expression analysis of members of the neuronal calcium sensor protein family: combining bioinformatics and Western blot analysis.

We have used in silico mining of public databases (NCBI UniGene and NCI SAGE Anatomic Viewer) as a tool to obtain the tissue distribution pattern of three members of the neuronal calcium sensor protein family, namely VILIP-1, hippocalcin, and NCS-1 in humans. The theoretical human mRNA expression profile of the calcium sensor proteins derived from expressed sequence tag (EST) and serial analysis of gene expression (SAGE) data was compared with expression data from human tissues obtained by Western blot analysis. Since the EST databank searches do not yet give comparable results for rat which is often used as model animal, we have also analyzed the protein expression in rat tissues. Similar to the human expression profile in rat tissues calcium sensor proteins are mainly detected in the nervous system, but the data consistently implicated the additional expression in peripheral tissues with remarkable differences between the calcium sensor proteins.

Animals↗

SAGE identification of gene transcripts with profiles unique to pluripotent mouse R1 embryonic stem cells.

The identification of signals that regulate pluripotentiality and self-renewal is fundamental to the understanding of stem cell biology. To quantify the functionally active genome of pluripotent R1 embryonic stem (ES) cells, we used the method of serial analysis of gene expression (SAGE) to sequence a total of 140,313 SAGE tags. Of 44,569 unique transcripts, 9% matched known genes in the nonredundant GenBank database, whereas >35% of the unique tags did not match any known mouse sequence. Comparisons of relatively abundant (> or = 20) tags in the ES cell SAGE catalog with publicly available SAGE data sets identified 16 transcripts with an abundance profile unique to pluripotent R1 ES cells. We confirmed 12 by RT-PCR including those encoding KLF2, a transcription factor; galanin, a hypothalamic neurohormone; BAX, a proapoptotic signaling factor; and CDK4 and PAL31, cell cycle progression associated proteins. The data from this study provide a starting point for detailed transcriptome analyses of stem cells.

Animals↗

Deep and comparative analysis of the mycelium and appressorium transcriptomes of Magnaporthe grisea using MPSS, RL-SAGE, and oligoarray methods.

BACKGROUND: Rice blast, caused by the fungal pathogen Magnaporthe grisea, is a devastating disease causing tremendous yield loss in rice production. The public availability of the complete genome sequence of M. grisea provides ample opportunities to understand the molecular mechanism of its pathogenesis on rice plants at the transcriptome level. To identify all the expressed genes encoded in the fungal genome, we have analyzed the mycelium and appressorium transcriptomes using massively parallel signature sequencing (MPSS), robust-long serial analysis of gene expression (RL-SAGE) and oligoarray methods. RESULTS: The MPSS analyses identified 12,531 and 12,927 distinct significant tags from mycelia and appressoria, respectively, while the RL-SAGE analysis identified 16,580 distinct significant tags from the mycelial library. When matching these 12,531 mycelial and 12,927 appressorial significant tags to the annotated CDS, 500 bp upstream and 500 bp downstream of CDS, 6,735 unique genes in mycelia and 7,686 unique genes in appressoria were identified. A total of 7,135 mycelium-specific and 7,531 appressorium-specific significant MPSS tags were identified, which correspond to 2,088 and 1,784 annotated genes, respectively, when matching to the same set of reference sequences. Nearly 85% of the significant MPSS tags from mycelia and appressoria and 65% of the significant tags from the RL-SAGE mycelium library matched to the M. grisea genome. MPSS and RL-SAGE methods supported the expression of more than 9,000 genes, representing over 80% of the predicted genes in M. grisea. About 40% of the MPSS tags and 55% of the RL-SAGE tags represent novel transcripts since they had no matches in the existing M. grisea EST collections. Over 19% of the annotated genes were found to produce both sense and antisense tags in the protein-coding region. The oligoarray analysis identified the expression of 3,793 mycelium-specific and 4,652 appressorium-specific genes. A total of 2,430 mycelial genes and 1,886 appressorial genes were identified by both MPSS and oligoarray. CONCLUSION: The comprehensive and deep transcriptome analysis by MPSS and RL-SAGE methods identified many novel sense and antisense transcripts in the M. grisea genome at two important growth stages. The differentially expressed transcripts that were identified, especially those specifically expressed in appressoria, represent a genomic resource useful for gaining a better understanding of the molecular basis of M. grisea pathogenicity. Further analysis of the novel antisense transcripts will provide new insights into the regulation and function of these genes in fungal growth, development and pathogenesis in the host plants.

DNA, Fungal↗

Data integration and warehousing: coordination between newborn screening and related public health programs.

At birth, patient demographic and health information begin to accumulate in varied databases. There are often multiple sources of the same or similar data. New public health programs are often created without considering data linkages. Recently, newborn hearing screening (NHS) programs and immunization programs have virtually ignored the existence of newborn dried blood spot (DBS) newborn screening databases containing similar demographic data, creating data duplication in their 'new' systems. Some progressive public health departments are developing data warehouses of basic, recurrent patient information, and linking these databases to other health program databases where programs and services can benefit from such linkages. Demographic data warehousing saves time (and money) by eliminating duplicative data entry and reducing the chances of data errors. While newborn screening data are usually the first data available, they should not be the only data source considered for early data linkage or for populating a data warehouse. Birth certificate information should also be considered along with other data sources for infants that may not have received newborn screening or who may have been born outside of the jurisdiction and not have birth certificate information locally available. This newborn screening serial number provides a convenient identification number for use in the DBS program and for linking with other systems. As a minimum, data linkages should exist between newborn dried blood spot screening, newborn hearing screening, immunizations, birth certificates and birth defect registries.

Birth Certificates↗

Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk.

The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority. Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure. To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk. C. trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times. Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C. trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity. On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell. Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina. Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C. trachomatis. Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.

Chlamydia trachomatis↗

[Public screening for early carcinoma of gastric cardia: rule of carcinogenetic development observed by endoscopy].

OBJECTIVE: To study the rule of development of early cancer of gastric cardia in vivo in public screening. METHODS: A prospective cohort study on gastric cardiac cancer was held in the high incidence area of cancer of esophagus and stomach in China. 106 subjects had been examined regularly by endoscopy to observe the change of mucosa in high incidence area of gastric cardiac carcinoma developing at the root of gastric cardiac ridge by taking serial biopsy specimens. All specimens were diagnosed through the normal pathological processes to study the prognosis of pre-cancerous lesion of gastric cardia. RESULTS: The result of 106 subjects who had been observed for four years were: 1. Of 8 normal persons, 3 stayed normal, 4 turned to chronic gastritis, 1 developed early gastric cardiac cancer. 2. Of 61 persons chronic gastritis, 11 was observed to have glandular atrophy, 4 with mild atypical hyperplasia, and 2 with highly atypical hyperplasia. 3. Of 9 subjects showing atrophic chronic gastritis, 5 revealed no change, and 4 became chronic gastritis. 4. Of 22 subjects who revealed mild atypical hyperplasia, 17 resolved, 4 showed no change, and 1 advanced to highly atypical hyperplasia. 5. One person with highly atypical hyperplasia reverted to mild atypical hyperplasia. 6. Of 5 subjects with early gastric cardiac cancer without any treatment, 1 became advanced cancer, 1 still stayed in early stage, and 3 turned to atypical hyperplasia. CONCLUSION: 1. The development of early cancer of gastric cardia would proceed through the stages of chronic gastritis, glandular atrophy, and atypical hyperplasia. 2. The early cancer and pre-cancerous lesion of gastric cardia is reversible, though possessing malignant possibility.

Adult↗

Atrial fibrillation: how to approach rate control.

The optimal management of atrial fibrillation is of considerable clinical importance, and with the recent publication of four studies suggesting the equivalence of rate and rhythm control strategies, new attention has been focused on rate control. Reasons for rate control include reduction of symptoms and the prevention of tachycardia-mediated cardiomyopathy; yet, evidence-based definitions of optimal rate control are lacking. This article examines an approach to rate control that includes serial assessment of heart rate and symptoms, both at rest and with exertion, and the use of therapy tailored to the individual and modified over time (as no single therapy demonstrates clear superiority). Often, multidrug regimens including digoxin and a calcium channel blocker or beta-blocker are required, and in a minority of patients atrioventricular nodal ablation and pacing are necessary. Several novel therapies currently under development are also discussed.

Adrenergic beta-Antagonists↗

Complications associated with silicone intracanalicular plugs.

PURPOSE: To assess American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) member physicians' experiences with complications associated with silicone intracanalicular plugs and publicize risks associated with this device. METHODS: Two case reports are presented. A survey was sent to 420 ASOPRS member physicians, questioning them on their experiences with complications associated with silicone intracanalicular plugs. RESULTS: We present two case reports of complications associated with migration of intracanalicular plugs. In the first case, a 41-year-old man underwent serial insertion of seven intracanalicular plugs in one eye over several years, he had a 3-month relapsing course of Nocardia asteroides canaliculitis, dacryocystitis, and cellulitis requiring systemic antibiotics and multiple surgeries. In the second case, a 72-year-old woman had acute dacryocystitis, eventually necessitating dacryocystorhinostomy; at surgery, an intracanalicular plug was discovered in the lacrimal sac. One hundred fifty-nine usable survey responses were obtained. Sixty-one percent of respondents reported various complications including tearing, canaliculitis, and dacryocystitis. Fifty-one percent of respondents performed surgery to treat complications associated with silicone intracanalicular plugs. CONCLUSIONS: Silicone intracanalicular plugs may be difficult to remove and may be associated with significant lacrimal complications.

Adult↗

Best evidence topic report. Brain natriuretic peptide as a potential marker of acute coronary syndromes.

A short cut review was carried out to establish whether brain natriuretic peptide (BNP) can be used as a marker for acute coronary syndromes. 685 citations were found, of which eight presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is that BNP shows promise as an early cardiac marker and may enhance prognostic stratification. NPV and PPV may be unacceptably low to enable use as a sole cardiac marker. Incorporation into a multimarker strategy and serial estimations may be necessary.

Acute Disease↗

Retrospective analysis of catheter-related infections in a hemodialysis unit.

OBJECTIVE: To compare the incidence rates of catheter-related bloodstream infection associated with different vascular access methods in patients receiving hemodialysis. SETTING: Tertiary care public hospital in Western Australia. DESIGN: Retrospective analysis of surveillance data collected by the hospital's infection control department. METHODS: The number of confirmed bloodstream infections for each type of vascular access was identified for the period from July 2002 through June 2003. The corresponding number of patient-days was determined to calculate the infection incidence rates. The serially correlated data were then analyzed using Poisson generalized estimating equations. RESULTS: A total of 32 confirmed bloodstream infections were identified. Infection rates, in number of infections per 1,000 patient-days, were as follows: 0.4 for native arteriovenous fistulae; 2.86 for synthetic arteriovenous grafts; 4.02 for permanent, tunneled, cuffed central venous catheters; and 20.2 for temporary, nontunneled, noncuffed central venous catheters. Compared with permanent catheters, the monthly infection rate associated with the temporary catheters was significantly higher (incident rate ratio [IRR], 5.025 [95% confidence interval {CI}, 1.532-16.484]; P=.008) and that of arteriovenous fistulae was significantly lower (IRR, 0.099 [95% CI, 0.030-0.324]; P=.001). The monthly infection rate for arteriovenous grafts was not significantly different from that for permanent central venous catheters (IRR, 0.702 [95% CI, 0.246-2.008]; P=.510). CONCLUSIONS: A hierarchy of infection risk associated with vascular access type is evident. Native arteriovenous fistulae should be recommended for all patients receiving chronic hemodialysis, to minimize infection.

Bacterial Infections↗

The pyridine scale for clinical measurement of olfactory threshold: a quantitative reevaluation.

Serial dilutions of pyridine in water are employed for measuring the olfactory detection thresholds of patients. Experimental precautions are described that improve the precision and accuracy of the method. Existing data on the sensitivities of hyposmic patients are confirmed, but the sensitivities of normal subjects and of hyperosmic patients are believed to have been substantially overestimated in some earlier publications. Routine clinical applications of the revised pyridine odor threshold test are discussed. In the author's experience, the average cystic fibrosis patient is slightly hyposmic, and some cases of pituitary tumor are accompanied by a 100,000-fold hyperosmia.

Cystic Fibrosis↗