A patient-centered framework for health systems engineering in gastroenterology: improving inpatient colonoscopy bowel preparation.

BACKGROUND: Inpatient colonoscopy bowel preparation (ICBP) is frequently inadequate and can lead to adverse events, delayed or repeated procedures, and negative patient outcomes. Guidelines to overcome the complex factors in this setting are not well established. Our aims were to use health systems engineering principles to comprehensively evaluate the ICBP process, create an ICBP protocol, increase adequate ICBP, and decrease length of stay. Our goal was to provide adaptable tools for other institutions and procedural specialties. METHODS: Patients admitted to our tertiary care academic hospital that underwent inpatient colonoscopy between July 3, 2017 to June 8, 2018 were included. Our multi-disciplinary team created a protocol employing health systems engineering techniques (i.e., process mapping, cause-effect diagrams, and plan-do-study-act cycles). We collected demographic and colonoscopy data. Our outcome measures were adequate preparation and length of stay. We compared pre-intervention (120 ICBP) vs. post-intervention (129 ICBP) outcomes using generalized linear regression models. Our new ICBP protocol included: split-dose 6-L polyethylene glycol-electrolyte solution, a gastroenterology electronic note template, and an education plan for patients, nurses, and physicians. RESULTS: The percent of adequate ICBPs significantly increased with the intervention from 61% pre-intervention to 74% post-intervention (adjusted odds ratio of 1.87, p value = 0.023). The median length of stay decreased by approximately 25%, from 4 days pre-intervention to 3 days post-intervention (p value = 0.11). CONCLUSIONS: By addressing issues at patient, provider, and system levels with health systems engineering principles, we addressed patient safety and quality of care provided by improving rates of adequate ICBP.

Development and validation of next generation sequencing based 35-gene hereditary cancer panel.

BACKGROUND: Understanding the genetic basis of cancer risk is a major international endeavor. The emergence of next-generation sequencing (NGS) in late 2000's has further accelerated the discovery of many cancer susceptibility genes. The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has proven to be a viable option, with the accurate and robust detection of a wide range of clinically relevant variants in the targeted genes being crucial. METHODS: We have developed and validated a targeted NGS-based test for hereditary cancer risk assessment using Illumina's NGS platform by analyzing the protein-coding regions of 35 hereditary cancer genes with a bioinformatics pipeline that utilizes standard practices in the field. This 35-gene hereditary cancer panel is designed to identify germline cancer-causing mutations for 8 different cancers: breast, ovarian, prostate, uterine, colorectal, pancreatic, stomach cancers and melanoma. The panel was validated using well-characterized DNA specimens [NIGMS Human Genetic Cell Repository], where DNA had been extracted using blood of individuals whose genetic variants had been previously characterized by the 1000 Genome Project and the Coriell Catalog. RESULTS: The 35-gene hereditary cancer panel shows high sensitivity (99.9%) and specificity (100%) across 4820 variants including single nucleotide variants (SNVs) and small insertions and deletions (indel; up to 25 bp). The reproducibility and repeatability are 99.8 and 100%, respectively. CONCLUSIONS: The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has been considered a viable option. In the present study, we developed and validated a 35-gene panel for testing 8 common cancers using next-generation sequencing (NGS). The performance of our hereditary cancer panel is assessed across a board range of variants in the 35 genes to support clinical use.

Prevalence and genotype distribution of cervical human papillomavirus infection in Macao.

Population-specific epidemiological data on human papillomavirus (HPV) infection are essential for formulating strategies to prevent cervical cancer. The age-specific prevalence of HPV infection was determined among 1,600 women enrolled for cervical screening in Macao. A U-shaped age-specific prevalence curve with a first peak (prevalence rate, 10%) at 20-25 years and a second peak (13%) at 51-55 years was observed. Co-infections with multiple types were detected in 32.5% of HPV-positive subjects and without significant variation among different age groups (P = 0.318). The majority (84.6%) of the positive samples harbored high- or probable high-risk HPV types, and these types also exhibited a similar U-shaped age-specific prevalence curve. In contrast, low and unknown-risk HPV types remained at a low prevalence (1.5-2.5%) throughout the age groups between 20 and 50 years, and with a small peak (4.5%) at 51-55 years. HPV 52 was the most common type found in 26.8% of positive samples, followed by HPV 16 (15.5%), HPV 68 (11.4%), HPV 18 and HPV 58 (8.9% each), HPV 54 (8.1%), HPV 53 (7.3%), HPV 39 (6.5%), HPV 33 and HPV 66 (5.7% each). In conclusion, because of the early peak of infection, vaccination and educational campaigns in Macao should start early and target at teenagers. The presence of a second peak containing mainly high-risk HPV types in older women indicates the need to evaluate the cover of the cervical screening programme for older women. Further study to determine the contribution of HPV 52 in high-grade cervical neoplasia and invasive cancers in Macao is warranted.

Comparison of powered drill & manual bone biopsy systems: Does the diagnostic yield justify the cost?

Bone biopsies are traditionally performed using manual drill devices. More recently, powered drill biopsy systems have been developed, ostensibly to improve diagnostic yield. We compare the powered drill biopsy system to traditional manual needle devices on the basis of diagnostic yield, specimen size and material costs. 309 consecutive bone biopsy procedures performed with imaging guidance from a single academic institution were retrospectively reviewed. Specimen diagnostic adequacy, qualitative interpretation of diagnostically inadequate specimens, aggregate specimen volume and material costs were assessed. Econometric analysis was performed to assess the relationship between materials cost and diagnostic yield. Diagnostic yield and average core specimen volume were significantly higher in the powered drill group, with 86% of cases yielding adequate biopsy specimens versus 67% of cases using the manual method. The materials cost associated with the powered drill device was higher than those of any of the manual needle devices with an average difference of $270.19 per case, however, this was offset due to higher diagnostic yield suggesting that the increased diagnostic accuracy achieved by the powered drill does not carry a significant added financial burden. The powered drill bone biopsy system results in a significantly higher yield of diagnostically adequate biopsy specimens compared to traditional manual needles, possibly attributed to larger and more intact obtained core specimen volumes and is more economically viable off-setting the higher cost.

Trueperella bernardiae: an unusual cause of septic thrombophlebitis in an injection drug user.

The clinical spectrum of human disease caused by Trueperella bernardiae is poorly described, partly as a result of historical difficulties with microbial identification. With the introduction of powerful new technologies, such as matrix-assisted desorption ionization-time of flight mass spectrometry, into routine microbiology laboratories, new insights into diseases caused by such organisms are being made. Here we report a case of septic thrombophlebitis with bacteraemia caused by this organism, together with a retrospective description of laboratory isolation of this organism over a period of 6 years in a hospital in London, UK.

Deep proteome profiling of sera from never-smoked lung cancer patients.

Previous studies on the serum proteome are hampered by the huge dynamic range of concentration of different protein species. The use of Equalizer Beads coupled with a combinatorial library of ligands has been shown to allow access to many low-abundance proteins or polypeptides undetectable by classical analytical methods. This study focused on never-smoked lung cancer, which is considered to be more homogeneous and distinct from smoking-related cases both clinically and biologically. Serum samples obtained from 42 never-smoked lung cancer patients (28 patients with active untreated disease and 14 patients with tumor resected) were compared with those from 30 normal control subjects using the pioneering Equalizer Beads technology followed by subsequent analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Eighty-five biomarkers were significantly different between lung cancer and normal control. The application of classification algorithms based on significant biomarkers achieved good accuracy of 91.7%, 80% and 87.5% in class-prediction with respect to presence or absence of disease, subsequent development of metastasis and length of survival (longer or shorter than median) respectively. Support vector machine (SVM) performed best overall. We have proved the feasibility and convenience of using the Equalizer Beads technology to study the deep proteome of the sera of lung cancer patients in a rapid and high-throughput fashion, and which enables detection of low abundance polypeptides/proteins biomarkers. Coupling with classification algorithms, the technologies will be clinically useful for diagnosis and prediction of prognosis in lung cancer.

Effects of ginseng saponins on beta-amyloid-induced amnesia in rats.

We have previously demonstrated that ginseng saponins (GS) can reverse the inhibitory effect of beta-amyloid on acetylcholine (ACh) release in the hippocampal slices. The present study was carried out to examine whether GS has any beneficial effects against amnesia induced by beta-amyloid peptides in vivo. Intracerebroventricular injection of 50 microg, but not 10 microg, beta-amyloid fragment(25-35) markedly impaired the performance of rats in avoiding a shock prod, confirming the amnesiac effect of beta-amyloid. Chronically treating the rats with GS (orally, 5 days before icv beta-amyloid injection and 7 days afterward) resulted in a dose-related improvement against beta-amyloid-induced amnesia; a significant reversion was observed at the highest GS dose (80 mg/kg/day). Post-treatment analysis on K(+)-evoked [(3)H]-ACh release from the hippocampal slices showed that beta-amyloid-treatment significantly reduced ACh release from that of the control group. However, pre-treatment with GS completely protected the animal against beta-amyloid-induced reduction of hippocampal ACh release. In contrast, treating the animals with the same optimal dose of GS and duration but only after icv beta-amyloid injection was found to be ineffective in obliterating beta-amyloid's amnesiac effect. Taken together, these observations indicated that GS pre-treatment can functionally prevent the beta-amyloid-induced memory loss possibly by minimizing the inhibitory effect of beta-amyloid on hippocampal cholinergic transmission.

Activation of inactive renin during the selective destruction of proteinase inhibitors in human plasma by a metalloproteinase in Bitis arietans venom.

Puff adder venom, which has been pretreated with phenylmethylsulphonyl fluoride and extensively dialysed, is capable of destroying selectively proteinase inhibitory activity in human plasma by an action of an EDTA-sensitive venom proteinase. We found that incubation of 1/5 vol. of such venom with human plasma at 25 degrees C leads to a concomitant increase in renin to 4.4 times control by 5 h. The activation of inactive renin was abolished by 10 mM EDTA and the rate of activation was reduced by 50% in the presence of 5 mM phenylmethylsulphonyl fluoride and by 90% when 0.32 mg/ml soybean trypsin inhibitor and 5 mM N-ethylmaleimide were added as well. The venom proteinase thus appears to activate inactive renin via an activation of endogenous plasma proteinases. This may be accomplished either by activation of proteinase precursors or action on proteinase inhibitor-proteinase complexes. By destroying proteinase inhibitors at the same time as it activates endogenous proteinases, Bitis arietans metalloproteinase would appear to be particularly useful for studies of the activation of inactive renin in human plasma, since endogenous proteinases are then free to activate inactive renin without subsequent inhibition by endogenous proteinase inhibitors.

Mechanism of activation of inactive renin in human plasma by puff adder venom.

Venom of the puff adder (Bitis arietans) contains a potent, basic, Mr 24,000 metalloproteinase activity that can destroy all detectable trypsin and chymotrypsin inhibitory activity, when venom is incubated with human plasma. We have found that during such incubation, concomitant activation of inactive renin occurs. In an examination of the mechanism involved we now report the activation, in addition, of plasma prekallikrein and serine proteinase activity, but not plasminogen, when human plasma is incubated with venom. Furthermore, venom was not able to release active trypsin from its complex with alpha 1-proteinase inhibitor and human renin was not inhibited by alpha 1-proteinase inhibitor. The activities in venom and venom/plasma mixtures were analysed using Sephacryl S-200 gel filtration and the effect of 10 mM EDTA and 5 mM phenylmethanesulphonyl fluoride on activities in column fractions was tested. The inactive-renin-activating, plasma prekallikrein-activating and serine proteinase-activating activities could be accounted for to a large extent by a venom metalloproteinase which was estimated to have a Mr of 24,000 by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis. This enzyme activity appeared to complex with alpha 2-macroglobulin when venom was mixed with plasma. Since both EDTA and phenylmethanesulphonyl fluoride could inhibit the activation of inactive renin by this metalloproteinase, it is suggested that the enzyme activates serine proteinase(s), which then activate inactive renin. Plasma kallikrein may have a role in this process. Additional peaks of inactive-renin-activating activity eluted from Sephacryl S-200 at Mr 30,000 and 80,000 (minor) and an additional, minor peak of caseinolytic activity eluted at Mr 60,000. The Mr 24,000 metalloproteinase in venom may have considerable utility in activating inactive renin at physiological pH owing to its ability to destroy plasma proteinase inhibitors at the same time.

A community study of sleep-disordered breathing in middle-aged Chinese women in Hong Kong: prevalence and gender differences.

STUDY OBJECTIVES: To investigate the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea syndrome (OSAS) in community-based, middle-aged Chinese women, and to compare the differences between gender with a similar study in men. DESIGN: A cross-sectional study conducted in Hong Kong from 1998 to 2000. SETTING: Sleep questionnaires were distributed to women (30 to 60 years old) in three offices and two community centers. All were invited to undergo full polysomnography in a sleep laboratory. PARTICIPANTS: Questionnaires were distributed to 1,532 women, and 854 questionnaires were returned. Polysomnography was conducted in 106 respondents. MEASUREMENTS AND RESULTS: Conservative estimated prevalence of SDB (apnea-hypopnea index [AHI] > = 5) and OSAS (AHI > or = 5 plus excessive daytime sleepiness [EDS]) were 3.7% and 2.1%, respectively. Age-specific prevalence of OSAS was 0.5%, 2.2%, and 6.1% in the 30- to 39-year-old, 40- to 49-year-old, and 50- to 60-year-old age groups, respectively. Stepwise multiple logistic regression analysis identified body mass index (BMI) and age as predictors of SDB. Compared to Chinese men, the prevalence of SDB and OSAS in women was lower, but the gender difference decreased with age. The AHI of affected women was also significantly lower despite comparable BMI. Compared to men, women with SDB had same degree of self-reported snoring and a similar degree of EDS despite the lower AHI. CONCLUSIONS: This study demonstrated an estimated prevalence of OSAS at 2.1% among middle-aged Chinese women in Hong Kong, with a 12-fold rise from the fourth to the sixth decade of life. BMI and age were significant independent predictors of SDB. Compared to men, women with SDB had lower AHIs, despite similar BMIs.

Transplacental transfer of Legionella pneumophila antibodies.

In order to determine the extent to which Legionella pneumophila antibodies are passively transferred transplacentally into the fetal circulation, 199 matched serums of mothers and their newborn infants were tested using the indirect fluorescent polyclonal antibody technique. Considering L. pneumophila antibody titers of greater than or equal to 1:64 as evidence of inapparent infection, the overall prevalence rate was 35.7% for the mothers and 14.1% for their newborns. Among the mothers who were seropositive at greater than or equal to 1:64, 36.6% of their matched infants acquired antibodies transplacentally. With only two exceptions there were no newborns with an antibody titer greater than or equal to 1:64 whose mothers did not also evidence at least the same titer.

False positive Legionella pneumophila direct immunofluorescent monoclonal antibody test caused by Bacillus cereus spores.

Direct immunofluorescent monoclonal antibody stain testing for Legionella pneumophila in Oklahoma lake water yielded an unknown bacillus with fluorescence intensity equal to that of L. pneumophila stock strains. The organism in question was identified as Bacillus cereus, a ubiquitous bacterium. When B. cereus cultures were studied, fluorescence was seen in spores but not in vegetative cells. Since a positive immunofluorescent monoclonal antibody test (alone) might be considered by some individuals as unequivocal to very good evidence for the presence of L. pneumophila, this finding emphasizes the importance of confirming positive stain results with cultures whenever possible.

Herbicidal properties of the thaxtomin group of phytotoxins.

The thaxtomins are a group of phytotoxins generated by the bacterium Streptomyces scabies (the main causal organism of potato common scab). Available members of the group were assessed for herbicidal activity by a variety of standard tests. Test results indicated that thaxtomin A, the predominant member, was also the most physiologically active. Injury symptoms in most instances were similar to those caused by known cellulose biosynthetic inhibitors such as dichlobenil and isoxaben. Although test results indicated that the thaxtomins had many of the biological properties desirable in a commercial herbicide, they nevertheless lacked the systemic phytotoxicity critical to deliver reliable weed control at low rates.

Microbial glucosylation of thaxtomin A, a partial detoxification.

Thaxtomin A (1) and B (2), the two major phytotoxins associated with the common scab of potato disease, were transformed into C-14 linked beta-glucosides (3) and (4), respectively, when individually incubated with cultures of Bacillus mycoides in oatmeal broth at 26 degrees C. These biotransformation products when assayed on aseptically produced potato minitubers proved to be much less phytotoxic than the parent compounds.

Incidence of Legionella pneumophila infections among Oklahoma pulmonary disease patients.

Prior studies by the authors suggested high levels of Legionella pneumophila in the recreational and water supply reservoirs in central Oklahoma. This high exposure potential was supported by a relatively high prevalence of seropositive, asymptomatic infections among healthy blood donors in the area. In contrast, the present 9-month laboratory-based study confirmed only one clinical Legionella infection among 117 unidentified pulmonary disease patients admitted to the Oklahoma City Veterans Administration Medical Center. Comparison with the reports of others and with reported legionellosis in Oklahoma indicates that differences in cohort definition and variations in utilization and interpretation of clinical analyses leads to wide variations in the reported incidence of legionellosis.

Prevalence of Lyme disease infection in Oklahoma.

Even though Lyme disease probably existed in Oklahoma prior to 1975 when the disease was first reported in Connecticut and even though ecological conditions favor a high prevalence, an unexpectedly low rate was evidenced in both a serological survey and the number of cases reported to the Oklahoma State Department of Health. Lyme disease does not appear to pose a significant public health threat in Oklahoma at the present time; however, the the presence of all the necessary factors for transmission and the rapidly increasing number of cases reported in nearby areas merits continued surveillance in this state. The need for consistent case definition is discussed.

Human ehrlichiosis--an overview.

Canine ehrlichiosis, previously thought to be restricted to dogs, has gained prominence in the human population since 1986. In the United States, human ehrlichiosis is a newly recognized disease ranging from a mild infection to a severe life threatening or fatal disease. Since antibody titers were found to be highest to E. canis in human ehrlichiosis patients, it was believed that E. canis or a closely related species was the etiologic agent. Investigators from the Centers for Disease Control recently have isolated a bacterium believed to be the etiologic agent of human ehrlichiosis and proposed the name Ehrlichia chaffeensis. Human cases of the disease have been identified primarily in the southeastern and south-central areas of the United States. Although relatively few cases are diagnosed, Oklahoma, according to one source, has been found to have the highest incidence rate. The human disease could be misdiagnosed as Rocky Mountain spotted fever, murine typhus fever, or Q fever.

Single layer linear array of microbeads for multiplexed analysis of DNA and proteins.

In this study, a microfluidic platform was developed to generate single layer, linear array of microbeads for multiplexed high-throughput analysis of biomolecules. The microfluidic device is comprised of eight microbead-trapping units, where microbeads were immobilized in a linear array format by the exertion of a negative pressure in the control channel connected to each sieving microstructure. Multiplexed assays were achieved by using a mixture of different spectrally-encoded microbeads functionalized with specific probes, followed by on-chip reaction and detection. The microfluidic-based microbeads array platform was employed for multiplexed analysis of DNA and proteins, as demonstrated by the simultaneous discrimination of four HPV genotypes and the parallel detection of six different proteins. Compared with the off-chip protocols, the on-chip analysis exhibited better reaction efficiency, higher sensitivity and wider linear detection range. Visual inspection and identification of functionalized microbeads were facilitated by the single layer arrangement of microbeads so that accurate data acquisition can be performed during the detection process.