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.

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.

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.

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.

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.

Pregnancy outcome of a patient with atypical polypoid adenomyoma.

OBJECTIVE: Detailed description and follow-up of a patient with atypical polypoid adenomyoma and infertility, from investigation until delivery of a healthy baby. DESIGN: Case report. SETTING: Tertiary infertility center. PATIENT(S): A patient suffering from persistent APA and infertility. INTERVENTION(S): Danggui (Angelica sinensis) and low-dose aspirin. MAIN OUTCOME MEASURE(S): Pregnancy and live birth. RESULT(S): Conception after Danggui but intrauterine death at 25 weeks. Successful live birth after Danggui plus low-dose aspirin. CONCLUSION(S): Danggui corrected atypical polypoid adenomyoma and led to pregnancy twice in the same patient. Low-dose aspirin may improve the circulation in the placental bed and lead to live birth.

Oral misoprostol for induction of labor in prelabor rupture of membranes (PROM) at term: a randomized control trial.

OBJECTIVE: To compare the efficacy of two different dosages of oral misoprostol (50 and 100 microg) with control, in medical induction of labor for patients with prelabor rupture of membranes (PROM) at term. METHODS: One hundred women with PROM at term were randomized to receive placebo (vitamin B6 50 mg, control), 50 microg (treatment group 1), or 100 microg (treatment group 2) of oral misoprostol every 4 h to a maximum of six doses. The main outcome measures included time interval from onset of PROM to delivery, duration of first stage of labor, and occurrence of vaginal delivery within 24 h from PROM. RESULTS: The time intervals from PROM to delivery were significantly reduced in both treatment groups compared to control (control, 25.1+/-10.5 h; treatment group 1, 14.5+/-6.2 h; and treatment group 2, 13.0+/-6.1 h, p<0.0001 for both). The duration of the first stage of labor was significantly shortened only in treatment group 2 compared to control (3.3+/-2.5 versus 6.2+/-3.4 h, p=0.01). Of those who delivered vaginally (93% in treatment group 1 and 97% in treatment group 2), significantly more women delivered within 24 h of PROM in the treatment group compared to the control group (50%, p<0.05). CONCLUSIONS: Oral misoprostol 50 microg every 4 h is safe, cheap, and as effective as 100 microg in reducing the PROM to delivery time interval and labor duration in primiparous women. The same effect is not observed in a multiparous group.

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.

Effect of ginkgolides on beta-amyloid-suppressed acetylocholine release from rat hippocampal slices.

As Ginkgo has been shown to improve age-related memory de fi cits and beta-amyloid-related peptides have been suggested to play a signi fi cant role in memory degeneration in Alzheimer's disease, the present study was carried out to examine the effect of two major ginkgolides, A and B, on beta-amyloid peptide-modulated acetylcholine (ACh) release from hippocampal brain slices. Addition of beta-amyloid fragment(25-35) (0.01-1 micro M) in the superfusion medium suppressed the K(+)-evoked [(3)H]-ACh release from the rat hippocampal slices in a concentration-related manner; a 40% reduction in ACh out fl ow was observed with the highest amyloid concentration used (1 micro M). Inclusion of ginkgolide B (GKB, 0.01-10 micro M) caused a concentration-related reversion of the inhibitory effect elicited by the effective concentration of beta-amyloid (1 micro M). The reversal of the beta-amyloid-inhibited ACh release by GKB (1 micro M) was not blocked by tetrodotoxin (1 micro M) indicating a direct interaction of GKB on the cholinergic nerve terminals. In contrast, addition of the same concentration range of ginkgolide A (GKA, 0.01-10 micro M) had no effect on beta-amyloid-inhibited ACh release. These results suggest that GKB may elicit its anti-amnesic effect by minimizing the inhibitory effect of beta-amyloid peptides on cholinergic transmission.

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.

Effects of desmopressin on prolonging survival in stable hypothermia in rats.

The aim of the present study was to examine whether minimizing plasma volume loss due to cold-induced diuresis can increase the survival time of rats maintained in long-term stable hypothermia (~24 h at a body temperature of 19 degrees C). Infusion of desmopressin (0.5-2.0 microg), a potent antidiuretic agent, during the cooling period enhanced survival over saline controls in a dose-related manner. The enhanced survival was accompanied by a significant delay in the expected increase of hematocrit and decrease of plasma volume as compared with those seen in saline controls. In contrast, treating the rats with the same dose range of another vasopressin analog, [beta-mercapto-beta,beta-cyclopentamethyl enepropionyl]-vasopressin, which has no antidiuretic action, failed to enhance survival over saline control. Further, treating the rats with the optimal dose of desmopressin (1 microg) at the later stage of hypothermia failed to elicit any beneficial effect. Our results indicate that by using desmopressin early during the cooling phase of the hypothermia, plasma volume and rheological parameters important for sustaining microcirculation can be better maintained than those seen in saline controls. These improvements may have contributed to the observed longer survival time in hypothermia.

Use of fetal-pelvic index in the prediction of vaginal birth following previous cesarean section.

AIM: To clarify the usefulness of the fetal-pelvic index as a predictor of vaginal birth after previous lower segment cesarean section. METHODS: One hundred and seventy women with one lower segment cesarean section who attempted for trial of vaginal birth were enrolled. Pelvimetry was performed to measure maternal pelvic inlet and mid-cavity circumferences at 37 weeks gestation. Ultrasound was performed to measure fetal head and abdominal circumferences at 38-39 weeks. The fetal-pelvic index was derived. The predictability of fetal-pelvic index in the predicting the outcome of delivery was calculated. RESULTS: Fifty-seven (33.5%) women required repeated cesarean section and 113 (66.5%) delivered vaginally. Twenty-two women with positive fetal-pelvic index had repeated cesarean section. The predictability of positive fetal-pelvic index was 48.9%. Ninety of the 125 patients with a negative fetal-pelvic index delivered vaginally. The predictability of negative fetal-pelvic index was 72.0%. CONCLUSIONS: Fetal-pelvic index derived in the antenatal period has low predictive value in predicting of successful vaginal birth after cesarean section. This index is not useful in clinical practice.

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.

A diving fatality due to oxygen toxicity during a "technical" dive.

An experienced diver drowned after a generalised seizure caused by oxygen toxicity during a 19-minute "technical" dive to a depth of 47 m. He had used a 50% oxygen/nitrogen gas mixture inappropriately during the dive. This case attests the risk of oxygen toxicity from oxygen-enriched air during deep dives, the shortcomings of the diver's equipment, and the need to examine, with knowledge of diving physiology and practice, both the body and equipment.

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.