tbuckley/cabot-search huggingface dataset:
Systematic review: clostridium difficile and IBD
Authors: J. R. Goodhand, W. Alazawi, D. Rampton
Journal: Gut (2011)

<h3>Introduction</h3> There is increasing concern about the apparently rising incidence and worsening outcome of <i>clostridium difficile</i> infection (CDI) associated with inflammatory bowel disease (IBD). We have systematically reviewed, using PRISMA guidelines, the literature to evaluate the incidence risk factors, endoscopic features, treatment and outcome of CDI complicating IBD. <h3>Methods</h3> Structured searches of PubMed up to September 2010 for cross-sectional, cohort and case controlled studies were undertaken. <h3>Results</h3> Of 407 studies identified, 42 met the inclusion criteria: their heterogeneity precluded formal meta-analysis. There were no significant differences between the weighted mean incidence (weighted 95% CI) in adult patients with UC or Crohn9s disease (CD) by either culture (UC 6.7% (5.6–11.4), Crohn9s disease 8.8% (2.5–15.1)) or toxin assay (UC 3.1% (0.1–6.2), Crohn9s disease 7.0% (1.8–12.2)). The weighted mean incidence of CDI, derived from two studies of children in relapse was significantly higher than in adults 26.1% (16.1–36.1). In remission, patients with IBD are more frequently colonised than otherwise healthy controls, the number of strains implicated suggests multiple community sources of acquisition. Certainty about a temporal trend to an increasing incidence of CDI in IBD, reportedly complicating about 3.9% and 1.2% admissions for UC and Crohn9s disease in 2004, increasing to 5.3% and 1.5% respectively in 2008, is compromised by detection bias as a result of more frequent testing and miscoding. Antibiotics are less of a pre-requisite for CDI in IBD than in the general population: where reported only 43% (23/54) toxin-positive relapse samples were associated with antibiotic usage. Similarly nosocomial acquisition is reportedly less frequently than in the general population: where reported nosocomial acquisition was suspected in only 26% (5/19) patients with toxin-positive relapses. Further risk factors for acquisition, like in control populations include increasing age, immunosuppressant and colonic disease involvement. 7 studies reported on the use of endoscopy in IBD with CDI: only 9% (13/150) patients had pseudomembranes. There are no controlled trials of CDI treatment IBD. Contradictory data, probably accounted for by differences in trial design, are reported for length of stay, colectomy and mortalities. <h3>Conclusion</h3> Patients with IBD seem to be at increased risk for CDI compared to controls and CDI in IBD has received increasing attention in the past decade, but whether its incidence is really increasing or its outcome worsening remains unproven. Endoscopy is unhelpful in diagnosing CDI in IBD. Therapeutic trials of CDI treatment are lacking and are urgently needed.
Superoxide differentially controls pulmonary and systemic vascular tone through multiple signalling pathways
Authors: Vladimir A. Snetkov, Sergey V. Smirnov, Justin Kua, Philip I. Aaronson, Jeremy P.T. Ward, Greg A. Knock
Journal: Cardiovascular Research (2010)

The aim of this study was to determine the relative importance of Ca2+ sensitization, ion channels, and intracellular Ca2+ ([Ca2+]i) in the mixed constrictor/relaxation actions of superoxide anion on systemic and pulmonary arteries. Pulmonary and mesenteric arteries were obtained from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8-quinolinequinone (LY83583). Following pre-constriction with U46619, 10 μmol/L LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries. Both constrictor and relaxant actions of LY83583 were inhibited by superoxide dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in α-toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot), was enhanced by LY83583 in pulmonary artery only. However, in both artery types, changes in tension were closely correlated with changes in phosphorylation of the 20 kDa myosin light chain as well as changes in [Ca2+]i (as measured with Fura PE-3), with LY83583 causing increases in pulmonary and decreases in mesenteric arteries. When U46619 was replaced by 30 mmol/L K+, all changes in [Ca2+]i were abolished and LY83583 constricted both artery types. The KV channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in mesenteric artery without affecting constriction in pulmonary artery. However, LY83583 caused a similar hyperpolarizing shift in the steady-state activation of KV current in isolated smooth muscle cells of both artery types. Superoxide only causes Rho-kinase-dependent Ca2+ sensitization in pulmonary artery, resulting in constriction, and whilst it opens KV channels in both artery types, this only results in relaxation in mesenteric.
Safety of Nighttime 2-Hour Suspension of Basal Insulin in Pump-Treated Type 1 Diabetes Even in the Absence of Low Glucose
Authors: Jennifer L. Sherr, Miladys Palau Collazo, Eda Cengiz, Camille Michaud, Lori Carria, Amy T. Steffen, Kate Weyman, Melinda Zgorski, Eileen Tichy, William V. Tamborlane, Stuart A. Weinzimer
Journal: Diabetes Care (2013)

OBJECTIVE An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood β-hydroxybutyrate levels despite widely varying glucose values prior to the suspension. RESEARCH DESIGN AND METHODS Subjects measured blood glucose and blood β-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m. RESULTS In 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood β-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P &amp;lt; 0.0001), and the frequency of fasting hypoglycemia decreased the morning following suspend nights (P &amp;lt; 0.0001). Morning blood β-hydroxybutyrate levels were slightly higher after suspension (0.13 ± 0.14 vs. 0.09 ± 0.11 mmol/L, P = 0.053), but the difference was not clinically important. CONCLUSIONS Systems that suspend basal insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension.
Pharmacologic and Surgical Management of Obesity in Primary Care: A Clinical Practice Guideline from the American College of Physicians
Authors: Vincenza Snow, Patricia Barry, Nick Fitterman, Amir Qaseem, Kevin Weiss
Journal: Annals of Internal Medicine (2005)

This guideline is based on the evidence report and accompanying background papers developed by the Southern California Evidence-Based Practice Center. The American College of Physicians nominated this topic to the Agency for Healthcare Research and Quality Evidence-Based Practice Center program as part of a concerted effort to complement the guidelines of the U.S. Preventive Services Task Force. The College recommends that all clinicians refer to the Task Force recommendations as part of an overall strategy for managing overweight and obesity, which should always include appropriate diet and exercise for all patients who are overweight or obese. The intent of this guideline is to provide recommendations based on a review of the evidence on pharmacologic and surgical treatments of obesity. The target audience is all clinicians caring for obese patients, defined as a body mass index of 30 kg/m2 or greater. This guideline is not intended to be used by commercial weight loss centers or for direct-to-consumer marketing by manufacturers and does not apply to patients with body mass indices below 30 kg/m2. *This paper, written by Vincenza Snow, MD; Patricia Barry, MD, MPH; Nick Fitterman, MD; Amir Qaseem, MD, PhD, MHA; and Kevin Weiss, MD, MPH, was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (ACP): Kevin Weiss, MD, MPH (Chair); Mark Aronson, MD; Patricia Barry, MD, MPH; Donald E. Casey Jr., MD, MPH, MBA; J. Thomas Cross Jr., MD, MPH; Nick Fitterman, MD; E. Rodney Hornbake, MD; Douglas K. Owens, MD; and Katherine D. Sherif, MD. Approved by the ACP Board of Regents in October 2004.
A New Test for Detecting Recent Positive Selection that is Free from the Confounding Impacts of Demography
Authors: H. Li
Journal: Molecular Biology and Evolution (2010)

It has been a long-standing interest in evolutionary biology to search for the traces of recent positive Darwinian selection in organisms. However, such efforts have been severely hindered by the confounding signatures of demography. As a consequence, neutrality tests often lead to false inference of positive selection because they detect the deviation from the standard neutral model. Here, using the maximum frequency of derived mutations (MFDM) to examine the unbalanceness of the tree of a locus, I propose a statistical test that is analytically free from the confounding effects of varying population size and has a high statistical power (up to 90.5%) to detect recent positive selection. When compared with five well-known neutrality tests for detecting selection (i.e., Tajima’s D test, Fu and Li’s D test, Fay and Wu’s H test, the E test, and the joint DH test), the MFDM test is indeed the only one free from the confounding impacts of bottlenecks and size expansions. Simulations based on wide-range parameters demonstrated that the MFDM test is robust to background selection, population subdivision, and admixture (including hidden population structure). Moreover, when two high-frequency mutations are introduced, the MFDM test is robust to the misinference of derived and ancestral variants of segregating sites due to multiple hits. Finally, the sensitivity of the MFDM test in detecting balancing selection is also discussed. In summary, it is demonstrated that summary statistics based on tree topology can be used to detect selection, and this work provides a reliable method that can distinguish selection from demography even when DNA polymorphism data from only one locus is available.
Overdiagnosis and Overtreatment in Cancer
Authors: Laura J. Esserman, Ian M. Thompson, Brian Reid
Journal: JAMA (2013)

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Tom22', an 8-kDa trans-Site Receptor in Plants and Protozoans, Is a Conserved Feature of the TOM Complex That Appeared Early in the Evolution of Eukaryotes
Authors: D. Macasev
Journal: Molecular Biology and Evolution (2004)

One of the earliest events in the evolution of mitochondria was the development a means to translocate proteins made in the cytosol into the "protomitochondrion." How this was achieved remains uncertain, and the nature of the earliest version of the protein translocation machinery is not known. Comparative sequence analysis suggests three subunits, Tom40, Tom7, and Tom22 as common elements of the protein translocase in the mitochondrial outer membrane in diverse extant eukaryotes. Tom22, the 22-kDa subunit, plays a critical role in the function of this complex in fungi and animals, and we show that an 8-kDa subunit of the plant translocase is a truncated form of Tom22. It has a single transmembrane segment conforming in sequence to the same region of Tom22 from other eukaryotic lineages and a short carboxy-terminal trans domain located in the mitochondrial intermembrane space. The trans domain from the Arabidopsis thaliana protein functions in yeast lacking their own Tom22 by complementing protein import defects and restoring cell growth. Moreover, we have identified orthologs of Tom22, Tom7, and Tom40 in diverse eukaryotes such as the diatom Phaeodactylum tricornutum, the amoebic slime Dictyostelium discoideum, and the protozoan parasite Plasmodium falciparum. This finding strongly suggests these subunits as the core of the protein translocase in the earliest mitochondria.
Acute Pesticide Illnesses Associated with Off-Target Pesticide Drift from Agricultural Applications: 11 States, 1998–2006
Authors: Soo-Jeong Lee, Louise Mehler, John Beckman, Brienne Diebolt-Brown, Joanne Prado, Michelle Lackovic, Justin Waltz, Prakash Mulay, Abby Schwartz, Yvette Mitchell, Stephanie Moraga-McHaley, Rita Gergely, Geoffrey M. Calvert
Journal: Environmental Health Perspectives (2011)

Pesticides are widely used in agriculture, and off-target pesticide drift exposes workers and the public to harmful chemicals.We estimated the incidence of acute illnesses from pesticide drift from outdoor agricultural applications and characterized drift exposure and illnesses.Data were obtained from the National Institute for Occupational Safety and Health's Sentinel Event Notification System for Occupational Risks-Pesticides program and the California Department of Pesticide Regulation. Drift included off-target movement of pesticide spray, volatiles, and contaminated dust. Acute illness cases were characterized by demographics, pesticide and application variables, health effects, and contributing factors.From 1998 through 2006, we identified 2,945 cases associated with agricultural pesticide drift from 11 states. Our findings indicate that 47% were exposed at work, 92% experienced low-severity illness, and 14% were children (< 15 years). The annual incidence ranged from 1.39 to 5.32 per million persons over the 9-year period. The overall incidence (in million person-years) was 114.3 for agricultural workers, 0.79 for other workers, 1.56 for nonoccupational cases, and 42.2 for residents in five agriculture-intensive counties in California. Soil applications with fumigants were responsible for the largest percentage (45%) of cases. Aerial applications accounted for 24% of cases. Common factors contributing to drift cases included weather conditions, improper seal of the fumigation site, and applicator carelessness near nontarget areas.Agricultural workers and residents in agricultural regions had the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard, causing large drift incidents. Our findings highlight areas where interventions to reduce off-target drift could be focused.
Cost-Effectiveness of Coronary Stenting in Acute Myocardial Infarction
Authors: David J. Cohen, Deborah A. Taira, Ronna Berezin, David A. Cox, Marie-Claude Morice, Gregg W. Stone, Cindy L. Grines
Journal: Circulation (2001)

Although several randomized trials have demonstrated that coronary stenting improves angiographic and clinical outcomes for patients with acute myocardial infarction (AMI), the cost-effectiveness of this practice is unknown. The objective of the present study was to evaluate the long-term costs and cost-effectiveness (C/E) of coronary stenting compared with primary balloon angioplasty as treatment for AMI. Methods and Results- Between December 1996 and November 1997, 900 patients with AMI were randomized to undergo balloon angioplasty (PTCA, n=448) or coronary stenting (n=452). Detailed resource utilization and cost data were collected for each patient's initial hospitalization and for 1 year after randomization. Compared with conventional PTCA, stenting increased procedural costs by approximately $2000 per patient ($6538+/-1778 versus $4561+/-1598, P<0.001). During the 1-year follow-up period, stenting was associated with significant reductions in the need for repeat revascularization and rehospitalization. Although follow-up costs were significantly lower with stenting ($3613+/-7743 versus $4592+/-8198, P=0.03), overall 1-year costs remained approximately $1000/patient higher with stenting than with PTCA ($20 571+/-10 693 versus 19 595+/-10 990, P=0.02). The C/E ratio for stenting compared with PTCA was $10 550 per repeat revascularization avoided. In analyses that incorporated recent changes in stent technology and pricing, the 1-year cost differential fell to <$350/patient, and the C/E ratio improved to $3753 per repeat revascularization avoided. The cost-utility ratio for primary stenting was <$50 000 per quality-adjusted life year gained only if stenting did not increase 1-year mortality by >0.2% compared with PTCA.As performed in Stent-PAMI, primary stenting for AMI increased 1-year medical care costs compared with primary PTCA. The overall cost-effectiveness of primary stenting depends on the societal value attributed to avoidance of symptomatic restenosis, as well as on the relative mortality rates of primary PTCA and stenting.
Effect of sodium phenobarbital on bilirubin metabolism in an infant with congenital, nonhemolytic, unconjugated hyperbilirubinemia, and kernicterus
Authors: John F. Crigler, Norman I. Gold
Journal: Journal of Clinical Investigation (1969)

Sodium phenobarbital and various hormones, compounds capable of hepatic enzyme induction, were given to an infant boy with congenital, nonhemolytic, unconjugated, hyperbilirubinemia and severe kernicterus for prolonged periods between the ages of 2 and 25 months to determine their effect on serum bilirubin concentrations. Phenobarbital, 5 mg/day orally, on two occasions decreased serum bilirubin concentrations approximately threefold over a period of 30 days. Withdrawal of phenobarbital after the first study resulted in a gradual (30 days) return of serum bilirubin to pretreatment levels. The lower serum bilirubin concentrations observed when phenobarbital therapy was reinstituted were maintained for 61 days on 2.5 mg/kg per day of the drug. Orally administered L-triiodothyronine, 0.05-0.1 mg/day for 71 days, intramuscular human growth hormone, 1 mg/day for 21 days, and testosterone propionate, 0.1 mg/day for 9 days, did not decrease serum bilirubin levels below lowest control values of 18 mg/100 ml.Bilirubin-(3)H was administered twice before and once with bilirubin-(14)C during phenobarbital therapy to study the kinetics of bilirubin metabolism. Results of the first and second control studies and of the bilirubin-(3)H and bilirubin-(14)C phenobarbital studies, respectively, were as follows: total body bilirubin pools, 200, 184, 73, and 72 mg; half-lives, 111, 84, 37, and 39 hr; and turnover, 30, 37, 33, and 31 mg/day. The data show that the approximate threefold decrease in serum bilirubin concentration and total body pool resulted from a comparable decrease in bilirubin half-life without a significant change in turnover. In vitro histological (electron microscopy) and enzymological studies of liver obtained by surgical biopsies before and during phenobaribtal administration showed that both the hepatocyte content of agranular endoplasmic reticulum (AER) and the ability of liver homogenate to conjugate p-nitrophenol were significantly increased during phenobarbital treatment. The observations suggest that phenobarbital affects bilirubin metabolism by the induction of an enzyme(s) with a slow rate(s) of degradation (or rapid rate of degradation with limited capacity).
The Influence of New European Union Driver’s License Legislation on Reporting of Severe Hypoglycemia by Patients With Type 1 Diabetes
Authors: Ulrik Pedersen-Bjergaard, Louise Færch, Marie-Louise Allingbjerg, Rikke Agesen, Birger Thorsteinsson
Journal: Diabetes Care (2014)

We test the hypotheses that the implementation in Denmark of new, stricter European Union (EU) legislation on driver's licensing, with the purpose to improve traffic safety in January 2012, has reduced the self-reported rate of severe hypoglycemia in a routine clinical setting and that anonymous reporting results in higher event rates.A cohort of 309 patients with type 1 diabetes was recruited in the outpatient clinic at Nordsjællands University Hospital Hillerød, Denmark. Yearly numbers of severe hypoglycemic events defined by need for treatment assistance from another person were retrieved from medical records in the years 2010 to 2012 and retrospectively reported in an anonymous questionnaire. Data from medical records in 2012 were compared with those from 2010 and 2011 and with data from the questionnaire.Reported rates of severe hypoglycemia in the medical records were reduced by 55% in 2012 compared with the prior years (P = 0.034). The proportion of subjects reporting recurrent episodes was grossly reduced from 5.6 to 1.5% (P = 0.014). Compared with anonymous reporting in the questionnaire, the rate of severe hypoglycemia in 2012 was 70% lower (P < 0.001).Reporting of severe hypoglycemia by patients with type 1 diabetes is significantly reduced following implementation of EU driver's licensing legislation that implies withdrawal of driver's licensing in case of recurrent episodes within 1 year. The resulting burden of concealed severe hypoglycemia may impair the safety of affected patients and unintentionally paradoxically reduce the general traffic safety.