tbuckley/cabot-search huggingface dataset:
The Incidence of Venous Thromboembolism in Family Members of Patients with Factor V Leiden Mutation and Venous Thrombosis
Authors: S Middeldorp, C M Henkens, M M Koopman, E C van Pampus, K Hamulyák, J van der Meer, M H Prins, H R Büller
Journal: Annals of Internal Medicine (1998)

Background: The factor V Leiden mutation is a genetic defect associated with an increased incidence of venous thromboembolism. When the incidence of venous thromboembolism in relatives of patients known to have the mutation outweighs the disadvantages of prophylactic strategies, family screening may be necessary. Objective: To determine the incidence of venous thromboembolism in first-degree relatives of symptomatic carriers of the factor V Leiden mutation. Design: Retrospective blinded study. Setting: University hospitals. Participants: 437 first-degree relatives of 112 heterozygous propositi and 30 relatives of 6 homozygous propositi. Measurements: Before DNA testing, information on previous venous thromboembolism and concomitant risk factors was obtained. Relatives with and without the FV: Q506 mutation were compared. Results: The annual incidence of thromboembolism in relatives of heterozygous propositi was 0.45% (95% CI, 0.28% to 0.61%) in those with the mutation and 0.10% (CI, 0.02% to 0.19%) in those without the mutation (relative risk, 4.2 [CI, 1.8 to 9.9]). Among carriers, the incidence increased from 0.25% (CI, 0.12% to 0.49%) in the 15- to 30-year-old age group to 1.1% (CI, 0.24% to 3.33%) in persons older than 60 years of age. Half of the episodes of venous thromboembolism occurred spontaneously, 20% were related to surgery, and 30% were associated with pregnancy or use of oral contraceptives. Conclusions: The observed low annual risk for venous thromboembolism in persons carrying the factor V Leiden mutation does not seem to outweigh the risks for bleeding associated with coumarin prophylaxis or justify discouragement of the use of oral contraceptives. A general policy of screening the families of all patients with the factor V Leiden mutation does not seem to be indicated. The observations in this moderate-size, retrospective study need to be confirmed by prospective follow-up studies.
Soluble Guanylate Cyclase Activator Reverses Acute Pulmonary Hypertension and Augments the Pulmonary Vasodilator Response to Inhaled Nitric Oxide in Awake Lambs
Authors: Oleg V. Evgenov, Fumito Ichinose, Natalia V. Evgenov, Mark J. Gnoth, George E. Falkowski, Yuchiao Chang, Kenneth D. Bloch, Warren M. Zapol
Journal: Circulation (2004)

Inhaled nitric oxide (NO) is a potent and selective pulmonary vasodilator, which induces cGMP synthesis by activating soluble guanylate cyclase (sGC) in ventilated lung regions. Carbon monoxide (CO) has also been proposed to influence smooth muscle tone via activation of sGC. We examined whether direct stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and augment the pulmonary responses to inhaled NO or CO.In awake, instrumented lambs, the thromboxane analogue U-46619 was intravenously administered to increase mean pulmonary arterial pressure to 35 mm Hg. Intravenous infusion of BAY 41-2272 (0.03, 0.1, and 0.3 mg x kg(-1) x h(-1)) reduced mean pulmonary arterial pressure and pulmonary vascular resistance and increased transpulmonary cGMP release in a dose-dependent manner. Larger doses of BAY 41-2272 also produced systemic vasodilation and elevated the cardiac index. N(omega)-nitro-l-arginine methyl ester abolished the systemic but not the pulmonary vasodilator effects of BAY 41-2272. Furthermore, infusing BAY 41-2272 at 0.1 mg x kg(-1) x h(-1) potentiated and prolonged the pulmonary vasodilation induced by inhaled NO (2, 10, and 20 ppm). In contrast, inhaled CO (50, 250, and 500 ppm) had no effect on U-46619-induced pulmonary vasoconstriction before or during administration of BAY 41-2272.In lambs with acute pulmonary hypertension, BAY 41-2272 is a potent pulmonary vasodilator that augments and prolongs the pulmonary vasodilator response to inhaled NO. Direct pharmacological stimulation of sGC, either alone or in combination with inhaled NO, may provide a novel approach for the treatment of pulmonary hypertension.
Testing the Drug Substitution Switching-Addictions Hypothesis
Authors: Carlos Blanco, Mayumi Okuda, Shuai Wang, Shang-Min Liu, Mark Olfson
Journal: JAMA Psychiatry (2014)

Adults who remit from a substance use disorder (SUD) are often thought to be at increased risk for developing another SUD. A greater understanding of the prevalence and risk factors for drug substitution would inform clinical monitoring and management.To determine whether remission from an SUD increases the risk of onset of a new SUD after a 3-year follow-up compared with lack of remission from an SUD and whether sociodemographic characteristics and psychiatric disorders, including personality disorders, independently predict a new-onset SUD.A prospective cohort study where data were drawn from a nationally representative sample of 34 653 adults from the National Epidemiologic Survey on Alcohol and Related Conditions. Participants were interviewed twice, 3 years apart (wave 1, 2001-2002; wave 2, 2004-2005).We compared new-onset SUDs among individuals with at least 1 current SUD at wave 1 who did not remit from any SUDs at wave 2 (n = 3275) and among individuals with at least 1 current SUD at wave 1 who remitted at wave 2 (n = 2741).Approximately one-fifth (n = 2741) of the total sample had developed a new-onset SUD at the wave 2 assessment. Individuals who remitted from 1 SUD during this period were significantly less likely than those who did not remit to develop a new SUD (13.1% vs 27.2%, P < .001). Results were robust to sample specification. An exception was that remission from a drug use disorder increased the odds of a new SUD (odds ratio [OR] = 1.46; 95% CI, 1.11-1.92). However, after adjusting for the number of SUDs at baseline, remission from drug use disorders decreased the odds of a new-onset SUD (OR = 0.66; 95% CI, 0.46-0.95) whereas the number of baseline SUDs increased those odds (OR=1.68; 95% CI, 1.43-1.98). Being male, younger in age, never married, having an earlier age at substance use onset, and psychiatric comorbidity significantly increased the odds of a new-onset SUD during the follow-up period.As compared with those who do not remit from an SUD, remitters have less than half the risk of developing a new SUD. Contrary to clinical lore, achieving remission does not typically lead to drug substitution but rather is associated with a lower risk of new SUD onsets.
Primary prevention of colorectal cancer with low-dose aspirin in combination with endoscopy: a cost-effectiveness analysis
Authors: Cesare Hassan, Douglas K Rex, Gregory S Cooper, Angelo Zullo, Robert Launois, Robert Benamouzig
Journal: Gut (2011)

<h3>Objective</h3> Low-dose aspirin reduces colorectal cancer (CRC) incidence and mortality. Recently, the aspirin effect has been shown to occur primarily in the proximal colon. Colonoscopy has been either less effective or ineffective in the proximal compared to the distal colon. The authors assessed the cost-effectiveness of adding low-dose aspirin to a simulated screening with colonoscopy or sigmoidoscopy. <h3>Design</h3> A Markov model comparing the strategies of 10-year colonoscopy or sigmoidoscopy screening and the combination of either of the two with low-dose aspirin in 100 000 subjects aged 50 years until death was constructed. Proximal and distal CRC prevention rates with endoscopy or aspirin were extracted from the literature. Screening and aspirin prevention were simulated to stop at 80 years. The cost of aspirin and aspirin-related complications, as well as aspirin-related mortality, was included. Incremental cost-effectiveness ratios between the different strategies were calculated. Sensitivity and probabilistic analyses were also performed. <h3>Results</h3> The addition of low-dose aspirin to colonoscopy and sigmoidoscopy screening increased the CRC death prevention rate from 68% and 39% to 81% and 69%, respectively. Lifetime aspirin-related mortality appeared to be 0.1%. Because of the substantial reduction in CRC care, the addition of aspirin to colonoscopy and sigmoidoscopy screening was cost-effective (incremental cost-effectiveness ratio: US$5413 per life-year saved) and cost saving (US$278 per person), respectively. When the proximal CRC prevention rate with colonoscopy was increased 56% to 73% from the baseline, the addition of aspirin was no longer cost-effective. The addition of aspirin to colonoscopy and sigmoidoscopy was a cost-effective strategy in 52% and 94% of the scenarios at probabilistic analysis. <h3>Conclusions</h3> When assuming a suboptimal efficacy of endoscopy in preventing CRC, the addition of low-dose aspirin may be an effective and cost-effective strategy, mainly because of its high efficacy in preventing proximal CRC.
Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex
Authors: Volney L Sheen, Vijay S Ganesh, Meral Topcu, Guillaume Sebire, Adria Bodell, R Sean Hill, P Ellen Grant, Yin Yao Shugart, Jaime Imitola, Samia J Khoury, Renzo Guerrini, Christopher A Walsh
Journal: Nature Genetics (2003)
Effect of upper airway cooling and CO2 on diaphragm and geniohyoid muscle activity in the rat
Authors: KD O'Halloran, AK Curran, A Bradford
Journal: European Respiratory Journal (1996)

Upper airway (UA) reflexes play an important role in regulating breathing and UA patency, but the effects of UA CO2 and cooling on ventilation and UA muscle activity are controversial. Diaphragm and geniohyoid electromyographic activities were recorded in anaesthetized rats, breathing spontaneously through a low-cervical tracheostomy. Warmed, humidified air containing 0 or 10% CO2 and cooled, room humidity air were applied at constant flow to the UA through a high- cervical tracheostomy. Spontaneous tracheal airflow, UA airflow and temperature, blood pressure, and rectal temperature were recorded. In all animals, the geniohyoid muscle had phasic inspiratory activity, which slightly preceded diaphragmatic activity. CO2 had no effect on mean peak integrated diaphragmatic activity and variable effects on geniohyoid activity. The coefficients of variation of these activities were unaffected by CO2. Similar results were obtained following bilateral mid-cervical vagotomy. Cool air decreased respiratory frequency (78+/-8%) (mean+/-SD % of control), peak inspiratory flow (78+/-5%) and diaphragmatic activity (77+/-4%), and increased geniohyoid activity (149+/-11%). Cutting the superior laryngeal nerves abolished these effects. In conclusion, whilst moderate upper airway cooling inhibits breathing and excites geniohyoid muscle activity, upper airway carbon dioxide has minimal effect.
Prospective Study of Shift Work and Risk of Coronary Heart Disease in Women
Authors: Ichiro Kawachi, Graham A. Colditz, Meir J. Stampfer, Walter C. Willett, JoAnn E. Manson, Frank E. Speizer, Charles H. Hennekens
Journal: Circulation (1995)

Background The purpose of this study was to examine prospectively the relation of shift work to risk of coronary heart disease (CHD) in a cohort of women. Methods and Results An ongoing prospective cohort of US female nurses, in whom we assessed (in 1988) the total number of years during which they worked rotating night shifts (at least three nights per month in addition to day and evening shifts), included 79 109 women, 42 to 67 years old in 1988, who were free of diagnosed CHD and stroke. Incident CHD was defined as nonfatal myocardial infarction and fatal CHD. During 4 years of follow-up (1988 to 1992), 292 cases of incident CHD (248 nonfatal myocardial infarction and 44 fatal CHD) occurred. The age-adjusted relative risk of CHD was 1.38 (95% CI, 1.08 to 1.76) in women who reported ever doing shift work compared with those who had never done so. The excess risk persisted after adjustment for cigarette smoking and a variety of other cardiovascular risk factors. Compared with women who had never done shift work, the multivariate adjusted relative risks of CHD were 1.21 (95% CI, 0.92 to 1.59) among women reporting less than 6 years and 1.51 (95% CI, 1.12 to 2.03) among those reporting 6 or more years of rotating night shifts. Conclusions These data are compatible with the possibility that 6 or more years of shift work may increase the risk of CHD in women.
CONTROLLED TRIAL OF ADJUVANT CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE, METHOTREXATE, AND FLUOROURACIL FOR BREAST CANCER
Authors: A. Howell, W.D. George, D. Crowther, R.D. Rubens, R.D. Bulbrook, H. Bush, J.M.T. Howat, R.A. Sellwood, J.L. Hayward, I.S. Fentiman, M. Chaudary
Journal: The Lancet (1984)
Quantitative analysis of the acute response to haemorrhage of the renin-angiotensin-vasoconstrictor feedback loop in areflexic dogs
Authors: R. B. BROUGH, A. W. COWLEY, A. C. GUYTON
Journal: Cardiovascular Research (1975)

The importance of the renin-angiotensin-vasoconstrictor system during haemorrhagic hypotension was quantitated in 44 areflexic dogs by determining the ability of the arterial pressure to recover following haemorrhage to 8.8 kPa (66 mm Hg). In 30 animals with intact kidneys, the arterial pressure following haemorrhage rose to a new steady-state level averaging 11.7 kPa (88 mm Hg), which represented 65.3 ± 1.8 (SE) % compensation. In 18 nephrectomized animals only 24.4 ± 1.5% compensation occurred. The system exhibited a relatively rapid time course for pressure compensation with the new steady state occurring 19.2 ±2.0 min after haemorrhage. Following reinfusion of blood, the pressure returned to the pre-haemorrhage level in 19.2 ± 3.0 min. Arterial renin activity was significantly elevated following haemorrhage in the intact kidney group and unchanged in the anephric group. The arterial pressure compensation of two animals with intact kidneys was significantly reduced when the angiotensin-converting enzyme inhibitor (SQ 20881) was infused before the haemorrhage. The results are consistent with a renin-angiotensin-vasoconstrictor mechanism of arterial pressure compensation and indicate that this mechanism possesses sufficient gain and time response characteristics to play a homeostatically significant role during haemorrhagic hypotension.
Vitamins C and E to Prevent Complications of Pregnancy-Associated Hypertension
Authors: James M. Roberts, Leslie Myatt, Catherine Y. Spong, Elizabeth A. Thom, John C. Hauth, Kenneth J. Leveno, Gail D. Pearson, Ronald J. Wapner, Michael W. Varner, John M. Thorp, Brian M. Mercer, Alan M. Peaceman, Susan M. Ramin, Marshall W. Carpenter, Philip Samuels, Anthony Sciscione, Margaret Harper, Wendy J. Smith, George Saade, Yoram Sorokin, Garland B. Anderson
Journal: New England Journal of Medicine (2010)

Oxidative stress has been proposed as a mechanism linking the poor placental perfusion characteristic of preeclampsia with the clinical manifestations of the disorder. We assessed the effects of antioxidant supplementation with vitamins C and E, initiated early in pregnancy, on the risk of serious adverse maternal, fetal, and neonatal outcomes related to pregnancy-associated hypertension.
Comparison of a Strategy Favoring Early Surgical Resection vs a Strategy Favoring Watchful Waiting in Low-Grade Gliomas
Authors: Asgeir S Jakola, Kristin S Myrmel, Roar Kloster, Sverre H Torp, Sigurd Lindal, Geirmund Unsgård, Ole Solheim
Journal: JAMA (2012)

There are no controlled studies on surgical treatment of diffuse low-grade gliomas (LGGs), and management is controversial.To examine survival in population-based parallel cohorts of LGGs from 2 Norwegian university hospitals with different surgical treatment strategies.Both neurosurgical departments are exclusive providers in adjacent geographical regions with regional referral practices. In hospital A diagnostic biopsies followed by a "wait and scan" approach has been favored (biopsy and watchful waiting), while early resections have been advocated in hospital B (early resection). Thus, the treatment strategy in individual patients has been highly dependent on the patient's residential address. Histopathology specimens from all adult patients diagnosed with LGG from 1998 through 2009 underwent a blinded histopathological review to ensure uniform classification and inclusion. Follow-up ended April 11, 2011. There were 153 patients (66 from the center favoring biopsy and watchful waiting and 87 from the center favoring early resection) with diffuse LGGs included.The prespecified primary end point was overall survival based on regional comparisons without adjusting for administered treatment. Results Initial biopsy alone was carried out in 47 (71%) patients served by the center favoring biopsy and watchful waiting and in 12 (14%) patients served by the center favoring early resection (P < .001). Median follow-up was 7.0 years (interquartile range, 4.5-10.9) at the center favoring biopsy and watchful waiting and 7.1 years (interquartile range, 4.2-9.9) at the center favoring early resection (P=.95). The 2 groups were comparable with respect to baseline parameters. Overall survival was significantly better with early surgical resection (P=.01). Median survival was 5.9 years (95% CI, 4.5-7.3) with the approach favoring biopsy only while median survival was not reached with the approach favoring early resection. Estimated 5-year survival was 60% (95% CI, 48%-72%) and 74% (95% CI, 64%-84%) for biopsy and watchful waiting and early resection, respectively. In an adjusted multivariable analysis the relative hazard ratio was 1.8 (95% CI, 1.1-2.9, P=.03) when treated at the center favoring biopsy and watchful waiting.For patients in Norway with LGG, treatment at a center that favored early surgical resection was associated with better overall survival than treatment at a center that favored biopsy and watchful waiting. This survival benefit remained after adjusting for validated prognostic factors.
Amygdala-Dependent Fear Is Regulated by <i>Oprl1</i> in Mice and Humans with PTSD
Authors: Raül Andero, Shaun P. Brothers, Tanja Jovanovic, Yen T. Chen, Hasib Salah-Uddin, Michael Cameron, Thomas D. Bannister, Lynn Almli, Jennifer S. Stevens, Bekh Bradley, Elisabeth B. Binder, Claes Wahlestedt, Kerry J. Ressler
Journal: Science Translational Medicine (2013)

The amygdala-dependent molecular mechanisms driving the onset and persistence of posttraumatic stress disorder (PTSD) are poorly understood. Recent observational studies have suggested that opioid analgesia in the aftermath of trauma may decrease the development of PTSD. Using a mouse model of dysregulated fear, we found altered expression within the amygdala of the Oprl1 gene (opioid receptor-like 1), which encodes the amygdala nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic and central amygdala infusion of SR-8993, a new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, a single-nucleotide polymorphism (SNP) within OPRL1 is associated with a self-reported history of childhood trauma and PTSD symptoms (n = 1847) after a traumatic event. This SNP is also associated with physiological startle measures of fear discrimination and magnetic resonance imaging analysis of amygdala-insula functional connectivity. Together, these data suggest that Oprl1 is associated with amygdala function, fear processing, and PTSD symptoms. Further, our data suggest that activation of the Oprl1/NOP receptor may interfere with fear memory consolidation, with implications for prevention of PTSD after a traumatic event.
Treatment of oligodendroglioma: An update
Authors: N A Paleologos, J G Cairncross
Journal: Neuro-Oncology (1999)

Oligodendrogliomas are rare primary brain tumors. Significant attention has recently been focused on these interesting neoplasms because of their unique chemosensitivity and the durability of some of these responses. Surgery and radiation continue to play important roles in the treatment of oligodendrogliomas. Molecular genetic analyses have given new insight into the allelic deletions that distinguish these tumors and their progression from indolent to more aggressive forms. In the future, molecular genetic analysis may guide therapeutic decisions concerning patients with oligodendroglioma and may help us learn more about how to best treat other malignant brain neoplasms.
Reader's guide to critical appraisal of cohort studies: 2. Assessing potential for confounding
Authors: Muhammad Mamdani, Kathy Sykora, Ping Li, Sharon-Lise T Normand, David L Streiner, Peter C Austin, Paula A Rochon, Geoffrey M Anderson
Journal: BMJ (2005)

Although confounding is an important problem of cohort studies, its effects can be minimised to enable valid comparison 

In cohort studies, who does or does not receive an intervention is determined by practice patterns, personal choice, or policy decisions. This raises the possibility that the intervention and comparison groups may differ in characteristics that affect the study outcome, a problem called selection bias. If these characteristics have independent effects on the observed outcome in each group, they will create differences in outcomes between the groups apart from those related to the interventions being assessed. This effect is known as confounding.1 In the first paper in the series we dealt with the design and use of cohort studies and how to identify selection bias.2 This paper focuses on the definition and assessment of confounders.

For a characteristic to be a confounder in a particular study, it must meet two criteria.1 The first is that it must be related to the outcome in terms of prognosis or susceptibility. For example, in the study of the association between antipsychotic use and hip fracture that we considered in the first paper,2 age is known to be related to risk of hip fracture and therefore has the potential to be a confounder.

The second criterion that defines a confounder is that the distribution of the characteristic is different in the groups being compared. It can differ in terms of either the mean or the degree of variation or variability in that characteristic. For example, for age to be a confounder in a cohort study, either the average age or the variation in the age in the groups being compared would have to be different. Assessing variation as well as average values is important because groups can have the same average value …