tbuckley/cabot-search huggingface dataset:
Reporting Bias in Clinical Trials Investigating the Efficacy of Second-Generation Antidepressants in the Treatment of Anxiety Disorders
Authors: Annelieke M. Roest, Peter de Jonge, Craig D. Williams, Ymkje Anna de Vries, Robert A. Schoevers, Erick H. Turner
Journal: JAMA Psychiatry (2015)

<h3>Importance</h3> Studies have shown that the scientific literature has overestimated the efficacy of antidepressants for depression, but other indications for these drugs have not been considered. <h3>Objective</h3> To examine reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantify the extent to which these biases inflate estimates of drug efficacy. <h3>Data Sources and Study Selection</h3> We included reviews obtained from the US Food and Drug Administration (FDA) for premarketing trials of 9 second-generation antidepressants in the treatment of anxiety disorders. A systematic search for matching publications (until December 19, 2012) was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. <h3>Data Extraction and Synthesis</h3> Double data extraction was performed for the FDA reviews and the journal articles. The Hedges<i>g</i>value was calculated as the measure of effect size. <h3>Main Outcomes and Measures</h3> Reporting bias was examined and classified as study publication bias, outcome reporting bias, or spin (abstract conclusion not consistent with published results on primary end point). Separate meta-analyses were conducted for the 2 sources, and the effect of publication status on the effect estimates was examined using meta-regression. <h3>Results</h3> The findings of 41 of the 57 trials (72%) were positive according to the FDA, but 43 of the 45 published article conclusions (96%) were positive (<i>P</i> &lt; .001). Trials that the FDA determined as positive were 5 times more likely to be published in agreement with that determination compared with trials determined as not positive (risk ratio, 5.20; 95% CI, 1.87 to 14.45;<i>P</i> &lt; .001). We found evidence for study publication bias (<i>P</i> &lt; .001), outcome reporting bias (<i>P</i> = .02), and spin (<i>P</i> = .02). The pooled effect size based on the published literature (Hedges<i>g</i>, 0.38; 95% CI, 0.33 to 0.42;<i>P</i> &lt; .001) was 15% higher than the effect size based on the FDA data (Hedges<i>g</i>, 0.33; 95% CI, 0.29 to 0.38;<i>P</i> &lt; .001), but this difference was not statistically significant (β = 0.04; 95% CI, –0.02 to 0.10;<i>P</i> = .18). <h3>Conclusions and Relevance</h3> Various reporting biases were present for trials on the efficacy of FDA-approved second-generation antidepressants for anxiety disorders. Although these biases did not significantly inflate estimates of drug efficacy, reporting biases led to significant increases in the number of positive findings in the literature.
Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans
Authors: A. S Jordan, A. Wellman, R. C Heinzer, Y.-L. Lo, K. Schory, L. Dover, S. Gautam, A. Malhotra, D. P White
Journal: Thorax (2007)

Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA.Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred.During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation.Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.
Suction Apparatus for Ambulances
Authors: B. S. Baker
Journal: BMJ (1965)

<b>Background:</b> There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. <b>Methods:</b> Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. <b>Results:</b> Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 <i>v</i> 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC<sub>20</sub>) &lt;8 mg/ml: 38% <i>v</i> 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). <b>Conclusion:</b> Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.
Lung cancer in women
Authors: D. J. B. Ashley, H. D. Davies
Journal: Thorax (1969)

Eighty-three instances of lung cancer in women are presented. The frequency of the condition is lower in women than in men but the tumours in women tend to be less well differentiated and are less likely to be resectable than in men. The frequency of extrathoracic metastases at the time of diagnosis is greater in women than in men. It is suggested that the immunological defences of women are better than those of men because of sex-linked genes, present in double dose in the female, which are concerned with the immunological mechanisms, and that the clinically apparent tumours are those which, by virtue of their greater intrinsic malignancy, can overcome the defence mechanisms.
Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia
Authors: John H. Gilmore, Chaeryon Kang, Dianne D. Evans, Honor M. Wolfe, J. Keith Smith, Jeffrey A. Lieberman, Weili Lin, Robert M. Hamer, Martin Styner, Guido Gerig
Journal: American Journal of Psychiatry (2010)

Objective: Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Method: Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Results: Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Conclusions: Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.
Funding allocations for patients across England are far from fair, says MPs' report
Authors: A. O'Dowd
Journal: BMJ (2015)

The money allocated to doctor led commissioners of NHS services varies widely across England, undermining the government’s policy to achieve equal access for equal need, MPs have concluded. Primary care has also suffered unfairly, they said, as its share of national funding has fallen from 29% to 23% over 10 years despite its recognised importance in tackling health inequalities. On 9 January MPs on the parliamentary Public Accounts Committee published their report, Funding Healthcare: Making Allocations to Local Areas ,1 in which they warned that funding allocations across England were far from fair. The report said that, for 2014-15, the Department of Health and NHS England had allocated a total of £79bn (€100bn; $120bn) to local healthcare commissioners (equivalent to £1400 a person) through three channels:
An antecedent diagnosis of refractory anemia with excess blasts has no prognostic relevance in acute myeloid leukemia of older adult patients
Authors: S. Palmieri, A.M. D'Arco, M. Celentano, G. Mele, C. Califano, F. Pollio, M.R. D'Amico, F. Ferrara
Journal: Annals of Oncology (2006)
T-cell-mediated cytotoxic immune responses to F9 teratocarcinoma cells: cytolytic effector T cells lyse H-2-negative F9 cells and syngeneic spermatogonia.
Authors: H Wagner, A Starzinski-Powitz, M Röllinghoff, P Golstein, H Jakob
Journal: The Journal of Experimental Medicine (1978)

Murine thymus derived (T) lymphocytes primed in vivo to mouse 129 (H-2bc) derived H-2-negative F9 embryonal carcinoma cells and rechallenged in vitro with X-irradiated F9 stimulator cells differentiated into anti-F9 cell immune cytotoxic T lymphocytes (CTL). Using CBA mouse derived splenic responder T cells, F9 stimulator cells triggered a primary cytotoxic anti-F9 response. The CTL generated lysed the F9 antigen-positive target cells F9. PCC3 and PCC4, but not the F9 antigen-negative mouse 129 derived PYS tumor cells, nor LPS induced H-2bc blast cells. Mouse 129 anti-F9 cell antisera but not H-2k anti-H-2bc antisera blocked the lytic interaction with F9 target cells. Similarily unlabeled F9 cells but not H-2bc blast cells inhibited the anti-F9 cell cytotoxicity H-2k anti-F9 cell immune CTL were found to be cytotoxic for syngeneic spermatogonia, known to express the F9 antigen. The results suggest not only that CTL can recognize and lyse H-2-negative target cells, but also that CTL precursors can be sensitized against H-2-negative stimulator cells. From the data available it may be inferred that anti-F9 Cell immune CTL recognize the F9 antigen, known to be linked with the T/t locus. Since anti-F9 cell immune CTL lyse syngeneic spermatogonia, the system may be useful to analyze in vitro the induction and effector phase of a T-cell-mediated cytotoxic autoimmune orchitis.
Encephalopathy of thiamine deficiency: studies of intracerebral mechanisms
Authors: David W. McCandless, Steven Schenker
Journal: Journal of Clinical Investigation (1968)

Thiamine-deficient encephalopathy is characterized by morphologic lesions in the brainstem and less extensively in the cerebellum, but the early neurologic signs reverse rapidly and fully with thiamine, indicating a metabolic disorder. The suggested causal mechanisms of the encephalopathy involve two thiamine-dependent enzymes: (a) impairment of pyruvate decarboxylase activity with decreased cerebral energy (ATP) synthesis, and (b) reduction of transketolase activity with possible impairment of the hexose monophosphate shunt and subsequent decrease in NADPH formation. The latter may be important in maintaining glutathione in a reduced form (GSH), which apparently functions by keeping enzymes in a reduced (active) conformation. To examine some of these postulated mechanisms, in this study we measured pyruvate decarboxylase and transketolase activity, lactate, ATP and GSH levels in the cerebral cortex, cerebellum, and brainstem, and thiamine concentration in whole brain of rats with diet-induced low thiamine encephalopathy. Pair-fed and normally fed asymptomatic control animals were similarly investigated. To assess the functional importance of some of our results, we repeated the studies in rats, immediately (16-36 hr) after reversal of the neurological signs with thiamine administration. THE DATA OBTAINED LED TO THE FOLLOWING CONCLUSIONS: (a) Brain contains a substantial reserve of thiamine in that thiamine level has to fall to below 20% of normal before the onset of overt encephalopathy and an increase in brain thiamine to only 26% of normal results in rapid reversal of neurologic signs. (b) Both cerebral transketolase and pyruvate decarboxylase activities are impaired in low thiamine encephalopathy and the abnormality in the pyruvate decarboxylase is reflected in a rise in brain lactate. These biochemical abnormalities occur primarily in the brainstem and cerebellum, the sites of the morphologic changes. (c) Although the fall in cerebral transketolase is about twofold greater than that of pyruvate decarboxylase activity during encephalopathy, both enzymes rise on reversal of neurologic signs and the degree of the transketolase rise is slight. Accordingly, this study cannot ascertain the relative functional importance of these two pathways in the induction of the encephalopathy. The data suggest, however, that the depression of transketolase is not functionally important per se, but may only be an index of some other critical aspect of the hexose monophosphate shunt. (d) The normal cerebral ATP concentration and small GSH fall during encephalopathy, with little GSH rise on reversal of neurologic signs, suggest that a depletion of neither substance is instrumental in inducing thiamine-deficient encephalopathy.
Reintroduction of gluten in adults and children with treated coeliac disease.
Authors: P J Kumar, D P O'Donoghue, K Stenson, A M Dawson
Journal: Gut (1979)

Twenty-eight patients, thought to have coeliac disease and on gluten free diets, were put on a normal diet to confirm their diagnoses. Nineteen had been diagnosed in adult life (ACD) and nine in childhood (CCD). Patients were assessed on jejunal, morphological, and symptomatic parameters. Eighteen patients with ACD relapsed within seven weeks. Nine patients with CCD relapsed at variable times but five took longer than seven weeks, the longest period beint 10 months. Seven patients had no symptoms despite morphological deterioration during challenge and one patient, with ACD, did not relapse and was HLA B8 negative. This patient with ACD had subtotal villous atrophy on two jejunal biopsies and later showed morphological improvement on a gluten free diet. There was no correlation between the relapse time and time spent on a gluten free diet.
Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation
Authors: A A den Broeder
Journal: Annals of the Rheumatic Diseases (2002)

Objectives: To investigate the effect of prolonged neutralisation of tumour necrosis factor α (TNFα) on the radiological course in rheumatoid arthritis (RA). To assess whether the radiological course can be predicted by clinical variables or biological markers of cartilage and synovium turnover and of endothelial activation. Patients and methods: Forty seven patients with active RA enrolled at our centre in monotherapy trials with adalimumab (D2E7), a fully human anti-TNFα monoclonal antibody, were studied for two years. Radiographs of hands and feet obtained at baseline and after one and two years were scored in chronological order by a single, blinded observer using the modified Sharp method. Radiological course was classified as stable or progressive using the smallest detectable difference as cut off point. The relation between radiological course and serum markers of cartilage and synovium turnover (metalloproteinases (MMP-1 and MMP-3), cartilage oligomeric matrix protein (COMP), human cartilage glycoprotein-39 (HC gp-39)), endothelial activation (soluble E-selectin and intercellular adhesion molecule (ICAM-1)), and integrated measures of disease activity were assessed using univariate and multivariate analysis. Results: Radiological evaluation was performed in 36 patients with paired sets of radiographs at baseline and two years. After two years a total of 15/36 (42%) presented no radiological progression. More patients with stable radiological course were still receiving anti-TNFα treatment after two years (13/15 (87%) <i>v</i> 11/21 (52%); p=0.03) and had lower baseline COMP and sICAM-1 levels (p=0.01 and 0.04, respectively) than those in the group with progressive disease. In a logistic regression model the combination of sustained TNF neutralisation and baseline COMP and sICAM-1 levels was predictive for radiological outcome (p=0.03). C reactive protein and disease activity score area under the curve were significantly correlated with changes in radiological scores after two years (<i>r</i>=0.40 and 0.37, p&lt;0.05). Long term TNFα neutralisation decreased the levels of COMP, sICAM, MMPs, and HC gp-39, but not sE-selectin. Conclusion: The results suggest that long term monotherapy with anti-TNFα has a positive effect on radiological outcome and modulates cartilage and synovium turnover as measured by biological markers. Baseline serum sICAM-1 levels and COMP levels may be helpful to identify patients with progressive or non-progressive radiological outcome.
Direct Demonstration of P-Selectin– and VCAM-1–Dependent Mononuclear Cell Rolling in Early Atherosclerotic Lesions of Apolipoprotein E–Deficient Mice
Authors: Carroll L. Ramos, Yuqing Huo, Unsu Jung, Shukti Ghosh, David R. Manka, Ian J. Sarembock, Klaus Ley
Journal: Circulation Research (1999)

Abstract —Apolipoprotein E–deficient (ApoE −/− ) mice develop atherosclerotic lesions throughout the arterial tree, including the carotid bifurcation. Although the expression of adhesion molecules such as ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin on endothelium that overlie atherosclerotic plaques has been implicated in monocyte recruitment to developing lesions, monocyte adhesion in atherosclerotic vessels has not been observed directly. To investigate which adhesion molecules may be important in monocyte adhesion to atherosclerotic lesions, an isolated mouse carotid artery preparation was developed and perfused with mononuclear cells. We show rolling and attachment of the human monocytic cell line U937 and the mouse monocyte-macrophage cell line P388D1 in carotid arteries from 10- to 12-week-old ApoE −/− and C57BL/6 wild-type mice fed a Western-type diet (21% fat wt/wt) for 4 to 5 weeks. No rolling was observed in carotid arteries from C57BL/6 or BALB/c wild-type mice fed a chow diet and little was observed in BALB/c mice fed a Western-type diet. This model represents early lesion development as shown by minimal macrophage infiltration in the intima of carotid arteries from ApoE −/− mice fed a Western-type diet. Rolling was observed at shear stresses that were characteristic of the low-shear recirculation zone near the carotid bifurcation. Mononuclear cell attachment and rolling were significantly inhibited by monoclonal antibody blockade of P-selectin or its leukocyte ligand P-selectin glycoprotein ligand-1. Rolling velocities increased after monoclonal antibody blockade of mononuclear cell α 4 -integrin or VCAM-1, which indicates that α 4 -integrin interacting with VCAM-1 stabilizes rolling interactions and prolongs monocyte transit times.
EFFICACY OF TRIFLUOPERAZINE IN CHRONIC MENTAL ILLNESS
Authors: ROBERT B. CAHAN
Journal: American Journal of Psychiatry (1960)

Trifluoperazine is considered to be of limited usefulness and considerable toxicity in an elderly female population. The 8 patients with increased muscular rigidity having 4 of their number improved by Stelazine should be contrasted with the absence of psychiatric improvement among the 8 women with muscular weakness. Investigation of this phenomenon may reveal clues to the operation of trifluoperazine. On the positive side, no agranulocytic, hepatotoxic, or biliary static effects were noted. A therapeutic agent which can improve the ward management of one-fifth of the severely and chronically ill patients should be considered as part of the psychotherapeutic armamentarium.