tbuckley/cabot-search huggingface dataset:
The<i>n</i>-of-1 Randomized Controlled Trial: Clinical Usefulness
Authors: Gordon H. Guyatt
Journal: Annals of Internal Medicine (1990)

Objective: To review the feasibility and effectiveness of n-of-1 randomized controlled trials (n-of-1 trials) in clinical practice. Design: Individual trials were double-blind, randomized, multiple crossover trials. The impact of n-of-1 trials was determined by eliciting physicians' plans of management and confidence in those plans before and after each trial. Setting: Referral service doing n-of-1 trials at the requests of community and academic physicians. Object of Analysis: All trials were planned, started, and completed by the n-of-1 service. Measures of Outcome: The proportion of planned n-of-1 trials that were completed and the proportion that provided a definite clinical or statistical answer. A definite clinical answer was achieved if an n-of-1 trial resulted in a high level of physician's confidence in the management plan. Specific criteria were developed for classifying an n-of-1 trial as providing a definite statistical answer. Main Results: Seventy-three n-of-1 trials were planned in various clinical situations. Of 70 n-of-1 trials begun, 57 were completed. The reasons for not completing n-of-1 trials were patients' or physicians' noncompliance or patients' concurrent illness. Of 57 n-of-1 trials completed, 50 provided a definite clinical or statistical answer. In 15 trials (39% of trials in which appropriate data were available), the results prompted physicians to change their "prior to the trial" plan of management (in 11 trials, the physicians stopped the drug therapy that they had planned to continue indefinitely). Conclusion: We interpret the results as supporting the feasibility and usefulness of n-of-1 trials in clinical practice.
A penny for your thoughts
Authors: D. Spence
Journal: BMJ (2009)

“How was the food?” My cranial nerve IX fired. “Lovely, thank you.” I pushed lettuce over the uneaten food. “Could we have the bill please?” my wife asked sweetly. On the street we fell into each other laughing and headed for a drink. We didn’t complain but enjoyed the story with friends. The restaurant passed away, but we still had our fond memories of the pretentious, overpriced nonsense of it all. Perhaps the business might have been saved by using a satisfaction questionnaire, …
Without integrated care within five years we risk another Mid Staffs, warns government
Authors: G. Iacobucci
Journal: BMJ (2013)

The UK government has set out ambitious plans to fully integrate health and social care in England within five years, in a new blueprint hailed by ministers as a landmark moment in the future of the NHS.

The coalition government has pledged to establish new integrated care arrangements in every area of the country by 2015, with a view to fully integrating healthcare and social care by 2018.

The plans will be kickstarted by 10 “pioneer” areas around the country, which will be chosen by September 2013 to take the lead in testing “innovative, practical approaches” to integration, with other areas then encouraged to follow.

The government said that the move to accelerate integrated care across England was essential to stop the NHS from “buckling under the pressure” of an ageing population …
Creation of an Atrial Septal Defect In Utero for Fetuses With Hypoplastic Left Heart Syndrome and Intact or Highly Restrictive Atrial Septum
Authors: Audrey C. Marshall, Mary E. van der Velde, Wayne Tworetzky, Carlen A. Gomez, Louise Wilkins-Haug, Carol B. Benson, Russell W. Jennings, James E. Lock
Journal: Circulation (2004)

Infants born with hypoplastic left heart syndrome and an intact or highly restrictive atrial septum face a neonatal mortality of at least 48% despite early postnatal left atrial decompression and palliative surgery. Prenatal left atrial decompression has been suggested as a means of improving these outcomes. This study reports the feasibility of fetal catheterization to create an interatrial communication and describes technical considerations.Seven fetuses at 26 to 34 weeks' gestation with hypoplastic left heart syndrome and intact or highly restrictive atrial septum underwent attempted prenatal intervention. Under ultrasound guidance, the atrial septum was approached with a needle introduced percutaneously from the maternal abdominal surface. In 6 of 7 fetuses, the atrial septum was successfully perforated, with balloon dilation of this iatrogenic defect resulting in a small but persistent interatrial communication. There were no maternal complications. One fetus died after the procedure. The remaining fetuses were liveborn at term, although 4 died as neonates.Ultrasound-guided fetal atrial septoplasty consisting of septal puncture and balloon dilation is feasible and can be performed percutaneously to minimize maternal risk. Although we have not demonstrated any positive clinical impact to date, it is our hope that further technical evolution will ultimately enable prenatal left atrial decompression and improvement of outcomes in fetuses with hypoplastic left heart syndrome and intact atrial septum.
Successful pregnancy in chronic renal failure.
Authors: M Reid
Journal: BMJ (1980)

prognosis, must naturally always take prece- dence over a desire to improve the mortality rate.For all these various reasons we would like to end with a plea that future investigations into the effectiveness of neonatal intensive care undertaken before 1975 should in parLicular focus on the outcome of the low birthweight group 1500-1999 g.Certainly infants of less than 1000 g are best excluded or dealt with separately.
The Unconscionable Gap Between What We Know and What We Do
Authors: Steven E. Hyman
Journal: Science Translational Medicine (2014)

Mental disorders have high aggregate prevalence, are responsible globally for nearly a quarter of all years lived with disability, and represent the largest cause of lost economic output among all classes of noncommunicable disease worldwide. Cost-effective treatments, including both generic drugs and brief, manualized cognitive therapies are available to address this burden. Nonetheless, treatment of mental disorders remains a low priority worldwide-disproportionately so in low- and middle-income countries. Here, I focus on possible reasons for the failure of policy-makers to respond effectively, and I suggest corrective approaches.
Government's response to alcohol report is "too complacent"
Authors: Z. Kmietowicz
Journal: BMJ (2010)

The Department of Health has rejected a call from MPs for tighter controls on advertising of alcohol, saying that its policy of self regulation and education is working well. But it has left open for the time being the decision on a minimum price for alcohol until more research on the strategy’s effect on crime and disorder is published at the end of March.

The department was responding to a report on alcohol from the cross party health select committee published in January. In their report MPs made a raft of recommendations, including a minimum price for a unit of alcohol, better detection of people with alcohol problems, and improved treatment services ( BMJ 2010;340:c136, 12 Jan, doi:10.1136/bmj.c136).

Don Shenker, chief executive of Alcohol Concern, said that the government’s response was “too complacent” and “fails to acknowledge the actions needed to drive down these …
Too Much to Read
Authors: MATTHEW CUSHING
Journal: Annals of Internal Medicine (1974)

Comments1 June 1974Too Much to ReadMATTHEW CUSHING JR., M.D.MATTHEW CUSHING JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-6-781_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: As a busy practicing physician, I am particularly concerned with budgeting my time to best serve my patients and my family. Among the items in the budget is, of necessity, postgraduate education. Like any physician who is conscious of the world around him, I am concerned with hospital affairs, community affairs, and politics in general and also am trying to maintain some semblance of acorpore sano. Because of the continual interruptions a busy practicing internist has, particularly night and weekend calls, I have a considerably limited time to pursue these aims, and the limitation extends to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 93 Main St. Andover, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1974Volume 80, Issue 6Page: 781-782 Issue Published: 1 June 1974 PDF DownloadLoading ...
888 SAFETY AND TOLERABILITY OF TELAPREVIR-BASED TRIPLE THERAPY IN HIV/HCV COINFECTED VERSUS HCV MONOINFECTED PATIENTS IN “REAL LIFE”: A MATCHED-COHORT STUDY
Authors: A. Pascale, A. Boyd, J. Bottero, H. Stitou, N. Valin, F. Benjelloun, O. Chazouillères, P.-M. Girard, L. Serfaty, K. Lacombe
Journal: Journal of Hepatology (2013)
Meal-Related Increases in Microvascular Vasomotion Are Impaired in Obese Individuals
Authors: Amy M. Jonk, Alfons J. Houben, Nicolaas C. Schaper, Peter W. de Leeuw, Erik H. Serné, Yvo M. Smulders, Coen D. Stehouwer
Journal: Diabetes Care (2011)

Obesity is associated with insulin resistance, hypertension, cardiovascular disease, and type 2 diabetes (1), but the mechanisms underlying these associations are incompletely understood. This article reviews and adds original data (i.e., in the postprandial state) to the evidence for microvascular dysfunction, including impairment of insulin-stimulated microvascular perfusion as a key element in the pathogenesis of obesity-related hypertension and insulin resistance (2,3).

The microcirculation is widely taken to encompass vessels <150 μm (i.e., arterioles, capillaries, and venules) (4) and has two important functions. First, arterioles regulate hydrostatic pressure and peripheral vascular resistance (4). Importantly, dysfunction of the microcirculation, with concomitant increases in vasoconstrictor tone, will increase total peripheral resistance and, other things being equal, blood pressure, as reviewed elsewhere (2,3). Second, it regulates tissue perfusion to optimize the delivery of nutrients and removal of waste products within tissues in response to variations in demand. In this respect, insulin has been shown to play an important role (5).

Insulin redirects blood flow within the muscle microvascular bed to increase available capillary surface area, an effect referred to as “capillary recruitment” (6,7). In addition, insulin induces vasodilation of resistance vessels, resulting in an increase in total muscle blood flow (8). Whether this increase in total muscle blood flow, which occurs later in time compared with the redirection of flow to nutritive capillary beds, serves to enhance insulin-mediated glucose uptake remains controversial (9). However, it has been generally accepted that capillary recruitment is crucial for the delivery of insulin and glucose to tissue. Indeed, several studies have shown that insulin-mediated increases in capillary recruitment account for approximately half of insulin-mediated muscle glucose uptake in vivo (10–14). Insulin’s effect on microvascular blood flow is, therefore, an important regulator of insulin-mediated muscle glucose uptake, the main …
Endemiological Study of Bact. typhosum Type D4
Authors: W. H. Bradley
Journal: BMJ (1943)

MEDITCAL OURNALThe control of typhoid fever depends ultimately on the control of the chronic carrier.The detection of a chronic carrier who is responsible for the infection of sporadic cases or of small groups of cases is usually a very difficult task.The introduction of refined culture media, particularly the bismuth sulphite medium of Wilson and Blair (1931), and of the Vi agglutination test, has made the problem less formidable than it was in earlier days.The new typing method devised by Craigie and Yen (1938a) has provided another weapon of great efficacy.It now seems possible to organize the fight against the chronic typhoid carrier in a manner that promises to lead far towards the ultimate goal, the eradication of the disease. SummaryDuring 1940-2 440 strains of typhoid bacilli isolated in England, Wales, and Scotland were examined by the Vi bacteriophage method of Craigie and Yen.Of 432 strains that were Vi forms 363 (84.1%) were successfully typed, while 69 (15.9%) were untypable, or "imperfect" Vi forms.The remaining 8 strains, including 6 from chronic carriers, could not be typed because the cultures were " O " forms.Most of the strains belonged to 8 of Craigie's original phage types.In addition 4 new Vi-phage types were identified.The bacteriophage test is a reliable guide to the epidemiological investigation of outbreaks or sporadic cases of typhoid lever.Its application greatly facilitates the detection of chronic harriers, especially those responsible for sporadic cases in endemic areas.Unquestionably the new method will soon be recognized as an indispensable laboratory aid to the control of typhoid fever.This investigation was made possible by the co-operation of many pathologists, medical officers of health, and superintendents of fever hospitals, and by the constant aid of Dr. J. R. Hutchinson and Dr.W. H. Bradley df the Ministry of Health.I wish to thankc all of them for their help.My thanks are also due to Miss B. R
Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion
Authors: Peter T. Kingham, Umer I. Chaudhry, George Plitas, Steven C. Katz, Jesse Raab, Ronald P. DeMatteo
Journal: Hepatology (2007)

The liver has unique immunological properties. Although dendritic cells (DCs) are central mediators of immune regulation, little is known about liver DCs. Plasmacytoid DCs (pDCs) are a recently identified subtype of murine liver DC. We sought to define the function of freshly isolated murine liver pDCs. We found that normal liver pDCs were weak in stimulating T cells, yet they possessed a proinflammatory cytokine profile with high tumor necrosis factor-α and low IL-10 secretion. To facilitate the investigation of murine liver pDCs, we expanded them in vivo with fms-like tyrosine kinase 3 ligand (Flt3L). After Toll-like receptor-9 ligation, expanded liver pDCs secreted high levels of IFN-α and were able to stimulate NK cells, NKT cells, and antigen-specific CD8+ T cells in vitro . In addition, Flt3L expansion alone generated pDCs capable of activating antigen-specific CD8+ T cells in vivo . Conclusion: Unstimulated liver pDCs exist in a latent state with the potential to become potent activators of the innate and adaptive immune systems through their interactions with other immune effectors. Our findings have implications for understanding the role of the liver in tolerance and immunity.
Sulfonylurea Use and Incident Cardiovascular Disease Among Patients With Type 2 Diabetes: Prospective Cohort Study Among Women
Authors: Yanping Li, Yang Hu, Sylvia H. Ley, Swapnil Rajpathak, Frank B. Hu
Journal: Diabetes Care (2014)

Evidence is inconsistent for the association between sulfonylurea use and risk of cardiovascular disease among patients with diabetes. We aimed to prospectively evaluate this association using the Nurses' Health Study (NHS), a well-established cohort of U.S. women with long-term follow-up.We followed 4,902 women (mean age 68 years) with diabetes (mean duration 11 years), but without cardiovascular disease at baseline. The use of sulfonylureas and other medications was self-reported at baseline and during the follow-up period of up to 10 years. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% CI for the association between the sulfonylurea use and incident cardiovascular disease while accounting for potential confounders, including age, diabetes duration, diabetes-related complications, other antihyperglycemic medications, BMI, lifestyle factors, family history of cardiovascular diseases, and present chronic conditions. We also applied the propensity score stratification method to address the possibility of residual confounding.We identified 339 incident cases of cardiovascular disease, including 191 cases of coronary heart disease (CHD) and 148 cases of stroke. A longer duration of sulfonylurea use was significantly associated with a higher risk of CHD (P for trend = 0.002); the RRs for CHD were 1.24 (95% CI 0.85-1.81) for patients who used sulfonylurea therapy for 1-5 years, 1.51 (0.94-2.42) for 6-10 years, and 2.15 (1.31-3.54) for >10 years, compared with nonusers. Compared with users of metformin monotherapy, the RR for CHD was 3.27 (1.31-8.17) for those who were treated with the combination of metformin and sulfonylurea. The analysis using propensity score stratification yielded similar results. We did not observe a significant association between sulfonylurea therapy and stroke risk.Long-term use of sulfonylureas was associated with a significantly higher risk of developing CHD among women with diabetes.
Polymorphism in the β <sub>2</sub> -Adrenergic Receptor and Lipoprotein Lipase Genes as Risk Determinants for Idiopathic Venous Thromboembolism
Authors: Robert Y.L. Zee, Nancy R. Cook, Suzanne Cheng, Henry A. Erlich, Klaus Lindpaintner, Paul M Ridker
Journal: Circulation (2006)

Candidate genes in inflammation, thrombosis, coagulation, and lipid metabolism pathways have been implicated in venous thromboembolism (VTE).Using DNA samples collected at baseline in the Physicians' Health Study cohort, we genotyped 92 polymorphisms from 56 candidate genes among 304 individuals who subsequently developed VTE (144 idiopathic, 156 secondary cases) and among 2070 individuals who remained free of reported vascular disease over a mean follow-up of 13.2 years to prospectively determine whether these gene polymorphisms contribute to the risk of VTE. For idiopathic VTE, in addition to the factor V (Leiden) mutation (odds ratio [OR], 5.13; 95% confidence interval [CI], 3.24 to 8.14; P<0.0001; false discovery rate [FDR], P<0.0001), an N291S lipoprotein lipase gene polymorphism (OR, 3.09; 95% CI, 1.56 to 6.09; P=0.001; FDR, P=0.036) and a Q27E beta2-adrenergic receptor gene polymorphism (OR, 1.40; 95% CI, 1.09 to 1.79; P=0.006; FDR, P=0.036) were found to be significantly associated with increased risk. For secondary VTE, a Q360H apolipoprotein A4 gene polymorphism (OR, 0.34; 95% CI, 0.18 to 0.65; P=0.001; FDR, P=0.07) and an I50V interleukin-4 receptor polymorphism (OR, 0.66; 95% CI, 0.52 to 0.84; P=0.0009; FDR, P=0.07) were moderately, but not statistically and significantly, associated with reduced risk after adjustment for multiple comparisons.These present findings are hypothesis generating and require replication and confirmation in an independent investigation.
Polymorphisms in the interleukin 13 and GATA binding protein 3 genes and the development of eczema during childhood
Authors: S.H. Arshad, W. Karmaus, R. Kurukulaaratchy, A. Sadeghnejad, M. Huebner, S. Ewart
Journal: British Journal of Dermatology (2008)

Atopic eczema is characterized by Th2-dominant immunity with the cytokine interleukin 13 and the transcription factor GATA binding protein 3 playing a critical role.We assessed the association of polymorphisms in the IL13 and GATA3 genes with childhood eczema.A birth cohort (n = 1456) was established on the Isle of Wight in 1989 and followed at the ages of 1 (n = 1167), 2 (n = 1174), 4 (n = 1218) and 10 years (n = 1373) to determine the prevalence of allergic disease including eczema. At 4 and 10 years, skin prick testing was performed. Whole blood samples (n = 923) were obtained at the 10-year assessment, stored frozen, and genotyped. Five polymorphisms from IL13 and seven from GATA3 were genotyped for this analysis. Repeated measurement analyses were conducted for the occurrence of eczema at ages 1, 2, 4 and 10 years. All analyses were adjusted for maternal and paternal eczema, low birth weight (< 2500 g), breastfeeding >or= 3 months and age.IL13 was not associated with childhood eczema. For GATA3, the single nucleotide polymorphism (SNP) rs2275806 (promoter region) showed an increased odds ratio for atopic eczema independent of whether the comparison group had a positive skin prick test. The SNP rs444762 (intron 3 region) was associated with atopic eczema in comparison with children without eczema. The increased relative risks remained significant after adjustment for multiple testing only for rs2275806 (P < 0.05).A SNP in GATA3 is associated with atopic eczema. This finding highlights the importance of GATA3 as an immune-modulating gene in atopic eczema.
Treatment of hypertension with methyldopa.
Authors: P. Johnson, A. H. Kitchin, C. P. Lowther, R. W. Turner
Journal: BMJ (1966)

In recent years there has been a progressive improvement in the agents available for lowering blood-pressure.In the majority of cases high blood-pressure can now be reduced to normal levels, though not always wisely or without side-effects.Previous reports have agreed that methyldopa has advantages over other drugs in being relatively free from severe side-effects, though these in some degree are experienced by most patients and some have to stop treatment altogether on this account.In many, also, it has not been possible to maintain adequate control over the blood-pressure.We feel there is now a place for a fairly definitive statement based on a large group of patients studied over a sufficient period of time to draw long-term conclusions.This paper describes our experience with methyldopa in the treatment of 114 patients.Fourteen of these had to discontinue treatment after less than six months.The remaining 100 were treated for periods of 6 to 36 months, and details are also given of a preliminary double-blind trial carried out on a small number of patients. Material and MethodsThe 100 patients (37 males, 63 females) in this series who completed six months' treatment were aged from 29 to 77, with an average of 54 years.The duration of follow-up is shown in Table I.TABLE I.-Duration of Follow-up 6-11 months .100cases 12-17 ,,.79 18-23 ,,.
Use of Dexamethasone in Cerebral Malaria
Authors: A. W. Woodruff, C. J. Dickinson
Journal: BMJ (1968)

In a man who had been in a coma for 24 hours with cerebral malaria dexamethasone had a dramatic, and probably life-saving, effect. We believe dexamethasone should be given routinely, together with antimalarial therapy, to patients with cerebral malaria.
Interferon regulator factor 1/retinoic inducible gene I (IRF1/RIG-I) axis mediates 25-hydroxycholesterol-induced interleukin-8 production in atherosclerosis
Authors: Feng Wang, Weiwei Xia, Feng Liu, Ji Li, Guang Wang, Jun Gu
Journal: Cardiovascular Research (2011)

In this study, the role of retinoic inducible gene I (RIG-I)-mediated signalling in the inflammation of atherosclerosis was investigated to explain the pathology of atherosclerosis. Human and mouse primary cells were exposed to 25-hydroxycholesterol followed by examination of gene expression and activation of the signal pathway with biochemical and molecular biological techniques. A mouse atherosclerotic model was also used. We found that RIG-I was induced in macrophages and endothelium by 25-hydroxycholesterol. Interferon regulatory factor 1 is a key transcription factor for the induction of RIG-I by 25-hydroxycholesterol. The induction of interleukin-8 and growth-regulated protein α, the mouse interleukin-8 homologue, by 25-hydroxycholesterol is mediated by RIG-I signalling. RIG-I transduces the signal to downstream molecules, mitochondrial antiviral-signalling protein, transforming growth factor-β-activated kinase 1, and mitogen-activated protein kinase, leading to the activation of nuclear factor κB, activator protein-1, and nuclear factor interleukin-6, all of which are required for the expression of interleukin-8. Finally, we observed that RIG-I is highly expressed in atherosclerotic lesions. Our data demonstrate that RIG-I signalling mediates atherosclerotic inflammation. Targeting RIG-I signalling should provide a way to inhibit atherosclerotic inflammation, which holds potential for the therapy of atherosclerosis.