tbuckley/cabot-search huggingface dataset:
Using Effectiveness and Cost-effectiveness to Make Drug Coverage Decisions
Authors: Fiona M. Clement, Anthony Harris, Jing Jing Li, Karen Yong, Karen M. Lee, Braden J. Manns
Journal: JAMA (2009)

National public insurance for drugs is often based on evidence of comparative effectiveness and cost-effectiveness. This study describes how that evidence has been used across 3 jurisdictions (Australia, Canada, and Britain) that have been at the forefront of evidence-based coverage internationally.To describe how clinical and cost-effectiveness evidence is used in coverage decisions both within and across jurisdictions and to identify common issues in the process of evidence-based coverage.Descriptive analysis of retrospective data from the Common Drug Review (CDR) of Canada, National Institute for Health and Clinical Excellence (NICE) in Britain, and Pharmaceutical Benefits Advisory Committee (PBAC) of Australia. All publicly available information as of December 31, 2008, was gathered from each committee's Web site (data set begins in January 2004 [CDR], February 2001 [NICE], and July 2005 [PBAC]).Listing recommendations for each drug by disease indication.NICE recommended 87.4% (174/199) of submissions for listing compared with a listing rate of 49.6% (60/121) and 54.3% (153/282) for the CDR and PBAC, respectively. Significant uncertainty around clinical effectiveness, typically resulting from inadequate study design or the use of inappropriate comparators and unvalidated surrogate end points, was identified as a key issue in coverage decisions. Recommendations varied considerably across countries, possibly because of differences in the medications reviewed; different agency processes, including the willingness to negotiate on price; and the approach to "me too" drugs. The data suggest that the 3 agencies make recommendations that are consistent with evidence on effectiveness and cost-effectiveness but that other factors are often important.NICE, PBAC, and CDR face common issues with respect to the quality and strength of the experimental evidence in support of a clinically meaningful effect. However, comparative effectiveness and cost-effectiveness, along with other relevant factors, can be used by national agencies to support drug decision making. The results of the evaluation process in different countries are influenced by the context, agency processes, ability to engage in price negotiation, and perhaps differences in social values.
Left ventricular relaxation in dilated cardiomyopathy: Relation to loading conditions and regional nonuniformity
Authors: Wataru Hayashida, Toshiaki Kumada, Fujimasa Kohno, Michiyo Noda, Noboru Ishikawa, Masashi Kambayashi, Chuichi Kawai
Journal: Journal of the American College of Cardiology (1992)
Is Cocaine a Sympathetic Stimulant During General Anesthesia?
Authors: Paul G. Barash
Journal: JAMA (1980)

Eighteen patients undergoing coronary artery surgery were observed to examine whether cocaine in a clinically used dose exerts sympathomimetic effects during general anesthesia. Eleven patients received cocaine hydrochloride as a 10% solution (1.5 mg/kg) applied topically to the nasal mucosa before nasotracheal intubation. Seven patients had a similar procedure without cocaine. Blood pressure, pulse rate, cardiac index, left ventricular stroke work index, total peripheral vascular resistance, and pulmonary vascular resistance were measured. There were no important differences in cardiovascular function between patient groups. The rapid rise in plasma cocaine concentration, reaching 331 ng/mL at 30 minutes and 320 ng/mL at 45 minutes, bore no apparent relationship to any changes in cardiovascular function. We conclude that under conditions of this study, administration of topical cocaine does not exert any clinically significant sympathomimetic effect and appears to be well tolerated in anesthetized patients with coronary artery disease.
A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity
Authors: Richard E. Straub, Charles J. MacLean, F. Anthony O'Neill, John Burke, Bernadette Murphy, Fiona Duke, Rosemarie Shinkwin, Bradley T. Webb, Jie Zhang, Dermot Walsh, Kenneth S. Kendler
Journal: Nature Genetics (1995)
813 HEPATITIS C VIRUS-SPECIFIC CELLULAR IMMUNITY DOES NOT PROTECT AGAINST FUTURE HCV INFECTION IN ANTI-HCV NEGATIVE INJECTING DRUG USERS
Authors: R. Sacks-Davis, C. Aitken, P. Higgs, S. Moneer, J. Flynn, V. Suppiah, L. Tracy, R. Ffrench, D. Bowden, H. Drummer, J. George, M. Bharadwaj, M. Hellard
Journal: Journal of Hepatology (2011)
Parents' perceptions of food intolerance in primary school children.
Authors: R J Rona, S Chinn
Journal: BMJ (1987)

In a study of about 7000 children, parents9 perceptions were used to examine the prevalence of food intolerance, the types of food implicated, the association of intolerance with diseases, and the social background of those identified as being food intolerant. One hundred and ninety two children (3%) were perceived as being food intolerant, with a further 105 (2%) being classed as intolerant under a less stringent definition of intolerance. For 128 (67%) of these children a doctor was consulted. The pattern of food avoided was very similar in children for whom the decision to exclude certain foods was made by health staff and in those for whom the parents themselves made decisions about their child9s diet. A strong association was seen between the mother9s level of education and the child being perceived as being food intolerant. Between 20% and 30% of children with a disease associated with food intolerance--for example, eczema--had currently or previously avoided some types of food. The results of this study emphasise the need to develop criteria to tackle the growing demand for National Health Service treatment by parents who believe their child to be food intolerant.
Hemodynamic changes after ligation of a major branch of the portal vein in rats: Comparison with rats with portal vein constriction
Authors: Soonho Um, Osamu Nishida, Masaki Tokubayashi, Fumiko Kimura, Yukinobu Takimoto, Hideyuki Yoshioka, Ryoichi Inque, Toru Kita
Journal: Hepatology (1994)

In chronic portal-hypertensive rat models, such as portal vein constriction or cirrhosis, the portal blood flow that effectively perfuses the hepatocytes is substantially reduced because of anatomical or functional shunts. It is possible therefore that a feedback mechanism from the liver to the splanchnic bed is responsible for the splanchnic hyperemia observed in chronic portal hypertension. To investigate the possible role of such a feedback mechanism, we examined the chronological changes in both portal and systemic hemodynamics in rats after ligation of a major branch of the portal vein that supplies about 80% of the liver circulation. Rats submitted to sham surgery and portal vein-constricted rats were also studied. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. For 7 days after portal-branch ligation, transient portal hypertension resulted from an elevated portal resistance. However, no significant changes in portal venous inflow or splanchnic arteriolar resistance were found in the portal branch-ligated rats, whereas in the portal vein-constricted rats significant hyperdynamic changes in these parameters were noted. On the other hand, transient hyperdynamic changes occurred in the systemic circulation during the period from the fourth to the sixth day after portal-branch ligation, similar to those observed in the portal vein-constricted rats. The lack of hyperdynamic changes in the portal territory of the portal branch-ligated rats suggests that the splanchnic hyperemia found in chronic portal-hypertensive states is unlikely to be caused by a feedback mechanism from the ischemic hepatic parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)
Hereditary conjugated hyperbilirubinaemia: 37years later
Authors: Daniel Dhumeaux, Serge Erlinger
Journal: Journal of Hepatology (2012)

Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that of Rotor syndrome, an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics, has remained enigmatic. Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3. These important detoxification-limiting proteins mediate uptake and clearance of countless drugs and drug conjugates across the sinusoidal hepatocyte membrane. OATP1B1 polymorphisms have previously been linked to drug hypersensitivities. Using mice deficient in Oatp1a/1b and in the multispecific sinusoidal export pump Abcc3, we found that Abcc3 secretes bilirubin conjugates into the blood, while Oatp1a/1b transporters mediate their hepatic re uptake. Transgenic expression of human OATP1B1 or OATP1B3 restored the function of this detoxification-enhancing liver-blood shuttle in Oatp1a/1b-deficient mice. Within liver lobules, this shuttle may allow flexible transfer of bilirubin conjugates (and probably also drug conjugates) formed in upstream hepatocytes to downstream hepatocytes, thereby preventing local saturation of further detoxification processes and hepatocyte toxic injury. Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks.
BENEFITS AND TOXICITY OF PHENYLBUTAZONE (BUTAZOLIDIN®) IN RHEUMATOID ARTHRITIS
Authors: Charles A. L. Stephens
Journal: JAMA (1952)

Studies in Europe on parenteral use of aminopyrine necessitated the development of a solvent, and a pyrazol synthetic derivative, phenylbutazone (butazolidin®), was developed for this purpose. The aminopyrine and phenylbutazone combination (igrapyrin®) was studied in Europe for its anti-inflammatory and antipyretic effect in rheumatic conditions. The reports<sup>1</sup>were enthusiastic, and the drug was introduced in the United States for evaluation. Because of the occasional serious hazards of aminopyrine therapy and because some of the clinical results obtained with the combination of aminopyrine and phenylbutazone were superior to those obtained with aminopyrine alone, it was decided to investigate the effect of the solvent, phenylbutazone, in the rheumatic diseases. Two recent clinical studies have been reported.<sup>2</sup> <h3>METHOD</h3><h3>Selection of Patients.</h3> —Of the 188 patients studied, 115 had peripheral rheumatoid arthritis, 32 had rheumatoid spondylitis, and 41 had miscellaneous diseases. Phenylbutazone alone was given to 107 of the 147
ABC of child abuse. Protecting the child.
Authors: B. Mitchels
Journal: BMJ (1989)

Child abuse appears in many diverse forms, entailing not only sexual but also physical or mental stress and often including cruelty or neglect.Recent events have highlighted the problems faced by everyone concerned with cases of child abuse: the needs and welfare of the child are balanced against the rights of parents and the legal requirements of the courts.Often there are conflicts of interest that prove extremely difficult to resolve.Doctors, lawyers, and social workers need to work together to protect the child, having first established that there is a real need for that protection.Legal procedures currently available to protect abused children are summarised below.The new Children Bill 1988 currently before parliament sets out to clarify and reform existing child care legislation.Proposals for reform are set out in the figure on the next page and are described in the text.Currently available legal procedures to protect children, with sequences ofaction Legal procedures to protect children
JAUNDICE AS AN EXPRESSION OF THE PHYSIOLOGICAL WASTAGE OF CORPUSCLES
Authors: Peyton Rous, D. R. Drury
Journal: The Journal of Experimental Medicine (1925)

The jaundice that develops after obstruction of the common duct in the absence of complications, expresses the physiological wastage of corpuscles occurring from day to day; and the intensity of the bilirubinemia varies as does the total of functioning hemoglobin-containing tissue from which this wastage takes place. There is to be observed a constantly readjusted direct relationship between hemoglobin percentage, bilirubinemia, and, by corollary, bilirubinuria. Induced losses of red cells find expression at once in a lessened accumulation and excretion of bile pigment; and as the regeneration of hemoglobin takes place the amount of bile pigment increases pari passu both in plasma and urine. The jaundice of bile retention is far less pronounced during secondary anemia than when the individual is full blooded, other things being equal. During uncomplicated obstructive jaundice the intercurrent changes in bilirubinemia correspond closely with those in circulating hemoglobin even when tissue icterus is of long standing. The fact indicates the presence of a barrier to the distribution of bile pigment from the blood, and such a barrier is to be found in the walls of the vessels. Its influence is at once evident on comparing lymph specimens and blood specimens from the long jaundiced animal. The amount of bile pigment in the lymph is then seen to be negligible, relatively speaking. Tissue icterus should be thought of as, ordinarily, the highly imperfect secondary expression of a condition which tends to be localized to the blood pool. On occasion more pigment than usual may escape from this pool, as for example into the wheats of the yellow urticaria described by clinicians.
A Case of Dermatomyositis
Authors: Edward J. Kamin
Journal: JAMA (1975)

<b>Dr. Gersh</b>: A 36-year-old housewife was admitted to Tripler Army Medical Center because of increasing shortness of breath over a period of three months. Six months before admission she had noted pain and swelling in her wrists, elbows, shoulders, and knees, as well as in the small joints of her hands. At the same time, a nonpruritic, erythematous rash spread over her face and trunk. Of 11 brothers and sisters, one had died of lupus erythematosus; a son had died of a cerebral neoplasm. Otherwise, the family history was unremarkable. <h3>Admission Examination.—</h3> Positive findings were limited to the following: fine basilar rales in both lungs; a palpable spleen edge; tenderness and minimal synovial thickening over the metacarpophalangeal and proximal interphalangeal joints, shoulders, and elbows; marked synovial thickening over knees and wrists; patchy erythema over the lower portion of the face, the trunk, and fingers; violaceous periorbital edema; decreased muscle strength,
Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal Caco-2 cell monolayers
Authors: M.M Thanou, A.F Kotzé, T Scharringhausen, H.L Lueßen, A.G de Boer, J.C Verhoef, H.E Junginger
Journal: Journal of Controlled Release (2000)
Women's Mental Health in Primary Care
Authors: Valerie P. Weil
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes18 January 2000Women's Mental Health in Primary CareValerie P. Weil, MDValerie P. Weil, MDHospital of the University of Pennsylvania, Philadelphia, Pennsylvania. (Weil)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-2-200001180-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Zerbe KJ. 366 pages. Philadelphia: WB Saunders; 1999. $39.00. ISBN 9721672396. Order phone 800-545-2522.Field of medicine: Psychiatry and women's health.Format: Softcover book.Audience: General practitioners, internists, family practitioners, obstetrician-gynecologists, and trainees.Purpose: To improve the clinician's skills in dealing with mental health issues that may arise in female patients.Content: Most of the 14 chapters in this book each cover a single mental health issue commonly seen in primary care practice. Each chapter contains epidemiologic and statistical information, case histories, recommended initial assessment, therapeutic options, and recommendations for referral. Guidelines for patients and caregivers are given, as well ... Author, Article, and Disclosure InformationAffiliations: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. (Weil) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 January 2000Volume 132, Issue 2Page: 168KeywordsElderlyEpidemiological statisticsInsomniaMenopauseObstetrics and gynecologyPatientsPregnancyPsychiatry and mental healthSoftware toolsSubstance abuse Issue Published: 18 January 2000 CopyrightCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Fine Structure of a Gene — DNA Sequencing
Authors: Nadia Rosenthal
Journal: New England Journal of Medicine (1995)

A molecular voyager entering the nucleus of a human cell in search of a gene would be hard pressed to discern its location, buried in the tangle of chromosomal DNA. Only a painstaking examination of the nucleotide sequence along the helical DNA strands would reveal those rare stretches of nucleotides that could be read as a code for the structure of a protein. We do not yet possess the means to delve directly into the nucleus and search for genes in their natural setting, but by molecular cloning we can isolate and amplify relatively short stretches of chromosomal DNA and . . .
Diagnosis and treatment of primary hypothyroidism
Authors: A. Allahabadia, S. Razvi, P. Abraham, J. Franklyn
Journal: BMJ (2009)

New guidance highlights how to do it in primary care

Primary hypothyroidism or underactivity of the thyroid gland is common and is usually managed in primary care.1 In recent years, increasing numbers of patients with and without confirmed thyroid disease have been diagnosed and treated inappropriately using levothyroxine and other thyroid hormones. Management that falls outside good practice as defined nationally and internationally by accredited thyroid experts may compromise patients’ safety. This is potentially an enormous problem, given that in any one year one in four people in the United Kingdom have their thyroid function checked.2 3

The Royal College of Physicians, working closely with several specialist professional associations and patient associations with interests in the safe management of thyroid diseases, has recently produced a statement on the diagnosis and management of primary hypothyroidism. This statement sets out clear guidance for general practitioners and the wider medical profession regarding the diagnosis and treatment of primary hypothyroidism in the United Kingdom.3 …
Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states.
Authors: S Vigano D'Angelo, P C Comp, C T Esmon, A D'Angelo
Journal: Journal of Clinical Investigation (1986)

Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals.
Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: A randomized double-blind study
Authors: Macarena Simón-Talero, Rita García-Martínez, Maria Torrens, Salvador Augustin, Susana Gómez, Gustavo Pereira, Mónica Guevara, Pere Ginés, Germán Soriano, Eva Román, Jordi Sánchez-Delgado, Roser Ferrer, Juan C. Nieto, Pilar Sunyé, Inma Fuentes, Rafael Esteban, Juan Córdoba
Journal: Journal of Hepatology (2013)
Hormone-Replacement Therapy and Cardiovascular Diseases
Authors: John Bailar
Journal: New England Journal of Medicine (2003)

Eighteen years ago, the Journal published two observational studies1,2 of the relations between postmenopausal hormone-replacement therapy and cardiovascular diseases. One found that women who used such therapy had about half the risk that nonusers had; the other found that they had almost twice the risk. In each study, the relative risk was statistically different from a relative risk of 1.0, or no effect. These results seemed to be in serious conflict, although each study taken alone looked sound. In an accompanying editorial,3 I noted differences in the drugs used, the groups of patients studied, the outcomes ascertained, and other . . .
The role of interleukin-converting enzyme in Fas-mediated apoptosis in HIV-1 infection.
Authors: E M Sloand, J P Maciejewski, T Sato, J Bruny, P Kumar, S Kim, F F Weichold, N S Young
Journal: Journal of Clinical Investigation (1998)

Apoptosis of CD4+ lymphocytes is partially responsible for the depletion of these cells in HIV-infected individuals. CD4+ lymphocytes from HIV-1-infected patients express higher membrane levels of the Fas receptor, and are particularly susceptible to apoptosis after Fas triggering. IL-1beta- converting enzyme (ICE) is a key enzyme of the apoptotic machinery involved in Fas-mediated apoptosis of normal lymphocytes. The role of ICE in mediating the increased susceptibility of CD4+ lymphocytes from HIV-1-infected patients to apoptosis has not been examined. In this study, we found that ICE mRNA was present in T cells from both HIV-1-infected patients and controls. Active ICE proteins, p10 and p20, were demonstrated by immunoblot in lymphocytes from HIV-1-infected patients and in normal lymphocytes after treatment with Fas agonist, CH11 mAb. Cocultivation of lymphocytes from HIV-1-infected persons with Fas antagonist, antibody ZB4, resulted in decreased expression of ICE protein in lymphocytes from HIV-infected patients, and decreased apoptosis. Similar effects were obtained when cells were treated with synthetic ICE inhibitors, which blocked apoptosis in response to Fas triggering. When CD4+ and CD8+ cells were sorted by flow cytometry and analyzed by reverse transcriptase PCR, ICE mRNA was present in both CD8+ and CD4+ cells. However, flow cytometric analysis of lymphocytes with intracellular staining for ICE demonstrated ICE protein in the CD4+ but not the CD8+ cell fraction derived from blood of HIV-1-infected patients. These data suggest that activation of ICE occurs in vivo in CD4+ lymphocytes from HIV-1-infected individuals, and may account for the increased susceptibility of CD4+ cells to apoptosis.