tbuckley/cabot-search huggingface dataset:
Is surgery ever justified?
Authors: M. G Cowling
Journal: BMJ (2010)

Many clinics and payers are beginning programs to collect and interpret outcomes related to quality of care and provider performance (ie, benchmarking). Outcomes assessment is commonly done using observational research designs, which makes it important for those involved in these endeavors to appreciate the underlying challenges and limitations of these designs. This perspective article discusses the advantages and limitations of using observational research to evaluate quality of care and provider performance in order to inform clinicians, researchers, administrators, and policy makers who want to use data to guide practice and policy or critically appraise observational studies and benchmarking efforts. Threats to internal validity, including potential confounding, patient selection bias, and missing data, are discussed along with statistical methods commonly used to address these limitations. An example is given from a recent study comparing physical therapy clinic performance in terms of patient outcomes and service utilization with and without the use of these methods. The authors demonstrate that crude differences in clinic outcomes and service utilization tend to be inflated compared with the differences that are statistically adjusted for selected threats to internal validity. The authors conclude that quality of care measurement and ranking procedures that do not use similar methods may produce findings that may be misleading.
Using decision analysis to compare policies for antenatal screening for Down's syndrome
Authors: J Fletcher, N R Hicks, J D S Kay, P A Boyd
Journal: BMJ (1995)

To compare different screening policies for Down's syndrome across a broad range of outcomes, using decision analysis, with particular reference to the role of maternal serum testing.A decision tree was used to combine data from local sources and the medical literature to predict the likely frequency of several outcomes. Sensitivity analyses were used to test the robustness of the conclusions drawn.Oxfordshire Health Authority.Live births with and without Down's syndrome; miscarriages with Down's syndrome; cases of Down's syndrome detected antenatally; amniocenteses performed (and associated miscarriages); direct NHS screening costs; number of women offered screening.Screening policies for Down's syndrome that include serum testing can produce better population outcomes than programmes that do not. Each option for screening for Down's syndrome that we considered had significant drawbacks. In Oxfordshire, offering serum testing to women of all ages would prevent the birth of approximately one more baby with Down's syndrome per year than would a policy of screening for women aged 30 years or more. The cost of preventing this one extra Down's birth would be one or two normal babies lost after amniocentesis, 4500 blood tests for young women (with the associated anxiety and counselling), approximately 200 false positive serum test results and amniocenteses (with the associated anxiety and distress), and 90,000 pounds for the extra tests, counselling, and amniocenteses. Opinions are divided as to which policy is the better option for the population.Decision analysis is a useful tool for determining the likely consequences of different policy options across a broad range of outcomes. This focuses debate and decision making on outcomes of care, which in turn makes it clear that the choice of screening programme for Down's syndrome depends on the relative importance ascribed to the different outcomes. If individuals' values vary widely it may be impossible to find one screening policy that meets the needs of all pregnant women.
A Sensitive New Prenatal Test for Sickle-Cell Anemia
Authors: Judy C. Chang, Yuet Wai Kan
Journal: New England Journal of Medicine (1982)

METHODS for prenatal diagnosis of sickle-cell anemia are improving rapidly.1 Initially the diagnostic procedure required fetal blood sampling, but new techniques for restriction-endonuclease analysis of DNA now permit the use of amniocentesis. A polymorphic HpaI site, present in 70 per cent of the American black population, was first used to diagnose the sickle mutation in the β-globin gene by linkage analysis.2 Recently the enzyme DdeI was shown to detect the sickle mutation directly in all cases.3 , 4 A drawback of the DdeI assay is that the amniotic cells must be cultured to provide a sufficient amount of DNA . . .
Time for a Change — A New Approach to ICD Replacement
Authors: Daniel B. Kramer, Alfred E. Buxton, Peter J. Zimetbaum
Journal: New England Journal of Medicine (2012)

Of the 100,000-plus implantable cardioverter–defibrillators (ICDs) implanted in the United States annually, at least 25% are generator replacements required for depleted batteries. Should all those patients be receiving replacement ICDs?
Capillary-Wall Collagen as a Biophysical Marker of Nanotherapeutic Permeability into the Tumor Microenvironment
Authors: Kenji Yokoi, Milos Kojic, Miljan Milosevic, Tomonori Tanei, Mauro Ferrari, Arturas Ziemys
Journal: Cancer Research (2014)

The capillary wall is the chief barrier to tissue entry of therapeutic nanoparticles, thereby dictating their efficacy. Collagen fibers are an important component of capillary walls, affecting leakiness in healthy or tumor vasculature. Using a computational model along with in vivo systems, we compared how collagen structure affects the diffusion flux of a 1-nm chemotherapeutic molecule [doxorubicin (DOX)] and an 80-nm chemotherapy-loaded pegylated liposome (DOX-PLD) in tumor vasculature. We found a direct correlation between the collagen content around a tumor vessel to the permeability of that vessel permeability to DOX-PLD, indicating that collagen content may offer a biophysical marker of extravasation potential of liposomal drug formulations. Our results also suggested that while pharmacokinetics determined the delivery of DOX and DOX-PLD to the same tumor phenotype, collagen content determined the extravasation of DOX-PLD to different tumor phenotypes. Transport physics may provide a deeper view into how nanotherapeutics cross biological barriers, possibly helping explain the balance between biological and physical aspects of drug delivery.
Digoxin toxicity presenting as dysphagia and dysphonia.
Authors: M F Cordeiro, K G Arnold
Journal: BMJ (1991)

longer deserves (although it certainly did from 1988 to 1990) for indiscriminately encouraging markets, and also opprobrium it certainly does deserve (currently) for interfering obsessively in increasing central control of a supposedly newly devolved NHS.In the end we are left with the contracting process and the purchaser's ability to identifyneed-yet the rhetoric of consumerism.This may produce two forces for higher spending.Firstly, rationing based on purchasers' priorities translated into contracts with providers may still be politically unacceptable (hence the recent problems over interleukin at the Christie Hospital, Manchester).Yet, secondly, consumers will demand "production line" medicine and "trendy" procedures, whether they meet need, defined by experts, or not.In aggregate these forces will push for higher NHS spending.This may be fine.After all, Britain is a very low spender on health.And public spending is the most effective and efficient way to increase expenditure on health.The problem hitherto has been the conventional wisdom, on the right and the left, that only moving to an insurance based or partly private financing system could boost aggregate spending.It would be an ironv to be savoured if the long term fallout of the review was higher public spending and little or no reliance on competitive markets.
Cataract Surgery in Patient Who Sneezes-Reply
Authors: David Shoch
Journal: JAMA (1985)

In Reply.—  Drs Gross and Hoffer recommend phacoemulsification cataract extraction for the patient described in the original question. I would agree that an extracapsular extraction is safer for this man, and I would prefer it to an intracapsular procedure. The question as to whether phacoemulsification is safer than a planned extracapsular is somewhat moot. It is true that phacoemulsification can be done through a 3-mm incision, but since we all agree that an intraocular lens is appropriate, the incision would have to be enlarged to 7 mm to insert the lens. Planned extracapsular cataract surgery can be done comfortably through a 10-mm incision. There may be some advantage to an incision 3 mm smaller, but I do not believe this is critical. The essential point is the one with which we all agree—an extracapsular procedure would be safer than intracapsular extraction.  As to general anesthesia for this patient, I agree
Antisense oligonucleotides in therapy for neurodegenerative disorders
Authors: Melvin M. Evers, Lodewijk J.A. Toonen, Willeke M.C. van Roon-Mom
Journal: Advanced Drug Delivery Reviews (2015)

Antisense oligonucleotides are synthetic single stranded strings of nucleic acids that bind to RNA and thereby alter or reduce expression of the target RNA. They can not only reduce expression of mutant proteins by breakdown of the targeted transcript, but also restore protein expression or modify proteins through interference with pre-mRNA splicing. There has been a recent revival of interest in the use of antisense oligonucleotides to treat several neurodegenerative disorders using different approaches to prevent disease onset or halt disease progression and the first clinical trials for spinal muscular atrophy and amyotrophic lateral sclerosis showing promising results. For these trials, intrathecal delivery is being used but direct infusion into the brain ventricles and several methods of passing the blood brain barrier after peripheral administration are also under investigation.
Clinic- Rather than Self-Monitoring of Home Blood Samples: Relevance of Day-to-Day Variability to Decision Making
Authors: E A Ward, M A Phillips, G M Ward, R W Simpson, R Mullins, R C Turner
Journal: Diabetes Care (1980)

The day-to-day variability of blood glucose concentrations in juvenile diabetes means that it is often more reasonable to aim to achieve a generally good pattern of blood glucose control, rather than regularly to assess the next insulin dose after each blood glucose measurement. This means that immediate assessment by the patient of his blood glucose concentrations is not always necessary. We have investigated control in 22 insulin-requiring diabetic patients by means of a monthly series of four blood samples taken during a day into collector bottles and transported to a laboratory for blood glucose assay. The overall means before breakfast, before lunch, before dinner, and before bed were 6.1, 5.8, 7.3, and 7.2 mmol/L, respectively. In many patients, sufficiently good control can be obtained by this method so that it is not necessary to ask them to measure their own blood glucose concentrations or to ask them to obtain the fairly expensive meters for reading glucose oxidase strips. Control would then probably be best assessed by a series of three daily profiles taken once per month, with, if necessary, the results being discussed with the patient. On the other hand, in more unstable diabetes, home assessment by patients of blood glucose measurements is indicated.
Interleukin 1 gene expression in adult T cell leukemia.
Authors: Y Wano, T Hattori, M Matsuoka, K Takatsuki, A O Chua, U Gubler, W C Greene
Journal: Journal of Clinical Investigation (1987)

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.
The IL-15 superagonist ALT-803 enhances anti-CD20 antibody-directed NK cell ADCC and in vivo clearance of B cell lymphomas
Authors: Maximillian Rosario, Bai Liu, Lin Kong, Stephanie E Schneider, Emily K Jeng, Peter R Rhode, Hing C Wong, Todd A Fehniger
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts NK cells are innate lymphoid cells that mediate potent anti-tumor responses against B cell malignancies in conjunction with anti-CD20 mAbs. ALT-803 is a superagonist IL-15 and dimeric IL-15Rα-IgG-Fc fusion protein that effectively trans-presents IL-15 and exhibits prolonged in
Fusion Inhibition — A Major but Costly Step Forward in the Treatment of HIV-1
Authors: Karen T. Tashima, Charles C.J. Carpenter
Journal: New England Journal of Medicine (2003)

Two studies reported in this issue of the Journal 1,2 provide heartening news of the success of a new antiretroviral drug in decreasing plasma human immunodeficiency virus (HIV) RNA levels in patients for whom the available combination antiretroviral regimens are no longer effective. These reports are especially noteworthy in that they describe the first controlled trials of the fusion inhibitor enfuvirtide, a representative of a new class of drugs that prevent the entry of HIV type 1 (HIV-1) into the target cells of the host.3 Enfuvirtide specifically prevents the fusion of the HIV-1 transmembrane (gp41) glycoprotein with the CD4 receptor . . .
Flaws of drug instrumentalization
Authors: Joel Swendsen, Michel Le Moal
Journal: Behavioral and Brain Sciences (2011)

Abstract The adaptive use of drugs, or “drug instrumentalization,” is presented as a reality that the scientific literature has largely ignored. In this commentary, we demonstrate why this concept has limited value from the standpoint of nosology, why it should not be viewed as “adaptive,” and why it has dangerous implications for policy and public health efforts.
A TRANSPARENT MASK
Authors: David Kaplan
Journal: JAMA (1930)

At the suggestion of a colleague who saw me using it, I am here describing a transparent mask which I made several years ago to protect my face during oral and nasal examinations. It consists of a film and two round head paper fasteners one-half inch long. A roentgenogram that has been spoiled or is of no more value as a negative is washed of its emulsion. A 14 by 17 inch film when cut into four parts will make shields 7 by 8½ inches each, which is the proper size for the average face. From the center of one of the 7 inch ends, an isosceles triangle of 3 inch base and 2½ inch vertex is cut. Two holes as large as the heads of the paper clasps are then cut 1 inch from the 8½ inch sides and one-half inch from the cut 7 inch end (fig. 1).
The Incidence of End-Stage Renal Disease Is Increasing Faster than the Prevalence of Chronic Renal Insufficiency
Authors: Chi-yuan Hsu, Eric Vittinghoff, Feng Lin, Michael G. Shlipak
Journal: Annals of Internal Medicine (2004)

Background: The steady increase in end-stage renal disease (ESRD) incidence is a worldwide public health crisis. Objective: To determine whether the increasing incidence of ESRD in the United States is preceded by increased prevalence of chronic renal insufficiency. Design: Birth cohort analysis. Setting: Nationally representative Second and Third National Health and Nutrition Examination Surveys (NHANES II [1976–1980] and III [1988–1994]) and nationally comprehensive U.S. Renal Data System registry. Patients: Adults, 20 to 74 years of age, surveyed in NHANES II (midpoint, 1978) and NHANES III (midpoint, 1991), and adults, 25 to 79 years of age, who developed ESRD in 1983 and 1996. Measurements: Prevalent chronic renal insufficiency (estimated glomerular filtration rate, 15 to 59 mL/min per 1.73 m2) and new ESRD cases. Results: From 1978 to 1991, the number of adults age 20 to 74 years with chronic renal insufficiency increased from 2.6 to 3.9 million, an increase in prevalence from 1970 to 2460 per 100 000 persons. However, the increased incidence of ESRD was even greater during this period. For every 1000 adults with chronic renal insufficiency in 1978, 9 new cases of ESRD developed in 1983, but every 1000 adults with chronic renal insufficiency in 1991 produced 16 new cases of ESRD in 1996 (relative risk, 1.7 [95% CI, 1.1 to 2.7]). Limitations: We could not follow individual patients with chronic renal insufficiency for the development of ESRD, and we used estimated rather than measured glomerular filtration rate. Conclusions: During the period examined, growth in incident ESRD outpaced growth in prevalent chronic renal insufficiency, demonstrating that the ESRD epidemic in the United States is not merely a function of more cases of kidney disease. Future research should examine other potential contributors to ESRD growth, such as improved survival from nonrenal diseases and more liberal entry into treatment programs.
Allospecific cytolytic T lymphocytes recognize conformational determinants on hybrid mouse transplantation antigens.
Authors: J A Bluestone, M Foo, H Allen, D Segal, R A Flavell
Journal: The Journal of Experimental Medicine (1985)

Alloreactive cytolytic T cell (CTL) lines and clones have been used to identify the sites of polymorphism of antigens of the major histocompatibility complex (MHC). Specific CTL were generated against wild-type H-2b products by cells from H-2b mutant mice that had one or a few amino acid changes in either the alpha 1 or alpha 2 domains of the Kb or Db class I molecules. These CTL populations, which might be expected to react with determinants expressed on single MHC domains, were examined for lytic activity on L cells expressing newly constructed hybrid class I molecules. Transformed cell lines expressing native class I molecules or hybrid class I molecules in which the alpha 1 and alpha 2 domains of H-2Kb had been substituted by those domains of H-2Db were lysed by H-2Db-specific CTL. Similarly, all H-2Kb-specific CTL recognized hybrid molecules in which the alpha 1 and alpha 2 domains of H-2Kb were inserted into the H-2Db molecule. In contrast, exchange of the alpha 1 domains of H-2Kb and H-2Db resulted in a total loss of recognition by Kb and Db-specific CTL. These results suggest that the allodeterminants recognized by H-2 mutant CTL are influenced by interactions between the alpha 1 and alpha 2 domains, findings similar to those seen using conventional alloreactive T cells (11). These results were compared to the binding of alloreactive mAbs, including 5 new mAbs specific for the Kb molecules. Finally, it was shown that primary and secondary CTL responses could be generated by direct sensitization against hybrid class I molecules, demonstrating that these molecules express neoantigenic determinants recognized by alloreactive CTL.
Cancer of the Genitourinary Tract
Authors: Harry W. Schoenberg
Journal: JAMA (1980)

<i>Cancer of the Genitourinary Tract</i>, edited by Johnson and Samuels, is a timely publication and one that should prove useful to urologists and oncologists who are actually engaged in the day-to-day treatment of patients with cancer of the genitourinary tract. This publication is not a text but a group of essays presented at the 23rd Annual Clinical Conference on Cancer of the M. D. Anderson Hospital and Tumor Institute of Houston. As such, it does not attempt to cover all aspects of genitourinary cancer or discuss established principles, but instead it places emphasis on those areas of diagnosis, treatment, and research where new information is being developed. Immunology, chemotherapy, radiation therapy, and combined therapies are clearly presented by established investigators who provide ample experimental and clinical data. The fact that the areas covered are those in which change is most likely to occur in no way detracts from the usefulness
Improved survival in multiple myeloma and the impact of novel therapies
Authors: Shaji K. Kumar, S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Steven R. Zeldenrust, David Dingli, Stephen J. Russell, John A. Lust, Philip R. Greipp, Robert A. Kyle, Morie A. Gertz
Journal: Blood (2007)
Points from Letters: Research into Alcoholism
Authors: A. L. Owen
Journal: BMJ (1972)

volve us in a bureaucratic jamboree, invite us to participate in the most unprofessional labour tactics, and suffer administrative counteraction.Simultaneously it could re- move one of the bases of our professional standing, full-time patient responsibility.It opens the door to future administrative elimination of "overtime," with substitution of alternative medical cover.Full-time consultants are likely to be hard hit."Right to private practice" invites the assumption of some remuneration from private practice when finally pricing the contract.But some full-time consultants re- ject this form of practice and others have deliberately rejected their access to private practice to leave this to their part-time colleagues or work in medical or geo- graphical areas where private practice is rare.Has anyone considered how these un-