tbuckley/cabot-search huggingface dataset:
Efficacy versus Effectiveness: A Direct Comparison of the Outcome of Treatment for Mild to Moderate Depression in Randomized Controlled Trials and Daily Practice
Authors: Rosalind van der Lem, Nic J.A. van der Wee, Tineke van Veen, Frans G. Zitman
Journal: Psychotherapy and Psychosomatics (2012)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Results from randomized controlled trials (RCTs) are considered to give the most reliable information on treatment outcome (efficacy). Yet, the generalizability of efficacy results to daily practice (effectiveness) might be diminished by the design of RCTs. The STAR*D trial approached daily practice as much as possible, but still has some properties of an RCT. In this study, we compare results from treatment of major depressive disorder (MDD) in routine clinical practice to those of RCTs and STAR*D. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Effectiveness in routine clinical practice was compared with efficacy results from 15 meta-analyses on antidepressant, psychotherapeutic and combination treatment and results from STAR*D. Data on daily practice patients and treatments were derived from a routine outcome monitoring (ROM) system. Treatment outcome was defined as proportion of remitters (MADRS ≤10) and within-group effect size. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; From ROM, 598 patients suffering from a MDD episode according to the MINI-plus were included. Remission percentages were lower in routine practice than in meta-analyses for all treatment modalities (32 vs.40–74%). Differences were less explicit for antidepressants (21 vs. 34–47%) than for individual psychotherapy (27 vs. 34–58%; effect size 0.85 vs. 1.71) and combination therapy (21 vs. 45–63%), since only 60% of the meta-analyses for antidepressants showed significant differences with ROM, while for psychotherapy and combination treatment almost all meta-analyses showed significant differences. No differences in effectiveness were found between routine practice and STAR*D (antidepressants 27 vs. 28%; individual psychotherapy 27 vs. 25%; combination treatment 21 vs. 23%, respectively). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Effectiveness of treatment for mild-to-moderate MDD in daily practice is similar to STAR*D and significantly lower than efficacy results from RCTs.
On Decision Making Surrounding Drug Therapy: A Continuing Dilemma
Authors: Mary Ellen Avery, Victor Chernick
Journal: New England Journal of Medicine (1977)

A time must exist when an established drug proposed for a new treatment is experimental and requires all the apparatus of informed consent, protocols and restricted availability; at some time later the drug enjoys the approbation of common use, accepted or even highly recommended for a stated condition. When, how, and with whose permission does this translation from experimental to standard therapy occur? The answers are not clear.The physician can be guilty of the sin of commission by premature use of a drug when long-term sequelae may not be known, or equally guilty of the sin of omission if . . .
Inhibition of glycogen synthase kinase 3 ameliorates liver ischemia/reperfusion injury via an energy-dependent mitochondrial mechanism
Authors: Hailong Fu, Haitao Xu, Huan Chen, Yonghua Li, Weiwei Li, Qiufeng Zhu, Qingqing Zhang, Hongbin Yuan, Fang Liu, Quanxing Wang, Mingyong Miao, Xueyin Shi
Journal: Journal of Hepatology (2014)
Renal Artery Stenosis, Hypertension, and Polycythaemia
Authors: R. G. Luke, A. C. Kennedy, W. B. Stirling, G. A. McDonald
Journal: BMJ (1965)

In 27 subjects without any disorder of calcium metabolism the plasma calcium, measured four times daily, was significantly reduced when the calcium intake was reduced.The urine calcium also fell significantly.Eleven normal subjects received a normal and a low-calcium diet on successive days.The ultrafilterable calcium fell significantly on the day of the low calcium intake.There was a significant correlation between the changes in the plasma and urinary calcium produced by the alteration in the calcium intake.The relative magnitude suggests that if a maximum tubular reabsorptive capacity for calcium exists it was not exceeded under the conditions of these observations.Thus it would appear that changes in urine calcium brought about by variations in calcium intake could be accounted for by small but significant changes in plasma ultrafilterable calcium.
Testing for rare variant associations in complex diseases
Authors: Jennifer Asimit, Eleftheria Zeggini
Journal: Genome Medicine (2011)

The study of rare variants holds the promise of accounting for some of the missing heritability in complex traits. Next-generation sequencing technologies enable probing of variation across the full spectrum of allele frequencies. Multiple methods for the analysis of rare variants have been proposed and, recently, Ionita-Laza et al. have presented an approach with the theoretical capacity to detect risk and protective variants. The identification of rare risk variants could have major implications in understanding complex disease etiopathogenesis.
The Changing Epidemiology of Invasive Meningococcal Disease in Canada, 1985 Through 1992
Authors: Christine M. Whalen
Journal: JAMA (1995)

<h3>Objective.</h3> —To describe the occurrence of invasive meningococcal disease (IMD) in Canada with respect to demographic variables and characteristics of the isolated strains of<i>Neisseria meningitidis</i>. <h3>Design.</h3> —National surveillance case series. <h3>Setting.</h3> —Canada, 1985 through 1992. <h3>Outcome Measures.</h3> —Morbidity and mortality. <h3>Main Results.</h3> —The incidence of IMD averaged 1.38 per 100 000 person-years, with considerable regional variation. In 1988, serogroup C organisms became more common, with one strain of the electrophoretic type 37 (ET-37) complex of<i>N meningitidis</i>, termed ET-15, the predominant group C strain identified. With the increase in group C disease, a greater proportion of cases were older than 5 years. By 1991, ET-15 was the most common strain identified in most parts of the country. Electrophoretic type 15 had a case fatality of 17.8% vs 8.1% for all other IMD (<i>P</i>&lt;.001). Among cases 20 years and older the case fatality for ET-15 was 22.4%. <h3>Conclusions.</h3> —The group C, ET-15 strain of<i>N meningitidis</i>, first identified in Canada, was more virulent than other prevalent strains during this period. Active surveillance, rapid identification, and typing of<i>N meningitidis</i>will assist public health decision making in the control of emerging strains. (<i>JAMA</i>. 1995;273:390-394)
P2 purinoceptors contribute to ATP-induced inhibition of L-type Ca2+ current in rabbit atrial myocytes
Authors: T Yamamoto
Journal: Cardiovascular Research (1999)

Adenine compounds, including adenosine-5'-triphosphate (ATP) and adenosine (Ado), exert inhibitory effects on myocardium via P1 (subtype A1) purinoceptors. However, ATP per se is a potent activator of P2 purinoceptors. Our aim was to elucidate the respective roles of P1 and P2 purinoceptors in the actions of ATP on L-type calcium current (ICa) in rabbit atrial cells.A whole cell clamp technique was used to record ICa in single atrial cells from the rabbit heart. ATP (0.1 mumol/1-3 mmol/l) produced an inhibitory effect on ICa prestimulated by isoproterenol (ISO, 30 nmol/l), even in the presence of Ado (1 mmol/l). Both 1,3-dipropyl-8-cyclopentylxanthine (A1 blocker) and suramin (P2 blocker) partially blocked the ATP-induced inhibition of ICa, while their co-application nearly completely abolished the effect of ATP. ATP-gamma S (30 mumol/l) inhibited ISO-stimulated ICa significantly, and this inhibition was completely blocked by suramin. alpha, beta-Methylene-ADP, an inhibitor of hydrolysis of AMP to Ado, eliminated the suramin-resistant component of ICa inhibition by ATP. Pretreatment with pertussis toxin (PTX) abolished the ATP inhibition of ICa. Both intracellular dialysis with 8Br cAMP and the application of forskolin plus 3-isobutyl-1-methylxanthine also eliminated the effect of ATP.Both P1 and P2 purinoceptors are involved in the ATP inhibition of ISO-stimulated ICa in rabbit atrial cells. The P1 stimulation by ATP results from hydrolysis of ATP to Ado. Both the P2- and the P1-mediated effects of ATP and Ado, respectively. involve a PTX-sensitive and cAMP-dependent pathway.
"THE RELATIONS OF MATTER AND MIND."
Authors: R. E. HAUGHTON
Journal: JAMA (1895)

<h3>REVIEW.</h3> In reading the article with the above title to its close, I find in the last paragraph this remarkable statement in the form of an interrogatory, viz.: "Do not these converging testimonies focus the truth in the proposition, that the somatic mind of man is (clearly enough) the highest manifestation and legitimate sequence of the primal law of<i>matter</i>and<i>motion</i>expressed by the Creator in the beginning on the elements of the earth?" The author of this paper paper said in his Presidential address before theAmerican Medical Association: "The progress in medicine in the immediate future must be along biologic lines." So in accentuating this thought, I accept the position assumed as to the progress in medicine, but do not accept the final conclusion arrived at in the quotation in the paragraph alluded to. It is to my mind the enunciation of the exploded idea of evolution,
Challenging and Emerging Conditions in Emergency Medicine
Authors: Arthur Pancioli
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
New communications technologies can improve responses to disasters, says report
Authors: P. Moszynski
Journal: BMJ (2012)

New communications technologies can contribute significantly to the work of humanitarian agencies, says a new study. They can help people “build their resilience to crises by improving livelihoods, mitigating risks, and preparing for disasters” and help provide health information through mass media and community mobilisation, it says.

The study is from BBC Media Action, the new name for the BBC’s international development charity formerly known as the World Service Trust. Its policy director, James Deane, told the BMJ that the charity used media and communication “to help people affected by humanitarian emergencies cope …
Journal Editors and the Press
Authors: Claude E. Welch
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The unusual editorials in<i>JAMA</i>by Gail McBride and Lawrence D. Grouse, MD, PhD (1981;245:375), concerning the "Ingelfinger Rule" and the "Relman Recommendation" suggest that the editors of the<i>New England Journal of Medicine (NEJM)</i>wish to become sole arbiters to decide what medical information is worthy of publication. Since these editorial policies of the NEJM were developed with the complete agreement of the Committee on Publications of the Massachusetts Medical Society, of which I was chairman during that period, responsibility for these decisions did not devolve solely on the editors. The policy of the<i>NEJM</i>in simple terms is that the value and accuracy of presentations, abstracts, and articles is impossible to determine in a few hours or days and that the public is served best by careful prepublication evaluation by appropriate experts. The<i>NEJM</i>certainly makes no claim of infallibility; however, this system of vigorous
Abstract 4990: PP2A signaling is overridden by MEK/ERK activity leading to suppression of Bim and protection of melanoma cells from ER stress-induced apoptosis
Authors: Kwang Hong Tay, Hsin-Yi Tseng, Lei Jing, Chen Chen Jiang, Yan Ye, Rick Thorne, Tao Liu, Peter Hersey, Xu Dong Zhang
Journal: Cancer Research (2012)

Abstract Endoplasmic reticulum (ER) stress triggers apoptosis by activating Bim in diverse types of cells. This involves dephosphorylation of Bim by protein phosphatase 2A (PP2A). However, melanoma cells are largely resistant to ER stress-induced apoptosis, indicating that Bim activation is suppressed in melanoma cells undergoing ER stress. We show here that this is due to increased activation of MEK/ERK signaling that overrides the PP2A activity leading to enhanced Bim phosphorylation and subsequent proteosomal degradation. Upon pharmacological ER stress, the Bim protein expression was rapidly downregulated after an initial increase, despite its sustained upregulation at the transcriptional level. Although PP2A exerted the dephosphorylating effect on BimEL, its activity appeared to be superseded by increased activation of MEK/ERK signaling that led to enchanced phosphorylation and accelerated turnover of the protein. Moreover, in contrast to its upregulation by ER stress in MCF-7 and HEK293 cells, PP2A was downregulated in melanoma cells undergoing ER stress. Pharmacological activation or enforced expression of PP2A decreased ERK and Bim phosphorylation, up-regulated Bim expression, and rendered melanoma cells sensitive to ER stress-induced apoptosis. Notably, instead of direct interaction with Bim, PP2A reduced Bim phosphorylation indirectly by dephosphorylating ERK in melanoma cells. Together, these results identify a key resistance mechanism of melanoma cells against apoptosis induced by ER stress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4990. doi:1538-7445.AM2012-4990
Unresponsiveness to Glucantime Treatment in Iranian Cutaneous Leishmaniasis due to Drug-Resistant Leishmania tropica Parasites
Authors: Ramtin Hadighi, Mehdi Mohebali, Patrick Boucher, Homa Hajjaran, Ali Khamesipour, Marc Ouellette
Journal: PLoS Medicine (2006)

Recent circumstantial evidence suggests that an increasing number of Iranian patients with cutaneous leishmaniasis are unresponsive to meglumine antimoniate (Glucantime), the first line of treatment in Iran. This study was designed to determine whether the clinical responses (healing, or non-healing) were correlated with the susceptibility of Leishmania parasites to Glucantime.In vitro susceptibility testing was first performed on 185 isolated parasites in the intracellular mouse peritoneal macrophage model. A strong correlation between the clinical outcome and the in vitro effective concentration 50% (EC50) values was observed. Parasites derived from patients with non-healing lesions had EC50 values at least 4-fold higher than parasites derived from lesions of healing patients. A selection of these strains was typed at the molecular level by pulsed-field gels and by sequencing the pteridine reductase 1 (PTR1) gene. These techniques indicated that 28 out of 31 selected strains were Leishmania tropica and that three were Leishmania major. The L. major isolates were part of a distinct pulsed-field group, and the L. tropica isolates could be classified in three related additional pulsed-field groups. For each pulsed-field karyotype, we selected sensitive and resistant parasites in which we transfected the firefly luciferase marker to assess further the in vitro susceptibility of field isolates in the monocyte cell line THP1. These determinations confirmed unequivocally that patients with non-healing lesions were infected with L. tropica parasites resistant to Glucantime. Additional characterization of the resistant isolates showed that resistance is stable and can be reversed by buthionine sulfoximine, an inhibitor of glutathione biosynthesis.To the authors' knowledge, this is the first report of proven resistant parasites contributing to treatment failure for cutaneous leishmaniasis and shows that primary Glucantime-resistant L. tropica field isolates are now frequent in Iran.
An Address on Acute Dilatation of the Heart in Diphtheria, Influenza, and Rheumatic Fever: Delivered before the Manchester Medical Society
Authors: D. B. Lees
Journal: BMJ (1901)

MEDICAL Juwho was languid and anaemic, with a spleen reaching half wayto' his umbilicus, and, decided -,excess of leucocytes; he improved under the use of arsenic, and I lost sight .ofhim.I eham lately had an opportunity of exaamining him, and-*found him quite well.' Hnorrhage, high-fever, diarrhba, '-voiiting; and cedeitL,.`4eficiionturea, and the pres6tce of acetone may be looked .ponas signs of grave prognostic significance; Dea'th may occur from general asthenia, from coma of Kussmauls'type closely resembling that' which occurs i'na diabetes,; from cerebral hlemorrhage, or from some intercurrent.affection.The tisueSgpot' i*rt'mmay be Ouhd, Ato be inflltrated with micr.orgarnisms,suggesting that theiir resisitan&e -to ordinary infections had been greatly reduced.' ' TIEA~TMENT..The 'treataent should be i to.place' the patient under the most favourable hygienie.oonditionsina healthy bracing climyate on a dr soil, 'itli'ic6d' ,ir good' food and favouiaPte; surroundings .-andhfbo4ld`i`f'.possfiblebe free from all sources of.worry or menab l eranction The most valuable-drug is arsenic,.whieh!i#hoi'ld.-be-.eonmenced in small doses and gradually increased-.',''A.1 the above indica- tions may probably be best fulfilled .bysending the patient to undergo.a course. of arsenical waters :at La.Bourboule, in France (Department Puy-de-DTme)._Cold douches with the alvanic and faradic currents m,ay possibly be useful.uinine and iron are often employeda-d oxygen inhalations may be tried, but are probalyonly.resortedto. in the later and more hopeless stages.The 'operation of splenectomy is hardly justified from our pregent.pathologicalstandpoint as.a rational proceeding; but it .hasalsQa-gainst it the ter- rible obJeetion that, out of.twenty-four' operations, only one patient has -recovered.The clief danger seems to be .that; in leukaemic patients the blood has lost the power.by-which normal haemostasis occurs, and, the cut surfaces continue to bleed from vessels which offer nothing that the surgeon can tie.Transfusion appears to be usel;ess.Ewart has recom- mended the inhalation of carbonic acid gas, but no one has confirmed his favourable opinion of this treatment.The-enlarged spleen may be supported by a, bandage or belt, and. the stomach troubles are relieved 'by the administra- tion of small doses of dilute mioeral aeid after meals.'
α-1-antitrypsin phenotypes in hepatocellular carcinoma
Authors: Sugantha Govindarajan, Mary Ashcavai, Robert L. Peters
Journal: Hepatology (1981)

α-1-Antitrypsin deficiency due to homozygous Pi ZZ state is reported to be associated with cirrhosis and hepatocellular carcinoma (HCC); however, the role of heterozygous Pi Z state is not definitively known. In order to investigate the possible association, we studied the phenotypic distribution of α-1-antitrypsin variants (Pi) in 124 cases of HCC. Two thousand ten normal American Red Cross blood donors were studied as controls. Twelve patients with HCC had aberrant pheno-types, an incidence of 9.67% as compared to 8.36% among normal controls. Nine of 12 patients with HCC with aberrant Pi type had cirrhosis; 5 of the 9 had cirrhosis due to hepatitis B virus; 2 of the 9 had alcoholic liver disease with cirrhosis, and 2 had cryptogenic cirrhosis. The three patients with HCC arising in noncirrhotic livers who also had aberrant Pi phenotypes, had a relatively rare variety of HCC called fibrolamellar type. Z gene was found in five patients: all five were MZ. Incidence of MZ phenotype in HCC was similar to that of the normal control population (4.0% in HCC and 2.9% in the controls). However, 3 of 5 MZ were associated with fibrolamellar HCC. Another aberrant phenotype found among the patients with HCC was MF (fast moving) which occurred with an incidence of 2.41% as compared to none in the control group. In conclusion, we found no significant increase in the incidence of Z gene among 124 patients with HCC as compared to the normal population.
Therapeutic Priority of the PI3K/AKT/mTOR Pathway in Small Cell Lung Cancers as Revealed by a Comprehensive Genomic Analysis
Authors: Shigeki Umemura, Sachiyo Mimaki, Hideki Makinoshima, Satoshi Tada, Genichiro Ishii, Hironobu Ohmatsu, Seiji Niho, Kiyotaka Yoh, Shingo Matsumoto, Akiko Takahashi, Masahiro Morise, Yuka Nakamura, Atsushi Ochiai, Kanji Nagai, Reika Iwakawa, Takashi Kohno, Jun Yokota, Yuichiro Ohe, Hiroyasu Esumi, Katsuya Tsuchihara, Koichi Goto
Journal: Journal of Thoracic Oncology (2014)

IntroductionThe information regarding therapeutically relevant genomic alterations in small cell lung cancer (SCLC) is not well developed. We analyzed the SCLC genome using an integrative approach to stratify the targetable alterations.MethodsWe performed whole exon sequencing (n = 51) and copy number analysis (n =47) on surgically resected tumors and matched normal tissue samples from treatment-naive Japanese SCLC patients.ResultsThe demographics of the 51 patients included in this study were as follows: median age, 67 years (range, 42–86 years); female, 9 (18%); history of smoking, 50 (98%); and pathological stage I/II/III/IV, 28/13/9/1, respectively. The average number of nonsynonymous mutations was 209 (range, 41–639; standard deviation, 130). We repeatedly confirmed the high prevalence of inactivating mutations in TP53 and RB1, and the amplification of MYC family members. In addition, genetic alterations in the PI3K/AKT/mTOR pathway were detected in 36% of the tumors: PIK3CA, 6%; PTEN, 4%; AKT2, 9%; AKT3, 4%; RICTOR, 9%; and mTOR, 4%. Furthermore, the individual changes in this pathway were mutually exclusive. Importantly, the SCLC cells harboring active PIK3CA mutations were potentially targetable with currently available PI3K inhibitors.ConclusionsThe PI3K/AKT/mTOR pathway is distinguishable in SCLC genomic alterations. Therefore, a sequencing-based comprehensive analysis could stratify SCLC patients by potential therapeutic targets.
Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy
Authors: K.B. GORDON, L.S. CHAN, D.T. WOODLEY
Journal: British Journal of Dermatology (1997)

Treatment of epidermolysis bullosa acquisita (EBA) with conventional therapy frequently does not result in improvement. Extracorporeal photochemotherapy (ECP) is a novel immunomodulating technique which might be of benefit in the treatment of autoimmune disease. We prospectively studied three patients with refractory EBA who were treated with ECP. All three patients had improvement in objective measurement of their disease severity while two of the three had significant subjective improvement in their skin fragility and the clinical activity of their disease. Both the objective and subjective manifestations of the disease continued to improve 6 months after completion of the protocol. ECP may be therapeutic option in the treatment of patients with EBA who are refractory to conventional therapy.