tbuckley/cabot-search huggingface dataset:
The Results of combined modality therapy for limited stage small cell lung cancer (LD-SCLC) in the elderly
Authors: S. E. Schild, P. J. Stella, B. J. Brooks, S. Mandrekar, J. A. Bonner, W. L. McGinnis, D. A. Nikcevich, A. A. Adjei, A. Jatoi, J. R. Jett
Journal: Journal of Clinical Oncology (2004)

7043 Background: A phase III trial was conducted by the NCCTG to determine whether chemotherapy (Etoposide and Cisplatin) plus either twice-daily radiotherapy(BID RT) or once-daily radiotherapy(QD RT) resulted in a better outcome for LD-SCLC. No difference in survival was identified between the 2 treatment arms. This secondary analysis examined the relationship between age and outcome for patients treated on this trial. Methods: This study included 263 patients with LD-SCLC and an ECOG performance status of ≤2 who were randomized to QD RT or split course BID RT. The outcomes of the 209(79%) younger patients(<70 years old) were compared to the 54(21%) elderly patients(≥70 years old). Results: Elderly patients presented with significantly greater weight loss and poorer performance status. The overall incidence of grade ≥3 (3+) or grade ≥4 (4+) toxicity was not significantly greater in elderly patients. However, one specific toxicity, grade 4+ pneumonitis occurred in 0% of those <70 years compared to 6% of older patients(p=0.008). Although hematologic toxicity was not significantly worse in those ≥70 years old, it was significantly worse in patients ≥65 years old compared to younger individuals. Grade 4+ hematologic toxicity occurred in 51% of patients ≥65 years old compared to 37% of younger individuals (p=0.03). Grade 5 toxicity occurred in 3/54(6%) patients ≥70 years old compared to 1/209(0.5%) younger individuals (p=0.03). These deaths occurred due to pneumonitis in 3 elderly patients and infection in the patient <70 years of age. The 2-year and 5-year survival rates were 48% and 22% in younger patients compared to 33% and 17% in the elderly patients(p=0.14). Conclusions: Despite having more weight loss, poorer performance status, and increased toxicity, survival was not significantly worse in older individuals. Fit elderly patients with LD-SCLC can receive combined modality therapy if carefully monitored. Future studies should explore ways to decrease toxicity of therapy in all patients but especially in the elderly. No significant financial relationships to disclose.
Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer’s Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial
Authors: Lon S. Schneider, Constantine Frangakis, Lea T. Drye, D.P. Devanand, Christopher M. Marano, Jacob Mintzer, Benoit H. Mulsant, Cynthia A. Munro, Jeffery A. Newell, Sonia Pawluczyk, Gregory Pelton, Bruce G. Pollock, Anton P. Porsteinsson, Peter V. Rabins, Lisa Rein, Paul B. Rosenberg, David Shade, Daniel Weintraub, Jerome Yesavage, Constantine G. Lyketsos
Journal: American Journal of Psychiatry (2016)

Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed.In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatment outcome were assessed, along with six additional predictors. The authors then used a two-stage multivariate method to select the most likely predictors; grouped participants into 10 subgroups by their index scores; and estimated the citalopram treatment effect for each.Five covariates were likely predictors, and treatment effect was heterogeneous across the subgroups. Patients for whom citalopram was more effective were more likely to be outpatients, have the least cognitive impairment, have moderate agitation, and be within the middle age range (76-82 years). Patients for whom placebo was more effective were more likely to be in long-term care, have more severe cognitive impairment, have more severe agitation, and be treated with lorazepam.Considering several covariates together allowed the identification of responders. Those with moderate agitation and with lower levels of cognitive impairment were more likely to benefit from citalopram, and those with more severe agitation and greater cognitive impairment were at greater risk for adverse responses. Considering the dosages used and the association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may be limited to a subgroup of people with dementia.
Adverse Effects Associated With Proton Pump Inhibitors
Authors: Adam Jacob Schoenfeld, Deborah Grady
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Abstract 12357: Enzyme Kinetic Model Reveals Novel Characteristics of Pharmacodynamic Interaction of NSAIDs and Aspirin at COX-1, Which Lead to High on Aspirin Platelet Reactivity (HAPR)
Authors: Saghar Bagheri, Dieter Hafner, Thomas Hohlfeld
Journal: Circulation (2014)

Introduction: Non-aspirin NSAIDs attenuate the antiplatelet action of aspirin leading to High on Aspirin Platelet Reactivity (HAPR). However, detailed features of this interaction are still unresolved. Both competitive as well as non-competitive interaction at the cyclooxygenase-1 (COX-1) enzyme have been proposed. Hypothesis: We examined whether competitive enzyme kinetics describe COX-1 inhibition by aspirin and HAPR and if they are compatible with results obtained experimentally. Methods: We have developed an enzyme kinetic model of the aspirin/NSAID interaction at COX-1 using mathematical modelling and have varied enzyme kinetic parameters to predict the occurrence and the extent of HAPR. Subsequently, the predictions obtained were experimentally verified with selected NSAIDs using light transmission aggregometry and immunoassay for platelet thromboxane (TX) synthesis. Results: Enzyme kinetic modelling predicted that only low- and medium-affinity NSAIDs (Ki ≥1 μM), but not high-affinity NSAIDs, interfere with COX-1 inhibition by aspirin. Furthermore, the interaction was predicted to be most extensive at high concentrations of arachidonic acid (1mM). Experimental results confirmed the model by showing that low or medium-affinity COX-1 inhibitors piroxicam, dipyrone and celecoxib (each n=5-10) largely prevented the inhibition of aggregation and platelet TX synthesis in vitro by 30 μmol/L aspirin whereas the high-affinity COX-1 inhibitor SC560 (n=6) did not interfere with aspirin at all. In accordance to the mathematical model, aspirin/NSAID interaction was more pronounced in presence of high (1mmol/L) versus low (0.3mmol/L) concentration of arachidonic acid. Hence, the kinetic model was validated experimentally. Conclusion: Both enzyme kinetic modelling and experimental results suggest competitive antagonism of NSAID and aspirin at COX-1 as a cause for HAPR, possibly resulting in cardiovascular events. Critical parameters that influence this interaction are drug concentrations and NSAID affinity. Interestingly, the concentration of arachidonic acid also influences the NSAID/aspirin interaction, suggesting that “fatty acid tone” and lipid metabolism may influence this unfavourable drug/drug interaction.
Resuscitating the Dying Autopsy
Authors: Quique Bassat, Paola Castillo, Pedro L. Alonso, Jaume Ordi, Clara Menéndez
Journal: PLoS Medicine (2016)

Points• Despite the relevant information that postmortem examinations can provide, autopsy rates have been declining worldwide in the last few decades.• Autopsies are especially necessary in low-income countries, where reliable information on cause of death is much more limited and in vivo clinical diagnosis is hampered by the scarce availability of diagnostic tools.• The use of the autopsy or of robust substitutes for this procedure needs to be encouraged as a mechanism for the continuous improvement of clinical diagnosis and as a complement for cause-of-death investigation and surveillance.
Old Soldier, Is It Like This?
Authors: Elizabeth Toll, Seymour I. Toll
Journal: JAMA (2016)

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
Effect of Treatment With Capsaicin on Daily Activities of Patients With Painful Diabetic Neuropathy
Journal: Diabetes Care (1992)

Objective — To establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy. Research Design and Methods — Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and/or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel randomized treatment assignments. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. A visual analogue scale of pain intensity and baseline measurements of the pain's interference with the ability to walk, work, participate in recreational activities, use shoes and socks, sleep, and eat were recorded at onset and at 2-wk intervals. A physician's global evaluation scale assessed changes in pain status from baseline. Results — Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle: 69.5 vs 53.4% with clinical improvement in pain status (P = 0.012), 26.1 vs. 14.6% with improvement in walking (P = 0.029), 18.3 vs. 9.2% with improvement in working (P = 0.019), 29.5 vs. 20.3% with improvement in sleeping (P = 0.036), and 22.8 vs. 12.1% with improvement in participating in recreational activities (P = 0.037). Conclusions — The results from this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities, enhancing the quality of the patient's life.
Evolving general practice consultation in Britain
Authors: P. Wilson
Journal: BMJ (2002)

Editor—Freeman et al plead for longer consultations in British general practice.1 A pilot study performed with six general practitioners in Glasgow shows that breaking the habit of short consultations may be difficult and longer consultations may lead to higher health service costs.

Our study piloted a randomised controlled trial of the effect of an increased booking interval on identification of the patient's psychological distress.2 Each doctor's surgery was randomised to either 10 minutes per patient (the normal booking interval) or 15 minutes. One of us (MS) offered locum sessions to make up the shortfall in available consultations. We recorded 65 consultations at each booking interval for each practitioner. After the consultation, patients completed the general health questionnaire-12; doctors estimated psychological distress using a six point scale and recorded important outcomes of the consultations. Consultations were timed by a research assistant.

Data were collected from 781 consultations. When booking interval was increased by 50% consultation length increased by 12%, from 8.7 minutes to 9.7 minutes. Longer booking intervals significantly increased the number of consultations in which the doctor arranged investigations (19.4% v 27.9%; P=0.0069) and follow up appointments (43.8% v 53.7%; P=0.0072). There was no significant effect on the proportion of consultations in which prescriptions were issued (51.0% v 54.7%; P=0.34), physical examination carried out (66.8% v 66.8%; P=0.96), or referral made (14.0% v 10.7%; P=0.20).

There were no significant differences in identification of psychological distress between long or normal booking intervals (odds ratio 1.00 (95% confidence interval 0.63 to 1.59)).

Although booking interval increased by 50%, consultation length increased by only 12%. This raises the question of what the doctors did with the extra time. It has been argued that increasing the length of consultations will save time and resources. Our results suggest that the opposite is true; doctors ask more patients to make follow up appointments after longer consultations and perform more investigations. Perhaps doctors given more time with patients simply uncover more problems. The lack of impact of an increased booking interval on the recognition of psychological distress in patients suggests that structural constraints are insufficient to explain low rates of recognition of distress by general practitioners.

Our results must be interpreted with caution. A more sustained intervention might have led to more major changes in consulting behaviour. Our data suggest, however, that longer consultation intervals may cost more than remuneration for extra general practitioners' time.
Response to Letter Regarding Article, “Frequent Physical Activity May Not Reduce Vascular Disease Risk as Much as Moderate Activity: Large Prospective Study of Women in the United Kingdom”
Authors: Miranda E. G. Armstrong, Jane Green, Gillian K. Reeves, Valerie Beral, Benjamin J. Cairns
Journal: Circulation (2015)

We thank Lin and colleagues for drawing attention to hypotheses about the possible role of heavy manual work and work-related stress in vascular disease.We previously reported associations between coronary heart disease, cerebrovascular disease, and venous thromboembolism risk and the frequency of strenuous activity and of any activity. 1We also assessed the associations between these diseases and walking, gardening, cycling, housework, and strenuous activity, which were reported for the first time ≈3 years after recruitment. 1 At that time, women were asked about whether or not they were in paid work: about half (53%) reported that they were not in paid work.Findings for women not in paid work cannot be confounded by heavy manual work or stress at work.We therefore conducted further analyses for vascular disease risk associated with physical activity, restricted to the 376 732 women who reported not being in paid work, using the date at which they reported their employment status as the start of follow-up.Similar to our previous findings for all women, 1 we again observed that the lowest risks were among women with a moderate frequency of physical activity, suggesting that these associations are not attributable to heavy manual work or stress at work.(There may, of course, be residual confounding with other factors, as discussed in our original article.)The results for the frequency of strenuous physical activity among women who reported not being in paid work are presented here, for comparison with our findings for all women.For coronary heart disease risk (20 861 cases), in comparison with inactive women, the women who were active at most once per week had a relative risk (RR) of 0.85 (95% confidence interval [CI], 0.82-0.87),women active 2 to 3 times per week had an RR of 0.80 (95% CI, 0.77-0.84),women active 4 to 6 times per week had an RR of 0.74 (95% CI, 0.67-0.81),and those active daily had an RR of 0.91 (95% CI, 0.84-0.99).For cerebrovascular disease (7638 cases), the corresponding RRs and 95% CIs were 0.83 (0.78-0.88), 0.84 (0.78-0.90), 0.84 (0.74-0.97), and 0.92 (0.80-1.05), and for venous thromboembolism (5999 cases), the corresponding RRs and 95% CIs were 0.85 (0.80-0.90), 0.82 (0.76-0.89), 0.86 (0.73-1.00), and 0.98 (0.84-1.13).
Radiation Therapy Advances for Treatment of Anal Cancer
Authors: Joseph M. Pepek, Christopher G. Willett, Brian G. Czito
Journal: Journal of the National Comprehensive Cancer Network (2010)

Radiation therapy (RT) is established as the primary treatment of squamous cell carcinoma of the anus. Multiple randomized trials have shown that combined modality therapy with RT, 5-fluorouracil, and mitomycin-C results in high rates of local control, disease-free survival, and sphincter preservation. However, treatment-related toxicity using conventional radiation approaches remains high and may compromise therapeutic efficacy because of prolonged treatment breaks and inability to deliver adequate radiation dose. Recent developments, including the use of PET for staging, radiation planning, and response assessment, and advanced RT planning using intensity-modulated radiation therapy (IMRT), may decrease acute and late treatment-related toxicity, provide high-dose target conformality, and permit safe radiation dose escalation. This article reviews the basic principles of IMRT and highlights current literature on these recent advances and the application of new RT techniques.
Possible Retroperitonel Fibrosis and Methysergide
Authors: D. S. Freestone
Journal: BMJ (1965)

capacity to synthesize this enzyme-though they do not entirely lack it-is not inconsistent with the Oxford report.Temporary suppressions of the already deficient enzyme, and the quantitative relationship between it and the substrate (gluten), could account for the episodic nature of multiple sclerosis;and in a population subsisting on a high gluten-containing diet the differencesbetween normal subjects and heterozygotes in remis- sion may be too subtle to be discerned by the immunological tests.-I am, etc.,
Abstract 15297: Anatomical Predictors of Major Adverse Limb Events after Infrapopliteal Angioplasty for Patients with Critical Limb Ischaemia due to Pure Isolated Infrapopliteal Lesions
Authors: Kei Sato, Osamu Iida, Terutoshi Yamaoka, Keisuke Hirano, Kiyonori Nanto, Yusuke Miyashita, Daizo Kawasaki, Taketsugu Tsuchiya, Yoshimitsu Soga, Yasutaka Yamauchi, Nobuhiro Suematsu, jyunichi Tazaki, Yoshiaki Shintani, Kenji Suzuki, Masaaki Uematsu
Journal: Circulation (2012)

Objective: To identify anatomical factors associated with major adverse limb events (MALE) after angioplasty as the basis for a novel morphology-driven classification of infrapopliteal lesions. Des...
Chemohormonal Therapy Versus Hormonal Therapy for Hormone Naïve High Volume Newly Metastatic Prostate Cancer (Prca): Ecog Led Phase III Randomized Trial
Authors: C. Sweeney, Y. Chen, M. Carducci, G. Liu, D. Jarrard, M. Eisenberger, Y. Wong, N.M. Hahn, M. Kohli, N. Vogelzang, M. Cooney, R. Dreicer, J. Picus, D. Shevrin, M. Hussain, J. Garcia, R. Dipaola
Journal: Annals of Oncology (2014)
Transgender Patients, Isotretinoin, and US Food and Drug Administration–Mandated Risk Evaluation and Mitigation Strategies
Authors: Kenneth A. Katz
Journal: JAMA Dermatology (2016)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology
Authors: Phillip G Febbo, Marc Ladanyi, Kenneth D Aldape, Angelo M De Marzo, M Elizabeth Hammond, Daniel F Hayes, A John Iafrate, R Kate Kelley, Guido Marcucci, Shuji Ogino, William Pao, Dennis C Sgroi, Marian L Birkeland
Journal: Journal of the National Comprehensive Cancer Network (2011)

The molecular analysis of biomarkers in oncology is rapidly advancing, but the incorporation of new molecular tests into clinical practice will require a greater understanding of the genetic changes that drive malignancy, the assays used to measure the resulting phenotypes and genotypes, and the regulatory processes that new molecular biomarkers must face to be accepted for clinical use. To address these issues and provide an overview of current molecular testing in 6 major malignancies, including glioma, breast cancer, colon cancer, lung cancer, prostate cancer, and acute myelogenous leukemia, an NCCN Task Force was convened on the topic of evaluating the clinical utility of tumor markers in oncology. The output of this meeting, contained within this report, describes the ways biomarkers have been developed and used; defines common terminology, including prognostic, predictive, and companion diagnostic markers, and analytic validity, clinical validity, and clinical utility; and proposes the use of a combination level of evidence score to aid in the evaluation of novel biomarker tests as they arise. The current state of regulatory oversight and anticipated changes in the regulation of molecular testing are also addressed.