tbuckley/cabot-search huggingface dataset:
Toward Patient-Centered Cancer Care: Patient Perceptions of Problematic Events, Impact, and Response
Authors: Kathleen M. Mazor, Douglas W. Roblin, Sarah M. Greene, Celeste A. Lemay, Cassandra L. Firneno, Josephine Calvi, Carolyn D. Prouty, Kathryn Horner, Thomas H. Gallagher
Journal: Journal of Clinical Oncology (2012)

Cancer treatments are complex, involving multiple clinicians, toxic therapies, and uncertain outcomes. Consequently, patients are vulnerable when breakdowns in care occur. This study explored cancer patients' perceptions of preventable, harmful events; the impact of these events; and interactions with clinicians after such events.In-depth telephone interviews were conducted with cancer patients from three clinical sites. Patients were eligible if they believed: something "went wrong" during their cancer care; the event could have been prevented; and the event caused, or could have caused, significant harm. Interviews focused on patients' perceptions of the event, its impact, and clinicians' responses to the event.Ninety-three of 416 patients queried believed something had gone wrong in their care that was preventable and caused or could have caused harm. Seventy-eight patients completed interviews. Of those interviewed, 28% described a problem with medical care, such as a delay in diagnosis or treatment; 47% described a communication problem, including problems with information exchange or manner; and 24% described problems with both medical care and communication. Perceived harms included physical and emotional harm, disruption of life, effect on family members, damaged physician-patient relationship, and financial expense. Few clinicians initiated discussion of the problematic events. Most patients did not formally report their concerns.Cancer patients who believe they experienced a preventable, harmful event during their cancer diagnosis or care often do not formally report their concerns. Systems are needed to encourage patients to report such events and to help physicians and health care systems respond effectively.
Allopurinol Use and Risk of Fatal Hypersensitivity Reactions
Authors: Chien-Yi Yang, Chi-Hua Chen, Shin-Tarng Deng, Chi-Shan Huang, Yu-Jr Lin, Yi-Ju Chen, Chun-Ying Wu, Shuen-Iu Hung, Wen-Hung Chung
Journal: JAMA Internal Medicine (2015)

Allopurinol, a first-line drug used for treating gout, is increasingly prescribed worldwide to patients with asymptomatic hyperuricemia and comorbid renal or cardiovascular diseases. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The overall risks of allopurinol use remain unclear.To investigate the incidence of, risk factors for, and mortality associated with allopurinol hypersensitivity in new users of allopurinol.A retrospective nationwide population study was conducted using data from the Taiwan National Health Insurance Research Database, which includes detailed medical records of more than 23 million insured enrollees. Data were collected from January 1, 2005, through December 31, 2011, using the Anatomical Therapeutic Chemical classification system and International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among 1,613,719 patients receiving allopurinol prescriptions, 495,863 were identified as new users.Allopurinol hypersensitivity was identified within 3 months since the first prescription. The period for measuring related hospitalizations was 1 month since the episode, and the period for measuring renal complications or mortality was 2 months since the episode. Poisson regression test and multivariable logistic regression analysis were performed, and P < .01 was considered statistically significant.Among the more than 23 million insured enrollees, the annual incidence rates were 4.68 per 1000 new users for allopurinol hypersensitivity, 2.02 per 1000 new users for related hospitalization, and 0.39 per 1000 new users for related mortality. The annual incidence of allopurinol hypersensitivity rose statistically significantly during the study period (P < .001). Risk factors for allopurinol hypersensitivity included female sex, age 60 years or older, initial allopurinol dosage exceeding 100 mg/d, renal or cardiovascular comorbidities, and use for treating asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia and renal or cardiovascular diseases had statistically significantly increased risk of allopurinol hypersensitivity (odds ratio [OR], 1.61; 95% CI, 1.33-1.94; P < .001 for renal diseases and OR, 1.52; 95% CI, 1.19-1.93; P < .001 for cardiovascular diseases). They also had statistically significantly increased risk of mortality (OR, 5.59; 95% CI, 2.61-11.94; P < .001 for renal diseases and OR, 3.57; 95% CI, 2.31-5.51; P < .001 for cardiovascular diseases).The use of allopurinol in patients with asymptomatic hyperuricemia accompanied by renal or cardiovascular diseases statistically significantly increased the risk of hypersensitivity reactions. Physicians should be cautious when prescribing allopurinol to high-risk populations and should consider the potential risks of fatal adverse reactions.
Reappraisal of Central Pancreatectomy
Authors: Yvain Goudard, Sebastien Gaujoux, Safi Dokmak, Jérôme Cros, Anne Couvelard, Maxime Palazzo, Maxime Ronot, Marie-Pierre Vullierme, Philippe Ruszniewski, Jacques Belghiti, Alain Sauvanet
Journal: JAMA Surgery (2014)

Central pancreatectomy, as an alternative to standard resection for benign and low-grade pancreatic neoplasms, has been described in mainly small retrospective series.To describe a large single-center experience with central pancreatectomy.A retrospective case series in a tertiary referral center included 100 consecutive patients undergoing central pancreatectomy with pancreaticogastrostomy from January 1, 2000, to March 1, 2012.Surgical indications, postoperative morbidity, mortality, and long-term outcomes regarding pancreatic function and recurrence.Central pancreatectomies were performed mainly for neuroendocrine tumors (35%), intraductal papillary mucinous neoplasms (33%), solid pseudopapillary neoplasms(12%), and mucinous cystadenomas (6%). The postoperative mortality rate was 3% (due to pulmonary embolisms in 2 patients and hemorrhage after pancreatic fistula in 1 patient). Clavien-Dindo III or IV complications occurred in 15%of patients and were due mainly to pancreatic fistula, requiring 10 radiologic drainage procedures, 7 endoscopic procedures, and 6 reoperations overall. After a median follow-up of 36 months, the rates of new-onset exocrine and endocrine insufficiency were 6%and 2%, respectively. Overall, 7 lesions could be considered undertreated, including 3 node-negative R0 microinvasive intraductal papillary mucinous neoplasms (without recurrence at 27, 29, and 34 months) and 4 node-positive neuroendocrine tumors (with 1 hepatic recurrence at 66 months). Among the 25 patients with a doubtful preoperative diagnosis, 9 could be considered over treated (ie, operated on for benign non evolutive asymptomatic lesions).Central pancreatectomy is associated with an excellent pancreatic function at the expense of a significant morbidity and a non-nil mortality rate,underestimated by the published literature. The procedure is best indicated for benign or low-grade lesions in young and fit patients who can sustain a significant postoperative morbidity and could benefit from the excellent long-term results.
Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells
Authors: William N. Kelley, James B. Wyngaarden
Journal: Journal of Clinical Investigation (1970)

In the present study we have examined the effects of allopurinol and oxipurinol on the de novo synthesis of purines in cultured human fibroblasts. Allopurinol inhibits de novo purine synthesis in the absence of xanthine oxidase. Inhibition at lower concentrations of the drug requires the presence of hypoxanthine-guanine phosphoribosyltransferase as it does in vivo. Although this suggests that the inhibitory effect of allopurinol at least at the lower concentrations tested is a consequence of its conversion to the ribonucleotide form in human cells, the nucleotide derivative could not be demonstrated. Several possible indirect consequences of such a conversion were also sought. There was no evidence that allopurinol was further utilized in the synthesis of nucleic acids in these cultured human cells and no effect of either allopurinol or oxipurinol on the long-term survival of human cells in vitro could be demonstrated. At higher concentrations, both allopurinol and oxipurinol inhibit the early steps of de novo purine synthesis in the absence of either xanthine oxidase or hypoxanthine-guanine phosphoribosyltransferase. This indicates that at higher drug concentrations, inhibition is occurring by some mechanism other than those previously postulated.
Lung function and clinical risk factors for asthma in infants and young children with recurrent wheeze
Authors: L M Borrego, J Stocks, P Leiria-Pinto, I Peralta, A M Romeira, N Neuparth, J E Rosado-Pinto, A-F Hoo
Journal: Thorax (2008)

Although several risk factors for asthma have been identified in infants and young children with recurrent wheeze, the relevance of assessing lung function in this group remains unclear. Whether lung function is reduced during the first 2 years in recurrently wheezy children, with and without clinical risk factors for developing subsequent asthma (ie, parental asthma, personal history of allergic rhinitis, wheezing without colds and/or eosinophil level >4%) compared with healthy controls was assessed in this study.Forced expiratory flows and volumes in steroid naïve young children with >or=3 episodes of physician confirmed wheeze and healthy controls, aged 8-20 months, were measured using the tidal and raised volume rapid thoracoabdominal compression manoeuvres.Technically acceptable results were obtained in 50 wheezy children and 30 controls using tidal rapid thoracoabdominal compression, and 44 wheezy children and 29 controls with the raised volume technique. After adjustment for sex, age, body length at test and maternal smoking, significant reductions in z scores for forced expiratory volume at 0.5 s (mean difference (95% CI) -1.0 (-1.5 to -0.5)), forced expired flow after 75% forced vital capacity (FVC) has been exhaled (FEF(25)) (-0.6 (-1.0 to -0.2)) and average forced expired flow over the mid 50% of FVC (FEF(25-75)) (-0.8 (-1.2 to -0.4)) were observed in those with recurrent wheeze compared with controls. Wheezy children with risk factors for asthma (n = 15) had significantly lower z scores for FVC (-0.7 (-1.4 to -0.04)) and FEF(25-75) (-0.6 (-1.2 to -0.1)) than those without such risk factors (n = 29).Compared with healthy controls, airway function is reduced in young children with recurrent wheeze, particularly those at risk for subsequent asthma. These findings provide further evidence for associations between clinical risk factors and impaired respiratory function in early life.
Fibrinopeptide A and platelet factor levels in unstable angina pectoris.
Authors: P Théroux, J G Latour, C Léger-Gauthier, J De Lara
Journal: Circulation (1987)

Fibrinopeptide A, platelet factor 4, beta-thromboglobulin, thromboxane B2, and 6-keto-prostaglandin F1 alpha were estimated by radioimmunoassay on venous plasma samples taken within 48 hr of admission from 16 consecutive patients with unstable angina and 15 patients with stable angina matched for clinical variables. The ratio of circulating platelet aggregates, platelet aggregation to increasing concentrations of ADP (0.455 to 1.82 micrograms/ml), and platelet thromboxane B2 production in vitro were also tested. The two groups of patients were statistically similar in terms of sex distribution, age, presence of risk factors, use of medication, extent of coronary artery disease and history of previous myocardial infarction. Mean plasma levels of fibrinopeptide A were 2.7 +/- 0.4 ng/ml (geometric means +/- SEM, range 1.5 to 5.5) in patients with stable angina vs 5.5 +/- 1.8 ng/ml (range 2.4 to 32; p less than .001) in those with unstable angina. In the latter group, after 6 to 8 days, fibrinopeptide A levels decreased to 3.6 +/- 0.5 ng/ml (range 1.5 to 9.3; p less than .04 vs admission). All other variables measured were statistically identical in the two groups. We conclude that plasma fibrinopeptide A levels, as opposed to platelet factors, discriminate between patients with unstable and stable angina, indicating an activation of the coagulation system in unstable angina.
Food and Fasting Absorption of a Single Dose of a Sustained Release Theophylline Sprinkle Formulation in Children
Authors: S. Pedersen, G. Steffensen
Journal: Allergy (1986)

The bioavailability and absorption pattern of theophylline from a single dose of a slow release theophylline sprinkle product (Somophyllin) were investigated in 10 asthmatic children both in fasting conditions and after a standardized breakfast. Theophylline given intravenously was used as a reference. The fasting absorption of Somophyllin was rather fast with peak serum theophylline levels 3-5 h (mean 3.7 h) after dosing. Food produced a small but statistically significant reduction in the rate of absorption of theophylline, so that the mean time to peak serum theophylline level was 5.6 h (range 4-8 h) after food. In no case was there any important difference between the absorption profiles on the test days, and the bioavailability was complete after both fasted and fed intake of the product (92.5% and 105%, respectively). It is suggested that to obtain the optimum absorption profile children should take Somophyllin with food rather than between meals.
A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients
Authors: S. Wilgenhof, A.M.T. Van Nuffel, D. Benteyn, J. Corthals, C. Aerts, C. Heirman, I. Van Riet, A. Bonehill, K. Thielemans, B. Neyns
Journal: Annals of Oncology (2013)
Gadd45β mediates the protective effects of CD40 costimulation against Fas-induced apoptosis
Authors: Francesca Zazzeroni, Salvatore Papa, Alicia Algeciras-Schimnich, Kellean Alvarez, Tiziana Melis, Concetta Bubici, Nathan Majewski, Nissim Hay, Enrico De Smaele, Marcus E. Peter, Guido Franzoso
Journal: Blood (2003)
Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity
Authors: Cheng-Lung Ku, Horst von Bernuth, Capucine Picard, Shen-Ying Zhang, Huey-Hsuan Chang, Kun Yang, Maya Chrabieh, Andrew C. Issekutz, Coleen K. Cunningham, John Gallin, Steven M. Holland, Chaim Roifman, Stephan Ehl, Joanne Smart, Mimi Tang, Franck J. Barrat, Ofer Levy, Douglas McDonald, Noorbibi K. Day-Good, Richard Miller, Hidetoshi Takada, Toshiro Hara, Sami Al-Hajjar, Abdulaziz Al-Ghonaium, David Speert, Damien Sanlaville, Xiaoxia Li, Frédéric Geissmann, Eric Vivier, László Maródi, Ben-Zion Garty, Helen Chapel, Carlos Rodriguez-Gallego, Xavier Bossuyt, Laurent Abel, Anne Puel, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2007)

Human interleukin (IL) 1 receptor–associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3– and TLR4–interferon (IFN)-a/b pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells (PBMCs) did not induce the 11 non-IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly(I:C). The patients' individual cell subsets from both myeloid (granulocytes, monocytes, monocyte-derived dendritic cells [MDDCs], myeloid DCs [MDCs], and plasmacytoid DCs) and lymphoid (B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly(I:C) and lipopolysaccharide in MDCs and MDDCs. Most patients (22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent (13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease (9 out of 28; 32%). Almost half of the patients died (12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK-4–dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK-4–dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria.
A phase I trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood
Authors: Regina I. Jakacki, Allan Yates, Susan M. Blaney, Tianni Zhou, Robert Timmerman, Ashish M. Ingle, Lynda Flom, Michael D. Prados, Peter C. Adamson, Ian F. Pollack
Journal: Neuro-Oncology (2008)

A phase I trial was conducted to determine the maximum tolerated dose (MTD) of temozolomide given in combination with lomustine in newly diagnosed pediatric patients with high-grade gliomas. Response was assessed following two courses of therapy at the MTD. Temozolomide was administered to cohorts of patients at doses of 100, 125, 160, or 200 mg/m2 on days 1-5, along with 90 mg/m2 lomustine on day 1. Two courses of lomustine/temozolomide were given prior to radiation therapy (RT) and up to six courses were administered afterward. Thirty-two patients were enrolled. Dose-limiting myelosuppression was seen in two of three patients enrolled at the 200 mg/m2 dose level. One of 14 patients in the expanded MTD cohort (160 mg/m2) experienced dose-limiting thrombocytopenia. After two courses at the MTD, one patient with a 5-mm enhancing nodule postoperatively had a complete response, one patient with a large residual temporal lobe glioblastoma had a partial response, and eight patients had stable disease. Several patients developed transient radiographic worsening after completing RT. Median 1- and 2-year overall survivals at the MTD were 60% ± 13% and 40% ± 13% with a median of 17.6 months. Thirteen of 20 patients (65%) who underwent MRI scans within 6 months prior to death developed metastatic disease. In conclusion, when administered with 90 mg/m2 lomustine on day 1, the MTD of temozolomide is 160 mg/m2/day × 5. Radiographic changes following RT make determination of early tumor progression difficult. Metastatic disease is common prior to death.
Activation of G Protein–Coupled Receptors: Beyond Two-State Models and Tertiary Conformational Changes
Authors: Paul S.-H. Park, David T. Lodowski, Krzysztof Palczewski
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Transformation of G protein-coupled receptors (GPCRs) from a quiescent to an active state initiates signal transduction. All GPCRs share a common architecture comprising seven transmembrane-spanning alpha-helices, which accommodates signal propagation from a diverse repertoire of external stimuli across biological membranes to a heterotrimeric G protein. Signal propagation through the transmembrane helices likely involves mechanistic features common to all GPCRs. The structure of the light receptor rhodopsin may serve as a prototype for the transmembrane architecture of GPCRs. Early biochemical, biophysical, and pharmacological studies led to the conceptualization of receptor activation based on the context of two-state equilibrium models and conformational changes in protein structure. More recent studies indicate a need to move beyond these classical paradigms and to consider additional aspects of the molecular character of GPCRs, such as the oligomerization and dynamics of the receptor.
Deficits on a Probabilistic Response-Reversal Task in Patients With Pediatric Bipolar Disorder
Authors: Tristan Gorrindo, R.J.R. Blair, Salima Budhani, Daniel P. Dickstein, Daniel S. Pine, Ellen Leibenluft
Journal: American Journal of Psychiatry (2005)

Patients with bipolar disorder become hyperhedonic when manic and anhedonic when depressed; therefore, it is important to test whether patients with bipolar disorder show deficits on behavioral paradigms exploring reward/punishment mechanisms.A probabilistic response-reversal task was administered to 24 bipolar children and 25 comparison subjects.Patients made more errors during probabilistic reversal, took longer to learn the new reward object, and were less likely to meet the learning criterion.Children with bipolar disorder may have a reversal learning deficit.
Patient- and Provider-Reported Information about Transplantation and Subsequent Waitlisting
Authors: Megan L. Salter, Babak Orandi, Mara A. McAdams-DeMarco, Andrew Law, Lucy A. Meoni, Bernard G. Jaar, Stephen M. Sozio, Wen Hong Linda Kao, Rulan S. Parekh, Dorry L. Segev
Journal: Journal of the American Society of Nephrology (2014)

Because informed consent requires discussion of alternative treatments, proper consent for dialysis should incorporate discussion about other renal replacement options including kidney transplantation (KT). Accordingly, dialysis providers are required to indicate KT provision of information (KTPI) on CMS Form-2728; however, provider-reported KTPI does not necessarily imply adequate provision of information. Furthermore, the effect of KTPI on pursuit of KT remains unclear. We compared provider-reported KTPI (Form-2728) with patient-reported KTPI (in-person survey of whether a nephrologist or dialysis staff had discussed KT) in a prospective ancillary study of 388 hemodialysis initiates. KTPI was reported by both patient and provider for 56.2% of participants, by provider only for 27.8%, by patient only for 8.3%, and by neither for 7.7%. Among participants with provider-reported KTPI, older age was associated with lack of patient-reported KTPI. Linkage with the Scientific Registry for Transplant Recipients showed that 20.9% of participants were subsequently listed for KT. Patient-reported KTPI was independently associated with a 2.95-fold (95% confidence interval [95% CI], 1.54 to 5.66; P=0.001) higher likelihood of KT listing, whereas provider-reported KTPI was not associated with listing (hazard ratio, 1.18; 95% CI, 0.60 to 2.32; P=0.62). Our findings suggest that patient perception of KTPI is more important for KT listing than provider-reported KTPI. Patient-reported and provider-reported KTPI should be collected for quality assessment in dialysis centers because factors associated with discordance between these metrics might inform interventions to improve this process.