tbuckley/cabot-search huggingface dataset:
Appropriateness of use of medicines in elderly inpatients: qualitative study
Authors: Anne Spinewine, Christian Swine, Soraya Dhillon, Bryony Dean Franklin, Paul M Tulkens, Léon Wilmotte, Vincent Lorant
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To explore the processes leading to inappropriate use of medicines for elderly patients admitted for acute care. <b>Design</b> Qualitative study with semistructured interviews with doctors, nurses, and pharmacists; focus groups with inpatients; and observation on the ward by clinical pharmacists for one month. <b>Setting</b> Five acute wards for care of the elderly in Belgium. <b>Participants</b> 5 doctors, 4 nurses, and 3 pharmacists from five acute wards for the interviews; all professionals and patients on two acute wards for the observation and 17 patients (from the same two wards) for the focus groups. <b>Results</b> Several factors contributed to inappropriate prescribing, counselling, and transfer of information on medicines to primary care. Firstly, review of treatment was driven by acute considerations, the transfer of information on medicines from primary to secondary care was limited, and prescribing was often not tailored to elderly patients. Secondly, some doctors had a passive attitude towards learning: they thought it would take too long to find the information they needed about medicines and lacked self directed learning. Finally, a paternalistic doctor-patient relationship and difficulties in sharing decisions about treatment between prescribers led to inappropriate use of medicines. Several factors, such as the input of geriatricians and good communication between members of the multidisciplinary geriatric team, led to better use of medicines. <b>Conclusions</b> In this setting, improvements targeted at the abilities of individuals, better doctor-patient and doctor-doctor relationships, and systems for transferring information between care settings will increase the appropriate use of medicines in elderly people.
Pharmacokinetic analysis of combination chemotherapy with carboplatin and etoposide in small-cell lung cancer patients undergoing hemodialysis
Authors: A. Inoue, Y. Saijo, T. Kikuchi, K. Gomi, T. Suzuki, M. Maemondo, M. Miki, T. Sato, T. Nukiwa
Journal: Annals of Oncology (2003)
The PBDEs: an emerging environmental challenge and another reason for breast-milk monitoring programs.
Authors: K Hooper, T A McDonald
Journal: Environmental Health Perspectives (2000)

Levels of the polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, appear to be rising rapidly in human tissues, as evidenced by studies of human breast milk. The case of the PBDEs illustrates the value of breast-milk monitoring programs in identifying important emerging pollutants, and highlights why such monitoring programs are needed in the United States. A review of the use, occurrence, and toxicity of PBDEs indicates many parallels between some PBDEs, PCBs, and other polyhalogenated persistent organic pollutants, and suggests that the PBDEs may be a significant environmental challenge in the future.
Impact of pay for performance on quality of chronic disease management by social class group in England
Authors: Danielle Crawley, Anthea Ng, Arch G Mainous, Azeem Majeed, Christopher Millett
Journal: Journal of the Royal Society of Medicine (2009)

Summary Objective To examine associations between social class and achievement of selected national audit targets for coronary heart disease (CHD), diabetes and hypertension in England before and after the introduction of a major pay for performance programme in 2004. Design Secondary analysis of 2003 and 2006 national survey data for respondents with CHD and diabetes and hypertension. Setting England. Main outcome measure Achievement of national audit targets for blood pressure, blood glucose and cholesterol control. Results There were no significant differences in achievement of blood pressure targets in individuals from manual and non-manual occupational groups with diabetes (2003: 65.9% v 60.3%, 2006: 67.6% v 69.7%) or hypertension (2003: 66.2% v 66.2%, 2006: 72.8% v 71.9%) before or after the introduction of pay for performance. Achievement of the cholesterol target was also similar in individuals from manual and non-manual groups with diabetes (2003: 52.5% v 46.6%, 2006: 68.7% v 70.5%) or CHD (2003: 54.3% v 53.3%, 2006: 68.6% v 71.3%). Differences in achievement of the blood pressure target in CHD [75.8% v 84.5%; AOR 0.44 (0.21-0.90)] were evident between manual and non-manual occupational groups after the introduction of pay for performance. Conclusion The quality of chronic disease management in England was broadly equitable between socioeconomic groups before this major pay for performance programme and remained so after its introduction.
Independent Effect of Depression and Anxiety on Chronic Obstructive Pulmonary Disease Exacerbations and Hospitalizations
Authors: Wanning Xu, Jean-Paul Collet, Stanley Shapiro, Yingxiang Lin, Ting Yang, Robert W. Platt, Chen Wang, Jean Bourbeau
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Depression and anxiety are significant comorbid and potentially modifiable conditions in chronic obstructive pulmonary disease (COPD), but their effects on exacerbations are not clear.To investigate the independent effect of depression and anxiety on the risk of COPD exacerbations and hospitalizations.A multicenter prospective cohort study in 491 patients with stable COPD in China. Multivariate Poisson and linear regression analyses were used, respectively, to estimate adjusted incidence rate ratios (IRRs) and adjusted effects on duration of events.Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS) at baseline. Other measurements included sociodemographic, clinical, psychosocial, and treatment characteristics. Patients were then monitored monthly for 12 months to document the occurrence and characteristics of COPD exacerbations and hospitalizations. Exacerbation was determined using both symptom-based (worsening of > or =1 key symptom) and event-based definitions (> or =1 symptom worsening plus > or =1 change in regular medications). A total of 876 symptom-based and 450 event-based exacerbations were recorded, among which 183 led to hospitalization. Probable depression (HADS depression score > or = 11) was associated with an increased risk of symptom-based exacerbations (adjusted IRR, 1.51; 95% confidence interval [CI], 1.01-2.24), event-based exacerbations (adjusted IRR, 1.56; 95% CI, 1.02-2.40), and hospitalization (adjusted IRR, 1.72; 95% CI, 1.04-2.85) compared with nondepression (score < or = 7). The duration of event-based exacerbations was 1.92 (1.04-3.54) times longer for patients with probable anxiety (HADS anxiety score > or = 11) than those with no anxiety (score < or = 7).This study suggests a possible causal effect of depression on COPD exacerbations and hospitalizations. Further studies are warranted to confirm this finding and to test the effectiveness of antidepressants and psychotherapies on reducing exacerbations and improving health resource utilizations.
Functional characterization of the basolateral rat liver organic anion transporting polypeptide
Authors: Gerd-Achim Kullak-Ublick, Bruno Hagenbuch, Bruno Stieger, Allan W. Wolkoff, Peter J. Meier
Journal: Hepatology (1994)

To characterize the transport functions of a recently cloned basolateral organic anion transporting polypeptide of rat hepatocytes we performed further kinetic transport and substrate cis-inhibition studies in organic anion-transporting polypeptide—cRNA injected Xenopus laevis oocytes. The studies demonstrate saturable Na+-independent sulfobromophthalein (Michaelis-Menten constant, 1.5 μmol/L) and taurocholate (Michaelis-Menten constant, 50 μmol/L) uptake by organic anion-transporting polypeptide. Sulfobromophthalein uptake was inhibited by the following organic anions: 0.01 mmol/L bilirubin (43%), 0.1 mmol/L indocyanine green (81%), 0.1 mmol/L 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS; 52%) and 1 mmol/L probenecid (74%). Competitive inhibition was shown for indocyanine green (inhibition constant about 1.3 μmol/L). Sulfobromophthalein and taurocholate uptakes were also inhibited by cholate, chenodeoxycholate, deoxycholate and ursodeoxycholate, as well as their glycine and taurine conjugates. Organic anion-transporting polypeptide also mediated uptake of glycocholate, tauroursodeoxycholate and taurochenodeoxycholate. No cis-inhibition of sulfobromophthalein uptake was seen in the presence of ATP, para-aminohippuric acid, bumetanide, digitoxin, reduced glutathione, leukotriene C4, nicotinic acid, ouabain, oxalate, rifampicin, succinate or sulfate. Furthermore, radioactively labeled paraaminohippuric acid, α-ketoglutarate and reduced glutathione were not taken up by organic aniontransporting polypeptide in cRNA-injected frog oocytes. These data confirm that organic aniontransporting polypeptide represents a novel hepatocellular organic anion uptake system that can mediate Na+-independent transport of monovalent (e.g., bile acids) and divalent (e.g., sulfobromophthalein and indocyanine green) cholephilic organic anions. A variety of substrates previously shown to inhibit uptake of sulfobromophthalein and bile acids in perfused rat livers, isolated hepatocytes and basolateral membrane vesicles had no cis-inhibitory effects on organic aniontransporting polypeptide—mediated organic anion transport in X. laevis oocytes. Thus additional Na+-independent organic anion carriers must be present in the basolateral membranes of rat hepatocytes. (Hepatology 1994;20:411-416.)
Independent Domains of Inhibitory Gating in Schizophrenia and the Effect of Stimulus Interval
Authors: L. Elliot Hong, Ann Summerfelt, Ikwunga Wonodi, Helene Adami, Robert W. Buchanan, Gunvant K. Thaker
Journal: American Journal of Psychiatry (2007)

Patients with schizophrenia are known to have inhibitory gating deficits in the suppression of evoked potential P50 response to repeated stimuli and the prepulse inhibition of the startle response. In the current study, the authors aimed to determine whether these two inhibitory gating measures are related in schizophrenia patients or whether abnormal P50 suppression and abnormal prepulse inhibition are independent neurophysiological characteristics of schizophrenia. The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations.Fifty-nine schizophrenia patients and 17 healthy comparison subjects were tested on both P50 suppression and prepulse inhibition. P50 suppression was measured using paired clicks with 500-msec interstimulus intervals. Prepulse inhibition was measured by using a series of prepulse-pulse pairs with interstimulus intervals ranging from 30 to 500 msec.Patients showed reduced P50 suppression and prepulse inhibition in relation to healthy comparison subjects. Concordance analysis showed that abnormal P50 suppression and abnormal prepulse inhibition do not necessarily occur together. Prepulse inhibition was most prominent at the 120-msec interstimulus interval, which was not correlated to P50 suppression. At the 500-msec interstimulus interval, prepulse inhibition was significantly but negatively correlated to P50 suppression. Prepulse inhibition at the other interstimulus intervals was not correlated with P50 suppression.These neurophysiological measures lack robust and direct relationships and likely mark independent aspects of abnormal brain inhibitory functions in schizophrenia.
CHD5 , a Tumor Suppressor Gene Deleted From 1p36.31 in Neuroblastomas
Authors: Tomoyuki Fujita, Jun Igarashi, Erin R. Okawa, Takahiro Gotoh, Jayanthi Manne, Venkatadri Kolla, Jessica Kim, Huaqing Zhao, Bruce R. Pawel, Wendy B. London, John M. Maris, Peter S. White, Garrett M. Brodeur
Journal: JNCI Journal of the National Cancer Institute (2008)

Neuroblastomas are characterized by hemizygous 1p deletions, suggesting that a tumor suppressor gene resides in this region. We previously mapped the smallest region of consistent deletion to a 2-Mb region of 1p36.31 that encodes 23 genes. Based on mutation analysis, expression pattern, and putative function, we identified CHD5 as the best tumor suppressor gene candidate.We determined the methylation status of the CHD5 gene promoter in NLF and IMR5 (with 1p deletion) and SK-N-SH and SK-N-FI neuroblastoma cell lines using methylation-specific sequencing and measured CHD5 mRNA expression by reverse transcription polymerase chain reaction in cells treated with or without 5-aza-2-deoxycytidine, an inhibitor of DNA methylation. We transfected the cells with CHD5 and antisense (AS) CHD5 DNA to assess the effect of CHD5 overexpression and suppression, respectively, on colony formation in soft agar and growth of xenograft tumors in athymic mice. We also analyzed the association of CDH5 expression with outcomes of 99 neuroblastoma patients. Statistical tests were two-sided.CHD5 expression was very low or absent in neuroblastoma cell lines. The CHD5 promoter was highly methylated in NLF and IMR5 lines, and CHD5 expression increased after treatment with 5-aza-2-deoxycytidine. Clonogenicity and tumor growth were abrogated in NLF and IMR5 cells overexpressing CHD5 compared with antisense CHD5 (clonogenicity: mean no. of colonies per plate, NLF-CHD5, 43 colonies, 95% confidence interval [CI] = 35 to 51 colonies, vs NLF-CHD5-AS, 74 colonies, 95% CI = 62 to 86 colonies, P < .001; IMR5-CHD5, 11 colonies, 95% CI = 2 to 20 colonies, vs IMR5-CHD5-AS, 39 colonies, 95% CI = 17 to 60 colonies, P = .01; tumor growth, n = 10 mice per group: mean tumor size at 5 weeks, NLF-CHD5, 0.36 cm(3), 95% CI = 0.17 to 0.44 cm(3), vs NLF-CHD5-AS, 1.65 cm(3), 95% CI = 0.83 to 2.46 cm(3), P = .002; IMR5-CHD5, 0.28 cm(3), 95% CI = 0.18 to 0.38 cm(3), vs IMR5-CHD5-AS, 1.15 cm(3), 95% CI = 0.43 to 1.87 cm(3); P = .01). High CHD5 expression was strongly associated with favorable event-free and overall survival (P < .001), even after correction for MYCN amplification and 1p deletion (P = .027).CHD5 is the strongest candidate tumor suppressor gene that is deleted from 1p36.31 in neuroblastomas, and inactivation of the second allele may occur by an epigenetic mechanism.
Current Issues in Chronic Myeloid Leukemia: Monitoring, Resistance, and Functional Cure
Authors: Jorge Cortes, John M. Goldman, Timothy Hughes
Journal: Journal of the National Comprehensive Cancer Network (2012)

Despite the success with tyrosine kinase inhibitors (TKIs) in most patients with chronic myelogenous leukemia (CML), some patients still experience resistance or intolerance and need alternative therapies. Monitoring response to TKI therapy is a critical component of managing CML, and molecular response seems to be the most important milestone for predicting long-term outcomes. How best to assess response, including how to define treatment failure, and how monitoring should be conducted remain controversial. Strategies for overcoming imatinib resistance include increasing the imatinib dose or switching to a second-generation TKI. Another approach is to use higher doses of imatinib or second-generation TKIs up front to increase the rate of earlier responses, with the hope that this will translate into a reduced risk of resistance. Several investigational therapies are also being evaluated as a means of overcoming TKI resistance, including ponatinib (AP24534), omacetaxine, and bosutinib (SKI-606). Allogeneic hematopoietic stem cell transplantation has also shown efficacy in patients with imatinib-resistant disease. Alternatives to long-term TKI therapy that are currently being explored include discontinuation of treatment and eradication of minimal residual disease with investigational treatment regimens, such as those involving interferon, hydroxychloroquine, BCL6 inhibitors, and the smoothened antagonists LDF225 and BMS-833923.
Effective Strategies for Management of Hypertension After Vascular Endothelial Growth Factor Signaling Inhibition Therapy: Results From a Phase II Randomized, Factorial, Double-Blind Study of Cediranib in Patients With Advanced Solid Tumors
Authors: Marlies H.G. Langenberg, Carla M.L. van Herpen, Johann De Bono, Jan H.M. Schellens, Clemens Unger, Klaas Hoekman, Hubert E. Blum, Walter Fiedler, Joachim Drevs, Florence Le Maulf, Anitra Fielding, Jane Robertson, Emile E. Voest
Journal: Journal of Clinical Oncology (2009)

PURPOSE Hypertension is a commonly reported adverse effect after administration of vascular endothelial growth factor (VEGF) inhibitors. Cediranib is a highly potent and selective VEGF signaling inhibitor of all three VEGFRs. This study prospectively investigated hypertension management to help minimize dose interruptions/reductions to maximize cediranib dose intensity. PATIENTS AND METHODS Patients (n = 126) with advanced solid tumors were randomly assigned to one of four groups: cediranib 30 or 45 mg/d with or without antihypertensive prophylaxis. All patients developing hypertension on cediranib treatment were treated with a standardized, predefined hypertension management protocol. Results Cediranib was generally well tolerated, and all groups achieved high-dose intensities in the first 12 weeks (> 74% in all groups). Antihypertensive prophylaxis did not result in fewer dose reductions or interruptions. Increases in blood pressure, including moderate and severe readings of hypertension, were seen early in treatment in all groups and successfully managed. Severe hypertension occurred in one patient receiving prophylaxis versus 18 in the nonprophylaxis groups. Overall, there were nine partial responses, and 38 patients experienced stable disease >/= 8 weeks. CONCLUSION To our knowledge, this is the first prospective investigation of hypertension management during administration of a VEGF signaling inhibitor. All four regimens were well tolerated with high-dose intensities and no strategy was clearly superior. The current cediranib hypertension management protocol appears to be effective in managing hypertension compared with previous cediranib studies where no plan was in place, and early recognition and treatment of hypertension is likely to reduce the number of severe hypertension events. This protocol is included in all ongoing cediranib clinical studies.
Early Changes in Bioelectrical Estimates of Body Composition in Chronic Kidney Disease
Authors: Vincenzo Bellizzi, Luca Scalfi, Vincenzo Terracciano, Luca De Nicola, Roberto Minutolo, Maurizio Marra, Bruna Guida, Bruno Cianciaruso, Giuseppe Conte, Biagio R. Di Iorio
Journal: Journal of the American Society of Nephrology (2006)

The aim of this study was to detect the potential occurrence of early abnormalities of body composition in patients with chronic kidney disease (CKD) at first referral to an outpatient nephrology clinic. Eighty-four patients with CKD (49 men and 35 women) were compared with 604 healthy control subjects (298 men and 306 women). Anthropometry and bioelectrical impedance analysis (BIA) were performed in all participants, whereas renal function, laboratory tests for nutritional status, and nutrient intake were assessed in the CKD group only. Creatinine clearance was 27.8 ± 13.8 and 27.4 ± 13.0 ml/min per 1.73 m2 in male and female patients with CKD, respectively. No patient showed peripheral edema; frank malnutrition, defined by presence of serum albumin <3.5 g/dl plus body mass index <20 kg/m2; or protein intake <0.6 g/kg per d. At the BIA, patients with CKD showed lower resistance (R) and abnormal mean impedance vectors for the bivariate normal distribution of R/height and reactance/height. Phase angle also was reduced (−22%), especially in patients with diabetes. When BIA-derived data were considered, total body water was slightly higher (+4.3% in men; +3.5% in women) and body cell mass was lower (−6.7% in men; −7.7% in women) in patients with CKD. No difference in either BIA parameters or nutritional indexes was observed among various CKD stages. Despite the absence of overt malnutrition, patients with CKD exhibit altered BIA variables from the early phases of renal disease. These alterations are related to the renal dysfunction, are more marked in the presence of diabetes, and mainly indicate the presence of overhydration in the absence of edema. Therefore, BIA represents an attractive clinical tool to detect impairment of body composition from the early stages of CKD.
Global Health Actors Claim To Support Health System Strengthening—Is This Reality or Rhetoric?
Authors: Bruno Marchal, Anna Cavalli, Guy Kegels
Journal: PLoS Medicine (2009)

Current HSS Programmes and ActivitiesOur review found that, on the ground, very different interventions are imple-The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.
Diagnostic Percutaneous Transthoracic Needle Biopsy Does Not Affect Survival in Stage I Lung Cancer
Authors: Juan P. Wisnivesky, Claudia I. Henschke, David F. Yankelevitz
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Lung cancer dissemination has been cited as a potential adverse consequence of diagnostic percutaneous transthoracic needle biopsy (PTNB) of lung nodules. Despite multiple reports in the literature of malignant spread along the needle track, the potential effect of lung cancer dissemination after PTNB on survival is unknown.To evaluate whether diagnostic PTNB is associated with increased risk of lung cancer death.This study included 8,607 cases of surgically resected stage I non-small cell lung cancer diagnosed between 1991 and 1999 from the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records. Overall and lung cancer-specific survival of patients who had and did not have PTNB was compared using Kaplan-Meier curves. Stratified survival analyses and Cox regression were used to compare survival with adjustment for potential confounders.Approximately 36% of patients underwent diagnostic PTNB. Overall and lung cancer-specific survival did not differ in patients that underwent PTNB as part of their cancer diagnostic work-up and those who did not (p = 0.57 and 0.46, respectively). In stratified and multivariate analysis, PTNB was not associated with an increased risk of death after controlling for age, race, income, access to care, comorbidities, tumor histology and size, and type of treatment received.In this large national sample, preoperative PTNB was not associated with increased risk of death. These data suggest that PTNB can be safely used for the work-up of pulmonary nodules when there is a suspicion of lung cancer.
Surgery and the respiratory muscles
Authors: N M Siafakas, I Mitrouska, D Bouros, D Georgopoulos
Journal: Thorax (1999)

EVect on neural control of respiratory muscles (e.g.phrenicotomy) EVect on integrity of respiratory muscles by the surgical incision Reflex mechanisms (phrenic nerve inhibition) Change in the length/tension relationship (change in FRC) Change in the thoracoabdominal mechanics (e.g.reduction of rib cage compliance) Anaesthesia (pharmacological agents/loads) and postoperative