tbuckley/cabot-search huggingface dataset:
P201 Living your life with bronchiectasis: an exploration of patients and carers information needs informing development of a novel information resource
Authors: KLM Hester, J Newton, A DeSoyza, T Rapley
Journal: Thorax (2015)

<h3>Introduction/background</h3> Bronchiectasis is a chronic lung condition, causing breathlessness and chronic productive cough, with intermittent infective exacerbations. Patients often have recurrent hospital admissions, poorer quality of life, and significant fatigue. Treatment concordance can be problematic. There is little patient information currently available, yet information and education could support patients to self-manage, improve understanding and optimise engagement with treatment. Previous exploratory interviews with patients suggested that a lack of credible patient information was available and that having information could help patients learn to live with and manage their condition. <h3>Aims/objectives</h3> To further identify, explore and understand the information needs of patients with bronchiectasis and their carers. To co-develop, with the user group, a novel patient information resource. <h3>Methods</h3> In-depth interviews were conducted with 17 people who have bronchiectasis and 9 carers. Three focus group style workshops were subsequently held with 11 patients and 3 carers in total. All were recruited from respiratory clinics in the North of England. Interviews and workshops were audio-recorded and transcribed and thematic analysis was undertaken to identify common themes. <h3>Results</h3> Ages ranged from 33 to 78 years, including both newly diagnosed and longstanding patients. The focus of the interviews was to identify, explore and understand information needs. A core mediating issue emerged, however: what it means to learn to live your life with bronchiectasis. Embedded in this journey are issues around developing support and coping mechanisms, how people learn to connect with information and how they start to take back control and develop new, active, partnerships with the medical team. Using these qualitative data in the workshops, we co-developed a novel online and paper-based information resource for patients and their families. This resource is currently being piloted in a feasibility study comparing use of the resource to usual care. <h3>Conclusions</h3> Understanding patient and carer experiences of living with bronchiectasis, the biographical disruption (s) that it imposes and the ways in which patients and carers connect with health information over time, has enhanced our understanding of their information needs and how these could be met. The outcomes of the feasibility study are expected in March 2016.
Nuclear magnetic resonance spectroscopy of expressed prostatic secretions: Metabolite citrate and derivatives are potential markers of prostate cancer
Authors: D. Crawford, N. Serkova, E. Gamito, R. Jones, C. O’Donnell, T. Hedlund
Journal: Journal of Clinical Oncology (2006)

4623 Background: Nuclear magnetic resonance spectroscopy (NMRS) along with a novel method for determining absolute concentrations of metabolites were utilized to analyze expressed prostatic secretions (EPS) from men with prostate cancer (PCa) and from healthy controls. Methods: Flash frozen EPS samples from 66 men (40 with PCa and 26 controls) were analyzed by high-resolution 1H-NMR spectroscopy using a Bruker 500 MHz DRX NMR spectrometer with a 1-mm microprobe. The total number of scans per fully relaxed 1H-NMR spectrum was n = 40 with water suppression. Absolute concentrations of endogenous metabolites (citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamate, acetate, hydroxybutyrate) were quantified using trimethylsilyl-propionic acid as an external standard reference. Stepwise multivariable logistic regression (LR) was used to model the risk of PCa based upon the levels of the measured metabolites. Results: The average age of the EPS donors was 54.7 ± 9.8 years. The median Gleason score for the men with PCa was 6 (range 5–9). The Wilcoxon rank sum test indicated that citrate, spermine, inositol, citrate/spermine, and citrate/lactate were all significant predictors of PCa (p &lt; .001). The LR models indicated that the absolute concentration of citrate was highly predictive of PCa with lower concentrations resulting in a higher risk of cancer. The area under the receiver operating characteristic curve (AUROC) for citrate alone was 0.79 (95% CI 0.75–0.83). Using relative concentrations (metabolite ratios) in a two-variable LR model, citrate/spermine and citrate/lactate were also predictive of PCa with an AUROC of 0.76 (95% CI 0.71–0.81). Conclusions: The results suggest that absolute concentration of citrate and its derivatives in EPS as measured by NMRS have promising potential as accurate markers of prostate cancer. No significant financial relationships to disclose.
Serum IgG4 Antibodies in Pediatric Subjects with Eosinophilic Esophagitis Treated with Cow's Milk Elimination Diet or Swallowed Fluticasone: High Levels of Specific IgG4 to Cow's Milk Components Despite Low to Negative IgE Antibodies
Authors: Alexander J. Schuyler, Anubha Tripathi, Patrice G. Kruszewski, John M. Russo, Lisa J. Workman, Thomas A.E. Platts-Mills, Elizabeth A. Erwin
Journal: Journal of Allergy and Clinical Immunology (2016)
Sequential administration of cisplatin (c), gemcitabine (g) and docetaxel (d), as first-line treatment in patients with advanced transitional cell carcinoma (TCC) of the urothelial tract: A multicenter phase II study
Authors: N. Androulakis, I. Boukovinas, V. Bozionelou, A. Kalykaki, A. Potamianou, A. Pallis, L. Vamvakas, I. Gkioulbasanis, I. Souglakos, G. Sfakiotaki
Journal: Journal of Clinical Oncology (2006)

14574 Background: The GC combination has become a standard of care for advanced TCC. D has demonstrated broad single agent activity in many solid tumors including bladder cancer. We evaluated the safety and the activity of their sequential administration in patients (pts) with locally advanced or metastatic TCC who have not received prior chemotherapy. Methods: Chemotherapy-naïve pts with histologically proven locally advanced or metastatic TCC were enrolled. G 1100 mg/m 2 was administered over 30-minutes IV on days 1 and 15, C 80 mg/m 2 on day 1 with the adequate hydration and D 80 mg/m 2 over 1 h on day 15. Results: From 4/2004–12/2005, 26 pts (25 male, 1 female), median age 65.5 years (range, 48–75), (PS 0/1/2: 16/8/2) were enrolled onto the study. The majority (19pts, 73.1%) had metastatic disease. A median of 4 cycles (range 1–9) was given for a total of 113 cycles. There were 12 delayed cycles due to toxicity and 15 dose reductions. Three (16.7%) complete responses (CRs) and 6 (33.3%) partial responses (PRs) [2 of them were converted to CR with additional surgery] were observed in 18 evaluable pts [overall RR of 50%; 95% CI 26.9%-3.1%]. The median time to progression was 7.9, and the months while median survival has not yet reached. The 1-year survival is 68.86%. Gr III-IV hematologic toxicity included neutropenia (61.5%), febrile neutropenia (11.5%), anemia (7.7%) and thrombocytopenia (7.6%). Non hematologic toxicity was mild (grade III vomiting and diarrhea in 7.7% and 3.8% of the pts, respectively). There was no neutropenic sepsis or toxic death. Conclusions: The sequential administration of cisplatin, gemcitabine and docetaxel is an active treatment for pts with advanced TCC. Toxicity is not manageable and this regimen warrants further investigation. No significant financial relationships to disclose.
Therapeutic biomarker differences between MSI-H and MSS colorectal cancers.
Authors: Zoran Gatalica, Namrata Vijayvergia, Semir Vranic, Joanne Xiu, Sandeep K. Reddy, Carrie L. Snyder, Henry T. Lynch, Wafik S. El-Deiry
Journal: Journal of Clinical Oncology (2015)

3597 Background: Approximately 15% of colorectal cancers (CRC) display high level of microsatellite instability (MSI-H) due to either hereditary predisposition (Lynch syndrome, LS) or somatic hypermethylation of MLH1. They carry a significantly different prognosis and responses to treatments compared with microsatellite stable (MSS) or low microsatellite instability (MSI-L) CRC. We investigated therapeutically important biomarkers, which may underlie different treatment options for CRC. Methods: Sixty-four MSI-H (including 20 confirmed LS cases), 9 MSI-L and 558 MSS cases were profiled at Caris Life Sciences (Phoenix, AZ) using immunohistochemistry and sequencing (NextGen and Sanger). Results: Compared with non-MSI-H, MSI-H tumors had significantly higher expression of Thymidylate Synthase (TS) (85% vs. 31%), PTEN (71% vs. 48%) expressions and significantly higher mutation rates of BRAF (35% vs. 5%), CTNNB1 (10% vs. 0.7%), HNF1A (32% vs. 0.2%), BRCA1 (19% vs. 5%) and BRCA2 (50% vs. 14%). MSI-H cancers were also significantly more often infiltrated with PD-1+ lymphocytes (71% vs. 43%). Features found specific to sporadic MSI-H tumors (defined as MSI-H and BRAF V600E) in comparison with non-MSI-H tumors included higher mutation rates on select genes within the PI3K/AKT/mTOR pathway, including FBXW7 (31% vs. 7%), PTEN (19% vs. 3%) and STK11 (18% vs. 1%). 20 confirmed LS cases also exhibited significantly higher TS (100%) expression, CTNNB1 (10%) and HNF1A (40%) mutations than non-MSI-H and lower FBXW7 (10% vs. 31%), PTEN (10% vs. 19%) and STK11 (0% vs. 18%) mutation rates than sporadic MSI-H tumors (all p < 0.02). Conclusions: Significantly higher TS expression is a characteristic of both sporadic MSI-H and Lynch tumors, potentially explaining the observed reduced clinical benefit from 5-FU. Higher PD-1+ TIL, BRCA1/2 and CTNNB1 mutations suggest MSI-H as a more promising group for targeted immunotherapy, PARP and Wnt pathway inhibitors. Different molecular features of sporadic MSI-H and Lynch subgroups including PI3K/AKT/mTOR offer insight into targeted therapies for these subgroups of CRC.
IgG4 Component Allergens Are Preferentially Increased in Eosinophilic Esophagitis As Compared to Patients with Milk Anaphylaxis or Galactose-Alpha-1,3-Galactose Allergy
Authors: Jeffrey M. Wilson, Alexander J. Schuyler, Anubha Tripathi, Elizabeth A. Erwin, Scott P. Commins, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2016)
Glucuronide Formation in Patients with Constitutional Hepatic Dysfunction (Gilbert's Disease)
Authors: Rudi Schmid, Lydia Hammaker
Journal: New England Journal of Medicine (1959)

IT has been shown that bilirubin has to be converted to its glucuronide or sulfate1 2 3 4 before it can be excreted in the bile. Retention of nonconjugated bilirubin in the plasma, associated with an enzymatic defect in glucuronide formation in the liver, has been demonstrated in a strain of rats with congenital icterus.5 , 6 A similar defect in glucuronide formation has been found in children with severe congenital nonhemolytic jaundice (Crigler–Najjar syndrome).7 8 9 It has been suggested that, in patients with constitutional hepatic dysfunction or so-called Gilbert disease,10 the mild and intermittent icterus may be the result of a similar but less severe . . .
S118 Circadian Glucose Patterns in Adult Cardiothoracic Transplant Recipients
Authors: A Nixon, S Manduell, B Issa, M Al-Aloul
Journal: Thorax (2015)

<h3>Introduction</h3> New onset diabetes after transplantation (NODAT) is a well-known complication of immunosuppressive therapy and is associated with excess morbidity and mortality. Early identification and treatment of impaired glucose regulation (IGR) is crucial to help prevent or delay the development of NODAT and its associated complications. <h3>Aim</h3> To define circadian glucose patterns of cardiothoracic transplant (CTTx) recipients using a continuous glucose monitoring system (CGMS) and compare the findings with conventional tests for diabetes. <h3>Method</h3> Cross-sectional study in a CTTx outpatient clinic. CGMS was used to construct circadian glucose profiles. Those with CGMS values in excess of 7.7 mmol/l were asked to complete oral glucose tolerance tests (OGTT) and HbA1c. <h3>Participants</h3> Convenience sampling was used to identify 12 stable CTTx recipients (2 heart, 3 single lung and 7 double lung Tx; 9 male; mean [SD] age 58 [8] years, BMI 28.6 [4.9] kg/m<sup>2</sup>, daily prednisolone dose 11.5 [2.2] mg; 4 on tacrolimus vs 8 on cyclosporine; median 477 days since Tx). <h3>Results</h3> None had symptoms of hyperglyaemia. CGMS duration range: 37 to 183 hrs/patient. A significant difference was seen between mean morning (06.00–12.00 hrs) and evening (14.00–20.00 hrs) glucose values (5.8 [1.2] vs 7.6 [1.4] mmol/l; p &lt; 0.001, Figure 1). On CGMS data all participants had glucose values &gt;7.7 mmol/l. Three (25%) had glucose values &gt;11.1 and &lt;3.5 mmol/l on CGMS and were diagnosed with impaired glucose tolerance on OGTT. Compared with 9 normal OGTT patients, the IGT group displayed a higher number of hyperglycaemic episodes/day and a greater% of time above 7.8 mmol/l. No cases of impaired fasting glycaemia or NODAT were identified using OGTT or HbA1c. <h3>Conclusion</h3> Findings of this pilot study emphasise the importance of improving screening for IGR in CTTx recipients. We identified diurnal variation in glucose patterns, with higher glucose values in the afternoon and evening than morning, which has implications for timing of random glucose sampling in clinic. Poor correlation was found between CGMS and conventional diagnostic tests for diabetes which may not be sensitive enough to identify IGR in CTTx recipients. This merits further investigation in a larger cohort.
Screening for depression in primary care
Authors: W. P Plummer
Journal: BMJ (2003)

Editor—The paper by Henkel et al contains several scientific and statistical errors, which should have been identified and eliminated by the BMJ's peer review process before publication.1 The study is described as a cohort study but is a cross sectional study.


The general health questionnaire is inappropriate as a screening test for depression and should not be compared with a gold standard test that is specific for depression. It is a screening test for the “common mental disorders” that often occur in primary care,2 with a good sensitivity but poor specificity for depression. 






Henkel et al choose sensitivity and negative predictive value as measures of how well their tests perform. Sensitivity should be paired with specificity. Sensitivity and negative predictive value are not independent.

They do not make clear their primary hypothesis or explain what questions they are seeking to examine in their analysis. With so many different measures that they could compare, a plan of analysis is essential. They could, for example, start with an omnibus test for sensitivity, such as Cochran's Q.3

Henkel et al use one sided statistical tests but should have used two sided tests. Exact P values or confidence intervals should have been given. Fleiss gives the procedure for confidence intervals in matched pairs.3

They have carried out multiple statistical tests without making a correction. To maintain the overall probability of obtaining a type I error at 0.05, a Bonferroni or other correction is usually made to the significance level of the test.

Henkel et al have not allowed for differences in the sensitivity, etc, between general practitioners. They should have measured the variation between general practitioners and the overall analysis should be adjusted for clustering.

The World Health Organization recommends screening patients in general practitioners' surgeries, but a systematic review of the use of routinely administered questionnaires for depression and anxiety showed that screening tests do not improve diagnosis rates or outcomes in primary care settings.4
Psychiatric aftercare: identified needs versus referral patterns
Authors: D A Wasylenki, P Goering, W Lancee, L Fischer, S J Freeman
Journal: American Journal of Psychiatry (1981)

Although psychiatric aftercare has received increased attention, little is known about patients' needs for community resources or about predischarge referral patterns. The authors interviewed hospital staff about needs and referrals for each of 747 patients about to be discharged. Nearly all patients had needs in the medical/therapeutic area and most received referrals. In three other nonmedical aftercare areas needs were identified for a much lower percentage of patients, and identified need was two to three times greater than referrals made. The authors discuss the implications of these findings for the provision of aftercare services.
In Vitro Splenic IgG Synthesis in Hodgkin's Disease
Authors: Robert L. Longmire, Robert McMillan, Robert Yelenosky, Samuel Armstrong, J. Eugene Lang, Charles G. Craddock
Journal: New England Journal of Medicine (1973)

Experimental and clinical observations suggest increased lymphoid reactivity in Hodgkin's disease. Since thymus-dependent lymphocyte function is often depressed whereas serum antibody responses appear normal, in vitro splenic IgG synthesis was studied to assess B lymphocyte activity. Increased total splenic IgG synthesis occurred in 20 of 22 patients with Hodgkin's disease. Mean IgG production by uninvolved and lightly involved spleens of the patients was five and 11 times normal, whereas heavily involved spleens averaged twice normal levels. Unstimulated IgG synthesis by uninvolved and lightly involved spleens of patients was similar to that of normal spleens after secondary antigenic stimulation, suggesting an in vitro response to an in vivo antigenic challenge. When IgG produced in culture by spleens affected by Hodgkin's disease was incubated with homologous lymphocytes, highly significant IgG binding levels were found. These data suggest that the spleen in Hodgkin's disease responds with a humoral antibody to some antigen associated with lymphocytes. (N Engl J Med 289:763–767, 1973)
Paralytic Poliomyelitis in Massachusetts, 1959
Authors: Sumner Berkovich, Jack E. Pickering, Sidney Kibrick, Barbara W. Bliss
Journal: New England Journal of Medicine (1961)

IN 1959, 137 paralytic among 157 cases of poliomyelitis were reported in Massachusetts. This was the highest incidence of paralytic disease since inactivated-poliovirus vaccine became generally available, and the largest number in Massachusetts since 1955, when 2771 paralytic cases were reported.1 The cases in 1959 were characterized by several additional features of interest. Nearly all were attributed to Type 3 poliovirus whereas Type 1 was most frequently responsible in the remainder of the nation. Altogether, they comprised the largest Type 3 poliovirus outbreak in the United States during 1959.2 A remarkably high proportion, moreover, occurred in persons who had received . . .
Electromyography in Latent Tetany
Authors: Robert G. Feldman, Carl V. Granger
Journal: New England Journal of Medicine (1963)

THE clinical manifestations of tetany are striking and include paresthesias, numbness, pain in the distal extremities or periorally, and sensations of tension in the muscles of the hands, feet, face and neck. Sometimes, spasm of the small muscles of the hand impedes fine movements and produces a feeling of weakness or clumsiness. In severe cases twitching, tremors and spasms may involve the carpal, pedal, facial, laryngeal, diaphragmatic and even the neck and trunk muscles. Subclinical or latent tetany may be unrecognized unless signs and symptoms are provoked by maneuvers such as tapping on the facial nerve (Chvostek's sign), ischemia caused . . .
The comparison of epirubicin-treated MCF-7 mammosphere cells to the treated monolayer cells
Authors: M. Huang, F. Zhang, Y. Xu, H. Wang, S. Lin, Y. Zhang
Journal: Journal of Clinical Oncology (2009)

e13542 Objective: To explore the different effects of epirubicin on the MCF-7 mammosphere cells and the monolayer cells. Methods: MCF-7 cells were cultured in suspension to generate primary mammospheres. The inhibitory effects of epirubicin on MCF-7 mammosphere cells and the monolayer cells by were measured by MTT assay. The change of CD44 + CD24 - expression and cell cycle distribution in MCF-7 mammosphere cells and the monolayer cells under epirubicin condition was analyzed by flow cytometry. Results: The cell inhibition was lower in MCF-7 mammosphere cells than that in the monolayer cells when induced by the same concentration of epirubicin (&gt;100 ng/ml),(P&lt;0.01). The CD44 + CD24 - expression was significantly higher in MCF-7 mammosphere cells than that in the monolayer cells under 400 ng/μl epirubicin for 72 h, (22.8% ± 4.8% Vs 3.3% ± 0.8%),(P&lt;0.01). The cell cycle indicated that MCF-7 mammosphere cells had higher proportion of G0/G1 phase than the monolayer cells, (74.33% ± 3.20% Vs 53.40% ± 3.45%) (P&lt;0.01). Epirubicin had little effect on the G0/G1 phase of MCF-7 mammosphere cells and the monolayer cells, but the S phase and G2 phase was not the case. Conclusion: Epirubicin had lower inhibitory effects on MCF-7 mammosphere cells and it can be used to enrich breast cancer stem cell. Epirubicin had lower effect on the G0/G1 phase of MCF-7 mammosphere cells as compared with control. No significant financial relationships to disclose.
Case 21-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Edward A. Nardell, George Kucyj
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 20-year-old man was admitted to the hospital because of recurrent hemoptysis and a pulmonary cavity.The patient had been well until 20 months earlier, when he was admitted to another hospital because of a spontaneous left pneumothorax. A chest tube was inserted, and the pneumothorax diminished. X-ray films of the chest, obtained on the day of discharge, showed a left apical hydropneumothorax and diffuse left pleural thickening or loculated fluid; the other lung regions and mediastinum were normal.The patient was well thereafter until five months before entry, when night sweats developed. One month later he . . .