tbuckley/cabot-search huggingface dataset:
S121 Co-morbidity and Pneumonia Risk in COPD Patients: A Population Database Analysis of Primary Care Patients
Authors: N Williams, NA Coombs, L Rigge, L Josephs, M Johnson, DM Thomas, TMA Wilkinson
Journal: Thorax (2015)

<h3>Background</h3> Co-morbidities are common in COPD and have been associated with poorer clinical outcomes. Furthermore, patients with COPD are at an increased risk of developing Community acquired pneumonia (CAP). We investigated the impact of concurrent co-morbidity on the risk of developing CAP, in a cohort of COPD patients identified from the Hampshire Health Record analytical database, a local NHS database containing anonymised primary and secondary care records. <h3>Methods</h3> Patients defined as having COPD, had a diagnostic Read code (classification of clinical terms for electronic information coding) in their primary care record at any time prior to 1<sup>st</sup> January 2010 and were aged ≥40 years at the start of the study period. Using clinician-coded diagnoses, CAP episodes which occurred over a 1-year period from the 1<sup>st</sup> January 2010 were identified using Read and ICD-10 code lists and were defined as taking up to 70 days to resolve. Listed co-morbidities were based on coded entries at any time prior to 1<sup>st</sup> January 2010. <h3>Results</h3> Included were 6707 patients with a complete history in 2010 and valid data for all variables considered in the analysis. 55% of patients were men and 36% were current smokers, the mean age was 70 years. 189 patients (2.8%) had at least one CAP episode during 2010. Compared to patients without CAP, patients with CAP were more likely to have ischaemic heart disease (IHD p = 0.005), congestive heart failure (CHF p = 0.021), hypertension (p = 0.017), cerebrovascular disease (CVD p &lt; 0.001), dementia (p &lt; 0.001), and bronchiectasis (p = 0.001). Using logistic regression and controlling for potential confounders, CVD and dementia were independent risk factors for CAP (p = 0.009 and 0.007, respectively), while bronchiectasis trended towards significance (p = 0.073) (Table 1). <h3>Conclusion</h3> In this large population database analysis, CVD and dementia were identified as being independently associated with an increased risk of CAP. Oro-pharyngeal dysfunction in CVD and use of sedative medications in dementia, may contribute to these findings. Further analysis of the complete cohort, over the full 5-year observation period will allow the formulation of robust conclusions about the important factors of CAP risk in COPD, including the impact of pharmacotherapy, blood markers and functional parameters.
“Safety” Testing of Carcinogenic Agents
Authors: Nathan Mantel, W. Ray Bryan
Journal: JNCI Journal of the National Cancer Institute (1961)

The problem of determining what dose levels of an agent are safe, e.g., non-carcinogenic, cannot be resolved unless one first defines some level of permissible risk, no matter how small, rather than insisting on absolute safety. Both because of practical considerations and statistical variation, the determination of low-risk dose levels, for example 1/100 million, cannot be made directly but must be by extrapolation from observed data. A conservative approach for doing so is given. In addition to an arbitrary definition of “virtual safety,” it is necessary to define an arbitrarily high statistical assurance level and a rule for extrapolation by use of an arbitrarily shallow slope. Illustrative data by Bryan and Shimkin (J. Nat. Cancer Inst. 3: 503–531, 1943) on the carcinogenic action of methylcholanthrene yield a “safe,” 1/100 million, dose of 9 × 10−8 mg per mouse when a statistical assurance level of 99 percent and a conservative probit slope of 1 normal deviate per log for extrapolation are used. The principles given are of general applicability in other safety-testing problems, the point of emphasis being that since direct observation cannot be made that the risk at some dose level is clearly low, indirect conservative procedures for the determination of low risk levels must be made. The arbitrary risks and definitions for so doing may change with circumstances. The procedure does not require specification of an experimental protocol; the “safe” dose is determined on the basis of whatever data are available. Minimum protocols may, however, be desirable, since greater amounts of data will ordinarily permit specifying large “safe” levels.
Inclusion of Women in Clinical Trials -- Policies for Population Subgroups
Authors: J. Claude Bennett
Journal: New England Journal of Medicine (1993)

Although the inclusion of women and minorities in medical research is necessary for valid inferences about health and disease in these groups, both women and members of minority groups have been excluded from or underrepresented in many clinical trials. Congress has therefore proposed that the National Institutes of Health (NIH) ensure that all federally funded clinical research include a valid analysis to determine whether the intervention under study affects women or members of minority groups differently from other subgroups. In particular, Section 429B of the NIH Revitalization Act1 provides that the director of the NIH shall ensure that women and . . .
Natural History of Paroxysmal Nocturnal Hemoglobinuria
Authors: Peter Hillmen, S.M. Lewis, Monica Bessler, Lucio Luzzatto, John V. Dacie
Journal: New England Journal of Medicine (1995)

Paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by intravascular hemolysis and venous thrombosis, is an acquired clonal disorder associated with a somatic mutation in a totipotent hematopoietic stem cell. An understanding of the natural history of PNH is essential to improve therapy.
Acquired Hyperoxaluria, Nephrolithiasis, and Intestinal Disease
Authors: Lynwood H. Smith, Hans Fromm, Alan F. Hofmann
Journal: New England Journal of Medicine (1972)

Abstract In seven patients with resection of the distal ileum, calcium oxalate nephrolithiasis and increased urinary excretion of oxalate (64 to 135 mg per 24 hours) developed. Cholestyramine therapy (4 g four times a day) lowered the 24-hour urinary excretion of oxalate to normal in the four patients in whom it was used. Urinary excretion of oxalate was measured in an additional 42 patients with various types of intestinal disorders without evidence of nephrolithiasis. Five of 18 patients with ileal resection, two of seven with bacterial over-growth, and six of 15 with miscellaneous conditions, including nontropical sprue and cirrhosis, had hyperoxaluria.
The Life Expectancy of Profoundly Handicapped People with Mental Retardation
Authors: Richard K. Eyman, Herbert J. Grossman, Robert H. Chaney, Thomas L. Call
Journal: New England Journal of Medicine (1990)

The life expectancy of people with mental retardation is shorter than that of the general population. Exact estimates of the length of survival for mentally retarded persons at especially high risk are not available, however.
Decreased Incidence of Ventricular Late Potentials after Successful Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Eli S. Gang, Allan S. Lew, Ma Hong, Fang Zheng Wang, Carol A. Siebert, Thomas Peter
Journal: New England Journal of Medicine (1989)

In some patients with acute myocardial infarction, low-amplitude potentials that prolong the QRS complex, termed "late potentials," can be recorded on a signal-averaged electrocardiogram. The presence of these late potentials is known to be associated with an increase in the risk of ventricular tachycardia and sudden death. Because patients with acute myocardial infarction who receive thrombolytic therapy have a reduced incidence of ventricular tachyarrhythmia and sudden death, we sought to determine whether such patients also have a decreased incidence of late potentials. We studied 106 patients less than 75 years of age who were admitted with a first myocardial infarction and in whom a signal-averaged electrocardiogram was recorded within 48 hours of admission. Within four hours of the onset of chest pain, tissue plasminogen activator (t-PA) was given to 44 patients, and 62 were treated conventionally. In the t-PA group, late potentials were recorded in 2 of 44 patients (5 percent), as compared with 14 of 62 (23 percent) in the conventionally treated group (P = 0.01). Furthermore, among the patients treated with t-PA, continued occlusion of the infarct-related artery was related to the presence of late potentials. In the t-PA group, late potentials were recorded within 24 hours of angiography in 2 of the 6 patients with an occluded infarct-related artery, as compared with none of the 38 patients with a patent infarct-related artery. Our data suggest that successful thrombolytic therapy is associated with a marked reduction in the incidence of late potentials on the signal-averaged electrocardiogram. Long-term follow-up will be required to determine whether this finding predicts a reduced incidence of subsequent ventricular tachyarrhythmia and sudden death. (N Engl J Med 1989; 321:712–6.)
Children at risk as junior contract dispute drags on, royal college says
Authors: Abi Rimmer
Journal: BMJ (2016)

Child health services are being put at risk because the imposition of the new junior doctors’ contract is forcing trainees out of the profession, the Royal College of Paediatrics and Child Health has warned.

In a statement issued after a meeting on 14 April with England’s health secretary Jeremy Hunt, Neena Modi, the college’s president, said that the government’s decision to impose a new contract on junior doctors in England …
Familial Clustering of Diabetic Kidney Disease
Authors: Elizabeth R. Seaquist, Frederick C. Goetz, Stephen Rich, José Barbosa
Journal: New England Journal of Medicine (1989)

Diabetic nephropathy develops in less than half of all patients with diabetes. To study heredity as a possible risk factor for diabetic kidney disease, we examined the concordance rates for diabetic nephropathy in two sets of families in which both probands and siblings had diabetes mellitus. In one set, the probands (n = 11) had no evidence of diabetic nephropathy, with normal creatinine clearance and a urinary albumin excretion rate below 45 mg per day. In the other set, the probands (n = 26) had undergone kidney transplantation because of diabetic nephropathy. Evidence of nephropathy was found in 2 of the 12 diabetic siblings of the probands without nephropathy (17 percent). Of the 29 diabetic siblings of probands with diabetic nephropathy, 24 (83 percent) had evidence of nephropathy (P<0.001), including 12 with end-stage renal disease. No significant differences were noted between the sibling groups with respect to the duration of diabetes, blood pressure, glycemic control, or glycosylated hemoglobin levels. Logistic regression analysis found nephropathy in the proband to be the only factor significantly predictive of the renal status of the diabetic sibling. We conclude that diabetic nephropathy occurs in familial clusters. This is consistent with the hypothesis that heredity helps to determine susceptibility to diabetic nephropathy. However, this study cannot rule out the possible influences of environmental factors shared by siblings. (N Engl J Med 1989; 320:1161–5.)
Ponatinib In Heavily Pretreated Patients With Chronic Phase Chronic Myeloid Leukemia (CP-CML): Management Of Adverse Events (AEs)
Authors: Philipp D. Le Coutre, Dong-Wook Kim, Javier Pinilla-Ibarz, Ronald Paquette, Charles Chuah, Franck E. Nicolini, Jane F Apperley, H. Jean Khoury, Moshe Talpaz, John F. Dipersio, Daniel J DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C Muller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Kumiko Yanase, Christopher D Turner, Frank G Haluska, Francois Guilhot, Michael W. Deininger, Andreas Hochhaus, Timothy P. Hughes, John M Goldman, Neil P. Shah, Hagop M. Kantarjian, Jorge E. Cortes
Journal: Blood (2013)
Cystathioninuria and Renal Iminoglycinuria in a Pedigree
Authors: Donald T. Whelan, Charles R. Scriver
Journal: New England Journal of Medicine (1968)

Cystathioninuria and hyperglycinuria both occurred in a male Ashkenazi-Jewish Infant. Both traits were dominantly inherited as the heterozygous forms of two independent mutant alleles. The patient was thus a double heterozygote. Renal iminoglycinuria appeared as an autosomal recessive trait in the mother of the proband and In four of her sibs. This condition is the homozygous form of the trait that presents as hyperglycinuria in the heterozygote; it is a benign inborn error of amino acid transport. Cystathioninuria is probably also a benign trait. Knowledge of the precise phenotypes and their significance were of practical value in counseling the family.
Seabather's Eruption
Authors: Anita R. Freudenthal, Paul R. Joseph
Journal: New England Journal of Medicine (1993)

Seabather's eruption is an annoying pruritic dermatitis that appears on the areas covered by the bathing suit as an erythematous macular or papular dermatitis, with or without urticaria. It occurs sporadically in Florida, the Caribbean, and as far north as Bermuda. The cause is not known.
Gas Exchange Abnormalities in Mild Bronchitis and Asymptomatic Asthma
Authors: Gerald Levine, F.. Housley, P. MacLeod, Peter T. Macklem
Journal: New England Journal of Medicine (1970)

Alveolar arterial tension differences for oxygen, and ratios of physiologic dead space to tidal volume measured at rest, were significantly greater in eight patients with mild bronchitis and seven with asymptomatic asthma as compared to normal controls. Routine pulmonary-function tests, including pulmonary resistance, gave normal or only minimally abnormal results. On exercise, oxygen tension differences became normal in three patients with bronchitis and four with asthma but remained abnormal in the others. Ratios of dead space to tidal volume were normal on exercise in only one bronchitic and three asthmatic patients. Abnormalities of ventilation distribution and gas exchange occur before other abnormalities of lung function become apparent.
Effectiveness of zoledronic acid for the prevention of bone metastases in high risk prostate cancer patients: A randomised, open label, multicenter study of the European Association of Urology (EAU) in cooperation with the Scandinavian Prostate Cancer Group (SPCG) and the Arbeitsgemeinschaft Urologische Onkologie (AUO). An initial report of the “ZEUS” study
Authors: W. Witjes, T. Tammela, M. Wirth
Journal: Journal of Clinical Oncology (2006)

14644 Background: Patients with advanced prostate cancer (PC) are at high risk of developing bone metastases resulting in clinically significant skeletal morbidity and debilitating bone pain. Zoledronic acid (ZA) significantly reduced the incidence and delayed the onset of skeletal complications and provided durable pain reduction compared with placebo in patients with PC metastatic to bone. Methods: We started a European study investigating the effect of ZA in the prevention of PC bone metastases in patients with high risk PC. This prospective, multi-centre, randomised, open-label study, the ZA EUropean Study (ZEUS), aims at randomising 1300 patients within 3 years in 13 European countries and Turkey. Patients are randomised for standard PC therapy plus 4 mg ZA intravenously every 3 months for a period of 48 months or standard PC therapy alone. Results: Presently, we have randomised 484 patients with a mean age of 67 years (range 45–86) in 13 countries. All patients had at least one of the following high risk prognostic factors: 281 (58%) patients had a PSA ≥ 20 ng/ml, 140 (29%) patients had lymphnode positive disease and 286 (59%) patients had a Gleason of 8–10. 124 (26%) patients had a PSA ≥ 20 ng/ml and a Gleason of 8–10; 60 (12%) patients had a PSA ≥ 20 ng/ml and N1 disease and 64 (13%) patients had a Gleason of 8–10 and N1 disease. 244 (50%) patients underwent a prior prostatectomy or radiotherapy with curative intent and 303 (63%) patients received hormonal treatment. The randomisation arms were equally distributed amongst prognostic groups, centres and countries. Conclusions: The ZEUS study is designed to evaluate if ZA can contribute in preventing or delaying bone metastases in high risk PC patients. Presently, the majority (59%) of patients have a Gleason of 8–10 or a PSA ≥ 20 ng/ml (58%) and they receive hormonal treatment (63%). Half (50%) of the patients underwent a prior prostatectomy or radiotherapy with curative intent. This is representative for the PC population that is at high risk for developing bone metastases. No significant financial relationships to disclose.
Prophylactic Doxycycline for Travelers' Diarrhea
Authors: David A. Sack, Donald C. Kaminsky, R. Bradley Sack, J. N. Itotia, Ray R. Arthur, Albert Z. Kapikian, Frits Ørskov, Ida Ørskov
Journal: New England Journal of Medicine (1978)

We performed a randomized double-blind study to determine the efficacy of doxycycline (100 mg daily) in preventing travelers' diarrhea among 39 Peace Corps volunteers during their first five weeks in Kenya. The volunteers took either doxycycline or placebo for three weeks and were observed for an additional two weeks. Nine of 21 taking placebo and one of 18 taking doxycycline had travelers' diarrhea during the treatment period (P = 0.012). The protection seemed to persist for at least one week after the drug was stopped. Enterotoxigenic Escherichia coli was the only pathogen isolated from the placebo group, but was not detected in persons taking doxycycline. None of these organisms were resistant to doxycycline or tetracycline, whereas resistance to tetracyclines and other antibiotics was common among the nonenterotoxigenic Esch. coli. We conclude that doxycycline effectively prevented most episodes of travelers' dirrhea.
Lipoprotein Lipase in Fat-Induced Hyperlipemia
Authors: G. Steiner
Journal: New England Journal of Medicine (1968)

Although able to hydrolyze a coconut-oil emulsion, the postheparin plasma of a patient with fat-induced (Type 5) hyperlipemia was unable to hydrolyze his own, normal human or rat chylomicrons. Postheparin plasma from normal controls were able to hydrolyze the emulsion and all chylomicron preparations. The inability of the patient's plasma to hydrolyze chylomicrons was not corrected by the addition of plasma (preheparin or postheparin) from normal subjects. The defect could not be produced in normal plasma by addition of the patient's plasma. Tests of lipolytic activity using the coconut-oil emulsion do not accurately reflect lipid-clearing ability. There appear to be at least two activities, one against the emulsion, and the other against chylomicrons. This and perhaps other Type 5 patients may lack the latter while possessing the former.
Modern Staging and Utility of PET Imaging in Esophageal Cancer Management
Authors: Kwang-Yu Chang, Jang-Yang Chang, Joseph Chao, Yun Yen
Journal: Journal of the National Comprehensive Cancer Network (2008)

Esophageal cancer is the eighth most common cancer worldwide, and one of the most fatal diseases despite modern medical treatment. Because correct staging and surveillance of neoadjuvant therapy for esophageal cancer is mandatory for further treatment planning, choosing a modern imaging system is important. The development of 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) has provided alternate means of tumor detection distinct from more conventional methods. This modality has extraordinary performance in detecting locoregional lymph node involvement and distant metastatic disease, and has been introduced as a powerful tool in many guidelines. However, some factors still lead to false-negative or -positive results, raising questions of its accuracy. This article discusses the clinical efficacy of PET in staging and surveillance of neoadjuvant therapy in esophageal cancer, comparing its accuracy with conventional imaging modalities.
Immediate Adjuvant Chemotherapy versus Observation with Treatment at Relapse in Pathological Stage II Testicular Cancer
Authors: S D Williams, D M Stablein, L H Einhorn, F M Muggia, R B Weiss, J P Donohue, D F Paulson, K W Brunner, E M Jacobs, J T Spaulding
Journal: New England Journal of Medicine (1987)

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.
Observational Study Of VMP (Bortezomib, melphalan, prednisolone) Regimen For Newly Diagnosed Korean Myeloma Patients Who Are Not Eligible For Transplantation
Authors: Kihyun Kim, Mark Lee, Hyo Jung Kim, Yang Soo Kim, Keon Woo Park, Sung Hwa Bae, Ho Jin Shin, Won Sik Lee, Jung-Hee Lee, Jeong Ok Lee, Sung-Soo Yoon, Ki Hwan Kim, Sung-Hyun Nam, Chang-Ki Min, Sang Byung Bae, Joon Seong Park, Myung Soo Hyun, Yeung-Chul Mun, Jae-Yong Kwak, Je-Jung Lee
Journal: Blood (2013)
Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity
Authors: Stephen J. Clark, Heather J. Lee, Sébastien A. Smallwood, Gavin Kelsey, Wolf Reik
Journal: Genome biology (2016)

Emerging single-cell epigenomic methods are being developed with the exciting potential to transform our knowledge of gene regulation. Here we review available techniques and future possibilities, arguing that the full potential of single-cell epigenetic studies will be realized through parallel profiling of genomic, transcriptional, and epigenetic information.
Mutation of the Prion Protein in Libyan Jews with Creutzfeldt–Jakob Disease
Authors: Karen Hsiao, Zeev Meiner, Esther Kahana, Carin Cass, Irit Kahana, Dana Avrahami, Guglielmo Scarlato, Oded Abramsky, Stanley B. Prusiner, Ruth Gabizon
Journal: New England Journal of Medicine (1991)

Creutzfeldt—Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease — 10 Libyan Jews from Israel and 1 Libyan Jew from Italy — to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease.