tbuckley/cabot-search huggingface dataset:
Screening for postnatal depression in primary care: cost effectiveness analysis
Authors: M. Paulden, S. Palmer, C. Hewitt, S. Gilbody
Journal: BMJ (2009)

<b>Objective</b> To evaluate the cost effectiveness of routine screening for postnatal depression in primary care. <b>Design</b> Cost effectiveness analysis with a decision model of alternative methods of screening for depression, including standardised postnatal depression and generic depression instruments. The performance of screening instruments was derived from a systematic review and bivariate meta-analysis at a range of instrument cut points; estimates of other relevant parameters were derived from literature sources and relevant databases. A decision tree considered the full treatment pathway from the possible onset of postnatal depression through identification, treatment, and possible relapse. <b>Setting</b> Primary care. <b>Participants</b> A hypothetical population of women assessed for postnatal depression either via routine care only or supplemented by use of formal identification methods six weeks postnatally, as recommended in recent guidelines. <b>Main outcome measures</b> Costs expressed in 2006-7 prices and impact on health outcomes expressed in terms of quality adjusted life years (QALYs). The time horizon of the analysis was one year. <b>Results</b> The routine application of either postnatal or general depression questionnaires did not seem to be cost effective compared with routine care only. The Edinburgh postnatal depression scale (at a cut point of 16) had an incremental cost effectiveness ratio (ICER) of £41 103 (€45 398, $67 130) per QALY compared with routine care only. The ICER for all other strategies ranged from £49 928 to £272 463 per QALY versus routine care only, while the probability that no formal identification strategy was cost effective was 88% (59%) at a cost effectiveness threshold of £20 000 (£30 000) per QALY. While sensitivity analysis indicated that the cost of managing incorrectly identified depression (false positive result) was an important driver of the model, formal identification approaches did not seem to be cost effective at any feasible estimate of this cost. <b>Conclusions</b> Formal identification methods for postnatal depression do not seem to represent value for money for the NHS. The major determinant of cost effectiveness seems to be the potential additional costs of managing women incorrectly diagnosed as depressed. Formal identification methods for postnatal depression do not currently satisfy the National Screening Committee's criteria for the adoption of a screening strategy as part of national health policy.
Trypsinogen activation peptides assay in the early prediction of severity of acute pancreatitis
Authors: A. M. Gudgeon, D. I. Heath, P. Hurley, Ahmed Jehanli, Geeta Patel, C. Wilson, A. Shenkin, B. M. Austen, C. W. Imrie, J. Hermon-Taylor
Journal: The Lancet (1990)
Increased cyclic AMP content accelerates protein synthesis in rat heart.
Authors: X P Xenophontos, P A Watson, B H Chua, T Haneda, H E Morgan
Journal: Circulation Research (1989)

Elevation of cyclic AMP (cAMP) content in perfused rat hearts by exposure to glucagon, forskolin, and 1-methyl-3-isobutylxanthine (IBMX) increased rates of protein synthesis during the second hour of perfusion with buffer that contained glucose in the absence of added insulin. When tetrodotoxin was added to arrest contractile activity, glucagon, forskolin, and IBMX still elevated cAMP content and rates of protein synthesis. Perfusion of beating rat hearts at elevated aortic pressure (120 mm Hg vs. 60 mm Hg) also accelerated rates of protein synthesis and raised cAMP content and cAMP-dependent protein kinase activity during the second hour of perfusion. Insulin accelerated rates of protein synthesis in beating hearts during the first and second hour of perfusion but did not increase cAMP content. Elevation of aortic pressure in insulin-treated hearts raised cAMP content but had no further effect on rates of protein synthesis. Perfusion of arrested hearts for as little as 2 minutes at 120 mm Hg resulted in a rapid and sustained increase in cAMP content, cAMP-dependent protein kinase activity, and rate of protein synthesis after 60-120 minutes of additional perfusion at 60 mm Hg. Exposure of arrested hearts to 0.2 mM methacholine, a muscarinic-cholinergic agonist, for 5 minutes before elevation of perfusion pressure blocked the pressure-induced increases in cAMP content, cAMP-dependent protein kinase activity, and rates of protein synthesis. When hearts were removed from pertussis toxin-treated animals, methacholine did not block the effects of forskolin on these same three parameters. These studies indicated that elevation of tissue cAMP by hormone binding, direct activation of adenylate cyclase, or inhibition of phosphodiesterase resulted in acceleration of protein synthesis. Furthermore, the effects of increased aortic pressure to accelerate synthesis appeared to involve a cAMP-dependent mechanism that was independent of changes in contractile activity but could be blocked with a muscarinic-cholinergic agonist. Acceleration of protein synthesis by insulin was not associated with an elevation of cAMP.
Hypopigmented mycosis fungoides: report of five cases with ultrastructural observations
Authors: S. M. BREATHNACH, P. H. McKEE, N. P. SMITH
Journal: British Journal of Dermatology (1982)

Five dark-skinned individuals presented with widespread well-demarcated hypopigmented lesions, biopsy of which revealed the histopathological features of mycosis fungoides. Ultrastructural studies showed focal invasion of the epidermis by mycosis cells with degenerative changes in adjacent melanocytes and keratinocytes. The majority of melanocytes exhibited swelling of cytoplasmic organelles and disordered melanogenesis with production of spherical incompletely melanized melanosomes. In addition disintegrating melanocytes were occasionally seen. Perifollicular repigmentation within hypopigmented areas occurred in two patients following clearing of the epidermal infiltrate with PUVA therapy. Mycosis fungoides may present with areas of cutaneous hypopigmentation.
A distinctive erythematous macular exanthem of the adult: a new entity?
Authors: F. Drago, M. Basso, A. Rebora
Journal: British Journal of Dermatology (2005)

Delineating a new exanthem is difficult. Atypical or modified types of already known conditions can easily be mistaken for new entities.To report 29 cases of an acute, self-limiting exanthem never described before.Clinical description, serology, polymerase chain reaction (PCR) and other laboratory investigations.The eruption starts with bright pink-red slightly oedematous macules symmetrically arranged on the trunk. The lesions tend to coalesce, and spread to the limbs on which they may acquire a marginated annular appearance. The lesions invariably spare the face (including oral mucous membranes), palms and soles. The eruption is pruritic and lasts 20-30 days, clearing spontaneously. The disease has a predilection for men aged 17-56 years and occurs mostly between spring and summer. Serological tests, PCR assays and investigations for bacteria, parasites or viruses were consistently negative.The clinical picture does not recall any of the classical exanthems or their atypical forms.
Pericyte Progenitors at the Crossroads Between Fibrosis and Regeneration
Authors: Matthew L. Steinhauser, Richard T. Lee
Journal: Circulation Research (2013)

Tissue repair after injury is generally inversely related to the extent of scarring, suggesting the possibility that regeneration could be promoted by interventions that inhibit scar formation. New work by Dulauroy et al has identified a myofibroblast progenitor with pericyte characteristics as an important mediator of scarring in skin and skeletal muscle after injury. The genetic ablation of this lineage, which was identifiable by the expression of ADAM12, led to a dramatic reduction in scarring and more complete regeneration. This work sharpens the conceptual rationale for therapeutic targeting of soluble or cellular mediators of scarring to promote tissue regeneration.
Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival
Authors: J. Delyon, C. Mateus, D. Lefeuvre, E. Lanoy, L. Zitvogel, N. Chaput, S. Roy, A.M.M. Eggermont, E. Routier, C. Robert
Journal: Annals of Oncology (2013)
Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis
Authors: E.T. Petridou, T.N. Sergentanis, C. Perlepe, P. Papathoma, G. Tsilimidos, E. Kontogeorgi, M. Kourti, M. Baka, M. Moschovi, S. Polychronopoulou, V. Sidi, E. Hatzipantelis, E. Stiakaki, A.N. Iliadou, C. La Vecchia, A. Skalkidou, H.O. Adami
Journal: Annals of Oncology (2014)
Access to Subspecialty Care for Patients With Mobility Impairment
Authors: Tara Lagu, Nicholas S. Hannon, Michael B. Rothberg, Annalee S. Wells, K. Laurie Green, McAllister O. Windom, Katherine R. Dempsey, Penelope S. Pekow, Jill S. Avrunin, Aaron Chen, Peter K. Lindenauer
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Adults who use wheelchairs have difficulty accessing physicians and receive less preventive care than their able-bodied counterparts. Objective: To learn about the accessibility of medical and surgical subspecialist practices for patients with mobility impairment. Design: A telephone survey was used to try to make an appointment for a fictional patient who was obese and hemiparetic, used a wheelchair, and could not self-transfer from chair to examination table. Setting: 256 endocrinology, gynecology, orthopedic surgery, rheumatology, urology, ophthalmology, otolaryngology, and psychiatry practices in 4 U.S. cities. Patients: None. Measurements: Accessibility of the practice, reasons for lack of accessibility, and planned method of transfer of the patient to an examination table. Results: Of 256 practices, 56 (22%) reported that they could not accommodate the patient, 9 (4%) reported that the building was inaccessible, 47 (18%) reported inability to transfer a patient from a wheelchair to an examination table, and 22 (9%) reported use of height-adjustable tables or a lift for transfer. Gynecology was the subspecialty with the highest rate of inaccessible practices (44%). Limitation: Small numbers of practices in 8 subspecialties in 4 cities and use of a fictional patient with obesity and hemiparesis limit generalizability. Conclusion: Many subspecialists could not accommodate a patient with mobility impairment because they could not transfer the patient to an examination table. Better awareness among providers about the requirements of the Americans with Disabilities Act and the standards of care for patients in wheelchairs is needed. Primary Funding Source: None.
Persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection
Authors: Carla S. Coffin, Tram N.Q. Pham, Patricia M. Mulrooney, Norma D. Churchill, Tomasz I. Michalak
Journal: Hepatology (2004)

Antibodies against virus nucleocapsid (anticore) normally accompany hepadnaviral hepatitis but they may also occur in the absence of symptoms and other serological indicators of the infection. This situation can be encountered following a clinically and serologically unapparent exposure to hepatitis B virus (HBV) or after recovery from hepatitis B. In this study, woodchucks inoculated with woodchuck hepatitis virus (WHV) were investigated to determine the relationship between anticore detection and the molecular status of virus replication in a primary WHV surface antigen (WHsAg)-negative infection or long-after resolution of WHV hepatitis. Serial, parallel samples of sera, peripheral blood mononuclear cells (PBMC) and liver tissue, collected for more than 5 years after inoculation with virus, were examined for WHV DNA by highly sensitive polymerase chain reaction (PCR)/nucleic acid hybridization assays. Sera were also tested for WHV DNA after DNase treatment and for WHV DNA and WHsAg after concentration in sucrose. Liver and PBMC were examined for WHV covalently closed circular DNA and viral RNA transcripts by PCR-based techniques to assess virus replication status. The study showed that anticore antibodies existing in the absence of other serological markers are a reliable indicator of occult WHV infection. This state can be accompanied by traces of circulating particles behaving as intact virions and by intermittent minimal-to-mild liver inflammation. In conclusion , the long-term presence of anticore antibodies alone is a consequence of sustained restimulation of the immune system by virus nucleocapsid produced during low-level hepadnaviral assembly. (Hepatology 2004.)
Effect of Cyclooxygenase-2 Inhibition on Renal Function in Elderly Persons Receiving a Low-Salt Diet
Authors: Suzanne K. Swan, David W. Rudy, Kenneth C. Lasseter, Charles F. Ryan, Kristin L. Buechel, Laurence J. Lambrecht, Manuel B. Pinto, Stacy C. Dilzer, Olga Obrda, Kimberly J. Sundblad, Carol P. Gumbs, David L. Ebel, Hui Quan, Patrick J. Larson, Jules I. Schwartz, Thomas A. Musliner, Barry J. Gertz, D. Craig Brater, Siu-Long Yao
Journal: Annals of Internal Medicine (2000)

Background: Most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1), whose inhibition is associated with gastrointestinal ulceration, and COX-2, whose inhibition is associated with therapeutic benefits. Although agents that do not produce COX-1 activity may have fewer adverse effects, targeted disruption of the COX-2 allele in mice has resulted in severe renal problems, suggesting that COX-2 inhibition may also produce adverse effects. Objective: To determine the effect of rofecoxib, a member of the coxib class of drugs and a specific inhibitor of the COX-2 enzyme, on renal function in elderly patients. Design: A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study. Setting: Clinical research units. Patients: 75 patients 60 to 80 years of age. Intervention: In the first study, single doses of rofecoxib, 250 mg (about 5-fold to 20-fold the recommended dose); indomethacin, 75 mg; and placebo were administered to 15 patients. In the second study, multiple doses of rofecoxib, 12.5 or 25 mg/d; indomethacin, 50 mg three times daily; or placebo were administered to 60 patients. Patients in both studies received a low-sodium diet. Measurements: Glomerular filtration rate, creatinine clearance, and urinary and serum sodium and potassium values. Results: Compared with placebo, single doses of rofecoxib and indomethacin decreased the glomerular filtration rate by 0.23 mL/s (P < 0.001) and 0.18 mL/s (P = 0.003), respectively. In contrast, respective decreases of 0.14, 0.13, and 0.10 mL/s were observed after multiple doses of rofecoxib, 12.5 mg/d (P = 0.019); rofecoxib, 25 mg (P = 0.029), and indomethacin (P = 0.086) were administered. Changes in creatinine clearance and serum and urinary sodium and potassium were less pronounced. Conclusions: The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.
p53-mediated disruption of FIP200 function cause autophagic dysregulation in a SCA7 polyglutamine disease model
Authors: Xin Yu, Andrés Muñoz Alarcón, Abiodun Ajayi, Kristin Webling, Anne Steinhof, Ülo Langel, Anna-Lena Ström
Journal: Molecular Neurodegeneration (2013)

Background Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine domains [1]. Aggregation of the different polyglutamine (polyQ) expanded disease proteins have been linked to the toxicity in these disorders [1]. We and others have shown that polyQ expanded proteins can be degraded by autophagy [2], and pharmacological activation of this pathway has hence been suggested as a therapeutic approach for these disorders. However, lately increasing evidence indicating that autophagy dysfunction occurs in several neurodegenerative disorders has emerged and raised concerns regarding using stimulation of this pathway as a therapeutic approach [3]. The aim of this study was to determine if and by which molecular mechanism(s) the expanded SCA7 disease protein ataxin-7 (ATXN7) affects the autophagic process.
Type 2 Diabetes Prevention in the Real World
Authors: Pilvikki Absetz, Brian Oldenburg, Nelli Hankonen, Raisa Valve, Heikki Heinonen, Aulikki Nissinen, Mikael Fogelholm, Martti Talja, Antti Uutela
Journal: Diabetes Care (2007)

OBJECTIVE We study the effectiveness of the GOAL Lifestyle Implementation Trial at the 36-month follow-up. RESEARCH DESIGN AND METHODS Participants (n = 352, type 2 diabetes risk score FINDRISC = 16.2 ± 3.3, BMI 32.6 ± 5.0 kg/m2) received six lifestyle counseling sessions over 8 months. Measurements were at baseline, 12 months (88.6%), and 36 months (77.0%). RESULTS Statistically significant risk reduction at 12 months was maintained at 36 months in weight (−1.0 ± 5.6 kg), BMI (−0.5 ± 2.1 kg/m2), and serum total cholesterol (−0.4 ± 1.1 mmol/l). CONCLUSIONS Maintenance of risk reduction in this “real world” trial proves the intervention's potential for significant public health impact.
Challenges of Coverage Policy Development for Next-Generation Tumor Sequencing Panels: Experts and Payers Weigh In
Authors: Julia R. Trosman, Christine B. Weldon, R. Kate Kelley, Kathryn A. Phillips
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Next-generation tumor sequencing (NGTS) panels, which include multiple established and novel targets across cancers, are emerging in oncology practice, but lack formal positive coverage by US payers. Lack of coverage may impact access and adoption. This study identified challenges of NGTS coverage by private payers. Methods: We conducted semi-structured interviews with 14 NGTS experts on potential NGTS benefits, and with 10 major payers, representing more than 125,000,000 enrollees, on NGTS coverage considerations. We used the framework approach of qualitative research for study design and thematic analyses and simple frequencies to further describe findings. Results: All interviewed payers see potential NGTS benefits, but all noted challenges to formal coverage: 80% state that inherent features of NGTS do not fit the medical necessity definition required for coverage, 70% view NGTS as a bundle of targets versus comprehensive tumor characterization and may evaluate each target individually, and 70% express skepticism regarding new evidence methods proposed for NGTS. Fifty percent of payers expressed sufficient concerns about NGTS adoption and implementation that will preclude their ability to issue positive coverage policies. Conclusions: Payers perceive that NGTS holds significant promise but, in its current form, poses disruptive challenges to coverage policy frameworks. Proactive multidisciplinary efforts to define the direction for NGTS development, evidence generation, and incorporation into coverage policy are necessary to realize its promise and provide patient access. This study contributes to current literature, as possibly the first study to directly interview US payers on NGTS coverage and reimbursement.
Phase II Trial of Sunitinib in Patients With Metastatic Colorectal Cancer After Failure of Standard Therapy
Authors: Leonard B. Saltz, Lee S. Rosen, John L. Marshall, Robert J. Belt, Herbert I. Hurwitz, S. Gail Eckhardt, Emily K. Bergsland, Daniel G. Haller, A. Craig Lockhart, Caio M. Rocha Lima, Xin Huang, Samuel E. DePrimo, Edna Chow-Maneval, Richard C. Chao, Heinz J. Lenz
Journal: Journal of Clinical Oncology (2007)

Purpose Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor receptor and multiple other growth factor receptors. We assessed the safety and efficacy of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. Patients and Methods Eighty-four patients were enrolled onto this two-stage phase II trial and were stratified by whether they had received prior bevacizumab (n = 43) or not (n = 41). Treatment comprised sunitinib 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles. Results By Response Evaluation Criteria in Solid Tumors criteria, one patient, who was in the prior bevacizumab cohort, achieved a partial response, and 13 patients (two in the prior bevacizumab cohort and 11 in the no prior bevacizumab cohort) achieved stable disease lasting ≥ 22 weeks. Median time to progression in the prior bevacizumab and bevacizumab-naïve cohorts was 2.2 months (95% CI, 1.9 to 2.3 months) and 2.5 months (95% CI, 2.3 to 3.1 months), respectively, whereas median overall survival time was 7.1 months (95% CI, 4.9 to 10.6 months) and 10.2 months (95% CI, 8.2 to 15.3 months), respectively. The most common adverse events were fatigue, diarrhea, nausea, vomiting, and anorexia. Twenty-six patients (32%) required dose reduction to 37.5 mg/d, and one patient required dose reduction to 25 mg/d. Conclusion Sunitinib did not demonstrate a meaningful single-agent objective response rate in colorectal cancer refractory to standard chemotherapy. However, the mechanisms of action and acceptable safety profile of sunitinib warrant further study in combination with standard regimens for metastatic colorectal cancer.
Recombination Gives a New Insight in the Effective Population Size and the History of the Old World Human Populations
Authors: Marta Melé, Asif Javed, Marc Pybus, Pierre Zalloua, Marc Haber, David Comas, Mihai G. Netea, Oleg Balanovsky, Elena Balanovska, Li Jin, Yajun Yang, R. M. Pitchappan, G. Arunkumar, Laxmi Parida, Francesc Calafell, Jaume Bertranpetit
Journal: Molecular Biology and Evolution (2011)

The information left by recombination in our genomes can be used to make inferences on our recent evolutionary history. Specifically, the number of past recombination events in a population sample is a function of its effective population size (Ne). We have applied a method, Identifying Recombination in Sequences (IRiS), to detect specific past recombination events in 30 Old World populations to infer their Ne. We have found that sub-Saharan African populations have an Ne that is approximately four times greater than those of non-African populations and that outside of Africa, South Asian populations had the largest Ne. We also observe that the patterns of recombinational diversity of these populations correlate with distance out of Africa if that distance is measured along a path crossing South Arabia. No such correlation is found through a Sinai route, suggesting that anatomically modern humans first left Africa through the Bab-el-Mandeb strait rather than through present Egypt.