tbuckley/cabot-search huggingface dataset:
A comparison of two primary care trials on tennis elbow: issues of external validity
Authors: N Smidt
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To assess clinical heterogeneity across two studies with respect to study population, interventions, and outcome measures, and to evaluate the influence of these sources of heterogeneity on the results of the studies. <b>Methods:</b> The individual patient data were used from two randomised controlled trials investigating the effectiveness of conservative treatments in patients with tennis elbow in primary care. Patients were allocated at random to treatment with steroid injection, wait and see policy, non-steroidal anti-inflammatory drugs, placebo tablets, or physiotherapy. Outcome measures included severity of the main complaint, inconvenience of the elbow complaints, pain during the day, elbow disability, pain-free grip strength, and global improvement. All outcomes were assessed at 1, 6, and 12 months after randomisation. <b>Results:</b> The two study populations were similar with respect to age, sex, comorbid neck/shoulder complaints, and baseline scores for the severity of pain. However, significant differences were observed for employment status, duration of elbow complaints, dominant side affected, previous history of elbow complaints, and use of analgesics. Local injections differed between the two studies with respect to volume, number, and steroid preparation. However, after 1, 6, and 12 months, the treatment effects of steroid injections were very similar between the study populations. <b>Conclusions:</b> Despite large differences in study population at baseline, the responses to steroid injections were remarkably similar. Also the responses to other conservative interventions and the placebo treatment were very consistent, suggesting a uniform course of a tennis elbow and a lack of influence of clinical heterogeneity.
Angiotensin-converting Enzyme Gene Polymorphism and Risk of Sarcoidosis
Authors: MARY J. MALIARIK, BENJAMIN A. RYBICKI, EMILY MALVITZ, ROBERTA G. SHEFFER, MARCIE MAJOR, JOHN POPOVICH, MICHAEL C. IANNUZZI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The angiotensin-converting enzyme (ACE) has been implicated in the pathophysiology of sarcoidosis. Serum ACE levels in normal and sarcoidosis patients are influenced by an insertion (I)/deletion (D) polymorphism in the ACE gene. To elucidate the role of this ACE gene polymorphism in sarcoidosis, we conducted a case-control study in African Americans and Caucasians. The ACE gene (I/D) polymorphism did not differ between 60 Caucasian cases and 48 control subjects (p = 0.577). In contrast, a comparison of 183 African-American cases and 111 control subjects resulted in a marked difference in genotypic distributions (p = 0.005). In African Americans, the risk for sarcoidosis was 1.30 (95% confidence interval [CI] = 0.72 to 2.36) for ID heterozygotes, and 3.17 (95% CI = 1.50 to 6.71) for deletion/deletion (DD) homozygotes. The risk associated with the DD homozygotes was even greater in African Americans when cases were restricted to those with a positive family history (odds ratio = 4.83; 95% CI = 1.86 to 12.59). Further analyses of African-American cases showed that the ACE genotype was not associated with disease severity, extrathoracic involvement, or overall radiographic change 2 to 4 yr after diagnosis. We did find a moderate association between the II genotype and radiographic progression (OR = 2.97; 95% CI = 1.01 to 8.76). Our results suggest the ACE genotype may play a more important role in sarcoidosis susceptibility and progression in African Americans than Caucasians.
S13 The bacteriology and epidemiology of pleural infection – a review of the literature and its relevance to clinical practise
Authors: JP Corcoran, JW Lockey, SL Zheng, JM Wrightson, NM Rahman
Journal: Thorax (2012)

<h3>Introduction</h3> Pleural infection is described in the medical literature as far back as Hippocrates, yet even now the best management strategy remains uncertain. A rising case incidence places an increasingly significant burden on healthcare systems worldwide, with 65,000 patients per annum diagnosed with pleural infection in the UK and USA alone. It is increasingly accepted that pleural infection is a separate phenomenon to parenchymal lung infection, with its own epidemiology and bacteriology. This review sought to identify the data on pleural infection in adults published since 2000, to create a detailed up-to-date record on its bacteriology that might inform future research and guidelines. <h3>Methods</h3> We searched the MEDLINE and EMBASE databases alongside the Cochrane Central Register of Controlled Trials using PubMed and OVID for studies relating to pleural infection in adults published since 2000. Studies were shortlisted for inclusion if they contained a record of confirmed microbiological diagnosis and methodology (using standard culture or nucleic acid amplification techniques); paediatric studies and tuberculous pleural infection were excluded. Studies were double-scored by clinicians with expertise in diagnosis and management of pleural infection to determine suitability and weighting. <h3>Results</h3> Our initial search strategy identified 6126 references; of these, 2572 abstracts were relevant to respiratory practise and subsequently 136 papers were shortlisted for assessment of suitability for inclusion. Streptococcal species, notably the <i>anginosus</i> (<i>milleri</i>) group and <i>pneumoniae</i> are the most commonly identified pathogens in pleural infection as a whole. However, there is substantial variation in bacteriology according to where the infection is acquired – both “locally” (community vs. nosocomial) and “globally” (geographical location). The likelihood that many pleural infections are polymicrobial in nature, with the pathogenicity of different organisms being uncertain, is also raised. <h3>Conclusions</h3> Pleural infection differs significantly in its bacteriology from parenchymal lung infection and according to where it is acquired. This has important implications for antibiotic choice and predicting morbidity and mortality. A high number of cases are undiagnosed using conventional culture and the role of techniques such as nucleic acid amplification is promising but requires further clarification. Research is necessary to further define these bacteriological characteristics of pleural infection and inform future guidelines.
Genetic indicators and susceptibility to osteoarthritis
Authors: J Loughlin
Journal: British Journal of Sports Medicine (2011)

A large number of experiments have been performed to identify genetic loci that influence osteoarthritis (OA) susceptibility, with a particular focus on the primary form of the disease. Unfortunately, the currently reported candidate-gene, genome-wide linkage scans and genome-wide association scans have tended to highlight the heterogeneous nature of OA rather than generate statistically compelling genome signals. Nevertheless, some breakthroughs have been made. For example, genetic susceptibility within genes coding for components of the transforming growth factor β pathway has emerged as a particularly interesting find, while completely novel loci are also being uncovered, such as the signal to a cluster of genes on chromosome 7q22. It also appears that quantitative effects on gene expression, rather than qualitative effects on protein function, are particularly important, and that we need to consider the effects of genetic susceptibility in joint formation as much as we do in joint maintenance. Nevertheless, we are still only at the beginning of our search, and much more sophisticated clinical and laboratory approaches will need to be applied before we get a clear understanding of the genetic indicators that influence OA susceptibility.
The Usefulness of the International Diabetes Federation and the National Cholesterol Education Program's Adult Treatment Panel III Definitions of the Metabolic Syndrome in Predicting Coronary Heart Disease in Subjects With Type 2 Diabetes
Authors: Peter C. Tong, Alice P. Kong, Wing-Yee So, Xilin Yang, Chung-Shun Ho, Ronald C. Ma, Risa Ozaki, Chun-Chung Chow, Christopher W. Lam, Juliana C.N. Chan, Clive S. Cockram
Journal: Diabetes Care (2007)

OBJECTIVE—The purpose of this study was to compare the predictive value for coronary heart disease (CHD) of the International Diabetes Federation (IDF) definition (with Asian criteria for central obesity) of the metabolic syndrome with existing criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—Subjects with type 2 diabetes and without macrovascular diseases or end-stage renal disease were categorized by the criteria of the IDF and the NCEP ATP III. CHD was defined as myocardial infarction, ischemic heart disease, coronary revascularization, heart failure, and death related to CHD. RESULTS—Of 4,350 patients (aged 54.4 ± 13.4 years; median follow-up period 7.1 [interquartile range 5.2–8.5] years), 65.9% had metabolic syndrome according to either IDF or NCEP ATP III criteria. The NCEP ATP III definition identified metabolic syndrome in 786 subjects (18.1%) who did not fulfill the criteria of the IDF. HDL cholesterol and systolic blood pressure were predictors of CHD after adjustment for other confounding factors. Compared with subjects without metabolic syndrome, the IDF criteria failed to predict CHD (hazard ratio 1.13 [95% CI 0.86–1.48], P = 0.374). In contrast, the NCEP ATP III definition (2.51 [1.80–3.50], P &amp;lt; 0.001) predicted an increased risk of CHD with the NCEP-only group having the highest risk (2.49 [1.66–3.73], P &amp;lt; 0.001). CONCLUSIONS—With established type 2 diabetes, the IDF definition of the metabolic syndrome failed to identify a subgroup of patients who had the highest risk for CHD. Practitioners must recognize the appropriate setting for its application.
Expression of beta-arrestins and beta-adrenergic receptor kinases in the failing human heart.
Authors: M Ungerer, G Parruti, M Böhm, M Puzicha, A DeBlasi, E Erdmann, M J Lohse
Journal: Circulation Research (1994)

The beta-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in beta-adrenergic receptor kinase (beta ARK) expression. beta ARK is thought to effect desensitization by acting in concert with an inhibitor protein, called beta-arrestin. Two isoforms have been identified both for beta ARK and for beta-arrestin. In the present study, we have investigated the expression of the individual isoforms of beta-arrestin and of beta ARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, beta-arrestin-1, beta-arrestin-2, beta ARK-1, and beta ARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for beta-arrestin-1 and beta-arrestin-2, a slight (&lt; 50%) increase of the mRNA for beta ARK-2, and a threefold increase for beta ARK-1 mRNA. At the protein level, beta-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were approximately 350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. beta-Arrestin-2 levels were too low to be detectable using the same methods. beta ARK levels as determined by enzymatic activity were approximately 20 fmol/mg cytosolic protein (beta ARK-1 plus beta ARK-2) and thus almost 20-fold lower than those of beta-arrestin. beta ARK levels were increased approximately twofold in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibitory effect of statins on fibrogenic mediator production from lung cells
Authors: Hiroaki Oka, Hiroshi Ishii, Kosaku Komiya, Hisako Kushima, Jun-ichi Kadota
Journal: European Respiratory Journal (2012)

Introduction:  The pathogenesis of idiopathic pulmonary fibrosis remains largely unknown. Pulmonary fibrosis also remains a devastating clinical disorder for which there are limited therapeutic options. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors of cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on cellular signaling involved in tissue inflammation and also in organ fibrosis/remodelling.   Objective:  To examine the preventive effects of statins on fibrogenic mediator expression and production in lung cells.   Methods:  Normal human lung fibroblasts and type II pneumocyte A549 cells, cultured with pitavastatin, pravastatin, or medium alone, were stimulated by transforming growth factor-β1 (TGF-β1). Then, mRNA expression and protein secretion of several mediators from these cells were evaluated by real-time PCR, ELISA, or multiplex assays.   Results:  The TGF-β1-induced expression or production of mediators, such as CXCL8, platelet-derived growth factor, vascular endothelial growth factor, and collagen-1, were significantly suppressed in both lung cells pretreated with statins, compared to non-treated cells.   Conclusion:  Statins inhibited TGF-β1-induced fibrogenic mediator production from lung fibroblasts and airway epithelial cells. Although further evaluation of the signaling pathways for these phenomena is needed, our results suggest the possibility of statins as anti-fibrotic agents for pulmonary fibrosis.
Olanzapine Versus Lithium in the Maintenance Treatment of Bipolar Disorder: A 12-Month, Randomized, Double-Blind, Controlled Clinical Trial
Authors: Mauricio Tohen, Waldemar Greil, Joseph R Calabrese, Gary S Sachs, Lakshmi N Yatham, Bruno Müller Oerlinghausen, Athanasios Koukopoulos, Giovanni B Cassano, Heinz Grunze, Rasmus W Licht, Liliana Dell'Osso, Angela R Evans, Richard Risser, Robert W Baker, Heidi Crane, Martin R Dossenbach, Charles L Bowden
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence. METHOD: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score ≥20 entered the study and received open-label cotreatment with olanzapine and lithium for 6–12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score ≤12; 21-item Hamilton depression scale score ≤8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5–20 mg/day (N=217), or lithium (target blood level: 0.6–1.2 meq/liter) (N=214). RESULTS: Symptomatic relapse/recurrence (score ≥15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (–0.1% to 17.8%) exceeded the predefined noninferiority margin (–7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label cotreatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (–1.4 kg). CONCLUSIONS: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium cotreatment. Both agents were comparable in preventing depression relapse/recurrence.
Quality of life after bypass surgery for unstable angina. 5-year follow-up results of a Veterans Affairs Cooperative Study.
Authors: D C Booth, R H Deupree, H N Hultgren, A N DeMaria, S M Scott, R J Luchi
Journal: Circulation (1991)

To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Gonadal cell apoptosis: hormone-regulated cell demise
Authors: H Billig
Journal: Human Reproduction Update (1996)

It has become evident that apoptosis, an active form of cell 'suicide', plays an important role in the normal function of all tissues. A balance of cell proliferation and apoptosis is maintained in a healthy individual and any imbalance of the two processes could lead to pathological changes. In both sexes, massive apoptosis accounts for the demise of a majority of gonadal cells (ovarian granulosa cells and male germ cells) during reproductive life. Recent studies have indicated the important role of gonadotrophins as survival factors in both the ovary and the testis. Furthermore, intragonadal survival factors in the ovary (oestrogens, insulin-like growth factor I, epidermal growth factor, basic fibroblast growth factor, interleukin-1β, nitric oxide, etc.) and testis (androgens) have been shown to act in concert with the gonadotrophins. In contrast, several apoptotic factors (androgens, gonadotrophin-releasing hormone-like peptide and interleukin-6) may be important in inducing the demise of ovarian follicles. Understanding of the hormonal and cellular mechanisms responsible for gonadal cell apoptosis will provide new approaches for the treatment of gonadal degenerative conditions such as premature ovarian failure and cryptorchidism, as well as for the design of new contraceptive approaches.
MicroRNA-202-3p Inhibits Cell Proliferation by Targeting ADP-Ribosylation Factor-like 5A in Human Colorectal Carcinoma
Authors: Qifeng Wang, Zhaohui Huang, Weijie Guo, Shujuan Ni, Xiuying Xiao, Lisha Wang, Dan Huang, Cong Tan, Qinghua Xu, Ruopeng Zha, Jiwei Zhang, Weiqi Sheng, Xianghuo He, Xiang Du
Journal: Clinical Cancer Research (2013)

MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of non-protein-coding RNAs. Here, we focused on the function and molecular mechanism of miR-202-3p and its potential clinical application in colorectal cancer.miR-202-3p expression was determined by quantitative reverse transcriptase PCR (qRT-PCR) in 94 colorectal cancer tissues and corresponding noncancerous tissues (NCT). Cell proliferation and colony formation assays in vitro and xenograft experiments in vivo were used to evaluate the effect of miR-202-3p on colorectal cancer cell proliferation. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-202-3p after the preliminary screening by online prediction and microarray analysis. The mRNA and protein levels of target genes were detected by qRT-PCR and immunohistochemical staining. The copy number of pre-miR-202 was measured by quantitative PCR.First, miR-202-3p was significantly downregulated in 46.7% colorectal cancer samples compared with NCTs. The overexpression of miR-202-3p inhibited colorectal cancer cell growth in vitro and repressed tumorigenesis in nude mice. Then, miR-202-3p downregulated ADP-ribosylation factor-like 5A (ARL5A) protein level by binding to its 3' untranslated region, and knockdown of ARL5A phenocopied the proliferation inhibition effect of miR-202-3p. Furthermore, both of ARL5A mRNA and protein levels were upregulated in colorectal cancer samples compared with NCTs and high ARL5A protein levels predicted a poor prognosis.miR-202-3p might function as a tumor suppressor in colorectal cancer, and ARL5A, the functional target of miR-202-3p in colorectal cancer, is a potential prognostic factor for colorectal cancer.
Cost to the NHS of Roche oncology treatments
Authors: M. Atkins
Journal: Journal of the Royal Society of Medicine (2007)

Further to the article in April's Journal (JRSM 2007;100:166-169) I would like to clarify the cited costs for Roche oncology treatments. The average cost to the NHS for a year's course of Herceptin for the treatment of early stage HER2-positive cancer is £24 420. When the costs for administration and management of side-effects are added this rises to £28 000, not the £50 000 annual cost quoted by Professor Sikora. The accurate total costs, including administration, are published on the NICE website.

Similarly, the average cost of Tarceva per patient for the second-line treatment of advanced non-small cell lung cancer is £7550 including hospital visits. When discussing drug costs in the context of NHS financial pressures it is far more appropriate to examine the incremental cost of a treatment, as this is the actual extra cost that needs to be funded by the NHS. Tarceva is £6 more costly per day compared to docetaxel. However, Tarceva is likely to save NHS money in terms of avoiding IV administration and side-effect management costs associated with docetaxel. It is therefore misleading to suggest that by using Tarceva, the NHS will incur an additional £65 000 annual cost per patient and we would welcome clarification as to how this figure was calculated.

In addition, the other costs cited inaccurately by Professor Sikora are for Avastin (colorectal cancer) and MabThera (non-Hodgkin's lymphoma). The average costs per patient for these treatments, again including administration, are £18 548 and £11 800—not the £70 000 (Avastin) and £40 000 (MabThera) quoted in the article.

Whilst we applaud Professor Sikora's intention to highlight a growing need for the NHS to review its financial provision for life-saving and life-extending cancer treatments, we feel that (in the interests of future accuracy and balanced reporting) the inflated and non-transparent costs suggested by Professor Sikora warrant a correction. I would be grateful if this were forthcoming in the next issue. For independent validation of the costs provided by Roche, the respective NICE technology appraisals, available at the NICE website, provide an accurate calculation of the actual drug and administration costs.